<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/NCT03799718</url>
  </required_header>
  <id_info>
    <org_study_id>BCT-101-US</org_study_id>
    <nct_id>NCT03799718</nct_id>
  </id_info>
  <brief_title>Safety and Efficacy of Repeated Administration of NurOwn (MSC-NTF Cells) in Participants With Progressive MS</brief_title>
  <official_title>A Phase 2 Open-label Multicenter Study to Evaluate the Safety and Efficacy of Repeated Administration of NurOwn® [Autologous Mesenchymal Stem Cells Secreting Neurotrophic Factors (NTF), MSC-NTF] Cells in Participants With Progressive MS</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Brainstorm-Cell Therapeutics</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </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>
      A multidose open-label study with autologous Mesenchymal Stromal Stem Cells Secreting&#xD;
      Neurotrophic Factors (MSC-NTF cells) involving 20 participants with progressive MS at&#xD;
      multiple investigational study sites.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      An open-label study with a single treatment arm involving 20 participants with progressive MS&#xD;
      at multiple investigational study sites. After providing informed consent, participants&#xD;
      meeting the inclusion and exclusion criteria will be randomized and approximately 4 weeks&#xD;
      later will undergo a bone-marrow aspiration (BMA). Each participants will receive three&#xD;
      Intrathecal cell transplantations within 16 weeks and will be followed for 12 weeks for&#xD;
      safety and efficacy.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">March 13, 2019</start_date>
  <completion_date type="Actual">March 30, 2021</completion_date>
  <primary_completion_date type="Actual">March 11, 2021</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <intervention_model_description>Open label</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Participants With Treatment-emergent Adverse Events</measure>
    <time_frame>Up to 28 weeks post-first treatment</time_frame>
    <description>Combined safety of all 3 intrathecal doses of NurOwn® (MSC-NTF cells) Number of participants who experienced Treatment-emergent Adverse Events during the study.&#xD;
Treatment-emergent Adverse Event is an adverse event that occurs for the first time after initiation of first treatment or if it had occurred prior to initiation first treatment, it worsens in severity after initiation of first treatment.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With 25% or Greater Improvement From Baseline in Time 25 Foot Walk (T25FW) Speed or Nine-Hole Peg Test (9-HPT)</measure>
    <time_frame>From Baseline (pre-first treatment) to 28 weeks post-first treatment</time_frame>
    <description>25% or greater improvement at 28 weeks from Baseline in Time 25 Foot Walk (T25FW) speed or 9 Hole Peg Test (9-HPT).&#xD;
The T25FW is a quantitative mobility and leg function performance test based on a timed 25-feet walk. The patient is directed to one end of a clearly marked 25-foot course and is instructed to walk 25 feet as quickly as possible, but safely. T25FW is the average of the two successive trials. Higher values represent better outcomes.&#xD;
The 9HPT is used to measure upper extremity function in patients with various neurological diagnoses. The participant is asked to pick up the nine pegs, puts them in the nine holes, and, once completed, removes them again as quickly as possible, replacing them into the container. The total time to complete the task is recorded.&#xD;
Higher values represent worse outcomes.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With 25% or Greater Improvement From Baseline to Week 28 in Timed 25 Foot Walk (T25FW) Speed</measure>
    <time_frame>From Baseline (pre-first treatment) to 28 weeks post-first treatment</time_frame>
    <description>≥25% improvement in T25FW speed over 28 weeks The T25FW is a quantitative mobility and leg function performance test based on a timed 25-feet walk.&#xD;
The patient is directed to one end of a clearly marked 25-foot course and is instructed to walk 25 feet as quickly as possible, but safely.&#xD;
The task is immediately administered again by having the patient walk back the same distance Baseline T25FW is the average of the two successive trials. Higher values represent better outcomes</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With 25% or Greater Improvement From Baseline to Week 28 in 9-HPT</measure>
    <time_frame>From Baseline (pre-first treatment) to 28 weeks post-first treatment</time_frame>
    <description>The Nine-Hole Peg Test (9HPT) is used to measure upper extremity function in patients with various neurological diagnoses.&#xD;
The participant is seated at a table with a small, shallow container holding nine pegs and a wood or plastic block containing nine empty holes. On a start command when a stopwatch is started, the participant picks up the nine pegs one at a time as quickly as possible, puts them in the nine holes, and, once they are in the holes, removes them again as quickly as possible one at a time, replacing them into the shallow container. The total time to complete the task is recorded. Two consecutive trials with the dominant hand are immediately followed by two consecutive trials with the non-dominant hand.&#xD;
Baseline 9HPT is the average of 2 trials of dominant hand and nondominant hand. The higher values represent a worse outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants Who Had &gt;5.5 in Expanded Disability Status Scale (EDSS) at Baseline, With ≥0.5 Points Improvement From Baseline to Week 28</measure>
    <time_frame>From Baseline (pre-first treatment) to 28 weeks post-first treatment</time_frame>
    <description>Expanded Disability Status Scale (EDSS) provides a total score on a scale that ranges from 0 (no disability) through 1 to 10 (death due to MS), in 0.5-point steps. The first levels 1.0 to 4.5 refer to people with a high degree of ambulatory ability and the sequent levels 5.0 to 9.5 refer to the loss of ambulatory ability. The higher score represents the worse outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With ≥10 Points Improvement From Baseline to Week 28 in Multiple Sclerosis Walking Scale (MSWS-12)</measure>
    <time_frame>From Baseline (pre-first treatment) to 28 weeks post-first treatment</time_frame>
    <description>The Multiple Sclerosis Walking Scale (MSWS)-12 is a patient-reported outcome measure of the walking limitations due to MS during the past 2 weeks.&#xD;
It contains 12 questions that assess the impact of MS on different aspects of walking function and quality.&#xD;
Total administration time should be approximately 5 minutes. Activities are rated by participant from min. 1 (not at all) to max. 5 (extremely) and summed to calculate a total score using a scale from 0 to 60 (ranging from low to high impact on walking). This score is then divided by 60 and multiplied by 100 to get a score between 0 and 100 A higher score represents a worse outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With ≥8 Letter Improvement From Baseline to Week 28 in LCLA Binocular 2.5% Contrast Level</measure>
    <time_frame>From Baseline (pre-first treatment) to 28 weeks post-first treatment</time_frame>
    <description>The Low contrast letter acuity (LCLA) is a leading outcome measure to assess visual disability in multiple sclerosis (MS) research Total administration time, for a typical MS patient, is approximately 10-15 minutes to complete, when testing each eye individually and binocular vision for two different contrast levels.&#xD;
