<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/NCT04475601</url>
  </required_header>
  <id_info>
    <org_study_id>COVIDENZA</org_study_id>
    <nct_id>NCT04475601</nct_id>
  </id_info>
  <brief_title>Enzalutamide Treatment in COVID-19</brief_title>
  <acronym>COVIDENZA</acronym>
  <official_title>A Prospective, Multicenter, Randomized PHASE II Clinical Trial of Enzalutamide Treatment to Decrease the Morbidity in Patients With Corona Virus Disease 2019 (COVID-19)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Andreas Josefsson</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Umeå University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Sahlgrenska University Hospital, Sweden</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University Hospital, Umeå</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Uppsala University Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Skane University Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Jonkoping County Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Sundsvall Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Helsingborgs Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Göteborg University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Astellas Pharma Europe Ltd.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Norrlands University Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Region Västerbotten</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      COVID-19 is a disease with high rate of morbidity if symptomatic. There is a great need of&#xD;
      treatments to decrease the severity. The vast majority of patients needing intensive care are&#xD;
      men, and this may be due to the androgens, either by regulation of TMPRSS2, necessary for&#xD;
      virus internalization, or other mechanisms. Enzalutamide is an antiandrogen inhibiting the&#xD;
      expression of androgen regulated proteins, such as TMPRSS2. The aim of this trial is to&#xD;
      evaluate a possible beneficial effect of short-term enzalutamide treatment of COVID-19&#xD;
      patients.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    By sponsor, based on DSMB recommendations&#xD;
  </why_stopped>
  <start_date type="Actual">July 15, 2020</start_date>
  <completion_date type="Actual">May 29, 2021</completion_date>
  <primary_completion_date type="Actual">March 24, 2021</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>
    <intervention_model_description>Prospective, randomized (2:1), open, multicentre, clinical controlled trial</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Time to worsening of disease</measure>
    <time_frame>Up to 30 days after inclusion</time_frame>
    <description>Clinical worsening to invasive mechanical ventilation or death as assessed by the 7-point ordinal scale</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Time to improvement of disease</measure>
    <time_frame>Up to 30 days after inclusion</time_frame>
    <description>Time to discharge from hospital assessed by the 7-point ordinal scale</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Adverse events</measure>
    <time_frame>Up to 6 months</time_frame>
    <description>Safety evaluation, as measured by AEs</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of supplemental oxygen (days)</measure>
    <time_frame>Up to 30 days</time_frame>
    <description>Total days of extra oxygen</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Admission to ICU</measure>
    <time_frame>Up to 30 days and up to 6 months</time_frame>
    <description>Frequence of admission to ICU</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Laboratory assessment of Hemoglobin concentration day 0, 2, 4 and 6</measure>
    <time_frame>Up to 30 days</time_frame>
    <description>Changes of laboratory parameters: Hb</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Virus load assessment day 0, 2, 4 and 6</measure>
    <time_frame>UP to 7 days</time_frame>
    <description>PCR based SARS-CoV-2 measurement from upper respiratory tract</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hospital stay (days)</measure>
    <time_frame>Up to30 days and 6 months</time_frame>
    <description>Total number of days evaluated at 30 days and 6 months</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Re-admission to hospital due to rebound COVID-19</measure>
    <time_frame>Evaluated for 30 days and after 6 months</time_frame>
    <description>If admitted to hospital due to COVID-19 disease after discharge from hospital</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mortality at 6 months</measure>
    <time_frame>up to 30 days and up to 6 months respectively</time_frame>
    <description>Death due to any cause</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Laboratory assessment of CRP concentration day 0, 2, 4 and 6</measure>
    <time_frame>Up to 30 days</time_frame>
    <description>Changes of laboratory parameters: CRP</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Laboratory assessment of liver function day 0, 2, 4 and 6</measure>
    <time_frame>Up to 30 days</time_frame>
    <description>Changes of laboratory parameters: ALAT, ASTA and/or ALP</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Laboratory assessment of creatinine concentration day 0, 2, 4 and 6</measure>
    <time_frame>Up to 30 days</time_frame>
