<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/NCT04399889</url>
  </required_header>
  <id_info>
    <org_study_id>Pro00105410</org_study_id>
    <nct_id>NCT04399889</nct_id>
  </id_info>
  <brief_title>hCT-MSCs for COVID19 ARDS</brief_title>
  <official_title>Pilot Study of Safety and Efficacy of Cord Tissue Derived Mesenchymal Stromal Cells (hCT-MSC) in COVID-19 Related Acute Respiratory Distress Syndrome (ARDS)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Joanne Kurtzberg, MD</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>The Marcus Foundation</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Duke University</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>
      This is a 50 patient, Phase 1/2a multi-center pilot study to test the safety and to describe&#xD;
      the preliminary efficacy of intravenous administration of allogenic human cord tissue&#xD;
      mesenchymal stromal cells (hCT-MSC) as an investigational agent, under U.S. INDs 19968 (Duke)&#xD;
      and 19937 (U Miami) to patients with acute respiratory distress syndrome (ARDS) due to&#xD;
      COVID-19 infection (COVID-ARDS). The first 10 consecutive patients will receive&#xD;
      investigational MSCs manufactured by Duke. In the second phase of the study, 40 additional&#xD;
      patients will be randomized to receive placebo or investigational MSCs manufactured by Duke&#xD;
      or University of Miami.&#xD;
&#xD;
      Patients will be eligible for infusion of 3 daily consecutive doses of hCT-MSC or placebo if&#xD;
      they have a confirmed diagnosis of COVID-19 and meet clinical and radiographic criteria for&#xD;
      ARDS.&#xD;
&#xD;
      Results from the first 10 patients will be compared with concurrent outcomes utilizing&#xD;
      standard of care treatments in participating hospitals and in published reports in the&#xD;
      medical literature. Results from the additional 40 patients will be combined with the first&#xD;
      10 and analyzed. The trial is relying on focused eligibility of the participants (patients&#xD;
      with ARDS), single cohort with short trial time (4 weeks), and simple assessment of clinical&#xD;
      outcome (survival, improvement of ARDS). This is a sequential design in the sense that after&#xD;
      the first 10 patients are evaluated a decision will be made by the PIs and the Data Safety&#xD;
      Monitoring Board whether to proceed with the exploratory randomized portion of the study.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a 50 patient, Phase 1/2a multi-center pilot study to test the safety and to describe&#xD;
      the preliminary efficacy of intravenous administration of allogenic human cord tissue&#xD;
      mesenchymal stromal cells (hCT- MSC) as an investigational agent, under U.S. INDs 19968&#xD;
      (Duke) and 19937 (U Miami) to patients with acute respiratory distress syndrome (ARDS) due to&#xD;
      COVID-19 infection (COVID-ARDS). Patients will be eligible for treatment with 3 daily&#xD;
      consecutive doses of hCT-MSC at 1 million cells/kg (max dose 100 million cells) in the phase&#xD;
      1 portion of the study or a fixed dose of 100 million cells daily x 3 days, 12-36 hours apart&#xD;
      in the phase 2 portion of the study, if they have a confirmed diagnosis of COVID-19 and meet&#xD;
      clinical and radiographic criteria for ARDS. The primary endpoint is short-term safety of&#xD;
      hCT-MSC infusions given on this schedule. The key secondary endpoints are 28 day survival, an&#xD;
      increase in PaO2/FiO2 ratio by 50% at 96 hours, days to hospital discharge to home or rehab,&#xD;
      and number of days requiring mechanical or non-invasive ventilation or high flow nasal&#xD;
      cannula.&#xD;
&#xD;
      The study will be executed in two phases. The first 10 consecutive patients will all receive&#xD;
      investigational product. The second part of the study is a randomized, controlled trial in 40&#xD;
      additional patients. The overall aim of the study is to establish safety and to gain critical&#xD;
      information as to whether patients with COVID-ARDS will benefit from MSC infusions. Results&#xD;
      from the first 10 patients will be compared with concurrent outcomes utilizing standard of&#xD;
      care treatments in participating hospitals and in published reports in the medical&#xD;
      literature. Results from the additional 40 patients will be analyzed as a randomized placebo&#xD;
      control trial. The trial is relying on focused eligibility of the participants (patients with&#xD;
      ARDS), single cohort with short trial time (4 weeks), and simple assessment of clinical&#xD;
      outcome (survival, improvement of ARDS). This is a sequential design in the sense that after&#xD;
      the first 10 patients are evaluated a decision will be made by the PIs and the Data Safety&#xD;
      Monitoring Board whether to proceed with the exploratory randomized portion of the study.&#xD;
&#xD;
      The MSCs are manufactured from allogeneic cord tissue donated to the Carolinas Cord Blood&#xD;
      Bank (CCBB) at Duke University. The CCBB is an FDA licensed public cord blood bank (licensed&#xD;
      name DUCORD). Cord tissue is donated by mothers delivering healthy term male babies by&#xD;
      Cesarean section, after written informed consent from the newborn infant's mother. Full donor&#xD;
      screening and testing is performed in accordance with regulatory requirements (21CFR 1271).&#xD;
      The hCT-MSCs will be manufactured in the Marcus Center for Cellular Cures in the Robertson&#xD;
      GMP Cell Manufacturing Laboratory and the Clinical Research Cell Manufacturing Program&#xD;
      (CRCMP) laboratory, Interdisciplinary Stem Cell Institute (ISCI), Miller School of Medicine,&#xD;
      University of Miami. These hCT-MSCs are already being utilized in clinical trials to treat&#xD;
      pediatric patients with autism spectrum disorder (IND 17313), cerebral palsy (IND 17921),&#xD;
      hypoxic ischemic encephalopathy (IND 17313) and adults with osteoarthritis of the knee&#xD;
      (IND18414). To date, over 210 doses of cells have been delivered to patients on these&#xD;
      clinical trials with an excellent safety profile. At University of Miami, hCT-MSCs are used&#xD;
      in the clinical trial to evaluate cytokine suppression in patients with chronic inflammation&#xD;
      due to metabolic syndrome (IND 17324), 12 subjects in the pilot phase of the study had&#xD;
      completed the dose without any treatment emergence SAE.&#xD;
&#xD;
      The rationale for using this approach for patients infected with COVID-19 is that ARDS, the&#xD;
      rate-limiting complication impacting survival, is caused, at least in part, by a cytokine&#xD;
      release syndrome (CRS) which results is severe immune dysregulation. Involved cytokines&#xD;
      include IL-6, IL-8, IL-10, THP-1M, TNF-alpha, and others. MSCs have strong anti-inflammatory&#xD;
      and immune-modulatory activities without apparent toxicity or further immunosuppression.&#xD;
      Approximately 3-5 % of patients with COVID-19 develop ARDS which carries a very high&#xD;
      mortality rate (30-60%) due to multi-system organ failure. Effective treatment of ARDS, the&#xD;
      most feared complication of COVID-19, may convert the COVID-19 pandemic into a more&#xD;
