<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/NCT01733186</url>
  </required_header>
  <id_info>
    <org_study_id>MP-0201-01</org_study_id>
    <nct_id>NCT01733186</nct_id>
  </id_info>
  <brief_title>Evaluation of Safety and Exploratory Efficacy of CARTISTEM®, a Cell Therapy Product for Articular Cartilage Defects</brief_title>
  <official_title>Evaluation of Safety and Exploratory Efficacy of CARTISTEM®, a Cell Therapy Product for Articular Cartilage Defects: A Phase I/IIa Clinical Trial in Patients With Focal, Full-thickness Grade 3-4 Articular Cartilage Defects of the Knee</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Medipost Co Ltd.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Medipost Co Ltd.</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to determine whether CARTISTEM, a cell therapeutic product, is&#xD;
      safe and effective in the treatment of articular cartilage defects of the knee as a result of&#xD;
      ageing, trauma, or degenerative diseases.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Conventional treatment modalities have not been able to provide complete and sustained&#xD;
      resolution of symptoms following damage to the articular cartilage. Despite the numerous&#xD;
      techniques available today, complete healing of damaged or defective cartilage or consistent&#xD;
      reproduction of normal hyaline cartilage does not occur, and continuous drug administration&#xD;
      or secondary surgeries are common.&#xD;
&#xD;
      Research in mesenchymal stem cells has had a rapid acceleration over the past decade and&#xD;
      MSC-based therapy has become one of the objects of investigation for a new branch of medicine&#xD;
      termed regenerative medicine. This emerging technology shows great promise for producing&#xD;
      transplantable cartilage constructs to restore the function of degenerated joints.&#xD;
&#xD;
      CARTISTEM®, a combination of human umbilical cord blood-derived mesenchymal stem cells and&#xD;
      sodium hyaluronate, is intended to be used as a single-dose cellular therapeutic agent for&#xD;
      cartilage regeneration in human subjects with cartilage defects of the knee as a result of&#xD;
      ageing, trauma, or degenerative diseases.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 7, 2013</start_date>
  <completion_date type="Actual">August 29, 2017</completion_date>
  <primary_completion_date type="Actual">June 2, 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>IKDC Score</measure>
    <time_frame>12 months</time_frame>
    <description>Subjects underwent a self-assessment of knee function using the IKDC (International Knee Documentation Committee Assessment)subjective knee evaluation before and after the administration of the IP. The assessment is designed to detect improvement or deterioration in symptoms, function, and sports activities due to knee impairment. The possible score ranges from 0 to 100, where 100 = no limitation with daily or sporting activities and the absence of symptoms.&#xD;
The IKDC assessment was performed before IP administration and at Months 12 after IP administration in an exploratory fashion. The IKDC score from the Month 12 visit was used as a primary indicator of the post operative change.&#xD;
The outcome was presented with the post-operative change amount from the baseline.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>VAS</measure>
    <time_frame>24 months</time_frame>
    <description>Subjects underwent a self-assessment of joint pain using the 100-mm VAS (Visual Analogue Scale) before and at Months 12 and 24 after IP (investigational product) administration. Higher values represent worse joint pain. Use of NSAIDs and any other analgesics had to be discontinued for 48 hours and 24 hours, respectively, prior to the 100 mm VAS evaluation. The outcome was presented with the post-operative change amount at Months 12 and 24 from the baseline.&#xD;
100-mm VAS scores range from 0 to 100. Higher values represent worse joint pain.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Lysholm Score</measure>
    <time_frame>24 months</time_frame>
    <description>The Lysholm knee scoring scale is a self-assessment that rates the severity of common complaints related to knee problems, such as pain, swelling, abnormal sensations, and ability to squat or climb stairs. The possible score ranges from 0 to 100, where 100 = no symptoms or disability. Scores are categorized as excellent (95 to 100), good (84 to 94), fair (65 to 83), and poor (≤64). Subjects underwent a self-assessment of knee function using the Lysholm score before IP administration and at Months 12 and 24 after IP administration. The outcome was presented with the post-operative change amount at Months 12 and 24 from the baseline.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>KOOS Score</measure>
    <time_frame>24 months</time_frame>
