<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/NCT04452097</url>
  </required_header>
  <id_info>
    <org_study_id>BXU001-COVID19</org_study_id>
    <nct_id>NCT04452097</nct_id>
  </id_info>
  <brief_title>Use of hUC-MSC Product (BX-U001) for the Treatment of COVID-19 With ARDS</brief_title>
  <official_title>A Phase 1/2a Study of the Safety and Efficacy of BX-U001 for the Treatment of Severe COVID-19 Pneumonia With Moderate to Severe Acute Respiratory Distress Syndrome (ARDS).</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Baylx Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Baylx 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>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a phase 1/2a study including 2 parts, phase 1 and phase 2a. The phase 1 part is an&#xD;
      open-label, single-arm, dose-escalating study to evaluate the safety and explore the dose&#xD;
      limiting toxicity and maximum tolerated dose of a human umbilical cord derived mesenchymal&#xD;
      stem cell product (BX-U001) in severe COVID-19 pneumonia patients with acute respiratory&#xD;
      distress syndrome (ARDS). Qualified subjects after the screening will be divided into low,&#xD;
      medium, or high dose groups to receive a single intravenous infusion of BX-U001 at the dose&#xD;
      of 0.5×10^6, 1.0×10^6, or 1.5×10^6 cells/kg of body weight, respectively. The Phase 2a part&#xD;
      is a randomized, placebo-controlled, double-blind clinical trial examining the safety and&#xD;
      biological effects of BX-U001 at the appropriate dose selected from phase 1 for severe&#xD;
      COVID-19 pneumonia patients with the same inclusion/exclusion criteria as the phase 1 part.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Not yet recruiting</overall_status>
  <start_date type="Anticipated">July 1, 2023</start_date>
  <completion_date type="Anticipated">May 31, 2024</completion_date>
  <primary_completion_date type="Anticipated">March 31, 2024</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>Non-Randomized</allocation>
    <intervention_model>Sequential Assignment</intervention_model>
    <intervention_model_description>In phase 1, eligible subjects will be divided into low, medium and high-dose groups with 3 patients/group. If there is no safety concerns for each group, the dose will be escalated from lower dose to the next higher dose. In phase 2a, a total of 30 subjects will be randomized into the treatment and control groups with a ratio of 3:2.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Incidence of infusion-related adverse events</measure>
    <time_frame>Day 3</time_frame>
    <description>Safety will be defined by the incidence of infusion-related adverse events as assessed by the treating physician</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence of any treatment-emergent adverse events (TEAEs) and treatment emergent serious adverse events (TESAEs)</measure>
    <time_frame>Day 28</time_frame>
    <description>Safety will be defined by the incidence of TEAEs and TESAEs as assessed by the treating physician</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Selection of an appropriate dose of BX-U001 for the following Phase 2 study</measure>
    <time_frame>Day 28</time_frame>
    <description>The dose will be selected based on the assessment of dose-limiting toxicity and maximum tolerated dose.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>All-cause mortality</measure>
    <time_frame>Day 28</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of patients achieving clinical response by the improvement of at least 2 points on the 7-point ordinal scale.</measure>
    <time_frame>Day 14</time_frame>
    <description>The scale is as follows: 1. Death 2. Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO) 3. Hospitalized, on non-invasive ventilation or high flow oxygen devices 4. Hospitalized, requiring low flow supplemental oxygen 5. Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise) 6. Hospitalized, not requiring supplemental oxygen - no longer required ongoing medical care 7. Not hospitalized.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of ICU stay</measure>
    <time_frame>Day 28</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of hospital stay</measure>
    <time_frame>Day 28</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in blood cytokine levels</measure>
    <time_frame>Day 28</time_frame>
  </secondary_outcome>
  <number_of_arms>5</number_of_arms>
  <enrollment type="Anticipated">39</enrollment>
  <condition>COVID-19</condition>
  <condition>ARDS</condition>
  <condition>Acute Respiratory Distress Syndrome</condition>
  <arm_group>
