<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/NCT04415151</url>
  </required_header>
  <id_info>
    <org_study_id>2000027848</org_study_id>
    <nct_id>NCT04415151</nct_id>
  </id_info>
  <brief_title>Tofacitinib for Treatment of Moderate COVID-19</brief_title>
  <acronym>I-TOMIC</acronym>
  <official_title>Investigation of Tofacitinib to Mitigate the Impact of COVID-19 (I-TOMIC) in Moderate SARS-CoV-2 (MODERATE I-TOMIC)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Yale University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Yale 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>
      The purpose of this randomized, double blinded, placebo controlled study is to assess the&#xD;
      efficacy and safety of tofacitinib in hospitalized adult (18-99 years old) patients with&#xD;
      SARS-CoV-2 and pneumonia who require supplemental oxygen and have serologic markers of&#xD;
      inflammation but do not need mechanical ventilation.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The purpose of this randomized, double blinded, placebo controlled Phase 2b study is to&#xD;
      assess the efficacy and safety of tofacitinib in hospitalized adult (18-99 years old) male&#xD;
      and female patients with SARS-CoV-2 and pneumonia who require supplemental oxygen and have&#xD;
      serologic markers of inflammation but do not need mechanical ventilation (see Inclusion&#xD;
      criteria). Sixty patients will be recruited to receive tofacitinib or placebo in addition to&#xD;
      standard of care (SOC) in a 1:1 ratio.&#xD;
&#xD;
      Subjects will be screened during hospitalization. Patients with confirmed SARS-CoV-2&#xD;
      infection, and meeting all other Inclusion and Exclusion criteria, will be randomized to&#xD;
      either treatment with tofacitinib or placebo in addition to SOC during hospitalization (dose&#xD;
      adjusted, if required), with the exception of pre-specified immunomodulatory agents (as&#xD;
      documented in the inclusion/exclusion criteria). Tofacitinib will be administered in a dose&#xD;
      of 10 mg PO BID until return to their clinical baseline (as defined by need for supplementary&#xD;
      oxygen), and will continue to be administered at 5 mg PO BID for a total duration of therapy&#xD;
      of 14 days; follow-up off tofacitinib will continue up to Day 90. We anticipate completion of&#xD;
      subject recruitment in 6 months.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Study terminated due to lack of enrollment reflecting the decrease in number of COVID&#xD;
    infections. There were no safety and/or efficacy concerns involved in the decision to stop&#xD;
    enrollment.&#xD;
  </why_stopped>
  <start_date type="Actual">October 14, 2020</start_date>
  <completion_date type="Actual">February 28, 2021</completion_date>
  <primary_completion_date type="Actual">February 28, 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>Triple (Participant, Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Disease Severity</measure>
    <time_frame>14 days</time_frame>
    <description>The primary objective of this study is to determine whether tofacitinib improves the clinical outcomes of patients with moderate SARS-CoV-2 infection as determined by the primary outcome measure: Proportion of subjects alive and not needing any form of mechanical ventilation, high flow oxygen, or ECMO by day 14.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Clinical improvement</measure>
    <time_frame>14 days</time_frame>
    <description>Clinical improvement as measured by NIAID 8-point ordinal scale (i.e., 1 = death and 8 = Not hospitalized, no limitations on activities) at day 14.&#xD;
The scale is as follows:&#xD;
Death&#xD;
Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO)&#xD;
Hospitalized, on non-invasive ventilation or high flow oxygen devices&#xD;
Hospitalized, requiring supplemental oxygen&#xD;
Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise)&#xD;
Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care&#xD;
Not hospitalized, limitation on activities and/or requiring home oxygen&#xD;
Not hospitalized, no limitations on activities.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinical improvement</measure>
    <time_frame>Up to 14 days</time_frame>
    <description>Clinical improvement as measured by NIAID 8-point ordinal scale (i.e., 1 = death and 8 = Not hospitalized, no limitations on activities) (days 3 through day 14):&#xD;
The scale is as follows:&#xD;
Death&#xD;
Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO)&#xD;
Hospitalized, on non-invasive ventilation or high flow oxygen devices&#xD;
Hospitalized, requiring supplemental oxygen&#xD;
Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise)&#xD;
Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care&#xD;
Not hospitalized, limitation on activities and/or requiring home oxygen&#xD;
Not hospitalized, no limitations on activities.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to recovery</measure>
    <time_frame>Up to 14 days</time_frame>
    <description>Time to recovery [ Time Frame: Day 1 through Day 14] (Day of recovery is defined as the first day on which the subject satisfies one of the following three categories from the ordinal scale:&#xD;
Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care&#xD;
Not hospitalized, limitation on activities and/or requiring home oxygen&#xD;
Not hospitalized, no limitations on activities)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to clinical improvement</measure>
    <time_frame>30 days</time_frame>
    <description>Time to clinical improvement (defined as a 2-point increase on the NIAID 8-point ordinal scale (i.e., 1 = death and 8 = Not hospitalized, no limitations on activities).&#xD;
The scale is as follows:&#xD;
Death&#xD;
Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO)&#xD;
Hospitalized, on non-invasive ventilation or high flow oxygen devices&#xD;
Hospitalized, requiring supplemental oxygen&#xD;
Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise)&#xD;
Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care&#xD;
Not hospitalized, limitation on activities and/or requiring home oxygen&#xD;
Not hospitalized, no limitations on activities.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinical status</measure>
    <time_frame>30 Days</time_frame>
    <description>Clinical status on the NIAID 8-point ordinal scale at day 30&#xD;
The scale is as follows:&#xD;
Death&#xD;
Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO)&#xD;
Hospitalized, on non-invasive ventilation or high flow oxygen devices&#xD;
Hospitalized, requiring supplemental oxygen&#xD;
Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise)&#xD;
Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care&#xD;
Not hospitalized, limitation on activities and/or requiring home oxygen&#xD;
Not hospitalized, no limitations on activities.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinical status</measure>
    <time_frame>60 Days</time_frame>
    <description>Clinical status on the NIAID 8-point ordinal scale at day 60&#xD;
The scale is as follows:&#xD;
Death&#xD;
Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO)&#xD;
Hospitalized, on non-invasive ventilation or high flow oxygen devices&#xD;
Hospitalized, requiring supplemental oxygen&#xD;
Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise)&#xD;
Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care&#xD;
Not hospitalized, limitation on activities and/or requiring home oxygen&#xD;
Not hospitalized, no limitations on activities.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinical status</measure>
    <time_frame>90 Days</time_frame>
    <description>Clinical status on the NIAID 8-point ordinal scale at day 90&#xD;
The scale is as follows:&#xD;
Death&#xD;
Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO)&#xD;
Hospitalized, on non-invasive ventilation or high flow oxygen devices&#xD;
Hospitalized, requiring supplemental oxygen&#xD;
Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise)&#xD;
Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care&#xD;
Not hospitalized, limitation on activities and/or requiring home oxygen&#xD;
Not hospitalized, no limitations on activities.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mortality</measure>
    <time_frame>30 Days</time_frame>
    <description>Mortality rate at day 30</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mortality</measure>
    <time_frame>60 Days</time_frame>
    <description>Mortality rate at day 60</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mortality</measure>
    <time_frame>90 Days</time_frame>
    <description>Mortality rate at day 90</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mechanical Ventilatory Support</measure>
    <time_frame>Up to 14 Days</time_frame>
    <description>Proportion of patients requiring mechanical ventilatory support.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mechanical Ventilatory Support Duration</measure>
    <time_frame>Up to 14 Days</time_frame>
    <description>Duration of invasive mechanical ventilation (days).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Freedom from mechanical ventilation</measure>
    <time_frame>Up to 14 Days</time_frame>
    <description>Invasive mechanical ventilation free days.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adverse events</measure>
    <time_frame>Up to 14 days</time_frame>
    <description>Adverse events reported for the first time or worsening of a pre-existing event after first dose of study drug/treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Additional intervention</measure>
    <time_frame>Up to 14 days</time_frame>
    <description>Did the patient receive an intervention with additional immunomodulatory agent (i.e. IL-6 targeting therapy)? (y/n)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Viral titer</measure>
    <time_frame>Up to 14 days</time_frame>
    <description>Change in SARS-CoV-2 viral titers during intervention.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">24</enrollment>
  <condition>COVID-19 Pneumonia</condition>
  <arm_group>