    <description>Changes of laboratory parameters: Createnin</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Laboratory assessment of D-dimer concentration day 0, 2, 4 and 6</measure>
    <time_frame>Up to 30 days</time_frame>
    <description>Changes of laboratory parameters: D-dimer</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Laboratory assessment of platelets concentration day 0, 2, 4 and 6</measure>
    <time_frame>Up to 30 days</time_frame>
    <description>Changes of laboratory parameters: TPK</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Laboratory assessment of IL-6 concentration day 0, 2, 4 and 6</measure>
    <time_frame>Up to 30 days</time_frame>
    <description>Changes of laboratory parameters: IL-6</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Laboratory assessment of B- and T-lyphocytes concentration day 0, 2, 4 and 6</measure>
    <time_frame>Up to 30 days</time_frame>
    <description>Changes of laboratory parameters: Differentiate count of leucocytes</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetic interaction of enzalutamide with steroids</measure>
    <time_frame>Up to 30 days</time_frame>
    <description>Maximum Plasma Concentration [Cmax] of steroids in blood</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">42</enrollment>
  <condition>COVID-19</condition>
  <condition>Corona Virus Infection</condition>
  <arm_group>
    <arm_group_label>Enzalutamide+Standard of Care</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Up to 5 days with 4x40 mg enzalutamide tablets orally once daily</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Standard of Care</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Standard of care</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Enzalutamide Pill</intervention_name>
    <description>The once daily dose will be given only during hospitalization and stop if starting invasive mechanical ventilation or at discharge from hospital</description>
    <arm_group_label>Enzalutamide+Standard of Care</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Positive COVID-19 test&#xD;
&#xD;
          -  Mild to severe symptoms of COVID-19&#xD;
&#xD;
          -  Hospitalization&#xD;
&#xD;
          -  WHO performance status 0-3&#xD;
&#xD;
          -  Age above or equal to 50 years&#xD;
&#xD;
          -  Can understand all the requirements of the study, provide informed consent, and&#xD;
             provide authorization of use and disclosure of personal health information.&#xD;
&#xD;
          -  Estimated expected survival of 1 year (excluding symptoms due to COVID-19)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Severe allergy to Enzalutamide&#xD;
&#xD;
          -  Pregnant or breast-feeding women&#xD;
&#xD;
          -  Need of immediate mechanical ventilation&#xD;
&#xD;
          -  Current medication includes enzalutamide treatment&#xD;
&#xD;
          -  Stroke or Transitory Ischemic attack in medical history&#xD;
&#xD;
          -  Treatment for HIV&#xD;
&#xD;
          -  Treatment with tamoxifen&#xD;
&#xD;
          -  Treatment with immunosuppressive agents&#xD;
&#xD;
          -  Severe immunosuppressive disease&#xD;
&#xD;
          -  Treatment with warfarin or NOAC (Non-vitamin K-antagonist anticoagulants)&#xD;
&#xD;
          -  Previous seizure in medical history&#xD;
&#xD;
          -  Other serious illness or medical condition&#xD;
&#xD;
          -  Unstable cardiovascular disease&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <gender_based>Yes</gender_based>
    <minimum_age>50 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Andreas Josefsson, MdPhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Norrlands University Hospital, Region Västerbotten</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Anders Bjartell</name>
      <address>
        <city>Malmö</city>
        <state>Skåne</state>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ryhovs Hospital</name>
      <address>
        <city>Jönköping</city>
        <state>Småland</state>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sahlgrenska University Hospital</name>
      <address>
        <city>Gothenburg</city>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Linköping University Hospital</name>
      <address>
        <city>Linköping</city>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sundsvall Region Hosptial</name>
      <address>
        <city>Sundsvall</city>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Umeå Univerisity Hospital</name>
      <address>
        <city>Umeå</city>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Sweden</country>
  </location_countries>
  <link>
    <url>https://doi.org/10.1016/j.eururo.2021.12.013</url>
    <description>Publication of the results</description>
  </link>
  <verification_date>August 2021</verification_date>
  <study_first_submitted>June 8, 2020</study_first_submitted>
  <study_first_submitted_qc>July 16, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 17, 2020</study_first_posted>
  <last_update_submitted>May 30, 2022</last_update_submitted>
  <last_update_submitted_qc>May 30, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">June 2, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Region Västerbotten</investigator_affiliation>
    <investigator_full_name>Andreas Josefsson</investigator_full_name>
    <investigator_title>Assistant Professor and Consultant Urologist</investigator_title>
