<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/NCT04476953</url>
  </required_header>
  <id_info>
    <org_study_id>20-003936</org_study_id>
    <nct_id>NCT04476953</nct_id>
  </id_info>
  <brief_title>COVID-FISETIN: Pilot in SARS-CoV-2 of Fisetin to Alleviate Dysfunction and Inflammation</brief_title>
  <official_title>COVID-FISETIN: A Phase 2 Placebo-Controlled Pilot Study in SARS-CoV-2 of Fisetin to Alleviate Dysfunction and Excessive Inflammatory Response in Hospitalized Adults</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Mayo Clinic</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Mayo Clinic</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>
      The purpose of this study is to test whether Fisetin, a senolytic drug, can assist in&#xD;
      preventing an increase in the disease's progression and alleviate complications of&#xD;
      coronavirus due to an excessive inflammatory reaction.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      To determine if Fisetin treatment can prevent deterioration of oxygenation status as measured&#xD;
      by S/F ratio: SpO2/ FiO2, as well as prevent deterioration in physical function (frailty) and&#xD;
      hyper-inflammation, other measures of oxygenation status (progression to supplemental oxygen&#xD;
      requirement, assisted breathing/ ventilation), and progression from mild/ moderate to severe/&#xD;
      critical proven SARS-CoV-2 infection in hospitalized patients and to evaluate the safety and&#xD;
      tolerability of Fisetin in this patient population.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Enrolling by invitation</overall_status>
  <start_date type="Actual">August 3, 2020</start_date>
  <completion_date type="Anticipated">September 2023</completion_date>
  <primary_completion_date type="Anticipated">September 2023</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Serious Adverse Events</measure>
    <time_frame>6 months</time_frame>
    <description>Number of participants to experience serious adverse events and hypersensitivity reactions.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in oxygenation status</measure>
    <time_frame>baseline, Day 3, 7, 10, 14, 17 and 30; Months 3 and 6</time_frame>
    <description>change in oxygenation levels as measured by S/F ratio (SPO2/FiO2)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>CoV Severity Category</measure>
    <time_frame>6 months</time_frame>
    <description>Number of participants to progress to severe or critical classification CoV</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">80</enrollment>
  <condition>Covid19</condition>
  <arm_group>
    <arm_group_label>Treatment Group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects will receive treatment drug Fisetin</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo Group</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Subjects will receive placebo</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Placebo looks exactly like the study drug, but it contains no active ingredient.</description>
    <arm_group_label>Placebo Group</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Fisetin</intervention_name>
    <description>~20 mg/kg/day oral, NG or D tube course for 2 consecutive days</description>
    <arm_group_label>Treatment Group</arm_group_label>
    <other_name>3,3',4',7-tetrahydroxyflavone</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria - Patients must meet all of the following inclusion criteria to be&#xD;
        enrolled in this study.&#xD;
&#xD;
          1. Men or women 60 years of age or older&#xD;
&#xD;
             OR&#xD;
&#xD;
             Age 18 - 59 years WITH at least one of the following comorbidities:&#xD;
&#xD;
               -  BMI greater than or equal to 35&#xD;
&#xD;
               -  Diabetes&#xD;
&#xD;
               -  Asthma/ Chronic Obstructive Pulmonary Disease (COPD)&#xD;
&#xD;
               -  Previous Myocardial Infarction&#xD;
&#xD;
               -  Previous Stroke/ Cerebrovascular Accident (CVA)&#xD;
&#xD;
               -  Hypertension/ Atherosclerosis/ Peripheral Vascular Disease&#xD;
&#xD;
               -  Smoking and/or vaping&#xD;
&#xD;
               -  Other conditions associated with senescent cell accumulation (i.e. previous&#xD;
                  chemotherapy or radiation)&#xD;
&#xD;
          2. SpO2 greater than or equal to 85% (on room air or less than or equal to 2 L of&#xD;
             supplemental oxygen)&#xD;
&#xD;
          3. Willing and able to provide written informed consent or have a legally authorized&#xD;
             representative (LAR) who will provide informed consent&#xD;
&#xD;
          4. SARS-CoV-2 infection confirmed by PCR test at Mayo Clinic (or other CLIA certified)&#xD;
             laboratory within 10 days prior to randomization.&#xD;
&#xD;
        Exclusion Criteria - Patients who meet any of the following exclusion criteria are not to&#xD;
