<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03280056</url>
  </required_header>
  <id_info>
    <org_study_id>BCT-002-US</org_study_id>
    <nct_id>NCT03280056</nct_id>
  </id_info>
  <brief_title>Safety and Efficacy of Repeated Administrations of NurOwn® in ALS Patients</brief_title>
  <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</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Brainstorm-Cell Therapeutics</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>California Institute for Regenerative Medicine (CIRM)</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Brainstorm-Cell Therapeutics</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study will evaluate the safety and efficacy of repeated administration of NurOwn®&#xD;
      (MSC-NTF cells) therapy, which is based on transplantation of autologous bone marrow derived&#xD;
      mesenchymal stromal cells (MSC), which are enriched from the patient's own bone marrow,&#xD;
      propagated ex vivo and induced to secrete Neurotrophic factors (NTFs).&#xD;
&#xD;
      The autologous NurOwn® (MSC-NTF cells) are back-transplanted into the patient intrathecally&#xD;
      by standard lumbar puncture where neurons and glial cells are expected to take up the&#xD;
      neurotrophic factors secreted by the transplanted cells&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Neurotrophic factors (NTFs) are potent survival factors for embryonic, neonatal, and adult&#xD;
      neurons and are considered potential therapeutic candidates for ALS. Delivery of multiple&#xD;
      NTFs to the immediate environment of afflicted neurons in ALS patients is expected to improve&#xD;
      their survival and thus slow down disease progression and alleviate symptoms. NTF-secreting&#xD;
      mesenchymal stromal cells (MSC-NTF cells) are a novel cell-therapeutic approach aimed at&#xD;
      effectively delivering NTFs directly to the site of damage in ALS patients.&#xD;
&#xD;
      Participants meeting the inclusion and exclusion criteria will be randomized and will undergo&#xD;
      bone-marrow aspiration. MSC of the participants randomized to the treatment group will be&#xD;
      induced into MSC-NTF cells. Participants will undergo a total of three intrathecal (IT)&#xD;
      transplantations with NurOwn® (MSC-NTF cells) or matching placebo at three bi-monthly&#xD;
      intervals&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 28, 2017</start_date>
  <completion_date type="Actual">October 30, 2020</completion_date>
  <primary_completion_date type="Actual">October 30, 2020</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>Randomized, Double-Blind, Placebo-Controlled Multicenter Study</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
    <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</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>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)</measure>
    <time_frame>28 weeks following the first treatment</time_frame>
    <description>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</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Biomarkers</measure>
    <time_frame>Through selected post-treatment time points up to 20 weeks post transplant</time_frame>
    <description>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)</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">263</enrollment>
  <condition>Amyotrophic Lateral Sclerosis (ALS)</condition>
  <arm_group>
    <arm_group_label>NurOwn® (MSC-NTF cells)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Three Intrathecal administrations of NurOwn® (MSC-NTF cells) at bi-monthly intervals</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Three Intrathecal administrations of Placebo at bi-monthly intervals</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>NurOwn® (MSC-NTF cells)</intervention_name>
    <description>Autologous transplantation of bone marrow derived mesenchymal stem cells propagated ex vivo and induced to secrete neurotrophic factors</description>
    <arm_group_label>NurOwn® (MSC-NTF cells)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Placebo</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Bone Marrow aspiration</intervention_name>
    <description>Bone Marrow aspiration</description>
    <arm_group_label>NurOwn® (MSC-NTF cells)</arm_group_label>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  ALS diagnosed as possible, laboratory-supported probable, probable, or definite as&#xD;
             defined by revised El Escorial criteria.&#xD;
&#xD;
          -  Having onset of ALS disease symptoms, including limb weakness within 24 months at the&#xD;
             Screening Visit.&#xD;
&#xD;
          -  ALSFRS-R ≥ 25 at the screening Visit.&#xD;
&#xD;
          -  Upright slow vital capacity (SVC) measure ≥ 65% of predicted for gender, height, and&#xD;
             age at the screening Visit.&#xD;
&#xD;
          -  Rapid progressors&#xD;
&#xD;
          -  Participants taking a stable dose of Riluzole are permitted in the study&#xD;
&#xD;
          -  Citizen or permanent resident of the United States or Canadian citizen able to travel&#xD;
             to a US site for all follow-up study visits&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Prior stem cell therapy of any kind&#xD;
&#xD;
          -  History of autoimmune or other serious disease (including malignancy and immune&#xD;
             deficiency) that may confound study results&#xD;
&#xD;
          -  Current use of immunosuppressant medication or anticoagulants (per Investigator&#xD;
             discretion)&#xD;
&#xD;
          -  Exposure to any other experimental agent or participation in an ALS clinical trial&#xD;
             within 30 days prior to Screening Visit&#xD;
&#xD;
