<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/NCT04425252</url>
  </required_header>
  <id_info>
    <org_study_id>CCB-CRISIS-01</org_study_id>
    <nct_id>NCT04425252</nct_id>
  </id_info>
  <brief_title>Safety and Anti-coronavirus Response of Suppression of Host Nucleotide Synthesis in Patients With COVID-19</brief_title>
  <acronym>CRISIS</acronym>
  <official_title>The CRISIS Study: A Randomized Open-label Study Assessing the Safety and Anti-coronavirus Response of Suppression of Host Nucleotide Synthesis in Hospitalized Adults With Coronavirus-19 (COVID-19)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Clear Creek Bio, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Clear Creek Bio, Inc.</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This will be a phase 1a randomized, open label, multi-center study with approximately 24&#xD;
      subjects. All subjects will receive standard of care (SOC) per institutional guidelines for&#xD;
      treatment of hospitalized patients with COVID-19 infection. In addition to SOC, the brequinar&#xD;
      group will receive 5 daily doses of brequinar 100 mg.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This will be a phase 1a randomized, open label, multi-center study with approximately 24&#xD;
      subjects. All subjects will receive standard of care (SOC) per institutional guidelines for&#xD;
      SARS-CoV-2 infection. Subjects will be randomly assigned in a 1:2 ratio to SOC alone or SOC&#xD;
      plus brequinar. The SOC plus brequinar group will receive 5 daily doses of brequinar 100 mg&#xD;
      on Days 1 - 5 in addition to SOC. Physical examinations, vital signs, laboratory assessments,&#xD;
      SARS-CoV-2 testing, and other observations will be conducted by experienced personnel&#xD;
      throughout the study based on the Schedule of Events. Blood chemistry tests include blood&#xD;
      urea nitrogen (BUN), creatinine, alkaline phosphatase (ALP), alanine amino transferase (ALT),&#xD;
      aspartate amino transferase (AST), bilirubin, total protein, albumin, glucose, serum&#xD;
      electrolytes (sodium, potassium, chloride, carbon dioxide/bicarbonate, and calcium), lactate&#xD;
      dehydrogenase (LDH). Plasma will be collected for inflammatory markers such as D-dimer,&#xD;
      ferritin, c-reactive protein (CRP), and erythrocyte sedimentation rate (ESR).&#xD;
      Pro-inflammatory markers will be measured. Serum is to be collected for research purposes.&#xD;
      Hematology tests include hemoglobin, hematocrit, complete blood count with full differential,&#xD;
      and platelet count. Nasopharyngeal swabs for viral load will be collected Days 1, 3, 5, 7,&#xD;
      and 15. Survival will be assessed through Day 29.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 19, 2020</start_date>
  <completion_date type="Actual">January 12, 2021</completion_date>
  <primary_completion_date type="Actual">December 29, 2020</primary_completion_date>
  <phase>Phase 1/Phase 2</phase>
  <study_type>Interventional</study_type>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>Randomized 1:2 to standard of care (SOC) alone or SOC + brequinar</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Safety/Tolerability Assessed by Rates of Grade 3 or 4 Post Randomization Adverse Events</measure>
    <time_frame>Through Day 15.</time_frame>
    <description>Safety/tolerability as assessed by number of participants with Grade 3 or 4 post randomization adverse events.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Safety/Tolerability as Assessed by Rates of Serious Adverse Events (SAEs).</measure>
    <time_frame>Through Day 15</time_frame>
    <description>Safety/tolerability as assessed by number of participants with Serious Adverse Events (SAEs).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Safety/Tolerability Measured by Mortality at Day 29</measure>
    <time_frame>Through Day 29</time_frame>
    <description>Safety/tolerability as measured by mortality at Day 29</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Hospitalization Status</measure>
    <time_frame>Days 3, 5, 7, and 15</time_frame>
    <description>All participants were hospitalized at time of study entry. This outcome measures participant hospitalization status at Days 3, 5, 7, and 15 in terms of: hospitalized in intensive care unit (ICU), hospitalized as part of initial admission, re-hospitalized (had been discharged from initial hospitalization and was re-admitted to the hospital) or was dead at the time of the assessment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of Hospitalization</measure>
    <time_frame>Through Day 15</time_frame>
    <description>Duration in number of days from admission to discharge; days counted as an integer only.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>NEWS2 Score</measure>
    <time_frame>Baseline, Days 3, 5, 7, and 15.</time_frame>
    <description>Measure Description: National Early Warning Score (NEWS) 2. Composite score of respiratory rate, oxygen saturation, systolic blood pressure, pulse, consciousness, and temperature. The NEWS2 provides a score of illness severity based on respiratory rate, SpO2, whether the patient is breathing room air or on oxygen, systolic blood pressure, heart rate, consciousness, and body temperature. The scale ranges from 20 (worst/sickest) to 0 (all measurements in a normal range). The NEWS2 was assessed at baseline, Days 3, 5, 7, and 15.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">25</enrollment>
  <condition>COVID-19</condition>
  <arm_group>
    <arm_group_label>Standard of Care</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Subjects are hospitalized for COVID-19 and will receive all supportive/interventional care per institutional guidelines.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Brequinar</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects will receive standard of care plus brequinar 100 mg daily (Study Days 1-5).</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Brequinar</intervention_name>