    <arm_group_label>Phase 1 Low-dose Group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Eligible subjects will receive a single infusion of hUC-MCS product at the dose of 0.5 million cells/kg in addition to standard of care treatment.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Phase 1 Middle-dose Group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Eligible subjects will receive a single infusion of hUC-MCS product at the dose of 1 million cells/kg in addition to standard of care treatment.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Phase 1 High-dose Group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Eligible subjects will receive a single infusion of hUC-MCS product at the dose of 1.5 million cells/kg in addition to standard of care treatment.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Phase 2a Treatment Group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Eligible subjects will receive a single infusion of hUC-MCS product at the selected dose from phase 1 in addition to standard of care treatment.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Phase 2a Control Group</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Eligible subjects will receive a single infusion of placebo control and standard of care treatment.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Human umbilical cord mesenchymal stem cells + best supportive care</intervention_name>
    <description>hUC-MSC product will be administered intravenously in addition to the standard of care treatment.</description>
    <arm_group_label>Phase 1 High-dose Group</arm_group_label>
    <arm_group_label>Phase 1 Low-dose Group</arm_group_label>
    <arm_group_label>Phase 1 Middle-dose Group</arm_group_label>
    <arm_group_label>Phase 2a Treatment Group</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo control + best supportive care</intervention_name>
    <description>Placebo control will be administered intravenously in addition to the standard of care treatment.</description>
    <arm_group_label>Phase 2a Control Group</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Male or female, aged between 18 and 80;&#xD;
&#xD;
          2. Laboratory (RT-PCR, Gene Sequencing or Antibody) confirmed cases of severe COVID-19&#xD;
             pneumonia with mild to moderate ARDS (Berlin definition);&#xD;
&#xD;
          3. Patients are intubated;&#xD;
&#xD;
          4. Patients who voluntarily adhere to the research procedures and ensure good compliance&#xD;
             during the research period;&#xD;
&#xD;
          5. Patients who fully understand the research nature of this study and sign written&#xD;
             informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Subjects who have received investigational drug (except for Remdesivir) for the&#xD;
             treatment of COVID-19 within 30 days before screening;&#xD;
&#xD;
          2. Subjects who are pregnant, breastfeeding or whose urinary pregnancy test is positive&#xD;
             before participation in the study; subjects who are pregnant, breastfeeding, have a&#xD;
             birth plan, or are unwillingness to use contraception during the study period and&#xD;
             within 12 months of infusion; except for subjects who have sterilization surgery or&#xD;
             menopause during the study period;&#xD;
&#xD;
          3. Within 3 days before screening/randomization, subjects who have used high-dose&#xD;
             corticosteroids that is equivalent to methylprednisolone &gt;240 mg/day or irregular use&#xD;
             of systemic corticosteroids to treat other diseases that could affect the efficacy&#xD;
             evaluated by the investigator;&#xD;
&#xD;
          4. Subjects receiving extracorporeal membrane oxygenation (ECMO) support.&#xD;
&#xD;
          5. Subjects who are allergic to low-molecular-weight heparin calcium or human albumin;&#xD;
&#xD;
          6. Subjects with ongoing malignant tumors.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Vincent Liao, MD. Ph.D.</last_name>
    <phone>949-308-1952</phone>
    <email>baylx@baylxinc.com</email>
  </overall_contact>
  <verification_date>August 2022</verification_date>
  <study_first_submitted>June 28, 2020</study_first_submitted>
  <study_first_submitted_qc>June 28, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 30, 2020</study_first_posted>
  <last_update_submitted>August 9, 2022</last_update_submitted>
  <last_update_submitted_qc>August 9, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">August 10, 2022</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>COVID-19</mesh_term>
    <mesh_term>Respiratory Distress Syndrome</mesh_term>
    <mesh_term>Respiratory Distress Syndrome, Newborn</mesh_term>
    <mesh_term>Acute Lung Injury</mesh_term>
    <mesh_term>Syndrome</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/NCT04452097
org study id: BXU001-COVID19
nct id: NCT04452097
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
This is a phase 1/2a study including 2 parts, phase 1 and phase 2a. The phase 1 part is an
      open-label, single-arm, dose-escalating study to evaluate the safety and explore the dose
      limiting toxicity and maximum tolerated dose of a human umbilical cord derived mesenchymal
      stem cell product (BX-U001) in severe COVID-19 pneumonia patients with acute respiratory
      distress syndrome (ARDS). Qualified subjects after the screening will be divided into low,
      medium, or high dose groups to receive a single intravenous infusion of BX-U001 at the dose
      of 0.5×10^6, 1.0×10^6, or 1.5×10^6 cells/kg of body weight, respectively. The Phase 2a part
      is a randomized, placebo-controlled, double-blind clinical trial examining the safety and
      biological effects of BX-U001 at the appropriate dose selected from phase 1 for severe
      COVID-19 pneumonia patients with the same inclusion/exclusion criteria as the phase 1 part.
