<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/NCT03000712</url>
  </required_header>
  <id_info>
    <org_study_id>HTO-MSCs</org_study_id>
    <nct_id>NCT03000712</nct_id>
  </id_info>
  <brief_title>Investigator Initiated Trial to Evaluate the Efficacy and Safety of Intra-articular Injection of ADMSC Comared to Negative Control After High Tibial Osteotomy in the Osteoarthritis Patients.</brief_title>
  <official_title>Single-center, Randomized, Open Label, Negative-controlled Investigator Initiated Trial to Evaluate the Efficacy and Safety of Intra-articular Injection of ADMSC(Autologous Adipose Tissue Derived Mesenchymal Stem Cells) After High Tibial Osteotomy Compared to Negative Control in the Osteoarthritis Patients.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>R-Bio</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>R-Bio</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to evaluate the efficacy and safety of intra-articular injection&#xD;
      of autologous adipose tissue derived mesenchymal stem cells compared after high tibial&#xD;
      osteotomy to negative control in the osteoarthritis patients&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      In this clinical trial, the investigational product is administered intra-articularly at 1&#xD;
      week after high tibial osteotomy in a patient with degenerative arthritis of the medial side.&#xD;
&#xD;
      The investigational product is autologous adipose-derived mesenchymal stem cells. As it does&#xD;
      not use allogenic tissue and is incubated without additional genetic modification or&#xD;
      mechanical and chemical modification through differentiation, it is classified as 'autologous&#xD;
      cell therapy' and is completely free of immunologic rejection.&#xD;
&#xD;
      It primarily aims to regenerate cartilage, to improve pain and joint function. The&#xD;
      intra-articular injection of the investigational product is expected to stimulate the&#xD;
      regeneration and growth of cartilage, and to innovatively improve pain and joint function&#xD;
      with cartilage regeneration compared to high tibial osteotomy alone.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 2, 2016</start_date>
  <completion_date type="Actual">May 22, 2020</completion_date>
  <primary_completion_date type="Actual">May 22, 2020</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>MRI scan</measure>
    <time_frame>24 months</time_frame>
    <description>MRI perform to measure cartilage defect size change from baseline up to 27 weeks</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>MRI scan</measure>
    <time_frame>15, 27 weeks, 18, 24 months</time_frame>
    <description>MRI perform to measure cartilage defect size change from baseline up to 15 weeks</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>WOMAC score</measure>
    <time_frame>15, 27 weeks, 18, 24 months</time_frame>
    <description>Change in WOMAC Total score from baseline up to 15, 27 weeks</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>WOMAC sub-scale</measure>
    <time_frame>15, 27 weeks, 18, 24 months</time_frame>
    <description>Change in WOMAC sub-scale from baseline up to 15, 27 weeks</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Kellgren &amp; Lawrence grade</measure>
    <time_frame>15, 27 weeks, 18, 24 months</time_frame>
    <description>Change in Kellgren &amp; Lawrence grade from baseline up to 15, 27 weeks</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>EQ5D</measure>
    <time_frame>15, 27 weeks, 18, 24 months</time_frame>
    <description>Change in the score of EQ-5D from baseline up to 15, 27 weeks</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>ROM</measure>
    <time_frame>15, 27 weeks, 18, 24 months</time_frame>
    <description>change from baseline in knee flexion Range of Motion(ROM) at 15,27 weeks by physical examination</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>KOOS (Knee Injury &amp; Osteoarthritis Outcome Score)</measure>
    <time_frame>15, 27 weeks, 18, 24 months</time_frame>
    <description>Symptoms, pain and functionality of the knee joint will be evaluated via the Knee Injury and Osteoarthritis Outcome Score (KOOS)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PGIC(Patient Global Impression of Change)</measure>
    <time_frame>15, 27 weeks, 18, 24 months</time_frame>
    <description>The percentage of subjects who were evaluated as improved at 15 weeks and 27 weeks in the patient global impression of change</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PSQI(Pittsburgh Sleep Quality Index)</measure>
    <time_frame>15, 27 weeks, 18, 24 months</time_frame>
    <description>Change in PSQI from baseline up to 15, 27 weeks</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Biomarkers</measure>
    <time_frame>15, 27 weeks, 18, 24 months</time_frame>
    <description>Change from baseline in Biomarkers up to 15, 27 weeks</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of adverse reactions and characteristics associated with investigational product</measure>
    <time_frame>15, 27 weeks, 18, 24 months</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">26</enrollment>
  <condition>Degenerative Arthritis</condition>
  <condition>Knee Osteoarthritis</condition>
  <arm_group>
    <arm_group_label>Autologous Adipose Tissue derived MSCs</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Biological: Autologous Adipose Tissue derived MSCs 1x10^8cells/3ml, 1 time injection(at 1week after high tibial osteotomy)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>No treatment</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>No treatment (after high tibial osteotomy)</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Autologous Adipose Tissue derived MSCs 1x10^8cells/3ml</intervention_name>
    <description>biological : Autologous Adipose Tissue derived MSCs 1x10^8cells/3ml drug: saline solution</description>