    <description>The Knee Injury and Osteoarthritis Outcome score (KOOS) knee survey is a self assessment of knee function and knee-related quality of life (QOL). Subjects responded to each question regarding knee-related symptoms, swelling, pain, impaired function, or changes in QOL with 1 of 5 possible answers that range from &quot;never/not at all&quot; to &quot;always/extremely.&quot; The possible score for each parameter ranges from 0 to 100, where 0=extreme problems and 100=no problems. Subjects completed the KOOS knee survey before IP (investigational product) administration and at Month 24 after IP administration. The outcome was presented with the post-operative change amount at Month 24 from the baseline.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>IKDC Score</measure>
    <time_frame>24 months</time_frame>
    <description>Subjects underwent a self-assessment of knee function using the IKDC subjective knee evaluation before and after the administration of the IP. The assessment is designed to detect improvement or deterioration in symptoms, function, and sports activities due to knee impairment. The possible score ranges from 0 to 100, where 100 = no limitation with daily or sporting activities and the absence of symptoms. The IKDC assessment was performed before IP administration and at Month 24 after IP administration in an exploratory fashion. The outcome was presented with the post-operative change amount at Month 24 from the baseline.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">12</enrollment>
  <condition>Degeneration Articular Cartilage Knee</condition>
  <arm_group>
    <arm_group_label>CARTISTEM®</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Drug name and ingredients: CARTISTEM [allogeneic-unrelated, umbilical cord blood-derived mesenchymal stem cells, ex vivo cultured, combined with sodium hyaluronate] Dosage: Administer 0.5 mL of the combination product per cm^2 of the cartilage defect</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>CARTISTEM®</intervention_name>
    <arm_group_label>CARTISTEM®</arm_group_label>
    <other_name>human umbilical cord blood-derived mesenchymal stem cells</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients with an intended- to- treat single focal, full-thickness cartilage defect&#xD;
             (ICRS [International Cartilage Repair Society] Grade 3 or 4) of the knee as a result&#xD;
             of ageing, trauma, or degenerative diseases.&#xD;
&#xD;
          -  Age ≥ 18 years old&#xD;
&#xD;
          -  Size of the articular cartilage lesion is ≥ 2 cm2&#xD;
&#xD;
          -  Swelling, tenderness and active range of motion ≤ Grade II&#xD;
&#xD;
          -  Joint pain : 20-mm - 60-mm on VAS (Visual Analog Scale) at the time of Screening&#xD;
&#xD;
          -  Appropriate blood coagulation, kidney and liver function laboratory parameters:&#xD;
             PT(INR) &lt; 1.5, APTT &lt;1.5×control Creatinine ≤ 2.0 mg/dL Albumin ≤ trace in urine&#xD;
             dipstick test Bilirubin ≤ 2.0 mg/dL, AST/ALT ≤ 100 IU/L&#xD;
&#xD;
          -  Ligament instability ≤ Grade II&#xD;
&#xD;
          -  Lower extremity alignment within 5 degrees of the neutral weight bearing axis&#xD;
&#xD;
          -  No meniscal surgery within the past 3 months and more than 5mm of meniscal rim&#xD;
             remaining&#xD;
&#xD;
          -  Ability and willingness to fully participate in the post-operative rehabilitation&#xD;
             program&#xD;
&#xD;
          -  Subject is informed of the investigational nature of this study, voluntarily agrees to&#xD;
             participate in the study, and signs an IRBapproved informed consent prior to&#xD;
             performing any of the screening procedures&#xD;
&#xD;
          -  Body Mass Index (BMI) ≤ 35 kg/m2&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients who have been treated previously and are asymptomatic&#xD;
&#xD;
          -  Avascular necrosis/ osteonecrosis&#xD;
&#xD;
          -  Autoimmune or inflammatory joint disease&#xD;
&#xD;
          -  History of infection within the past 6 weeks&#xD;
&#xD;
          -  Surgery or radiation therapy within the past 6 weeks&#xD;
&#xD;
          -  Serious medical co-morbidities, which would otherwise contraindicate surgery, as&#xD;
             determined by the investigator&#xD;
&#xD;
          -  Currently pregnant or nursing&#xD;
&#xD;
          -  Psychotic diseases, epilepsy, or any history of such diseases&#xD;
&#xD;
          -  Current abuse of alcohol (&gt; 10 drinks weekly) and/or regular exposure to other&#xD;
             substances of abuse, currently an active smoker&#xD;
&#xD;
          -  Chronic inflammatory articular diseases such as rheumatoid arthritis&#xD;
&#xD;
          -  Enrolled in any other clinical trials within the past 4 weeks&#xD;
&#xD;
          -  Administered immunosuppressants such as Cyclosporin A or azathioprine within the past&#xD;
             6 weeks&#xD;
&#xD;
          -  Ligament instability &gt; Grade II&#xD;
&#xD;
