<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/NCT04446429</url>
  </required_header>
  <id_info>
    <org_study_id>AB-DRUG-SARS-004</org_study_id>
    <nct_id>NCT04446429</nct_id>
  </id_info>
  <brief_title>Anti-Androgen Treatment for COVID-19</brief_title>
  <official_title>Anti-Androgen Treatment for COVID-19</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Applied Biology, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Applied Biology, Inc.</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>
      This study is intended to explore the possible protective role of anti-androgens in&#xD;
      SARS-CoV-2 infection&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      During the continuing SARS-CoV-2 (COVID-19) pandemic, several studies have reported a&#xD;
      significant difference in the rate of severe cases between adult females and adult males (42%&#xD;
      vs 58%).Among children under the age of 14, the rate of severe cases was reported to be&#xD;
      extremely low. To explain this difference, several theories have been proposed including&#xD;
      cigarette smoking and lifestyle habits. However, no theory fits both the gender difference in&#xD;
      severe cases as well as reduced risk in pre-pubescent children. Our past research on male&#xD;
      androgenetic alopecia (AGA) has led us to investigate an association between androgens and&#xD;
      COVID-19 pathogenesis. In normal subjects, androgen expression demonstrates significant&#xD;
      variation between men and women as well as between adults and pre-pubescent children.&#xD;
&#xD;
      SARS-CoV-2 primarily infects type II pneumocytes in the human lung. SARS-CoV-2 enters&#xD;
      pneumocytes, by anchoring to the ACE2 cell surface receptor. Prior to receptor binding, viral&#xD;
      spike proteins undergo proteolytic priming by the transmembrane protease, serine 2 (TMPRSS2).&#xD;
      TMPRSS2 inhibition or knock down reduces ability of SARS-CoV-1 (a related virus to&#xD;
      SARS-CoV-2) to infect cells in vitro. Additionally, TMPRSS2 also facilitates entry of&#xD;
      influenza A and influenza B into primary human airway cells and type II pneumocytes.&#xD;
&#xD;
      The human TMPRSS2 gene has a 15 bp androgen response element and in humans, androgens are the&#xD;
      only known transcription promoters for the TMPRSS2 gene. In a study of androgen-stimulated&#xD;
      prostate cancer cells (LNCaP), TMPRSS2 mRNA expression increase was mediated by the androgen&#xD;
      receptor. Further, the ACE2 receptor, also critical for SARS-CoV-2 viral infectivity, is&#xD;
      affected by male sex hormones with higher activity found in males.&#xD;
&#xD;
      Androgenetic alopecia (AGA), often referred to as male pattern hair loss, is the most common&#xD;
      form of hair loss among men. The development of androgenetic alopecia is androgen mediated&#xD;
      and is dependent on genetic variants found in the androgen receptor gene located on the X&#xD;
      chromosome; thus, it is hypothesized that men with AGA would be more prone to severe COVID-19&#xD;
      disease. The investigators conducted a preliminary observational study of hospitalized&#xD;
      COVID-19 patients at two Spanish tertiary hospitals between March 23-April 6, 2020 to test&#xD;
      this theory. In total, 41 Caucasian males admitted to the hospitals with a diagnosis of&#xD;
      bilateral SARS-CoV-2 pneumonia were analyzed. The mean age of patients was 58 years (range&#xD;
      23-79). Among them, 29 (71%) were diagnosed with AGA (16 (39%) were classified as severe AGA&#xD;
      (Hamilton IV or above)) and 12 (29%) did not present clinical signs of AGA. The diagnosis of&#xD;
      AGA was performed clinically by a dermatologist. The precise prevalence of AGA among&#xD;
      otherwise healthy Spanish Caucasian males is unknown; however, based on published literature,&#xD;
      the expected prevalence of a similar age-matched Caucasian population is approximately&#xD;
      31-53%.&#xD;
&#xD;
      Based on the scientific rationale combined with this preliminary observation, the&#xD;
      investigators propose to test an anti-androgen as a treatment for patients recently diagnosed&#xD;
      with COVID-19.&#xD;
&#xD;
      We have chosen the use of the novel second generation androgen receptor (AR) antagonist&#xD;
      proxalutamide as a means for rapid reduction in AR activity. Proxalutamide (GT0918)&#xD;
      demonstrates a dual mechanism of action. It is highly effective in inhibiting AR as well as&#xD;
      exhibiting pharmacological effects of inducing the down-regulation of AR expression; the&#xD;
      mechanism that is not present in bicalutamide and enzalutamide. Additionally, it has been&#xD;
