<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/NCT03773328</url>
  </required_header>
  <id_info>
    <org_study_id>CK0801-201-1</org_study_id>
    <nct_id>NCT03773328</nct_id>
  </id_info>
  <brief_title>A Clinical Trial of CK0801 (a New Drug) In Patients With Treatment-Resistant Guillain-Barré Syndrome (GBS)</brief_title>
  <official_title>Phase I Trial To Evaluate The Safety Of CK0801 In Treatment-Resistant Guillain-Barré Syndrome (GBS)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Cellenkos, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Cellenkos, Inc.</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The goal of this research study is to determine whether it is safe and practical to give&#xD;
      CK0801 (a cord-blood derived T-regulatory cell product) to patients with Guillain-Barré&#xD;
      Syndrome (GBS). Researchers also want to determine the highest possible dose that is safe to&#xD;
      be given and to learn if CK0801 may improve the symptoms of GBS. There will be three doses of&#xD;
      CK0801 given during this study. A minimum of three patients will be treated in each dose&#xD;
      level. The dose a patient receives is dependent on the timing of when they enter the study,&#xD;
      as after each dose level is completed the following patients will receive the next highest&#xD;
      dose level.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      CK0801 (Cord blood-derived T-regulatory cells) consists of ex vivo expanded T-regulatory&#xD;
      cells with a flow cytometry phenotype of ≥ 60% CD4+CD25+ T-regulatory (Treg) cells and &lt; 10%&#xD;
      CD4-CD8+ T-cytotoxic/suppressor cells. The cellular starting material of CK0801 is a single&#xD;
      unit of umbilical cord blood (CBU) from a normal, healthy unrelated donor. Because Treg cells&#xD;
      are present only at low frequency in circulating blood or umbilical cord blood, production of&#xD;
      clinically relevant Treg cell doses requires ex vivo enrichment and expansion of Treg cells&#xD;
      with a CD4+CD25+ phenotype. In their natural state, T-regulatory (Treg) cells play an&#xD;
      important role in maintaining immune homeostasis and limiting autoimmune responses by&#xD;
      modulating both innate and adaptive immunity. Based on literature reports of animal studies&#xD;
      showing induction of immune tolerance by Treg cells in autoimmune diseases, graft-versus-host&#xD;
      disease, and solid organ transplant rejection, the administration of Treg cells in human&#xD;
      clinical trials has become an attractive strategy to induce immune tolerance in patients in a&#xD;
      variety of clinical settings.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    Pending contract negotiations&#xD;
  </why_stopped>
  <start_date type="Anticipated">November 2022</start_date>
  <completion_date type="Anticipated">February 2027</completion_date>
  <primary_completion_date type="Anticipated">February 2025</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>
    <intervention_model_description>Open-label, single arm study using a Simon 3 + 3 design. Study will utilize 3 dose cohorts with a minimum of 3 patients in each cohort.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Participants with Severe Infusion Toxicity as Assessed by CTCAE v4.0</measure>
    <time_frame>24 hours post-intervention</time_frame>
    <description>Number of Participants with Severe (Grade 3 or 4) Toxicity</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of Participants with Regimen Related Death</measure>
    <time_frame>30 days post-intervention</time_frame>
    <description>• severe (grade 3 or 4) cytokine release syndrome (CRS) within 30 days</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of Participants with Severe Cytokine Release Syndrome (CRS)</measure>
    <time_frame>30 days post-intervention</time_frame>
    <description>Number of Participants with Severe (Grade 3 or 4) CRS</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Guillain-Barré Syndrome</condition>
  <arm_group>
    <arm_group_label>CK0801, 50ml</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>All subjects will receive adoptive therapy with an infusion of unrelated cord blood-derived regulatory T cells: CK0801. Subjects will receive one 50mL intravenous dose of CK0801 (Treg cells) on study Day 0. A total of three cohorts will be evaluated.&#xD;
Cohort dosing will be as follows:&#xD;
Dose level 1 = 1x10e6/kg Treg cells per kg recipient ideal body weight (IBW); Dose level 2 = 3x10e6/kg Treg cells per kg recipient ideal body weight (IBW); Dose level 3 = 1x10e7/kg Treg cells per kg recipient ideal body weight (IBW).</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>CK0801</intervention_name>
    <description>CK0801 (Cord blood-derived T-regulatory cells)</description>
