<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/NCT01671072</url>
  </required_header>
  <id_info>
    <org_study_id>KS-TGC-01-2B</org_study_id>
    <nct_id>NCT01671072</nct_id>
  </id_info>
  <brief_title>Efficacy and Safety Study of TissueGene-C to Degenerative Arthritis</brief_title>
  <official_title>A Placebo Controlled, Single-blind, Randomized, Multi-center Phase 2B Study to Determine the Efficacy and Safety of TissueGene-C, an Allogeneic Human Chondrocytes Expressing TGF-b1, in Patients With Degenerative Arthritis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Kolon Life Science</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Kolon Life Science</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to determine whether TissueGene-C, an allogeneic human&#xD;
      chondrocytes expressing Transforming Growth Factor(TGF)-b1, is effective and safe in patients&#xD;
      with degenerative arthritis&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      TissueGene-C is a biological new drug which consists of normal chondrocytes and transduced&#xD;
      chondrocytes that express growth factors to regenerate the damaged cartilage tissues.&#xD;
&#xD;
      In the clinical trial Phase 2b, the investigators compared TissueGene-C to placebo during 6 -&#xD;
      months trial with 54 outpatients who have had degenerative arthritis. The outpatients are&#xD;
      assigned to TissueGene-C or placebo in 1:1 ratio, and will be monitored and recorded for&#xD;
      improving clinical symptoms, sports activities, and function of the knee, and for the&#xD;
      presence of adverse events.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>July 2011</start_date>
  <completion_date type="Actual">January 2013</completion_date>
  <primary_completion_date type="Actual">October 2012</primary_completion_date>
  <phase>Phase 2</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>Single (Participant)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Changes in IKDC Subjective Score.</measure>
    <time_frame>Week 0 and 24</time_frame>
    <description>Symptoms, sports activities, and function of the knee will be measured by the International Knee Documentation Committee (IKDC)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Changes in WOMAC scores.</measure>
    <time_frame>Week 0 and 24</time_frame>
    <description>Pain, stiffness, and physical function of the knee will be measured by the Western Ontario and McMaster Universities (WOMAC)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in KOOS scores.</measure>
    <time_frame>Week 0 and 24</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>Changes in 100 mm-VAS.</measure>
    <time_frame>Week 0 and 24</time_frame>
    <description>Pain of the knee will be measured by the 100mm Visual Analogue Scale (VAS)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>MRI scan</measure>
    <time_frame>Week 0 and 24</time_frame>
    <description>Comparison of pre-procedure MRI scans to those obtained at pre-dosing and at months 6 and 12 following dosing by an independent radiographic reviewer.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of Patients Use of Rescue Medication</measure>
    <time_frame>Week 4, 12 and 24</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">54</enrollment>
  <condition>Degenerative Arthritis</condition>
  <arm_group>
    <arm_group_label>TissueGene-C</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Single intra-articular injection to the damaged knee joint a dose of 1.8 x 10^7 cells</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Normal Saline</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Single intra-articular injection to the damaged knee joint at the same volume</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>TissueGene-C</intervention_name>
    <description>TissueGene-C at 1.8 x 10^7 cells</description>
    <arm_group_label>TissueGene-C</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Normal Saline</intervention_name>
    <description>Sodium chloride 0.9%, 3.5ml</description>
    <arm_group_label>Normal Saline</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Female or male aged 18 years or more&#xD;
&#xD;
          2. Diagnosed with degenerative arthritis of the knee&#xD;
&#xD;
          3. With an IKDC score of 60 or lower at the screening visit&#xD;
&#xD;
          4. With Grade 2 or 3 osteoarthritis as determined by the radiographic criteria of&#xD;
             Kellgren and Lawrence&#xD;
&#xD;
          5. With a Body Mass Index(BMI) of higher than18.5 and lower than 30&#xD;
&#xD;
