<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/NCT04412785</url>
  </required_header>
  <id_info>
    <org_study_id>842998</org_study_id>
    <nct_id>NCT04412785</nct_id>
  </id_info>
  <brief_title>Cyclosporine in Patients With Moderate COVID-19</brief_title>
  <official_title>Phase I Trial for the Prevention of Cytokine Release Syndrome (CRS) With Cyclosporine in Patients With Moderate COVID-19</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Pennsylvania</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Pennsylvania</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Phase 1 safety study to determine the tolerability, clinical effects, and changes in&#xD;
      laboratory parameters of short course oral or IV cyclosporine (CSA) administration in&#xD;
      patients with COVID-19 disease requiring oxygen supplementation but not requiring ventilator&#xD;
      support.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Our overall hypothesis is that CSA is safe in this patient population and that it will have&#xD;
      antiviral and anti-cytokine effects as measured in laboratory tests.&#xD;
&#xD;
      The initial dose will be 9 mg/kg/day oral divided q12h or 3 mg/kg/day by continuous IV&#xD;
      infusion. Oral administration is generally preferred, however IV administration can be used&#xD;
      if oral administration is not feasible or cannot be tolerated, or at the&#xD;
      physician-investigator's clinical discretion. The dose will be adjusted to target a trough&#xD;
      level of 200 to 300 ng/ml, which is in alignment with common clinical practice. The planned&#xD;
      duration of CSA treatment is up to 14 days, with planned discontinuation upon discharge from&#xD;
      the hospital. Dose reduction of 25% to 50% can be made for patients who experience adverse&#xD;
      events such as hypertension or serum creatinine elevation.&#xD;
&#xD;
      The end of study will be study day 30 for those patients who have been discharged from the&#xD;
      hospital. If the patient remains in the hospital, the subject will still complete the end of&#xD;
      study visit at day 30 as planned, but will continue to be followed until date of discharge.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">June 30, 2020</start_date>
  <completion_date type="Actual">October 25, 2021</completion_date>
  <primary_completion_date type="Actual">October 25, 2021</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Safety-oxygen, ICU transfer and ventilation</measure>
    <time_frame>3 months</time_frame>
    <description>Safety will be measured: By assessing the proportion of participants requiring increase in oxygen requirements, transfer to intensive care unit, and/or mechanical ventilation</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Safety-changes in absolute lymphocyte count</measure>
    <time_frame>3 months</time_frame>
    <description>Safety will be assessed: By monitoring changes in absolute lymphocyte counts</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Safety-changes in creatinine clearance</measure>
    <time_frame>3 months</time_frame>
    <description>Safety will be assessed: By monitoring changes in creatinine clearance. Creatinine clearance will be estimated using the Cockcroft-Gault formula.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Safety-secondary bacterial infections</measure>
    <time_frame>3 months</time_frame>
    <description>Safety will be assessed: By monitoring the incidence of secondary bacterial infections complicating COVID-19 hospitalization</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Laboratory measurements of safety and antiviral efficacy related to COVID-19-SARS-CoV-2 by measuring the clearance of SARS-CoV-2 from respiratory secretions</measure>
    <time_frame>3 months</time_frame>
    <description>To measure time to SARS-CoV-2 clearance (PCR negativity) at Days 7 and 14 by deep nasal swab</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Laboratory measurements-D-dimer levels</measure>
    <time_frame>3 months</time_frame>
    <description>To measure the laboratory correlatives of CRS/ Hemophagocytic lymphohistiocytosis (HLH) by measuring: D-dimer levels</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Laboratory measurements-ferritin</measure>
    <time_frame>3 months</time_frame>
    <description>To measure the laboratory correlatives of CRS/ Hemophagocytic lymphohistiocytosis (HLH) by measuring: ferritin levels</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Laboratory measurements- IL-6</measure>
    <time_frame>3 months</time_frame>
    <description>To measure the laboratory correlatives of CRS/ Hemophagocytic lymphohistiocytosis (HLH) by measuring: IL-6 levels</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">11</enrollment>
  <condition>COVID-19</condition>
  <arm_group>
    <arm_group_label>Single Arm</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Cyclosporine; oral or IV route of administration, per investigator discretion. Duration of administration up to 14 days, as tolerated.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cyclosporine</intervention_name>
    <description>• The initial dose will be 9 mg/kg/day oral divided q12h. For IV, the dose will be 3mg/kg/day by continuous IV infusion.</description>
    <arm_group_label>Single Arm</arm_group_label>
    <other_name>Sandimmune, Neoral, Gengraf</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Provision of signed and dated informed consent form&#xD;
&#xD;
          2. Stated willingness to comply with all study procedures and availability for the&#xD;
             duration of the study&#xD;
&#xD;
          3. Male or female, aged &gt;18.&#xD;
&#xD;
          4. Admitted to hospital with laboratory confirmation of SARS-CoV-2 infection.&#xD;
&#xD;