    <arm_group_label>CK0801, 50ml</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Subject fulfills the diagnostic criteria for Guillain-Barré syndrome (GBS) (Appendix&#xD;
             1).&#xD;
&#xD;
          2. HLA matched (≥ 3/6 at HLA-A, HLA-B, and HLA-DRB1) cord blood unit available for CK0801&#xD;
             generation.&#xD;
&#xD;
          3. Subjects age 18 to 70 years.&#xD;
&#xD;
          4. Subject has GBS disability scale score of 4 and unchanged 1 week after IVIG or PE&#xD;
             treatment (Appendix 2).&#xD;
&#xD;
          5. Subject has completed IVIG/PE treatment ≥ 4 weeks prior to CK0801 infusion.&#xD;
&#xD;
          6. Subject has modified Erasmus GBS outcome score (mEGOS score) of ≥7 at the time of&#xD;
             presentation and unchanged 1 week after IVIG or PE treatment (Table 3).&#xD;
&#xD;
          7. Bilirubin ≤ 2 x ULN and, ALT ≤ 2 x ULN (unless Gilbert's syndrome).&#xD;
&#xD;
          8. Calculated creatinine clearance of &gt; 50mL/min using the Cockroft-Gault equation for&#xD;
             adult patients 18 - 70 years old.&#xD;
&#xD;
          9. Female subjects of child bearing potential (FPCP) must have a negative urine or serum&#xD;
             pregnancy test. NOTE: FPCP is defined as premenopausal and not surgically sterilized.&#xD;
             FPCP must agree to use maximally effective birth control or to abstain from&#xD;
             heterosexual activity throughout the study. Effective contraceptive methods include&#xD;
             intra-uterine device, oral and/or injectable hormonal; contraception, or 2 adequate&#xD;
             barrier methods (e.g., cervical cap with spermicide, diaphragm with spermicide).&#xD;
&#xD;
         10. Subject has agreed to abide by all protocol required procedures including&#xD;
             study-related assessments, visits and long term follow up.&#xD;
&#xD;
         11. Subject is willing and able to provide written informed consent. If subject is&#xD;
             temporarily unable to sign the consent due to disease-related complications (e.g.,&#xD;
             upper extremity paralysis), a legally authorized representative (LAR) will be used.&#xD;
             The subject will sign the consent as soon as they are capable.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Subject has received immunotherapy, chemotherapy, biologic or investigational agent&#xD;
             within 4 weeks prior to CK0801 infusion.&#xD;
&#xD;
          2. Subject has received prior CB Treg therapy.&#xD;
&#xD;
          3. Subject has uncontrolled infection, not responding to appropriate antimicrobial agents&#xD;
             after seven days of therapy. The Protocol PI is the final arbiter of eligibility.&#xD;
&#xD;
          4. Subject has received a vaccination with a Live virus (e.g., Measles, Mumps, Rubella,&#xD;
             Varicella).&#xD;
&#xD;
          5. Subject is pregnant or breastfeeding.&#xD;
&#xD;
          6. HIV seropositivity&#xD;
&#xD;
          7. Subjects who are unable to provide consent or who, in the opinion of the Investigator&#xD;
             will be unlikely to fully comply with protocol requirements.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Tara Sadeghi</last_name>
    <role>Study Director</role>
    <affiliation>Sponsor GmbH</affiliation>
  </overall_official>
  <removed_countries>
    <country>United States</country>
  </removed_countries>
  <verification_date>January 2023</verification_date>
  <study_first_submitted>October 23, 2018</study_first_submitted>
  <study_first_submitted_qc>December 10, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 12, 2018</study_first_posted>
  <last_update_submitted>January 3, 2023</last_update_submitted>
  <last_update_submitted_qc>January 3, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">January 4, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Guillain-Barre Syndrome</mesh_term>
    <mesh_term>Syndrome</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/NCT03773328
org study id: CK0801-201-1
nct id: NCT03773328
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
The goal of this research study is to determine whether it is safe and practical to give
      CK0801 (a cord-blood derived T-regulatory cell product) to patients with Guillain-Barré
      Syndrome (GBS). Researchers also want to determine the highest possible dose that is safe to
      be given and to learn if CK0801 may improve the symptoms of GBS. There will be three doses of
      CK0801 given during this study. A minimum of three patients will be treated in each dose
      level. The dose a patient receives is dependent on the timing of when they enter the study,
      as after each dose level is completed the following patients will receive the next highest
      dose level.
