<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/NCT02221258</url>
  </required_header>
  <id_info>
    <org_study_id>KSB-RA</org_study_id>
    <nct_id>NCT02221258</nct_id>
  </id_info>
  <brief_title>Safety of FURESTEM-RA Inj. in Patients With Moderate to Severe Rheumatoid Arthritis(RA)</brief_title>
  <acronym>RA</acronym>
  <official_title>Phase 1 Clinical Trial to Evaluate the Safety of FURESTEM-RA Inj. in Patients With Moderate to Severe Rheumatoid Arthritis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Kang Stem Biotech Co., Ltd.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Kang Stem Biotech Co., Ltd.</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of phase 1 clinical trial is to to evaluate safety in subjects with moderate to&#xD;
      severe rheumatoid arthritis after infusion.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Rheumatoid arthritis(RA) is a chronic and progressive autoimmune disease characterized by&#xD;
      synovial hyperplasia and joint damage leading to clinically significant functional&#xD;
      impairment. In RA, for some unknown reason, immune cells infiltrate into synovium of joint&#xD;
      and produce the 'rheumatoid factor', prostaglandins, cytokines and other mediators. It&#xD;
      damages joint and cartilage, even other organs. 80% of the RA patients have Rheumatoid factor&#xD;
      which is caused by high expression ratio of auto-antibodies in blood. Produced immune&#xD;
      complexes, immune cells and antigen-presenting cells(including macrophages, B cells,&#xD;
      dendritic cells) activate and release cytokines and then synovial tissue becomes thickened&#xD;
      and damaged.&#xD;
&#xD;
      It has been reported that synthetic DMARDs(disease-modifying antirheumatic drugs) including&#xD;
      methotrexate(MTX), sulfasalazine and biological DMARDs such as tumor necrosis factors(TNF)-α&#xD;
      blockers, abatacept and rituximab, often in combination with MTX, are effective. But they&#xD;
      still are limited by lack or loss of efficacy in certain patients and serious complications&#xD;
      such as serious infections and malignancies. So, there is a need to identify new treatment.&#xD;
&#xD;
      FURESTEM-RA Inj. is composed of allogeneic hUCB-MSC(human Umbilical Cord Blood&#xD;
      derived-Mesenchymal Stem cell). hUCB-MSCs are mesenchymal stem cells from umbilical cord&#xD;
      blood. Mesenchymal stem cells are well-known for immunosuppression, anti-inflammatory ability&#xD;
      and capable of differentiating into a wide range of cell types including osteocytes and&#xD;
      chondrocytes. Therefore, FURESTEM-RA Inj. has huge possibility as cell therapy products for&#xD;
      RA patients.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>October 2014</start_date>
  <completion_date type="Actual">October 2015</completion_date>
  <primary_completion_date type="Actual">October 2015</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Safety of FURESTEM-RA Inj. treatment</measure>
    <time_frame>4 weeks follow-up after treatment</time_frame>
    <description>Evaluate the number of adverse events, including clinically significant changes in physical examination, safety lab tests, ECG, vital signs</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">9</enrollment>
  <condition>Rheumatoid Arthritis</condition>
  <arm_group>
    <arm_group_label>FURESTEM-RA Inj.+DMARDs</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>FURESTEM-RA Inj. 1. 2.5x10^7 stem cells+DMARDs after registration FURESTEM-RA Inj. 2. 5.0x10^7 stem cells+DMARDs after registration FURESTEM-RA Inj. 3. 1.0x10^8 stem cells+DMARDs after registration</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>FURESTEM-RA Inj.</intervention_name>
    <description>Patients will be treated FURESTEM-RA Inj.+DMARDs(Disease-Modifying antirheumatic drugs)</description>
    <arm_group_label>FURESTEM-RA Inj.+DMARDs</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. of either gender, 19-80years old&#xD;
&#xD;
          2. Subjects must be diagnosed with ACR functional class I. II, III Rheumatoid Arthritis&#xD;
             according to the 2010 ACR/EULAR criteria for at least 12 weeks duration.&#xD;
&#xD;
          3. Subjects must be taking DMARDs or NSAIDs including methotrexate, sulfasalazine,&#xD;
             hydroxychloroquine, leflunomide of stable dose within 12 weeks before screening visit&#xD;
             and be willing to remain on stable dose throughout the study&#xD;
&#xD;
          4. If subject is currently administering steroids everyday, when steroid dose is&#xD;
             converted into prednisolone oral dose, the subject should take a stable&#xD;
             dose(≤10mg/day) over 4 weeks on screening visit&#xD;
&#xD;
          5. Subject who has moderate to severe disease activity (DAS28-ESR&gt;3.2) on screening visit&#xD;
&#xD;
          6. Subject who understands and voluntarily sign an informed consent form&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Subjects who is diagnosed ACR function class IV Rheumatoid Arthritis&#xD;
&#xD;
          2. Subjects who has cardiovascular disorders, blood dyscrasia, AIDS(Acquired Immune&#xD;
             Deficiency Syndrome), other rheumatic disease(Crohn's disease, systemic lupus&#xD;
             erythematosus, lyme disease, psoriatic arthritis, spondylarthropathy, infectious or&#xD;
             reactive arthritis, reiter's syndrome, etc.)&#xD;
&#xD;
          3. subject who has administered the following biological DMARDs&#xD;
&#xD;
               -  subject who has administered more than 1 drugs(Infliximab, Adalimumab,&#xD;
                  Etanercept, Anakinra, Abatacept) within 6 months before screening visit&#xD;
&#xD;
               -  subject who has administered Rituximab within 1 year before screening visit&#xD;