The score for each chart is quantified as the number of letters identified correctly with a minimum scrore of 0 letter and a maximum score of 70 letters. The higher score represents the better outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With ≥ 3 Points Improvement From Baseline to Week 28 in Symbol Digit Modalities Test (SDMT) Score</measure>
    <time_frame>From Baseline (pre-first treatment) to 28 weeks post-first treatment</time_frame>
    <description>Symbol Digit Modalities test (SDMT) is a commonly used test to assess psychomotor speed, which measures processing speed as well as motor speed.&#xD;
It is a paper-pencil measure which requires an individual to substitute digits for abstract symbols using a reference key Scoring involves summing the number of correct substitutions within the 90 second interval (max = 110) Minimum score is 0 and maximum score 110. The higher score represents the better outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Concentration of Vascular Endothelial Growth Factor (VEGF) Neuroprotective Biomarker From Baseline in the Cerebrospinal Fluid (CSF) 16 Weeks Following First NurOwn® Treatment</measure>
    <time_frame>From Baseline (pre-first treatment) to 16 weeks post first treatment</time_frame>
    <description>Change from baseline (pre-first treatment) in the concentration of Vascular endothelial growth factor (VEGF) neuroprotective biomarker in the Cerebrospinal fluid (CSF) at 16 weeks following first NurOwn® treatment The concentration of the biomarker is measured as Picogram per milliliter (pg/ml). A higher concentration of neuroprotective biomarkers suggests a better outcome</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Concentration of Hepatocyte Growth Factor (HGF) Neuroprotective Biomarker From Baseline in the Cerebrospinal Fluid (CSF) 16 Weeks Following NurOwn® Treatment</measure>
    <time_frame>From Baseline (pre-first treatment) to 16 weeks post first treatment</time_frame>
    <description>Change from baseline in the concentration of Hepatocyte growth factor (HGF) neuroprotective biomarker in the Cerebrospinal Fluid (CSF) at 16 weeks following the first NurOwn® treatment The concentration of the biomarker is measured as Picogram per milliliter (pg/ml). A higher concentration of neuroprotective biomarkers suggests a better outcome</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">23</enrollment>
  <condition>Multiple Sclerosis, Chronic Progressive</condition>
  <arm_group>
    <arm_group_label>NurOwn (MSC-NTF cells)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Autologous Mesenchymal Stem Cells Secreting Neurotrophic Factors</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>NurOwn (MSC-NTF cells)</intervention_name>
    <description>Autologous Mesenchymal Stem Cells Secreting Neurotrophic Factors</description>
    <arm_group_label>NurOwn (MSC-NTF cells)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Males and females ages 18 to 65 years old, inclusive, at the Screening Visit.&#xD;
&#xD;
          2. Clinical diagnosis of Progressive MS (Primary and Secondary) based on the 2017 revised&#xD;
             MacDonald Criteria and confirmation by the Investigator that the disease has entered&#xD;
             the progressive stage for at least 6 months prior to enrollment.&#xD;
&#xD;
          3. No evidence of clinical MS relapse or high dose pulse corticosteroid treatment within&#xD;
             6 months prior to screening&#xD;
&#xD;
          4. Disability status at screening with an Expanded Disability Status Scale (EDSS)&#xD;
             3.0-6.5, inclusive.&#xD;
&#xD;
          5. Able to walk 25 feet in 60 seconds or less.&#xD;
&#xD;
          6. Stable dose of non-excluded MS Disease Modifying Therapy for at least 6 months prior&#xD;
             to Screening Visit (Visit 1).&#xD;
&#xD;
          7. Women of childbearing potential shall either be surgically sterile, or must agree not&#xD;
             to become pregnant for the duration of the study. Women must be willing to undergo a&#xD;
             serum pregnancy test at screening, and at the conclusion of the study. Participants of&#xD;
             childbearing potential must agree to use a medically approved form of birth control&#xD;
             (abstinence, intrauterine device (IUD), oral contraception, barrier and spermicide or&#xD;
             hormonal implant) throughout the duration of the study and for at least 3 months&#xD;
             following the last transplantation. For those women who are sexually active and using&#xD;
             oral contraceptives, a second form of barrier contraception is required. Men must be&#xD;
             willing to consistently use two forms of contraceptive if their partners are of&#xD;
             childbearing age.&#xD;
&#xD;
          8. Capable of providing informed consent and willing and able to follow study procedures,&#xD;
             including willingness to undergo multiple/repeated lumbar puncture.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Prior stem cell therapy of any kind.&#xD;
&#xD;
          2. Active participation in any other MS interventional study or use of unapproved MS&#xD;
             investigational therapy within 90 days prior to the Screening Visit (Visit 1).&#xD;
&#xD;
          3. Inability to lie flat for the duration of intrathecal cell transplantation and/or bone&#xD;
             marrow biopsy, or inability to tolerate study procedures for any other reason.&#xD;
&#xD;
          4. History of clinically significant autoimmune disease (excluding thyroid disease) that&#xD;
             may confound study results, in the opinion of the Investigator and the medical&#xD;
             monitor, myelodysplastic or myeloproliferative disorder, leukemia or lymphoma, whole&#xD;
             body irradiation, hip fracture, or severe scoliosis.&#xD;
&#xD;
          5. Any unstable clinically significant medical condition other than multiple sclerosis&#xD;
             (e.g., within six months of Screening Visit (Visit 1), had myocardial infarction,&#xD;
             angina pectoris, and/or congestive heart failure), treatment with anticoagulants that,&#xD;
             in the opinion of the investigator, would compromise the safety of participants.&#xD;
&#xD;
          6. Any history of malignancy within the previous 5 years, except for non-melanoma&#xD;
             localized skin cancers (with no evidence of metastasis, significant invasion, or&#xD;
             reoccurrence within three years of Screening Visit (Visit 1)).&#xD;
&#xD;
          7. Serum aspartate aminotransferase (AST) or alanine aminotransferase (ALT) value &gt;3.0&#xD;
             times the upper normal limit.&#xD;
&#xD;
          8. Serum creatinine value &gt;2.0 times the upper normal limit.&#xD;
&#xD;
          9. Positive test for Hepatitis B (HBV; surface antigen (HBsAg) and antibodies to core&#xD;
             antigen (IgG and IgM anti-HBc)), Hepatitis C (HCV), or human immunodeficiency virus&#xD;
             (HIV) 1 and 2.&#xD;
&#xD;
         10. Current use of immunosuppressant medication or use of such medication within 6 months&#xD;
             of study enrollment (aside from Rituximab or other approved B-cell immunotherapy).&#xD;
             Alemtuzumab (Lemtrada), Cladribine (NDA submitted), Natalizumab (Tysabri), S1P&#xD;
             modulators (Gilenya) are excluded for safety reasons due to the known risk of systemic&#xD;
             autoimmune disease, malignancy, opportunistic infections, and cardiovascular toxicity&#xD;
             associated with these therapies, as well as theoretical effects on MSC-NTF cell homing&#xD;
             and migration, that may be associated with Natalizumab and/or S1P modulators&#xD;
             (Gilenya).&#xD;
&#xD;