    <arm_group_label>Tofacitinib</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Tofacitinib will be administered in a dose of 10 mg PO BID until return to their clinical baseline (as defined by supplementary oxygen requirement), and then will continue to be administered at 5 mg PO BID for a total treatment duration of 14 days.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Matching placebo will be administered.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tofacitinib 10 mg</intervention_name>
    <description>Tofacitinib will be administered in a dose of 10 mg twice daily by mouth (PO BID) until return to their clinical baseline (as defined by supplementary oxygen requirement), and then will continue to be administered at 5 mg PO BID for a total treatment duration of 14 days.</description>
    <arm_group_label>Tofacitinib</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Matching placebo tablets will be administered.</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Participants who are willing and able to comply with all scheduled visits, treatment&#xD;
             plan, laboratory tests, lifestyle considerations, and other study procedures.&#xD;
&#xD;
          2. Participants with laboratory-confirmed novel coronavirus (SARS-CoV-2) infection as&#xD;
             determined by polymerase chain reaction (PCR) or other commercially available or&#xD;
             public health assay prior to Day 1.&#xD;
&#xD;
          3. Participants with evidence of pneumonia assessed by radiographic imaging (chest x ray&#xD;
             or chest CT scan) AND Requiring ≥ 3L O2 OR ≥ 2L O2 and hsCRP &gt; 70 mg/L&#xD;
&#xD;
          4. Participants who are hospitalized and receiving supportive care for COVID-19.&#xD;
&#xD;
          5. Participant (or legally authorized representative/surrogate) capable of giving signed&#xD;
             informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Medical Conditions:&#xD;
&#xD;
          1. Require mechanical ventilation or ECMO on Day 1 at the time of randomization.&#xD;
&#xD;
          2. Have current, or history of, venous thromboembolism (deep vein thrombosis or pulmonary&#xD;
             embolism).&#xD;
&#xD;
          3. Have a personal or first-degree family history of blood clotting disorders.&#xD;
&#xD;
          4. Participants who are immunocompromised, with known immunodeficiencies, or taking&#xD;
             potent immunosuppressive agents (eg, azathioprine, cyclosporine).&#xD;
&#xD;
          5. Participants with any current malignancy or lymphoproliferative disorders that&#xD;
             requires active treatment&#xD;
&#xD;
          6. Females of child bearing potential who are pregnant or breastfeeding&#xD;
&#xD;
          7. Other medical or psychiatric condition including recent (within the past year) or&#xD;
             active suicidal ideation/behavior or laboratory abnormality that may increase the risk&#xD;
             associated with study participation or, in the investigator's judgment, make the&#xD;
             participant inappropriate for the study.&#xD;
&#xD;
          8. Anticipated survival &lt; 72 hours as assessed by the Investigator.&#xD;
&#xD;
        Infection History:&#xD;
&#xD;
        • Suspected or known active systemic bacterial, fungal, or viral infections (with the&#xD;
        exception of COVID-19) including but not limited to:&#xD;
&#xD;
          -  Secondary bacterial pneumonia;&#xD;
&#xD;
          -  Active herpes zoster infection;&#xD;
&#xD;
          -  Known active tuberculosis or history of inadequately treated tuberculosis;&#xD;
&#xD;
          -  Known HBV, HCV, or HIV.&#xD;
&#xD;
        Prior/Concomitant Therapy:&#xD;
&#xD;
        Have received any of the following treatment regimens specified in the timeframes outlined&#xD;
        below:&#xD;
&#xD;
        Within 4 weeks prior to the first dose of study intervention:&#xD;
&#xD;
          -  Prior treatment with any JAK inhibitors, potent immunosuppressants, or any biologic&#xD;
             agents including IL-6 inhibitors (eg, tocilizumab) or IL-1 inhibitors (eg, anakinra);&#xD;
&#xD;
          -  Prior treatment with any potent cytochrome P450 inducer, such as rifampin, within the&#xD;
             past 28 days or 5 half-lives, whichever is longer.&#xD;
&#xD;
        Within 48 hours prior to the first dose of study intervention:&#xD;
&#xD;
        o Treatment with herbal supplements.&#xD;
&#xD;
        Received &gt;/= 20 mg/day of prednisone or equivalent for &gt;/=14 consecutive days in the 4&#xD;
        weeks prior to screening.&#xD;
&#xD;
        Diagnostic Assessments:&#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 laboratory tests at screening,&#xD;
             confirmed by a single repeat, if deemed necessary:&#xD;
&#xD;
          -  WBC &lt;1000/mm3&#xD;
&#xD;
          -  Absolute lymphocyte count &lt;500 cells/mm3;&#xD;
&#xD;
          -  Absolute neutrophil count &lt;1000 cells/mm3.&#xD;
&#xD;
          -  Alanine transaminase/aspartate transaminase (ALT/AST) &gt; 5 times the upper limit of&#xD;
             normal;&#xD;
&#xD;
          -  Estimated glomerular filtration rate (eGFR) &lt; 40 mL/min/1.73 m2);&#xD;
&#xD;
        Other Exclusions:&#xD;
&#xD;
          -  Known allergy to tofacitinib.&#xD;
&#xD;
          -  Investigator site staff or Pfizer employees directly involved in the conduct of the&#xD;