      manageable &quot;flu-like&quot; illness that every American is expected to experience, and most will&#xD;
      survive, on an annual basis.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    low accrual&#xD;
  </why_stopped>
  <start_date type="Actual">June 18, 2020</start_date>
  <completion_date type="Actual">February 16, 2022</completion_date>
  <primary_completion_date type="Actual">February 16, 2022</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>Randomized</allocation>
    <intervention_model>Sequential Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Infusion Reactions</measure>
    <time_frame>24 hours</time_frame>
    <description>Number of infusion reactions measured by any one of the following: fever, anaphylaxis, rash, hypertension, hypotension, tachycardia, nausea, vomiting, or any other new or worsening symptoms associated with the infusion.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of Delayed Reactions</measure>
    <time_frame>28 days</time_frame>
    <description>Number of later reactions attributed to the investigational product as measured by any one of the following: rash, infection, allergic reaction, or any other delayed symptoms associated with infusion of the investigational product.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of Participants With Formation of New Anti-HLA Antibodies</measure>
    <time_frame>28 days</time_frame>
    <description>Number of participants who form new anti-HLA antibodies as measured by an antibody screen test at 28 days post first infusion of the investigational product.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Time to Recovery</measure>
    <time_frame>up to 90 days</time_frame>
    <description>Time to recovery, defined as discharge from the hospital (alive) or remaining in the hospital without the need for supplemental oxygen or other COVID-related medical care.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With an Increase in PaO2/FiO2 Ratio</measure>
    <time_frame>4 days after MSCs</time_frame>
    <description>Increase in PaO2/FiO2 ratio by 50% by Day 4 (96 hours after first infusion). PaO2/FiO2 may be calculated from an arterial blood gas or imputed from the SpO2/FiO2 table.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Days to Hospital Discharge to Home</measure>
    <time_frame>90 days</time_frame>
    <description>The number of days from hospitalization to discharge to home.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Ventilator Free Days</measure>
    <time_frame>90 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Oxygen-free Days</measure>
    <time_frame>28 days</time_frame>
    <description>Number of oxygen-free days defined as: 0 if the subject dies within 28 days of supplemental oxygen, 28-x if successfully liberated from supplemental oxygen x days after initiation, and 0 if the subject receives supplemental oxygen for &gt; 28 days.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Screened Patients Who Are Enrolled and Randomized</measure>
    <time_frame>90 days</time_frame>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">12</enrollment>
  <condition>COVID</condition>
  <condition>Corona Virus Infection</condition>
  <condition>COVID19</condition>
  <arm_group>
    <arm_group_label>Open Label infusion of hCT-MSC</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The first 10 consecutive patients will all receive investigational product.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Randomized infusion of hCT-MSC</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>An interim analysis, for safety will be conducted and reviewed by the Data Safety and Monitoring Board (DSMB) after the first 10 patients have completed treatment and reached the 28 day endpoint. If there are no safety concerns, the trial will proceed with enrollment on the phase 2 portion of the study where the subsequent 40 patients will be randomized in a 1:1 fashion between treatment with MSCs and placebo. The investigational product will be further randomized to the MSCs manufactured by Duke or University of Miami. These products are considered to be comparable.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Randomized infusion of Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>An interim analysis, for safety will be conducted and reviewed by the Data Safety and Monitoring Board (DSMB) after the first 10 patients have completed treatment and reached the 28 day endpoint. If there are no safety concerns, the trial will proceed with enrollment on the phase 2 portion of the study where the subsequent 40 patients will be randomized in a 1:1 fashion between treatment with MSCs and placebo</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Human cord tissue mesenchymal stromal cells (hCT-MSC) manufactured by Duke University.</intervention_name>
    <description>Human cord tissue mesenchymal stromal cells (hCT-MSC) manufactured by Duke University or University of Miami.</description>
    <arm_group_label>Open Label infusion of hCT-MSC</arm_group_label>
    <arm_group_label>Randomized infusion of hCT-MSC</arm_group_label>
    <other_name>hCT-MSC</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Placebo will be comprised of 40-80 mL of Plasmalyte-A + 1% Human Serum Albumin (HAS) prepared in an identical container to the one used for cell administration. The placebo product will undergo the same process of sterility testing including release inspection, transport and product custodian.</description>
    <arm_group_label>Randomized infusion of Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. The patient or legally authorized representative (LAR) must have the ability to&#xD;
             understand and the willingness to provide a signed and dated informed consent form.&#xD;
&#xD;
          2. Age 18 years and over&#xD;
&#xD;
          3. The patient agrees to use adequate contraception for the duration of the treatment&#xD;
             protocol and for 6 months post treatment.&#xD;
&#xD;
          4. Positive RT- PCR testing for COVID-19 nucleic acid using nasopharyngeal swabbing or&#xD;
             any other site&#xD;
&#xD;
          5. Patient meets ARDS criteria and is on non-invasive or mechanical ventilation or high&#xD;
             flow nasal cannula&#xD;
&#xD;
               1. bilateral opacities on chest imaging consistent with pulmonary edema&#xD;
&#xD;
               2. A need for positive pressure ventilation or high flow nasal cannula&#xD;
&#xD;
               3. PaO2/FiO2 ratio ≤ 300 mmHg by arterial blood gas or SpO2/FiO2 imputation.&#xD;
&#xD;
               4. Infiltrates not fully explained by cardiac failure or fluid overload in the&#xD;
                  physician's best clinical judgement&#xD;
&#xD;
          6. Subjects requiring dialysis as a result of a COVID-19 infection will not be excluded.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Evidence of multiorgan failure involving one or more organs, excluding the lungs as&#xD;
             defined below:&#xD;
&#xD;
               1. Presence of shock, defined as MAP &lt; 65 mmHg with signs of peripheral&#xD;
                  hypoperfusion, or continuous infusion of 2 or more vasopressor or inotrope agents&#xD;
                  to maintain MAP ≥ 65 mmHg.&#xD;