         11. Any history of acquired or inherited immune deficiency syndrome.&#xD;
&#xD;
         12. Any history of either substance abuse within the past year, or unstable psychiatric&#xD;
             disease according to the Investigator's judgment.&#xD;
&#xD;
         13. Pregnant women or women currently breastfeeding.&#xD;
&#xD;
         14. Subjects for whom MRI is contraindicated (i.e., have a pacemaker or other metallic&#xD;
             implanted device, or are unable to remain in the machine for period of time needed to&#xD;
             acquire a scan.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jeffrey Cohen, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>The Cleveland Clinic</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Southern California</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90033</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Stanford University School of Medicine</name>
      <address>
        <city>Redwood City</city>
        <state>California</state>
        <zip>94305</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Mount Sinai Hospital</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10029</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cleveland Clinic</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <zip>44195</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2021</verification_date>
  <study_first_submitted>January 7, 2019</study_first_submitted>
  <study_first_submitted_qc>January 9, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 10, 2019</study_first_posted>
  <results_first_submitted>September 11, 2022</results_first_submitted>
  <results_first_submitted_qc>October 20, 2022</results_first_submitted_qc>
  <results_first_posted type="Actual">November 14, 2022</results_first_posted>
  <last_update_submitted>October 20, 2022</last_update_submitted>
  <last_update_submitted_qc>October 20, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">November 14, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Multiple Sclerosis</mesh_term>
    <mesh_term>Multiple Sclerosis, Chronic Progressive</mesh_term>
  </condition_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>June 1, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/18/NCT03799718/Prot_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>April 12, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/18/NCT03799718/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>Not meeting inclusion exclusion criteria</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>NurOwn (MSC-NTF Cells)</title>
          <description>Autologous Mesenchymal Stem Cells Secreting Neurotrophic Factors NurOwn (MSC-NTF cells). Study drug was supplied in one 5 mL syringe containing 4 mL of NurOwn (MSC-NTF cells) suspension at a dose of 100-125 x106 cells for IT administration. 3 doses of NurOwn (MSC-NTF cells) were transplanted intrathecally at 8-week intervals (Day 0-1, week 8, and week 16)</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="20">20 participants underwent bone marrow aspiration. In two participants, autologous bone marrow culture failed to meet specific MSC-NTF cell product release criteria and they did not receive treatment</participants>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="18">Of the 20 participants enrolled, 18 were treated, 17 received all three treatments and one received two treatments.</participants>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Baseline characteristics are for participants with a clinical diagnosis of primary or secondary progressive MS (PPMS or SPMS) based on the 2017 revised McDonald Criteria and confirmation by the Investigator that the disease has entered the progressive stage at least 6 months prior to enrollment</population>
      <group_list>
        <group group_id="B1">
          <title>NurOwn (MSC-NTF Cells)</title>
          <description>Autologous Mesenchymal Stem Cells Secreting Neurotrophic Factors&#xD;
NurOwn (MSC-NTF cells): Autologous Mesenchymal Stem Cells Secreting Neurotrophic Factors</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="18"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="47.4" spread="9.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="18"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="15"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="18"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Timed 25-foot walk speed</title>
          <description>The T25FW is a quantitative mobility and leg function performance test based on a timed 25-feet walk. The patient is directed to one end of a clearly marked 25-foot course and is instructed to walk 25 feet as quickly as possible, but safely. The time is calculated from the initiation of the instruction to start and ends when the patient has reached the 25-foot mark. The task is immediately administered again by having the patient walk back the same distance. Baseline T25FW is the average of the two successive trials. Higher values represent better outcomes</description>
          <units>Feet/seconds</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2.4" spread="1.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Nine-Hole Peg Test (9HPT)</title>
          <description>The Nine-Hole Peg Test (9HPT) is used to measure upper extremity function in patients with various neurological diagnoses The participant is seated at a table with a container holding nine pegs and a block with 9 empty holes. On a start command, the participant picks up the nine pegs, puts them in the nine holes, and, once completed, removes them again as quickly as possible, replacing them into the container. The total time to complete the task is recorded.&#xD;
Baseline 9HPT is the average of 2 trials of dominant hand and nondominant hand. Higher values represent a worse outcome.</description>
          <units>Seconds</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="35.2" spread="15.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants With Treatment-emergent Adverse Events</title>
        <description>Combined safety of all 3 intrathecal doses of NurOwn® (MSC-NTF cells) Number of participants who experienced Treatment-emergent Adverse Events during the study.&#xD;
Treatment-emergent Adverse Event is an adverse event that occurs for the first time after initiation of first treatment or if it had occurred prior to initiation first treatment, it worsens in severity after initiation of first treatment.</description>
        <time_frame>Up to 28 weeks post-first treatment</time_frame>
        <population>The primary, secondary, and exploratory efficacy endpoints were analyzed using the modified intent to treat (mITT) and Efficacy Evaluable (EE) populations The mITT population was defined in this study as all participants who received at least 1 treatment and had at least 1 T25FW or 9-HPT assessment post baseline. Baseline was defined as the most recent assessment prior to receiving the first transplantation on Day 0, at Visit 3</population>
        <group_list>
          <group group_id="O1">
            <title>NurOwn (MSC-NTF Cells)</title>
            <description>Autologous Mesenchymal Stem Cells Secreting Neurotrophic Factors&#xD;
NurOwn (MSC-NTF cells): Autologous Mesenchymal Stem Cells Secreting Neurotrophic Factors</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Treatment-emergent Adverse Events</title>
          <description>Combined safety of all 3 intrathecal doses of NurOwn® (MSC-NTF cells) Number of participants who experienced Treatment-emergent Adverse Events during the study.&#xD;