             study, site staff otherwise supervised by the investigator, and their respective&#xD;
             family members.&#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>Hyung Chun, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Yale School of Medicine</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Yale New Haven Health System</name>
      <address>
        <city>New Haven</city>
        <state>Connecticut</state>
        <zip>06511</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2022</verification_date>
  <study_first_submitted>June 2, 2020</study_first_submitted>
  <study_first_submitted_qc>June 2, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 4, 2020</study_first_posted>
  <disposition_first_submitted>December 29, 2021</disposition_first_submitted>
  <disposition_first_submitted_qc>December 29, 2021</disposition_first_submitted_qc>
  <disposition_first_posted type="Actual">January 3, 2022</disposition_first_posted>
  <last_update_submitted>August 26, 2022</last_update_submitted>
  <last_update_submitted_qc>August 26, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">August 31, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Yale University</investigator_affiliation>
    <investigator_full_name>Hyung Chun</investigator_full_name>
    <investigator_title>Associate Professor of Internal Medicine</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>COVID-19</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Tofacitinib</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted, but a results disposition has been submitted           -->
</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/NCT04415151
org study id: 2000027848
nct id: NCT04415151
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
The purpose of this randomized, double blinded, placebo controlled study is to assess the
      efficacy and safety of tofacitinib in hospitalized adult (18-99 years old) patients with
      SARS-CoV-2 and pneumonia who require supplemental oxygen and have serologic markers of
      inflammation but do not need mechanical ventilation.
The purpose of this randomized, double blinded, placebo controlled Phase 2b study is to
      assess the efficacy and safety of tofacitinib in hospitalized adult (18-99 years old) male
      and female patients with SARS-CoV-2 and pneumonia who require supplemental oxygen and have
      serologic markers of inflammation but do not need mechanical ventilation (see Inclusion
      criteria). Sixty patients will be recruited to receive tofacitinib or placebo in addition to
      standard of care (SOC) in a 1:1 ratio.

      Subjects will be screened during hospitalization. Patients with confirmed SARS-CoV-2
      infection, and meeting all other Inclusion and Exclusion criteria, will be randomized to
      either treatment with tofacitinib or placebo in addition to SOC during hospitalization (dose
      adjusted, if required), with the exception of pre-specified immunomodulatory agents (as
      documented in the inclusion/exclusion criteria). Tofacitinib will be administered in a dose
      of 10 mg PO BID until return to their clinical baseline (as defined by need for supplementary
      oxygen), and will continue to be administered at 5 mg PO BID for a total duration of therapy
      of 14 days; follow-up off tofacitinib will continue up to Day 90. We anticipate completion of
      subject recruitment in 6 months.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
measure: Disease Severity
time frame: 14 days
description: The primary objective of this study is to determine whether tofacitinib improves the clinical outcomes of patients with moderate SARS-CoV-2 infection as determined by the primary outcome measure: Proportion of subjects alive and not needing any form of mechanical ventilation, high flow oxygen, or ECMO by day 14.
measure: Clinical improvement
time frame: 14 days
description: Clinical improvement as measured by NIAID 8-point ordinal scale (i.e., 1 = death and 8 = Not hospitalized, no limitations on activities) at day 14.
The scale is as follows:
Death
Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO)
Hospitalized, on non-invasive ventilation or high flow oxygen devices
Hospitalized, requiring supplemental oxygen
Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise)
Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care
Not hospitalized, limitation on activities and/or requiring home oxygen
Not hospitalized, no limitations on activities.
measure: Clinical improvement
time frame: Up to 14 days
description: Clinical improvement as measured by NIAID 8-point ordinal scale (i.e., 1 = death and 8 = Not hospitalized, no limitations on activities) (days 3 through day 14):
The scale is as follows:
Death
Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO)
Hospitalized, on non-invasive ventilation or high flow oxygen devices
Hospitalized, requiring supplemental oxygen
Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise)
Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care
Not hospitalized, limitation on activities and/or requiring home oxygen
Not hospitalized, no limitations on activities.
