<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/NCT04487886</url>
  </required_header>
  <id_info>
    <org_study_id>STUDY00000701</org_study_id>
    <nct_id>NCT04487886</nct_id>
  </id_info>
  <brief_title>Duvelisib Ameliorates Manifestations of Pneumonia in Established Novel Coronavirus Infection (COVID-19)</brief_title>
  <acronym>DAMPEN-CI</acronym>
  <official_title>Duvelisib Ameliorates Manifestations of Pneumonia in Established Novel Coronavirus Infection</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Emory University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Verastem, Inc.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Emory University</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>
      In this study, patients with severe coronavirus disease 2019 (COVID-19) infection will be&#xD;
      randomized to receive duvelisib or a placebo. Participants will be enrolled at Emory&#xD;
      University Hospital and will be identified and recruited by their treating physician and&#xD;
      research team.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This randomized placebo-controlled phase 2 study will evaluate whether a two-week exposure to&#xD;
      duvelisib, a gamma/delta phosphoinositide 3-kinase (PI3K) inhibitor, reduces inflammation in&#xD;
      the lungs in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)&#xD;
      infection and COVID-19 who do not require mechanical ventilation at study initiation. The&#xD;
      primary objective of the study is to determine the efficacy of duvelisib treatment in&#xD;
      preventing death or the need for mechanical ventilation among patients with World Health&#xD;
      Organization (WHO)-defined severe COVID-19. Key secondary endpoints will be reductions in&#xD;
      oxygen requirements of patients and improvements in their performance status, safety and&#xD;
      tolerability of duvelisib in the setting of COVID-19, biomarkers of inflammation, and&#xD;
      generation of immunoglobulin G (IgG) and immunoglobulin M (IgM) antibody responses to&#xD;
      SARS-Cov-2 spike protein. The study will determine if a two-week exposure to duvelisib&#xD;
      beginning soon after presentation with severe COVID-19 warrants further evaluation in a&#xD;
      larger clinical study.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 18, 2020</start_date>
  <completion_date type="Actual">June 10, 2021</completion_date>
  <primary_completion_date type="Actual">June 10, 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, Care Provider)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Participants Requiring Mechanical Ventilation or Dying</measure>
    <time_frame>Up to Day 29</time_frame>
    <description>This is a composite endpoint of the number of participants who require mechanical ventilation or who die within four weeks of randomization.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Days to Recovery</measure>
    <time_frame>Up to Day 29</time_frame>
    <description>Time to recovery is measured in days, from the day of randomization to the day of recovery, with recovery defined as a score of equal to or greater than 5 from the eight categories from the National Institute of Allergy and Infectious Diseases (NIAID) ordinal scale. The scale is as follows: 1 = Death, 2 = Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO), 3 = Hospitalized, on non-invasive ventilation or high flow oxygen devices, 4 = Hospitalized, requiring supplemental oxygen, 5 = Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise), 6 = Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care;=, 7 = Not hospitalized, limitation on activities and/or requiring home oxygen, and 8 = Not hospitalized, no limitations on activities.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of Hospitalization</measure>
    <time_frame>Up to Day 29</time_frame>
    <description>The number of days spent hospitalized is presented for both study arms.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Days on Study Drug</measure>
    <time_frame>Up to Day 29</time_frame>
    <description>The number of days that participants took any doses of the study drug that they were randomized to receive is presented for both study arms.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Total Doses of Study Drug</measure>
    <time_frame>Up to Day 29</time_frame>
    <description>The study medication was taken twice per day for 14 days. The number of doses of study medication that was taken is presented for both study arms.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants Dying</measure>
    <time_frame>Up to Day 29</time_frame>
    <description>The incidence of death within 29 days of randomization is compared between study arms.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants Transferred to ICU</measure>
    <time_frame>Up to Day 29</time_frame>
    <description>The number of participants who were transferred to the intensive care unit (ICU) within 29 days of randomization.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Eastern Cooperative Oncology Group (ECOG) Performance Status Score</measure>
    <time_frame>Between Day 14 and 28, Between Day 29 and 60</time_frame>
    <description>The ECOG Performance Status instrument includes a single item assessing overall physical status. Health status is rated on a scale of 0 to 5 where 0 = fully active, 1 = restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, 2 = ambulatory and capable of all selfcare but unable to carry out any work activities, 3 = capable of only limited selfcare, completely disabled, and 5 = dead. Median ECOG performance is compared between study arms.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Grade III-V Adverse Events</measure>
    <time_frame>Up to Day 29</time_frame>
    <description>The incidence of grade III-V adverse events or serious adverse events (SAEs), as defined by Common Terminology Criteria for Adverse Events (CTCAE) version 5, is compared between study arms. Grade 3 lab values that required no special treatment are excluded from this outcome measure.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Secondary Bacterial or Viral Infections</measure>
    <time_frame>Up to Day 29</time_frame>
    <description>The incidence of documented secondary bacterial or viral infections among participants is compared between study arms.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>T Helper 1 (Th1) T Cell Frequency</measure>
    <time_frame>Week 1, Week 2</time_frame>
    <description>The mean frequency of Th1 T cells in peripheral blood mononuclear cells (PBMCs) is compared between study arms.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Th17 T Cell Frequency</measure>
    <time_frame>Week 1, Week 2</time_frame>
    <description>The mean frequency of Th17 T cells in PBMCs is compared between study arms.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Interleukin-2 (IL-2) Levels</measure>
    <time_frame>Week 1, Week 2</time_frame>
    <description>Mean levels of the inflammatory serum biomarker IL-2 is compared between study arms.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Interleukin-2 Receptor (IL-2R) Levels</measure>
    <time_frame>Week 1, Week 2</time_frame>
    <description>Mean levels of the inflammatory serum biomarker IL-2R is compared between study arms.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Interleukin-6 (IL-6) Levels</measure>
    <time_frame>Week 1, Week 2</time_frame>
    <description>Mean levels of the inflammatory serum biomarker IL-6 is compared between study arms.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Interleukin-7 (IL-7) Levels</measure>
    <time_frame>Week 1, Week 2</time_frame>
    <description>Mean levels of the inflammatory serum biomarker IL-7 is compared between study arms.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Interleukin-8 (IL-8) Levels</measure>
    <time_frame>Week 1, Week 2</time_frame>
    <description>Mean levels of the inflammatory serum biomarker IL-8 is compared between study arms.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Interleukin-10 (IL-10) Levels</measure>
    <time_frame>Week 1, Week 2</time_frame>
    <description>Mean levels of the inflammatory serum biomarker IL-10 is compared between study arms.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Interferon Gamma-induced Protein 10 (IP-10) Levels</measure>
    <time_frame>Week 1, Week 2</time_frame>
    <description>Mean levels of the inflammatory serum biomarker IP-10is compared between study arms.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Macrophage Inflammatory Protein 1alpha (MIP-1a) Levels</measure>
    <time_frame>Week 1, Week 2</time_frame>
    <description>Mean levels of the inflammatory serum biomarker MIP-1a is compared between study arms.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Monocyte Chemoattractant Protein-1 (MCP-1) Levels</measure>
    <time_frame>Week 1, Week 2</time_frame>
    <description>Mean levels of the inflammatory serum biomarker MCP-1 are compared between study arms.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Granulocyte Colony-stimulating Factor (G-CSF) Levels</measure>
    <time_frame>Week 1, Week 2</time_frame>
    <description>Mean levels of the inflammatory serum biomarker G-CSF are compared between study arms.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tumor Necrosis Factor (TNF)-Alpha Levels</measure>
    <time_frame>Week 1, Week 2</time_frame>
    <description>Mean levels of the inflammatory serum biomarker TNF-alpha are compared between study arms.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Gene Expression Profile of Regulatory T Cells (Tregs)</measure>
    <time_frame>Week 1, Week 2</time_frame>
    <description>Single-cell ribonucleic acid (RNA) sequencing is a powerful gene expression profiling tool to acquire transcriptional level information of each gene. Mean levels of the Tregs will be compared between study arms.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Gene Expression Profile of Cluster of Differentiation 8 (CD8)+Interferon Gamma (IFNg)+ Granulocyte-macrophage Colony-stimulating Factor (GM-CSF)+</measure>
    <time_frame>Week 1, Week 2</time_frame>
    <description>Single-cell RNA sequencing is a powerful gene expression profiling tool to acquire transcriptional level information of each gene. Mean levels of CD8+IFNg+GM-CSF+ will be compared between study arms.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Gene Expression Profile of CD8+ T Cell Immunoglobulin and Mucin Domain-containing Protein 3 (Tim3)+ Programmed Cell Death Protein 1 (PD-1)+</measure>
    <time_frame>Week 1, Week 2</time_frame>
    <description>Single-cell RNA sequencing is a powerful gene expression profiling tool to acquire transcriptional level information of each gene. Mean levels of CD8+Tim3+PD-1+ will be compared between study arms.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Gene Expression Profile of Cluster of Differentiation 14 (CD14)+ Cluster of Differentiation (CD16)+ Monocytes</measure>
    <time_frame>Week 1, Week 2</time_frame>
    <description>Single-cell RNA sequencing is a powerful gene expression profiling tool to acquire transcriptional level information of each gene. Mean levels of CD14+CD16+ monocytes will be compared between study arms.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Immunoglobin G (IgG) Antibodies</measure>
