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Safety and Efficacy of Baricitinib for COVID-19

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04340232
Recruitment Status : Not yet recruiting
First Posted : April 9, 2020
Last Update Posted : August 25, 2020
Sponsor:
Information provided by (Responsible Party):
University of Colorado, Denver

Brief Summary:

This study plans to learn more about the effects of a medicine called baricitinib on the progression of COVID-19 (coronavirus disease of 2019), the medical condition caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Baricitinib is FDA-approved for the treatment of rheumatoid arthritis, an autoimmune condition. This study intends to define the impact of baricitinib on the severity and progression of COVID-19. This drug might to lower the hyperinflammation caused by the virus, which would prevent damage to the lungs and possibly other organs.

The study will recruit patients who have been diagnosed with COVID-19.

The goal is to recruit 80 patients.


Condition or disease Intervention/treatment Phase
COVID-19 Drug: Baricitinib Phase 2 Phase 3

Detailed Description:
This is an adaptive Phase 2/3 clinical trial, with a focus on the assessment of safety in the first 20 participants (Phase 2), followed by a much broader assessment of efficacy, while continuing to monitor safety, in an additional 60 participants (Phase 3, total participants across Phase 2/3 n=80). Both phases are single arm, open label, and occur at a single site at the University of Colorado Hospital (UCH). Data from participants in this study will be compared with data from other COVID-19 patients not receiving baricitinib. Study participants will receive 2 mg/day of baricitinib for 14 days and will be followed for up to 29 days.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 80 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: This is a single arm, open label, single site study. Data from participants in this study with data from other COVID-19 patients not receiving baricitinib.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Safety and Efficacy of Baricitinib for COVID-19
Estimated Study Start Date : November 2020
Estimated Primary Completion Date : August 2021
Estimated Study Completion Date : October 2021

Arm Intervention/treatment
Experimental: Baricitinib Arm
This study is an Adaptive Phase 2/3 trial designed to test the safety (Phase 2) and efficacy (Phase 2 and 3) of baricitinib to treat COVID-19. Phase 2 consists of a single-arm, open-label assignment of 20 participants receiving 2 mg baricitinib once daily for 14 days. Phase 3 consists of a single-arm, open-label assignment of 60 additional participants receiving baricitinib at the same dose. In both phases, participants will be monitored daily while hospitalized for 29 days, or until discharge, whichever occurs first. Participants who are discharged will be followed up with via phone on Day 15 and Day 29.
Drug: Baricitinib
Subjects will receive a 2 mg oral dose of baricitinib.




Primary Outcome Measures :
  1. Phase 2: Cumulative incidence of Grade 3 and 4 adverse events (AEs) [ Time Frame: Day 0 (screening) through Day 29 ]
    Description: Grade 3 AEs are defined as events that interrupt usual activities of daily living, or significantly affects clinical status, or may require intensive therapeutic intervention. Severe events are usually incapacitating. Grade 4 AEs are defined as events that are potentially life threatening. AEs will be collected and graded daily and cumulative incidence will be reported.

  2. Phase 2: Cumulative incidence of serious adverse events (SAEs) [ Time Frame: Day 0 (screening) through Day 29 ]
    Description: An SAE is defined as an AE that is life-threatening or results in death, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, or a congenital anomaly/birth defect. SAEs will be collected and graded daily and cumulative incidence will be reported.

  3. Phase 2: Changes in white blood cell count (CBC) through Day 15 [ Time Frame: Day 1 to Day 15 ]
    Safety assessment via standard blood chemistry and metabolic panels will be performed daily as recommended by participant's physician as standard of care (SOC). Mean changes from baseline to Day 15 will be reported.

  4. Phase 2: Changes in hemoglobin through Day 15 [ Time Frame: Day 1 to Day 15 ]
  5. Phase 2: Changes in platelets through Day 15 [ Time Frame: Day 1 to Day 15 ]
  6. Phase 2: Changes in creatinine through Day 15 [ Time Frame: Day 1 to Day 15 ]
  7. Phase 2: Changes in glucose through Day 15 [ Time Frame: Day 1 to Day 15 ]
  8. Phase 2: Changes in prothrombin time (PT) through Day 15 [ Time Frame: Day 1 to Day 15 ]
  9. Phase 2: Changes in total bilirubin through Day 15 [ Time Frame: Day 1 to Day 15 ]
  10. Phase 2: Changes in ALT through Day 15 [ Time Frame: Day 1 to Day 15 ]
  11. Phase 2: Changes in AST through Day 15 [ Time Frame: Day 1 to Day 15 ]
  12. Phase 2: Changes in white blood cell count (CBC) through End of Study (EOS) [ Time Frame: Day through Day 29 or hospital discharge, whichever is first ]
    Safety assessment via standard blood chemistry and metabolic panels will be performed daily as recommended by participant's physician as SOC. Mean changes from baseline to EOS will be reported.