&#xD;
               2. Serum bilirubin &gt; 10 mg/dl&#xD;
&#xD;
               3. Platelet count &lt; 50,000/ml&#xD;
&#xD;
               4. Subjects requiring dialysis as a result of anything other than a COVID-19&#xD;
                  infection will be excluded&#xD;
&#xD;
          2. Evidence of acquired or congenital immunodeficiency (due to immunosuppressive therapy&#xD;
             excluding steroid use for treatment of COVID-19 acute respiratory failure, HIV,&#xD;
             previous treatment for cancer, etc.)&#xD;
&#xD;
          3. History of metastatic cancer diagnosis or treatment in the past 1 year&#xD;
&#xD;
          4. History of previous treatments with MSCs or other cell therapies&#xD;
&#xD;
          5. Patient is co-enrolled in any other IND-sponsored clinical trials for COVID-19 or&#xD;
             ARDs. Drugs that are administered under emergency use authorizations (EUA) by the FDA&#xD;
             are permitted.&#xD;
&#xD;
          6. Evidence of pregnancy or lactation&#xD;
&#xD;
          7. Moribund patient not expected to survive &gt;24 hours&#xD;
&#xD;
          8. Unable/unwilling to deliver lung protective ventilation&#xD;
&#xD;
          9. Patient is receiving Extracorporeal Membrane Oxygenation (ECMO)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Joanne Kurtzberg, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Duke Health</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Lingye Chen, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Duke Health</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Boca Raton Regional Hospital</name>
      <address>
        <city>Boca Raton</city>
        <state>Florida</state>
        <zip>33486</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Jackson Memorial Hospital</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33136</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Miami Hospital</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33136</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>New York Medical College</name>
      <address>
        <city>Valhalla</city>
        <state>New York</state>
        <zip>10595</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Duke Hospital</name>
      <address>
        <city>Durham</city>
        <state>North Carolina</state>
        <zip>27705</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>November 2022</verification_date>
  <study_first_submitted>May 21, 2020</study_first_submitted>
  <study_first_submitted_qc>May 21, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">May 22, 2020</study_first_posted>
  <results_first_submitted>October 24, 2022</results_first_submitted>
  <results_first_submitted_qc>November 29, 2022</results_first_submitted_qc>
  <results_first_posted type="Actual">December 20, 2022</results_first_posted>
  <last_update_submitted>November 29, 2022</last_update_submitted>
  <last_update_submitted_qc>November 29, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">December 20, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Duke University</investigator_affiliation>
    <investigator_full_name>Joanne Kurtzberg, MD</investigator_full_name>
    <investigator_title>Jerome S. Harris Distinguished Professor of Pediatrics</investigator_title>
  </responsible_party>
  <keyword>COVID</keyword>
  <keyword>Coronavirus infection</keyword>
  <keyword>COVID19</keyword>
  <keyword>Covid ARDS</keyword>
  <keyword>Acute Respiratory Distress Syndrome</keyword>
  <keyword>ARDS</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>COVID-19</mesh_term>
    <mesh_term>Coronavirus Infections</mesh_term>
    <mesh_term>Respiratory Distress Syndrome</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>March 16, 2021</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/89/NCT04399889/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Open Label Infusion of hCT-MSC</title>
          <description>The first 10 consecutive patients all received 3 daily consecutive doses of hCT-MSC at a dose of 1 million cells/kg (maximum 100 million cells).&#xD;
Human cord tissue mesenchymal stromal cells (hCT-MSC) manufactured by Duke University.: Human cord tissue mesenchymal stromal cells (hCT-MSC) manufactured by Duke University or University of Miami.</description>
        </group>
        <group group_id="P2">
          <title>Randomized Infusion of hCT-MSC</title>
          <description>Randomized to 3 daily consecutive doses of hCT-MSC at a dose of 100 million cells.&#xD;
Human cord tissue mesenchymal stromal cells (hCT-MSC) manufactured by Duke University.: Human cord tissue mesenchymal stromal cells (hCT-MSC) manufactured by Duke University or University of Miami.</description>
        </group>
        <group group_id="P3">
          <title>Randomized Infusion of Placebo</title>
          <description>Randomized to 3 daily consecutive infusions of placebo.&#xD;
Placebo: Placebo will be comprised of 40-80 mL of Plasmalyte-A + 1% Human Serum Albumin (HAS) prepared in an identical container to the one used for cell administration. The placebo product will undergo the same process of sterility testing including release inspection, transport and product custodian.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="10"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="1"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Death</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Open Label Infusion of hCT-MSC</title>
          <description>The first 10 consecutive patients all received 3 daily consecutive doses of hCT-MSC at a dose of 1 million cells/kg (maximum 100 million cells).&#xD;
Human cord tissue mesenchymal stromal cells (hCT-MSC) manufactured by Duke University.: Human cord tissue mesenchymal stromal cells (hCT-MSC) manufactured by Duke University or University of Miami.</description>
        </group>
        <group group_id="B2">
          <title>Randomized Infusion of hCT-MSC</title>
          <description>Randomized to 3 daily consecutive doses of hCT-MSC at a dose of 100 million cells.&#xD;
Human cord tissue mesenchymal stromal cells (hCT-MSC) manufactured by Duke University.: Human cord tissue mesenchymal stromal cells (hCT-MSC) manufactured by Duke University or University of Miami.</description>
        </group>
        <group group_id="B3">
          <title>Randomized Infusion of Placebo</title>
          <description>Randomized to 3 daily consecutive infusions of placebo.&#xD;
Placebo: Placebo will be comprised of 40-80 mL of Plasmalyte-A + 1% Human Serum Albumin (HAS) prepared in an identical container to the one used for cell administration. The placebo product will undergo the same process of sterility testing including release inspection, transport and product custodian.</description>
        </group>
        <group group_id="B4">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="10"/>
            <count group_id="B2" value="1"/>
            <count group_id="B3" value="1"/>
            <count group_id="B4" value="12"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="63.2" spread="12.3"/>
                    <measurement group_id="B2" value="72" spread="0"/>
                    <measurement group_id="B3" value="62" spread="0"/>