    <time_frame>Week 4</time_frame>
    <description>Median titers of IgG antibodies to SARS-CoV-2 at 4 weeks will be assessed for both study arms.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants Surviving</measure>
    <time_frame>Up to Day 60</time_frame>
    <description>Overall survival is defined as days from randomization to death and censored at last follow up.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Vasoactive Intestinal Peptide (VIP)</measure>
    <time_frame>Week 1, Week 2</time_frame>
    <description>VIP is a peptide hormone with immunosuppressive properties. Mean levels VIP will be compared between study arms.</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">47</enrollment>
  <condition>COVID-19</condition>
  <arm_group>
    <arm_group_label>Duvelisib</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants with severe COVID-19 who do not require mechanical ventilation randomized to receive duvelisib for 14 days.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Participants with severe COVID-19 who do not require mechanical ventilation randomized to receive a placebo to match duvelisib for 14 days.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Duvelisib</intervention_name>
    <description>Duvelisib will be taken orally at an initial dose of 25 milligrams (mg) twice per day for 14 days. The dose will be de-escalated to 15 mg, twice per day, under certain clinical circumstances.</description>
    <arm_group_label>Duvelisib</arm_group_label>
    <other_name>Copiktra</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>A placebo to match duvelisib will be taken orally twice per day for 14 days.</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Hospitalized in participating facility.&#xD;
&#xD;
          -  Documentation of pneumonia with radiographic evidence of infiltrates by imaging (e.g.,&#xD;
             chest x-ray or CT scan).&#xD;
&#xD;
          -  Laboratory-confirmed SARS-CoV-2 infection as determined by polymerase chain reaction&#xD;
             (PCR) or other authorized or approved assay in any specimen collected within 72 hours&#xD;
             prior to enrollment. Note - An exception must be requested to the Sponsor if ≥72 hours&#xD;
             since positive test.&#xD;
&#xD;
          -  Symptoms suggestive of severe systemic illness with COVID-19, such as respiratory rate&#xD;
             &gt; 30 breaths per minute, heart rate &gt;125 beats per minute, oxygen saturation (O2 sat)&#xD;
             in the blood of &lt;93% on room air at sea level or the ratio of arterial oxygen partial&#xD;
             pressure to fractional inspired oxygen (PaO2/FiO2)&lt; 300&#xD;
&#xD;
          -  18 years of age or older&#xD;
&#xD;
          -  Patients with hematological parameters at screening consistent with &lt; grade 2 NCI&#xD;
             CTCAE v5.0 toxicity: hemoglobin &gt;8 g/dL, platelet count &gt;50,000 K/mcl, an absolute&#xD;
             neutrophil count (ANC) &gt;1,000/mm3, and an absolute lymphocyte count (ALC) &gt;500/mm3.&#xD;
&#xD;
          -  Patients with laboratory measurements of liver function at screening consistent with &lt;&#xD;
             grade 2 NCI CTCAE v5.0 toxicity: alanine aminotransferase (ALT) &lt; 5 times the upper&#xD;
             limit of normal (ULN); aspartate aminotransferase (AST) &lt; 5 times ULN; and bilirubin &lt;&#xD;
             3 times ULN.&#xD;
&#xD;
          -  The effects of duvelisib on the developing human fetus are unknown. For this reason,&#xD;
             women of child-bearing potential (WOCBP) must have a negative serum or urine&#xD;
             pr5egnancy test prior to starting therapy. WOCBP and men must agree to use adequate&#xD;
             contraception (hormonal or barrier method of birth control; abstinence) from&#xD;
             enrollment into this study until at least 60 days after the first dose of duvelisib. A&#xD;
             woman of childbearing potential (WOCBP) is a sexually mature woman who: 1) has not&#xD;
             undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally&#xD;
             postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in&#xD;
             the preceding 24 consecutive months. Should a woman become pregnant or suspect she is&#xD;
             pregnant while she or her partner is participating in this study, she should inform&#xD;
             her treating physician immediately. Men treated or enrolled on this protocol must also&#xD;
             agree to use adequate contraception prior to the study, for the duration of study&#xD;
             participation, and 2 months after completion of duvelisib administration. WOCBP must&#xD;
             have a negative pregnancy test within 24 hours of the first dose of duvelisib.&#xD;
&#xD;
          -  The patient must be willing to comply with fertility requirements as below:&#xD;
&#xD;
               -  Total abstinence (when this is in line with the usual practice and lifestyle of&#xD;
                  the patient) will be accepted. Periodic abstinence (i.e., calendar, ovulation,&#xD;
                  post-ovulation methods) and withdrawals are not acceptable forms&#xD;
&#xD;
               -  If a female participant is of reproductive potential, the participant (and her&#xD;
                  partner) must agree to use of one of the following combinations of birth control&#xD;
                  during the study and for 2 months after the last dose of study drug (or tubal&#xD;
                  ligation as a single method):&#xD;
&#xD;
                    -  Use of a double-barrier method of contraception: condoms (male or female)&#xD;
                       and a diaphragm or cervical cap with spermicide;&#xD;
&#xD;
                    -  Use of an IUD and a barrier method: condoms (male or female, with or without&#xD;
                       spermicide) or a diaphragm or cervical cap with spermicide;&#xD;
&#xD;
                    -  Tubal ligation.&#xD;
&#xD;
               -  Women who are post-menopausal, defined as age greater than 45 and no menses for&#xD;
                  at least 24 consecutive months, or who have had a hysterectomy, are considered&#xD;
                  not of reproductive potential.&#xD;
&#xD;
               -  Males must agree to using contraception during the study and for 2 months after&#xD;
                  the last dose of study drug or have undergone a male sterilization procedure (at&#xD;
                  least 6 months prior to screening.&#xD;
&#xD;
               -  Use of oral (estrogen and progesterone), injected or implanted hormonal methods&#xD;
                  of contraception, or placement of an intrauterine device (IUD) or intrauterine&#xD;
                  system (IUS) or other forms of contraception that comparable efficacy (failure&#xD;
                  rate &lt;1%). In case of oral contraception, the woman should be stable on the same&#xD;
                  pill for a minimum of 3 months prior to enrollment on the study.&#xD;
&#xD;
          -  Patients must agree not to donate blood, sperm/ova or any other organs while taking&#xD;
             protocol therapy and for at least 2 weeks after stopping treatment.&#xD;
&#xD;
          -  Willingness and ability of the patient to comply with scheduled visits, drug&#xD;
             administration plan, protocol specified laboratory tests, other study procedures and&#xD;
             study restrictions&#xD;
&#xD;
          -  Evidence of personally signed informed consent indicating that the subject is aware of&#xD;
             the life-threatening nature of the disease and has been informed on the procedures to&#xD;
             be followed, the experimental nature of the therapy, alternative, potential risks and&#xD;
             discomforts, potential benefits and other pertinent aspects of study participation.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients requiring mechanical ventilation (intubation or Bi-PAP) at the time&#xD;
             randomization.&#xD;
&#xD;
          -  Patients receiving any investigational drugs other than drugs or therapies to treat&#xD;
             COVID-19, with the exception of investigational immune-modulatory drugs as per section&#xD;
             5.4.&#xD;
&#xD;
          -  Pregnant women are excluded from this study because duvelisib is agent with the&#xD;
             potential for teratogenic or abortifacient effects. Because there is an unknown but&#xD;
             potential risk for adverse events in nursing infants secondary to treatment of the&#xD;
             mother with duvelisib, breastfeeding should be discontinued before starting study drug&#xD;
             and breastfeeding should not be resumed until at least 1 month after last dose of&#xD;
             study drug.&#xD;
&#xD;
          -  Clinical suspicion that the etiology of acute illness (acute decompensation) is&#xD;
             primarily due to a condition other than COVID-19&#xD;
&#xD;
          -  Known contraindication to duvelisib&#xD;
&#xD;
          -  Patients with hepatic cirrhosis as defined by symptomatic liver dysfunction; liver&#xD;
             fibrosis by biopsy; ALT &gt; 5 times ULN, AST&gt; 5 times ULN, or bilirubin &gt; 3 times ULN.&#xD;
&#xD;
          -  Patients with autoimmune diseases or patients on chronic immunosuppressive medications&#xD;
             at the time of hospital admission or screening.&#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>Edmund Waller, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Emory University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Emory Saint Joseph's Hospital</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30308</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Emory University Hospital Midtown</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30308</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Emory University Hospital</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30322</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>March 2023</verification_date>
  <study_first_submitted>July 23, 2020</study_first_submitted>
  <study_first_submitted_qc>July 23, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 27, 2020</study_first_posted>
  <results_first_submitted>December 22, 2022</results_first_submitted>
  <results_first_submitted_qc>March 14, 2023</results_first_submitted_qc>
  <results_first_posted type="Actual">April 7, 2023</results_first_posted>
  <disposition_first_submitted>June 1, 2022</disposition_first_submitted>
  <disposition_first_submitted_qc>March 14, 2023</disposition_first_submitted_qc>
  <disposition_first_posted type="Actual">April 7, 2023</disposition_first_posted>
  <last_update_submitted>March 14, 2023</last_update_submitted>
  <last_update_submitted_qc>March 14, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">April 7, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Emory University</investigator_affiliation>
    <investigator_full_name>Edmund Waller</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <keyword>SARS-CoV-2</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>COVID-19</mesh_term>
    <mesh_term>Pneumonia</mesh_term>