          -  Uncorrected significant lower extremity malalignment (i.e. &gt; 5 degrees)&#xD;
&#xD;
          -  (sub-) Total meniscectomy (&lt;5mm rim remaining)&#xD;
&#xD;
          -  Corticosteroid or viscosupplementation injection to the affected knee in the past 3&#xD;
             months&#xD;
&#xD;
          -  Principal investigator considers inappropriate for the clinical trial due to any&#xD;
             reasons other than those listed above&#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>Brian J Cole, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Cartilage Restoration Center, Rush University Medical Center</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Andreas H Gomoll, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Cartilage Repair Center, Brigham and Women's Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Cartilage Restoration Center; RUSH University Medical Center</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60612</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cartilage Repair Center; Brigham and Women's Hospital</name>
      <address>
        <city>Chestnut Hill</city>
        <state>Massachusetts</state>
        <zip>02467</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://clinicaltrials.gov/ct2/show/NCT01041001?term=cartistem&amp;rank=2</url>
    <description>Study to Compare the Efficacy and Safety of Cartistem® and Microfracture in Patients With Knee Articular Cartilage Injury or Defect</description>
  </link>
  <verification_date>July 2021</verification_date>
  <study_first_submitted>November 20, 2012</study_first_submitted>
  <study_first_submitted_qc>November 20, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 26, 2012</study_first_posted>
  <results_first_submitted>May 25, 2021</results_first_submitted>
  <results_first_submitted_qc>July 11, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">July 30, 2021</results_first_posted>
  <disposition_first_submitted>August 22, 2018</disposition_first_submitted>
  <disposition_first_submitted_qc>August 27, 2018</disposition_first_submitted_qc>
  <disposition_first_posted type="Actual">August 29, 2018</disposition_first_posted>
  <last_update_submitted>July 11, 2021</last_update_submitted>
  <last_update_submitted_qc>July 11, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">July 30, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>human umbilical cord blood-derived mesenchymal stem cells</keyword>
  <keyword>MSC</keyword>
  <keyword>cartilage lesion</keyword>
  <keyword>cartilage defect</keyword>
  <keyword>degenerative arthritis</keyword>
  <keyword>stem cell implantation</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cartilage Diseases</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>March 15, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/86/NCT01733186/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Dose A Cohort</title>
          <description>Drug name and ingredients: CARTISTEM [allogeneic-unrelated, umbilical cord blood-derived mesenchymal stem cells, ex vivo cultured, combined with sodium hyaluronate] Dosage: Administer 0.5 mL of the combination product per cm^2 of the cartilage defect&#xD;
Cartilage defect size range: 2 to 5 cm2 (Dose A)&#xD;
CARTISTEM®</description>
        </group>
        <group group_id="P2">
          <title>Dose B Cohort</title>
          <description>Drug name and ingredients: CARTISTEM [allogeneic-unrelated, umbilical cord blood-derived mesenchymal stem cells, ex vivo cultured, combined with sodium hyaluronate] Dosage: Administer 0.5 mL of the combination product per cm^2 of the cartilage defect&#xD;
Cartilage defect size range: above 5 cm2 (Dose B)&#xD;
CARTISTEM®</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="6"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="6"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Dose A Cohort</title>
          <description>Drug name and ingredients: CARTISTEM [allogeneic-unrelated, umbilical cord blood-derived mesenchymal stem cells, ex vivo cultured, combined with sodium hyaluronate] Dosage: Administer 0.5 mL of the combination product per cm^2 of the cartilage defect&#xD;
Cartilage defect size range: 2 to 5 cm2 (Dose A)&#xD;
CARTISTEM®</description>
        </group>
        <group group_id="B2">
          <title>Dose B Cohort</title>
          <description>Drug name and ingredients: CARTISTEM [allogeneic-unrelated, umbilical cord blood-derived mesenchymal stem cells, ex vivo cultured, combined with sodium hyaluronate] Dosage: Administer 0.5 mL of the combination product per cm^2 of the cartilage defect&#xD;
Cartilage defect size range: above 5 cm2 (Dose B)&#xD;
CARTISTEM®</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="6"/>
            <count group_id="B2" value="6"/>
            <count group_id="B3" value="12"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="36.3" spread="8.2"/>
                    <measurement group_id="B2" value="39.7" spread="8.0"/>