                    <measurement group_id="B4" value="63.8" spread="11.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="7"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="9"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Black or African American</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>White</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Other</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Number of Infusion Reactions</title>
        <description>Number of infusion reactions measured by any one of the following: fever, anaphylaxis, rash, hypertension, hypotension, tachycardia, nausea, vomiting, or any other new or worsening symptoms associated with the infusion.</description>
        <time_frame>24 hours</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Open Label Infusion of hCT-MSC</title>
            <description>The first 10 consecutive patients all received 3 daily consecutive doses of hCT-MSC at a dose of 1 million cells/kg.&#xD;
Human cord tissue mesenchymal stromal cells (hCT-MSC) manufactured by Duke University.: Human cord tissue mesenchymal stromal cells (hCT-MSC) manufactured by Duke University or University of Miami.</description>
          </group>
          <group group_id="O2">
            <title>Randomized Infusion of hCT-MSC</title>
            <description>Randomized to 3 daily consecutive doses of hCT-MSC at a dose of 100 million cells.&#xD;
Human cord tissue mesenchymal stromal cells (hCT-MSC) manufactured by Duke University.: Human cord tissue mesenchymal stromal cells (hCT-MSC) manufactured by Duke University or University of Miami.</description>
          </group>
          <group group_id="O3">
            <title>Randomized Infusion of Placebo</title>
            <description>Randomized to 3 daily consecutive infusions of placebo.&#xD;
Placebo: Placebo will be comprised of 40-80 mL of Plasmalyte-A + 1% Human Serum Albumin (HAS) prepared in an identical container to the one used for cell administration. The placebo product will undergo the same process of sterility testing including release inspection, transport and product custodian.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Infusion Reactions</title>
          <description>Number of infusion reactions measured by any one of the following: fever, anaphylaxis, rash, hypertension, hypotension, tachycardia, nausea, vomiting, or any other new or worsening symptoms associated with the infusion.</description>
          <units>infusion reactions</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
                <count group_id="O2" value="1"/>
                <count group_id="O3" value="1"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Number of Delayed Reactions</title>
        <description>Number of later reactions attributed to the investigational product as measured by any one of the following: rash, infection, allergic reaction, or any other delayed symptoms associated with infusion of the investigational product.</description>
        <time_frame>28 days</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Open Label Infusion of hCT-MSC</title>
            <description>The first 10 consecutive patients all received 3 daily consecutive doses of hCT-MSC at a dose of 1 million cells/kg.&#xD;
Human cord tissue mesenchymal stromal cells (hCT-MSC) manufactured by Duke University.: Human cord tissue mesenchymal stromal cells (hCT-MSC) manufactured by Duke University or University of Miami.</description>
          </group>
          <group group_id="O2">
            <title>Randomized Infusion of hCT-MSC</title>
            <description>Randomized to 3 daily consecutive doses of hCT-MSC at a dose of 100 million cells.&#xD;
Human cord tissue mesenchymal stromal cells (hCT-MSC) manufactured by Duke University.: Human cord tissue mesenchymal stromal cells (hCT-MSC) manufactured by Duke University or University of Miami.</description>
          </group>
          <group group_id="O3">
            <title>Randomized Infusion of Placebo</title>
            <description>Randomized to 3 daily consecutive infusions of placebo.&#xD;
Placebo: Placebo will be comprised of 40-80 mL of Plasmalyte-A + 1% Human Serum Albumin (HAS) prepared in an identical container to the one used for cell administration. The placebo product will undergo the same process of sterility testing including release inspection, transport and product custodian.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Delayed Reactions</title>
          <description>Number of later reactions attributed to the investigational product as measured by any one of the following: rash, infection, allergic reaction, or any other delayed symptoms associated with infusion of the investigational product.</description>
          <units>delayed reactions</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
                <count group_id="O2" value="1"/>
                <count group_id="O3" value="1"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants With Formation of New Anti-HLA Antibodies</title>
        <description>Number of participants who form new anti-HLA antibodies as measured by an antibody screen test at 28 days post first infusion of the investigational product.</description>
        <time_frame>28 days</time_frame>
        <population>Data not collected on eight participants.</population>
        <group_list>
          <group group_id="O1">
            <title>Open Label Infusion of hCT-MSC</title>
            <description>The first 10 consecutive patients all received 3 daily consecutive doses of hCT-MSC at a dose of 1 million cells/kg.&#xD;
Human cord tissue mesenchymal stromal cells (hCT-MSC) manufactured by Duke University.: Human cord tissue mesenchymal stromal cells (hCT-MSC) manufactured by Duke University or University of Miami.</description>
          </group>
          <group group_id="O2">
            <title>Randomized Infusion of hCT-MSC</title>
            <description>Randomized to 3 daily consecutive doses of hCT-MSC at a dose of 100 million cells.&#xD;
Human cord tissue mesenchymal stromal cells (hCT-MSC) manufactured by Duke University.: Human cord tissue mesenchymal stromal cells (hCT-MSC) manufactured by Duke University or University of Miami.</description>
          </group>
          <group group_id="O3">
            <title>Randomized Infusion of Placebo</title>
            <description>Randomized to 3 daily consecutive infusions of placebo.&#xD;
Placebo: Placebo will be comprised of 40-80 mL of Plasmalyte-A + 1% Human Serum Albumin (HAS) prepared in an identical container to the one used for cell administration. The placebo product will undergo the same process of sterility testing including release inspection, transport and product custodian.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Formation of New Anti-HLA Antibodies</title>
          <description>Number of participants who form new anti-HLA antibodies as measured by an antibody screen test at 28 days post first infusion of the investigational product.</description>
          <population>Data not collected on eight participants.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="4"/>
                <count group_id="O2" value="0"/>
                <count group_id="O3" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time to Recovery</title>
