<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/NCT04483973</url>
  </required_header>
  <id_info>
    <org_study_id>SPI-1005-292</org_study_id>
    <nct_id>NCT04483973</nct_id>
  </id_info>
  <brief_title>SPI-1005 Treatment in Severe COVID-19 Patients</brief_title>
  <official_title>A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Dose Escalation Study to Evaluate the Safety and Efficacy of SPI-1005 in Severe COVID-19 Patients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Sound Pharmaceuticals, Incorporated</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Sound Pharmaceuticals, Incorporated</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 study is a randomized, double-blind, placebo-controlled, dose escalation, multi-center&#xD;
      clinical trial (RCT) of SPI-1005 in adult subjects with positive PCR test for novel&#xD;
      SARS-CoV-2 (nCoV2) and severe symptoms of COVID-19 disease.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Enrolling by invitation</overall_status>
  <start_date type="Actual">August 27, 2021</start_date>
  <completion_date type="Anticipated">April 2023</completion_date>
  <primary_completion_date type="Anticipated">April 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>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of participants with treatment-related adverse events</measure>
    <time_frame>30 days</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>WHO Ordinal Scale</measure>
    <time_frame>30 days</time_frame>
    <description>Clinical outcome assessed by WHO Ordinal Scale for Clinical Improvement. Scale is 0-8 where higher score is worse outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Degree of supplemental oxygen</measure>
    <time_frame>30 days</time_frame>
    <description>Respiratory status assessed by degree of supplemental oxygen (e.g. mask oxygen, mechanical ventilation)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Peripheral Oxygen Saturation (SpO2)</measure>
    <time_frame>30 days</time_frame>
    <description>Peripheral oxygen saturation measured by pulse oximetry</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Anticipated">60</enrollment>
  <condition>Covid19</condition>
  <condition>Coronavirus</condition>
  <condition>Coronavirus Infection</condition>
  <condition>Corona Virus Infection</condition>
  <arm_group>
    <arm_group_label>SPI-1005 400 mg BID</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Oral administration of SPI-1005 400 mg BID for 14 days, with 30-day follow-up</description>
  </arm_group>
  <arm_group>
    <arm_group_label>SPI-1005 800 mg BID</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Oral administration of SPI-1005 800 mg BID for 14 days, with 30-day follow-up</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Oral administration of matching placebo BID for 14 days, with 30-day follow-up</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ebselen</intervention_name>
    <description>Glutathione peroxidase mimetic</description>
    <arm_group_label>SPI-1005 400 mg BID</arm_group_label>
    <arm_group_label>SPI-1005 800 mg BID</arm_group_label>
    <other_name>SPI-1005</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Matching placebo containing excipients</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Adults ≥18 years of age&#xD;
&#xD;
          -  Positive nCoV2 PCR test by nasopharyngeal, oral, saliva, or respiratory sample&#xD;
&#xD;
          -  Clinical signs, symptoms, and respiratory status consistent with severe COVID-19&#xD;
&#xD;
          -  Score of 5-7 on the WHO Ordinal Scale&#xD;
&#xD;
          -  Onset of severe COVID-19 symptoms ≤7 days of study enrollment&#xD;
&#xD;
          -  Subject is in-patient at time of randomization to study treatment&#xD;
&#xD;
          -  Subject or legally authorized representative is willing and able to provide informed&#xD;
             consent, and agrees for subject to comply with planned study procedures including&#xD;
             reproductive requirements&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Female patients who are pregnant or breastfeeding.&#xD;
&#xD;
          -  Participation in another interventional investigational drug or device study&#xD;
             concurrently or within 30 days prior to study consent.&#xD;
&#xD;
          -  Patients with impaired hepatic or renal function.&#xD;
&#xD;
          -  Subject has any other illness or condition that, in the opinion of the investigator,&#xD;
             would prohibit the subject from participating.&#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>Miriam Treggiari, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Yale University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Yale University</name>
      <address>
        <city>New Haven</city>
        <state>Connecticut</state>
        <zip>96510</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St. Luke's Cystic Fibrosis Center of Idaho</name>
