<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/NCT04404361</url>
  </required_header>
  <id_info>
    <org_study_id>PAC319</org_study_id>
    <nct_id>NCT04404361</nct_id>
  </id_info>
  <brief_title>PRE-VENT Study in Hospitalized Patients With Severe COVID-19 With or Without Cancer</brief_title>
  <official_title>A Phase 2 Randomized, Double-blind, Placebo-controlled, Multicenter Study of Pacritinib Plus Standard of Care Versus Placebo and Standard of Care in Hospitalized Patients With Severe COVID-19 With or Without Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>CTI BioPharma</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>CTI BioPharma</source>
  <oversight_info>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a Phase 2 randomized, double-blind, placebo-controlled, multicenter study to evaluate&#xD;
      the efficacy and safety of pacritinib in hospitalized patients with severe COVID-19 with or&#xD;
      without cancer.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a Phase 2 randomized, double-blind, placebo-controlled, multicenter study to evaluate&#xD;
      the efficacy and safety of pacritinib in hospitalized patients with severe COVID-19 with or&#xD;
      without cancer. Severe COVID-19 is defined as confirmed disease in patients who are&#xD;
      hospitalized with hypoxia (blood oxygen saturation [SpO2] ≤93% on room air at sea level),&#xD;
      respiratory rate &gt;30, arterial oxygen partial pressure [PaO2]/ fraction of inspired oxygen&#xD;
      [FiO2] &lt;300, or lung infiltrates &gt;50% but do not require IMV.&#xD;
&#xD;
      Patients will be randomized 1:1 to receive pacritinib (400 mg once daily [QD] on Day 1, then&#xD;
      200 mg twice daily [BID] from Day 2 to Day 14) + SOC or placebo + SOC.&#xD;
&#xD;
      Assigned treatment will continue for up to Day 14 or until the patient experiences&#xD;
      intolerable adverse events (AEs), withdraws consent, or initiates another investigational&#xD;
      therapy or until the study is terminated. Assigned therapy may be given for an additional 7&#xD;
      days (for a total of 21 days) with the approval of the Medical Monitor if, in the opinion of&#xD;
      the investigator, the patient's clinical signs and symptoms are improving and the potential&#xD;
      benefit outweighs the potential risk.In the event of hospital discharge, patients will&#xD;
      complete treatment with the assigned therapy as an outpatient.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    decision to close enrollment early&#xD;
  </why_stopped>
  <start_date type="Actual">May 22, 2020</start_date>
  <completion_date type="Actual">September 21, 2021</completion_date>
  <primary_completion_date type="Actual">September 21, 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>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Proportion of patients who progress to IMV and/or ECMO or death during the 28 days following randomization</measure>
    <time_frame>28 days</time_frame>
    <description>The proportion is calculated as the number of patients who progress divided by the total number of patients in the ITT population.</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">200</enrollment>
  <condition>COVID19</condition>
  <condition>COVID-19</condition>
  <condition>COVID</condition>
  <arm_group>
    <arm_group_label>Pacritinib and SOC</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Pacritinib 400 mg once daily [QD] on Day 1, then 200 mg twice daily [BID] from Day 2 to Day 14) + SOC</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo and SOC</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>4 capsules once daily [QD] on Day 1, then 2 capsules twice daily [BID] from Day 2 to Day 14) + SOC</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Pacritinib</intervention_name>
    <description>100 mg capsules</description>
    <arm_group_label>Pacritinib and SOC</arm_group_label>
    <other_name>SB1518</other_name>
    <other_name>Oral Jak Inhibitor</other_name>
    <other_name>Oral Irak inhibitor</other_name>
    <other_name>Oral Csf1 inhibitor</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Placebo capsules matching pacritinib 100 mg capsules</description>
    <arm_group_label>Placebo and SOC</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Hospitalized or will be hospitalized prior to randomization for the treatment of&#xD;
             severe COVID-19 with SARS-CoV-2 infection confirmed by either a) a positive reverse&#xD;
             transcriptase polymerase chain reaction (RT PCR) or b) an antigen-based test from any&#xD;
             respiratory, nasopharyngeal, saliva, blood, or stool specimen at Screening or&#xD;
             documented within 1 week prior to the start of Screening (Severe COVID-19 is defined&#xD;
             as confirmed disease in patients who are hospitalized with hypoxia [SpO2 ≤93% on room&#xD;
             air], respiratory rate &gt;30, PaO2/FiO2 &lt;300, but do not require IMV).&#xD;
&#xD;
          2. Age ≥ 18 years&#xD;
&#xD;
          3. Platelet count ≥ 50,000/µL&#xD;
&#xD;
          4. If fertile, willing to use effective birth control methods during the study&#xD;
&#xD;
