<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/NCT01730547</url>
  </required_header>
  <id_info>
    <org_study_id>MSC-MS</org_study_id>
    <nct_id>NCT01730547</nct_id>
  </id_info>
  <brief_title>Mesenchymal Stem Cells for Multiple Sclerosis</brief_title>
  <official_title>Phase 1/2 Clinical Trial With Autologous Mesenchymal Stem Cells for the Therapy of Multiple Sclerosis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Karolinska Institutet</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Karolinska Institutet</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The aim of the study is to evaluate the safety and efficacy of autologous mesenchymal stromal&#xD;
      cells as treatment for Multiple Sclerosis.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      MESEMS is a randomised phase 2 trial done at 15 sites in nine countries. Patients (aged 18-50&#xD;
      years) with active relapsing-remitting or progressive multiple sclerosis were included if&#xD;
      they had a disease duration of 2-15 years since onset of multiple sclerosis and an Expanded&#xD;
      Disability Status Scale score of 2·5-6·5. Patients were randomly assigned (1:1), according to&#xD;
      a crossover design, to receive a single intravenous dose of autologous bone marrow-derived&#xD;
      MSCs followed by placebo at week 24, or to receive placebo followed by autologous MSCs at&#xD;
      week 24, with a follow-up visit at week 48. Primary objectives were to test safety and&#xD;
      activity of MSC treatment. The primary safety endpoint was to assess the number and severity&#xD;
      of adverse events within each treatment arm. The primary efficacy endpoint was the number of&#xD;
      gadolinium-enhancing lesions (GELs) counted over week 4, 12, and 24 compared between&#xD;
      treatment groups. The primary efficacy endpoint was assessed in the full analyis set, after&#xD;
      all participants completed the week 24 visit. Efficacy endpoints were evaluated using a&#xD;
      predefined statistical testing procedure. Safety was monitored throughout the study by&#xD;
      recording vital signs and adverse events at each visit.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>February 2013</start_date>
  <completion_date type="Actual">November 20, 2021</completion_date>
  <primary_completion_date type="Actual">May 9, 2019</primary_completion_date>
  <phase>Phase 1/Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>To assess the safety of IV therapy with autologous Mesenchymal Stem Cells (MSCs) in MS patients.</measure>
    <time_frame>48 weeks</time_frame>
    <description>The primary objective of the study is to assess the safety of IV therapy with autologous MSCs in MS. Number of participants with adverse events will be documented at week 0,4,8,12,16,20,24,28,32,36,40,44,48 post treatment. Co-primary objective of the study is to evaluate the activity of autologous MSCS in MS patients, in terms of reduction as compared to placebo in the total number of contrast-enhancing lesions (GEL) at MRI acquired on conventional 1,5 T MRI scans over 24 weeks.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>To gather preliminary information of the efficacy of the experimental treatment in terms of combined MRI activity and clinical efficacy (incidence of relapses and disability progression).</measure>
    <time_frame>48 weeks</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">2</enrollment>
  <condition>Multiple Sclerosis</condition>
  <arm_group>
    <arm_group_label>Early treatment with mesenchymal stem cells</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patients receive a single intravenous dose of autologous bone marrow-derived MSCs followed by placebo at week 24. Fommow up at week 48</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Delayed treatment with mesenchymal stem cells</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patients receive placebo for 24 weeks followed by autologous MSCs at week 24, with a follow-up visit at week 48.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Autologous mesenchymal stem cells</intervention_name>
    <arm_group_label>Delayed treatment with mesenchymal stem cells</arm_group_label>
    <arm_group_label>Early treatment with mesenchymal stem cells</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Diagnosis of MS&#xD;
&#xD;
             a. Relapsing remitting MS (RRMS) not responding to at least a year of attempted&#xD;
             therapy with one or more of the approved therapies (beta-interferon, glatiramer&#xD;
             acetate, natalizumab, mitoxantrone, fingolimod) as evidenced by one or more of the&#xD;
             following: i. ≥1 clinically documented relapse in past 12 months ii. ≥2 clinically&#xD;
             documented relapses in last 24 months iii. ≥1 GEL at MRI performed within the last 12&#xD;
             months&#xD;
&#xD;
             b. Secondary progressive MS (SPMS) not responding to at least a year of attempted&#xD;
             therapy with one or more of the approved therapies (beta-interferon, glatiramer&#xD;
             acetate, natalizumab, mitoxantrone, fingolimod) as evidenced by both: i. an increase&#xD;
             of ≥1 EDSS point (if at randomization EDSS ≤ 5.0) or 0.5 EDSS point (if at&#xD;
             randomization EDSS ≥ 5.5) in the last 12 months ii. ≥1 clinically documented relapse&#xD;
             or ≥ 1 GEL at MRI within the last twelve months.&#xD;
&#xD;
             c. Primary progressive MS (PPMS) patients with all the following features: i. an&#xD;
             increase of ≥1 EDSS point (if at randomization EDSS ≤ 5.0) or 0.5 EDSS point (if at&#xD;
             randomization EDSS ≥5.5), in the last twelve months ii. ≥ 1 GEL at MRI performed&#xD;
             within the last 12 months iii. positive cerebrospinal fluid (CSF) (oligoclonal&#xD;
             banding)&#xD;
&#xD;
          2. Age 18 to 50 years&#xD;
&#xD;
          3. Disease duration 2 to 10 years (included)&#xD;
&#xD;
          4. EDSS 3.0 to 6.5&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. RRMS not fulfilling inclusion criteria&#xD;
&#xD;
          2. SPMS not fulfilling inclusion criteria&#xD;
&#xD;
          3. PPMS not fulfilling inclusion criteria&#xD;
&#xD;