    <mesh_term>Coronavirus Infections</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>The researchers plan to share individual participant data including participant status ordinal score at baseline and end of treatment, study drug allocation, duration of treatment, and survival status at Day 60.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_time_frame>Data will be made available for sharing at the conclusion of the study and will be available for one year.</ipd_time_frame>
    <ipd_access_criteria>Data will be available for sharing with academic or pharmaceutical investigators for analyses including comparison of DAMPEN-CI results with those from other drug trials in similar patient cohorts. Researchers wishing to use data should email the investigators of DAMPEN-Cl. A summary of the research plan will be required prior to release of the DAMPEN-CI data.</ipd_access_criteria>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</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>June 30, 2021</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/86/NCT04487886/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Participants were recruited at Emory University Hospital in Atlanta, Georgia, USA. Participant enrollment began November 18, 2020 and all follow-up assessments were completed by June 10, 2021.</recruitment_details>
      <group_list>
        <group group_id="P1">
          <title>Duvelisib</title>
          <description>Participants with severe COVID-19 who do not require mechanical ventilation randomized to receive duvelisib for 14 days.&#xD;
Duvelisib will be taken orally at an initial dose of 25 milligrams (mg) twice per day for 14 days. The dose will be de-escalated to 15 mg, twice per day, under certain clinical circumstances.</description>
        </group>
        <group group_id="P2">
          <title>Placebo</title>
          <description>Participants with severe COVID-19 who do not require mechanical ventilation randomized to receive a placebo to match duvelisib for 14 days.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="25"/>
                <participants group_id="P2" count="22"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="25"/>
                <participants group_id="P2" count="22"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Duvelisib</title>
          <description>Participants with severe COVID-19 who do not require mechanical ventilation randomized to receive duvelisib for 14 days.</description>
        </group>
        <group group_id="B2">
          <title>Placebo</title>
          <description>Participants with severe COVID-19 who do not require mechanical ventilation randomized to receive a placebo to match duvelisib for 14 days.</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="25"/>
            <count group_id="B2" value="22"/>
            <count group_id="B3" value="47"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</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>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="18"/>
                    <measurement group_id="B2" value="15"/>
                    <measurement group_id="B3" value="33"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="14"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <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="56.1" spread="12.2"/>
                    <measurement group_id="B2" value="58.9" spread="17.1"/>
                    <measurement group_id="B3" value="57.4" spread="14.6"/>
                  </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="11"/>
                    <measurement group_id="B2" value="10"/>
                    <measurement group_id="B3" value="21"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="14"/>
                    <measurement group_id="B2" value="12"/>
                    <measurement group_id="B3" value="26"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</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>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</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>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="17"/>
                    <measurement group_id="B2" value="12"/>
                    <measurement group_id="B3" value="29"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="8"/>
                    <measurement group_id="B3" value="15"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</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>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="25"/>
                    <measurement group_id="B2" value="22"/>
                    <measurement group_id="B3" value="47"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants Requiring Mechanical Ventilation or Dying</title>
        <description>This is a composite endpoint of the number of participants who require mechanical ventilation or who die within four weeks of randomization.</description>
        <time_frame>Up to Day 29</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Duvelisib</title>
            <description>Participants with severe COVID-19 who do not require mechanical ventilation randomized to receive duvelisib for 14 days.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants with severe COVID-19 who do not require mechanical ventilation randomized to receive a placebo to match duvelisib for 14 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants Requiring Mechanical Ventilation or Dying</title>
          <description>This is a composite endpoint of the number of participants who require mechanical ventilation or who die within four weeks of randomization.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="25"/>
                <count group_id="O2" value="22"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Days to Recovery</title>
        <description>Time to recovery is measured in days, from the day of randomization to the day of recovery, with recovery defined as a score of equal to or greater than 5 from the eight categories from the National Institute of Allergy and Infectious Diseases (NIAID) ordinal scale. The scale is as follows: 1 = Death, 2 = Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO), 3 = Hospitalized, on non-invasive ventilation or high flow oxygen devices, 4 = Hospitalized, requiring supplemental oxygen, 5 = Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise), 6 = Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care;=, 7 = Not hospitalized, limitation on activities and/or requiring home oxygen, and 8 = Not hospitalized, no limitations on activities.</description>
        <time_frame>Up to Day 29</time_frame>
        <population>This analysis includes participants who recovered; one participant in the placebo study arm passed away and is not included in this analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Duvelisib</title>
            <description>Participants with severe COVID-19 who do not require mechanical ventilation randomized to receive duvelisib for 14 days.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants with severe COVID-19 who do not require mechanical ventilation randomized to receive a placebo to match duvelisib for 14 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Days to Recovery</title>
          <description>Time to recovery is measured in days, from the day of randomization to the day of recovery, with recovery defined as a score of equal to or greater than 5 from the eight categories from the National Institute of Allergy and Infectious Diseases (NIAID) ordinal scale. The scale is as follows: 1 = Death, 2 = Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO), 3 = Hospitalized, on non-invasive ventilation or high flow oxygen devices, 4 = Hospitalized, requiring supplemental oxygen, 5 = Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise), 6 = Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care;=, 7 = Not hospitalized, limitation on activities and/or requiring home oxygen, and 8 = Not hospitalized, no limitations on activities.</description>
          <population>This analysis includes participants who recovered; one participant in the placebo study arm passed away and is not included in this analysis.</population>
          <units>days</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="25"/>
                <count group_id="O2" value="21"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.00" spread="6.19"/>
                    <measurement group_id="O2" value="5.29" spread="4.19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Duration of Hospitalization</title>
        <description>The number of days spent hospitalized is presented for both study arms.</description>
        <time_frame>Up to Day 29</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Duvelisib</title>
            <description>Participants with severe COVID-19 who do not require mechanical ventilation randomized to receive duvelisib for 14 days.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants with severe COVID-19 who do not require mechanical ventilation randomized to receive a placebo to match duvelisib for 14 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Duration of Hospitalization</title>
          <description>The number of days spent hospitalized is presented for both study arms.</description>
          <units>days</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="25"/>
                <count group_id="O2" value="22"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.72" spread="7.48"/>
                    <measurement group_id="O2" value="6.95" spread="6.41"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Days on Study Drug</title>
        <description>The number of days that participants took any doses of the study drug that they were randomized to receive is presented for both study arms.</description>
        <time_frame>Up to Day 29</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Duvelisib</title>
            <description>Participants with severe COVID-19 who do not require mechanical ventilation randomized to receive duvelisib for 14 days.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants with severe COVID-19 who do not require mechanical ventilation randomized to receive a placebo to match duvelisib for 14 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Days on Study Drug</title>
          <description>The number of days that participants took any doses of the study drug that they were randomized to receive is presented for both study arms.</description>
          <units>days</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="25"/>
                <count group_id="O2" value="22"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.6" spread="3.55"/>
                    <measurement group_id="O2" value="5.18" spread="2.77"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Total Doses of Study Drug</title>
        <description>The study medication was taken twice per day for 14 days. The number of doses of study medication that was taken is presented for both study arms.</description>
        <time_frame>Up to Day 29</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Duvelisib</title>
