<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/NCT04412252</url>
  </required_header>
  <id_info>
    <org_study_id>A3921377</org_study_id>
    <nct_id>NCT04412252</nct_id>
  </id_info>
  <brief_title>Safety and Efficacy of Tofacitinib in Hospitalized Participants With COVID-19 Pneumonia Who Are Receiving Standard of Care Therapy</brief_title>
  <official_title>A MULTICENTER, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, PARALLEL GROUP STUDY ASSESSING THE SAFETY AND EFFICACY OF TOFACITINIB IN HOSPITALIZED PARTICIPANTS WITH COVID-19 PNEUMONIA WHO ARE RECEIVING STANDARD OF CARE THERAPY</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Pfizer</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Pfizer</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The study is designed as a multicenter, randomized, double-blind, placebo-controlled,&#xD;
      parallel group study of the safety and efficacy of tofacitinib in hospitalized adult&#xD;
      participants with COVID-19 pneumonia who are receiving SoC therapy and who are not on HFNC,&#xD;
      noninvasive ventilation, invasive mechanical ventilation, or ECMO on Day 1 at the time of&#xD;
      randomization.&#xD;
&#xD;
      Participants with laboratory confirmed SARS-CoV-2 infection as determined by a positive PCR&#xD;
      or other commercially available or public health assay, who have agreed to participate will&#xD;
      be screened within 48 hours after hospitalization to determine eligibility. This should be&#xD;
      completed within 48 hours prior to Day 1.&#xD;
&#xD;
      Eligible participants will be randomized on Day 1 in a 1:1 ratio to the tofacitinib treatment&#xD;
      group or the placebo treatment group and will receive treatment for up to 14 days, or until&#xD;
      discharge from the hospital, whichever is earlier. If a participant requires intubation prior&#xD;
      to the end of the 14-day treatment period, they will continue to receive tofacitinib or&#xD;
      matching placebo until Day 14 (or until discharge from the hospital, if earlier than Day 14),&#xD;
      if clinically appropriate.&#xD;
&#xD;
      Participants will be assessed daily (up to Day 28) while hospitalized for clinical, safety,&#xD;
      and laboratory parameters. Follow-up visits will occur on Day 28, 28 to 35 days after the&#xD;
      ET/ED/EOT visit, and on Day 60.&#xD;
&#xD;
      An independent, external DSMB will be convened to oversee the safety of participants and make&#xD;
      recommendations regarding the conduct of the trial in accordance with the Charter.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    Due to the pursuit of other SARS-CoV-2-related research including alternative trials with&#xD;
    tofacitinib, this trial was canceled prior to subject enrollment.&#xD;
  </why_stopped>
  <start_date type="Anticipated">July 6, 2020</start_date>
  <completion_date type="Anticipated">October 18, 2020</completion_date>
  <primary_completion_date type="Anticipated">September 16, 2020</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Clinical status using ordinal scale</measure>
    <time_frame>Day 28</time_frame>
    <description>Death or respiratory failure (1, 2, or 3, on an 8-point ordinal scale of disease severity) at Day 28. 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; 8) Not hospitalized, no limitations on activities.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Clinical status using ordinal scale</measure>
    <time_frame>Day 14</time_frame>
    <description>Ordinal scale of disease severity. 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; 8) Not hospitalized, no limitations on activities.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Status of alive and not using mechanical ventilation or extracorporeal membrane oxygenation (ECMO)</measure>
    <time_frame>Day 14 and Day 28</time_frame>
    <description>Category 3 to 8 on an ordinal scale of disease severity. The scale is as follows: 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; 8) Not hospitalized, no limitations on activities.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Status of discharged or not requiring supplemental oxygen</measure>
    <time_frame>Day 28</time_frame>
    <description>Category 5 to 8 on an ordinal scale of disease severity. The scale is as follows: 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; 8) Not hospitalized, no limitations on activities.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mortality</measure>
    <time_frame>Day 60</time_frame>
    <description>Category 1 on an ordinal scale of disease severity. The scale is as follows: 1) Death.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>COVID-19</condition>
  <arm_group>
    <arm_group_label>Tofacitinib</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive tofacitinib 10 mg twice per day for 14 days and standard of care therapy.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Participants will receive tofacitinib-matching placebo twice per day for 14 days and standard of care therapy.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tofacitinib</intervention_name>