    <description>DHODH inhibitor, 100 mg daily x 5 days</description>
    <arm_group_label>Brequinar</arm_group_label>
    <other_name>Standard of Care + Brequinar</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Standard of Care</intervention_name>
    <description>Standard of Care per institutional guidelines for COVID-19 patients</description>
    <arm_group_label>Standard of Care</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Willing and able to provide informed consent for the trial, written, electronic,&#xD;
             verbal or other method deemed acceptable by the institution and IRB.&#xD;
&#xD;
          2. 18 years of age or older.&#xD;
&#xD;
          3. If discharged from the hospital prior to Study Day 15 or if follow up is needed for&#xD;
             study drug-related adverse event, willing to go to an outpatient facility if feasible&#xD;
             or be in contact with the study team (phone call or other digital media) for remaining&#xD;
             study assessments.&#xD;
&#xD;
          4. Laboratory-confirmed SARS-CoV-2 infection as determined by real time polymerase chain&#xD;
             reaction (RT-PCR) or other Food and Drug Administration (FDA)-cleared commercial or&#xD;
             public health assay.&#xD;
&#xD;
          5. Hospitalized (in patient with expected duration ≥ 24 hours)&#xD;
&#xD;
          6. The effects of brequinar on the developing human fetus are unknown. For this reason,&#xD;
             women of child-bearing potential and men must agree to use adequate contraception&#xD;
             (hormonal or barrier method of birth control; abstinence) prior to study entry and for&#xD;
             the duration of study participation. Should a woman become pregnant or suspect she is&#xD;
             pregnant while she or her partner is participating in this study, she should inform&#xD;
             her treating physician immediately. Men and women treated or enrolled on this protocol&#xD;
             must also agree to use adequate contraception for the duration of study participation&#xD;
             and for 90 days after completion of brequinar administration.&#xD;
&#xD;
          7. Male subjects must agree to refrain from sperm donation from initial study drug&#xD;
             administration until 90 days after the last dose of brequinar.&#xD;
&#xD;
          8. ≤ 10 days since first COVID-19 symptom as determined by treating clinician.&#xD;
&#xD;
          9. Able to swallow capsules.&#xD;
&#xD;
         10. At least one COVID-19 symptom including but not limited to fever, cough, sore throat,&#xD;
             malaise, headache, muscle pain, gastrointestinal symptoms, shortness of breath,&#xD;
             dyspnea, dysgeusia, or other symptom commonly associated with COVID-19.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Any physical examination findings and/or history of any illness that, in the opinion&#xD;
             of the study investigator, might confound the results of the study or pose an&#xD;
             additional risk to the patient.&#xD;
&#xD;
          2. Active malignancy other than squamous cell carcinoma; anticancer treatment such as&#xD;
             chemotherapy or radiation therapy within the past month.&#xD;
&#xD;
          3. Nursing women or women of childbearing potential (WOCBP) with a positive pregnancy&#xD;
             test.&#xD;
&#xD;
          4. Treatment with another DHODH inhibitor (e.g., leflunomide or teriflunomide),&#xD;
             tacrolimus, sirolimus.&#xD;
&#xD;
          5. Platelets ≤150,000 cell/mm3.&#xD;
&#xD;
          6. Hemoglobin &lt; 10 gm/dL&#xD;
&#xD;
          7. Absolute neutrophil count &lt; 1500 cells/mm3&#xD;
&#xD;
          8. Renal dysfunction, i.e., creatinine clearance &lt; 30 mL/min&#xD;
&#xD;
          9. AST and/or ALT &gt; 1.5 ULN, or total bilirubin &gt; ULN&#xD;
&#xD;
         10. History of bleeding disorders or recent surgery in the six weeks preceding enrollment&#xD;
&#xD;
         11. Concomitant use of agents known to cause bone marrow suppression leading to&#xD;
             thrombocytopenia&#xD;
&#xD;
         12. History of gastrointestinal ulcer, or history of gastrointestinal bleeding.&#xD;
&#xD;
         13. History of hepatitis B and/or C infection, active liver disease and/or cirrhosis.&#xD;
&#xD;
         14. Heart failure, current uncontrolled cardiovascular disease, including unstable angina,&#xD;
             uncontrolled arrhythmias, major adverse cardiac event within 6 months (e.g. stroke,&#xD;
             myocardial infarction, hospitalization due to heart failure, or revascularization&#xD;
             procedure).&#xD;
&#xD;
         15. Life expectancy of &lt; 5 days in the judgment of the treating clinician.&#xD;
&#xD;
         16. Evidence of critical illness defined by at least one of the following:&#xD;
&#xD;
             a. Respiratory failure requiring at least one of the following: i. Endotracheal&#xD;
             intubation and mechanical ventilation, noninvasive positive pressure ventilation,&#xD;
             ECMO, or clinical diagnosis of respiratory failure (i.e., clinical need for one of the&#xD;
             preceding therapies, but preceding therapies may not be able to be administered in&#xD;
             setting of resource limitation) ii. Shock (defined by systolic blood pressure &lt; 90 mm&#xD;
             Hg, or diastolic blood pressure &lt; 60 mm Hg or requiring vasopressors) b. Multi-organ&#xD;
             dysfunction/failure.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Hartford Hospital</name>
      <address>
        <city>Hartford</city>
        <state>Connecticut</state>