                    <measurement group_id="B3" value="38.0" spread="7.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="12"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="10"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Body mass index</title>
          <units>kg/m^2</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="28.6" spread="4.1"/>
                    <measurement group_id="B2" value="26.6" spread="4.5"/>
                    <measurement group_id="B3" value="27.6" spread="4.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>IKDC Score</title>
        <description>Subjects underwent a self-assessment of knee function using the IKDC (International Knee Documentation Committee Assessment)subjective knee evaluation before and after the administration of the IP. The assessment is designed to detect improvement or deterioration in symptoms, function, and sports activities due to knee impairment. The possible score ranges from 0 to 100, where 100 = no limitation with daily or sporting activities and the absence of symptoms.&#xD;
The IKDC assessment was performed before IP administration and at Months 12 after IP administration in an exploratory fashion. The IKDC score from the Month 12 visit was used as a primary indicator of the post operative change.&#xD;
The outcome was presented with the post-operative change amount from the baseline.</description>
        <time_frame>12 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Dose A Cohort</title>
            <description>Drug name and ingredients: CARTISTEM [allogeneic-unrelated, umbilical cord blood-derived mesenchymal stem cells, ex vivo cultured, combined with sodium hyaluronate] Dosage: Administer 0.5 mL of the combination product per cm^2 of the cartilage defect&#xD;
Cartilage defect size range: 2 to 5 cm2 (Dose A)&#xD;
CARTISTEM®</description>
          </group>
          <group group_id="O2">
            <title>Dose B Cohort</title>
            <description>Drug name and ingredients: CARTISTEM [allogeneic-unrelated, umbilical cord blood-derived mesenchymal stem cells, ex vivo cultured, combined with sodium hyaluronate] Dosage: Administer 0.5 mL of the combination product per cm^2 of the cartilage defect&#xD;
Cartilage defect size range: above 5 cm2 (Dose B)&#xD;
CARTISTEM®</description>
          </group>
        </group_list>
        <measure>
          <title>IKDC Score</title>
          <description>Subjects underwent a self-assessment of knee function using the IKDC (International Knee Documentation Committee Assessment)subjective knee evaluation before and after the administration of the IP. The assessment is designed to detect improvement or deterioration in symptoms, function, and sports activities due to knee impairment. The possible score ranges from 0 to 100, where 100 = no limitation with daily or sporting activities and the absence of symptoms.&#xD;
The IKDC assessment was performed before IP administration and at Months 12 after IP administration in an exploratory fashion. The IKDC score from the Month 12 visit was used as a primary indicator of the post operative change.&#xD;
The outcome was presented with the post-operative change amount from the baseline.</description>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="32.0" spread="27.7"/>
                    <measurement group_id="O2" value="25.5" spread="18.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>VAS</title>
        <description>Subjects underwent a self-assessment of joint pain using the 100-mm VAS (Visual Analogue Scale) before and at Months 12 and 24 after IP (investigational product) administration. Higher values represent worse joint pain. Use of NSAIDs and any other analgesics had to be discontinued for 48 hours and 24 hours, respectively, prior to the 100 mm VAS evaluation. The outcome was presented with the post-operative change amount at Months 12 and 24 from the baseline.&#xD;
100-mm VAS scores range from 0 to 100. Higher values represent worse joint pain.</description>
        <time_frame>24 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Dose A Cohort</title>
            <description>Drug name and ingredients: CARTISTEM [allogeneic-unrelated, umbilical cord blood-derived mesenchymal stem cells, ex vivo cultured, combined with sodium hyaluronate] Dosage: Administer 0.5 mL of the combination product per cm^2 of the cartilage defect&#xD;
Cartilage defect size range: 2 to 5 cm2 (Dose A)&#xD;
CARTISTEM®</description>
          </group>
          <group group_id="O2">
            <title>Dose B Cohort</title>
            <description>Drug name and ingredients: CARTISTEM [allogeneic-unrelated, umbilical cord blood-derived mesenchymal stem cells, ex vivo cultured, combined with sodium hyaluronate] Dosage: Administer 0.5 mL of the combination product per cm^2 of the cartilage defect&#xD;
Cartilage defect size range: above 5 cm2 (Dose B)&#xD;
CARTISTEM®</description>
          </group>
        </group_list>
        <measure>