    <description>10 mg tofacitinib administered as two 5 mg tablets or solution taken orally twice daily for 14 days</description>
    <arm_group_label>Tofacitinib</arm_group_label>
    <other_name>xeljanz</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Tofacitinib-matching placebo administered as tablets or solution taken orally twice daily for 14 days</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male or female between 18 and 65 years. A female is eligible if she is not pregnant or&#xD;
             breastfeeding. WOCBP must use 2 highly effective forms of contraception.&#xD;
&#xD;
          -  Participants with laboratory-confirmed novel coronavirus (SARS-CoV-2) infection prior&#xD;
             to Day 1.&#xD;
&#xD;
          -  Participants with evidence of COVID-19 pneumonia assessed by radiographic imaging&#xD;
             (chest x ray or chest CT scan).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Require HFNC, non-invasive ventilation, invasive mechanical ventilation, or ECMO on&#xD;
             Day 1 at the time of randomization.&#xD;
&#xD;
          -  Have history of or current thrombosis. Only if current thrombosis is suspected,&#xD;
             imaging testing is recommended (e.g. CTPA or per local guidance) to exclude&#xD;
             thrombosis.&#xD;
&#xD;
          -  Have a personal or first degree family history of blood clotting disorders.&#xD;
&#xD;
          -  Participants who are immunocompromised, with known immunodeficiencies, or taking&#xD;
             potent immunosuppressive agents (e.g. azathioprine, cyclosporine).&#xD;
&#xD;
          -  Participants with any current malignancy or lymphoproliferative disorders that&#xD;
             requires active treatment.&#xD;
&#xD;
          -  Suspected or known active systemic bacterial, fungal, or viral infections (with the&#xD;
             exception of COVID-19).&#xD;
&#xD;
          -  Severe hepatic impairment, defined as Child-Pugh class C.&#xD;
&#xD;
          -  Severe anemia (hemoglobin &lt; 8 g/dL)&#xD;
&#xD;
          -  ANY of the following abnormalities in clinical lab tests at screening, confirmed by a&#xD;
             single repeat, if deemed necessary: ALC &lt; 500 cells/mm3, ANC &lt; 1000 cells/mm3&#xD;
&#xD;
          -  Known allergy to tofacitinib&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>99 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Pfizer CT.gov Call Center</last_name>
    <role>Study Director</role>
    <affiliation>Pfizer</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Hartford Hospital (HH)</name>
      <address>
        <city>Hartford</city>
        <state>Connecticut</state>
        <zip>06102</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Iowa Hospitals &amp; Clinics Investigational Drug Services</name>
      <address>
        <city>Iowa City</city>
        <state>Iowa</state>
        <zip>52242</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Iowa</name>
      <address>
        <city>Iowa City</city>
        <state>Iowa</state>
        <zip>52242</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>LSUHSC-Shreveport</name>
      <address>
        <city>Shreveport</city>
        <state>Louisiana</state>
        <zip>71103</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ochsner LSU Health Shreveport Academic Medical Center</name>
      <address>
        <city>Shreveport</city>
        <state>Louisiana</state>
        <zip>71103</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospitals Cleveland Medical Center</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <zip>44106</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://pmiform.com/clinical-trial-info-request?StudyID=A3921377</url>
    <description>To obtain contact information for a study center near you, click here.</description>
  </link>
  <verification_date>July 2020</verification_date>
  <study_first_submitted>May 30, 2020</study_first_submitted>
  <study_first_submitted_qc>May 30, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 2, 2020</study_first_posted>
  <last_update_submitted>July 29, 2020</last_update_submitted>
  <last_update_submitted_qc>July 29, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">July 31, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>COVID-19</keyword>
  <keyword>Pneumonia</keyword>
  <keyword>SARS-CoV-2</keyword>
  <keyword>Novel Coronavirus</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>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Tofacitinib</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.</ipd_description>
    <ipd_url>https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests</ipd_url>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04412252
org study id: A3921377
nct id: NCT04412252
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
The study is designed as a multicenter, randomized, double-blind, placebo-controlled,
      parallel group study of the safety and efficacy of tofacitinib in hospitalized adult
      participants with COVID-19 pneumonia who are receiving SoC therapy and who are not on HFNC,
      noninvasive ventilation, invasive mechanical ventilation, or ECMO on Day 1 at the time of
      randomization.