      reported that Proxalutamide lowers the expression of ACE2. Both would be beneficial for&#xD;
      preventing SARS-CoV-2 entry into lung cells.&#xD;
&#xD;
      This study is intended to explore the possible protective role of anti-androgens in&#xD;
      SARS-CoV-2 infection. Provided anti-androgens are effective in reducing the rate of COVID-19&#xD;
      hospitalization, subjects enrolled in this study may experience a lower rate of&#xD;
      hospitalization.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 21, 2020</start_date>
  <completion_date type="Actual">January 21, 2021</completion_date>
  <primary_completion_date type="Actual">December 24, 2020</primary_completion_date>
  <phase>N/A</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>This study is designed as a prospective, interventional, placebo controlled, double-blinded, randomized parallel assignment study.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>COVID-19 Hospitalization</measure>
    <time_frame>30 days</time_frame>
    <description>Percentage of subjects hospitalized due to COVID-19</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">268</enrollment>
  <condition>COVID-19</condition>
  <condition>SARS-CoV2</condition>
  <condition>Androgenetic Alopecia</condition>
  <condition>Prostate Cancer</condition>
  <condition>Benign Prostatic Hyperplasia</condition>
  <condition>SARS (Severe Acute Respiratory Syndrome)</condition>
  <arm_group>
    <arm_group_label>Usual Care</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Usual care as determined by the PI</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Proxalutamide + Usual Care</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Proxalutamide + Usual care as determined by the PI</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Proxalutamide</intervention_name>
    <description>200 mg q.d.</description>
    <arm_group_label>Proxalutamide + Usual Care</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Standard of Care</intervention_name>
    <description>Standard of care as determined by the PI</description>
    <arm_group_label>Usual Care</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Male age ≥18 years old&#xD;
&#xD;
          2. Laboratory confirmed positive SARS-CoV-2 rtPCR test within 7 days prior to&#xD;
             randomization&#xD;
&#xD;
          3. Clinical status on the COVID-19 8-point Ordinal Scale of 1 or 2&#xD;
&#xD;
          4. Coagulation: INR ≤ 1.5×ULN, and APTT ≤ 1.5×ULN&#xD;
&#xD;
          5. Subject (or legally authorized representative) gives written informed consent prior to&#xD;
             any study screening procedures&#xD;
&#xD;
          6. Subject (or legally authorized representative) agree that subject will not participate&#xD;
             in another COVID-19 trial while participating in this study&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Subject enrolled in a study to investigate a treatment for COVID-19&#xD;
&#xD;
          2. Subject taking an anti-androgen of any type including: androgen depravation therapy,&#xD;
             5-alpha reductase inhibitors, etc…&#xD;
&#xD;
          3. Patients who are allergic to the investigational product or similar drugs (or any&#xD;
             excipients);&#xD;
&#xD;
          4. Subjects who have malignant tumors in the past 5 years, with the exception of&#xD;
             completed resected basal cell and squamous cell skin cancer and completely resected&#xD;
             carcinoma in situ of any type&#xD;
&#xD;
          5. Subjects with known serious cardiovascular diseases, congenital long QT syndrome,&#xD;
             torsade de pointes, myocardial infarction in the past 6 months, or arterial&#xD;
             thrombosis, or unstable angina pectoris, or congestive heart failure which is&#xD;
             classified as New York Heart Association (NYHA) class 3 or higher, or left ventricular&#xD;
             ejection fraction (LVEF) &lt; 50%, QTcF &gt; 450 ms&#xD;
&#xD;
          6. Subjects with uncontrolled medical conditions that could compromise participation in&#xD;
             the study(e.g. uncontrolled hypertension, hypothyroidism, diabetes mellitus)&#xD;
&#xD;
          7. Known diagnosis of human immunodeficiency virus(HIV) , hepatitis C, active hepatitis&#xD;
             B, treponema pallidum (testing is not mandatory）&#xD;
&#xD;
          8. Alanine Transaminase (ALT) or Aspartate Transaminase (AST) &gt; 5 times the upper limit&#xD;
             of normal.&#xD;
&#xD;
          9. Estimated glomerular filtration rate (eGFR) &lt; 30 ml/min&#xD;
&#xD;
         10. Severe kidney disease requiring dialysis&#xD;
&#xD;
         11. Subject unlikely to return for day 15 site visit for reasons other then remission&#xD;
&#xD;