    <arm_group_label>Autologous Adipose Tissue derived MSCs</arm_group_label>
    <other_name>JOINTSTEM</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Patients must consent in writing to participate in the study by signing and dating an&#xD;
             informed consent document&#xD;
&#xD;
          2. Patients who can communicate (exclusion of anyone who cannot understand the&#xD;
             questionnaire)&#xD;
&#xD;
          3. between 20 years and 80 years of age&#xD;
&#xD;
          4. BMI≤30&#xD;
&#xD;
          5. Diagnosis of osteoarthritis by radiographic criteria of Kellgren and Lawrence grade&#xD;
             2-4&#xD;
&#xD;
          6. Diagnosis of osteoarthritis by ACR(American College of Rheumatology Criteria) Global&#xD;
             functional criteria : There is the pain of the knee and radiographic osteophyte and at&#xD;
             least one of the following (1) age &gt;50 years (2) Less than 30 minutes of morning&#xD;
             stiffness (3) The friction When moving weighted the knee&#xD;
&#xD;
          7. Patients who agree with contraception&#xD;
&#xD;
          8. Patients who agree to stop the existing osteoarthritis treatment and to get enough&#xD;
             washout periods until medication time&#xD;
&#xD;
          9. Patients scheduled for High tibial osteotomy due to medial gonarthrosis&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. patients with osteoporosis&#xD;
&#xD;
          2. Preparing for Pregnancy or Pregnant women or lactating mothers.&#xD;
&#xD;
          3. Patients with positive human immunodeficiency (HIV), hepatitis B (HBV), hepatitis C&#xD;
             (HCV), venereal disease research laboratory(VDRL)&#xD;
&#xD;
          4. Patients with hypersensitivity to investigator product or investigational product&#xD;
             component or those with a history&#xD;
&#xD;
          5. Patients who had participated in other clinical trials within 12 weeks prior to this&#xD;
             study&#xD;
&#xD;
          6. Patients who received any drug by intra-articular injection for treatment within 2&#xD;
             months prior to this enrollment.&#xD;
&#xD;
          7. Patients who experienced as the knee joint cartilage and stem cell therapy or failure&#xD;
             to treat&#xD;
&#xD;
          8. Patents who started or changed the physical therapy program established within 2 weeks&#xD;
             before the start of the study or during the study(An established physical therapy&#xD;
             program may continue for the duration of the trial, provided that it does not change&#xD;
             in frequency and intensity)&#xD;
&#xD;
          9. Patents included in the following specific risk groups that may influence safety and&#xD;
             efficacy assessments at the discretion of the investigator:: septic arthtritis,&#xD;
             rheumatic disease, gout, recurrent pseudogout, paget disease, joint fracture,&#xD;
             alcaptonuria, acromegaly, hemochromatosis, wilson's disease, primary osteochondrosis,&#xD;
             hereditary disorder(ex: hyperkinesia), collagen gene abnormality ,etc&#xD;
&#xD;
         10. Patients who have clinically significant severe medical illnesses judged the principal&#xD;
             investigator&#xD;
&#xD;
         11. Patients who have been diagnosed with malignancy within 5 years before screening&#xD;
             (except for patients who were completely remissioned three years before screening&#xD;
             criteria)&#xD;
&#xD;
         12. Patients who the principal investigator consider inappropriate for the clinical trial&#xD;
             due to any other reasons&#xD;
&#xD;
         13. Patients who received concomitant contraindications and who have not passed the&#xD;
             prescribed wash-out period before participating in the clinical trial&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>20 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>KANGIL KIM, M.D., Ph.D</last_name>
    <role>Principal Investigator</role>
    <affiliation>KyungHee University Gangdong Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>KyungHee University Gangdong Hospital</name>
      <address>
        <city>Seoul</city>
        <zip>134-727</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Korea, Republic of</country>
  </location_countries>
  <verification_date>June 2019</verification_date>
  <study_first_submitted>December 18, 2016</study_first_submitted>
  <study_first_submitted_qc>December 18, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 22, 2016</study_first_posted>
  <last_update_submitted>January 28, 2021</last_update_submitted>
  <last_update_submitted_qc>January 28, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">January 29, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>adipose tissue derived mesenchymal stem cell</keyword>
  <keyword>osteoarthritis</keyword>
  <keyword>degenerative arthritis</keyword>
  <keyword>kyung hee university hospital</keyword>
  <keyword>biostar</keyword>
  <keyword>Rbio</keyword>
  <keyword>Osteoarthritis, Knee</keyword>
  <keyword>High tibial osteotomy</keyword>
  <keyword>Joint Diseases</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Arthritis</mesh_term>
    <mesh_term>Osteoarthritis</mesh_term>
  </condition_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/NCT03000712
org study id: HTO-MSCs
nct id: NCT03000712
lead sponsor: 
has dmc: No
The purpose of this study is to evaluate the efficacy and safety of intra-articular injection
      of autologous adipose tissue derived mesenchymal stem cells compared after high tibial
      osteotomy to negative control in the osteoarthritis patients
In this clinical trial, the investigational product is administered intra-articularly at 1
      week after high tibial osteotomy in a patient with degenerative arthritis of the medial side.