            <description>Participants with severe COVID-19 who do not require mechanical ventilation randomized to receive duvelisib for 14 days.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants with severe COVID-19 who do not require mechanical ventilation randomized to receive a placebo to match duvelisib for 14 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Total Doses of Study Drug</title>
          <description>The study medication was taken twice per day for 14 days. The number of doses of study medication that was taken is presented for both study arms.</description>
          <units>drug doses</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="25"/>
                <count group_id="O2" value="22"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.76" spread="6.79"/>
                    <measurement group_id="O2" value="8.91" spread="5.61"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants Dying</title>
        <description>The incidence of death within 29 days of randomization is compared between study arms.</description>
        <time_frame>Up to Day 29</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Duvelisib</title>
            <description>Participants with severe COVID-19 who do not require mechanical ventilation randomized to receive duvelisib for 14 days.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants with severe COVID-19 who do not require mechanical ventilation randomized to receive a placebo to match duvelisib for 14 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants Dying</title>
          <description>The incidence of death within 29 days of randomization is compared between study arms.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="25"/>
                <count group_id="O2" value="22"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants Transferred to ICU</title>
        <description>The number of participants who were transferred to the intensive care unit (ICU) within 29 days of randomization.</description>
        <time_frame>Up to Day 29</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Duvelisib</title>
            <description>Participants with severe COVID-19 who do not require mechanical ventilation randomized to receive duvelisib for 14 days.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants with severe COVID-19 who do not require mechanical ventilation randomized to receive a placebo to match duvelisib for 14 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants Transferred to ICU</title>
          <description>The number of participants who were transferred to the intensive care unit (ICU) within 29 days of randomization.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="25"/>
                <count group_id="O2" value="22"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Eastern Cooperative Oncology Group (ECOG) Performance Status Score</title>
        <description>The ECOG Performance Status instrument includes a single item assessing overall physical status. Health status is rated on a scale of 0 to 5 where 0 = fully active, 1 = restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, 2 = ambulatory and capable of all selfcare but unable to carry out any work activities, 3 = capable of only limited selfcare, completely disabled, and 5 = dead. Median ECOG performance is compared between study arms.</description>
        <time_frame>Between Day 14 and 28, Between Day 29 and 60</time_frame>
        <population>This analysis includes participants who were able to be contacted for this assessment, or those with relevant information in the medical chart.</population>
        <group_list>
          <group group_id="O1">
            <title>Duvelisib</title>
            <description>Participants with severe COVID-19 who do not require mechanical ventilation randomized to receive duvelisib for 14 days.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants with severe COVID-19 who do not require mechanical ventilation randomized to receive a placebo to match duvelisib for 14 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Eastern Cooperative Oncology Group (ECOG) Performance Status Score</title>
          <description>The ECOG Performance Status instrument includes a single item assessing overall physical status. Health status is rated on a scale of 0 to 5 where 0 = fully active, 1 = restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, 2 = ambulatory and capable of all selfcare but unable to carry out any work activities, 3 = capable of only limited selfcare, completely disabled, and 5 = dead. Median ECOG performance is compared between study arms.</description>
          <population>This analysis includes participants who were able to be contacted for this assessment, or those with relevant information in the medical chart.</population>
          <units>score on a scale</units>
          <param>Median</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="22"/>
                <count group_id="O2" value="22"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Single assessment between Day 14 and 28</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="22"/>
                    <count group_id="O2" value="18"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2" spread="1.01"/>
                    <measurement group_id="O2" value="1.5" spread="1.04"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Single assessment between Day 29 and 60</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="19"/>
                    <count group_id="O2" value="22"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1" spread="0.69"/>
                    <measurement group_id="O2" value="1" spread="1.04"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Grade III-V Adverse Events</title>
        <description>The incidence of grade III-V adverse events or serious adverse events (SAEs), as defined by Common Terminology Criteria for Adverse Events (CTCAE) version 5, is compared between study arms. Grade 3 lab values that required no special treatment are excluded from this outcome measure.</description>
        <time_frame>Up to Day 29</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Duvelisib</title>
            <description>Participants with severe COVID-19 who do not require mechanical ventilation randomized to receive duvelisib for 14 days.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants with severe COVID-19 who do not require mechanical ventilation randomized to receive a placebo to match duvelisib for 14 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Grade III-V Adverse Events</title>
          <description>The incidence of grade III-V adverse events or serious adverse events (SAEs), as defined by Common Terminology Criteria for Adverse Events (CTCAE) version 5, is compared between study arms. Grade 3 lab values that required no special treatment are excluded from this outcome measure.</description>
          <units>grade III-V adverse events</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="25"/>
                <count group_id="O2" value="22"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6"/>
                    <measurement group_id="O2" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Secondary Bacterial or Viral Infections</title>
        <description>The incidence of documented secondary bacterial or viral infections among participants is compared between study arms.</description>
        <time_frame>Up to Day 29</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Duvelisib</title>
            <description>Participants with severe COVID-19 who do not require mechanical ventilation randomized to receive duvelisib for 14 days.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants with severe COVID-19 who do not require mechanical ventilation randomized to receive a placebo to match duvelisib for 14 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Secondary Bacterial or Viral Infections</title>
          <description>The incidence of documented secondary bacterial or viral infections among participants is compared between study arms.</description>
          <units>infections</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="25"/>
                <count group_id="O2" value="22"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Count of bacterial infections</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Count of viral infections</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>T Helper 1 (Th1) T Cell Frequency</title>
        <description>The mean frequency of Th1 T cells in peripheral blood mononuclear cells (PBMCs) is compared between study arms.</description>
        <time_frame>Week 1, Week 2</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Duvelisib</title>
            <description>Participants with severe COVID-19 who do not require mechanical ventilation randomized to receive duvelisib for 14 days.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants with severe COVID-19 who do not require mechanical ventilation randomized to receive a placebo to match duvelisib for 14 days.</description>
          </group>
        </group_list>
        <measure>
          <title>T Helper 1 (Th1) T Cell Frequency</title>
          <description>The mean frequency of Th1 T cells in peripheral blood mononuclear cells (PBMCs) is compared between study arms.</description>
          <units>percentage of CD4 T cells</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="25"/>
                <count group_id="O2" value="22"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Week 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="19.52" spread="4.77"/>
                    <measurement group_id="O2" value="20.14" spread="7.52"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="19.98" spread="6.24"/>
                    <measurement group_id="O2" value="18.27" spread="6.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Th17 T Cell Frequency</title>
        <description>The mean frequency of Th17 T cells in PBMCs is compared between study arms.</description>
        <time_frame>Week 1, Week 2</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Duvelisib</title>
            <description>Participants with severe COVID-19 who do not require mechanical ventilation randomized to receive duvelisib for 14 days.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants with severe COVID-19 who do not require mechanical ventilation randomized to receive a placebo to match duvelisib for 14 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Th17 T Cell Frequency</title>
          <description>The mean frequency of Th17 T cells in PBMCs is compared between study arms.</description>
          <units>percentage of CD4 T cells</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="25"/>
                <count group_id="O2" value="22"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Week 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.24" spread="4.65"/>
                    <measurement group_id="O2" value="3.43" spread="3.78"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.16" spread="2.44"/>
                    <measurement group_id="O2" value="4.25" spread="3.21"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Interleukin-2 (IL-2) Levels</title>
        <description>Mean levels of the inflammatory serum biomarker IL-2 is compared between study arms.</description>
        <time_frame>Week 1, Week 2</time_frame>