        <description>Time to recovery, defined as discharge from the hospital (alive) or remaining in the hospital without the need for supplemental oxygen or other COVID-related medical care.</description>
        <time_frame>up to 90 days</time_frame>
        <population>Participants who recovered.</population>
        <group_list>
          <group group_id="O1">
            <title>Open Label Infusion of hCT-MSC</title>
            <description>The first 10 consecutive patients all received 3 daily consecutive doses of hCT-MSC at a dose of 1 million cells/kg.&#xD;
Human cord tissue mesenchymal stromal cells (hCT-MSC) manufactured by Duke University.: Human cord tissue mesenchymal stromal cells (hCT-MSC) manufactured by Duke University or University of Miami.</description>
          </group>
          <group group_id="O2">
            <title>Randomized Infusion of hCT-MSC</title>
            <description>Randomized to 3 daily consecutive doses of hCT-MSC at a dose of 100 million cells.&#xD;
Human cord tissue mesenchymal stromal cells (hCT-MSC) manufactured by Duke University.: Human cord tissue mesenchymal stromal cells (hCT-MSC) manufactured by Duke University or University of Miami.</description>
          </group>
          <group group_id="O3">
            <title>Randomized Infusion of Placebo</title>
            <description>Randomized to 3 daily consecutive infusions of placebo.&#xD;
Placebo: Placebo will be comprised of 40-80 mL of Plasmalyte-A + 1% Human Serum Albumin (HAS) prepared in an identical container to the one used for cell administration. The placebo product will undergo the same process of sterility testing including release inspection, transport and product custodian.</description>
          </group>
        </group_list>
        <measure>
          <title>Time to Recovery</title>
          <description>Time to recovery, defined as discharge from the hospital (alive) or remaining in the hospital without the need for supplemental oxygen or other COVID-related medical care.</description>
          <population>Participants who recovered.</population>
          <units>days</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="5"/>
                <count group_id="O2" value="0"/>
                <count group_id="O3" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="18" lower_limit="7" upper_limit="39"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With an Increase in PaO2/FiO2 Ratio</title>
        <description>Increase in PaO2/FiO2 ratio by 50% by Day 4 (96 hours after first infusion). PaO2/FiO2 may be calculated from an arterial blood gas or imputed from the SpO2/FiO2 table.</description>
        <time_frame>4 days after MSCs</time_frame>
        <population>Data not collected on eight participants.</population>
        <group_list>
          <group group_id="O1">
            <title>Open Label Infusion of hCT-MSC</title>
            <description>The first 10 consecutive patients all received 3 daily consecutive doses of hCT-MSC at a dose of 1 million cells/kg.&#xD;
Human cord tissue mesenchymal stromal cells (hCT-MSC) manufactured by Duke University.: Human cord tissue mesenchymal stromal cells (hCT-MSC) manufactured by Duke University or University of Miami.</description>
          </group>
          <group group_id="O2">
            <title>Randomized Infusion of hCT-MSC</title>
            <description>Randomized to 3 daily consecutive doses of hCT-MSC at a dose of 100 million cells.&#xD;
Human cord tissue mesenchymal stromal cells (hCT-MSC) manufactured by Duke University.: Human cord tissue mesenchymal stromal cells (hCT-MSC) manufactured by Duke University or University of Miami.</description>
          </group>
          <group group_id="O3">
            <title>Randomized Infusion of Placebo</title>
            <description>Randomized to 3 daily consecutive infusions of placebo.&#xD;
Placebo: Placebo will be comprised of 40-80 mL of Plasmalyte-A + 1% Human Serum Albumin (HAS) prepared in an identical container to the one used for cell administration. The placebo product will undergo the same process of sterility testing including release inspection, transport and product custodian.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With an Increase in PaO2/FiO2 Ratio</title>
          <description>Increase in PaO2/FiO2 ratio by 50% by Day 4 (96 hours after first infusion). PaO2/FiO2 may be calculated from an arterial blood gas or imputed from the SpO2/FiO2 table.</description>
          <population>Data not collected on eight participants.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="4"/>
                <count group_id="O2" value="0"/>
                <count group_id="O3" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Days to Hospital Discharge to Home</title>
        <description>The number of days from hospitalization to discharge to home.</description>
        <time_frame>90 days</time_frame>
        <population>Participants who were discharged to home.</population>
        <group_list>
          <group group_id="O1">
            <title>Open Label Infusion of hCT-MSC</title>
            <description>The first 10 consecutive patients all received 3 daily consecutive doses of hCT-MSC at a dose of 1 million cells/kg.&#xD;
Human cord tissue mesenchymal stromal cells (hCT-MSC) manufactured by Duke University.: Human cord tissue mesenchymal stromal cells (hCT-MSC) manufactured by Duke University or University of Miami.</description>
          </group>
          <group group_id="O2">
            <title>Randomized Infusion of hCT-MSC</title>
            <description>Randomized to 3 daily consecutive doses of hCT-MSC at a dose of 100 million cells.&#xD;
Human cord tissue mesenchymal stromal cells (hCT-MSC) manufactured by Duke University.: Human cord tissue mesenchymal stromal cells (hCT-MSC) manufactured by Duke University or University of Miami.</description>
          </group>
          <group group_id="O3">
            <title>Randomized Infusion of Placebo</title>
            <description>Randomized to 3 daily consecutive infusions of placebo.&#xD;
Placebo: Placebo will be comprised of 40-80 mL of Plasmalyte-A + 1% Human Serum Albumin (HAS) prepared in an identical container to the one used for cell administration. The placebo product will undergo the same process of sterility testing including release inspection, transport and product custodian.</description>
          </group>
        </group_list>
        <measure>
          <title>Days to Hospital Discharge to Home</title>
          <description>The number of days from hospitalization to discharge to home.</description>
          <population>Participants who were discharged to home.</population>
          <units>days</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
                <count group_id="O2" value="0"/>
                <count group_id="O3" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="18" lower_limit="8" upper_limit="18"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Ventilator Free Days</title>
        <time_frame>90 days</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Open Label Infusion of hCT-MSC</title>
            <description>The first 10 consecutive patients all received 3 daily consecutive doses of hCT-MSC at a dose of 1 million cells/kg.&#xD;
Human cord tissue mesenchymal stromal cells (hCT-MSC) manufactured by Duke University.: Human cord tissue mesenchymal stromal cells (hCT-MSC) manufactured by Duke University or University of Miami.</description>