      The investigational product is autologous adipose-derived mesenchymal stem cells. As it does
      not use allogenic tissue and is incubated without additional genetic modification or
      mechanical and chemical modification through differentiation, it is classified as 'autologous
      cell therapy' and is completely free of immunologic rejection.

      It primarily aims to regenerate cartilage, to improve pain and joint function. The
      intra-articular injection of the investigational product is expected to stimulate the
      regeneration and growth of cartilage, and to innovatively improve pain and joint function
      with cartilage regeneration compared to high tibial osteotomy alone.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: MRI scan
time frame: 24 months
description: MRI perform to measure cartilage defect size change from baseline up to 27 weeks
measure: MRI scan
time frame: 15, 27 weeks, 18, 24 months
description: MRI perform to measure cartilage defect size change from baseline up to 15 weeks
measure: WOMAC score
time frame: 15, 27 weeks, 18, 24 months
description: Change in WOMAC Total score from baseline up to 15, 27 weeks
measure: WOMAC sub-scale
time frame: 15, 27 weeks, 18, 24 months
description: Change in WOMAC sub-scale from baseline up to 15, 27 weeks
measure: Kellgren & Lawrence grade
time frame: 15, 27 weeks, 18, 24 months
description: Change in Kellgren & Lawrence grade from baseline up to 15, 27 weeks
measure: EQ5D
time frame: 15, 27 weeks, 18, 24 months
description: Change in the score of EQ-5D from baseline up to 15, 27 weeks
measure: ROM
time frame: 15, 27 weeks, 18, 24 months
description: change from baseline in knee flexion Range of Motion(ROM) at 15,27 weeks by physical examination
measure: KOOS (Knee Injury & Osteoarthritis Outcome Score)
time frame: 15, 27 weeks, 18, 24 months
description: Symptoms, pain and functionality of the knee joint will be evaluated via the Knee Injury and Osteoarthritis Outcome Score (KOOS)
measure: PGIC(Patient Global Impression of Change)
time frame: 15, 27 weeks, 18, 24 months
description: The percentage of subjects who were evaluated as improved at 15 weeks and 27 weeks in the patient global impression of change
measure: PSQI(Pittsburgh Sleep Quality Index)
time frame: 15, 27 weeks, 18, 24 months
description: Change in PSQI from baseline up to 15, 27 weeks
measure: Biomarkers
time frame: 15, 27 weeks, 18, 24 months
description: Change from baseline in Biomarkers up to 15, 27 weeks
measure: Incidence of adverse reactions and characteristics associated with investigational product
time frame: 15, 27 weeks, 18, 24 months
arm group label: Autologous Adipose Tissue derived MSCs
arm group type: Experimental
description: Biological: Autologous Adipose Tissue derived MSCs 1x10^8cells/3ml, 1 time injection(at 1week after high tibial osteotomy)
arm group label: No treatment
arm group type: No Intervention
description: No treatment (after high tibial osteotomy)
intervention type: Biological
intervention name: Autologous Adipose Tissue derived MSCs 1x10^8cells/3ml
description: biological : Autologous Adipose Tissue derived MSCs 1x10^8cells/3ml drug: saline solution
arm group label: Autologous Adipose Tissue derived MSCs
other name: JOINTSTEM
criteria: 
gender: All
minimum age: 20 Years
maximum age: 80 Years
healthy volunteers: No
last name: KANGIL KIM, M.D., Ph.D
role: Principal Investigator
affiliation: KyungHee University Gangdong Hospital
facility: 
country: Korea, Republic of
responsible party type: Sponsor
mesh term: Arthritis
mesh term: Osteoarthritis
sharing ipd: No