         12. Subject (or legally authorized representative) not willing or unable to provide&#xD;
             informed consent&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <gender_based>Yes</gender_based>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Flavio A Cadegiani, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Corpometria Institute</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Andy Goren, MD</last_name>
    <role>Study Director</role>
    <affiliation>Applied Biology, Inc.</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Corpometria Institute</name>
      <address>
        <city>Brasilia</city>
        <zip>70390-150</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Brazil</country>
  </location_countries>
  <reference>
    <citation>Goren A, McCoy J, Wambier CG, Vano-Galvan S, Shapiro J, Dhurat R, Washenik K, Lotti T. What does androgenetic alopecia have to do with COVID-19? An insight into a potential new therapy. Dermatol Ther. 2020 Jul;33(4):e13365. doi: 10.1111/dth.13365. Epub 2020 Apr 8. No abstract available.</citation>
    <PMID>32237190</PMID>
  </reference>
  <reference>
    <citation>Goren A, Vano-Galvan S, Wambier CG, McCoy J, Gomez-Zubiaur A, Moreno-Arrones OM, Shapiro J, Sinclair RD, Gold MH, Kovacevic M, Mesinkovska NA, Goldust M, Washenik K. A preliminary observation: Male pattern hair loss among hospitalized COVID-19 patients in Spain - A potential clue to the role of androgens in COVID-19 severity. J Cosmet Dermatol. 2020 Jul;19(7):1545-1547. doi: 10.1111/jocd.13443. Epub 2020 Apr 23.</citation>
    <PMID>32301221</PMID>
  </reference>
  <reference>
    <citation>McCoy J, Wambier CG, Vano-Galvan S, Shapiro J, Sinclair R, Ramos PM, Washenik K, Andrade M, Herrera S, Goren A. Racial variations in COVID-19 deaths may be due to androgen receptor genetic variants associated with prostate cancer and androgenetic alopecia. Are anti-androgens a potential treatment for COVID-19? J Cosmet Dermatol. 2020 Jul;19(7):1542-1543. doi: 10.1111/jocd.13455. Epub 2020 Jun 14. No abstract available.</citation>
    <PMID>32333494</PMID>
  </reference>
  <reference>
    <citation>Wambier CG, Goren A, Vano-Galvan S, Ramos PM, Ossimetha A, Nau G, Herrera S, McCoy J. Androgen sensitivity gateway to COVID-19 disease severity. Drug Dev Res. 2020 Nov;81(7):771-776. doi: 10.1002/ddr.21688. Epub 2020 May 15.</citation>
    <PMID>32412125</PMID>
  </reference>
  <reference>
    <citation>Wambier CG, Vano-Galvan S, McCoy J, Gomez-Zubiaur A, Herrera S, Hermosa-Gelbard A, Moreno-Arrones OM, Jimenez-Gomez N, Gonzalez-Cantero A, Fonda-Pascual P, Segurado-Miravalles G, Shapiro J, Perez-Garcia B, Goren A. Androgenetic alopecia present in the majority of patients hospitalized with COVID-19: The &quot;Gabrin sign&quot;. J Am Acad Dermatol. 2020 Aug;83(2):680-682. doi: 10.1016/j.jaad.2020.05.079. Epub 2020 May 22.</citation>
    <PMID>32446821</PMID>
  </reference>
  <reference>
    <citation>Montopoli M, Zumerle S, Vettor R, Rugge M, Zorzi M, Catapano CV, Carbone GM, Cavalli A, Pagano F, Ragazzi E, Prayer-Galetti T, Alimonti A. Androgen-deprivation therapies for prostate cancer and risk of infection by SARS-CoV-2: a population-based study (N = 4532). Ann Oncol. 2020 Aug;31(8):1040-1045. doi: 10.1016/j.annonc.2020.04.479. Epub 2020 May 6.</citation>
    <PMID>32387456</PMID>
  </reference>
  <verification_date>December 2021</verification_date>
  <study_first_submitted>June 22, 2020</study_first_submitted>
  <study_first_submitted_qc>June 23, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 24, 2020</study_first_posted>
  <results_first_submitted>January 22, 2021</results_first_submitted>
  <results_first_submitted_qc>January 29, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">February 3, 2021</results_first_posted>
  <last_update_submitted>December 8, 2021</last_update_submitted>
  <last_update_submitted_qc>December 8, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">December 10, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Anti-Androgen</keyword>
  <keyword>Proxalutamide</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>COVID-19</mesh_term>
    <mesh_term>Severe Acute Respiratory Syndrome</mesh_term>
    <mesh_term>Prostatic Hyperplasia</mesh_term>
    <mesh_term>Alopecia</mesh_term>
    <mesh_term>Hyperplasia</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan: Study Protocol (English Translation)</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>September 17, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/29/NCT04446429/Prot_SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Usual Care</title>
          <description>Usual care as determined by the PI&#xD;
Usualf Care: Care as determined by the PI</description>
        </group>
        <group group_id="P2">