Treatment-emergent Adverse Event is an adverse event that occurs for the first time after initiation of first treatment or if it had occurred prior to initiation first treatment, it worsens in severity after initiation of first treatment.</description>
          <population>The primary, secondary, and exploratory efficacy endpoints were analyzed using the modified intent to treat (mITT) and Efficacy Evaluable (EE) populations The mITT population was defined in this study as all participants who received at least 1 treatment and had at least 1 T25FW or 9-HPT assessment post baseline. Baseline was defined as the most recent assessment prior to receiving the first transplantation on Day 0, at Visit 3</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="18"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="18"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With 25% or Greater Improvement From Baseline in Time 25 Foot Walk (T25FW) Speed or Nine-Hole Peg Test (9-HPT)</title>
        <description>25% or greater improvement at 28 weeks from Baseline in Time 25 Foot Walk (T25FW) speed or 9 Hole Peg Test (9-HPT).&#xD;
The T25FW is a quantitative mobility and leg function performance test based on a timed 25-feet walk. The patient is directed to one end of a clearly marked 25-foot course and is instructed to walk 25 feet as quickly as possible, but safely. T25FW is the average of the two successive trials. Higher values represent better outcomes.&#xD;
The 9HPT is used to measure upper extremity function in patients with various neurological diagnoses. The participant is asked to pick up the nine pegs, puts them in the nine holes, and, once completed, removes them again as quickly as possible, replacing them into the container. The total time to complete the task is recorded.&#xD;
Higher values represent worse outcomes.</description>
        <time_frame>From Baseline (pre-first treatment) to 28 weeks post-first treatment</time_frame>
        <population>The modified intent to treat (mITT) population was defined in this study as all participants who received at least 1 treatment and had at least 1 T25FW or 9-HPT assessment post baseline. Baseline was defined as the most recent assessment prior to receiving the first transplantation on Day 0, at Visit 3</population>
        <group_list>
          <group group_id="O1">
            <title>NurOwn (MSC-NTF Cells)</title>
            <description>Autologous Mesenchymal Stem Cells Secreting Neurotrophic Factors&#xD;
NurOwn (MSC-NTF cells): Autologous Mesenchymal Stem Cells Secreting Neurotrophic Factors</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With 25% or Greater Improvement From Baseline in Time 25 Foot Walk (T25FW) Speed or Nine-Hole Peg Test (9-HPT)</title>
          <description>25% or greater improvement at 28 weeks from Baseline in Time 25 Foot Walk (T25FW) speed or 9 Hole Peg Test (9-HPT).&#xD;
The T25FW is a quantitative mobility and leg function performance test based on a timed 25-feet walk. The patient is directed to one end of a clearly marked 25-foot course and is instructed to walk 25 feet as quickly as possible, but safely. T25FW is the average of the two successive trials. Higher values represent better outcomes.&#xD;
The 9HPT is used to measure upper extremity function in patients with various neurological diagnoses. The participant is asked to pick up the nine pegs, puts them in the nine holes, and, once completed, removes them again as quickly as possible, replacing them into the container. The total time to complete the task is recorded.&#xD;
Higher values represent worse outcomes.</description>
          <population>The modified intent to treat (mITT) population was defined in this study as all participants who received at least 1 treatment and had at least 1 T25FW or 9-HPT assessment post baseline. Baseline was defined as the most recent assessment prior to receiving the first transplantation on Day 0, at Visit 3</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="18"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Number of Participants with 25% or greater improvement from Baseline inT25FW speed or 9-HPT</title>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Number of Participants with &lt;25% improvement from Baseline inT25FW speed or 9-HPT</title>
                  <measurement_list>
                    <measurement group_id="O1" value="13"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Number of Participants with missing data at week 28</title>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With 25% or Greater Improvement From Baseline to Week 28 in Timed 25 Foot Walk (T25FW) Speed</title>
        <description>≥25% improvement in T25FW speed over 28 weeks The T25FW is a quantitative mobility and leg function performance test based on a timed 25-feet walk.&#xD;
The patient is directed to one end of a clearly marked 25-foot course and is instructed to walk 25 feet as quickly as possible, but safely.&#xD;
The task is immediately administered again by having the patient walk back the same distance Baseline T25FW is the average of the two successive trials. Higher values represent better outcomes</description>
        <time_frame>From Baseline (pre-first treatment) to 28 weeks post-first treatment</time_frame>
        <population>mITT population</population>
        <group_list>
          <group group_id="O1">
            <title>NurOwn (MSC-NTF Cells)</title>
            <description>Autologous Mesenchymal Stem Cells Secreting Neurotrophic Factors&#xD;
NurOwn (MSC-NTF cells): Autologous Mesenchymal Stem Cells Secreting Neurotrophic Factors</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With 25% or Greater Improvement From Baseline to Week 28 in Timed 25 Foot Walk (T25FW) Speed</title>
          <description>≥25% improvement in T25FW speed over 28 weeks The T25FW is a quantitative mobility and leg function performance test based on a timed 25-feet walk.&#xD;
The patient is directed to one end of a clearly marked 25-foot course and is instructed to walk 25 feet as quickly as possible, but safely.&#xD;
The task is immediately administered again by having the patient walk back the same distance Baseline T25FW is the average of the two successive trials. Higher values represent better outcomes</description>
          <population>mITT population</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="18"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Number of participants with 25% or more improvement</title>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Number of participants without 25% or more improvement</title>
                  <measurement_list>
                    <measurement group_id="O1" value="12"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Number of participants with missing values at week 28</title>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With 25% or Greater Improvement From Baseline to Week 28 in 9-HPT</title>
        <description>The Nine-Hole Peg Test (9HPT) is used to measure upper extremity function in patients with various neurological diagnoses.&#xD;
The participant is seated at a table with a small, shallow container holding nine pegs and a wood or plastic block containing nine empty holes. On a start command when a stopwatch is started, the participant picks up the nine pegs one at a time as quickly as possible, puts them in the nine holes, and, once they are in the holes, removes them again as quickly as possible one at a time, replacing them into the shallow container. The total time to complete the task is recorded. Two consecutive trials with the dominant hand are immediately followed by two consecutive trials with the non-dominant hand.&#xD;
Baseline 9HPT is the average of 2 trials of dominant hand and nondominant hand. The higher values represent a worse outcome.</description>
