<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/NCT03828123</url>
  </required_header>
  <id_info>
    <org_study_id>AMSC-ALS-001</org_study_id>
    <nct_id>NCT03828123</nct_id>
  </id_info>
  <brief_title>Autologous Multipotent Mesenchymal Stromal Cells in the Treatment of Amyotrophic Lateral Sclerosis</brief_title>
  <acronym>AMSC-ALS-001</acronym>
  <official_title>A Prospective, Non-randomized, Open Label Study to Assess the Safety and the Efficacy of Autologous Multipotent Mesenchymal Stromal Cells in the Treatment of Amyotrophic Lateral Sclerosis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Bioinova, s.r.o.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Department of Neurology, University Hospital Motol, Prague, Czech Republic</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Bioinova, s.r.o.</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disease that targets&#xD;
      motor neurons. Prognosis is invariably fatal within 3-5 years since manifestation of the&#xD;
      disease. Despite improved understanding of the mechanisms underlying ALS, the treatment&#xD;
      remains essentially only supportive and focused on symptoms relief. Over the past few years,&#xD;
      stem cell research has expanded greatly as a tool for developing new therapies to treat&#xD;
      incurable diseases. Stem cell therapy has been shown as promising in several animal ALS&#xD;
      models and human clinical trials.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Subjects will be assigned to autologous mesenchymal stromal cell (AMSC) treatment according&#xD;
      to inclusion and exclusion criteria (see below) screened four times prior to administration.&#xD;
      Then the subjects will be observed for three consecutive yearsAfter a half year of screening&#xD;
      period, the autologous multipotent mesenchymal stromal cells from bone marrow will be&#xD;
      isolated. The cells will be cultivated for 3 passages (3 - 4 weeks) in order to get&#xD;
      sufficient amount for therapy, cell suspension for intrathecal application will be prepared&#xD;
      and introduced intrathecally through lumbar puncture. Subsequently, all the subjects will be&#xD;
      observed at the range of standard medical care used at these types of interventions.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 2012</start_date>
  <completion_date type="Actual">August 18, 2017</completion_date>
  <primary_completion_date type="Actual">August 18, 2017</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>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Safety: Complications related to the medicinal product application - new neurological deficit and occurrence of other adverse events</measure>
    <time_frame>1 year</time_frame>
    <description>Complications at the site of intrathecal infusion of the medicinal product and no new neurological deficit (meningism, paraplegia, urinary incontinence) not attributed to the natural progression of the ALS disease will be recorded at Visits I, III, IV, V, VI, and IX. Occurrence of other potential adverse events, including headache, respiratory failure, leukocytosis, cervical spine stenosis, cystitis and hyperhydrosis will be evaluated on the severity scale (1=mild, 2=moderate, 3=severe).&#xD;
Brain and spinal cord MRI will be performed at Visits I and IX to exclude treatment-related tumor formation, pathological contrast enhancement or other structural pathology.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Efficacy: Inhibition of the disease progression - ALS functional rating scale</measure>
    <time_frame>18 months</time_frame>
    <description>Inhibition of the disease progression will be recorded by ALS functional rating scale (ALSFRS) at Visits I, III, and VI through X.&#xD;
Measures (all 4-0):&#xD;
speech&#xD;
salivation&#xD;
swallowing&#xD;
handwriting&#xD;
cutting food and handling utensils (with or without gastrostomy)&#xD;
dressing and hygiene&#xD;
turning in bed and adjusting bed clothes&#xD;
walking&#xD;
climbing stairs&#xD;
breathing&#xD;
ALSFRS = SUM (points for all 10 measures)&#xD;
Interpretation:&#xD;
minimum score: 0 maximum score: 40 The higher the score the more function is retained.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Efficacy: Inhibition of the disease progression - Norris scale</measure>
    <time_frame>18 months</time_frame>
    <description>Inhibition of the disease progression will be recorded by Norris scale at Visits I, III, and VI through X.&#xD;