          -  Use of RADICAVA (edaravone injection) within 30 days of screening or intent to use&#xD;
             edaravone at any time during the course of the study including the follow up period&#xD;
&#xD;
          -  Use of non-invasive ventilation (BIPAP), diaphragm pacing system or invasive&#xD;
             ventilation (tracheostomy)&#xD;
&#xD;
          -  Feeding tube&#xD;
&#xD;
          -  Pregnant women or women currently breastfeeding&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Merit E. Cudkowicz, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Massachusetts General Hospital</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Robert H. Brown, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>UMass Medical School</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Anthony J. Windebank, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Mayo Clinic</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Namita A. Goyal, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>UC Irvine</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Robert G. Miller, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>California Pacific Medical Center (CPM) Research Institute</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Robert Baloh, MD, Ph.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Cedars-Sinai Medical Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of California Irvine Alpha Stem Cell Clinic</name>
      <address>
        <city>Irvine</city>
        <state>California</state>
        <zip>92697</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cedars-Sinai Medical Center</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90048</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>California Pacific Medical Center</name>
      <address>
        <city>San Francisco</city>
        <state>California</state>
        <zip>94115</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Massachusetts General Hospital</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02115</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Massachusetts Medical School</name>
      <address>
        <city>Worcester</city>
        <state>Massachusetts</state>
        <zip>01655</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mayo Clinic</name>
      <address>
        <city>Rochester</city>
        <state>Minnesota</state>
        <zip>55905</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>October 2021</verification_date>
  <study_first_submitted>August 29, 2017</study_first_submitted>
  <study_first_submitted_qc>September 10, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 12, 2017</study_first_posted>
  <disposition_first_submitted>October 3, 2021</disposition_first_submitted>
  <disposition_first_submitted_qc>October 3, 2021</disposition_first_submitted_qc>
  <disposition_first_posted type="Actual">October 5, 2021</disposition_first_posted>
  <last_update_submitted>October 5, 2021</last_update_submitted>
  <last_update_submitted_qc>October 5, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">October 6, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>MSC</keyword>
  <keyword>Autologous</keyword>
  <keyword>Neurotrophic factors</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Motor Neuron Disease</mesh_term>
    <mesh_term>Amyotrophic Lateral Sclerosis</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted, but a results disposition has been submitted           -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03280056
org study id: BCT-002-US
nct id: NCT03280056
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
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
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
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Randomized, Double-Blind, Placebo-Controlled Multicenter Study
primary purpose: Treatment
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
measure: 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
description: 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
measure: Biomarkers
time frame: Through selected post-treatment time points up to 20 weeks post transplant
description: 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)
arm group label: NurOwn® (MSC-NTF cells)
arm group type: Active Comparator
description: Three Intrathecal administrations of NurOwn® (MSC-NTF cells) at bi-monthly intervals
arm group label: Placebo
arm group type: Placebo Comparator
description: Three Intrathecal administrations of Placebo at bi-monthly intervals
intervention type: Biological
intervention name: NurOwn® (MSC-NTF cells)
description: Autologous transplantation of bone marrow derived mesenchymal stem cells propagated ex vivo and induced to secrete neurotrophic factors
arm group label: NurOwn® (MSC-NTF cells)
intervention type: Other
intervention name: Placebo
description: Placebo
arm group label: Placebo
intervention type: Other
intervention name: Bone Marrow aspiration
description: Bone Marrow aspiration
arm group label: NurOwn® (MSC-NTF cells)
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 60 Years
healthy volunteers: No
last name: Merit E. Cudkowicz, MD
role: Principal Investigator
affiliation: Massachusetts General Hospital
last name: Robert H. Brown, MD, PhD
role: Principal Investigator
affiliation: UMass Medical School
last name: Anthony J. Windebank, MD
role: Principal Investigator
affiliation: Mayo Clinic
last name: Namita A. Goyal, MD
role: Principal Investigator
affiliation: UC Irvine
last name: Robert G. Miller, MD
role: Principal Investigator
affiliation: California Pacific Medical Center (CPM) Research Institute
last name: Robert Baloh, MD, Ph.D.
role: Principal Investigator
affiliation: Cedars-Sinai Medical Center
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Motor Neuron Disease
mesh term: Amyotrophic Lateral Sclerosis
sharing ipd: No