        <zip>06102</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Baptist Medical Center</name>
      <address>
        <city>Jacksonville</city>
        <state>Florida</state>
        <zip>32207</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of South Florida/Tampa General</name>
      <address>
        <city>Tampa</city>
        <state>Florida</state>
        <zip>33606</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of New Mexico</name>
      <address>
        <city>Albuquerque</city>
        <state>New Mexico</state>
        <zip>87106</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Temple University</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19140</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>February 2022</verification_date>
  <study_first_submitted>June 9, 2020</study_first_submitted>
  <study_first_submitted_qc>June 9, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 11, 2020</study_first_posted>
  <results_first_submitted>February 1, 2022</results_first_submitted>
  <results_first_submitted_qc>February 10, 2022</results_first_submitted_qc>
  <results_first_posted type="Actual">February 16, 2022</results_first_posted>
  <last_update_submitted>February 15, 2022</last_update_submitted>
  <last_update_submitted_qc>February 15, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">February 17, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>DHODH inhibition</keyword>
  <keyword>antiviral</keyword>
  <keyword>coronavirus</keyword>
  <keyword>SARS-CoV-2</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>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Brequinar</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>September 10, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/52/NCT04425252/Prot_002.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>December 17, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/52/NCT04425252/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>First Patient Enrolled: 19 AUG 2020 Last Patient Completed the study: 12 JAN 2021 Patients were hospitalized with COVID-19 and were recruited at the hospital where they were being treated as in-patients.</recruitment_details>
      <pre_assignment_details>All subjects were hospitalized as in-patients as part of the inclusion criteria. 25 patients were enrolled, but 2 withdrew consent prior to treatment and had no post-randomization assessments for a total of 23 subjects randomized in the study and included in the modified intent-to-treat population.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Standard of Care</title>
          <description>Subjects were hospitalized for COVID-19 and received standard of care per institutional guidelines for COVID-19 patients.</description>
        </group>
        <group group_id="P2">
          <title>Standard of Care + Brequinar</title>
          <description>Subjects were hospitalized for COVID-19 and received standard of care per institutional guidelines for COVID-19 patients plus brequinar 100 mg daily x 5 days.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="8"/>
                <participants group_id="P2" count="15"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="13"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Subject did not return due to COVID-19 restrictions.</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Standard of Care</title>
          <description>Subjects were hospitalized with COVID-19 and received institutional standard of care for COVID-19.</description>
        </group>
        <group group_id="B2">
          <title>Standard of Care + Brequinar</title>
          <description>Subjects were hospitalized with COVID-19 and received institutional standard of care for COVID-19 plus brequinar 100 mg daily x 5 days.</description>
        </group>
        <group group_id="B3">
          <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="8"/>
            <count group_id="B2" value="15"/>
            <count group_id="B3" value="23"/>
          </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="51.38" spread="16.02"/>
                    <measurement group_id="B2" value="55.59" spread="14.78"/>
                    <measurement group_id="B3" value="54.24" spread="15.63"/>
                  </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="4"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="11"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="8"/>
                    <measurement group_id="B3" value="12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="8"/>
                    <measurement group_id="B3" value="15"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="4"/>
                  </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_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                    <measurement group_id="B2" value="15"/>
                    <measurement group_id="B3" value="23"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Safety/Tolerability Assessed by Rates of Grade 3 or 4 Post Randomization Adverse Events</title>
        <description>Safety/tolerability as assessed by number of participants with Grade 3 or 4 post randomization adverse events.</description>
        <time_frame>Through Day 15.</time_frame>
        <population>All subjects in the Modified Intent-to-Treat Population included those with at least one post randomization assessment.</population>
        <group_list>
          <group group_id="O1">
            <title>Standard of Care</title>
            <description>Subjects were hospitalized for COVID-19 and received standard of care per institutional guidelines for COVID-19 patients.</description>
          </group>
          <group group_id="O2">
            <title>Standard of Care + Brequinar</title>