      <address>
        <city>Boise</city>
        <state>Idaho</state>
        <zip>83702</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kansas University Medical Center</name>
      <address>
        <city>Kansas City</city>
        <state>Kansas</state>
        <zip>66160</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Washington University in St. Louis</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63130</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Duke University</name>
      <address>
        <city>Durham</city>
        <state>North Carolina</state>
        <zip>27710</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Wake Forest University</name>
      <address>
        <city>Winston-Salem</city>
        <state>North Carolina</state>
        <zip>27109</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Texas Southwestern</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75390</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Jin Z, Du X, Xu Y, Deng Y, Liu M, Zhao Y, Zhang B, Li X, Zhang L, Peng C, Duan Y, Yu J, Wang L, Yang K, Liu F, Jiang R, Yang X, You T, Liu X, Yang X, Bai F, Liu H, Liu X, Guddat LW, Xu W, Xiao G, Qin C, Shi Z, Jiang H, Rao Z, Yang H. Structure of Mpro from SARS-CoV-2 and discovery of its inhibitors. Nature. 2020 Jun;582(7811):289-293. doi: 10.1038/s41586-020-2223-y. Epub 2020 Apr 9.</citation>
    <PMID>32272481</PMID>
  </reference>
  <reference>
    <citation>Menendez CA, Bylehn F, Perez-Lemus GR, Alvarado W, de Pablo JJ. Molecular characterization of ebselen binding activity to SARS-CoV-2 main protease. Sci Adv. 2020 Sep 11;6(37):eabd0345. doi: 10.1126/sciadv.abd0345. Print 2020 Sep.</citation>
    <PMID>32917717</PMID>
  </reference>
  <reference>
    <citation>Weglarz-Tomczak E, Tomczak JM, Talma M, Burda-Grabowska M, Giurg M, Brul S. Identification of ebselen and its analogues as potent covalent inhibitors of papain-like protease from SARS-CoV-2. Sci Rep. 2021 Feb 11;11(1):3640. doi: 10.1038/s41598-021-83229-6.</citation>
    <PMID>33574416</PMID>
  </reference>
  <reference>
    <citation>Brown AS, Ackerley DF, Calcott MJ. High-Throughput Screening for Inhibitors of the SARS-CoV-2 Protease Using a FRET-Biosensor. Molecules. 2020 Oct 13;25(20):4666. doi: 10.3390/molecules25204666.</citation>
    <PMID>33066278</PMID>
  </reference>
  <reference>
    <citation>Haritha CV, Sharun K, Jose B. Ebselen, a new candidate therapeutic against SARS-CoV-2. Int J Surg. 2020 Dec;84:53-56. doi: 10.1016/j.ijsu.2020.10.018. Epub 2020 Oct 23. No abstract available.</citation>
    <PMID>33120196</PMID>
  </reference>
  <reference>
    <citation>Chen T, Fei CY, Chen YP, Sargsyan K, Chang CP, Yuan HS, Lim C. Synergistic Inhibition of SARS-CoV-2 Replication Using Disulfiram/Ebselen and Remdesivir. ACS Pharmacol Transl Sci. 2021 Mar 26;4(2):898-907. doi: 10.1021/acsptsci.1c00022. eCollection 2021 Apr 9. Erratum In: ACS Pharmacol Transl Sci. 2021 Apr 29;4(3):1246.</citation>
    <PMID>33855277</PMID>
  </reference>
  <reference>
    <citation>Sies H, Parnham MJ. Potential therapeutic use of ebselen for COVID-19 and other respiratory viral infections. Free Radic Biol Med. 2020 Aug 20;156:107-112. doi: 10.1016/j.freeradbiomed.2020.06.032. Epub 2020 Jun 26.</citation>
    <PMID>32598985</PMID>
  </reference>
  <verification_date>November 2022</verification_date>
  <study_first_submitted>July 13, 2020</study_first_submitted>
  <study_first_submitted_qc>July 21, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 23, 2020</study_first_posted>
  <last_update_submitted>November 4, 2022</last_update_submitted>
  <last_update_submitted_qc>November 4, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">November 8, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>ebselen</keyword>
  <keyword>SPI-1005</keyword>
  <keyword>COVID-19</keyword>
  <keyword>Covid</keyword>
  <keyword>SARS-COV-2</keyword>
  <keyword>Mpro</keyword>
  <keyword>main protease</keyword>
  <keyword>PLpro</keyword>
  <keyword>papain-like protease</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Infections</mesh_term>
    <mesh_term>Communicable Diseases</mesh_term>
    <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>Ebselen</mesh_term>
  </intervention_browse>
  <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/NCT04483973
org study id: SPI-1005-292
nct id: NCT04483973
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
The study is a randomized, double-blind, placebo-controlled, dose escalation, multi-center
      clinical trial (RCT) of SPI-1005 in adult subjects with positive PCR test for novel
      SARS-CoV-2 (nCoV2) and severe symptoms of COVID-19 disease.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Number of participants with treatment-related adverse events
time frame: 30 days
measure: WHO Ordinal Scale
time frame: 30 days
description: Clinical outcome assessed by WHO Ordinal Scale for Clinical Improvement. Scale is 0-8 where higher score is worse outcome.
