<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/NCT04495582</url>
  </required_header>
  <id_info>
    <org_study_id>CS10BR05-MSA101-E</org_study_id>
    <nct_id>NCT04495582</nct_id>
  </id_info>
  <brief_title>Long-term Follow-up of Phase 1 Clinical Trial of CS10BR05(CS10BR05-MSA101)</brief_title>
  <official_title>Observational Study of Long-term Safety and Efficacy of Subjects Who Participated in CS10BR05 Inj. Phase 1 Study</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 study purpose is conducting follow-up surveillance for the incidence of adverse events&#xD;
      and efficacy of subjects participated in phase 1 trial to evaluate the safety and&#xD;
      tolerability of autologous bone marrow-derived mesenchymal stem cells (CS10BR05) in subjects&#xD;
      with Multiple System Atrophy until 60 months from administering investigational product (IP).&#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 and&#xD;
      erectile dysfunction), Parkinson's symptoms (movement decreases and limb tremors) and&#xD;
      cerebellar ataxia symptoms (grogginess and incorrect pronunciation). It shows signs similar&#xD;
      to Parkinson's disease, however, it doesn't show improvement of symptoms by dopaminergic&#xD;
      drugs and occurs at any age.&#xD;
&#xD;
      The purpose is conducting follow-up surveillance for the incidence of adverse events and&#xD;
      efficacy of subjects participated in phase 1 trial to evaluate the safety and tolerability of&#xD;
      autologous bone marrow-derived mesenchymal stem cells (CS10BR05) in subjects with Multiple&#xD;
      System Atrophy until 60 months from administering investigational product (IP).&#xD;
&#xD;
      Because it is the following observational study for subjects participated in phase 1 trial,&#xD;
      there is no additional administration of the investigational product in the study.&#xD;
&#xD;
      If the subjects who participated in phase 1 trial voluntarily consent in writing to take part&#xD;
      in this observational study, the subjects visit the institution according to the protocol&#xD;
      that designed the follow-up visits every 3 months (Visit 1, Visit 2) until 6 months from&#xD;
      administration of investigational product and since then 6 months later (Visit 3), every 12&#xD;
      months (Visit 4~7) to observe the incidence of adverse events and efficacy.&#xD;
&#xD;
      As a result of evaluating severity of AE divided into subjective, objective in accordance&#xD;
      with the CTCAE (Version 4.0) standards.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">August 28, 2018</start_date>
  <completion_date type="Anticipated">November 2024</completion_date>
  <primary_completion_date type="Anticipated">November 2024</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Other</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Safety assessment(evaluation)</measure>
    <time_frame>5 years</time_frame>
    <description>Adverse events(AE): After the completion of the CS10BR05-MSA101 phase 1 trial, new adverse events, including tumor are assessed and detailed information is collected at each visit. Whole body PET test is performed for tumor observation at visit 7.&#xD;
Laboratory test: The following laboratory tests are performed at each visit.&#xD;
Hematology test: WBC, RBC, Hemoglobin, Hematocrit, Platelets count, WBC Diffcount&#xD;
Chemistry test: Na, K, Ca, Cl, BUN, Creatinine, Uric acid, Total bilirubin, Albumin, Total protein, Creatine Kinase, Cystatin-C, ALT, AST, r-GT, ALP, LDH, Glucose, Total cholesterol, Triglyceride&#xD;
Urine test: Protein, Glucose, Urobilinogen, WBC, RBC&#xD;
Measuring vital signs (blood pressure in mmHg, heart rate in bpm, body temperature in Celsius) is performed at each visit.&#xD;
Physical examination is performed at each visit. If clinically significant abnormal findings are recorded in the CRF and collected as AEs.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Efficacy assessment(evaluation)</measure>
    <time_frame>5 years</time_frame>
    <description>The following tests are conducted at each visit to exploratively evaluate the efficacy. Evaluate the change of score of each tools.&#xD;
-UMSARS(Unified Multiple System Atrophy rating scale)&#xD;
The scale comprises the following components:&#xD;
Part I, historical, 12 items; Part II, motor examination, 14 items; Part III, autonomic examination; and Part IV, global disability scale (total UMSARS with scores ranging from 1 to 109)&#xD;
-K-MMSE(Korea Mini-Mental Status Examination)&#xD;
The scale comprises the following components:&#xD;
Orientation, memory, attention and calculation, naming and language, and drawing (total K-MMSE score of 30)&#xD;
-DSM-Ⅳ(Diagnostic and Statistical Manual of Mental Disorders)</description>
  </primary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Actual">8</enrollment>
  <condition>Multiple System Atrophy</condition>
  <arm_group>
    <arm_group_label>Non-Interventional Study group</arm_group_label>
    <description>Subjects participating in this observational study originally participated in CS10BR05 Inj. phase 1 study.</description>
  </arm_group>
  <eligibility>
    <study_pop>
      <textblock>
        The subjects who participated in the phase 1 clinical trial(NCT03265444, Protocol No.:&#xD;
        CS10BR05-MSA101) will be enrolled in this study, so the number of enrolled subjects will&#xD;
        depend on the number of actual enrolled subjects for the phase 1 clinical trial.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Subjects who participated in the phase 1 clinical trial(Protocol No.: CS10BR05-&#xD;
             MSA101) at 3 months after administering investigational product&#xD;
&#xD;
          -  Subjects who give a written, signed and dated informed consent spontaneously&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Subjects who decided as inappropriate cases to participate in the observational study&#xD;
             by investigator&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>N/A</maximum_age>
  </eligibility>
  <overall_official>
    <last_name>Phil Hyu Lee, MD</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://corestem.com/</url>
    <description>Corestem Inc.</description>
  </link>
  <link>
    <url>http://mdctc.yuhs.ac/HPC/Sinchon/IRB/IrbIntro</url>
    <description>Severance hospital Institutional Review Board</description>
  </link>
  <verification_date>August 2023</verification_date>
  <study_first_submitted>July 21, 2020</study_first_submitted>
  <study_first_submitted_qc>July 28, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">August 3, 2020</study_first_posted>
  <last_update_submitted>August 1, 2023</last_update_submitted>
  <last_update_submitted_qc>August 1, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 2, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Mesenchymal stem cell</keyword>
  <keyword>Cell therapy</keyword>
  <keyword>Multiple system atrophy</keyword>
  <keyword>Neuroprotection</keyword>
  <keyword>CS10BR05</keyword>
  <keyword>Long-term Safety Study</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/NCT04495582
org study id: CS10BR05-MSA101-E
nct id: NCT04495582
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
The study purpose is conducting follow-up surveillance for the incidence of adverse events
      and efficacy of subjects participated in phase 1 trial to evaluate the safety and
      tolerability of autologous bone marrow-derived mesenchymal stem cells (CS10BR05) in subjects
      with Multiple System Atrophy until 60 months from administering investigational product (IP).
Multiple system atrophy is a neurodegenerative disease of the central nervous system which is
      accompanied by signs of autonomic imbalance (orthostatic hypotension, urinary problems and
      erectile dysfunction), Parkinson's symptoms (movement decreases and limb tremors) and
      cerebellar ataxia symptoms (grogginess and incorrect pronunciation). 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 purpose is conducting follow-up surveillance for the incidence of adverse events and
      efficacy of subjects participated in phase 1 trial to evaluate the safety and tolerability of
      autologous bone marrow-derived mesenchymal stem cells (CS10BR05) in subjects with Multiple
      System Atrophy until 60 months from administering investigational product (IP).

