<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/NCT03827096</url>
  </required_header>
  <id_info>
    <org_study_id>AMSC-DSD-001</org_study_id>
    <nct_id>NCT03827096</nct_id>
  </id_info>
  <brief_title>Utilization of Autologous Mesenchymal Cells in Posterolateral Spinal Fusion in Degenerative Spine Disease</brief_title>
  <acronym>AMSC-DSD-001</acronym>
  <official_title>Utilization of Autologous Mesenchymal Cells in Posterolateral Spinal Fusion in Degenerative Spine Disease to Assess the Safety and the Efficacy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Bioinova, s.r.o.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Department of Spine Surgery, University Hospital Motol, Prague, Czech Republilc</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Bioinova, s.r.o.</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Subjects in whom a posterolateral fusion surgery has been planned and who meet the inclusion&#xD;
      and exclusion criteria were proposed to receive a single-dose AMSC treatment, in order to&#xD;
      assess its safety and efficacy on posterolateral interbody fusion. After the surgery, the&#xD;
      subjects were followed up as out-patients during 5 study visits for 12 months in total.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Following informed consent collection at the screening visit and verification of all&#xD;
      inclusion and exclusion criteria, eligible patients will undergo the procedure of bone marrow&#xD;
      cell aspiration from iliac crest for the purpose of receiving autologous multipotent&#xD;
      mesenchymal stem cells. The cells will be cultivated for 3 passages (for 3 - 4 weeks) in&#xD;
      order to expand them to sufficient quantity. Suspension of the cultured AMSC will then be&#xD;
      sterilely packed and transported to the surgery site. During the posterolateral spine fusion&#xD;
      operation, 1.5 ml of cell suspension will be mixed with 5 cc of beta-tricalcium phosphate&#xD;
      foam (Vitoss™, Orthovita) and 3.5 ml of patient's blood, and inserted between the transverse&#xD;
      processes of the lumbar spine.&#xD;
&#xD;
      All subjects will be hospitalized and followed up as per standard medical care rules used in&#xD;
      the investigational site hospital for this type of intervention.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Primary endpoint (Safety) has been achieved&#xD;
  </why_stopped>
  <start_date type="Actual">August 27, 2013</start_date>
  <completion_date type="Actual">December 14, 2016</completion_date>
  <primary_completion_date type="Actual">December 14, 2016</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: To demonstrate absence of complications at the site of spinal fusion</measure>
    <time_frame>1 year</time_frame>
    <description>Complications at the site of spinal fusion and other treatment-related adverse events will be recorded in ten patients at Visits I through VII. All adverse events (AEs) will be classified by seriousness, severity and relationship to hAMSC application.&#xD;
All AEs will be collected as symptoms spontaneously reported by the patient, clinically relevant changes and abnormalities observed by the Investigator (clinically significant laboratory measurements confirmed by repeated measurement, results of physical examinations) Intensity&#xD;
The following 3-point rating scale will be used for rating of the intensity of each AE:&#xD;
Mild: Awareness of signs or symptoms, but no disruption of usual activity Moderate: Event sufficient to affect usual activities (disturbing) Severe: Inability to work or perform usual activities (unacceptable)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Efficacy: To assess the quality of life determined by Oswestry Questionnaire.</measure>
    <time_frame>1 year</time_frame>
    <description>The quality of life determined by Oswestry Questionnaire will be recorded in ten patients at Visits II, and IV through VII. The test has 10 sections and maximum score is 50 points; change from the baseline valie will be recorded. The points are then transferred into percentage and interpreted in a standard way when 0-20% means minimal disability while 81-100% means bed-bound condition. Minimum detectable change (90 % confidence) is 10 % (5 points).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Efficacy: To assess the quality of spinal fusion by X-ray imaging</measure>
    <time_frame>1 year</time_frame>