          <title>Proxalutamide + Usual Care</title>
          <description>Proxalutamide + usual care as determined by the PI&#xD;
Proxalutamide: 200 mg q.d.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="134"/>
                <participants group_id="P2" count="134"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="128">In placebo group, 6 patients were lost to follow-up but were included in intention-to-treat analysis.</participants>
                <participants group_id="P2" count="134"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Usual Care</title>
          <description>Usual care as determined by the PI&#xD;
Usual Care: Care as determined by the PI</description>
        </group>
        <group group_id="B2">
          <title>Proxalutamide + Usual Care</title>
          <description>Proxalutamide + usual care as determined by the PI&#xD;
Proxalutamide: 200 mg q.d.</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="134"/>
            <count group_id="B2" value="134"/>
            <count group_id="B3" value="268"/>
          </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="45" spread="10.8"/>
                    <measurement group_id="B2" value="44.2" spread="14"/>
                    <measurement group_id="B3" value="44.5" spread="7.7"/>
                  </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="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="134"/>
                    <measurement group_id="B2" value="134"/>
                    <measurement group_id="B3" value="268"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Mixed ethnicity (Brazil)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="134"/>
                    <measurement group_id="B2" value="134"/>
                    <measurement group_id="B3" value="268"/>
                  </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>Brazil</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="134"/>
                    <measurement group_id="B2" value="134"/>
                    <measurement group_id="B3" value="268"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Coexisting conditions</title>
          <description>At least one coexisting conditions: Type 2 diabetes, Hypertension, COPD and Obesity</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="20"/>
                    <measurement group_id="B2" value="29"/>
                    <measurement group_id="B3" value="49"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>COVID-19 Hospitalization</title>
        <description>Percentage of subjects hospitalized due to COVID-19</description>
        <time_frame>30 days</time_frame>
        <population>All randomized patients were included. 6 patients from the placebo arm lost to follow-up were assumed to be non-hospitalized (COVID-19 8-point ordinal scale 1) and were included in the intention-to-treat analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Usual Care</title>
            <description>Usual care as determined by the PI&#xD;
Usual Care: Care as determined by the PI</description>
          </group>
          <group group_id="O2">
            <title>Proxalutamide + Usual Care</title>
            <description>Proxalutamide + usual care as determined by the PI&#xD;
Proxalutamide: 200 mg q.d.</description>
          </group>
        </group_list>
        <measure>
          <title>COVID-19 Hospitalization</title>
          <description>Percentage of subjects hospitalized due to COVID-19</description>
          <population>All randomized patients were included. 6 patients from the placebo arm lost to follow-up were assumed to be non-hospitalized (COVID-19 8-point ordinal scale 1) and were included in the intention-to-treat analysis.</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="134"/>
                <count group_id="O2" value="134"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="35"/>
                    <measurement group_id="O2" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>30 days</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Usual Care</title>
          <description>Usual care as determined by the PI&#xD;
Usual Care: Care as determined by the PI</description>
        </group>
        <group group_id="E2">
          <title>Proxalutamide + Usual Care</title>
          <description>Proxalutamide + usual care as determined by the PI&#xD;
Proxalutamide: 200 mg q.d.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA (19.0)</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="2" subjects_at_risk="134"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="134"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="35" subjects_at_risk="134"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="134"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Death</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="134"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="134"/>