          <title>VAS</title>
          <description>Subjects underwent a self-assessment of joint pain using the 100-mm VAS (Visual Analogue Scale) before and at Months 12 and 24 after IP (investigational product) administration. Higher values represent worse joint pain. Use of NSAIDs and any other analgesics had to be discontinued for 48 hours and 24 hours, respectively, prior to the 100 mm VAS evaluation. The outcome was presented with the post-operative change amount at Months 12 and 24 from the baseline.&#xD;
100-mm VAS scores range from 0 to 100. Higher values represent worse joint pain.</description>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>12 MONTHS</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-23.8" spread="22.9"/>
                    <measurement group_id="O2" value="-12.5" spread="31.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>24 MONTHS</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-31.7" spread="18.0"/>
                    <measurement group_id="O2" value="-11.3" spread="30.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Lysholm Score</title>
        <description>The Lysholm knee scoring scale is a self-assessment that rates the severity of common complaints related to knee problems, such as pain, swelling, abnormal sensations, and ability to squat or climb stairs. The possible score ranges from 0 to 100, where 100 = no symptoms or disability. Scores are categorized as excellent (95 to 100), good (84 to 94), fair (65 to 83), and poor (≤64). Subjects underwent a self-assessment of knee function using the Lysholm score before IP administration and at Months 12 and 24 after IP administration. The outcome was presented with the post-operative change amount at Months 12 and 24 from the baseline.</description>
        <time_frame>24 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Dose A Cohort</title>
            <description>Drug name and ingredients: CARTISTEM [allogeneic-unrelated, umbilical cord blood-derived mesenchymal stem cells, ex vivo cultured, combined with sodium hyaluronate] Dosage: Administer 0.5 mL of the combination product per cm^2 of the cartilage defect&#xD;
Cartilage defect size range: 2 to 5 cm2 (Dose A)&#xD;
CARTISTEM®</description>
          </group>
          <group group_id="O2">
            <title>Dose B Cohort</title>
            <description>Drug name and ingredients: CARTISTEM [allogeneic-unrelated, umbilical cord blood-derived mesenchymal stem cells, ex vivo cultured, combined with sodium hyaluronate] Dosage: Administer 0.5 mL of the combination product per cm^2 of the cartilage defect&#xD;
Cartilage defect size range: above 5 cm2 (Dose B)&#xD;
CARTISTEM®</description>
          </group>
        </group_list>
        <measure>
          <title>Lysholm Score</title>
          <description>The Lysholm knee scoring scale is a self-assessment that rates the severity of common complaints related to knee problems, such as pain, swelling, abnormal sensations, and ability to squat or climb stairs. The possible score ranges from 0 to 100, where 100 = no symptoms or disability. Scores are categorized as excellent (95 to 100), good (84 to 94), fair (65 to 83), and poor (≤64). Subjects underwent a self-assessment of knee function using the Lysholm score before IP administration and at Months 12 and 24 after IP administration. The outcome was presented with the post-operative change amount at Months 12 and 24 from the baseline.</description>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>12 MONTHS</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="26.7" spread="20.5"/>
                    <measurement group_id="O2" value="22.5" spread="18.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>24 MONTHS</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="32.0" spread="20.9"/>
                    <measurement group_id="O2" value="10.2" spread="13.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>KOOS Score</title>
        <description>The Knee Injury and Osteoarthritis Outcome score (KOOS) knee survey is a self assessment of knee function and knee-related quality of life (QOL). Subjects responded to each question regarding knee-related symptoms, swelling, pain, impaired function, or changes in QOL with 1 of 5 possible answers that range from &quot;never/not at all&quot; to &quot;always/extremely.&quot; The possible score for each parameter ranges from 0 to 100, where 0=extreme problems and 100=no problems. Subjects completed the KOOS knee survey before IP (investigational product) administration and at Month 24 after IP administration. The outcome was presented with the post-operative change amount at Month 24 from the baseline.</description>
        <time_frame>24 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Dose A Cohort</title>
            <description>Drug name and ingredients: CARTISTEM [allogeneic-unrelated, umbilical cord blood-derived mesenchymal stem cells, ex vivo cultured, combined with sodium hyaluronate] Dosage: Administer 0.5 mL of the combination product per cm^2 of the cartilage defect&#xD;