          6. With an International Cartilage Repair Society(ICRS) Grade IV cartilage damage in the&#xD;
             major lesions, as confirmed through an MRI scan&#xD;
&#xD;
          7. With major lesions concentrated in one section of the knee, and with the major lesions&#xD;
             considered the main cause of the clinical symptoms&#xD;
&#xD;
          8. With no alleviation of the symptoms even after at least three months of non-surgical&#xD;
             treatment&#xD;
&#xD;
          9. Healthy, with no major findings from the physical examination, hematology, serum&#xD;
             chemistry, and urine tests, and no significant medical history&#xD;
&#xD;
         10. Agreed to use an effective contraceptive method during the study period&#xD;
&#xD;
         11. Voluntarily agreed to participate in this study, and signed the informed consent form&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Showed clinically significant hematology, serum chemistry, and urine test results at&#xD;
             the screening visit&#xD;
&#xD;
          2. Falls under Inclusion Criteria 6 but with the damage in the relevant lesion considered&#xD;
             ICRS Grade IV sized more than 6 cm2&#xD;
&#xD;
          3. Took glucosamine, chondroitin, or any natural medicine within 14 days before the&#xD;
             injection of the investigational product (but if the 14-day washout period had&#xD;
             elapsed, the patient can be enrolled in this study)&#xD;
&#xD;
          4. Has taken anti-inflammatory drugs (prescribed or over-the-counter) within 14 days&#xD;
             before the injection of the investigational product (but if the 14-day washout period&#xD;
             had elapsed, the patient can be enrolled in this study)&#xD;
&#xD;
          5. Has taken immunosuppressive agents, including antirheumatic drugs (e.g., methotrexate&#xD;
             or antimetabolites) within 3 months before enrollment in this study&#xD;
&#xD;
          6. With a history of drug abuse within one year prior to enrollment in this study, or&#xD;
             showed positive results in the urine drug test or the serum alcohol test at the&#xD;
             screening visit&#xD;
&#xD;
          7. Received an injection in the target knee within two months before enrollment in this&#xD;
             study&#xD;
&#xD;
          8. Pregnant or breastfeeding female&#xD;
&#xD;
          9. With another joint disease apart from degenerative arthritis (e.g., systemic rheumatic&#xD;
             inflammatory disease associated with the knee or chondrocalcinosis, hemachromatosis,&#xD;
             inflammatory arthritis, necrosis of the trochanter, Paget's disease adjacent to a&#xD;
             joint in the femur or tibia, ochronosis, hemophilic arthropathy, infectious arthritis,&#xD;
             Charcot's disease in the knee joint, villonodular synovitis, synovial chondromas)&#xD;
&#xD;
         10. With an infectious disease, including HIV or hepatitis&#xD;
&#xD;
         11. With any of the following clinically significant diseases:&#xD;
&#xD;
               -  heart disease [e.g., myocardial infarction, arrhythmia, other serious heart&#xD;
                  diseases, coronary artery bypass graft (CABG)]&#xD;
&#xD;
               -  kidney disease (e.g., chronic renal failure, glomerulonephritis)&#xD;
&#xD;
               -  liver disease (e.g., liver cirrhosis, fatty liver, acute or chronic liver&#xD;
                  disease)&#xD;
&#xD;
               -  endocrine disease (e.g., hyperthyroidism, hypothyroidism, thyroiditis, diabetes&#xD;
                  insipidus, Cushing's disease)&#xD;
&#xD;
               -  insulin-dependent diabetes mellitus&#xD;
&#xD;
               -  medical history of past or current malignant tumor&#xD;
&#xD;
               -  In particular, the tumors that TissueGene-C may aggravate can be screened using&#xD;
                  the following tests:&#xD;
&#xD;
                    -  Leukemia (White Blood Cell level in the hematology)&#xD;
&#xD;
                    -  Osteochondroma, Chondromas, Chondroblastoma, Chondromyxoid fibroma,&#xD;
                       Chondrosarcoma (Alkaline phosphatase level in the hematology)&#xD;
&#xD;
         12. Participated in another clinical trial (using the investigational drug or a medical&#xD;
             device) within 30 days before enrollment in this study&#xD;
&#xD;