              </event>
              <event>
                <sub_title>Hospitalization</sub_title>
                <counts group_id="E1" events="35" subjects_affected="35" subjects_at_risk="134"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="134"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA (19.0)</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="78" subjects_at_risk="134"/>
                <counts group_id="E2" subjects_affected="45" subjects_at_risk="134"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Tachycardia</sub_title>
                <counts group_id="E1" subjects_affected="45" subjects_at_risk="134"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="134"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" subjects_affected="20" subjects_at_risk="134"/>
                <counts group_id="E2" subjects_affected="39" subjects_at_risk="134"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="15" subjects_at_risk="134"/>
                <counts group_id="E2" subjects_affected="21" subjects_at_risk="134"/>
              </event>
              <event>
                <sub_title>Abdominal pain or discomfort</sub_title>
                <counts group_id="E1" subjects_affected="18" subjects_at_risk="134"/>
                <counts group_id="E2" subjects_affected="22" subjects_at_risk="134"/>
              </event>
              <event>
                <sub_title>Dyspepsia or Heartburn</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="134"/>
                <counts group_id="E2" subjects_affected="23" subjects_at_risk="134"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="71" subjects_at_risk="134"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="134"/>
              </event>
              <event>
                <sub_title>Fever</sub_title>
                <counts group_id="E1" subjects_affected="34" subjects_at_risk="134"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="134"/>
              </event>
              <event>
                <sub_title>Disease progression</sub_title>
                <counts group_id="E1" subjects_affected="43" subjects_at_risk="134"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="134"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" subjects_affected="36" subjects_at_risk="134"/>
                <counts group_id="E2" subjects_affected="16" subjects_at_risk="134"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Ageusia</sub_title>
                <counts group_id="E1" subjects_affected="23" subjects_at_risk="134"/>
                <counts group_id="E2" subjects_affected="13" subjects_at_risk="134"/>
              </event>
              <event>
                <sub_title>Anosmia</sub_title>
                <counts group_id="E1" subjects_affected="26" subjects_at_risk="134"/>
                <counts group_id="E2" subjects_affected="14" subjects_at_risk="134"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="12" subjects_at_risk="134"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="134"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Shortness of breath</sub_title>
                <counts group_id="E1" subjects_affected="40" subjects_at_risk="134"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="134"/>
              </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>
    <point_of_contact>
      <name_or_title>Director of Clinical Trials</name_or_title>
      <organization>Applied Biology</organization>
      <phone>+1-949-387-4526</phone>
      <email>monican@appliedbiology.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/NCT04446429
org study id: AB-DRUG-SARS-004
nct id: NCT04446429
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This study is intended to explore the possible protective role of anti-androgens in
      SARS-CoV-2 infection
During the continuing SARS-CoV-2 (COVID-19) pandemic, several studies have reported a
      significant difference in the rate of severe cases between adult females and adult males (42%
      vs 58%).Among children under the age of 14, the rate of severe cases was reported to be
      extremely low. To explain this difference, several theories have been proposed including
      cigarette smoking and lifestyle habits. However, no theory fits both the gender difference in
      severe cases as well as reduced risk in pre-pubescent children. Our past research on male
      androgenetic alopecia (AGA) has led us to investigate an association between androgens and
      COVID-19 pathogenesis. In normal subjects, androgen expression demonstrates significant
      variation between men and women as well as between adults and pre-pubescent children.