        be enrolled in this study.&#xD;
&#xD;
        General Exclusion Criteria&#xD;
&#xD;
          1. Presence of any condition that the Investigator or the subject's attending physician&#xD;
             believes would put the subject at risk or would preclude the patient from successfully&#xD;
             completing the trial&#xD;
&#xD;
          2. Pregnant and/or lactating. Women of childbearing potential (WCBP) must have a negative&#xD;
             pregnancy test within 72 hours prior to randomization&#xD;
&#xD;
          3. WCBP who are unwilling to abstain from sex or use an adequate method of contraception&#xD;
             from the time of the first IP administration through 48 hours after the last IP&#xD;
             administration&#xD;
&#xD;
          4. Men who are unwilling to abstain from sex with WCBP or use an adequate method of&#xD;
             contraception from the time of the first IP administration through 48 hours after the&#xD;
             last IP administration&#xD;
&#xD;
             Laboratory Exclusion Criteria&#xD;
&#xD;
          5. Total bilirubin &gt;3X upper limit of normal or as per clinical judgment.&#xD;
&#xD;
          6. Serum aspartate transaminase (AST) or alanine aminotransferase (ALT) &gt;4x the upper&#xD;
             limits of normal or as per clinical judgment.&#xD;
&#xD;
          7. Hemoglobin &lt;7 g/dL; white blood cell count ≤ 2,000/mm3 (&lt; or = 2.0 x 109/L) or &gt; or =&#xD;
             20,000/mm3 (&gt; or = 20 x 109/L); platelet count &lt; or = 40,000/µL (&lt; or = 40 x 109/L);&#xD;
             absolute neutrophil count &lt; or = 1 x 109/L; lymphocyte count &lt;0.3 x 109/L at screening&#xD;
             or as per clinical judgment.&#xD;
&#xD;
          8. Unstable (as per clinical judgment) major cardiovascular, renal, endocrine,&#xD;
             immunological, or hepatic disorder.&#xD;
&#xD;
          9. eGFR &lt;25 ml/ min/ 1.73 m2 or as per clinical judgment.&#xD;
&#xD;
         10. Plasma and/or serum glucose &gt;300 or as per clinical judgment.&#xD;
&#xD;
             Clinical History Exclusion Criteria&#xD;
&#xD;
         11. Human immunodeficiency virus infection.&#xD;
&#xD;
         12. Known active hepatitis B or C infection.&#xD;
&#xD;
         13. Invasive fungal infection.&#xD;
&#xD;
         14. Uncontrolled (as per clinical judgement) pleural/pericardial effusions or ascites.&#xD;
&#xD;
         15. New/active invasive cancer except non-melanoma skin cancers.&#xD;
&#xD;
             Medication Exclusion Criteria (See Appendices 1-3 for additional information)&#xD;
&#xD;
         16. Known hypersensitivity or allergy to Fisetin.&#xD;
&#xD;
         17. Patients currently using medications which utilize CYP450 2C9 for metabolism. These&#xD;
             medications include: Fosphenytoin, Phenytoin, Warfarin, Glimepiride, Diclofenac,&#xD;
             Bosentan, and Glyburide. Patients taking any of these medications may participate if&#xD;
             the medications can be held immediately before the 1st IP administration until at&#xD;
             least 10 hours after the last (2nd) IP administration and the patient is otherwise&#xD;
             eligible.&#xD;
&#xD;
         18. Patients currently using medications which utilize CYP2C9, CYP2C19, CYP1A2, OATP1B1.&#xD;
             These medications include: Olanzapine, Clozapine, Theophylline, Tizanidine, Warfarin,&#xD;
             Rameltoen, Tacrine, Duloxetine, Mexiletine, Riluzole, and Atomoxetine. Patients taking&#xD;
             any of these medications may participate if the medications can be held immediately&#xD;
             before the 1st IP administration until at least 10 hours after the last (2nd) IP&#xD;
             administration and the patient is otherwise eligible.&#xD;
&#xD;
         19. Patients currently using medications which are strong inhibitors of CYP3A4. These&#xD;
             medications include: Atazanavir, Ceritinib, Clarithromycin, Darunavir, Idelalisib,&#xD;
             Indinavir, Itraconazole, Ketoconazole, Lopinavir, Mefipristone, Nefazodone,&#xD;
             Nelfinavir, Ombitasivir-paritaprevir-ritonivir,&#xD;
             Ombitasivir-paritaprevir-ritonivir-plus dasabuvir, Posaconazole, Saquinavir,&#xD;
             Telithromycin, Tucatinib, and Voriconazole. Patients taking any of these medications&#xD;
             may participate if the medications can be held immediately before the 1st IP&#xD;
             administration until at least 10 hours after the last (2nd) IP administration and the&#xD;
             patient is otherwise eligible.&#xD;
&#xD;
         20. Patients currently using antifungals. If antifungals are absolutely necessary from an&#xD;
             infectious disease perspective, then they will be allowed only if the levels are&#xD;
             subtherapeutic or therapeutic.&#xD;
&#xD;
         21. Patients taking any of these medications may participate if the medications can be&#xD;