    <description>The quality of spinal fusion will be measured by X-ray imaging at Visits V and VII. Dynamic X-ray of the lumbar spine will be performed at 3 and 12 months following the surgery and hAMSC application to measure the angle of the spine movement in the fusion area. The angle will be recorded in degrees. The movements above 10 degrees will beregarded as &quot;unstable&quot;.&#xD;
The bone fusion morphology will be evaluated based on the following scale:&#xD;
Cyst or pseudo-cyst formation&#xD;
Fusion not visible&#xD;
Pseudo-joint (or false joint) development&#xD;
Low degree of bone fusion&#xD;
High degree of bone fusion</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Efficacy: To assess the quality of spinal fusion measured by computed tomography (CT).</measure>
    <time_frame>1 year</time_frame>
    <description>The quality of spinal fusion will be measured by CT in ten patients at Visits V and VII.&#xD;
The density will of the fusion will be expressed as % on a linear scale between two standardized measuring points: soft tissue= 0%, vertebral arch= 100%.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">10</enrollment>
  <condition>Degenerative Disc Disease</condition>
  <arm_group>
    <arm_group_label>Human AMSC (passage 3) 3P in 1.5 mL</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patient receiving the investigational medicinal product - suspension of human autologous MSC 3P in 1.5 mL</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Suspension of human autologous MSC 3P in 1.5 ml</intervention_name>
    <description>During the posterolateral spine fusion operation, 1.5 ml of cell suspension was mixed with 5cc of beta-tricalcium phosphate foam and 3.5 ml of patient's blood, and inserted between the right transverse processes of the lumbar spine.</description>
    <arm_group_label>Human AMSC (passage 3) 3P in 1.5 mL</arm_group_label>
    <other_name>hAMSC</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. established diagnosis of spinal degenerative disease indicated for lumbar spine&#xD;
             surgery,&#xD;
&#xD;
          2. patients indicated for fusion therapy,&#xD;
&#xD;
          3. patients between 18-55 years, both sexes,&#xD;
&#xD;
          4. patients able to provide written informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. previous lumbar spine surgery in the same segment of the spine, in order to achieve&#xD;
             vertebral fusion,&#xD;
&#xD;
          2. osteoporosis,&#xD;
&#xD;
          3. diabetes mellitus,&#xD;
&#xD;
          4. pregnancy or breastfeeding,&#xD;
&#xD;
          5. 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;
          6. fertile men not using proven contraceptive measures including effective contraception&#xD;
             method in their partner (established oral contraception, intrauterine device, ligation&#xD;
             of the uterine tube),&#xD;
&#xD;
          7. coagulopathy,&#xD;
&#xD;
          8. malnutrition, primary biliary cirrhosis,&#xD;
&#xD;
          9. skin infection at the site of bone marrow aspiration or at the site of spinal fusion,&#xD;
&#xD;
         10. gastrostomy,&#xD;
&#xD;
         11. 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, systemic infection, recurrent thromboembolic disease .....),&#xD;
&#xD;
         12. alcohol or drug abuse,&#xD;
&#xD;
         13. cancer (compulsory clinical oncological screening),&#xD;
&#xD;
         14. ongoing or recent (last 3 months) systemic corticosteroid or immunosuppressive&#xD;
             therapy.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>55 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <verification_date>January 2020</verification_date>
  <study_first_submitted>January 14, 2019</study_first_submitted>
  <study_first_submitted_qc>January 31, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 1, 2019</study_first_posted>
  <last_update_submitted>January 14, 2020</last_update_submitted>
  <last_update_submitted_qc>January 14, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">January 18, 2020</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>Intervertebral Disc Degeneration</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>The data will be published</ipd_description>
  </patient_data>
  <!-- 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/NCT03827096
org study id: AMSC-DSD-001
nct id: NCT03827096
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Subjects in whom a posterolateral fusion surgery has been planned and who meet the inclusion
      and exclusion criteria were proposed to receive a single-dose AMSC treatment, in order to
      assess its safety and efficacy on posterolateral interbody fusion. After the surgery, the
      subjects were followed up as out-patients during 5 study visits for 12 months in total.
Following informed consent collection at the screening visit and verification of all
      inclusion and exclusion criteria, eligible patients will undergo the procedure of bone marrow
      cell aspiration from iliac crest for the purpose of receiving autologous multipotent
      mesenchymal stem cells. The cells will be cultivated for 3 passages (for 3 - 4 weeks) in
      order to expand them to sufficient quantity. Suspension of the cultured AMSC will then be
      sterilely packed and transported to the surgery site. During the posterolateral spine fusion
      operation, 1.5 ml of cell suspension will be mixed with 5 cc of beta-tricalcium phosphate
      foam (Vitoss™, Orthovita) and 3.5 ml of patient's blood, and inserted between the transverse
      processes of the lumbar spine.

      All subjects will be hospitalized and followed up as per standard medical care rules used in
      the investigational site hospital for this type of intervention.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Safety: To demonstrate absence of complications at the site of spinal fusion
time frame: 1 year
description: Complications at the site of spinal fusion and other treatment-related adverse events will be recorded in ten patients at Visits I through VII. All adverse events (AEs) will be classified by seriousness, severity and relationship to hAMSC application.
All AEs will be collected as symptoms spontaneously reported by the patient, clinically relevant changes and abnormalities observed by the Investigator (clinically significant laboratory measurements confirmed by repeated measurement, results of physical examinations) Intensity
The following 3-point rating scale will be used for rating of the intensity of each AE:
Mild: Awareness of signs or symptoms, but no disruption of usual activity Moderate: Event sufficient to affect usual activities (disturbing) Severe: Inability to work or perform usual activities (unacceptable)
measure: Efficacy: To assess the quality of life determined by Oswestry Questionnaire.
time frame: 1 year
description: The quality of life determined by Oswestry Questionnaire will be recorded in ten patients at Visits II, and IV through VII. The test has 10 sections and maximum score is 50 points; change from the baseline valie will be recorded. The points are then transferred into percentage and interpreted in a standard way when 0-20% means minimal disability while 81-100% means bed-bound condition. Minimum detectable change (90 % confidence) is 10 % (5 points).
measure: Efficacy: To assess the quality of spinal fusion by X-ray imaging
time frame: 1 year
description: The quality of spinal fusion will be measured by X-ray imaging at Visits V and VII. Dynamic X-ray of the lumbar spine will be performed at 3 and 12 months following the surgery and hAMSC application to measure the angle of the spine movement in the fusion area. The angle will be recorded in degrees. The movements above 10 degrees will beregarded as "unstable".
The bone fusion morphology will be evaluated based on the following scale:
Cyst or pseudo-cyst formation
Fusion not visible
Pseudo-joint (or false joint) development
Low degree of bone fusion
High degree of bone fusion
measure: Efficacy: To assess the quality of spinal fusion measured by computed tomography (CT).
time frame: 1 year
description: The quality of spinal fusion will be measured by CT in ten patients at Visits V and VII.
The density will of the fusion will be expressed as % on a linear scale between two standardized measuring points: soft tissue= 0%, vertebral arch= 100%.
arm group label: Human AMSC (passage 3) 3P in 1.5 mL
arm group type: Experimental
description: Patient receiving the investigational medicinal product - suspension of human autologous MSC 3P in 1.5 mL
intervention type: Drug
intervention name: Suspension of human autologous MSC 3P in 1.5 ml
description: During the posterolateral spine fusion operation, 1.5 ml of cell suspension was mixed with 5cc of beta-tricalcium phosphate foam and 3.5 ml of patient's blood, and inserted between the right transverse processes of the lumbar spine.
arm group label: Human AMSC (passage 3) 3P in 1.5 mL
other name: hAMSC
criteria: 
gender: All
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: No
responsible party type: Sponsor
mesh term: Intervertebral Disc Degeneration
sharing ipd: No
ipd description: The data will be published