<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/NCT04456439</url>
  </required_header>
  <id_info>
    <org_study_id>MSB-MSC-MISC001</org_study_id>
    <nct_id>NCT04456439</nct_id>
  </id_info>
  <brief_title>Intermediate-size Expanded Access Program (EAP), Mesenchymal Stromal Cells (MSC) for Multisystem Inflammatory Syndrome in Children (MIS-C) Associated With Coronavirus Disease (COVID-19)</brief_title>
  <official_title>Intermediate-size Expanded Access of Remestemcel-L, Human Mesenchymal Stromal Cells, for Multisystem Inflammatory Syndrome in Children (MIS-C) Associated With Coronavirus Disease (COVID-19)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Mesoblast International Sàrl</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Mesoblast, Ltd.</source>
  <brief_summary>
    <textblock>
      The objectives of this intermediate-size expanded access protocol are to assess the safety&#xD;
      and efficacy of remestemcel-L in participants with MIS-C associated with COVID-19.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This intermediate-size expanded access protocol plans to treat approximately 50 children or&#xD;
      adolescents, male and female, with MIS-C associated with COVID-19. Participants who are 2&#xD;
      months to 17 years of age, inclusive, will be enrolled at multiple clinical sites across the&#xD;
      United States.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Available</overall_status>
  <study_type>Expanded Access</study_type>
  <has_expanded_access>No</has_expanded_access>
  <expanded_access_info>
    <expanded_access_type_intermediate>Yes</expanded_access_type_intermediate>
  </expanded_access_info>
  <condition>Multisystem Inflammatory Syndrome in Children (MIS-C) Associated With Coronavirus Disease (COVID-19)</condition>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Remestemcel-L</intervention_name>
    <description>Participants may receive up to 2 infusions of 2 x 10^6 remestemcel-L within a 5-day period.</description>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Hydrocortisone</intervention_name>
    <description>Participants who are not currently taking a corticosteroid will receive hydrocortisone, 0.5-1 milligram per kilogram (mg/kg), up to 50 mg IV, at least 30 minutes prior to the infusion of remestemcel-L.</description>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Diphenhydramine</intervention_name>
    <description>Participants will receive diphenhydramine, 0.5-1 mg/kg, up to 50 mg IV, at least 30 minutes prior to the infusion of remestemcel-L.</description>
    <other_name>Benadryl®</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria&#xD;
&#xD;
          1. 2 months to 17 years of age, inclusive&#xD;
&#xD;
          2. Positive for current or recent SARS-CoV-2 (COVID-19) infection by real-time reverse&#xD;
             transcription polymerase chain reaction (RT-PCR), serology, or antigen test; or&#xD;
             COVID-19 exposure within the 4 weeks prior to the onset of symptoms AND no alternative&#xD;
             plausible diagnoses&#xD;
&#xD;
          3. Presenting with:&#xD;
&#xD;
               -  Fever (&gt;38.0°C or &gt;100.4°F for ≥24 hours) or reporting subjective fever lasting&#xD;
                  ≥24 hours&#xD;
&#xD;
               -  Laboratory evidence of inflammation with high sensitivity C-reactive protein&#xD;
                  (hsCRP) ≥4.0 milligrams per deciliter (mg/dL) and associated abnormalities of at&#xD;
                  least one of the following:&#xD;
&#xD;
                    -  elevated erythrocyte sedimentation rate (ESR)&#xD;
&#xD;
                    -  elevated fibrinogen&#xD;
&#xD;
                    -  elevated procalcitonin&#xD;
&#xD;
                    -  elevated d-dimer&#xD;
&#xD;
                    -  elevated ferritin&#xD;
&#xD;
                    -  elevated lactic dehydrogenase (LDH)&#xD;
&#xD;
                    -  elevated interleukin 6 (IL-6)&#xD;
&#xD;
                    -  elevated neutrophils&#xD;
&#xD;
                    -  reduced lymphocytes&#xD;
&#xD;
                    -  low albumin&#xD;
&#xD;
               -  Clinically severe multisystem illness requiring hospitalization with evidence for&#xD;
                  cardiac involvement plus at least one other organ involvement (renal,&#xD;
                  respiratory, hematologic, gastrointestinal, dermatologic or neurological)&#xD;
&#xD;
                    -  Cardiac involvement is defined as reduced left ventricular ejection fraction&#xD;
                       (&lt;55%) in addition to at least one of the following:&#xD;
&#xD;
                         -  increased troponin I,&#xD;
&#xD;
                         -  increased N-terminal pro-B-type natriuretic peptide (NT-proBNP) or BNP&#xD;
                            and/or&#xD;
&#xD;
                         -  echocardiographic and/or other imaging evidence of left anterior&#xD;
                            descending coronary artery (LAD) and/or right coronary artery (RCA)&#xD;
                            dilation associated with a z-score &gt; 2.5&#xD;
&#xD;
          4. If on mechanical ventilation or ECMO, ≤72 hours post initiation of the respiratory&#xD;