  </responsible_party>
  <keyword>Enzalutamide</keyword>
  <keyword>Randomized clinical trial</keyword>
  <keyword>COVID-19</keyword>
  <keyword>Sars-CoV2</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>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
    <ipd_description>The extent of sharing will be regulated during the trial to consider the integrity of the data according GDPR and national laws</ipd_description>
  </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/NCT04475601
org study id: COVIDENZA
nct id: NCT04475601
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
is us export: No
COVID-19 is a disease with high rate of morbidity if symptomatic. There is a great need of
      treatments to decrease the severity. The vast majority of patients needing intensive care are
      men, and this may be due to the androgens, either by regulation of TMPRSS2, necessary for
      virus internalization, or other mechanisms. Enzalutamide is an antiandrogen inhibiting the
      expression of androgen regulated proteins, such as TMPRSS2. The aim of this trial is to
      evaluate a possible beneficial effect of short-term enzalutamide treatment of COVID-19
      patients.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Prospective, randomized (2:1), open, multicentre, clinical controlled trial
primary purpose: Treatment
masking: None (Open Label)
measure: Time to worsening of disease
time frame: Up to 30 days after inclusion
description: Clinical worsening to invasive mechanical ventilation or death as assessed by the 7-point ordinal scale
measure: Time to improvement of disease
time frame: Up to 30 days after inclusion
description: Time to discharge from hospital assessed by the 7-point ordinal scale
measure: Adverse events
time frame: Up to 6 months
description: Safety evaluation, as measured by AEs
measure: Duration of supplemental oxygen (days)
time frame: Up to 30 days
description: Total days of extra oxygen
measure: Admission to ICU
time frame: Up to 30 days and up to 6 months
description: Frequence of admission to ICU
measure: Laboratory assessment of Hemoglobin concentration day 0, 2, 4 and 6
time frame: Up to 30 days
description: Changes of laboratory parameters: Hb
measure: Virus load assessment day 0, 2, 4 and 6
time frame: UP to 7 days
description: PCR based SARS-CoV-2 measurement from upper respiratory tract
measure: Hospital stay (days)
time frame: Up to30 days and 6 months
description: Total number of days evaluated at 30 days and 6 months
measure: Re-admission to hospital due to rebound COVID-19
time frame: Evaluated for 30 days and after 6 months
description: If admitted to hospital due to COVID-19 disease after discharge from hospital
measure: Mortality at 6 months
time frame: up to 30 days and up to 6 months respectively
description: Death due to any cause
measure: Laboratory assessment of CRP concentration day 0, 2, 4 and 6
time frame: Up to 30 days
description: Changes of laboratory parameters: CRP
measure: Laboratory assessment of liver function day 0, 2, 4 and 6
time frame: Up to 30 days
description: Changes of laboratory parameters: ALAT, ASTA and/or ALP
measure: Laboratory assessment of creatinine concentration day 0, 2, 4 and 6
time frame: Up to 30 days
description: Changes of laboratory parameters: Createnin
measure: Laboratory assessment of D-dimer concentration day 0, 2, 4 and 6
time frame: Up to 30 days
description: Changes of laboratory parameters: D-dimer
measure: Laboratory assessment of platelets concentration day 0, 2, 4 and 6
time frame: Up to 30 days
description: Changes of laboratory parameters: TPK
measure: Laboratory assessment of IL-6 concentration day 0, 2, 4 and 6
time frame: Up to 30 days
description: Changes of laboratory parameters: IL-6
measure: Laboratory assessment of B- and T-lyphocytes concentration day 0, 2, 4 and 6
time frame: Up to 30 days
description: Changes of laboratory parameters: Differentiate count of leucocytes
measure: Pharmacokinetic interaction of enzalutamide with steroids
time frame: Up to 30 days
description: Maximum Plasma Concentration [Cmax] of steroids in blood
arm group label: Enzalutamide+Standard of Care
arm group type: Experimental
description: Up to 5 days with 4x40 mg enzalutamide tablets orally once daily
arm group label: Standard of Care
arm group type: No Intervention
description: Standard of care
intervention type: Drug
intervention name: Enzalutamide Pill
description: The once daily dose will be given only during hospitalization and stop if starting invasive mechanical ventilation or at discharge from hospital
arm group label: Enzalutamide+Standard of Care
criteria: 
gender: All
gender based: Yes
minimum age: 50 Years
maximum age: N/A
healthy volunteers: No
last name: Andreas Josefsson, MdPhD
role: Principal Investigator
affiliation: Norrlands University Hospital, Region Västerbotten
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Sweden
url: https://doi.org/10.1016/j.eururo.2021.12.013
description: Publication of the results
responsible party type: Sponsor-Investigator
investigator affiliation: Region Västerbotten
investigator full name: Andreas Josefsson
investigator title: Assistant Professor and Consultant Urologist
mesh term: COVID-19
mesh term: Coronavirus Infections
sharing ipd: Undecided
ipd description: The extent of sharing will be regulated during the trial to consider the integrity of the data according GDPR and national laws