          5. Provision of informed consent within 96 hours after hospitalization&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. In the opinion of the investigator, progression to death is imminent and inevitable&#xD;
             within the next 24 hours, irrespective of the provision of treatments&#xD;
&#xD;
          2. Currently intubated or intubated between screening and randomization&#xD;
&#xD;
          3. Suspected active uncontrolled bacterial, fungal, viral, or other infection (besides&#xD;
             COVID 19)&#xD;
&#xD;
          4. Prior allogenic hematopoietic stem cell transplantation&#xD;
&#xD;
          5. Active lung cancer or history of lung cancer within the past 12 months&#xD;
&#xD;
          6. Any active grade 2 or higher hemorrhage&#xD;
&#xD;
          7. Any active gastrointestinal or metabolic condition that could interfere with&#xD;
             absorption of oral medication&#xD;
&#xD;
          8. Uncontrolled intercurrent illness that, in the judgment of the treating physician,&#xD;
             would limit compliance with study requirements&#xD;
&#xD;
          9. Known seropositivity for human immunodeficiency virus with cluster of differentiation&#xD;
             4 (CD4) count &lt; 200/mm3 within 3 months prior to randomization&#xD;
&#xD;
         10. Pregnant or breastfeeding, or positive pregnancy test in a pre-dose examination&#xD;
&#xD;
         11. Concurrent enrollment in another interventional trial (investigational COVID-19&#xD;
             antiviral studies are permitted)&#xD;
&#xD;
         12. Serum creatinine &gt; 2.5 mg/dL&#xD;
&#xD;
         13. Total bilirubin &gt; 4× the upper limit of normal&#xD;
&#xD;
         14. QT corrected by the Fridericia method (QTcF) prolongation &gt; 480 msec&#xD;
&#xD;
         15. Known history of New York Heart Association Class II, III, or IV congestive heart&#xD;
             failure prior to hospital admission&#xD;
&#xD;
         16. Known allergic reaction to any Janus kinase 2 (JAK2) inhibitor&#xD;
&#xD;
         17. Exposure to any JAK2 inhibitor within 28 days&#xD;
&#xD;
         18. Currently receiving a strong CYP3A4 inhibitor or strong P450 inducer (Appendix 1 and&#xD;
             Appendix 2, respectively) and unable to stop the medication prior to the first dose of&#xD;
             study drug and throughout the duration of study drug administration&#xD;
&#xD;
         19. Treatment with cytoreductive chemotherapy administered within 14 days prior to&#xD;
             randomization&#xD;
&#xD;
         20. Administration of an IL 1 or IL 6 blocking immunomodulatory agent (such as&#xD;
             tocilizumab, canakinumab, sarilumab, anakinra) within 48 hours prior to randomization&#xD;
&#xD;
         21. Currently receiving therapeutic anticoagulation or anti platelet medication and unable&#xD;
             to stop the medication prior to randomization. Prophylactic anticoagulation therapy or&#xD;
             aspirin (≤ 100mg) are permitted.&#xD;
&#xD;
         22. Unable to ingest capsules or tablets at randomization&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>St. Jude Hospital Yorba Linda dba St. Joseph Heritage Healthcare</name>
      <address>
        <city>Orange</city>
        <state>California</state>
        <zip>92868</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ascension St. Vincent's Riverside Hospital</name>
      <address>
        <city>Jacksonville</city>
        <state>Florida</state>
        <zip>32204</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Grady Memorial Hospital</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30303</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St. Vincent Medical Group, Inc</name>
      <address>
        <city>Indianapolis</city>
        <state>Indiana</state>
        <zip>46220</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St. Agnes Healthcare</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21229</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Brigham and Women's Hospital</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02115</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Michigan</name>
      <address>
        <city>Ann Arbor</city>
        <state>Michigan</state>
        <zip>48109</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ascension St. John Hospital</name>
      <address>
        <city>Detroit</city>
        <state>Michigan</state>
        <zip>48236</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ascension Providence Hospital - Novi Campus</name>
      <address>
        <city>Novi</city>
        <state>Michigan</state>
        <zip>48374</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Providence Cancer Institute</name>
      <address>
        <city>Southfield</city>
        <state>Michigan</state>
        <zip>48075</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Atlantic Melanoma Center</name>
      <address>
        <city>Morristown</city>
        <state>New Jersey</state>
        <zip>07960</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Overlook Medical Center</name>
      <address>
        <city>Morristown</city>
        <state>New Jersey</state>
        <zip>07960</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Chilton Medical Center</name>
      <address>