      Participants with laboratory confirmed SARS-CoV-2 infection as determined by a positive PCR
      or other commercially available or public health assay, who have agreed to participate will
      be screened within 48 hours after hospitalization to determine eligibility. This should be
      completed within 48 hours prior to Day 1.

      Eligible participants will be randomized on Day 1 in a 1:1 ratio to the tofacitinib treatment
      group or the placebo treatment group and will receive treatment for up to 14 days, or until
      discharge from the hospital, whichever is earlier. If a participant requires intubation prior
      to the end of the 14-day treatment period, they will continue to receive tofacitinib or
      matching placebo until Day 14 (or until discharge from the hospital, if earlier than Day 14),
      if clinically appropriate.

      Participants will be assessed daily (up to Day 28) while hospitalized for clinical, safety,
      and laboratory parameters. Follow-up visits will occur on Day 28, 28 to 35 days after the
      ET/ED/EOT visit, and on Day 60.

      An independent, external DSMB will be convened to oversee the safety of participants and make
      recommendations regarding the conduct of the trial in accordance with the Charter.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Clinical status using ordinal scale
time frame: Day 28
description: Death or respiratory failure (1, 2, or 3, on an 8-point ordinal scale of disease severity) at Day 28. 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; 8) Not hospitalized, no limitations on activities.
measure: Clinical status using ordinal scale
time frame: Day 14
description: Ordinal scale of disease severity. 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; 8) Not hospitalized, no limitations on activities.
measure: Status of alive and not using mechanical ventilation or extracorporeal membrane oxygenation (ECMO)
time frame: Day 14 and Day 28
description: Category 3 to 8 on an ordinal scale of disease severity. The scale is as follows: 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; 8) Not hospitalized, no limitations on activities.
measure: Status of discharged or not requiring supplemental oxygen
time frame: Day 28
description: Category 5 to 8 on an ordinal scale of disease severity. The scale is as follows: 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; 8) Not hospitalized, no limitations on activities.
measure: Mortality
time frame: Day 60
description: Category 1 on an ordinal scale of disease severity. The scale is as follows: 1) Death.
arm group label: Tofacitinib
arm group type: Experimental
description: Participants will receive tofacitinib 10 mg twice per day for 14 days and standard of care therapy.
arm group label: Placebo
arm group type: Placebo Comparator
description: Participants will receive tofacitinib-matching placebo twice per day for 14 days and standard of care therapy.
intervention type: Drug
intervention name: Tofacitinib
description: 10 mg tofacitinib administered as two 5 mg tablets or solution taken orally twice daily for 14 days
arm group label: Tofacitinib
other name: xeljanz
intervention type: Other
intervention name: Placebo
description: Tofacitinib-matching placebo administered as tablets or solution taken orally twice daily for 14 days
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 99 Years
healthy volunteers: No
last name: Pfizer CT.gov Call Center
role: Study Director
affiliation: Pfizer
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
url: https://pmiform.com/clinical-trial-info-request?StudyID=A3921377
description: To obtain contact information for a study center near you, click here.
responsible party type: Sponsor
mesh term: COVID-19
mesh term: Pneumonia
mesh term: Tofacitinib
sharing ipd: Yes
ipd description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
ipd url: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests