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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

Tracking Information
First Submitted Date  ICMJE August 29, 2017
First Posted Date  ICMJE September 12, 2017
Results First Submitted Date  ICMJE December 1, 2023
Results First Posted Date  ICMJE February 29, 2024
Last Update Posted Date February 29, 2024
Actual Study Start Date  ICMJE August 28, 2017
Actual Primary Completion Date September 29, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 4, 2024)
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.
Original Primary Outcome Measures  ICMJE
 (submitted: September 10, 2017)
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
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 5, 2024)
  • 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.
  • 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.
  • 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: September 10, 2017)
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)
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety and Efficacy of Repeated Administrations of NurOwn® in ALS Patients
Official Title  ICMJE 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
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

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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE 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
Condition  ICMJE Amyotrophic Lateral Sclerosis (ALS)
Intervention  ICMJE
  • 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: 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
Study Arms  ICMJE
  • Active Comparator: NurOwn® (MSC-NTF cells)
    Three Intrathecal administrations of NurOwn® (MSC-NTF cells) at bi-monthly intervals
    Interventions:
    • Biological: NurOwn® (MSC-NTF cells)
    • Other: Bone Marrow aspiration
  • Placebo Comparator: Placebo
    Three Intrathecal administrations of Placebo at bi-monthly intervals
    Interventions:
    • Other: Placebo
    • Other: Bone Marrow aspiration
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: December 1, 2023)
196
Original Estimated Enrollment  ICMJE
 (submitted: September 10, 2017)
200
Actual Study Completion Date  ICMJE September 29, 2020
Actual Primary Completion Date September 29, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 60 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03280056
Other Study ID Numbers  ICMJE BCT-002-US
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Current Responsible Party Brainstorm-Cell Therapeutics
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Brainstorm-Cell Therapeutics
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE California Institute for Regenerative Medicine (CIRM)
Investigators  ICMJE
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
PRS Account Brainstorm-Cell Therapeutics
Verification Date February 2024

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP