<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/NCT04453111</url>
  </required_header>
  <id_info>
    <org_study_id>#7/09.26.2018</org_study_id>
    <nct_id>NCT04453111</nct_id>
  </id_info>
  <brief_title>Efficacy of Bone-marrow-derived and Placenta-derived Multipotent Mesenchymal Stem / Stromal Cells for Osteoarthritis</brief_title>
  <official_title>Efficacy of Bone-marrow-derived and Placenta-derived Multipotent Mesenchymal Stem / Stromal Cells for Osteoarthritis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Institute of Cell Therapy</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>The Institute of Traumatology and Orthopedics of NAMS of Ukraine</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Kyiv City Clinical Hospital № 6</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Institute of Cell Therapy</source>
  <oversight_info>
    <has_dmc>Yes</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>
      To define the clinical effects of intra-articular transplantation of bone-marrow-derived&#xD;
      (BM-MMSCs) and placenta-derived multipotent mesenchymal stem / stromal cells (P-MMSCs) for&#xD;
      knee osteoarthritis.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Multipotent mesenchymal stem / stromal cells (MMSCs) of different origin are the novel&#xD;
      therapeutic agents that can slow down cartilage degeneration, improve reparation and&#xD;
      ultimately prevent joint prosthetics. MSCs are capable to direct differentiation into&#xD;
      chondrocytes, produce cytokines and growth factors with immunomodulatory and&#xD;
      anti-inflammatory effects, stimulate angiogenesis, as well as induce chemotaxis of endogenous&#xD;
      progenitors. Bone marrow-derived and placenta-derived MMSCs can be considered the most&#xD;
      promising source for cell therapy of joints disorders according to availability, safety and&#xD;
      expected therapeutic efficacy.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">January 2, 2020</start_date>
  <completion_date type="Anticipated">October 2021</completion_date>
  <primary_completion_date type="Anticipated">August 2021</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>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>Experimental: HA + stem cells therapy Experimental Group 1: three intra-articular injection of allogeneic P-MMSCs with up to 2•107cells (target dose up to 6•107 cells) with 20 mg Hyaluronic Acid at 4-weeks intervals - 15 patients Experimental Group 2: three intra-articular injection of autologous BM-MMSCs up to 2•107cells (target dose up to 6•107 cells) with 20 mg Hyaluronic Acid at 4-weeks intervals - 15 patients Control Group: three intra-articular injection of 20 mg Hyaluronic Acid, no cell therapy - 15 patients</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of participants with adverse events and changes in physical examinations, vital signs and the results of clinical lab tests.</measure>
    <time_frame>12 months</time_frame>
    <description>Treatment-related adverse events</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Physical function improvement measured by Western Ontario and McMaster Universities Arthritis Index (WOMAC).</measure>
    <time_frame>12 months.</time_frame>
    <description>Change in joint function from baseline WOMAC assessment. The WOMAC used a scoring scale of 0-4 (lower scores indicate lower levels of symptoms or physical disability). The higher the score, the higher the amount of pain, stiffness, and a high level of functional limitations.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Radiographic evidence. Whole-Organ Magnetic Resonance Imaging Score (WORMS)</measure>
    <time_frame>12 months</time_frame>
    <description>Change in cartilage thickness of the knee using MRI</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of Life (QOL) assessment</measure>
    <time_frame>12 months</time_frame>
    <description>Change in scores on the QOL</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The Visual Analog Scale (VAS) assessment</measure>
    <time_frame>12 months</time_frame>
    <description>VAS - measure of pain intensity. The scale is most commonly anchored by &quot;no pain &quot; (score of 0) and &quot;worst imaginable pain&quot; (score of 10).</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Anticipated">45</enrollment>
  <condition>Knee Osteoarthritis</condition>
  <arm_group>
    <arm_group_label>Hyaluronic Acid (HA) + P-MMSCs</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Experimental Group 1: Three intra-articular injection of allogeneic P-MMSCs up to 2•107cells (target dose up to 6•107 cells) with 20 mg Hyaluronic Acid at 4-weeks intervals - 15 patients</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Hyaluronic Acid (HA) + BM-MMSCs</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Experimental Group 2: Three intra-articular injection of autologous BM-MMSCs up to 2•107cells (target dose up to 6•107 cells) with 20 mg Hyaluronic Acid at 4-weeks intervals - 15 patients</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Hyaluronic Acid (HA)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Three intra-articular injection of 20 mg Hyaluronic Acid - 15 patients</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Placenta-derived MMSCs</intervention_name>
    <description>Cryopreserved placenta-derived multipotent mesenchymal stem / stromal cells</description>
    <arm_group_label>Hyaluronic Acid (HA) + P-MMSCs</arm_group_label>
    <other_name>P-MMSCs</other_name>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Bone marrow-derived MMSCs</intervention_name>
    <description>Cryopreserved bone marrow-derived multipotent mesenchymal stem / stromal cells</description>
    <arm_group_label>Hyaluronic Acid (HA) + BM-MMSCs</arm_group_label>
    <other_name>BM-MMSCs</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Hyalgan 20 mg in 2 ML Prefilled Syringe</intervention_name>
    <description>Hyaluronic Acid 20 mg</description>
    <arm_group_label>Hyaluronic Acid (HA)</arm_group_label>
    <arm_group_label>Hyaluronic Acid (HA) + BM-MMSCs</arm_group_label>
    <arm_group_label>Hyaluronic Acid (HA) + P-MMSCs</arm_group_label>
    <other_name>HA</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Clinical diagnosis of knee osteoarthritis.&#xD;
&#xD;
          2. Age: 18 to 75 years old.&#xD;
&#xD;
          3. Kellgren-Lawrence Grade 2 or 3 according to X-ray imaging.&#xD;
&#xD;
          4. Knee pain.&#xD;
&#xD;
          5. Written informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Age &lt;18 or &gt;75 years of age by time of infusion.&#xD;
&#xD;
          2. Participation in an on-going investigational therapeutic or device trial 30 days of&#xD;
             consent.&#xD;
&#xD;
          3. Rheumatoid arthritis.&#xD;
&#xD;
          4. Psoriatic arthritis.&#xD;
&#xD;
          5. Juvenile idiopathic arthritis.&#xD;
&#xD;
          6. Gout.&#xD;
&#xD;
          7. Infectious arthritis.&#xD;
&#xD;
          8. Osteomyelitis.&#xD;
&#xD;
          9. Osteonecrosis.&#xD;
&#xD;
         10. Inflammatory arthritis.&#xD;
&#xD;
         11. Chondropathy.&#xD;
&#xD;
         12. Joint contracture.&#xD;
&#xD;
         13. Arthroplasty.&#xD;
&#xD;
         14. Arthroscopy within 6 months prior to study entry.&#xD;
&#xD;
         15. Intra-articular injection within 3 months prior to study entry.&#xD;
&#xD;
         16. Hormone intake.&#xD;
&#xD;
         17. Antiaggregants and anticoagulants intake.&#xD;
&#xD;
         18. Immunosuppressants intake.&#xD;
&#xD;
         19. Allergy to hyaluronic acid.&#xD;
&#xD;
         20. History of organ or cell transplantation.&#xD;
&#xD;
         21. Hematologic abnormality evidenced by hematocrit &lt; 25%, white blood cell &lt; 2,500/ul or&#xD;
             platelet count &lt; 100,000/ul.&#xD;
&#xD;
         22. Active infection.&#xD;
&#xD;
         23. Positive for HIV antigen.&#xD;
&#xD;
         24. History of hepatitis B, hepatitis C.&#xD;
&#xD;
         25. History of malignancy in the last 5 years prior to study entry.&#xD;
&#xD;
         26. Active tumors.&#xD;
&#xD;
         27. History of myocardial infarction.&#xD;
&#xD;
         28. History of stroke.&#xD;
&#xD;
         29. Renal failure with chronic hemodialysis.&#xD;
&#xD;
         30. Liver Cirrhosis (ICGR 15 &gt;30%).&#xD;
&#xD;
         31. Chromosomal abnormality.&#xD;
&#xD;
         32. Peripheral nervous system disorders.&#xD;
&#xD;
         33. Cognitive or language barriers that prohibit obtaining informed consent or any study&#xD;
             elements.&#xD;
&#xD;
         34. History of drug abuse or alcohol abuse, or documented medical, occupational, or legal&#xD;
             problems arising from the use of alcohol or drugs within the past 24 months.&#xD;
&#xD;
         35. Pregnant/nursing women or women of child-bearing potential.&#xD;
&#xD;
         36. Other condition that limits lifespan to &lt; 1 year.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Peter Nemtinov, MD</last_name>
    <role>Study Director</role>
    <affiliation>Institute of Cell Therapy</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Peter Nemtinov, MD</last_name>
    <phone>+380442079207</phone>
    <email>nemtinov@stemcellclinic.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Vitalii Kyryk, MD, PhD</last_name>
    <phone>+380442079207</phone>
    <email>kyryk@stemcellclinic.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Institute of Cell Therapy</name>
      <address>
        <city>Kyiv</city>
        <zip>04073</zip>
        <country>Ukraine</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Peter Nemtinov, MD</last_name>
      <phone>+380442079207</phone>
      <email>nemtinov@stemcellclinic.com</email>
    </contact>
    <contact_backup>
      <last_name>Vitalii Kyryk, PhD</last_name>
      <phone>+380442079207</phone>
      <email>kyryk@stemcellclinic.com</email>
    </contact_backup>
    <investigator>
      <last_name>Evgen Goliuk, MD, PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Roman Birsa, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Ukraine</country>
  </location_countries>
  <verification_date>July 2020</verification_date>
  <study_first_submitted>June 15, 2020</study_first_submitted>
  <study_first_submitted_qc>June 26, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 1, 2020</study_first_posted>
  <last_update_submitted>July 1, 2020</last_update_submitted>
  <last_update_submitted_qc>July 1, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">July 7, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>BM-MMSCs;</keyword>
  <keyword>P-MMSCs;</keyword>
  <keyword>Hyaluronic Acid</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Osteoarthritis</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hyaluronic Acid</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </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/NCT04453111
org study id: #7/09.26.2018
nct id: NCT04453111
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
To define the clinical effects of intra-articular transplantation of bone-marrow-derived
      (BM-MMSCs) and placenta-derived multipotent mesenchymal stem / stromal cells (P-MMSCs) for
      knee osteoarthritis.
Multipotent mesenchymal stem / stromal cells (MMSCs) of different origin are the novel
      therapeutic agents that can slow down cartilage degeneration, improve reparation and
      ultimately prevent joint prosthetics. MSCs are capable to direct differentiation into
      chondrocytes, produce cytokines and growth factors with immunomodulatory and
      anti-inflammatory effects, stimulate angiogenesis, as well as induce chemotaxis of endogenous
      progenitors. Bone marrow-derived and placenta-derived MMSCs can be considered the most
      promising source for cell therapy of joints disorders according to availability, safety and
      expected therapeutic efficacy.
allocation: Non-Randomized
intervention model: Parallel Assignment
intervention model description: Experimental: HA + stem cells therapy Experimental Group 1: three intra-articular injection of allogeneic P-MMSCs with up to 2•107cells (target dose up to 6•107 cells) with 20 mg Hyaluronic Acid at 4-weeks intervals - 15 patients Experimental Group 2: three intra-articular injection of autologous BM-MMSCs up to 2•107cells (target dose up to 6•107 cells) with 20 mg Hyaluronic Acid at 4-weeks intervals - 15 patients Control Group: three intra-articular injection of 20 mg Hyaluronic Acid, no cell therapy - 15 patients
primary purpose: Treatment
masking: None (Open Label)
measure: Number of participants with adverse events and changes in physical examinations, vital signs and the results of clinical lab tests.
time frame: 12 months
description: Treatment-related adverse events
measure: Physical function improvement measured by Western Ontario and McMaster Universities Arthritis Index (WOMAC).
time frame: 12 months.
description: Change in joint function from baseline WOMAC assessment. The WOMAC used a scoring scale of 0-4 (lower scores indicate lower levels of symptoms or physical disability). The higher the score, the higher the amount of pain, stiffness, and a high level of functional limitations.
measure: Radiographic evidence. Whole-Organ Magnetic Resonance Imaging Score (WORMS)
time frame: 12 months
description: Change in cartilage thickness of the knee using MRI
measure: Quality of Life (QOL) assessment
time frame: 12 months
description: Change in scores on the QOL
measure: The Visual Analog Scale (VAS) assessment
time frame: 12 months
description: VAS - measure of pain intensity. The scale is most commonly anchored by "no pain " (score of 0) and "worst imaginable pain" (score of 10).
arm group label: Hyaluronic Acid (HA) + P-MMSCs
arm group type: Experimental
description: Experimental Group 1: Three intra-articular injection of allogeneic P-MMSCs up to 2•107cells (target dose up to 6•107 cells) with 20 mg Hyaluronic Acid at 4-weeks intervals - 15 patients
arm group label: Hyaluronic Acid (HA) + BM-MMSCs
arm group type: Experimental
description: Experimental Group 2: Three intra-articular injection of autologous BM-MMSCs up to 2•107cells (target dose up to 6•107 cells) with 20 mg Hyaluronic Acid at 4-weeks intervals - 15 patients
arm group label: Hyaluronic Acid (HA)
arm group type: Active Comparator
description: Three intra-articular injection of 20 mg Hyaluronic Acid - 15 patients
intervention type: Biological
intervention name: Placenta-derived MMSCs
description: Cryopreserved placenta-derived multipotent mesenchymal stem / stromal cells
arm group label: Hyaluronic Acid (HA) + P-MMSCs
other name: P-MMSCs
intervention type: Biological
intervention name: Bone marrow-derived MMSCs
description: Cryopreserved bone marrow-derived multipotent mesenchymal stem / stromal cells
arm group label: Hyaluronic Acid (HA) + BM-MMSCs
other name: BM-MMSCs
intervention type: Drug
intervention name: Hyalgan 20 mg in 2 ML Prefilled Syringe
description: Hyaluronic Acid 20 mg
arm group label: Hyaluronic Acid (HA)
arm group label: Hyaluronic Acid (HA) + BM-MMSCs
arm group label: Hyaluronic Acid (HA) + P-MMSCs
other name: HA
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Peter Nemtinov, MD
role: Study Director
affiliation: Institute of Cell Therapy
last name: Peter Nemtinov, MD
phone: +380442079207
email: nemtinov@stemcellclinic.com
last name: Vitalii Kyryk, MD, PhD
phone: +380442079207
email: kyryk@stemcellclinic.com
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
investigator: 
country: Ukraine
responsible party type: Sponsor
mesh term: Osteoarthritis
mesh term: Hyaluronic Acid
sharing ipd: No