Cartilage defect size range: 2 to 5 cm2 (Dose A)&#xD;
CARTISTEM®</description>
          </group>
          <group group_id="O2">
            <title>Dose B Cohort</title>
            <description>Drug name and ingredients: CARTISTEM [allogeneic-unrelated, umbilical cord blood-derived mesenchymal stem cells, ex vivo cultured, combined with sodium hyaluronate] Dosage: Administer 0.5 mL of the combination product per cm^2 of the cartilage defect&#xD;
Cartilage defect size range: above 5 cm2 (Dose B)&#xD;
CARTISTEM®</description>
          </group>
        </group_list>
        <measure>
          <title>KOOS Score</title>
          <description>The Knee Injury and Osteoarthritis Outcome score (KOOS) knee survey is a self assessment of knee function and knee-related quality of life (QOL). Subjects responded to each question regarding knee-related symptoms, swelling, pain, impaired function, or changes in QOL with 1 of 5 possible answers that range from &quot;never/not at all&quot; to &quot;always/extremely.&quot; The possible score for each parameter ranges from 0 to 100, where 0=extreme problems and 100=no problems. Subjects completed the KOOS knee survey before IP (investigational product) administration and at Month 24 after IP administration. The outcome was presented with the post-operative change amount at Month 24 from the baseline.</description>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>ADL (24 MONTHS)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="28.2" spread="25.7"/>
                    <measurement group_id="O2" value="12.3" spread="19.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>PAIN (24 MONTHS)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="23.6" spread="24.3"/>
                    <measurement group_id="O2" value="15.8" spread="13.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>QOL (24 MONTHS)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="50.0" spread="36.4"/>
                    <measurement group_id="O2" value="19.8" spread="24.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>SPORTS (24 MONTHS)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="39.2" spread="37.2"/>
                    <measurement group_id="O2" value="36.7" spread="31.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>SYMPTOM (24 MONTHS)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="24.4" spread="19.9"/>
                    <measurement group_id="O2" value="8.3" spread="12.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>IKDC Score</title>
        <description>Subjects underwent a self-assessment of knee function using the IKDC subjective knee evaluation before and after the administration of the IP. The assessment is designed to detect improvement or deterioration in symptoms, function, and sports activities due to knee impairment. The possible score ranges from 0 to 100, where 100 = no limitation with daily or sporting activities and the absence of symptoms. The IKDC assessment was performed before IP administration and at Month 24 after IP administration in an exploratory fashion. The outcome was presented with the post-operative change amount at Month 24 from the baseline.</description>
        <time_frame>24 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Dose A Cohort</title>
            <description>Drug name and ingredients: CARTISTEM [allogeneic-unrelated, umbilical cord blood-derived mesenchymal stem cells, ex vivo cultured, combined with sodium hyaluronate] Dosage: Administer 0.5 mL of the combination product per cm^2 of the cartilage defect&#xD;
Cartilage defect size range: 2 to 5 cm2 (Dose A)&#xD;
CARTISTEM®</description>
          </group>
          <group group_id="O2">
            <title>Dose B Cohort</title>
            <description>Drug name and ingredients: CARTISTEM [allogeneic-unrelated, umbilical cord blood-derived mesenchymal stem cells, ex vivo cultured, combined with sodium hyaluronate] Dosage: Administer 0.5 mL of the combination product per cm^2 of the cartilage defect&#xD;
Cartilage defect size range: above 5 cm2 (Dose B)&#xD;
CARTISTEM®</description>
          </group>
        </group_list>
        <measure>
          <title>IKDC Score</title>
          <description>Subjects underwent a self-assessment of knee function using the IKDC subjective knee evaluation before and after the administration of the IP. The assessment is designed to detect improvement or deterioration in symptoms, function, and sports activities due to knee impairment. The possible score ranges from 0 to 100, where 100 = no limitation with daily or sporting activities and the absence of symptoms. The IKDC assessment was performed before IP administration and at Month 24 after IP administration in an exploratory fashion. The outcome was presented with the post-operative change amount at Month 24 from the baseline.</description>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="41.2" spread="25.8"/>