             support device&#xD;
&#xD;
        Exclusion Criteria&#xD;
&#xD;
          1. Documented other microbial cause for MIS-C including bacterial sepsis, staphylococcal&#xD;
             or streptococcal shock syndromes, or infections associated with myocarditis such as&#xD;
             enterovirus. Of importance, waiting for results of these investigations should not&#xD;
             delay initiation of remestemcel-L therapy.&#xD;
&#xD;
          2. Females who are pregnant or lactating&#xD;
&#xD;
          3. Body mass index (BMI) ≥40 kilograms per square meter (kg/m^2)&#xD;
&#xD;
          4. Known hypersensitivity to dimethyl sulfoxide (DMSO) or to porcine or bovine proteins&#xD;
&#xD;
          5. Aspartate aminotransferase/alanine transaminase (AST/ALT) ≥5x upper limit of normal&#xD;
             (ULN)&#xD;
&#xD;
          6. Creatinine clearance &lt;30 mL/min&#xD;
&#xD;
          7. Serum creatinine &gt;2 mg/dL&#xD;
&#xD;
          8. Any end-stage organ disease which in the opinion of the treating physician may&#xD;
             possibly affect the safety of the remestemcel-L treatment.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>2 Months</minimum_age>
    <maximum_age>17 Years</maximum_age>
  </eligibility>
  <overall_official>
    <last_name>Kenneth M. Borow, MD</last_name>
    <role>Study Director</role>
    <affiliation>Mesoblast, Inc.</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Elizabeth Burke, ANP-C</last_name>
    <phone>646-315-1725</phone>
    <email>elizabeth.burke@mesoblast.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Kenneth M. Borow, MD</last_name>
    <phone>610-299-7855</phone>
    <email>ken.borow@mesoblast.com</email>
  </overall_contact_backup>
  <results_reference>
    <citation>Eckard AR, Borow KM, Mack EH, Burke E, Atz AM. Remestemcel-L Therapy for COVID-19-Associated Multisystem Inflammatory Syndrome in Children. Pediatrics. 2021 May;147(5):e2020046573. doi: 10.1542/peds.2020-046573. Epub 2021 Feb 12.</citation>
    <PMID>33579813</PMID>
  </results_reference>
  <verification_date>May 2023</verification_date>
  <study_first_submitted>June 29, 2020</study_first_submitted>
  <study_first_submitted_qc>June 30, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 2, 2020</study_first_posted>
  <last_update_submitted>May 3, 2023</last_update_submitted>
  <last_update_submitted_qc>May 3, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">May 6, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>MIS-C</keyword>
  <keyword>COVID-19</keyword>
  <keyword>MSC</keyword>
  <keyword>remestemcel-L</keyword>
  <keyword>Mesoblast</keyword>
  <keyword>mesenchymal</keyword>
  <keyword>cellular therapy</keyword>
  <keyword>cells</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>Syndrome</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Diphenhydramine</mesh_term>
    <mesh_term>Promethazine</mesh_term>
    <mesh_term>Remestemcel-l</mesh_term>
    <mesh_term>Hydrocortisone</mesh_term>
  </intervention_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/NCT04456439
org study id: MSB-MSC-MISC001
nct id: NCT04456439
lead sponsor: 
The objectives of this intermediate-size expanded access protocol are to assess the safety
      and efficacy of remestemcel-L in participants with MIS-C associated with COVID-19.
This intermediate-size expanded access protocol plans to treat approximately 50 children or
      adolescents, male and female, with MIS-C associated with COVID-19. Participants who are 2
      months to 17 years of age, inclusive, will be enrolled at multiple clinical sites across the
      United States.
expanded access type intermediate: Yes
intervention type: Biological
intervention name: Remestemcel-L
description: Participants may receive up to 2 infusions of 2 x 10^6 remestemcel-L within a 5-day period.
intervention type: Drug
intervention name: Hydrocortisone
description: Participants who are not currently taking a corticosteroid will receive hydrocortisone, 0.5-1 milligram per kilogram (mg/kg), up to 50 mg IV, at least 30 minutes prior to the infusion of remestemcel-L.
intervention type: Drug
intervention name: Diphenhydramine
description: Participants will receive diphenhydramine, 0.5-1 mg/kg, up to 50 mg IV, at least 30 minutes prior to the infusion of remestemcel-L.
other name: Benadryl®
criteria: 
gender: All
minimum age: 2 Months
maximum age: 17 Years
last name: Kenneth M. Borow, MD
role: Study Director
affiliation: Mesoblast, Inc.
last name: Elizabeth Burke, ANP-C
phone: 646-315-1725
email: elizabeth.burke@mesoblast.com
last name: Kenneth M. Borow, MD
phone: 610-299-7855
email: ken.borow@mesoblast.com
citation: Eckard AR, Borow KM, Mack EH, Burke E, Atz AM. Remestemcel-L Therapy for COVID-19-Associated Multisystem Inflammatory Syndrome in Children. Pediatrics. 2021 May;147(5):e2020046573. doi: 10.1542/peds.2020-046573. Epub 2021 Feb 12.
PMID: 33579813
responsible party type: Sponsor
mesh term: COVID-19
mesh term: Coronavirus Infections
mesh term: Syndrome
mesh term: Diphenhydramine
mesh term: Promethazine
mesh term: Remestemcel-l
mesh term: Hydrocortisone