allocation: Non-Randomized
intervention model: Sequential Assignment
intervention model description: In phase 1, eligible subjects will be divided into low, medium and high-dose groups with 3 patients/group. If there is no safety concerns for each group, the dose will be escalated from lower dose to the next higher dose. In phase 2a, a total of 30 subjects will be randomized into the treatment and control groups with a ratio of 3:2.
primary purpose: Treatment
masking: None (Open Label)
measure: Incidence of infusion-related adverse events
time frame: Day 3
description: Safety will be defined by the incidence of infusion-related adverse events as assessed by the treating physician
measure: Incidence of any treatment-emergent adverse events (TEAEs) and treatment emergent serious adverse events (TESAEs)
time frame: Day 28
description: Safety will be defined by the incidence of TEAEs and TESAEs as assessed by the treating physician
measure: Selection of an appropriate dose of BX-U001 for the following Phase 2 study
time frame: Day 28
description: The dose will be selected based on the assessment of dose-limiting toxicity and maximum tolerated dose.
measure: All-cause mortality
time frame: Day 28
measure: Proportion of patients achieving clinical response by the improvement of at least 2 points on the 7-point ordinal scale.
time frame: Day 14
description: The scale is as follows: 1. Death 2. Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO) 3. Hospitalized, on non-invasive ventilation or high flow oxygen devices 4. Hospitalized, requiring low flow supplemental oxygen 5. Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise) 6. Hospitalized, not requiring supplemental oxygen - no longer required ongoing medical care 7. Not hospitalized.
measure: Duration of ICU stay
time frame: Day 28
measure: Duration of hospital stay
time frame: Day 28
measure: Changes in blood cytokine levels
time frame: Day 28
arm group label: Phase 1 Low-dose Group
arm group type: Experimental
description: Eligible subjects will receive a single infusion of hUC-MCS product at the dose of 0.5 million cells/kg in addition to standard of care treatment.
arm group label: Phase 1 Middle-dose Group
arm group type: Experimental
description: Eligible subjects will receive a single infusion of hUC-MCS product at the dose of 1 million cells/kg in addition to standard of care treatment.
arm group label: Phase 1 High-dose Group
arm group type: Experimental
description: Eligible subjects will receive a single infusion of hUC-MCS product at the dose of 1.5 million cells/kg in addition to standard of care treatment.
arm group label: Phase 2a Treatment Group
arm group type: Experimental
description: Eligible subjects will receive a single infusion of hUC-MCS product at the selected dose from phase 1 in addition to standard of care treatment.
arm group label: Phase 2a Control Group
arm group type: Placebo Comparator
description: Eligible subjects will receive a single infusion of placebo control and standard of care treatment.
intervention type: Biological
intervention name: Human umbilical cord mesenchymal stem cells + best supportive care
description: hUC-MSC product will be administered intravenously in addition to the standard of care treatment.
arm group label: Phase 1 High-dose Group
arm group label: Phase 1 Low-dose Group
arm group label: Phase 1 Middle-dose Group
arm group label: Phase 2a Treatment Group
intervention type: Other
intervention name: Placebo control + best supportive care
description: Placebo control will be administered intravenously in addition to the standard of care treatment.
arm group label: Phase 2a Control Group
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
last name: Vincent Liao, MD. Ph.D.
phone: 949-308-1952
email: baylx@baylxinc.com
responsible party type: Sponsor
mesh term: COVID-19
mesh term: Respiratory Distress Syndrome
mesh term: Respiratory Distress Syndrome, Newborn
mesh term: Acute Lung Injury
mesh term: Syndrome