      Because it is the following observational study for subjects participated in phase 1 trial,
      there is no additional administration of the investigational product in the study.

      If the subjects who participated in phase 1 trial voluntarily consent in writing to take part
      in this observational study, the subjects visit the institution according to the protocol
      that designed the follow-up visits every 3 months (Visit 1, Visit 2) until 6 months from
      administration of investigational product and since then 6 months later (Visit 3), every 12
      months (Visit 4~7) to observe the incidence of adverse events and efficacy.

      As a result of evaluating severity of AE divided into subjective, objective in accordance
      with the CTCAE (Version 4.0) standards.
observational model: Other
time perspective: Prospective
measure: Safety assessment(evaluation)
time frame: 5 years
description: Adverse events(AE): After the completion of the CS10BR05-MSA101 phase 1 trial, new adverse events, including tumor are assessed and detailed information is collected at each visit. Whole body PET test is performed for tumor observation at visit 7.
Laboratory test: The following laboratory tests are performed at each visit.
Hematology test: WBC, RBC, Hemoglobin, Hematocrit, Platelets count, WBC Diffcount
Chemistry test: Na, K, Ca, Cl, BUN, Creatinine, Uric acid, Total bilirubin, Albumin, Total protein, Creatine Kinase, Cystatin-C, ALT, AST, r-GT, ALP, LDH, Glucose, Total cholesterol, Triglyceride
Urine test: Protein, Glucose, Urobilinogen, WBC, RBC
Measuring vital signs (blood pressure in mmHg, heart rate in bpm, body temperature in Celsius) is performed at each visit.
Physical examination is performed at each visit. If clinically significant abnormal findings are recorded in the CRF and collected as AEs.
measure: Efficacy assessment(evaluation)
time frame: 5 years
description: The following tests are conducted at each visit to exploratively evaluate the efficacy. Evaluate the change of score of each tools.
-UMSARS(Unified Multiple System Atrophy rating scale)
The scale comprises the following components:
Part I, historical, 12 items; Part II, motor examination, 14 items; Part III, autonomic examination; and Part IV, global disability scale (total UMSARS with scores ranging from 1 to 109)
-K-MMSE(Korea Mini-Mental Status Examination)
The scale comprises the following components:
Orientation, memory, attention and calculation, naming and language, and drawing (total K-MMSE score of 30)
-DSM-Ⅳ(Diagnostic and Statistical Manual of Mental Disorders)
arm group label: Non-Interventional Study group
description: Subjects participating in this observational study originally participated in CS10BR05 Inj. phase 1 study.
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: N/A
maximum age: N/A
last name: Phil Hyu Lee, MD
role: Principal Investigator
affiliation: Yonsei University
facility: 
country: Korea, Republic of
url: http://corestem.com/
description: Corestem Inc.
url: http://mdctc.yuhs.ac/HPC/Sinchon/IRB/IrbIntro
description: Severance hospital Institutional Review Board
responsible party type: Sponsor
mesh term: Multiple System Atrophy
mesh term: Shy-Drager Syndrome
mesh term: Atrophy
sharing ipd: No