          5. Estimated creatinine clearance &gt;50 ml/min using standard Cockcroft-Gault formula.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Are admitted to the ICU at time of enrollment.&#xD;
&#xD;
          2. Have an active uncontrolled infection with a non-COVID-19 agent.&#xD;
&#xD;
          3. Have an active malignancy, not including non-melanoma skin cancer, superficial&#xD;
             cervical or bladder cancer, MGUS, or prostate cancer with PSA &lt;1.0.&#xD;
&#xD;
          4. Are on chronic immune suppressive medications, including&#xD;
&#xD;
          5. corticosteroid therapy at a prednisone equivalent dose of 10 mg per day or higher;&#xD;
             therapy with calcineurin inhibitors or mTOR inhibitors.&#xD;
&#xD;
          6. Are pregnant&#xD;
&#xD;
          7. Are lactating&#xD;
&#xD;
          8. Have a known allergic reaction to components of the CSA or its diluents.&#xD;
&#xD;
          9. Are receiving investigational vaccine for SARS-CoV-2.&#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>Emily Blumberg, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Pennsylvania</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Pennsylvania</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>January 2022</verification_date>
  <study_first_submitted>June 1, 2020</study_first_submitted>
  <study_first_submitted_qc>June 1, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 2, 2020</study_first_posted>
  <last_update_submitted>January 7, 2022</last_update_submitted>
  <last_update_submitted_qc>January 7, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">January 11, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>COVID-19</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cyclosporine</mesh_term>
    <mesh_term>Cyclosporins</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/NCT04412785
org study id: 842998
nct id: NCT04412785
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
Phase 1 safety study to determine the tolerability, clinical effects, and changes in
      laboratory parameters of short course oral or IV cyclosporine (CSA) administration in
      patients with COVID-19 disease requiring oxygen supplementation but not requiring ventilator
      support.
Our overall hypothesis is that CSA is safe in this patient population and that it will have
      antiviral and anti-cytokine effects as measured in laboratory tests.

      The initial dose will be 9 mg/kg/day oral divided q12h or 3 mg/kg/day by continuous IV
      infusion. Oral administration is generally preferred, however IV administration can be used
      if oral administration is not feasible or cannot be tolerated, or at the
      physician-investigator's clinical discretion. The dose will be adjusted to target a trough
      level of 200 to 300 ng/ml, which is in alignment with common clinical practice. The planned
      duration of CSA treatment is up to 14 days, with planned discontinuation upon discharge from
      the hospital. Dose reduction of 25% to 50% can be made for patients who experience adverse
      events such as hypertension or serum creatinine elevation.

      The end of study will be study day 30 for those patients who have been discharged from the
      hospital. If the patient remains in the hospital, the subject will still complete the end of
      study visit at day 30 as planned, but will continue to be followed until date of discharge.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Safety-oxygen, ICU transfer and ventilation
time frame: 3 months
description: Safety will be measured: By assessing the proportion of participants requiring increase in oxygen requirements, transfer to intensive care unit, and/or mechanical ventilation
measure: Safety-changes in absolute lymphocyte count
time frame: 3 months
description: Safety will be assessed: By monitoring changes in absolute lymphocyte counts
measure: Safety-changes in creatinine clearance
time frame: 3 months
description: Safety will be assessed: By monitoring changes in creatinine clearance. Creatinine clearance will be estimated using the Cockcroft-Gault formula.
measure: Safety-secondary bacterial infections
time frame: 3 months
description: Safety will be assessed: By monitoring the incidence of secondary bacterial infections complicating COVID-19 hospitalization
measure: Laboratory measurements of safety and antiviral efficacy related to COVID-19-SARS-CoV-2 by measuring the clearance of SARS-CoV-2 from respiratory secretions
time frame: 3 months
description: To measure time to SARS-CoV-2 clearance (PCR negativity) at Days 7 and 14 by deep nasal swab
measure: Laboratory measurements-D-dimer levels
time frame: 3 months
description: To measure the laboratory correlatives of CRS/ Hemophagocytic lymphohistiocytosis (HLH) by measuring: D-dimer levels
measure: Laboratory measurements-ferritin
time frame: 3 months
description: To measure the laboratory correlatives of CRS/ Hemophagocytic lymphohistiocytosis (HLH) by measuring: ferritin levels
measure: Laboratory measurements- IL-6
time frame: 3 months
description: To measure the laboratory correlatives of CRS/ Hemophagocytic lymphohistiocytosis (HLH) by measuring: IL-6 levels
arm group label: Single Arm
arm group type: Experimental
description: Cyclosporine; oral or IV route of administration, per investigator discretion. Duration of administration up to 14 days, as tolerated.
intervention type: Drug
intervention name: Cyclosporine
description: • The initial dose will be 9 mg/kg/day oral divided q12h. For IV, the dose will be 3mg/kg/day by continuous IV infusion.
arm group label: Single Arm
other name: Sandimmune, Neoral, Gengraf
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Emily Blumberg, MD
role: Principal Investigator
affiliation: University of Pennsylvania
facility: 
country: United States
responsible party type: Sponsor
mesh term: COVID-19
mesh term: Cyclosporine
mesh term: Cyclosporins