        <population>This analysis includes participants who had blood samples obtained at both study time points. Two participants in the placebo arm had samples missing for one of the time points.</population>
        <group_list>
          <group group_id="O1">
            <title>Duvelisib</title>
            <description>Participants with severe COVID-19 who do not require mechanical ventilation randomized to receive duvelisib for 14 days.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants with severe COVID-19 who do not require mechanical ventilation randomized to receive a placebo to match duvelisib for 14 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Interleukin-2 (IL-2) Levels</title>
          <description>Mean levels of the inflammatory serum biomarker IL-2 is compared between study arms.</description>
          <population>This analysis includes participants who had blood samples obtained at both study time points. Two participants in the placebo arm had samples missing for one of the time points.</population>
          <units>pg/mL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="25"/>
                <count group_id="O2" value="20"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Week 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.08723" spread="18.065"/>
                    <measurement group_id="O2" value="62.8596" spread="18.171"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="17.3632" spread="40.588"/>
                    <measurement group_id="O2" value="0.3158" spread="32.3258"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Interleukin-2 Receptor (IL-2R) Levels</title>
        <description>Mean levels of the inflammatory serum biomarker IL-2R is compared between study arms.</description>
        <time_frame>Week 1, Week 2</time_frame>
        <population>This analysis includes participants who had blood samples obtained at both study time points. Two participants in the placebo arm had samples missing for one of the time points.</population>
        <group_list>
          <group group_id="O1">
            <title>Duvelisib</title>
            <description>Participants with severe COVID-19 who do not require mechanical ventilation randomized to receive duvelisib for 14 days.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants with severe COVID-19 who do not require mechanical ventilation randomized to receive a placebo to match duvelisib for 14 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Interleukin-2 Receptor (IL-2R) Levels</title>
          <description>Mean levels of the inflammatory serum biomarker IL-2R is compared between study arms.</description>
          <population>This analysis includes participants who had blood samples obtained at both study time points. Two participants in the placebo arm had samples missing for one of the time points.</population>
          <units>pg/mL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="25"/>
                <count group_id="O2" value="20"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Week 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1172.80" spread="529.75"/>
                    <measurement group_id="O2" value="3569.93" spread="540.08"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="912.47" spread="976.08"/>
                    <measurement group_id="O2" value="2005.94" spread="1207.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Interleukin-6 (IL-6) Levels</title>
        <description>Mean levels of the inflammatory serum biomarker IL-6 is compared between study arms.</description>
        <time_frame>Week 1, Week 2</time_frame>
        <population>This analysis includes participants who had blood samples obtained at both study time points. Two participants in the placebo arm had samples missing for one of the time points.</population>
        <group_list>
          <group group_id="O1">
            <title>Duvelisib</title>
            <description>Participants with severe COVID-19 who do not require mechanical ventilation randomized to receive duvelisib for 14 days.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants with severe COVID-19 who do not require mechanical ventilation randomized to receive a placebo to match duvelisib for 14 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Interleukin-6 (IL-6) Levels</title>
          <description>Mean levels of the inflammatory serum biomarker IL-6 is compared between study arms.</description>
          <population>This analysis includes participants who had blood samples obtained at both study time points. Two participants in the placebo arm had samples missing for one of the time points.</population>
          <units>pg/mL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="25"/>
                <count group_id="O2" value="20"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Week 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.9388" spread="41.3498"/>
                    <measurement group_id="O2" value="149.73" spread="42.0497"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="14.2294" spread="75.829"/>
                    <measurement group_id="O2" value="52.2227" spread="94.026"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Interleukin-7 (IL-7) Levels</title>
        <description>Mean levels of the inflammatory serum biomarker IL-7 is compared between study arms.</description>
        <time_frame>Week 1, Week 2</time_frame>
        <population>This analysis includes participants who had blood samples obtained at both study time points. Two participants in the placebo arm had samples missing for one of the time points.</population>
        <group_list>
          <group group_id="O1">
            <title>Duvelisib</title>
            <description>Participants with severe COVID-19 who do not require mechanical ventilation randomized to receive duvelisib for 14 days.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants with severe COVID-19 who do not require mechanical ventilation randomized to receive a placebo to match duvelisib for 14 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Interleukin-7 (IL-7) Levels</title>
          <description>Mean levels of the inflammatory serum biomarker IL-7 is compared between study arms.</description>
          <population>This analysis includes participants who had blood samples obtained at both study time points. Two participants in the placebo arm had samples missing for one of the time points.</population>
          <units>pg/mL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="25"/>
                <count group_id="O2" value="20"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Week 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.6018" spread="54.6831"/>
                    <measurement group_id="O2" value="198.80" spread="55.2375"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.2255" spread="98.8781"/>
                    <measurement group_id="O2" value="48.5118" spread="123.46"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Interleukin-8 (IL-8) Levels</title>
        <description>Mean levels of the inflammatory serum biomarker IL-8 is compared between study arms.</description>
        <time_frame>Week 1, Week 2</time_frame>
        <population>This analysis includes participants who had blood samples obtained at both study time points. Two participants in the placebo arm had samples missing for one of the time points.</population>
        <group_list>
          <group group_id="O1">
            <title>Duvelisib</title>
            <description>Participants with severe COVID-19 who do not require mechanical ventilation randomized to receive duvelisib for 14 days.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants with severe COVID-19 who do not require mechanical ventilation randomized to receive a placebo to match duvelisib for 14 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Interleukin-8 (IL-8) Levels</title>
          <description>Mean levels of the inflammatory serum biomarker IL-8 is compared between study arms.</description>
          <population>This analysis includes participants who had blood samples obtained at both study time points. Two participants in the placebo arm had samples missing for one of the time points.</population>
          <units>pg/mL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="25"/>
                <count group_id="O2" value="20"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Week 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.1109" spread="28.2498"/>
                    <measurement group_id="O2" value="104.03" spread="28.5967"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.4120" spread="51.3241"/>
                    <measurement group_id="O2" value="26.6383" spread="63.927"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Interleukin-10 (IL-10) Levels</title>
        <description>Mean levels of the inflammatory serum biomarker IL-10 is compared between study arms.</description>
        <time_frame>Week 1, Week 2</time_frame>
        <population>This analysis includes participants who had blood samples obtained at both study time points. Two participants in the placebo arm had samples missing for one of the time points.</population>
        <group_list>
          <group group_id="O1">
            <title>Duvelisib</title>
            <description>Participants with severe COVID-19 who do not require mechanical ventilation randomized to receive duvelisib for 14 days.&#xD;
Duvelisib will be taken orally at an initial dose of 25 milligrams (mg) twice per day for 14 days. The dose will be de-escalated to 15 mg, twice per day, under certain clinical circumstances.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants with severe COVID-19 who do not require mechanical ventilation randomized to receive a placebo to match duvelisib for 14 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Interleukin-10 (IL-10) Levels</title>
          <description>Mean levels of the inflammatory serum biomarker IL-10 is compared between study arms.</description>
          <population>This analysis includes participants who had blood samples obtained at both study time points. Two participants in the placebo arm had samples missing for one of the time points.</population>
          <units>pg/mL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="25"/>
                <count group_id="O2" value="20"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Week 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="389.02" spread="838.50"/>
                    <measurement group_id="O2" value="808.09" spread="831.24"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="658.17" spread="1411.11"/>
                    <measurement group_id="O2" value="250.00" spread="1836.14"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Interferon Gamma-induced Protein 10 (IP-10) Levels</title>
        <description>Mean levels of the inflammatory serum biomarker IP-10is compared between study arms.</description>
        <time_frame>Week 1, Week 2</time_frame>
        <population>This analysis includes participants who had blood samples obtained at both study time points. Two participants in the placebo arm had samples missing for one of the time points.</population>
        <group_list>
          <group group_id="O1">
            <title>Duvelisib</title>