            <description>Subjects were hospitalized for COVID-19 and received standard of care per institutional guidelines for COVID-19 patients plus brequinar 100 mg daily x 5 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Safety/Tolerability Assessed by Rates of Grade 3 or 4 Post Randomization Adverse Events</title>
          <description>Safety/tolerability as assessed by number of participants with Grade 3 or 4 post randomization adverse events.</description>
          <population>All subjects in the Modified Intent-to-Treat Population included those with at least one post randomization assessment.</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="8"/>
                <count group_id="O2" value="15"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Safety/Tolerability as Assessed by Rates of Serious Adverse Events (SAEs).</title>
        <description>Safety/tolerability as assessed by number of participants with Serious Adverse Events (SAEs).</description>
        <time_frame>Through Day 15</time_frame>
        <population>Modified intent-to-treat population included all subjects with at least one post randomization assessment.</population>
        <group_list>
          <group group_id="O1">
            <title>Standard of Care</title>
            <description>Subjects were hospitalized for COVID-19 and received standard of care per institutional guidelines for COVID-19 patients.</description>
          </group>
          <group group_id="O2">
            <title>Standard of Care + Brequinar</title>
            <description>Subjects were hospitalized for COVID-19 and received standard of care per institutional guidelines for COVID-19 patients plus brequinar 100 mg daily x 5 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Safety/Tolerability as Assessed by Rates of Serious Adverse Events (SAEs).</title>
          <description>Safety/tolerability as assessed by number of participants with Serious Adverse Events (SAEs).</description>
          <population>Modified intent-to-treat population included all subjects with at least one post randomization assessment.</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="8"/>
                <count group_id="O2" value="15"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Safety/Tolerability Measured by Mortality at Day 29</title>
        <description>Safety/tolerability as measured by mortality at Day 29</description>
        <time_frame>Through Day 29</time_frame>
        <population>Modified intent-to-treat population included all participants with at least one post-randomization assessment.</population>
        <group_list>
          <group group_id="O1">
            <title>Standard of Care</title>
            <description>Subjects were hospitalized for COVID-19 and received standard of care per institutional guidelines for COVID-19 patients.</description>
          </group>
          <group group_id="O2">
            <title>Standard of Care + Brequinar</title>
            <description>Subjects were hospitalized for COVID-19 and received standard of care per institutional guidelines for COVID-19 patients plus Brequinar 100 mg daily x 5 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Safety/Tolerability Measured by Mortality at Day 29</title>
          <description>Safety/tolerability as measured by mortality at Day 29</description>
          <population>Modified intent-to-treat population included all participants with at least one post-randomization assessment.</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="8"/>
                <count group_id="O2" value="15"/>
              </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_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Hospitalization Status</title>
        <description>All participants were hospitalized at time of study entry. This outcome measures participant hospitalization status at Days 3, 5, 7, and 15 in terms of: hospitalized in intensive care unit (ICU), hospitalized as part of initial admission, re-hospitalized (had been discharged from initial hospitalization and was re-admitted to the hospital) or was dead at the time of the assessment.</description>
        <time_frame>Days 3, 5, 7, and 15</time_frame>
        <population>Modified intent-to-treat population which includes all participants with at least one post-randomization study assessment.</population>
        <group_list>
          <group group_id="O1">
            <title>Standard of Care</title>
            <description>Subjects were hospitalized with COVID-19 and received institutional standard of care for COVID-19.</description>
          </group>
          <group group_id="O2">
            <title>Standard of Care + Brequinar</title>
            <description>Subjects were hospitalized with COVID-19 and received institutional standard of care for COVID-19 plus brequinar 100 mg daily x 5 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Hospitalization Status</title>
          <description>All participants were hospitalized at time of study entry. This outcome measures participant hospitalization status at Days 3, 5, 7, and 15 in terms of: hospitalized in intensive care unit (ICU), hospitalized as part of initial admission, re-hospitalized (had been discharged from initial hospitalization and was re-admitted to the hospital) or was dead at the time of the assessment.</description>
          <population>Modified intent-to-treat population which includes all participants with at least one post-randomization study assessment.</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="8"/>
                <count group_id="O2" value="15"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Day 3 Died</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="8"/>
                    <count group_id="O2" value="15"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 3 Hospitalized in ICU</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="8"/>