      SARS-CoV-2 primarily infects type II pneumocytes in the human lung. SARS-CoV-2 enters
      pneumocytes, by anchoring to the ACE2 cell surface receptor. Prior to receptor binding, viral
      spike proteins undergo proteolytic priming by the transmembrane protease, serine 2 (TMPRSS2).
      TMPRSS2 inhibition or knock down reduces ability of SARS-CoV-1 (a related virus to
      SARS-CoV-2) to infect cells in vitro. Additionally, TMPRSS2 also facilitates entry of
      influenza A and influenza B into primary human airway cells and type II pneumocytes.

      The human TMPRSS2 gene has a 15 bp androgen response element and in humans, androgens are the
      only known transcription promoters for the TMPRSS2 gene. In a study of androgen-stimulated
      prostate cancer cells (LNCaP), TMPRSS2 mRNA expression increase was mediated by the androgen
      receptor. Further, the ACE2 receptor, also critical for SARS-CoV-2 viral infectivity, is
      affected by male sex hormones with higher activity found in males.

      Androgenetic alopecia (AGA), often referred to as male pattern hair loss, is the most common
      form of hair loss among men. The development of androgenetic alopecia is androgen mediated
      and is dependent on genetic variants found in the androgen receptor gene located on the X
      chromosome; thus, it is hypothesized that men with AGA would be more prone to severe COVID-19
      disease. The investigators conducted a preliminary observational study of hospitalized
      COVID-19 patients at two Spanish tertiary hospitals between March 23-April 6, 2020 to test
      this theory. In total, 41 Caucasian males admitted to the hospitals with a diagnosis of
      bilateral SARS-CoV-2 pneumonia were analyzed. The mean age of patients was 58 years (range
      23-79). Among them, 29 (71%) were diagnosed with AGA (16 (39%) were classified as severe AGA
      (Hamilton IV or above)) and 12 (29%) did not present clinical signs of AGA. The diagnosis of
      AGA was performed clinically by a dermatologist. The precise prevalence of AGA among
      otherwise healthy Spanish Caucasian males is unknown; however, based on published literature,
      the expected prevalence of a similar age-matched Caucasian population is approximately
      31-53%.

      Based on the scientific rationale combined with this preliminary observation, the
      investigators propose to test an anti-androgen as a treatment for patients recently diagnosed
      with COVID-19.

      We have chosen the use of the novel second generation androgen receptor (AR) antagonist
      proxalutamide as a means for rapid reduction in AR activity. Proxalutamide (GT0918)
      demonstrates a dual mechanism of action. It is highly effective in inhibiting AR as well as
      exhibiting pharmacological effects of inducing the down-regulation of AR expression; the
      mechanism that is not present in bicalutamide and enzalutamide. Additionally, it has been
      reported that Proxalutamide lowers the expression of ACE2. Both would be beneficial for
      preventing SARS-CoV-2 entry into lung cells.

      This study is intended to explore the possible protective role of anti-androgens in
      SARS-CoV-2 infection. Provided anti-androgens are effective in reducing the rate of COVID-19
      hospitalization, subjects enrolled in this study may experience a lower rate of
      hospitalization.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: This study is designed as a prospective, interventional, placebo controlled, double-blinded, randomized parallel assignment study.