measure: Degree of supplemental oxygen
time frame: 30 days
description: Respiratory status assessed by degree of supplemental oxygen (e.g. mask oxygen, mechanical ventilation)
measure: Peripheral Oxygen Saturation (SpO2)
time frame: 30 days
description: Peripheral oxygen saturation measured by pulse oximetry
arm group label: SPI-1005 400 mg BID
arm group type: Experimental
description: Oral administration of SPI-1005 400 mg BID for 14 days, with 30-day follow-up
arm group label: SPI-1005 800 mg BID
arm group type: Experimental
description: Oral administration of SPI-1005 800 mg BID for 14 days, with 30-day follow-up
arm group label: Placebo
arm group type: Placebo Comparator
description: Oral administration of matching placebo BID for 14 days, with 30-day follow-up
intervention type: Drug
intervention name: Ebselen
description: Glutathione peroxidase mimetic
arm group label: SPI-1005 400 mg BID
arm group label: SPI-1005 800 mg BID
other name: SPI-1005
intervention type: Drug
intervention name: Placebo
description: Matching placebo containing excipients
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Miriam Treggiari, MD
role: Principal Investigator
affiliation: Yale University
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
citation: Jin Z, Du X, Xu Y, Deng Y, Liu M, Zhao Y, Zhang B, Li X, Zhang L, Peng C, Duan Y, Yu J, Wang L, Yang K, Liu F, Jiang R, Yang X, You T, Liu X, Yang X, Bai F, Liu H, Liu X, Guddat LW, Xu W, Xiao G, Qin C, Shi Z, Jiang H, Rao Z, Yang H. Structure of Mpro from SARS-CoV-2 and discovery of its inhibitors. Nature. 2020 Jun;582(7811):289-293. doi: 10.1038/s41586-020-2223-y. Epub 2020 Apr 9.
PMID: 32272481
citation: Menendez CA, Bylehn F, Perez-Lemus GR, Alvarado W, de Pablo JJ. Molecular characterization of ebselen binding activity to SARS-CoV-2 main protease. Sci Adv. 2020 Sep 11;6(37):eabd0345. doi: 10.1126/sciadv.abd0345. Print 2020 Sep.
PMID: 32917717
citation: Weglarz-Tomczak E, Tomczak JM, Talma M, Burda-Grabowska M, Giurg M, Brul S. Identification of ebselen and its analogues as potent covalent inhibitors of papain-like protease from SARS-CoV-2. Sci Rep. 2021 Feb 11;11(1):3640. doi: 10.1038/s41598-021-83229-6.
PMID: 33574416
citation: Brown AS, Ackerley DF, Calcott MJ. High-Throughput Screening for Inhibitors of the SARS-CoV-2 Protease Using a FRET-Biosensor. Molecules. 2020 Oct 13;25(20):4666. doi: 10.3390/molecules25204666.
PMID: 33066278
citation: Haritha CV, Sharun K, Jose B. Ebselen, a new candidate therapeutic against SARS-CoV-2. Int J Surg. 2020 Dec;84:53-56. doi: 10.1016/j.ijsu.2020.10.018. Epub 2020 Oct 23. No abstract available.
PMID: 33120196
citation: Chen T, Fei CY, Chen YP, Sargsyan K, Chang CP, Yuan HS, Lim C. Synergistic Inhibition of SARS-CoV-2 Replication Using Disulfiram/Ebselen and Remdesivir. ACS Pharmacol Transl Sci. 2021 Mar 26;4(2):898-907. doi: 10.1021/acsptsci.1c00022. eCollection 2021 Apr 9. Erratum In: ACS Pharmacol Transl Sci. 2021 Apr 29;4(3):1246.
PMID: 33855277
citation: Sies H, Parnham MJ. Potential therapeutic use of ebselen for COVID-19 and other respiratory viral infections. Free Radic Biol Med. 2020 Aug 20;156:107-112. doi: 10.1016/j.freeradbiomed.2020.06.032. Epub 2020 Jun 26.
PMID: 32598985
responsible party type: Sponsor
mesh term: Infections
mesh term: Communicable Diseases
mesh term: COVID-19
mesh term: Coronavirus Infections
mesh term: Ebselen
sharing ipd: No