<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/NCT04456049</url>
  </required_header>
  <id_info>
    <org_study_id>COVID_ENZA</org_study_id>
    <nct_id>NCT04456049</nct_id>
  </id_info>
  <brief_title>Randomized Open Label Phase II Study to Evaluate the Efficacy of Enzalutamide in High Risk Male Outpatients With COVID-1</brief_title>
  <official_title>COVID_ENZA Trial: Randomized Open Label Phase II Study to Evaluate the Efficacy of Enzalutamide in High Risk Male Outpatients With COVID-1</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Ricardo Pereira Mestre</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Oncology Institute of Southern Switzerland</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Institute of Oncology Research</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Institute for Research in Biomedicine</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Ente Ospedaliero Cantonale, Bellinzona</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      High risk outpatient adult males with a confirmed SARS-CoV-2 infection will be included in&#xD;
      the study.&#xD;
&#xD;
      Patients will be randomized to receive Enzalutamide with standard of care (SOC) or SOC alone.&#xD;
      Enzalutamide will be administered daily p.o. from Day 1 to Day 28 or until confirmed&#xD;
      negativization of Nasopharyngeal swap (NPS) Polymerase chain reaction (PCR) (2 consecutive&#xD;
      negative samples), whichever occurs first.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Low accrual&#xD;
  </why_stopped>
  <start_date type="Actual">August 24, 2020</start_date>
  <completion_date type="Actual">June 9, 2021</completion_date>
  <primary_completion_date type="Actual">June 9, 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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Efficacy of Enzalutamide by decreasing SARS-CoV-2 viral expression</measure>
    <time_frame>28 days</time_frame>
    <description>efficacy of Enzalutamide in decreasing the nasopharyngeal swap SARS-CoV-2 viral load until negativization</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Tollerability of Enzalutamide by identifying Adverse Events</measure>
    <time_frame>28 days</time_frame>
    <description>Evaluation of Enzalutamide tolerability in terms of incidence and severity grade of side effects</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disease progression by unresolved SARS-CoV-2 viral expression after treatment</measure>
    <time_frame>28 days</time_frame>
    <description>Efficacy of Enzalutamide in controlling disease progression of SARS-CoV-2 viral load</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">7</enrollment>
  <condition>COVID-19 Infection</condition>
  <arm_group>
    <arm_group_label>Enzalutamide (Xtandi®)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Interventional treatment</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Standard of care (SOC)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Supportive treatment</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Enzalutamide</intervention_name>
    <description>40 mg oral tablets once daily for a maximum of 28 days.</description>
    <arm_group_label>Enzalutamide (Xtandi®)</arm_group_label>
    <arm_group_label>Standard of care (SOC)</arm_group_label>
    <other_name>XTANDI</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Documented COVID-19 infection (confirmed by NPS positive PCR for SARS-CoV-2) with mild&#xD;
             symptoms not requiring hospitalization&#xD;
&#xD;
          -  First NPS ≤4 days (96 hours) since onset of symptoms&#xD;
&#xD;
          -  Randomization ≤72 hours since first NPS&#xD;
&#xD;
          -  Adult Males aged ≥ 50 years&#xD;
&#xD;
          -  Indication for outpatient treatment but at high risk for complications, at least 1&#xD;
             risk factor (age ≥ 65 years, hypertension, diabetes, cardiovascular disease, active&#xD;
             malignancy, COPD)&#xD;
&#xD;
          -  WHO performance status 0-1&#xD;
&#xD;
          -  Adequate hematologic values: haemoglobin ≥ 100 g/L, neutrophils ≥ 1.0 x 10(9)/L,&#xD;
             platelets ≥ 150 x 10(9)/L.&#xD;
&#xD;
          -  Adequate hepatic function: ALT and AST ≤ 2.5 x ULN, bilirubin ≤ 1.5 x ULN (exception&#xD;
             if Gilbert's syndrome ≤ 2.5 x ULN)&#xD;
&#xD;
          -  Adequate renal function: calculated creatinine clearance ≥ 50 mL/min according to the&#xD;
             formula of Cockcroft-Gault&#xD;
&#xD;
          -  Patient is able to swallow the trial drugs and to comply with trial requirements&#xD;
&#xD;
          -  Patient agrees not to father a child during participation in the trial and for 3&#xD;
             months thereafter&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Female sex&#xD;
&#xD;
          -  Moderate to severe COVID-19 symptoms requiring hospitalization&#xD;
&#xD;
          -  Patients requiring inpatient treatment&#xD;
&#xD;
          -  Concurrent antiviral drugs or ongoing interventional clinical trial or any off label&#xD;
             drug for COVID-19&#xD;
&#xD;
          -  Patients with ongoing prostate cancer treatment&#xD;
&#xD;
          -  Clinically significant cardiovascular disease including:&#xD;
&#xD;