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: COVID-19 Hospitalization
time frame: 30 days
description: Percentage of subjects hospitalized due to COVID-19
arm group label: Usual Care
arm group type: Active Comparator
description: Usual care as determined by the PI
arm group label: Proxalutamide + Usual Care
arm group type: Experimental
description: Proxalutamide + Usual care as determined by the PI
intervention type: Drug
intervention name: Proxalutamide
description: 200 mg q.d.
arm group label: Proxalutamide + Usual Care
intervention type: Other
intervention name: Standard of Care
description: Standard of care as determined by the PI
arm group label: Usual Care
criteria: 
gender: Male
gender based: Yes
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Flavio A Cadegiani, MD
role: Principal Investigator
affiliation: Corpometria Institute
last name: Andy Goren, MD
role: Study Director
affiliation: Applied Biology, Inc.
facility: 
country: Brazil
citation: Goren A, McCoy J, Wambier CG, Vano-Galvan S, Shapiro J, Dhurat R, Washenik K, Lotti T. What does androgenetic alopecia have to do with COVID-19? An insight into a potential new therapy. Dermatol Ther. 2020 Jul;33(4):e13365. doi: 10.1111/dth.13365. Epub 2020 Apr 8. No abstract available.
PMID: 32237190
citation: Goren A, Vano-Galvan S, Wambier CG, McCoy J, Gomez-Zubiaur A, Moreno-Arrones OM, Shapiro J, Sinclair RD, Gold MH, Kovacevic M, Mesinkovska NA, Goldust M, Washenik K. A preliminary observation: Male pattern hair loss among hospitalized COVID-19 patients in Spain - A potential clue to the role of androgens in COVID-19 severity. J Cosmet Dermatol. 2020 Jul;19(7):1545-1547. doi: 10.1111/jocd.13443. Epub 2020 Apr 23.
PMID: 32301221
citation: McCoy J, Wambier CG, Vano-Galvan S, Shapiro J, Sinclair R, Ramos PM, Washenik K, Andrade M, Herrera S, Goren A. Racial variations in COVID-19 deaths may be due to androgen receptor genetic variants associated with prostate cancer and androgenetic alopecia. Are anti-androgens a potential treatment for COVID-19? J Cosmet Dermatol. 2020 Jul;19(7):1542-1543. doi: 10.1111/jocd.13455. Epub 2020 Jun 14. No abstract available.
PMID: 32333494
citation: Wambier CG, Goren A, Vano-Galvan S, Ramos PM, Ossimetha A, Nau G, Herrera S, McCoy J. Androgen sensitivity gateway to COVID-19 disease severity. Drug Dev Res. 2020 Nov;81(7):771-776. doi: 10.1002/ddr.21688. Epub 2020 May 15.
PMID: 32412125
citation: Wambier CG, Vano-Galvan S, McCoy J, Gomez-Zubiaur A, Herrera S, Hermosa-Gelbard A, Moreno-Arrones OM, Jimenez-Gomez N, Gonzalez-Cantero A, Fonda-Pascual P, Segurado-Miravalles G, Shapiro J, Perez-Garcia B, Goren A. Androgenetic alopecia present in the majority of patients hospitalized with COVID-19: The "Gabrin sign". J Am Acad Dermatol. 2020 Aug;83(2):680-682. doi: 10.1016/j.jaad.2020.05.079. Epub 2020 May 22.
PMID: 32446821
citation: Montopoli M, Zumerle S, Vettor R, Rugge M, Zorzi M, Catapano CV, Carbone GM, Cavalli A, Pagano F, Ragazzi E, Prayer-Galetti T, Alimonti A. Androgen-deprivation therapies for prostate cancer and risk of infection by SARS-CoV-2: a population-based study (N = 4532). Ann Oncol. 2020 Aug;31(8):1040-1045. doi: 10.1016/j.annonc.2020.04.479. Epub 2020 May 6.
PMID: 32387456
responsible party type: Sponsor
mesh term: COVID-19
mesh term: Severe Acute Respiratory Syndrome
mesh term: Prostatic Hyperplasia
mesh term: Alopecia
mesh term: Hyperplasia
sharing ipd: No
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 