        <time_frame>From Baseline (pre-first treatment) to 28 weeks post-first treatment</time_frame>
        <population>The mITT population was defined in this study as all participants who received at least 1 treatment and had at least 1 T25FW or 9-HPT assessment post baseline. Baseline was defined as the most recent assessment prior to receiving the first transplantation on Day 0, at Visit 3.</population>
        <group_list>
          <group group_id="O1">
            <title>NurOwn (MSC-NTF Cells)</title>
            <description>Autologous Mesenchymal Stem Cells Secreting Neurotrophic Factors&#xD;
NurOwn (MSC-NTF cells): Autologous Mesenchymal Stem Cells Secreting Neurotrophic Factors</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With 25% or Greater Improvement From Baseline to Week 28 in 9-HPT</title>
          <description>The Nine-Hole Peg Test (9HPT) is used to measure upper extremity function in patients with various neurological diagnoses.&#xD;
The participant is seated at a table with a small, shallow container holding nine pegs and a wood or plastic block containing nine empty holes. On a start command when a stopwatch is started, the participant picks up the nine pegs one at a time as quickly as possible, puts them in the nine holes, and, once they are in the holes, removes them again as quickly as possible one at a time, replacing them into the shallow container. The total time to complete the task is recorded. Two consecutive trials with the dominant hand are immediately followed by two consecutive trials with the non-dominant hand.&#xD;
Baseline 9HPT is the average of 2 trials of dominant hand and nondominant hand. The higher values represent a worse outcome.</description>
          <population>The mITT population was defined in this study as all participants who received at least 1 treatment and had at least 1 T25FW or 9-HPT assessment post baseline. Baseline was defined as the most recent assessment prior to receiving the first transplantation on Day 0, at Visit 3.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="18"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Number of Participants with 25% or greater improvement from Baseline to Week 28 in 9-HPT</title>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Number of Participants with less than 25% improvement from Baseline to Week 28 in 9-HPT</title>
                  <measurement_list>
                    <measurement group_id="O1" value="13"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Number of participants with missing values at week 28</title>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants Who Had &gt;5.5 in Expanded Disability Status Scale (EDSS) at Baseline, With ≥0.5 Points Improvement From Baseline to Week 28</title>
        <description>Expanded Disability Status Scale (EDSS) provides a total score on a scale that ranges from 0 (no disability) through 1 to 10 (death due to MS), in 0.5-point steps. The first levels 1.0 to 4.5 refer to people with a high degree of ambulatory ability and the sequent levels 5.0 to 9.5 refer to the loss of ambulatory ability. The higher score represents the worse outcome.</description>
        <time_frame>From Baseline (pre-first treatment) to 28 weeks post-first treatment</time_frame>
        <population>The mITT population was defined in this study as all participants who received at least 1 treatment and had at least 1 T25FW or 9-HPT assessment post baseline.&#xD;
Baseline was defined as the most recent assessment prior to receiving the first transplantation on Day 0, at Visit 3.&#xD;
The participants in mITT population whose EDSS Score was &gt;5.5 at Baseline was analyzed.</population>
        <group_list>
          <group group_id="O1">
            <title>NurOwn (MSC-NTF Cells)</title>
            <description>Autologous Mesenchymal Stem Cells Secreting Neurotrophic Factors&#xD;
NurOwn (MSC-NTF cells): Autologous Mesenchymal Stem Cells Secreting Neurotrophic Factors</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants Who Had &gt;5.5 in Expanded Disability Status Scale (EDSS) at Baseline, With ≥0.5 Points Improvement From Baseline to Week 28</title>
          <description>Expanded Disability Status Scale (EDSS) provides a total score on a scale that ranges from 0 (no disability) through 1 to 10 (death due to MS), in 0.5-point steps. The first levels 1.0 to 4.5 refer to people with a high degree of ambulatory ability and the sequent levels 5.0 to 9.5 refer to the loss of ambulatory ability. The higher score represents the worse outcome.</description>
          <population>The mITT population was defined in this study as all participants who received at least 1 treatment and had at least 1 T25FW or 9-HPT assessment post baseline.&#xD;
Baseline was defined as the most recent assessment prior to receiving the first transplantation on Day 0, at Visit 3.&#xD;
The participants in mITT population whose EDSS Score was &gt;5.5 at Baseline was analyzed.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>No of Participants with &gt;5.5 in EDSS at Baseline with ≥0.5 Points Improvement from Baseline to Wk 28</title>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>No of Participants with &gt;5.5 in EDSS at Baseline with &lt;0.5 Points Improvement from Baseline to Wk 28</title>
                  <measurement_list>
                    <measurement group_id="O1" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With ≥10 Points Improvement From Baseline to Week 28 in Multiple Sclerosis Walking Scale (MSWS-12)</title>
        <description>The Multiple Sclerosis Walking Scale (MSWS)-12 is a patient-reported outcome measure of the walking limitations due to MS during the past 2 weeks.&#xD;
It contains 12 questions that assess the impact of MS on different aspects of walking function and quality.&#xD;
Total administration time should be approximately 5 minutes. Activities are rated by participant from min. 1 (not at all) to max. 5 (extremely) and summed to calculate a total score using a scale from 0 to 60 (ranging from low to high impact on walking). This score is then divided by 60 and multiplied by 100 to get a score between 0 and 100 A higher score represents a worse outcome.</description>
        <time_frame>From Baseline (pre-first treatment) to 28 weeks post-first treatment</time_frame>
        <population>The mITT population was defined in this study as all participants who received at least 1 treatment and had at least 1 T25FW or 9-HPT assessment post baseline. Baseline was defined as the most recent assessment prior to receiving the first transplantation on Day 0, at Visit 3</population>
        <group_list>
          <group group_id="O1">
            <title>NurOwn (MSC-NTF Cells)</title>
            <description>Autologous Mesenchymal Stem Cells Secreting Neurotrophic Factors&#xD;
NurOwn (MSC-NTF cells): Autologous Mesenchymal Stem Cells Secreting Neurotrophic Factors</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With ≥10 Points Improvement From Baseline to Week 28 in Multiple Sclerosis Walking Scale (MSWS-12)</title>
          <description>The Multiple Sclerosis Walking Scale (MSWS)-12 is a patient-reported outcome measure of the walking limitations due to MS during the past 2 weeks.&#xD;
It contains 12 questions that assess the impact of MS on different aspects of walking function and quality.&#xD;
Total administration time should be approximately 5 minutes. Activities are rated by participant from min. 1 (not at all) to max. 5 (extremely) and summed to calculate a total score using a scale from 0 to 60 (ranging from low to high impact on walking). This score is then divided by 60 and multiplied by 100 to get a score between 0 and 100 A higher score represents a worse outcome.</description>
          <population>The mITT population was defined in this study as all participants who received at least 1 treatment and had at least 1 T25FW or 9-HPT assessment post baseline. Baseline was defined as the most recent assessment prior to receiving the first transplantation on Day 0, at Visit 3</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="18"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Number of Participants with ≥10 Points Improvement from Baseline to Week 28 in MSWS-12</title>
                  <measurement_list>
                    <measurement group_id="O1" value="6"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Number of Participants with &lt;10 Points Improvement from Baseline to Week 28 in MSWS-12</title>
                  <measurement_list>
                    <measurement group_id="O1" value="10"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Number of Participants with missing data at week 28</title>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With ≥8 Letter Improvement From Baseline to Week 28 in LCLA Binocular 2.5% Contrast Level</title>
        <description>The Low contrast letter acuity (LCLA) is a leading outcome measure to assess visual disability in multiple sclerosis (MS) research Total administration time, for a typical MS patient, is approximately 10-15 minutes to complete, when testing each eye individually and binocular vision for two different contrast levels.&#xD;
The score for each chart is quantified as the number of letters identified correctly with a minimum scrore of 0 letter and a maximum score of 70 letters. The higher score represents the better outcome.</description>
        <time_frame>From Baseline (pre-first treatment) to 28 weeks post-first treatment</time_frame>
        <population>The mITT population was defined in this study as all participants who received at least 1 treatment and had at least 1 T25FW or 9-HPT assessment post baseline. Baseline was defined as the most recent assessment prior to receiving the first transplantation on Day 0, at Visit 3</population>
        <group_list>
          <group group_id="O1">
            <title>NurOwn (MSC-NTF Cells)</title>
            <description>Autologous Mesenchymal Stem Cells Secreting Neurotrophic Factors&#xD;
NurOwn (MSC-NTF cells): Autologous Mesenchymal Stem Cells Secreting Neurotrophic Factors</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With ≥8 Letter Improvement From Baseline to Week 28 in LCLA Binocular 2.5% Contrast Level</title>
          <description>The Low contrast letter acuity (LCLA) is a leading outcome measure to assess visual disability in multiple sclerosis (MS) research Total administration time, for a typical MS patient, is approximately 10-15 minutes to complete, when testing each eye individually and binocular vision for two different contrast levels.&#xD;
The score for each chart is quantified as the number of letters identified correctly with a minimum scrore of 0 letter and a maximum score of 70 letters. The higher score represents the better outcome.</description>
          <population>The mITT population was defined in this study as all participants who received at least 1 treatment and had at least 1 T25FW or 9-HPT assessment post baseline. Baseline was defined as the most recent assessment prior to receiving the first transplantation on Day 0, at Visit 3</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="18"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>No. of participants with ≥8 Letter improvement at Week 28 in LCLA Binocular 2.5% Contrast Level</title>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>No. of Participants with &lt;8 Letter Improvement at week 28 in LCLA Binocular 2.5% Contrast Level</title>
                  <measurement_list>
                    <measurement group_id="O1" value="11"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Number of Participants with missing data at week 28</title>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With ≥ 3 Points Improvement From Baseline to Week 28 in Symbol Digit Modalities Test (SDMT) Score</title>
        <description>Symbol Digit Modalities test (SDMT) is a commonly used test to assess psychomotor speed, which measures processing speed as well as motor speed.&#xD;
It is a paper-pencil measure which requires an individual to substitute digits for abstract symbols using a reference key Scoring involves summing the number of correct substitutions within the 90 second interval (max = 110) Minimum score is 0 and maximum score 110. The higher score represents the better outcome.</description>
        <time_frame>From Baseline (pre-first treatment) to 28 weeks post-first treatment</time_frame>
        <population>The mITT population was defined in this study as all participants who received at least 1 treatment and had at least 1 T25FW or 9-HPT assessment post baseline. Baseline was defined as the most recent assessment prior to receiving the first transplantation on Day 0, at Visit 3.</population>
        <group_list>
          <group group_id="O1">
            <title>NurOwn (MSC-NTF Cells)</title>
            <description>Autologous Mesenchymal Stem Cells Secreting Neurotrophic Factors&#xD;
NurOwn (MSC-NTF cells): Autologous Mesenchymal Stem Cells Secreting Neurotrophic Factors</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With ≥ 3 Points Improvement From Baseline to Week 28 in Symbol Digit Modalities Test (SDMT) Score</title>
          <description>Symbol Digit Modalities test (SDMT) is a commonly used test to assess psychomotor speed, which measures processing speed as well as motor speed.&#xD;
It is a paper-pencil measure which requires an individual to substitute digits for abstract symbols using a reference key Scoring involves summing the number of correct substitutions within the 90 second interval (max = 110) Minimum score is 0 and maximum score 110. The higher score represents the better outcome.</description>
          <population>The mITT population was defined in this study as all participants who received at least 1 treatment and had at least 1 T25FW or 9-HPT assessment post baseline. Baseline was defined as the most recent assessment prior to receiving the first transplantation on Day 0, at Visit 3.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="18"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Number of Participants with ≥ 3 points Improvement from Baseline to Week 28 in SDMT Score</title>
                  <measurement_list>
                    <measurement group_id="O1" value="10"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Number of Participants with &lt; 3 points Improvement from Baseline to Week 28 in SDMT Score</title>
                  <measurement_list>
                    <measurement group_id="O1" value="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Number of Participants with missing data at week 28</title>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Concentration of Vascular Endothelial Growth Factor (VEGF) Neuroprotective Biomarker From Baseline in the Cerebrospinal Fluid (CSF) 16 Weeks Following First NurOwn® Treatment</title>
        <description>Change from baseline (pre-first treatment) in the concentration of Vascular endothelial growth factor (VEGF) neuroprotective biomarker in the Cerebrospinal fluid (CSF) at 16 weeks following first NurOwn® treatment The concentration of the biomarker is measured as Picogram per milliliter (pg/ml). A higher concentration of neuroprotective biomarkers suggests a better outcome</description>
        <time_frame>From Baseline (pre-first treatment) to 16 weeks post first treatment</time_frame>