                    <count group_id="O2" value="15"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 3 Hospitalized</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="8"/>
                    <count group_id="O2" value="15"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 3 Discharged</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="8"/>
                    <count group_id="O2" value="15"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5"/>
                    <measurement group_id="O2" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 5 Died</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="8"/>
                    <count group_id="O2" value="15"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 5 Hospitalized in ICU</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="8"/>
                    <count group_id="O2" value="15"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 5 Hospitalized</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="8"/>
                    <count group_id="O2" value="15"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 5 Discharged</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="8"/>
                    <count group_id="O2" value="15"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5"/>
                    <measurement group_id="O2" value="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 7 Died</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="8"/>
                    <count group_id="O2" value="15"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 7 Hospitalized in ICU</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="8"/>
                    <count group_id="O2" value="15"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 7 Hospitalized</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="8"/>
                    <count group_id="O2" value="15"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 7 Discharged</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="8"/>
                    <count group_id="O2" value="15"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7"/>
                    <measurement group_id="O2" value="15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 15 Died</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="15"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 15 Hospitalized in ICU</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="15"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 15 Hospitalized</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="15"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 15 Discharged</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="15"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6"/>
                    <measurement group_id="O2" value="14"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 15 Missing</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="8"/>
                    <count group_id="O2" value="15"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Duration of Hospitalization</title>
        <description>Duration in number of days from admission to discharge; days counted as an integer only.</description>
        <time_frame>Through Day 15</time_frame>
        <population>The modified intent-to-treat population included all participants with at least one post-randomization assessment.</population>
        <group_list>
          <group group_id="O1">
            <title>Standard of Care</title>
            <description>Subjects were hospitalized for COVID-19 and received standard of care per institutional guidelines for COVID-19 patients.</description>
          </group>
          <group group_id="O2">
            <title>Standard of Care + Brequinar</title>
            <description>Subjects were hospitalized for COVID-19 and received standard of care per institutional guidelines for COVID-19 patients plus Brequinar 100 mg daily x 5 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Duration of Hospitalization</title>
          <description>Duration in number of days from admission to discharge; days counted as an integer only.</description>
          <population>The modified intent-to-treat population included all participants with at least one post-randomization assessment.</population>
          <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="8"/>
                <count group_id="O2" value="15"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2" lower_limit="1.5" upper_limit="4"/>
                    <measurement group_id="O2" value="4" lower_limit="3" upper_limit="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>NEWS2 Score</title>
        <description>Measure Description: National Early Warning Score (NEWS) 2. Composite score of respiratory rate, oxygen saturation, systolic blood pressure, pulse, consciousness, and temperature. The NEWS2 provides a score of illness severity based on respiratory rate, SpO2, whether the patient is breathing room air or on oxygen, systolic blood pressure, heart rate, consciousness, and body temperature. The scale ranges from 20 (worst/sickest) to 0 (all measurements in a normal range). The NEWS2 was assessed at baseline, Days 3, 5, 7, and 15.</description>
        <time_frame>Baseline, Days 3, 5, 7, and 15.</time_frame>
        <population>Participants with at least one post randomization assessment who were able to return to the clinic for a study visit. Multiple subjects were unable to return for scheduled study assessments at various time points due to COVID-19 restrictions in place at the institutions where the study was conducted.</population>
        <group_list>
          <group group_id="O1">
            <title>Standard of Care</title>
            <description>Subjects were hospitalized with COVID-19 and received institutional standard of care for COVID-19.</description>