CK0801 (Cord blood-derived T-regulatory cells) consists of ex vivo expanded T-regulatory
      cells with a flow cytometry phenotype of ≥ 60% CD4+CD25+ T-regulatory (Treg) cells and < 10%
      CD4-CD8+ T-cytotoxic/suppressor cells. The cellular starting material of CK0801 is a single
      unit of umbilical cord blood (CBU) from a normal, healthy unrelated donor. Because Treg cells
      are present only at low frequency in circulating blood or umbilical cord blood, production of
      clinically relevant Treg cell doses requires ex vivo enrichment and expansion of Treg cells
      with a CD4+CD25+ phenotype. In their natural state, T-regulatory (Treg) cells play an
      important role in maintaining immune homeostasis and limiting autoimmune responses by
      modulating both innate and adaptive immunity. Based on literature reports of animal studies
      showing induction of immune tolerance by Treg cells in autoimmune diseases, graft-versus-host
      disease, and solid organ transplant rejection, the administration of Treg cells in human
      clinical trials has become an attractive strategy to induce immune tolerance in patients in a
      variety of clinical settings.
allocation: N/A
intervention model: Single Group Assignment
intervention model description: Open-label, single arm study using a Simon 3 + 3 design. Study will utilize 3 dose cohorts with a minimum of 3 patients in each cohort.
primary purpose: Treatment
masking: None (Open Label)
measure: Number of Participants with Severe Infusion Toxicity as Assessed by CTCAE v4.0
time frame: 24 hours post-intervention
description: Number of Participants with Severe (Grade 3 or 4) Toxicity
measure: Number of Participants with Regimen Related Death
time frame: 30 days post-intervention
description: • severe (grade 3 or 4) cytokine release syndrome (CRS) within 30 days
measure: Number of Participants with Severe Cytokine Release Syndrome (CRS)
time frame: 30 days post-intervention
description: Number of Participants with Severe (Grade 3 or 4) CRS
arm group label: CK0801, 50ml
arm group type: Experimental
description: All subjects will receive adoptive therapy with an infusion of unrelated cord blood-derived regulatory T cells: CK0801. Subjects will receive one 50mL intravenous dose of CK0801 (Treg cells) on study Day 0. A total of three cohorts will be evaluated.
Cohort dosing will be as follows:
Dose level 1 = 1x10e6/kg Treg cells per kg recipient ideal body weight (IBW); Dose level 2 = 3x10e6/kg Treg cells per kg recipient ideal body weight (IBW); Dose level 3 = 1x10e7/kg Treg cells per kg recipient ideal body weight (IBW).
intervention type: Biological
intervention name: CK0801
description: CK0801 (Cord blood-derived T-regulatory cells)
arm group label: CK0801, 50ml
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Tara Sadeghi
role: Study Director
affiliation: Sponsor GmbH
country: United States
responsible party type: Sponsor
mesh term: Guillain-Barre Syndrome
mesh term: Syndrome
sharing ipd: No