<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/NCT03265444</url>
  </required_header>
  <id_info>
    <org_study_id>CS10BR05-MSA101</org_study_id>
    <nct_id>NCT03265444</nct_id>
  </id_info>
  <brief_title>Safety and Tolerability of CS10BR05 Inj. in Subjects With Multiple System Atrophy</brief_title>
  <official_title>A Phase 1 Study to Evaluate the Safety and Tolerability of Autologous Bone Marrow Derived Mesenchymal Stem Cells in Subjects With Multiple System Atrophy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Corestemchemon, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Corestemchemon, Inc.</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of conducting phase 1 trial is to evaluate the safety and tolerability of&#xD;
      autologous bone marrow-derived mesenchymal stem cells(CS10BR05) in subjects with Multiple&#xD;
      System Atrophy.&#xD;
&#xD;
      Evaluation of DLT by carotid artery(intra-arterial) injection according to dose-escalating in&#xD;
      Multiple System Atrophy.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Multiple system atrophy is a neurodegenerative disease of the central nervous system which is&#xD;
      accompanied by signs of autonomic imbalance (orthostatic hypotension, urinary problems,&#xD;
      erectile dysfunction), Parkinson's symptoms (movement decreases, limb tremors) and cerebellar&#xD;
      ataxia symptoms (grogginess, pronounced incorrectly). It shows signs similar to Parkinson's&#xD;
      disease, however, it doesn't show improvement of symptoms by dopaminergic drugs and occurs at&#xD;
      any age.&#xD;
&#xD;
      The clinical trial was designed as a single center, open-label, public phase 1 clinical&#xD;
      trials.&#xD;
&#xD;
      If that subject's written consent to participate in this clinical trial will be conducted the&#xD;
      required examinations and tests in accordance with the study protocol.&#xD;
&#xD;
      Then, the register for each dose step. For the final 3 subjects in the inclusion / exclusion&#xD;
      criteria and be administered a drug test.&#xD;
&#xD;
      And check the adverse events for more than four hours after administration of the&#xD;
      investigational drug, and will determine whether the expression of adverse drug reaction(ADR)&#xD;
      by the visit after 1 days, 14 days and 28 days.&#xD;
&#xD;
      Except for dose administration, all subject are tested in the same schedule. As a result of&#xD;
      evaluating severity of AE divided into subjective, objective in accordance with the CTCAE&#xD;
      (Version 4.0) standards.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">April 13, 2018</start_date>
  <completion_date type="Actual">December 5, 2019</completion_date>
  <primary_completion_date type="Actual">December 5, 2019</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>Dose-Limiting Toxicity and Maximum Tolerated Dose of CS10BR05 Inj.</measure>
    <time_frame>up to 28days</time_frame>
    <description>To evaluate the safety and tolerability of CS10BR05 Inj. in patients with Multiple System Atrophy including determination of its Dose Limiting Toxicity (DLT) and Maximum Tolerated Dose (MTD).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Adverse events, frequency and rate of vitals sign, laboratory test, physical examination, ECG, etc.</measure>
    <time_frame>up to 28days</time_frame>
    <description>To evaluate the safety and tolerability of CS10BR05 Inj. in patients with Multiple System Atrophy.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Unified Multiple System Atrophy Rating Scale(UMSARS)</measure>
    <time_frame>-35days, 28days</time_frame>
    <description>Part I (Historical review), part II (Motor examination scale), part III (Autonomic examination), part IV (Global disability scale) assessment</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">9</enrollment>
  <condition>Multiple System Atrophy</condition>
  <arm_group>
    <arm_group_label>CS10BR05</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The single injection of CS10BR05 Inj. in the carotid artery</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>CS10BR05</intervention_name>
    <description>The single injection of CS10BR05 Inj. in the carotid artery; Step 1 dose : 3.0x105cells/kg; Step 2 dose : 6.0x105cells/kg; Step 3 dose : 9.0x105cells/kg; The duration of follow up study following the single dose of CS10BR05 is 28 days.</description>
    <arm_group_label>CS10BR05</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male and Female patients aged ≥30 years and ≤ 75 years&#xD;
&#xD;
          -  Meet criteria for diagnosis of probable MSA -cerebellar type according to the Gilman&#xD;
             Criteria(2008)&#xD;
&#xD;
          -  MRI or PET imaging showed a decrease in the cerebellar atrophy or cerebral metabolism&#xD;
&#xD;
          -  Patients who are less than 4 years from the time of documented MSA diagnosis&#xD;
&#xD;
          -  Patients unified MSA rating scale 30~50&#xD;
&#xD;
          -  Those who have no hematologic abnormalities and who are not suspected of failing bone&#xD;
             marrow function&#xD;
&#xD;
          -  Patients who consented to participate in the study in writing by themselves or their&#xD;
             legal representatives&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Suspected clear Dementia (K-MMSE &lt; 24)&#xD;
&#xD;
          -  DSM-IV criteria for Dementia&#xD;
&#xD;
          -  Radiologic imaging findings suggest that vascular encephalopathy coexist&#xD;
&#xD;
          -  Other central nervous system diseases except MSA (Parkinsons disease etc.)&#xD;
&#xD;
          -  Patients with Stroke or Brain surgery&#xD;
&#xD;
          -  If there is a coexistence of severe medical illness, or if it is in a severe pyrexia&#xD;
             state&#xD;
&#xD;
          -  Serum SGOT / SGPT measures above three times of upper limit of normal or creatine&#xD;
             levels were above 1.5 times of upper limit of normal levels were more than 1.5 times&#xD;
             normal&#xD;
&#xD;
          -  disease that affects the patient's long-term survival(Tumor, Serious Heart failure)&#xD;
&#xD;
          -  Patients with genetic tests showed that spinocerebellar ataxia 1, 2, 3, 6, 7, 17&#xD;
&#xD;
          -  Patients with unstable vital signs&#xD;
&#xD;
          -  Patients with uncontrolled comorbidities such as moderate to severe infections,&#xD;
             bleeding&#xD;
&#xD;
          -  Those who are found to be active to viral infection(HBV, HCV, HIV, CMV, HTLVⅠ/Ⅱ, VDRL)&#xD;
&#xD;
          -  Patients who are hypersensitive to bovine protein or antibiotics such as penicillin&#xD;
             and streptomycin&#xD;
&#xD;
          -  Patients with difficult catheter insertion(bleeding disorder, artery hardening&#xD;
             narrowness, Patients who are at risk of stroke in cerebral angiography)&#xD;
&#xD;
          -  Patients with cardiovascular disease(for example, hypertension, myocardial infarction&#xD;
             etc;)&#xD;
&#xD;
          -  Severe disease uncontrolled (diabetes)&#xD;
&#xD;
          -  Those who are using drug likely to affect bone marrow functions&#xD;
&#xD;
          -  Pregnant women or nursing women&#xD;
&#xD;
          -  Women of childbearing age and male who do not consent to use proper contraception to&#xD;
             prevent his partner from being pregnant during participation in the study&#xD;
&#xD;
          -  Now clinical trials treated with other drugs and in clinical trials the previous 4&#xD;
             weeks&#xD;
&#xD;
          -  Subjects who by the investigator to make them ineligible for participation in this&#xD;
             clinical study&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>30 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Phil Hyu Lee, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Yonsei University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Yonsei University College of Medicine</name>
      <address>
        <city>Seoul</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Korea, Republic of</country>
  </location_countries>
  <link>
    <url>http://www.corestem.com</url>
    <description>Corestem Inc.</description>
  </link>
  <verification_date>August 2020</verification_date>
  <study_first_submitted>August 6, 2017</study_first_submitted>
  <study_first_submitted_qc>August 25, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 29, 2017</study_first_posted>
  <last_update_submitted>August 6, 2020</last_update_submitted>
  <last_update_submitted_qc>August 6, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">August 7, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>MSA</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Multiple System Atrophy</mesh_term>
    <mesh_term>Shy-Drager Syndrome</mesh_term>
    <mesh_term>Atrophy</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03265444
org study id: CS10BR05-MSA101
nct id: NCT03265444
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
The purpose of conducting phase 1 trial is to evaluate the safety and tolerability of
      autologous bone marrow-derived mesenchymal stem cells(CS10BR05) in subjects with Multiple
      System Atrophy.