            <description>Participants with severe COVID-19 who do not require mechanical ventilation randomized to receive duvelisib for 14 days.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants with severe COVID-19 who do not require mechanical ventilation randomized to receive a placebo to match duvelisib for 14 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Interferon Gamma-induced Protein 10 (IP-10) Levels</title>
          <description>Mean levels of the inflammatory serum biomarker IP-10is compared between study arms.</description>
          <population>This analysis includes participants who had blood samples obtained at both study time points. Two participants in the placebo arm had samples missing for one of the time points.</population>
          <units>pg/mL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="25"/>
                <count group_id="O2" value="20"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Week 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3136.50" spread="652.84"/>
                    <measurement group_id="O2" value="4781.42" spread="649.35"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2956.68" spread="1122.8"/>
                    <measurement group_id="O2" value="3809.83" spread="1442.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Macrophage Inflammatory Protein 1alpha (MIP-1a) Levels</title>
        <description>Mean levels of the inflammatory serum biomarker MIP-1a is compared between study arms.</description>
        <time_frame>Week 1, Week 2</time_frame>
        <population>This analysis includes participants who had blood samples obtained at both study time points. Two participants in the placebo arm had samples missing for one of the time points.</population>
        <group_list>
          <group group_id="O1">
            <title>Duvelisib</title>
            <description>Participants with severe COVID-19 who do not require mechanical ventilation randomized to receive duvelisib for 14 days.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants with severe COVID-19 who do not require mechanical ventilation randomized to receive a placebo to match duvelisib for 14 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Macrophage Inflammatory Protein 1alpha (MIP-1a) Levels</title>
          <description>Mean levels of the inflammatory serum biomarker MIP-1a is compared between study arms.</description>
          <population>This analysis includes participants who had blood samples obtained at both study time points. Two participants in the placebo arm had samples missing for one of the time points.</population>
          <units>pg/mL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="25"/>
                <count group_id="O2" value="20"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Week 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="29.0477" spread="26.449"/>
                    <measurement group_id="O2" value="123.60" spread="26.8550"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="43.0115" spread="48.356"/>
                    <measurement group_id="O2" value="57.5810" spread="60.045"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Monocyte Chemoattractant Protein-1 (MCP-1) Levels</title>
        <description>Mean levels of the inflammatory serum biomarker MCP-1 are compared between study arms.</description>
        <time_frame>Week 1, Week 2</time_frame>
        <population>This analysis includes participants who had blood samples obtained at both study time points. Two participants in the placebo arm had samples missing for one of the time points.</population>
        <group_list>
          <group group_id="O1">
            <title>Duvelisib</title>
            <description>Participants with severe COVID-19 who do not require mechanical ventilation randomized to receive duvelisib for 14 days.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants with severe COVID-19 who do not require mechanical ventilation randomized to receive a placebo to match duvelisib for 14 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Monocyte Chemoattractant Protein-1 (MCP-1) Levels</title>
          <description>Mean levels of the inflammatory serum biomarker MCP-1 are compared between study arms.</description>
          <population>This analysis includes participants who had blood samples obtained at both study time points. Two participants in the placebo arm had samples missing for one of the time points.</population>
          <units>pg/mL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="25"/>
                <count group_id="O2" value="20"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Week 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="122.63" spread="28.2616"/>
                    <measurement group_id="O2" value="124.80" spread="27.9714"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="255.30" spread="46.5051"/>
                    <measurement group_id="O2" value="187.12" spread="61.2899"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Granulocyte Colony-stimulating Factor (G-CSF) Levels</title>
        <description>Mean levels of the inflammatory serum biomarker G-CSF are compared between study arms.</description>
        <time_frame>Week 1, Week 2</time_frame>
        <population>This analysis includes participants who had blood samples obtained at both study time points. Two participants in the placebo arm had samples missing for one of the time points.</population>
        <group_list>
          <group group_id="O1">
            <title>Duvelisib</title>
            <description>Participants with severe COVID-19 who do not require mechanical ventilation randomized to receive duvelisib for 14 days.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants with severe COVID-19 who do not require mechanical ventilation randomized to receive a placebo to match duvelisib for 14 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Granulocyte Colony-stimulating Factor (G-CSF) Levels</title>
          <description>Mean levels of the inflammatory serum biomarker G-CSF are compared between study arms.</description>
          <population>This analysis includes participants who had blood samples obtained at both study time points. Two participants in the placebo arm had samples missing for one of the time points.</population>
          <units>pg/mL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="25"/>
                <count group_id="O2" value="20"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Week 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8.1585" spread="42.8679"/>
                    <measurement group_id="O2" value="157.86" spread="43.5125"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8.6447" spread="78.3263"/>
                    <measurement group_id="O2" value="39.7275" spread="97.289"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Tumor Necrosis Factor (TNF)-Alpha Levels</title>
        <description>Mean levels of the inflammatory serum biomarker TNF-alpha are compared between study arms.</description>
        <time_frame>Week 1, Week 2</time_frame>
        <population>This analysis includes participants who had blood samples obtained at both study time points. Two participants in the placebo arm had samples missing for one of the time points.</population>
        <group_list>
          <group group_id="O1">
            <title>Duvelisib</title>
            <description>Participants with severe COVID-19 who do not require mechanical ventilation randomized to receive duvelisib for 14 days.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants with severe COVID-19 who do not require mechanical ventilation randomized to receive a placebo to match duvelisib for 14 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Tumor Necrosis Factor (TNF)-Alpha Levels</title>
          <description>Mean levels of the inflammatory serum biomarker TNF-alpha are compared between study arms.</description>
          <population>This analysis includes participants who had blood samples obtained at both study time points. Two participants in the placebo arm had samples missing for one of the time points.</population>
          <units>pg/mL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="25"/>
                <count group_id="O2" value="20"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Week 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.3291" spread="21.8406"/>
                    <measurement group_id="O2" value="81.0170" spread="22.236"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.6108" spread="40.1411"/>
                    <measurement group_id="O2" value="17.0332" spread="49.723"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Gene Expression Profile of Regulatory T Cells (Tregs)</title>
        <description>Single-cell ribonucleic acid (RNA) sequencing is a powerful gene expression profiling tool to acquire transcriptional level information of each gene. Mean levels of the Tregs will be compared between study arms.</description>
        <time_frame>Week 1, Week 2</time_frame>
        <population>Due to funding limitations single-cell RNA sequencing was not performed. As the focus of this study was to determine the immune profile consisting of immune cell composition and serum cytokine/chemokine other laboratory experiments provided sufficient data for this purpose.</population>
        <group_list>
          <group group_id="O1">
            <title>Duvelisib</title>
            <description>Participants with severe COVID-19 who do not require mechanical ventilation randomized to receive duvelisib for 14 days.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants with severe COVID-19 who do not require mechanical ventilation randomized to receive a placebo to match duvelisib for 14 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Gene Expression Profile of Regulatory T Cells (Tregs)</title>
          <description>Single-cell ribonucleic acid (RNA) sequencing is a powerful gene expression profiling tool to acquire transcriptional level information of each gene. Mean levels of the Tregs will be compared between study arms.</description>
          <population>Due to funding limitations single-cell RNA sequencing was not performed. As the focus of this study was to determine the immune profile consisting of immune cell composition and serum cytokine/chemokine other laboratory experiments provided sufficient data for this purpose.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Gene Expression Profile of Cluster of Differentiation 8 (CD8)+Interferon Gamma (IFNg)+ Granulocyte-macrophage Colony-stimulating Factor (GM-CSF)+</title>
        <description>Single-cell RNA sequencing is a powerful gene expression profiling tool to acquire transcriptional level information of each gene. Mean levels of CD8+IFNg+GM-CSF+ will be compared between study arms.</description>
        <time_frame>Week 1, Week 2</time_frame>
        <population>Due to funding limitations single-cell RNA sequencing was not performed. As the focus of this study was to determine the immune profile consisting of immune cell composition and serum cytokine/chemokine other laboratory experiments provided sufficient data for this purpose.</population>
        <group_list>
          <group group_id="O1">
            <title>Duvelisib</title>