          </group>
          <group group_id="O2">
            <title>Standard of Care + Brequinar</title>
            <description>Subjects were hospitalized with COVID-19 and received institutional standard of care for COVID-19 plus brequinar 100 mg daily x 5 days.</description>
          </group>
        </group_list>
        <measure>
          <title>NEWS2 Score</title>
          <description>Measure Description: National Early Warning Score (NEWS) 2. Composite score of respiratory rate, oxygen saturation, systolic blood pressure, pulse, consciousness, and temperature. The NEWS2 provides a score of illness severity based on respiratory rate, SpO2, whether the patient is breathing room air or on oxygen, systolic blood pressure, heart rate, consciousness, and body temperature. The scale ranges from 20 (worst/sickest) to 0 (all measurements in a normal range). The NEWS2 was assessed at baseline, Days 3, 5, 7, and 15.</description>
          <population>Participants with at least one post randomization assessment who were able to return to the clinic for a study visit. Multiple subjects were unable to return for scheduled study assessments at various time points due to COVID-19 restrictions in place at the institutions where the study was conducted.</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="8"/>
                <count group_id="O2" value="13"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline (Day 1 pre dose)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="8"/>
                    <count group_id="O2" value="13"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.9" spread="0.69"/>
                    <measurement group_id="O2" value="3.9" spread="0.80"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 3</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="3"/>
                    <count group_id="O2" value="10"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.0" spread="1.15"/>
                    <measurement group_id="O2" value="2.8" spread="0.47"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 5</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="4"/>
                    <count group_id="O2" value="5"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.5" spread="1.55"/>
                    <measurement group_id="O2" value="3.8" spread="1.07"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="4"/>
                    <count group_id="O2" value="4"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.3" spread="1.03"/>
                    <measurement group_id="O2" value="3.8" spread="1.75"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 15</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="4"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.00" spread="0.00"/>
                    <measurement group_id="O2" value="2.6" spread="0.97"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>29 days</time_frame>
      <desc>Events that occurred prior to informed consent were entered as medical history; AEs that occurred after informed consent were entered on the AE form. Subjects were questioned and observed for evidence of AEs, whether or not judged by the Investigator or designated person to be related to study drug.</desc>
      <group_list>
        <group group_id="E1">
          <title>Standard of Care</title>
          <description>Subjects were hospitalized with COVID-19 and received institutional standard of care for COVID-19.</description>
        </group>
        <group group_id="E2">
          <title>Standard of Care + Brequinar</title>
          <description>Subjects were hospitalized with COVID-19 and received institutional standard of care for COVID-19 plus brequinar 100 mg daily x 5 days.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA Version 23.0</default_vocab>
        <default_assessment>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="0" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Angina pectoris</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Atrial fibrillation</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>COVID-19 pneumonia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Fall</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Orthostatic hypotension</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA Version 23.0</default_vocab>
        <default_assessment>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="0" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Endocrine disorders</title>
            <event_list>
              <event>
                <sub_title>Hyperglycemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT 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>
    <limitations_and_caveats>CCB-CRISIS-01 was a small, open-label study with small numbers of subjects analyzed. In addition, the study was conducted prior to availability of COVID-19 vaccinations and there were many missed visits and assessments due to COVID-19 restrictions in place at the time that prohibited return visits to the hospital or clinic. Standard of care for these hospitalized subjects included remdesivir and steroids.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Vice President Clinical Operations</name_or_title>
      <organization>Clear Creek Bio, Inc.</organization>
      <phone>(617) 765-2252</phone>
      <email>clinical@clearcreekbio.com</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/NCT04425252
org study id: CCB-CRISIS-01
nct id: NCT04425252
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This will be a phase 1a randomized, open label, multi-center study with approximately 24
      subjects. All subjects will receive standard of care (SOC) per institutional guidelines for
      treatment of hospitalized patients with COVID-19 infection. In addition to SOC, the brequinar
      group will receive 5 daily doses of brequinar 100 mg.