      Evaluation of DLT by carotid artery(intra-arterial) injection according to dose-escalating in
      Multiple System Atrophy.
Multiple system atrophy is a neurodegenerative disease of the central nervous system which is
      accompanied by signs of autonomic imbalance (orthostatic hypotension, urinary problems,
      erectile dysfunction), Parkinson's symptoms (movement decreases, limb tremors) and cerebellar
      ataxia symptoms (grogginess, pronounced incorrectly). It shows signs similar to Parkinson's
      disease, however, it doesn't show improvement of symptoms by dopaminergic drugs and occurs at
      any age.

      The clinical trial was designed as a single center, open-label, public phase 1 clinical
      trials.

      If that subject's written consent to participate in this clinical trial will be conducted the
      required examinations and tests in accordance with the study protocol.

      Then, the register for each dose step. For the final 3 subjects in the inclusion / exclusion
      criteria and be administered a drug test.

      And check the adverse events for more than four hours after administration of the
      investigational drug, and will determine whether the expression of adverse drug reaction(ADR)
      by the visit after 1 days, 14 days and 28 days.

      Except for dose administration, all subject are tested in the same schedule. As a result of
      evaluating severity of AE divided into subjective, objective in accordance with the CTCAE
      (Version 4.0) standards.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Dose-Limiting Toxicity and Maximum Tolerated Dose of CS10BR05 Inj.
time frame: up to 28days
description: To evaluate the safety and tolerability of CS10BR05 Inj. in patients with Multiple System Atrophy including determination of its Dose Limiting Toxicity (DLT) and Maximum Tolerated Dose (MTD).
measure: Adverse events, frequency and rate of vitals sign, laboratory test, physical examination, ECG, etc.
time frame: up to 28days
description: To evaluate the safety and tolerability of CS10BR05 Inj. in patients with Multiple System Atrophy.
measure: Unified Multiple System Atrophy Rating Scale(UMSARS)
time frame: -35days, 28days
description: Part I (Historical review), part II (Motor examination scale), part III (Autonomic examination), part IV (Global disability scale) assessment
arm group label: CS10BR05
arm group type: Experimental
description: The single injection of CS10BR05 Inj. in the carotid artery
intervention type: Biological
intervention name: CS10BR05
description: The single injection of CS10BR05 Inj. in the carotid artery; Step 1 dose : 3.0x105cells/kg; Step 2 dose : 6.0x105cells/kg; Step 3 dose : 9.0x105cells/kg; The duration of follow up study following the single dose of CS10BR05 is 28 days.
arm group label: CS10BR05
criteria: 
gender: All
minimum age: 30 Years
maximum age: 75 Years
healthy volunteers: No
last name: Phil Hyu Lee, M.D.
role: Principal Investigator
affiliation: Yonsei University
facility: 
country: Korea, Republic of
url: http://www.corestem.com
description: Corestem Inc.
responsible party type: Sponsor
mesh term: Multiple System Atrophy
mesh term: Shy-Drager Syndrome
mesh term: Atrophy
sharing ipd: No