             held immediately before the 1st IP administration until at least 10 hours after the&#xD;
             last (2nd) IP administration and the patient is otherwise eligible:&#xD;
&#xD;
               -  Cardiac: digoxin, flecainide, amiodarone&#xD;
&#xD;
               -  Psychiatric: lithium, thioridazine&#xD;
&#xD;
               -  Neurologic: carbamazepine, phenobarbital&#xD;
&#xD;
               -  Antimicrobial/fungal: aminoglycosides (e.g. amikacin, gentamicin, kanamycin,&#xD;
                  neomycin, netilmicin, paromomysin, streptomycin, tobramycin), rifampin&#xD;
&#xD;
               -  Anticoagulants/ Antiplatelets: warfarin&#xD;
&#xD;
               -  Others: methotrexate, nitroglycerin, St. John's wort, tyrosine kinase inhibitors,&#xD;
                  tacrine, diclofenac&#xD;
&#xD;
         22. Participation in other clinical trials involving treatment for SARS-CoV-2. (unless&#xD;
             reviewed and approved by the Principal Investigator). Note that institutional standard&#xD;
             of care treatment of SARS-CoV-2 including glucocorticoids, hydroxychloroquine,&#xD;
             azithromycin, remdesivir, anti-spike antibodies, and/or convalescent plasma are not&#xD;
             excluded from the study.&#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>James L Kirkland, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Mayo Clinic</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Mayo Clinic in Rochester</name>
      <address>
        <city>Rochester</city>
        <state>Minnesota</state>
        <zip>55905</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://www.mayo.edu/research/clinical-trials</url>
    <description>Mayo Clinic Clinical Trials</description>
  </link>
  <verification_date>January 2023</verification_date>
  <study_first_submitted>July 15, 2020</study_first_submitted>
  <study_first_submitted_qc>July 16, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 20, 2020</study_first_posted>
  <last_update_submitted>January 23, 2023</last_update_submitted>
  <last_update_submitted_qc>January 23, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">January 25, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Mayo Clinic</investigator_affiliation>
    <investigator_full_name>James L. Kirkland, MD, PhD</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>SARS-CoV-2</keyword>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- 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/NCT04476953
org study id: 20-003936
nct id: NCT04476953
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
The purpose of this study is to test whether Fisetin, a senolytic drug, can assist in
      preventing an increase in the disease's progression and alleviate complications of
      coronavirus due to an excessive inflammatory reaction.
To determine if Fisetin treatment can prevent deterioration of oxygenation status as measured
      by S/F ratio: SpO2/ FiO2, as well as prevent deterioration in physical function (frailty) and
      hyper-inflammation, other measures of oxygenation status (progression to supplemental oxygen
      requirement, assisted breathing/ ventilation), and progression from mild/ moderate to severe/
      critical proven SARS-CoV-2 infection in hospitalized patients and to evaluate the safety and
      tolerability of Fisetin in this patient population.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Serious Adverse Events
time frame: 6 months
description: Number of participants to experience serious adverse events and hypersensitivity reactions.
measure: Change in oxygenation status
time frame: baseline, Day 3, 7, 10, 14, 17 and 30; Months 3 and 6
description: change in oxygenation levels as measured by S/F ratio (SPO2/FiO2)
measure: CoV Severity Category
time frame: 6 months
description: Number of participants to progress to severe or critical classification CoV
arm group label: Treatment Group
arm group type: Experimental
description: Subjects will receive treatment drug Fisetin
arm group label: Placebo Group
arm group type: Placebo Comparator
description: Subjects will receive placebo
intervention type: Drug
intervention name: Placebo
description: Placebo looks exactly like the study drug, but it contains no active ingredient.
arm group label: Placebo Group
intervention type: Drug
intervention name: Fisetin
description: ~20 mg/kg/day oral, NG or D tube course for 2 consecutive days
arm group label: Treatment Group
other name: 3,3',4',7-tetrahydroxyflavone
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: James L Kirkland, MD, PhD
role: Principal Investigator
affiliation: Mayo Clinic
facility: 
country: United States
url: https://www.mayo.edu/research/clinical-trials
description: Mayo Clinic Clinical Trials
responsible party type: Principal Investigator
investigator affiliation: Mayo Clinic
investigator full name: James L. Kirkland, MD, PhD
investigator title: Principal Investigator
sharing ipd: No