          4. Any active or chronic infection including infection with HIV1-2 or chronic Hepatitis B&#xD;
             or Hepatitis C&#xD;
&#xD;
          5. Treatment with any immunosuppressive therapy, including natalizumab and fingolimod,&#xD;
             within the 3 months prior to randomization&#xD;
&#xD;
          6. Treatment with interferon-beta or glatiramer acetate within the 30 days prior to&#xD;
             randomization&#xD;
&#xD;
          7. Treatment with corticosteroids within the 30 days prior to randomization&#xD;
&#xD;
          8. Relapse occurred during the 60 days prior to randomization&#xD;
&#xD;
          9. Previous history of a malignancy other than basal cell carcinoma of the skin or&#xD;
             carcinoma in situ that has been in remission for more than one year&#xD;
&#xD;
         10. Severely limited life expectancy by another co-morbid illness&#xD;
&#xD;
         11. History of previous diagnosis of myelodysplasia or previous hematologic disease or&#xD;
             current clinically relevant abnormalities of white blood cell counts&#xD;
&#xD;
         12. Pregnancy or risk or pregnancy (this includes patients that are unwilling to practice&#xD;
             active contraception during the duration of the study)&#xD;
&#xD;
         13. eGFR &lt; 60 mL/min/1.73m2 or known renal failure or inability to undergo MRI&#xD;
             examination.&#xD;
&#xD;
         14. Inability to give written informed consent in accordance with research ethics board&#xD;
             guidelines&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>50 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Karolinska Institute, Karolinska University Hospital Solna</name>
      <address>
        <city>Stockholm</city>
        <zip>171 76</zip>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Sweden</country>
  </location_countries>
  <verification_date>May 2023</verification_date>
  <study_first_submitted>November 9, 2012</study_first_submitted>
  <study_first_submitted_qc>November 20, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 21, 2012</study_first_posted>
  <last_update_submitted>May 30, 2023</last_update_submitted>
  <last_update_submitted_qc>May 30, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">June 1, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Karolinska Institutet</investigator_affiliation>
    <investigator_full_name>Lou Brundin</investigator_full_name>
    <investigator_title>MD, PhD</investigator_title>
  </responsible_party>
  <keyword>Mesenchymal stem cells</keyword>
  <keyword>Multiple Sclerosis</keyword>
  <keyword>Autoimmune diseases</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Multiple Sclerosis</mesh_term>
    <mesh_term>Sclerosis</mesh_term>
  </condition_browse>
  <!-- Results have not yet been posted for this study                                          -->
</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/NCT01730547
org study id: MSC-MS
nct id: NCT01730547
lead sponsor: 
has dmc: Yes
The aim of the study is to evaluate the safety and efficacy of autologous mesenchymal stromal
      cells as treatment for Multiple Sclerosis.
MESEMS is a randomised phase 2 trial done at 15 sites in nine countries. Patients (aged 18-50
      years) with active relapsing-remitting or progressive multiple sclerosis were included if
      they had a disease duration of 2-15 years since onset of multiple sclerosis and an Expanded
      Disability Status Scale score of 2·5-6·5. Patients were randomly assigned (1:1), according to
      a crossover design, to receive a single intravenous dose of autologous bone marrow-derived
      MSCs followed by placebo at week 24, or to receive placebo followed by autologous MSCs at
      week 24, with a follow-up visit at week 48. Primary objectives were to test safety and
      activity of MSC treatment. The primary safety endpoint was to assess the number and severity
      of adverse events within each treatment arm. The primary efficacy endpoint was the number of
      gadolinium-enhancing lesions (GELs) counted over week 4, 12, and 24 compared between
      treatment groups. The primary efficacy endpoint was assessed in the full analyis set, after
      all participants completed the week 24 visit. Efficacy endpoints were evaluated using a
      predefined statistical testing procedure. Safety was monitored throughout the study by
      recording vital signs and adverse events at each visit.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: To assess the safety of IV therapy with autologous Mesenchymal Stem Cells (MSCs) in MS patients.
time frame: 48 weeks
description: The primary objective of the study is to assess the safety of IV therapy with autologous MSCs in MS. Number of participants with adverse events will be documented at week 0,4,8,12,16,20,24,28,32,36,40,44,48 post treatment. Co-primary objective of the study is to evaluate the activity of autologous MSCS in MS patients, in terms of reduction as compared to placebo in the total number of contrast-enhancing lesions (GEL) at MRI acquired on conventional 1,5 T MRI scans over 24 weeks.
measure: To gather preliminary information of the efficacy of the experimental treatment in terms of combined MRI activity and clinical efficacy (incidence of relapses and disability progression).
time frame: 48 weeks
arm group label: Early treatment with mesenchymal stem cells
arm group type: Active Comparator
description: Patients receive a single intravenous dose of autologous bone marrow-derived MSCs followed by placebo at week 24. Fommow up at week 48
arm group label: Delayed treatment with mesenchymal stem cells
arm group type: Active Comparator
description: Patients receive placebo for 24 weeks followed by autologous MSCs at week 24, with a follow-up visit at week 48.
intervention type: Biological
intervention name: Autologous mesenchymal stem cells
arm group label: Delayed treatment with mesenchymal stem cells
arm group label: Early treatment with mesenchymal stem cells
criteria: 
gender: All
minimum age: 18 Years
maximum age: 50 Years
healthy volunteers: No
facility: 
country: Sweden
responsible party type: Principal Investigator
investigator affiliation: Karolinska Institutet
investigator full name: Lou Brundin
investigator title: MD, PhD
mesh term: Multiple Sclerosis
mesh term: Sclerosis