Norris scal has has 22 items examining bulbar, respiratory, trunk, arm, leg, and general domains involving reflexes, fasciculation, and muscle atrophy. The scale also measures emotional lability, fatigability and leg rigidity. The Norris scale has a linear decline during the course of ALS.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Efficacy: Inhibition of the disease progression - Forced vital capacity (FVC)</measure>
    <time_frame>18 months</time_frame>
    <description>FVC (%) will be measured at Visits I, and VI through X.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">26</enrollment>
  <condition>Motor Neuron Disease, Amyotrophic Lateral Sclerosis</condition>
  <arm_group>
    <arm_group_label>Autologous Multipotent MSC</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients with intrathecal administration of Suspension of human autologous MSC 3P in 1.5 ml</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Suspension of human autologous MSC 3P in 1.5 ml</intervention_name>
    <description>Intrathecal application of Autologous Multipotent Mesenchymal Stromal Cells 3P suspension</description>
    <arm_group_label>Autologous Multipotent MSC</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. established diagnosis of definite ALS according to El Escorial criteria&#xD;
&#xD;
          2. riluzole naive or stable dose for at least 2 months,&#xD;
&#xD;
          3. life expectancy more than 2 years&#xD;
&#xD;
          4. patients able to provide written informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. FVC less than 70%&#xD;
&#xD;
          2. in case of primary bulbar paralysis less than 15 points on Norris bulbar scale,&#xD;
&#xD;
          3. less than 15 points on Norris spinal scale,&#xD;
&#xD;
          4. pregnancy, breastfeeding&#xD;
&#xD;
          5. coagulopathy,&#xD;
&#xD;
          6. skin infection at the site of bone marrow aspiration or application of the cell&#xD;
             product,&#xD;
&#xD;
          7. gastrostomy,&#xD;
&#xD;
          8. any significant medical condition that would compromise the safety of the patient&#xD;
             (e.g. recent myocardial infarction, congestive heart failure, renal failure, liver&#xD;
             failure, cancer, systemic infection, recurrent thromboembolic disease .....),&#xD;
&#xD;
          9. alcohol or drug abuse&#xD;
&#xD;
         10. cancer.&#xD;
&#xD;
         11. women of childbearing potential not using effective contraception (established oral&#xD;
             contraception, intrauterine device, ligation of the uterine tube) including proven&#xD;
             contraceptive measures taken by their sexual partners&#xD;
&#xD;
         12. fertile men not using proven contraceptive measures including effective contraception&#xD;
             of their partner (established oral contraception, intrauterine device, ligation of the&#xD;
             uterine tube)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <results_reference>
    <citation>Sykova E, Rychmach P, Drahoradova I, Konradova S, Ruzickova K, Vorisek I, Forostyak S, Homola A, Bojar M. Transplantation of Mesenchymal Stromal Cells in Patients With Amyotrophic Lateral Sclerosis: Results of Phase I/IIa Clinical Trial. Cell Transplant. 2017 Apr 13;26(4):647-658. doi: 10.3727/096368916X693716. Epub 2016 Nov 7.</citation>
    <PMID>27938483</PMID>
  </results_reference>
  <verification_date>February 2019</verification_date>
  <study_first_submitted>July 20, 2017</study_first_submitted>
  <study_first_submitted_qc>February 1, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 4, 2019</study_first_posted>
  <last_update_submitted>February 11, 2019</last_update_submitted>
  <last_update_submitted_qc>February 11, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">February 12, 2019</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>Motor Neuron Disease</mesh_term>
    <mesh_term>Amyotrophic Lateral 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/NCT03828123
org study id: AMSC-ALS-001
nct id: NCT03828123
lead sponsor: 
collaborator: 
has dmc: No
Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disease that targets
      motor neurons. Prognosis is invariably fatal within 3-5 years since manifestation of the
      disease. Despite improved understanding of the mechanisms underlying ALS, the treatment
      remains essentially only supportive and focused on symptoms relief. Over the past few years,
      stem cell research has expanded greatly as a tool for developing new therapies to treat
      incurable diseases. Stem cell therapy has been shown as promising in several animal ALS
      models and human clinical trials.