            <description>Participants with severe COVID-19 who do not require mechanical ventilation randomized to receive duvelisib for 14 days.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants with severe COVID-19 who do not require mechanical ventilation randomized to receive a placebo to match duvelisib for 14 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Gene Expression Profile of Cluster of Differentiation 8 (CD8)+Interferon Gamma (IFNg)+ Granulocyte-macrophage Colony-stimulating Factor (GM-CSF)+</title>
          <description>Single-cell RNA sequencing is a powerful gene expression profiling tool to acquire transcriptional level information of each gene. Mean levels of CD8+IFNg+GM-CSF+ will be compared between study arms.</description>
          <population>Due to funding limitations single-cell RNA sequencing was not performed. As the focus of this study was to determine the immune profile consisting of immune cell composition and serum cytokine/chemokine other laboratory experiments provided sufficient data for this purpose.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Gene Expression Profile of CD8+ T Cell Immunoglobulin and Mucin Domain-containing Protein 3 (Tim3)+ Programmed Cell Death Protein 1 (PD-1)+</title>
        <description>Single-cell RNA sequencing is a powerful gene expression profiling tool to acquire transcriptional level information of each gene. Mean levels of CD8+Tim3+PD-1+ will be compared between study arms.</description>
        <time_frame>Week 1, Week 2</time_frame>
        <population>Due to funding limitations single-cell RNA sequencing was not performed. As the focus of this study was to determine the immune profile consisting of immune cell composition and serum cytokine/chemokine other laboratory experiments provided sufficient data for this purpose.</population>
        <group_list>
          <group group_id="O1">
            <title>Duvelisib</title>
            <description>Participants with severe COVID-19 who do not require mechanical ventilation randomized to receive duvelisib for 14 days.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants with severe COVID-19 who do not require mechanical ventilation randomized to receive a placebo to match duvelisib for 14 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Gene Expression Profile of CD8+ T Cell Immunoglobulin and Mucin Domain-containing Protein 3 (Tim3)+ Programmed Cell Death Protein 1 (PD-1)+</title>
          <description>Single-cell RNA sequencing is a powerful gene expression profiling tool to acquire transcriptional level information of each gene. Mean levels of CD8+Tim3+PD-1+ will be compared between study arms.</description>
          <population>Due to funding limitations single-cell RNA sequencing was not performed. As the focus of this study was to determine the immune profile consisting of immune cell composition and serum cytokine/chemokine other laboratory experiments provided sufficient data for this purpose.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Gene Expression Profile of Cluster of Differentiation 14 (CD14)+ Cluster of Differentiation (CD16)+ Monocytes</title>
        <description>Single-cell RNA sequencing is a powerful gene expression profiling tool to acquire transcriptional level information of each gene. Mean levels of CD14+CD16+ monocytes will be compared between study arms.</description>
        <time_frame>Week 1, Week 2</time_frame>
        <population>Due to funding limitations single-cell RNA sequencing was not performed. As the focus of this study was to determine the immune profile consisting of immune cell composition and serum cytokine/chemokine other laboratory experiments provided sufficient data for this purpose.</population>
        <group_list>
          <group group_id="O1">
            <title>Duvelisib</title>
            <description>Participants with severe COVID-19 who do not require mechanical ventilation randomized to receive duvelisib for 14 days.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants with severe COVID-19 who do not require mechanical ventilation randomized to receive a placebo to match duvelisib for 14 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Gene Expression Profile of Cluster of Differentiation 14 (CD14)+ Cluster of Differentiation (CD16)+ Monocytes</title>
          <description>Single-cell RNA sequencing is a powerful gene expression profiling tool to acquire transcriptional level information of each gene. Mean levels of CD14+CD16+ monocytes will be compared between study arms.</description>
          <population>Due to funding limitations single-cell RNA sequencing was not performed. As the focus of this study was to determine the immune profile consisting of immune cell composition and serum cytokine/chemokine other laboratory experiments provided sufficient data for this purpose.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Immunoglobin G (IgG) Antibodies</title>
        <description>Median titers of IgG antibodies to SARS-CoV-2 at 4 weeks will be assessed for both study arms.</description>
        <time_frame>Week 4</time_frame>
        <population>Due to budget limitations other laboratory experiments were prioritized and Immunoglobulin G (IgG) antibodies were not measured.</population>
        <group_list>
          <group group_id="O1">
            <title>Duvelisib</title>
            <description>Participants with severe COVID-19 who do not require mechanical ventilation randomized to receive duvelisib for 14 days.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants with severe COVID-19 who do not require mechanical ventilation randomized to receive a placebo to match duvelisib for 14 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Immunoglobin G (IgG) Antibodies</title>
          <description>Median titers of IgG antibodies to SARS-CoV-2 at 4 weeks will be assessed for both study arms.</description>
          <population>Due to budget limitations other laboratory experiments were prioritized and Immunoglobulin G (IgG) antibodies were not measured.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants Surviving</title>
        <description>Overall survival is defined as days from randomization to death and censored at last follow up.</description>
        <time_frame>Up to Day 60</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Duvelisib</title>
            <description>Participants with severe COVID-19 who do not require mechanical ventilation randomized to receive duvelisib for 14 days.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants with severe COVID-19 who do not require mechanical ventilation randomized to receive a placebo to match duvelisib for 14 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants Surviving</title>
          <description>Overall survival is defined as days from randomization to death and censored at last follow up.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="25"/>
                <count group_id="O2" value="22"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="25"/>
                    <measurement group_id="O2" value="21"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Vasoactive Intestinal Peptide (VIP)</title>
        <description>VIP is a peptide hormone with immunosuppressive properties. Mean levels VIP will be compared between study arms.</description>
        <time_frame>Week 1, Week 2</time_frame>
        <population>Due to budget limitations other laboratory experiments were prioritized and VIP (an exploratory outcome) was not analyzed.</population>
        <group_list>
          <group group_id="O1">
            <title>Duvelisib</title>
            <description>Participants with severe COVID-19 who do not require mechanical ventilation randomized to receive duvelisib for 14 days.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants with severe COVID-19 who do not require mechanical ventilation randomized to receive a placebo to match duvelisib for 14 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Vasoactive Intestinal Peptide (VIP)</title>
          <description>VIP is a peptide hormone with immunosuppressive properties. Mean levels VIP will be compared between study arms.</description>
          <population>Due to budget limitations other laboratory experiments were prioritized and VIP (an exploratory outcome) was not analyzed.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Information on adverse events was collected beginning at the time study treatment began until 14 days following cessation of duvelisib or placebo (up to Day 29). Survival status was assessed up to Day 60.</time_frame>
      <desc>Adverse events that began or worsened after informed consent to participate was given were recorded.</desc>
      <group_list>
        <group group_id="E1">
          <title>Duvelisib</title>
          <description>Participants with severe COVID-19 who do not require mechanical ventilation randomized to receive duvelisib for 14 days.</description>
        </group>
        <group group_id="E2">
          <title>Placebo</title>
          <description>Participants with severe COVID-19 who do not require mechanical ventilation randomized to receive a placebo to match duvelisib for 14 days.</description>
        </group>
      </group_list>
      <serious_events>
        <default_assessment>Non-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="0" subjects_at_risk="25"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="25"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="22"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Transfer to ICU and/or initiation of mechanical ventilation</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="25"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Post-discharge hospitalization</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="25"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="22"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_assessment>Non-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="5" subjects_at_risk="25"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="22"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Leukopenia - grade 2</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="25"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Lymphopenia - grade 2 or 3</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="25"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="22"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>High alanine transaminase (ALT) - grade 2</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="25"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="22"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE 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>Edmund Waller, MD, PhD</name_or_title>
      <organization>Emory University</organization>
      <phone>404-727-4995</phone>
      <email>ewaller@emory.edu</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/NCT04487886
org study id: STUDY00000701
nct id: NCT04487886
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
In this study, patients with severe coronavirus disease 2019 (COVID-19) infection will be
      randomized to receive duvelisib or a placebo. Participants will be enrolled at Emory
      University Hospital and will be identified and recruited by their treating physician and
      research team.