          </group>
          <group group_id="O2">
            <title>Randomized Infusion of hCT-MSC</title>
            <description>Randomized to 3 daily consecutive doses of hCT-MSC at a dose of 100 million cells.&#xD;
Human cord tissue mesenchymal stromal cells (hCT-MSC) manufactured by Duke University.: Human cord tissue mesenchymal stromal cells (hCT-MSC) manufactured by Duke University or University of Miami.</description>
          </group>
          <group group_id="O3">
            <title>Randomized Infusion of Placebo</title>
            <description>Randomized to 3 daily consecutive infusions of placebo.&#xD;
Placebo: Placebo will be comprised of 40-80 mL of Plasmalyte-A + 1% Human Serum Albumin (HAS) prepared in an identical container to the one used for cell administration. The placebo product will undergo the same process of sterility testing including release inspection, transport and product custodian.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Ventilator Free Days</title>
          <units>days</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
                <count group_id="O2" value="1"/>
                <count group_id="O3" value="1"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="25.5" lower_limit="0" upper_limit="80"/>
                    <measurement group_id="O2" value="0" lower_limit="0" upper_limit="0"/>
                    <measurement group_id="O3" value="0" lower_limit="0" upper_limit="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Oxygen-free Days</title>
        <description>Number of oxygen-free days defined as: 0 if the subject dies within 28 days of supplemental oxygen, 28-x if successfully liberated from supplemental oxygen x days after initiation, and 0 if the subject receives supplemental oxygen for &gt; 28 days.</description>
        <time_frame>28 days</time_frame>
        <population>Data not collected on one participant.</population>
        <group_list>
          <group group_id="O1">
            <title>Open Label Infusion of hCT-MSC</title>
            <description>The first 10 consecutive patients all received 3 daily consecutive doses of hCT-MSC at a dose of 1 million cells/kg.&#xD;
Human cord tissue mesenchymal stromal cells (hCT-MSC) manufactured by Duke University.: Human cord tissue mesenchymal stromal cells (hCT-MSC) manufactured by Duke University or University of Miami.</description>
          </group>
          <group group_id="O2">
            <title>Randomized Infusion of hCT-MSC</title>
            <description>Randomized to 3 daily consecutive doses of hCT-MSC at a dose of 100 million cells.&#xD;
Human cord tissue mesenchymal stromal cells (hCT-MSC) manufactured by Duke University.: Human cord tissue mesenchymal stromal cells (hCT-MSC) manufactured by Duke University or University of Miami.</description>
          </group>
          <group group_id="O3">
            <title>Randomized Infusion of Placebo</title>
            <description>Randomized to 3 daily consecutive infusions of placebo.&#xD;
Placebo: Placebo will be comprised of 40-80 mL of Plasmalyte-A + 1% Human Serum Albumin (HAS) prepared in an identical container to the one used for cell administration. The placebo product will undergo the same process of sterility testing including release inspection, transport and product custodian.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Oxygen-free Days</title>
          <description>Number of oxygen-free days defined as: 0 if the subject dies within 28 days of supplemental oxygen, 28-x if successfully liberated from supplemental oxygen x days after initiation, and 0 if the subject receives supplemental oxygen for &gt; 28 days.</description>
          <population>Data not collected on one participant.</population>
          <units>days</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="9"/>
                <count group_id="O2" value="1"/>
                <count group_id="O3" value="1"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0" lower_limit="0" upper_limit="21"/>
                    <measurement group_id="O2" value="0" lower_limit="0" upper_limit="0"/>
                    <measurement group_id="O3" value="0" lower_limit="0" upper_limit="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Screened Patients Who Are Enrolled and Randomized</title>
        <time_frame>90 days</time_frame>
        <population>Open Label infusion of hCT-MSC participants were not randomized.</population>
        <group_list>
          <group group_id="O1">
            <title>Open Label Infusion of hCT-MSC</title>
            <description>The first 10 consecutive patients all received 3 daily consecutive doses of hCT-MSC at a dose of 1 million cells/kg.&#xD;
Human cord tissue mesenchymal stromal cells (hCT-MSC) manufactured by Duke University.: Human cord tissue mesenchymal stromal cells (hCT-MSC) manufactured by Duke University or University of Miami.</description>
          </group>
          <group group_id="O2">
            <title>Randomized Infusion of hCT-MSC</title>
            <description>Randomized to 3 daily consecutive doses of hCT-MSC at a dose of 100 million cells.&#xD;
Human cord tissue mesenchymal stromal cells (hCT-MSC) manufactured by Duke University.: Human cord tissue mesenchymal stromal cells (hCT-MSC) manufactured by Duke University or University of Miami.</description>
          </group>
          <group group_id="O3">
            <title>Randomized Infusion of Placebo</title>
            <description>Randomized to 3 daily consecutive infusions of placebo.&#xD;
Placebo: Placebo will be comprised of 40-80 mL of Plasmalyte-A + 1% Human Serum Albumin (HAS) prepared in an identical container to the one used for cell administration. The placebo product will undergo the same process of sterility testing including release inspection, transport and product custodian.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Screened Patients Who Are Enrolled and Randomized</title>
          <population>Open Label infusion of hCT-MSC participants were not randomized.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="1"/>
                <count group_id="O3" value="1"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>90 days</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Open Label Infusion of hCT-MSC</title>
          <description>The first 10 consecutive patients will all receive investigational product.&#xD;
Human cord tissue mesenchymal stromal cells (hCT-MSC) manufactured by Duke University.: Human cord tissue mesenchymal stromal cells (hCT-MSC) manufactured by Duke University or University of Miami.</description>
        </group>
        <group group_id="E2">
          <title>Randomized Infusion of hCT-MSC</title>
          <description>An interim analysis, for safety will be conducted and reviewed by the Data Safety and Monitoring Board (DSMB) after the first 10 patients have completed treatment and reached the 28 day endpoint. If there are no safety concerns, the trial will proceed with enrollment on the phase 2 portion of the study where the subsequent 40 patients will be randomized in a 1:1 fashion between treatment with MSCs and placebo. The investigational product will be further randomized to the MSCs manufactured by Duke or University of Miami. These products are considered to be comparable.&#xD;