Subjects will be assigned to autologous mesenchymal stromal cell (AMSC) treatment according
      to inclusion and exclusion criteria (see below) screened four times prior to administration.
      Then the subjects will be observed for three consecutive yearsAfter a half year of screening
      period, the autologous multipotent mesenchymal stromal cells from bone marrow will be
      isolated. The cells will be cultivated for 3 passages (3 - 4 weeks) in order to get
      sufficient amount for therapy, cell suspension for intrathecal application will be prepared
      and introduced intrathecally through lumbar puncture. Subsequently, all the subjects will be
      observed at the range of standard medical care used at these types of interventions.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Safety: Complications related to the medicinal product application - new neurological deficit and occurrence of other adverse events
time frame: 1 year
description: Complications at the site of intrathecal infusion of the medicinal product and no new neurological deficit (meningism, paraplegia, urinary incontinence) not attributed to the natural progression of the ALS disease will be recorded at Visits I, III, IV, V, VI, and IX. Occurrence of other potential adverse events, including headache, respiratory failure, leukocytosis, cervical spine stenosis, cystitis and hyperhydrosis will be evaluated on the severity scale (1=mild, 2=moderate, 3=severe).
Brain and spinal cord MRI will be performed at Visits I and IX to exclude treatment-related tumor formation, pathological contrast enhancement or other structural pathology.
measure: Efficacy: Inhibition of the disease progression - ALS functional rating scale
time frame: 18 months
description: Inhibition of the disease progression will be recorded by ALS functional rating scale (ALSFRS) at Visits I, III, and VI through X.
Measures (all 4-0):
speech
salivation
swallowing
handwriting
cutting food and handling utensils (with or without gastrostomy)
dressing and hygiene
turning in bed and adjusting bed clothes
walking
climbing stairs
breathing
ALSFRS = SUM (points for all 10 measures)
Interpretation:
minimum score: 0 maximum score: 40 The higher the score the more function is retained.
measure: Efficacy: Inhibition of the disease progression - Norris scale
time frame: 18 months
description: Inhibition of the disease progression will be recorded by Norris scale at Visits I, III, and VI through X.
Norris scal has has 22 items examining bulbar, respiratory, trunk, arm, leg, and general domains involving reflexes, fasciculation, and muscle atrophy. The scale also measures emotional lability, fatigability and leg rigidity. The Norris scale has a linear decline during the course of ALS.
measure: Efficacy: Inhibition of the disease progression - Forced vital capacity (FVC)
time frame: 18 months
description: FVC (%) will be measured at Visits I, and VI through X.
arm group label: Autologous Multipotent MSC
arm group type: Experimental
description: Patients with intrathecal administration of Suspension of human autologous MSC 3P in 1.5 ml
intervention type: Biological
intervention name: Suspension of human autologous MSC 3P in 1.5 ml
description: Intrathecal application of Autologous Multipotent Mesenchymal Stromal Cells 3P suspension
arm group label: Autologous Multipotent MSC
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
citation: Sykova E, Rychmach P, Drahoradova I, Konradova S, Ruzickova K, Vorisek I, Forostyak S, Homola A, Bojar M. Transplantation of Mesenchymal Stromal Cells in Patients With Amyotrophic Lateral Sclerosis: Results of Phase I/IIa Clinical Trial. Cell Transplant. 2017 Apr 13;26(4):647-658. doi: 10.3727/096368916X693716. Epub 2016 Nov 7.
PMID: 27938483
responsible party type: Sponsor
mesh term: Motor Neuron Disease
mesh term: Amyotrophic Lateral Sclerosis
mesh term: Sclerosis