        <population>mITT Population with data available at week 16</population>
        <group_list>
          <group group_id="O1">
            <title>NurOwn (MSC-NTF Cells)</title>
            <description>Autologous Mesenchymal Stem Cells Secreting Neurotrophic Factors&#xD;
NurOwn (MSC-NTF cells): Autologous Mesenchymal Stem Cells Secreting Neurotrophic Factors</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Concentration of Vascular Endothelial Growth Factor (VEGF) Neuroprotective Biomarker From Baseline in the Cerebrospinal Fluid (CSF) 16 Weeks Following First NurOwn® Treatment</title>
          <description>Change from baseline (pre-first treatment) in the concentration of Vascular endothelial growth factor (VEGF) neuroprotective biomarker in the Cerebrospinal fluid (CSF) at 16 weeks following first NurOwn® treatment The concentration of the biomarker is measured as Picogram per milliliter (pg/ml). A higher concentration of neuroprotective biomarkers suggests a better outcome</description>
          <population>mITT Population with data available at week 16</population>
          <units>Picograms per milliliter</units>
          <param>Geometric Mean</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="17"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="90.17" lower_limit="-9.16" upper_limit="124.80"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Concentration of Hepatocyte Growth Factor (HGF) Neuroprotective Biomarker From Baseline in the Cerebrospinal Fluid (CSF) 16 Weeks Following NurOwn® Treatment</title>
        <description>Change from baseline in the concentration of Hepatocyte growth factor (HGF) neuroprotective biomarker in the Cerebrospinal Fluid (CSF) at 16 weeks following the first NurOwn® treatment The concentration of the biomarker is measured as Picogram per milliliter (pg/ml). A higher concentration of neuroprotective biomarkers suggests a better outcome</description>
        <time_frame>From Baseline (pre-first treatment) to 16 weeks post first treatment</time_frame>
        <population>mITT population with data available at week 16</population>
        <group_list>
          <group group_id="O1">
            <title>NurOwn (MSC-NTF Cells)</title>
            <description>Autologous Mesenchymal Stem Cells Secreting Neurotrophic Factors&#xD;
NurOwn (MSC-NTF cells): Autologous Mesenchymal Stem Cells Secreting Neurotrophic Factors</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Concentration of Hepatocyte Growth Factor (HGF) Neuroprotective Biomarker From Baseline in the Cerebrospinal Fluid (CSF) 16 Weeks Following NurOwn® Treatment</title>
          <description>Change from baseline in the concentration of Hepatocyte growth factor (HGF) neuroprotective biomarker in the Cerebrospinal Fluid (CSF) at 16 weeks following the first NurOwn® treatment The concentration of the biomarker is measured as Picogram per milliliter (pg/ml). A higher concentration of neuroprotective biomarkers suggests a better outcome</description>
          <population>mITT population with data available at week 16</population>
          <units>picograms per milliliter</units>
          <param>Geometric Mean</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="17"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="15.16" lower_limit="0.2" upper_limit="19.44"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>28 weeks</time_frame>
      <desc>Adverse Events (AE) were collected over a period of 38 weeks from the time of informed consent at the screening visit through the last study visit (Visit 7 or an Early Termination visit) Treatment Emergent Adverse Events (TEAE) were collected over a period of 28 weeks from the time of the first treatment through the last study visit (Visit 7 or an Early Termination visit)</desc>
      <group_list>
        <group group_id="E1">
          <title>NurOwn (MSC-NTF Cells)</title>
          <description>Autologous Mesenchymal Stem Cells Secreting Neurotrophic Factors&#xD;
NurOwn (MSC-NTF cells): Autologous Mesenchymal Stem Cells Secreting Neurotrophic Factors</description>
        </group>
      </group_list>
      <serious_events>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Arachnoiditis</sub_title>
                <description>[1] Two participants experienced an SAE of arachnoiditis in one of three treatments (one participant with Grade 1 and one participant with Grade 3) that were considered probably related to the IT injection procedure and/or study treatment.</description>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="18" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Injection site pain</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" events="5" subjects_affected="4" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" events="8" subjects_affected="6" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Fall</sub_title>
                <counts group_id="E1" events="4" subjects_affected="3" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" events="29" subjects_affected="15" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Musculoskeletal pain</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Muscular weakness</sub_title>
                <counts group_id="E1" events="4" subjects_affected="3" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Musculoskeletal stiffness</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" events="4" subjects_affected="3" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="35" subjects_affected="16" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Ralph Kern, MD, Chief Medical Officer</name_or_title>
      <organization>Brainstorm Cell therapeutics</organization>
      <phone>201-488-0460</phone>
      <email>rkern@brainstorm-cell.com</email>
    </point_of_contact>
  </clinical_results>
</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/NCT03799718
org study id: BCT-101-US
nct id: NCT03799718
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
A multidose open-label study with autologous Mesenchymal Stromal Stem Cells Secreting
      Neurotrophic Factors (MSC-NTF cells) involving 20 participants with progressive MS at
      multiple investigational study sites.
An open-label study with a single treatment arm involving 20 participants with progressive MS
      at multiple investigational study sites. After providing informed consent, participants
      meeting the inclusion and exclusion criteria will be randomized and approximately 4 weeks
      later will undergo a bone-marrow aspiration (BMA). Each participants will receive three
      Intrathecal cell transplantations within 16 weeks and will be followed for 12 weeks for
      safety and efficacy.
allocation: N/A
intervention model: Single Group Assignment
intervention model description: Open label
primary purpose: Treatment
masking: None (Open Label)
measure: Number of Participants With Treatment-emergent Adverse Events
time frame: Up to 28 weeks post-first treatment
description: Combined safety of all 3 intrathecal doses of NurOwn® (MSC-NTF cells) Number of participants who experienced Treatment-emergent Adverse Events during the study.
Treatment-emergent Adverse Event is an adverse event that occurs for the first time after initiation of first treatment or if it had occurred prior to initiation first treatment, it worsens in severity after initiation of first treatment.
measure: Number of Participants With 25% or Greater Improvement From Baseline in Time 25 Foot Walk (T25FW) Speed or Nine-Hole Peg Test (9-HPT)
time frame: From Baseline (pre-first treatment) to 28 weeks post-first treatment
description: 25% or greater improvement at 28 weeks from Baseline in Time 25 Foot Walk (T25FW) speed or 9 Hole Peg Test (9-HPT).