               -  Myocardial infarction within 6 months prior to registration,&#xD;
&#xD;
               -  Uncontrolled angina within 3 months prior to registration,&#xD;
&#xD;
               -  Congestive heart failure NYHA class III or VI&#xD;
&#xD;
               -  QTc interval &gt; 480 ms&#xD;
&#xD;
               -  History of clinically significant ventricular arrhythmias (e.g. ventricular&#xD;
                  tachycardia, ventricular fibrillation, torsades de pointes)&#xD;
&#xD;
               -  History of Mobitz II second or third degree heart block without a permanent&#xD;
                  pacemaker in place&#xD;
&#xD;
               -  Uncontrolled hypertension as indicated by systolic blood pressure &gt; 170 mmHg or&#xD;
                  diastolic blood pressure &gt; 105 mmHg&#xD;
&#xD;
               -  Deep venous thrombosis or pulmonary embolism within 6 months&#xD;
&#xD;
               -  History of cerebrovascular disease&#xD;
&#xD;
          -  Severe concurrent disease, infection or co-morbidity that, in the judgment of the&#xD;
             investigator, would make the patient inappropriate for enrolment.&#xD;
&#xD;
          -  Known history of HIV, hepatitis B, hepatitis C&#xD;
&#xD;
          -  Known history of seizures or any conditions that may predispose to seizure. History of&#xD;
             loss of consciousness or ischemic cerebrovascular attack within 12 months prior to&#xD;
             registration&#xD;
&#xD;
          -  Concurrent anticoagulation with rivaroxaban or warfarin. Concomitant and continuous&#xD;
             use of systemic corticosteroids exceeding 10 mg/day of prednisone or a dose equivalent&#xD;
             corticosteroid within 14 days before registration.&#xD;
&#xD;
          -  Known hypersensitivity to Enzalutamide or hypersensitivity to any of its components&#xD;
&#xD;
          -  Any concomitant drugs contraindicated for use with Enzalutamide according to the&#xD;
             Swissmedic approved product information&#xD;
&#xD;
          -  Any psychological, familial, sociological or geographical condition potentially&#xD;
             hampering compliance with the trial protocol and follow-up.&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>50 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Oncology Institute of Southern Switzerland (IOSI)</name>
      <address>
        <city>Bellinzona</city>
        <zip>6500</zip>
        <country>Switzerland</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Switzerland</country>
  </location_countries>
  <verification_date>August 2022</verification_date>
  <study_first_submitted>July 1, 2020</study_first_submitted>
  <study_first_submitted_qc>July 1, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 2, 2020</study_first_posted>
  <last_update_submitted>August 7, 2022</last_update_submitted>
  <last_update_submitted_qc>August 7, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">August 10, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Ente Ospedaliero Cantonale, Bellinzona</investigator_affiliation>
    <investigator_full_name>Ricardo Pereira Mestre</investigator_full_name>
    <investigator_title>MD</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>COVID-19</mesh_term>
  </condition_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04456049
org study id: COVID_ENZA
nct id: NCT04456049
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
High risk outpatient adult males with a confirmed SARS-CoV-2 infection will be included in
      the study.

      Patients will be randomized to receive Enzalutamide with standard of care (SOC) or SOC alone.
      Enzalutamide will be administered daily p.o. from Day 1 to Day 28 or until confirmed
      negativization of Nasopharyngeal swap (NPS) Polymerase chain reaction (PCR) (2 consecutive
      negative samples), whichever occurs first.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Efficacy of Enzalutamide by decreasing SARS-CoV-2 viral expression
time frame: 28 days
description: efficacy of Enzalutamide in decreasing the nasopharyngeal swap SARS-CoV-2 viral load until negativization
measure: Tollerability of Enzalutamide by identifying Adverse Events
time frame: 28 days
description: Evaluation of Enzalutamide tolerability in terms of incidence and severity grade of side effects
measure: Disease progression by unresolved SARS-CoV-2 viral expression after treatment
time frame: 28 days
description: Efficacy of Enzalutamide in controlling disease progression of SARS-CoV-2 viral load
arm group label: Enzalutamide (Xtandi®)
arm group type: Experimental
description: Interventional treatment
arm group label: Standard of care (SOC)
arm group type: Active Comparator
description: Supportive treatment
intervention type: Drug
intervention name: Enzalutamide
description: 40 mg oral tablets once daily for a maximum of 28 days.
arm group label: Enzalutamide (Xtandi®)
arm group label: Standard of care (SOC)
other name: XTANDI
criteria: 
gender: Male
minimum age: 50 Years
maximum age: N/A
healthy volunteers: No
facility: 
country: Switzerland
responsible party type: Sponsor-Investigator
investigator affiliation: Ente Ospedaliero Cantonale, Bellinzona
investigator full name: Ricardo Pereira Mestre
investigator title: MD
mesh term: COVID-19