This will be a phase 1a randomized, open label, multi-center study with approximately 24
      subjects. All subjects will receive standard of care (SOC) per institutional guidelines for
      SARS-CoV-2 infection. Subjects will be randomly assigned in a 1:2 ratio to SOC alone or SOC
      plus brequinar. The SOC plus brequinar group will receive 5 daily doses of brequinar 100 mg
      on Days 1 - 5 in addition to SOC. Physical examinations, vital signs, laboratory assessments,
      SARS-CoV-2 testing, and other observations will be conducted by experienced personnel
      throughout the study based on the Schedule of Events. Blood chemistry tests include blood
      urea nitrogen (BUN), creatinine, alkaline phosphatase (ALP), alanine amino transferase (ALT),
      aspartate amino transferase (AST), bilirubin, total protein, albumin, glucose, serum
      electrolytes (sodium, potassium, chloride, carbon dioxide/bicarbonate, and calcium), lactate
      dehydrogenase (LDH). Plasma will be collected for inflammatory markers such as D-dimer,
      ferritin, c-reactive protein (CRP), and erythrocyte sedimentation rate (ESR).
      Pro-inflammatory markers will be measured. Serum is to be collected for research purposes.
      Hematology tests include hemoglobin, hematocrit, complete blood count with full differential,
      and platelet count. Nasopharyngeal swabs for viral load will be collected Days 1, 3, 5, 7,
      and 15. Survival will be assessed through Day 29.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Randomized 1:2 to standard of care (SOC) alone or SOC + brequinar
primary purpose: Treatment
masking: None (Open Label)
measure: Safety/Tolerability Assessed by Rates of Grade 3 or 4 Post Randomization Adverse Events
time frame: Through Day 15.
description: Safety/tolerability as assessed by number of participants with Grade 3 or 4 post randomization adverse events.
measure: Safety/Tolerability as Assessed by Rates of Serious Adverse Events (SAEs).
time frame: Through Day 15
description: Safety/tolerability as assessed by number of participants with Serious Adverse Events (SAEs).
measure: Safety/Tolerability Measured by Mortality at Day 29
time frame: Through Day 29
description: Safety/tolerability as measured by mortality at Day 29
measure: Hospitalization Status
time frame: Days 3, 5, 7, and 15
description: All participants were hospitalized at time of study entry. This outcome measures participant hospitalization status at Days 3, 5, 7, and 15 in terms of: hospitalized in intensive care unit (ICU), hospitalized as part of initial admission, re-hospitalized (had been discharged from initial hospitalization and was re-admitted to the hospital) or was dead at the time of the assessment.
measure: Duration of Hospitalization
time frame: Through Day 15
description: Duration in number of days from admission to discharge; days counted as an integer only.
measure: NEWS2 Score
time frame: Baseline, Days 3, 5, 7, and 15.
description: Measure Description: National Early Warning Score (NEWS) 2. Composite score of respiratory rate, oxygen saturation, systolic blood pressure, pulse, consciousness, and temperature. The NEWS2 provides a score of illness severity based on respiratory rate, SpO2, whether the patient is breathing room air or on oxygen, systolic blood pressure, heart rate, consciousness, and body temperature. The scale ranges from 20 (worst/sickest) to 0 (all measurements in a normal range). The NEWS2 was assessed at baseline, Days 3, 5, 7, and 15.
arm group label: Standard of Care
arm group type: Other
description: Subjects are hospitalized for COVID-19 and will receive all supportive/interventional care per institutional guidelines.
arm group label: Brequinar
arm group type: Experimental
description: Subjects will receive standard of care plus brequinar 100 mg daily (Study Days 1-5).
intervention type: Drug
intervention name: Brequinar
description: DHODH inhibitor, 100 mg daily x 5 days
arm group label: Brequinar
other name: Standard of Care + Brequinar
intervention type: Other
intervention name: Standard of Care
description: Standard of Care per institutional guidelines for COVID-19 patients
arm group label: Standard of Care
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: COVID-19
mesh term: Coronavirus Infections
mesh term: Brequinar
sharing ipd: No
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: CCB-CRISIS-01 was a small, open-label study with small numbers of subjects analyzed. In addition, the study was conducted prior to availability of COVID-19 vaccinations and there were many missed visits and assessments due to COVID-19 restrictions in place at the time that prohibited return visits to the hospital or clinic. Standard of care for these hospitalized subjects included remdesivir and steroids.
point of contact: 