This randomized placebo-controlled phase 2 study will evaluate whether a two-week exposure to
      duvelisib, a gamma/delta phosphoinositide 3-kinase (PI3K) inhibitor, reduces inflammation in
      the lungs in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
      infection and COVID-19 who do not require mechanical ventilation at study initiation. The
      primary objective of the study is to determine the efficacy of duvelisib treatment in
      preventing death or the need for mechanical ventilation among patients with World Health
      Organization (WHO)-defined severe COVID-19. Key secondary endpoints will be reductions in
      oxygen requirements of patients and improvements in their performance status, safety and
      tolerability of duvelisib in the setting of COVID-19, biomarkers of inflammation, and
      generation of immunoglobulin G (IgG) and immunoglobulin M (IgM) antibody responses to
      SARS-Cov-2 spike protein. The study will determine if a two-week exposure to duvelisib
      beginning soon after presentation with severe COVID-19 warrants further evaluation in a
      larger clinical study.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Care Provider)
measure: Number of Participants Requiring Mechanical Ventilation or Dying
time frame: Up to Day 29
description: This is a composite endpoint of the number of participants who require mechanical ventilation or who die within four weeks of randomization.
measure: Days to Recovery
time frame: Up to Day 29
description: Time to recovery is measured in days, from the day of randomization to the day of recovery, with recovery defined as a score of equal to or greater than 5 from the eight categories from the National Institute of Allergy and Infectious Diseases (NIAID) ordinal scale. The scale is as follows: 1 = Death, 2 = Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO), 3 = Hospitalized, on non-invasive ventilation or high flow oxygen devices, 4 = Hospitalized, requiring supplemental oxygen, 5 = Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise), 6 = Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care;=, 7 = Not hospitalized, limitation on activities and/or requiring home oxygen, and 8 = Not hospitalized, no limitations on activities.
measure: Duration of Hospitalization
time frame: Up to Day 29
description: The number of days spent hospitalized is presented for both study arms.
measure: Days on Study Drug
time frame: Up to Day 29
description: The number of days that participants took any doses of the study drug that they were randomized to receive is presented for both study arms.
measure: Total Doses of Study Drug
time frame: Up to Day 29
description: The study medication was taken twice per day for 14 days. The number of doses of study medication that was taken is presented for both study arms.
measure: Number of Participants Dying
time frame: Up to Day 29
description: The incidence of death within 29 days of randomization is compared between study arms.
measure: Number of Participants Transferred to ICU
time frame: Up to Day 29
description: The number of participants who were transferred to the intensive care unit (ICU) within 29 days of randomization.
measure: Eastern Cooperative Oncology Group (ECOG) Performance Status Score
time frame: Between Day 14 and 28, Between Day 29 and 60
description: The ECOG Performance Status instrument includes a single item assessing overall physical status. Health status is rated on a scale of 0 to 5 where 0 = fully active, 1 = restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, 2 = ambulatory and capable of all selfcare but unable to carry out any work activities, 3 = capable of only limited selfcare, completely disabled, and 5 = dead. Median ECOG performance is compared between study arms.
measure: Number of Grade III-V Adverse Events
time frame: Up to Day 29
description: The incidence of grade III-V adverse events or serious adverse events (SAEs), as defined by Common Terminology Criteria for Adverse Events (CTCAE) version 5, is compared between study arms. Grade 3 lab values that required no special treatment are excluded from this outcome measure.
measure: Number of Secondary Bacterial or Viral Infections
time frame: Up to Day 29
description: The incidence of documented secondary bacterial or viral infections among participants is compared between study arms.
measure: T Helper 1 (Th1) T Cell Frequency
time frame: Week 1, Week 2
description: The mean frequency of Th1 T cells in peripheral blood mononuclear cells (PBMCs) is compared between study arms.
measure: Th17 T Cell Frequency
time frame: Week 1, Week 2
description: The mean frequency of Th17 T cells in PBMCs is compared between study arms.
measure: Interleukin-2 (IL-2) Levels
time frame: Week 1, Week 2
description: Mean levels of the inflammatory serum biomarker IL-2 is compared between study arms.
measure: Interleukin-2 Receptor (IL-2R) Levels
time frame: Week 1, Week 2
description: Mean levels of the inflammatory serum biomarker IL-2R is compared between study arms.
measure: Interleukin-6 (IL-6) Levels
time frame: Week 1, Week 2
description: Mean levels of the inflammatory serum biomarker IL-6 is compared between study arms.
measure: Interleukin-7 (IL-7) Levels
time frame: Week 1, Week 2
description: Mean levels of the inflammatory serum biomarker IL-7 is compared between study arms.
measure: Interleukin-8 (IL-8) Levels
time frame: Week 1, Week 2
description: Mean levels of the inflammatory serum biomarker IL-8 is compared between study arms.
measure: Interleukin-10 (IL-10) Levels
time frame: Week 1, Week 2
description: Mean levels of the inflammatory serum biomarker IL-10 is compared between study arms.
measure: Interferon Gamma-induced Protein 10 (IP-10) Levels
time frame: Week 1, Week 2
description: Mean levels of the inflammatory serum biomarker IP-10is compared between study arms.
measure: Macrophage Inflammatory Protein 1alpha (MIP-1a) Levels
time frame: Week 1, Week 2
description: Mean levels of the inflammatory serum biomarker MIP-1a is compared between study arms.
measure: Monocyte Chemoattractant Protein-1 (MCP-1) Levels
time frame: Week 1, Week 2
description: Mean levels of the inflammatory serum biomarker MCP-1 are compared between study arms.
measure: Granulocyte Colony-stimulating Factor (G-CSF) Levels
time frame: Week 1, Week 2
description: Mean levels of the inflammatory serum biomarker G-CSF are compared between study arms.
measure: Tumor Necrosis Factor (TNF)-Alpha Levels
time frame: Week 1, Week 2
description: Mean levels of the inflammatory serum biomarker TNF-alpha are compared between study arms.
measure: Gene Expression Profile of Regulatory T Cells (Tregs)
time frame: Week 1, Week 2
description: Single-cell ribonucleic acid (RNA) sequencing is a powerful gene expression profiling tool to acquire transcriptional level information of each gene. Mean levels of the Tregs will be compared between study arms.
measure: Gene Expression Profile of Cluster of Differentiation 8 (CD8)+Interferon Gamma (IFNg)+ Granulocyte-macrophage Colony-stimulating Factor (GM-CSF)+
time frame: Week 1, Week 2
description: Single-cell RNA sequencing is a powerful gene expression profiling tool to acquire transcriptional level information of each gene. Mean levels of CD8+IFNg+GM-CSF+ will be compared between study arms.
measure: Gene Expression Profile of CD8+ T Cell Immunoglobulin and Mucin Domain-containing Protein 3 (Tim3)+ Programmed Cell Death Protein 1 (PD-1)+
time frame: Week 1, Week 2
description: Single-cell RNA sequencing is a powerful gene expression profiling tool to acquire transcriptional level information of each gene. Mean levels of CD8+Tim3+PD-1+ will be compared between study arms.
measure: Gene Expression Profile of Cluster of Differentiation 14 (CD14)+ Cluster of Differentiation (CD16)+ Monocytes
time frame: Week 1, Week 2
description: Single-cell RNA sequencing is a powerful gene expression profiling tool to acquire transcriptional level information of each gene. Mean levels of CD14+CD16+ monocytes will be compared between study arms.
measure: Immunoglobin G (IgG) Antibodies
time frame: Week 4
description: Median titers of IgG antibodies to SARS-CoV-2 at 4 weeks will be assessed for both study arms.
measure: Number of Participants Surviving
time frame: Up to Day 60
description: Overall survival is defined as days from randomization to death and censored at last follow up.
measure: Vasoactive Intestinal Peptide (VIP)
time frame: Week 1, Week 2
description: VIP is a peptide hormone with immunosuppressive properties. Mean levels VIP will be compared between study arms.
arm group label: Duvelisib
arm group type: Experimental
description: Participants with severe COVID-19 who do not require mechanical ventilation randomized to receive duvelisib for 14 days.
arm group label: Placebo
arm group type: Placebo Comparator
description: Participants with severe COVID-19 who do not require mechanical ventilation randomized to receive a placebo to match duvelisib for 14 days.
intervention type: Drug
intervention name: Duvelisib
description: Duvelisib will be taken orally at an initial dose of 25 milligrams (mg) twice per day for 14 days. The dose will be de-escalated to 15 mg, twice per day, under certain clinical circumstances.
arm group label: Duvelisib
other name: Copiktra
intervention type: Drug
intervention name: Placebo
description: A placebo to match duvelisib will be taken orally twice per day for 14 days.
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Edmund Waller, MD, PhD
role: Principal Investigator
affiliation: Emory University
facility: 
facility: 
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Emory University
investigator full name: Edmund Waller
investigator title: Professor
mesh term: COVID-19
mesh term: Pneumonia
mesh term: Coronavirus Infections
sharing ipd: Yes
ipd description: The researchers plan to share individual participant data including participant status ordinal score at baseline and end of treatment, study drug allocation, duration of treatment, and survival status at Day 60.
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd time frame: Data will be made available for sharing at the conclusion of the study and will be available for one year.
ipd access criteria: Data will be available for sharing with academic or pharmaceutical investigators for analyses including comparison of DAMPEN-CI results with those from other drug trials in similar patient cohorts. Researchers wishing to use data should email the investigators of DAMPEN-Cl. A summary of the research plan will be required prior to release of the DAMPEN-CI data.
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 