measure: Time to recovery
time frame: Up to 14 days
description: Time to recovery [ Time Frame: Day 1 through Day 14] (Day of recovery is defined as the first day on which the subject satisfies one of the following three categories from the ordinal scale:
Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care
Not hospitalized, limitation on activities and/or requiring home oxygen
Not hospitalized, no limitations on activities)
measure: Time to clinical improvement
time frame: 30 days
description: Time to clinical improvement (defined as a 2-point increase on the NIAID 8-point ordinal scale (i.e., 1 = death and 8 = Not hospitalized, no limitations on activities).
The scale is as follows:
Death
Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO)
Hospitalized, on non-invasive ventilation or high flow oxygen devices
Hospitalized, requiring supplemental oxygen
Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise)
Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care
Not hospitalized, limitation on activities and/or requiring home oxygen
Not hospitalized, no limitations on activities.
measure: Clinical status
time frame: 30 Days
description: Clinical status on the NIAID 8-point ordinal scale at day 30
The scale is as follows:
Death
Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO)
Hospitalized, on non-invasive ventilation or high flow oxygen devices
Hospitalized, requiring supplemental oxygen
Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise)
Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care
Not hospitalized, limitation on activities and/or requiring home oxygen
Not hospitalized, no limitations on activities.
measure: Clinical status
time frame: 60 Days
description: Clinical status on the NIAID 8-point ordinal scale at day 60
The scale is as follows:
Death
Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO)
Hospitalized, on non-invasive ventilation or high flow oxygen devices
Hospitalized, requiring supplemental oxygen
Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise)
Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care
Not hospitalized, limitation on activities and/or requiring home oxygen
Not hospitalized, no limitations on activities.
measure: Clinical status
time frame: 90 Days
description: Clinical status on the NIAID 8-point ordinal scale at day 90
The scale is as follows:
Death
Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO)
Hospitalized, on non-invasive ventilation or high flow oxygen devices
Hospitalized, requiring supplemental oxygen
Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise)
Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care
Not hospitalized, limitation on activities and/or requiring home oxygen
Not hospitalized, no limitations on activities.
measure: Mortality
time frame: 30 Days
description: Mortality rate at day 30
measure: Mortality
time frame: 60 Days
description: Mortality rate at day 60
measure: Mortality
time frame: 90 Days
description: Mortality rate at day 90
measure: Mechanical Ventilatory Support
time frame: Up to 14 Days
description: Proportion of patients requiring mechanical ventilatory support.
measure: Mechanical Ventilatory Support Duration
time frame: Up to 14 Days
description: Duration of invasive mechanical ventilation (days).
measure: Freedom from mechanical ventilation
time frame: Up to 14 Days
description: Invasive mechanical ventilation free days.
measure: Adverse events
time frame: Up to 14 days
description: Adverse events reported for the first time or worsening of a pre-existing event after first dose of study drug/treatment.
measure: Additional intervention
time frame: Up to 14 days
description: Did the patient receive an intervention with additional immunomodulatory agent (i.e. IL-6 targeting therapy)? (y/n)
measure: Viral titer
time frame: Up to 14 days
description: Change in SARS-CoV-2 viral titers during intervention.
arm group label: Tofacitinib
arm group type: Experimental
description: Tofacitinib will be administered in a dose of 10 mg PO BID until return to their clinical baseline (as defined by supplementary oxygen requirement), and then will continue to be administered at 5 mg PO BID for a total treatment duration of 14 days.
arm group label: Placebo
arm group type: Placebo Comparator
description: Matching placebo will be administered.
intervention type: Drug
intervention name: Tofacitinib 10 mg
description: Tofacitinib will be administered in a dose of 10 mg twice daily by mouth (PO BID) until return to their clinical baseline (as defined by supplementary oxygen requirement), and then will continue to be administered at 5 mg PO BID for a total treatment duration of 14 days.
arm group label: Tofacitinib
intervention type: Drug
intervention name: Placebo
description: Matching placebo tablets will be administered.
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 99 Years
healthy volunteers: No
last name: Hyung Chun, MD
role: Principal Investigator
affiliation: Yale School of Medicine
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Yale University
investigator full name: Hyung Chun
investigator title: Associate Professor of Internal Medicine
mesh term: COVID-19
mesh term: Tofacitinib
sharing ipd: No