Human cord tissue mesenchymal stromal cells (hCT-MSC) manufactured by Duke University.: Human cord tissue mesenchymal stromal cells (hCT-MSC) manufactured by Duke University or University of Miami.</description>
        </group>
        <group group_id="E3">
          <title>Randomized Infusion of Placebo</title>
          <description>An interim analysis, for safety will be conducted and reviewed by the Data Safety and Monitoring Board (DSMB) after the first 10 patients have completed treatment and reached the 28 day endpoint. If there are no safety concerns, the trial will proceed with enrollment on the phase 2 portion of the study where the subsequent 40 patients will be randomized in a 1:1 fashion between treatment with MSCs and placebo&#xD;
Placebo: Placebo will be comprised of 40-80 mL of Plasmalyte-A + 1% Human Serum Albumin (HAS) prepared in an identical container to the one used for cell administration. The placebo product will undergo the same process of sterility testing including release inspection, transport and product custodian.</description>
        </group>
      </group_list>
      <serious_events>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Cardiac arrest</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Cardiac disorders - Other, specify</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Death NOS</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Multi-organ failure</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Sepsis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Renal and urinary disorders - Other, specify</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Respiratory failure</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Thromboembolic event</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Atrial fibrillation</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Heart failure</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Sinus bradycardia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Ventricular tachycardia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Edema limbs</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Fever</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hyperglycemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Hyperkalemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Hypertriglyceridemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Hypocalcemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Hypokalemia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Encephalopathy</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Syncope</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Delirium</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Acute kidney injury</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Pneumothorax</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Emily Poehlein, MB</name_or_title>
      <organization>Duke University</organization>
      <phone>919-668-8473</phone>
      <email>emily.poehlein@duke.edu</email>
    </point_of_contact>
  </clinical_results>
</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/NCT04399889
org study id: Pro00105410
nct id: NCT04399889
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This is a 50 patient, Phase 1/2a multi-center pilot study to test the safety and to describe
      the preliminary efficacy of intravenous administration of allogenic human cord tissue
      mesenchymal stromal cells (hCT-MSC) as an investigational agent, under U.S. INDs 19968 (Duke)
      and 19937 (U Miami) to patients with acute respiratory distress syndrome (ARDS) due to
      COVID-19 infection (COVID-ARDS). The first 10 consecutive patients will receive
      investigational MSCs manufactured by Duke. In the second phase of the study, 40 additional
      patients will be randomized to receive placebo or investigational MSCs manufactured by Duke
      or University of Miami.

      Patients will be eligible for infusion of 3 daily consecutive doses of hCT-MSC or placebo if
      they have a confirmed diagnosis of COVID-19 and meet clinical and radiographic criteria for
      ARDS.

      Results from the first 10 patients will be compared with concurrent outcomes utilizing
      standard of care treatments in participating hospitals and in published reports in the
      medical literature. Results from the additional 40 patients will be combined with the first
      10 and analyzed. The trial is relying on focused eligibility of the participants (patients
      with ARDS), single cohort with short trial time (4 weeks), and simple assessment of clinical
      outcome (survival, improvement of ARDS). This is a sequential design in the sense that after
      the first 10 patients are evaluated a decision will be made by the PIs and the Data Safety
      Monitoring Board whether to proceed with the exploratory randomized portion of the study.
This is a 50 patient, Phase 1/2a multi-center pilot study to test the safety and to describe
      the preliminary efficacy of intravenous administration of allogenic human cord tissue
      mesenchymal stromal cells (hCT- MSC) as an investigational agent, under U.S. INDs 19968
      (Duke) and 19937 (U Miami) to patients with acute respiratory distress syndrome (ARDS) due to
      COVID-19 infection (COVID-ARDS). Patients will be eligible for treatment with 3 daily
      consecutive doses of hCT-MSC at 1 million cells/kg (max dose 100 million cells) in the phase
      1 portion of the study or a fixed dose of 100 million cells daily x 3 days, 12-36 hours apart
      in the phase 2 portion of the study, if they have a confirmed diagnosis of COVID-19 and meet
      clinical and radiographic criteria for ARDS. The primary endpoint is short-term safety of
      hCT-MSC infusions given on this schedule. The key secondary endpoints are 28 day survival, an
      increase in PaO2/FiO2 ratio by 50% at 96 hours, days to hospital discharge to home or rehab,
      and number of days requiring mechanical or non-invasive ventilation or high flow nasal
      cannula.

      The study will be executed in two phases. The first 10 consecutive patients will all receive
      investigational product. The second part of the study is a randomized, controlled trial in 40
      additional patients. The overall aim of the study is to establish safety and to gain critical
      information as to whether patients with COVID-ARDS will benefit from MSC infusions. Results
      from the first 10 patients will be compared with concurrent outcomes utilizing standard of
      care treatments in participating hospitals and in published reports in the medical
      literature. Results from the additional 40 patients will be analyzed as a randomized placebo
      control trial. The trial is relying on focused eligibility of the participants (patients with
      ARDS), single cohort with short trial time (4 weeks), and simple assessment of clinical
      outcome (survival, improvement of ARDS). This is a sequential design in the sense that after
      the first 10 patients are evaluated a decision will be made by the PIs and the Data Safety
      Monitoring Board whether to proceed with the exploratory randomized portion of the study.