                    <measurement group_id="O2" value="27.5" spread="20.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>24 months</time_frame>
      <desc>General safety was evaluated via the following assessments: adverse events (AEs), routine clinical laboratory tests (hematology, clinical chemistry, and urinalysis), thrombin generation (prothrombin time and activated partial thromboplastin time [aPTT]), immunogenicity tests (T cell subset), vital signs, physical examinations, and magnetic resonance imaging (MRI) for tumorigenicity.</desc>
      <group_list>
        <group group_id="E1">
          <title>Dose A Cohort</title>
          <description>Drug name and ingredients: CARTISTEM [allogeneic-unrelated, umbilical cord blood-derived mesenchymal stem cells, ex vivo cultured, combined with sodium hyaluronate] Dosage: Administer 0.5 mL of the combination product per cm^2 of the cartilage defect&#xD;
Cartilage defect size range: 2 to 5 cm2 (Dose A)&#xD;
CARTISTEM®</description>
        </group>
        <group group_id="E2">
          <title>Dose B Cohort</title>
          <description>Drug name and ingredients: CARTISTEM [allogeneic-unrelated, umbilical cord blood-derived mesenchymal stem cells, ex vivo cultured, combined with sodium hyaluronate] Dosage: Administer 0.5 mL of the combination product per cm^2 of the cartilage defect&#xD;
Cartilage defect size range: above 5 cm2 (Dose B)&#xD;
CARTISTEM®</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>bone marrow oedema</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>sinusitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>procedural pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>soft tissue injury</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>blood creatine phosphokinase increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>blood pressure increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>nuclear magnetic resonance imaging abnormal</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>JOINT RANGE OF MOTION DECREASED</sub_title>
                <counts group_id="E1" events="8" subjects_affected="6" subjects_at_risk="6"/>
                <counts group_id="E2" events="6" subjects_affected="6" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>arthralgia</sub_title>
                <counts group_id="E1" events="6" subjects_affected="5" subjects_at_risk="6"/>
                <counts group_id="E2" events="9" subjects_affected="6" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>joint effusion</sub_title>
                <counts group_id="E1" events="4" subjects_affected="3" subjects_at_risk="6"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>joint swelling</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="6"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>muscle atrophy</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>joint crepitation</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>chondromalacia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>chondropathy</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>exostosis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>haemarthrosis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>joint lock</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>plica syndrome</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>tendonitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>prehypertension</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Director of Product Development Department</name_or_title>
      <organization>MEDIPOST Co., Ltd.</organization>
      <phone>+82-2-3465-6740</phone>
      <email>meehyunj@medi-post.co.kr</email>
    </point_of_contact>
  </clinical_results>
</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/NCT01733186
org study id: MP-0201-01
nct id: NCT01733186
lead sponsor: 
has dmc: Yes
The purpose of this study is to determine whether CARTISTEM, a cell therapeutic product, is
      safe and effective in the treatment of articular cartilage defects of the knee as a result of
      ageing, trauma, or degenerative diseases.
Conventional treatment modalities have not been able to provide complete and sustained
      resolution of symptoms following damage to the articular cartilage. Despite the numerous
      techniques available today, complete healing of damaged or defective cartilage or consistent
      reproduction of normal hyaline cartilage does not occur, and continuous drug administration
      or secondary surgeries are common.

      Research in mesenchymal stem cells has had a rapid acceleration over the past decade and
      MSC-based therapy has become one of the objects of investigation for a new branch of medicine
      termed regenerative medicine. This emerging technology shows great promise for producing
      transplantable cartilage constructs to restore the function of degenerated joints.