        <city>Pompton Plains</city>
        <state>New Jersey</state>
        <zip>07444</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mount Sinai Medical Center</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10029</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Carl and Edyth Lindner Center for Research and Education at The Christ Hospital</name>
      <address>
        <city>Cincinnati</city>
        <state>Ohio</state>
        <zip>45219</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St. John Medical Center</name>
      <address>
        <city>Tulsa</city>
        <state>Oklahoma</state>
        <zip>74104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Albert Einstein Medical Center</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19141</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rhode Island Hospital</name>
      <address>
        <city>Providence</city>
        <state>Rhode Island</state>
        <zip>02903</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Miriam Hospital</name>
      <address>
        <city>Providence</city>
        <state>Rhode Island</state>
        <zip>02903</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ascension St. Francis Hospital</name>
      <address>
        <city>Milwaukee</city>
        <state>Wisconsin</state>
        <zip>53215</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ascension All Saints</name>
      <address>
        <city>Racine</city>
        <state>Wisconsin</state>
        <zip>53405</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>June 2023</verification_date>
  <study_first_submitted>May 22, 2020</study_first_submitted>
  <study_first_submitted_qc>May 22, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">May 27, 2020</study_first_posted>
  <last_update_submitted>June 30, 2023</last_update_submitted>
  <last_update_submitted_qc>June 30, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">July 5, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>COVID19</keyword>
  <keyword>COVID-19</keyword>
  <keyword>COVID</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>COVID-19</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Janus Kinase Inhibitors</mesh_term>
  </intervention_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/NCT04404361
org study id: PAC319
nct id: NCT04404361
lead sponsor: 
is fda regulated drug: Yes
is fda regulated device: No
This is a Phase 2 randomized, double-blind, placebo-controlled, multicenter study to evaluate
      the efficacy and safety of pacritinib in hospitalized patients with severe COVID-19 with or
      without cancer.
This is a Phase 2 randomized, double-blind, placebo-controlled, multicenter study to evaluate
      the efficacy and safety of pacritinib in hospitalized patients with severe COVID-19 with or
      without cancer. Severe COVID-19 is defined as confirmed disease in patients who are
      hospitalized with hypoxia (blood oxygen saturation [SpO2] ≤93% on room air at sea level),
      respiratory rate >30, arterial oxygen partial pressure [PaO2]/ fraction of inspired oxygen
      [FiO2] <300, or lung infiltrates >50% but do not require IMV.

      Patients will be randomized 1:1 to receive pacritinib (400 mg once daily [QD] on Day 1, then
      200 mg twice daily [BID] from Day 2 to Day 14) + SOC or placebo + SOC.

      Assigned treatment will continue for up to Day 14 or until the patient experiences
      intolerable adverse events (AEs), withdraws consent, or initiates another investigational
      therapy or until the study is terminated. Assigned therapy may be given for an additional 7
      days (for a total of 21 days) with the approval of the Medical Monitor if, in the opinion of
      the investigator, the patient's clinical signs and symptoms are improving and the potential
      benefit outweighs the potential risk.In the event of hospital discharge, patients will
      complete treatment with the assigned therapy as an outpatient.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Proportion of patients who progress to IMV and/or ECMO or death during the 28 days following randomization
time frame: 28 days
description: The proportion is calculated as the number of patients who progress divided by the total number of patients in the ITT population.
arm group label: Pacritinib and SOC
arm group type: Experimental
description: Pacritinib 400 mg once daily [QD] on Day 1, then 200 mg twice daily [BID] from Day 2 to Day 14) + SOC
arm group label: Placebo and SOC
arm group type: Placebo Comparator
description: 4 capsules once daily [QD] on Day 1, then 2 capsules twice daily [BID] from Day 2 to Day 14) + SOC
intervention type: Drug
intervention name: Pacritinib
description: 100 mg capsules
arm group label: Pacritinib and SOC
other name: SB1518
other name: Oral Jak Inhibitor
other name: Oral Irak inhibitor
other name: Oral Csf1 inhibitor
intervention type: Drug
intervention name: Placebo
description: Placebo capsules matching pacritinib 100 mg capsules
arm group label: Placebo and SOC
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
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country: United States
responsible party type: Sponsor
mesh term: COVID-19
mesh term: Janus Kinase Inhibitors