The T25FW is a quantitative mobility and leg function performance test based on a timed 25-feet walk. The patient is directed to one end of a clearly marked 25-foot course and is instructed to walk 25 feet as quickly as possible, but safely. T25FW is the average of the two successive trials. Higher values represent better outcomes.
The 9HPT is used to measure upper extremity function in patients with various neurological diagnoses. The participant is asked to pick up the nine pegs, puts them in the nine holes, and, once completed, removes them again as quickly as possible, replacing them into the container. The total time to complete the task is recorded.
Higher values represent worse outcomes.
measure: Number of Participants With 25% or Greater Improvement From Baseline to Week 28 in Timed 25 Foot Walk (T25FW) Speed
time frame: From Baseline (pre-first treatment) to 28 weeks post-first treatment
description: ≥25% improvement in T25FW speed over 28 weeks The T25FW is a quantitative mobility and leg function performance test based on a timed 25-feet walk.
The patient is directed to one end of a clearly marked 25-foot course and is instructed to walk 25 feet as quickly as possible, but safely.
The task is immediately administered again by having the patient walk back the same distance Baseline T25FW is the average of the two successive trials. Higher values represent better outcomes
measure: Number of Participants With 25% or Greater Improvement From Baseline to Week 28 in 9-HPT
time frame: From Baseline (pre-first treatment) to 28 weeks post-first treatment
description: The Nine-Hole Peg Test (9HPT) is used to measure upper extremity function in patients with various neurological diagnoses.
The participant is seated at a table with a small, shallow container holding nine pegs and a wood or plastic block containing nine empty holes. On a start command when a stopwatch is started, the participant picks up the nine pegs one at a time as quickly as possible, puts them in the nine holes, and, once they are in the holes, removes them again as quickly as possible one at a time, replacing them into the shallow container. The total time to complete the task is recorded. Two consecutive trials with the dominant hand are immediately followed by two consecutive trials with the non-dominant hand.
Baseline 9HPT is the average of 2 trials of dominant hand and nondominant hand. The higher values represent a worse outcome.
measure: Number of Participants Who Had >5.5 in Expanded Disability Status Scale (EDSS) at Baseline, With ≥0.5 Points Improvement From Baseline to Week 28
time frame: From Baseline (pre-first treatment) to 28 weeks post-first treatment
description: Expanded Disability Status Scale (EDSS) provides a total score on a scale that ranges from 0 (no disability) through 1 to 10 (death due to MS), in 0.5-point steps. The first levels 1.0 to 4.5 refer to people with a high degree of ambulatory ability and the sequent levels 5.0 to 9.5 refer to the loss of ambulatory ability. The higher score represents the worse outcome.
measure: Number of Participants With ≥10 Points Improvement From Baseline to Week 28 in Multiple Sclerosis Walking Scale (MSWS-12)
time frame: From Baseline (pre-first treatment) to 28 weeks post-first treatment
description: The Multiple Sclerosis Walking Scale (MSWS)-12 is a patient-reported outcome measure of the walking limitations due to MS during the past 2 weeks.
It contains 12 questions that assess the impact of MS on different aspects of walking function and quality.
Total administration time should be approximately 5 minutes. Activities are rated by participant from min. 1 (not at all) to max. 5 (extremely) and summed to calculate a total score using a scale from 0 to 60 (ranging from low to high impact on walking). This score is then divided by 60 and multiplied by 100 to get a score between 0 and 100 A higher score represents a worse outcome.
measure: Number of Participants With ≥8 Letter Improvement From Baseline to Week 28 in LCLA Binocular 2.5% Contrast Level
time frame: From Baseline (pre-first treatment) to 28 weeks post-first treatment
description: The Low contrast letter acuity (LCLA) is a leading outcome measure to assess visual disability in multiple sclerosis (MS) research Total administration time, for a typical MS patient, is approximately 10-15 minutes to complete, when testing each eye individually and binocular vision for two different contrast levels.
The score for each chart is quantified as the number of letters identified correctly with a minimum scrore of 0 letter and a maximum score of 70 letters. The higher score represents the better outcome.
measure: Number of Participants With ≥ 3 Points Improvement From Baseline to Week 28 in Symbol Digit Modalities Test (SDMT) Score
time frame: From Baseline (pre-first treatment) to 28 weeks post-first treatment
description: Symbol Digit Modalities test (SDMT) is a commonly used test to assess psychomotor speed, which measures processing speed as well as motor speed.
It is a paper-pencil measure which requires an individual to substitute digits for abstract symbols using a reference key Scoring involves summing the number of correct substitutions within the 90 second interval (max = 110) Minimum score is 0 and maximum score 110. The higher score represents the better outcome.
measure: Change in Concentration of Vascular Endothelial Growth Factor (VEGF) Neuroprotective Biomarker From Baseline in the Cerebrospinal Fluid (CSF) 16 Weeks Following First NurOwn® Treatment
time frame: From Baseline (pre-first treatment) to 16 weeks post first treatment
description: Change from baseline (pre-first treatment) in the concentration of Vascular endothelial growth factor (VEGF) neuroprotective biomarker in the Cerebrospinal fluid (CSF) at 16 weeks following first NurOwn® treatment The concentration of the biomarker is measured as Picogram per milliliter (pg/ml). A higher concentration of neuroprotective biomarkers suggests a better outcome
measure: Change in Concentration of Hepatocyte Growth Factor (HGF) Neuroprotective Biomarker From Baseline in the Cerebrospinal Fluid (CSF) 16 Weeks Following NurOwn® Treatment
time frame: From Baseline (pre-first treatment) to 16 weeks post first treatment
description: Change from baseline in the concentration of Hepatocyte growth factor (HGF) neuroprotective biomarker in the Cerebrospinal Fluid (CSF) at 16 weeks following the first NurOwn® treatment The concentration of the biomarker is measured as Picogram per milliliter (pg/ml). A higher concentration of neuroprotective biomarkers suggests a better outcome
arm group label: NurOwn (MSC-NTF cells)
arm group type: Experimental
description: Autologous Mesenchymal Stem Cells Secreting Neurotrophic Factors
intervention type: Biological
intervention name: NurOwn (MSC-NTF cells)
description: Autologous Mesenchymal Stem Cells Secreting Neurotrophic Factors
arm group label: NurOwn (MSC-NTF cells)
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Jeffrey Cohen, MD
role: Principal Investigator
affiliation: The Cleveland Clinic
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Multiple Sclerosis
mesh term: Multiple Sclerosis, Chronic Progressive
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 