&#xD;
          4. Subject who has history of hypersensitivity, heavy metal poisoning, etc. to drugs&#xD;
             which is composed of similar components.&#xD;
&#xD;
          5. Subject who has treated intra-articular steroid injection within 4 weeks before&#xD;
             screening visit&#xD;
&#xD;
          6. Subject who has administered ACTH(adrenocorticotropic hormone) agents within 4 weeks&#xD;
             before screening visit&#xD;
&#xD;
          7. Subject who has undergone administration of any investigational drug within 30 days&#xD;
             before screening visit.&#xD;
&#xD;
          8. Subject who has diseases or takes medicine which are prohibited prescription of&#xD;
             NSAIDs.&#xD;
&#xD;
          9. Subject who needs to take the medicine which is prohibited to take at the same time&#xD;
&#xD;
         10. Pregnant, breast-feeding women&#xD;
&#xD;
         11. Subject who has sever dyshepatia (Serum creatinine level ≥ 1.7mg/dl)&#xD;
&#xD;
         12. Subject who has severe renal dysfunction (ALT/AST/bilirubin value ≥ 2 upper limit of&#xD;
             the normal range at screening test)&#xD;
&#xD;
         13. Any other condition which the PI Judges would make patient unsuitable for study&#xD;
             participation&#xD;
&#xD;
         14. Subject who experienced stem cell therapy&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>19 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Kichul Shin</last_name>
    <role>Principal Investigator</role>
    <affiliation>SMG-SNU Boramae Medical Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Seoul national University Boramae medical center</name>
      <address>
        <city>Seoul</city>
        <zip>156-707</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Korea, Republic of</country>
  </location_countries>
  <verification_date>March 2015</verification_date>
  <study_first_submitted>August 18, 2014</study_first_submitted>
  <study_first_submitted_qc>August 19, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 20, 2014</study_first_posted>
  <last_update_submitted>October 5, 2016</last_update_submitted>
  <last_update_submitted_qc>October 5, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">October 6, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Rheumatoid Arthritis</keyword>
  <keyword>Rheumatic Disease</keyword>
  <keyword>RA</keyword>
  <keyword>Stem cell</keyword>
  <keyword>Cell therapy</keyword>
  <keyword>furestem</keyword>
  <keyword>Umbilical cord Blood</keyword>
  <keyword>hUCB-MSC</keyword>
  <keyword>UCB-MSC</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Arthritis</mesh_term>
    <mesh_term>Arthritis, Rheumatoid</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/NCT02221258
org study id: KSB-RA
nct id: NCT02221258
lead sponsor: 
has dmc: Yes
The purpose of phase 1 clinical trial is to to evaluate safety in subjects with moderate to
      severe rheumatoid arthritis after infusion.
Rheumatoid arthritis(RA) is a chronic and progressive autoimmune disease characterized by
      synovial hyperplasia and joint damage leading to clinically significant functional
      impairment. In RA, for some unknown reason, immune cells infiltrate into synovium of joint
      and produce the 'rheumatoid factor', prostaglandins, cytokines and other mediators. It
      damages joint and cartilage, even other organs. 80% of the RA patients have Rheumatoid factor
      which is caused by high expression ratio of auto-antibodies in blood. Produced immune
      complexes, immune cells and antigen-presenting cells(including macrophages, B cells,
      dendritic cells) activate and release cytokines and then synovial tissue becomes thickened
      and damaged.

      It has been reported that synthetic DMARDs(disease-modifying antirheumatic drugs) including
      methotrexate(MTX), sulfasalazine and biological DMARDs such as tumor necrosis factors(TNF)-α
      blockers, abatacept and rituximab, often in combination with MTX, are effective. But they
      still are limited by lack or loss of efficacy in certain patients and serious complications
      such as serious infections and malignancies. So, there is a need to identify new treatment.

      FURESTEM-RA Inj. is composed of allogeneic hUCB-MSC(human Umbilical Cord Blood
      derived-Mesenchymal Stem cell). hUCB-MSCs are mesenchymal stem cells from umbilical cord
      blood. Mesenchymal stem cells are well-known for immunosuppression, anti-inflammatory ability
      and capable of differentiating into a wide range of cell types including osteocytes and
      chondrocytes. Therefore, FURESTEM-RA Inj. has huge possibility as cell therapy products for
      RA patients.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Safety of FURESTEM-RA Inj. treatment
time frame: 4 weeks follow-up after treatment
description: Evaluate the number of adverse events, including clinically significant changes in physical examination, safety lab tests, ECG, vital signs
arm group label: FURESTEM-RA Inj.+DMARDs
arm group type: Experimental
description: FURESTEM-RA Inj. 1. 2.5x10^7 stem cells+DMARDs after registration FURESTEM-RA Inj. 2. 5.0x10^7 stem cells+DMARDs after registration FURESTEM-RA Inj. 3. 1.0x10^8 stem cells+DMARDs after registration
intervention type: Biological
intervention name: FURESTEM-RA Inj.
description: Patients will be treated FURESTEM-RA Inj.+DMARDs(Disease-Modifying antirheumatic drugs)
arm group label: FURESTEM-RA Inj.+DMARDs
criteria: 
gender: All
minimum age: 19 Years
maximum age: 80 Years
healthy volunteers: No
last name: Kichul Shin
role: Principal Investigator
affiliation: SMG-SNU Boramae Medical Center
facility: 
country: Korea, Republic of
responsible party type: Sponsor
mesh term: Arthritis
mesh term: Arthritis, Rheumatoid