         13. Considered inappropriate by the investigator for participation in this study&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Chul Won Ha, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Samsung Medical Center</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Seong Il Bin, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Asan Medical Center</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Myung Chul Lee, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Seoul National Univ. Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Samsung Medical Center</name>
      <address>
        <city>Gangnam-gu</city>
        <state>Seoul</state>
        <zip>135-710</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Seoul National Univ. Hospital</name>
      <address>
        <city>Seoul</city>
        <zip>110-744</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Asan Medical Center</name>
      <address>
        <city>Seoul</city>
        <zip>138-736</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Korea, Republic of</country>
  </location_countries>
  <verification_date>January 2015</verification_date>
  <study_first_submitted>August 20, 2012</study_first_submitted>
  <study_first_submitted_qc>August 22, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 23, 2012</study_first_posted>
  <last_update_submitted>January 21, 2015</last_update_submitted>
  <last_update_submitted_qc>January 21, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">January 22, 2015</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Chondrocyte cells</keyword>
  <keyword>Osteoarthritis</keyword>
  <keyword>Gene therapy</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>
  <!-- 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/NCT01671072
org study id: KS-TGC-01-2B
nct id: NCT01671072
lead sponsor: 
has dmc: Yes
The purpose of this study is to determine whether TissueGene-C, an allogeneic human
      chondrocytes expressing Transforming Growth Factor(TGF)-b1, is effective and safe in patients
      with degenerative arthritis
TissueGene-C is a biological new drug which consists of normal chondrocytes and transduced
      chondrocytes that express growth factors to regenerate the damaged cartilage tissues.

      In the clinical trial Phase 2b, the investigators compared TissueGene-C to placebo during 6 -
      months trial with 54 outpatients who have had degenerative arthritis. The outpatients are
      assigned to TissueGene-C or placebo in 1:1 ratio, and will be monitored and recorded for
      improving clinical symptoms, sports activities, and function of the knee, and for the
      presence of adverse events.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Participant)
measure: Changes in IKDC Subjective Score.
time frame: Week 0 and 24
description: Symptoms, sports activities, and function of the knee will be measured by the International Knee Documentation Committee (IKDC)
measure: Changes in WOMAC scores.
time frame: Week 0 and 24
description: Pain, stiffness, and physical function of the knee will be measured by the Western Ontario and McMaster Universities (WOMAC)
measure: Changes in KOOS scores.
time frame: Week 0 and 24
description: Symptoms, pain and functionality of the knee joint will be evaluated via the Knee Injury and Osteoarthritis Outcome Score (KOOS)
measure: Changes in 100 mm-VAS.
time frame: Week 0 and 24
description: Pain of the knee will be measured by the 100mm Visual Analogue Scale (VAS)
measure: MRI scan
time frame: Week 0 and 24
description: Comparison of pre-procedure MRI scans to those obtained at pre-dosing and at months 6 and 12 following dosing by an independent radiographic reviewer.
measure: Proportion of Patients Use of Rescue Medication
time frame: Week 4, 12 and 24
arm group label: TissueGene-C
arm group type: Experimental
description: Single intra-articular injection to the damaged knee joint a dose of 1.8 x 10^7 cells
arm group label: Normal Saline
arm group type: Placebo Comparator
description: Single intra-articular injection to the damaged knee joint at the same volume
intervention type: Biological
intervention name: TissueGene-C
description: TissueGene-C at 1.8 x 10^7 cells
arm group label: TissueGene-C
intervention type: Drug
intervention name: Normal Saline
description: Sodium chloride 0.9%, 3.5ml
arm group label: Normal Saline
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Chul Won Ha, MD, PhD
role: Principal Investigator
affiliation: Samsung Medical Center
last name: Seong Il Bin, MD, PhD
role: Principal Investigator
affiliation: Asan Medical Center
last name: Myung Chul Lee, MD, PhD
role: Principal Investigator
affiliation: Seoul National Univ. Hospital
facility: 
facility: 
facility: 
country: Korea, Republic of
responsible party type: Sponsor
mesh term: Arthritis
mesh term: Osteoarthritis