      The MSCs are manufactured from allogeneic cord tissue donated to the Carolinas Cord Blood
      Bank (CCBB) at Duke University. The CCBB is an FDA licensed public cord blood bank (licensed
      name DUCORD). Cord tissue is donated by mothers delivering healthy term male babies by
      Cesarean section, after written informed consent from the newborn infant's mother. Full donor
      screening and testing is performed in accordance with regulatory requirements (21CFR 1271).
      The hCT-MSCs will be manufactured in the Marcus Center for Cellular Cures in the Robertson
      GMP Cell Manufacturing Laboratory and the Clinical Research Cell Manufacturing Program
      (CRCMP) laboratory, Interdisciplinary Stem Cell Institute (ISCI), Miller School of Medicine,
      University of Miami. These hCT-MSCs are already being utilized in clinical trials to treat
      pediatric patients with autism spectrum disorder (IND 17313), cerebral palsy (IND 17921),
      hypoxic ischemic encephalopathy (IND 17313) and adults with osteoarthritis of the knee
      (IND18414). To date, over 210 doses of cells have been delivered to patients on these
      clinical trials with an excellent safety profile. At University of Miami, hCT-MSCs are used
      in the clinical trial to evaluate cytokine suppression in patients with chronic inflammation
      due to metabolic syndrome (IND 17324), 12 subjects in the pilot phase of the study had
      completed the dose without any treatment emergence SAE.

      The rationale for using this approach for patients infected with COVID-19 is that ARDS, the
      rate-limiting complication impacting survival, is caused, at least in part, by a cytokine
      release syndrome (CRS) which results is severe immune dysregulation. Involved cytokines
      include IL-6, IL-8, IL-10, THP-1M, TNF-alpha, and others. MSCs have strong anti-inflammatory
      and immune-modulatory activities without apparent toxicity or further immunosuppression.
      Approximately 3-5 % of patients with COVID-19 develop ARDS which carries a very high
      mortality rate (30-60%) due to multi-system organ failure. Effective treatment of ARDS, the
      most feared complication of COVID-19, may convert the COVID-19 pandemic into a more
      manageable "flu-like" illness that every American is expected to experience, and most will
      survive, on an annual basis.
allocation: Randomized
intervention model: Sequential Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Number of Infusion Reactions
time frame: 24 hours
description: Number of infusion reactions measured by any one of the following: fever, anaphylaxis, rash, hypertension, hypotension, tachycardia, nausea, vomiting, or any other new or worsening symptoms associated with the infusion.
measure: Number of Delayed Reactions
time frame: 28 days
description: Number of later reactions attributed to the investigational product as measured by any one of the following: rash, infection, allergic reaction, or any other delayed symptoms associated with infusion of the investigational product.
measure: Number of Participants With Formation of New Anti-HLA Antibodies
time frame: 28 days
description: Number of participants who form new anti-HLA antibodies as measured by an antibody screen test at 28 days post first infusion of the investigational product.
measure: Time to Recovery
time frame: up to 90 days
description: Time to recovery, defined as discharge from the hospital (alive) or remaining in the hospital without the need for supplemental oxygen or other COVID-related medical care.
measure: Number of Participants With an Increase in PaO2/FiO2 Ratio
time frame: 4 days after MSCs
description: Increase in PaO2/FiO2 ratio by 50% by Day 4 (96 hours after first infusion). PaO2/FiO2 may be calculated from an arterial blood gas or imputed from the SpO2/FiO2 table.
measure: Days to Hospital Discharge to Home
time frame: 90 days
description: The number of days from hospitalization to discharge to home.
measure: Number of Ventilator Free Days
time frame: 90 days
measure: Number of Oxygen-free Days
time frame: 28 days
description: Number of oxygen-free days defined as: 0 if the subject dies within 28 days of supplemental oxygen, 28-x if successfully liberated from supplemental oxygen x days after initiation, and 0 if the subject receives supplemental oxygen for > 28 days.
measure: Number of Screened Patients Who Are Enrolled and Randomized
time frame: 90 days
arm group label: Open Label infusion of hCT-MSC
arm group type: Experimental
description: The first 10 consecutive patients will all receive investigational product.
arm group label: Randomized infusion of hCT-MSC
arm group type: Experimental
description: An interim analysis, for safety will be conducted and reviewed by the Data Safety and Monitoring Board (DSMB) after the first 10 patients have completed treatment and reached the 28 day endpoint. If there are no safety concerns, the trial will proceed with enrollment on the phase 2 portion of the study where the subsequent 40 patients will be randomized in a 1:1 fashion between treatment with MSCs and placebo. The investigational product will be further randomized to the MSCs manufactured by Duke or University of Miami. These products are considered to be comparable.
arm group label: Randomized infusion of Placebo
arm group type: Placebo Comparator
description: An interim analysis, for safety will be conducted and reviewed by the Data Safety and Monitoring Board (DSMB) after the first 10 patients have completed treatment and reached the 28 day endpoint. If there are no safety concerns, the trial will proceed with enrollment on the phase 2 portion of the study where the subsequent 40 patients will be randomized in a 1:1 fashion between treatment with MSCs and placebo
intervention type: Biological
intervention name: Human cord tissue mesenchymal stromal cells (hCT-MSC) manufactured by Duke University.
description: Human cord tissue mesenchymal stromal cells (hCT-MSC) manufactured by Duke University or University of Miami.
arm group label: Open Label infusion of hCT-MSC
arm group label: Randomized infusion of hCT-MSC
other name: hCT-MSC
intervention type: Other
intervention name: Placebo
description: Placebo will be comprised of 40-80 mL of Plasmalyte-A + 1% Human Serum Albumin (HAS) prepared in an identical container to the one used for cell administration. The placebo product will undergo the same process of sterility testing including release inspection, transport and product custodian.
arm group label: Randomized infusion of Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Joanne Kurtzberg, MD
role: Principal Investigator
affiliation: Duke Health
last name: Lingye Chen, MD
role: Principal Investigator
affiliation: Duke Health
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor-Investigator
investigator affiliation: Duke University
investigator full name: Joanne Kurtzberg, MD
investigator title: Jerome S. Harris Distinguished Professor of Pediatrics
mesh term: COVID-19
mesh term: Coronavirus Infections
mesh term: Respiratory Distress Syndrome
sharing ipd: No
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 