      CARTISTEM®, a combination of human umbilical cord blood-derived mesenchymal stem cells and
      sodium hyaluronate, is intended to be used as a single-dose cellular therapeutic agent for
      cartilage regeneration in human subjects with cartilage defects of the knee as a result of
      ageing, trauma, or degenerative diseases.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: IKDC Score
time frame: 12 months
description: Subjects underwent a self-assessment of knee function using the IKDC (International Knee Documentation Committee Assessment)subjective knee evaluation before and after the administration of the IP. The assessment is designed to detect improvement or deterioration in symptoms, function, and sports activities due to knee impairment. The possible score ranges from 0 to 100, where 100 = no limitation with daily or sporting activities and the absence of symptoms.
The IKDC assessment was performed before IP administration and at Months 12 after IP administration in an exploratory fashion. The IKDC score from the Month 12 visit was used as a primary indicator of the post operative change.
The outcome was presented with the post-operative change amount from the baseline.
measure: VAS
time frame: 24 months
description: Subjects underwent a self-assessment of joint pain using the 100-mm VAS (Visual Analogue Scale) before and at Months 12 and 24 after IP (investigational product) administration. Higher values represent worse joint pain. Use of NSAIDs and any other analgesics had to be discontinued for 48 hours and 24 hours, respectively, prior to the 100 mm VAS evaluation. The outcome was presented with the post-operative change amount at Months 12 and 24 from the baseline.
100-mm VAS scores range from 0 to 100. Higher values represent worse joint pain.
measure: Lysholm Score
time frame: 24 months
description: The Lysholm knee scoring scale is a self-assessment that rates the severity of common complaints related to knee problems, such as pain, swelling, abnormal sensations, and ability to squat or climb stairs. The possible score ranges from 0 to 100, where 100 = no symptoms or disability. Scores are categorized as excellent (95 to 100), good (84 to 94), fair (65 to 83), and poor (≤64). Subjects underwent a self-assessment of knee function using the Lysholm score before IP administration and at Months 12 and 24 after IP administration. The outcome was presented with the post-operative change amount at Months 12 and 24 from the baseline.
measure: KOOS Score
time frame: 24 months
description: The Knee Injury and Osteoarthritis Outcome score (KOOS) knee survey is a self assessment of knee function and knee-related quality of life (QOL). Subjects responded to each question regarding knee-related symptoms, swelling, pain, impaired function, or changes in QOL with 1 of 5 possible answers that range from "never/not at all" to "always/extremely." The possible score for each parameter ranges from 0 to 100, where 0=extreme problems and 100=no problems. Subjects completed the KOOS knee survey before IP (investigational product) administration and at Month 24 after IP administration. The outcome was presented with the post-operative change amount at Month 24 from the baseline.
measure: IKDC Score
time frame: 24 months
description: Subjects underwent a self-assessment of knee function using the IKDC subjective knee evaluation before and after the administration of the IP. The assessment is designed to detect improvement or deterioration in symptoms, function, and sports activities due to knee impairment. The possible score ranges from 0 to 100, where 100 = no limitation with daily or sporting activities and the absence of symptoms. The IKDC assessment was performed before IP administration and at Month 24 after IP administration in an exploratory fashion. The outcome was presented with the post-operative change amount at Month 24 from the baseline.
arm group label: CARTISTEM®
arm group type: Experimental
description: Drug name and ingredients: CARTISTEM [allogeneic-unrelated, umbilical cord blood-derived mesenchymal stem cells, ex vivo cultured, combined with sodium hyaluronate] Dosage: Administer 0.5 mL of the combination product per cm^2 of the cartilage defect
intervention type: Biological
intervention name: CARTISTEM®
arm group label: CARTISTEM®
other name: human umbilical cord blood-derived mesenchymal stem cells
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Brian J Cole, MD
role: Principal Investigator
affiliation: Cartilage Restoration Center, Rush University Medical Center
last name: Andreas H Gomoll, MD
role: Principal Investigator
affiliation: Cartilage Repair Center, Brigham and Women's Hospital
facility: 
facility: 
country: United States
url: http://clinicaltrials.gov/ct2/show/NCT01041001?term=cartistem&rank=2
description: Study to Compare the Efficacy and Safety of Cartistem® and Microfracture in Patients With Knee Articular Cartilage Injury or Defect
responsible party type: Sponsor
mesh term: Cartilage Diseases
sharing ipd: Undecided
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 