  13. Phase 2: Changes in hemoglobin through End of Study (EOS) [ Time Frame: Day 1 through Day 29 or hospital discharge, whichever is first ]
  14. Phase 2: Changes in platelets through End of Study (EOS) [ Time Frame: Day 1 through Day 29 or hospital discharge, whichever is first ]
  15. Phase 2: Changes in creatinine through End of Study (EOS) [ Time Frame: Day 1 through Day 29 or hospital discharge, whichever is first ]
  16. Phase 2: Changes in glucose through End of Study (EOS) [ Time Frame: Day 1 through Day 29 or hospital discharge, whichever is first ]
  17. Phase 2: Changes in prothrombin time (PT) though End of Study (EOS) [ Time Frame: Day 1 through Day 29 or hospital discharge, whichever is first ]
  18. Phase 2: Changes in total bilirubin through End of Study (EOS) [ Time Frame: Day 1 through Day 29 or hospital discharge, whichever is first ]
  19. Phase 2: Changes in ALT through End of Study (EOS) [ Time Frame: Day 1 through Day 29 or hospital discharge, whichever is first ]
  20. Phase 2: Changes in AST through End of Study (EOS) [ Time Frame: Day 1 through Day 29 or hospital discharge, whichever is first ]
  21. Phase 3: Percentage of patients reporting each severity on an 8-point ordinal scale at Day 15 [ Time Frame: Day 15 ]

    The 8-point ordinal scale described below, where a lower score indicates a worse outcome, will be performed daily or as recommended by participant's physician as SOC. The percent of participants scored at each severity will be reported on Day 15.

    The 8-point ordinal 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


Secondary Outcome Measures :
  1. Phase 2: Change in the 8-point ordinal scale [ Time Frame: Day 1 to Day 29 ]
    The 8-point ordinal scale described above will be assessed using MR data collected as SOC or follow-up phone call on Day 29, where a lower score indicates a worse outcome. Mean changes from baseline to Day 29 will be reported.

  2. Phase 2: Change in National Early Warning Score (NEWS) [ Time Frame: Day 1 through Day 29 or hospital discharge, whichever is first ]
    The NEWS is a cumulative score (range: 0 - 20) based on 7 clinical parameters as depicted below and discriminates patients at risk of poor outcomes. A higher score indicates a higher risk. The assessment will be calculated daily using MR data collected as SOC. Mean changes from baseline to End of Study (Day 29 or discharge) will be reported.

  3. Phase 3: Change in the 8-point ordinal scale [ Time Frame: Day 1 to Day 29 ]
    The 8-point ordinal scale described above will be assessed daily using MR data collected as SOC or follow-up phone call, where a lower score indicates a worse outcome. Mean changes from baseline to Day 29 will be reported.

  4. Phase 3: Change in National Early Warning Score (NEWS) [ Time Frame: Day 1 to Day 29 or hospital discharge, whichever is first ]
    The NEWS is a cumulative score (range: 0 - 20) based on 7 clinical parameters as depicted below and discriminates patients at risk of poor outcomes. A higher score indicates a higher risk. The assessment will be calculated daily using MR data collected as SOC. Mean changes from baseline to End of Study (Day 29 or discharge) will be reported.

  5. Phase 3: Time to an improvement of one category using the 8-point ordinal scale [ Time Frame: Day 1 to Day 29 or hospital discharge, whichever is first ]
    The 8-point ordinal scale described above will be assessed daily using MR data collected as SOC, where a lower score indicates a worse outcome. Mean time in days to a one-category improvement will be reported.

  6. Phase 3: Time to an improvement of two categories using the 8-point ordinal scale [ Time Frame: Day 1 to Day 29 or hospital discharge, whichever is first ]
    The 8-point ordinal scale described above will be assessed daily, where a lower score indicates a worse outcome. Mean time in days to a two-category improvement will be reported.

  7. Phase 3: Time to discharge or to a NEWS ≤2 and maintained for 24 hours, whichever occurs first [ Time Frame: Day 1 through Day 29 or hospital discharge, whichever is first ]
    The NEWS will be calculated daily. Mean time in days to achieve a score of ≤2 and maintain this score for at least 24 hours OR to be discharged from the hospital, whichever occurs first, will be reported. A higher score indicates a higher risk. End of study is defined as day 29 or discharge, whichever occurs first.

  8. Phase 3: Cumulative incidence of Grade 3 and 4 adverse events (AEs) [ Time Frame: Day 0 (screening) through Day 29 ]
    Grade 3 AEs are defined as events that interrupt usual activities of daily living, or significantly affects clinical status, or may require intensive therapeutic intervention. Severe events are usually incapacitating. Grade 4 AEs are defined as events that are potentially life threatening. AEs will be collected and graded daily and cumulative incidence will be reported.

  9. Phase 3: Cumulative incidence of serious adverse events (SAEs) [ Time Frame: Day 0 (screening) through Day 29 ]
    An SAE is defined as an AE that is life-threatening or results in death, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, or a congenital anomaly/birth defect. SAEs will be collected and graded daily and cumulative incidence will be reported.

  10. Phase 3: Duration of hospitalization [ Time Frame: Day 1 through Day 29 or hospital discharge, whichever is first ]
    The mean duration of hospitalization will be reported, measured in days.

  11. Phase 3: Duration of new oxygen use [ Time Frame: Day 1 through Day 29 or hospital discharge, whichever is first ]
    The mean duration of new oxygen use will be reported, measured in days.

  12. Phase 3: Duration of new ventilator or ECMO use [ Time Frame: Day 1 to Day 29 or hospital discharge, whichever is first ]
    The mean duration of new ventilator or ECMO use will be reported, measured in days.

  13. Phase 3: Incidence of discontinuation or temporary suspension of drug for any reason [ Time Frame: Day 1 through Day 29 or hospital discharge, whichever is first ]
    The incidence of interruption of baricitinib treatment, along with mean duration and reasons for the interruptions, will be reported.

  14. Phase 3: Incidence of new oxygen use [ Time Frame: Day 1 to Day 29 or hospital discharge, whichever is first ]
    The incidence of new oxygen use will be reported.

  15. Phase 3: Incidence of new ventilator use [ Time Frame: Day 1 to Day 29 or hospital discharge, whichever is first ]
    The incidence of new ventilator or ECMO use will be reported.

  16. Phase 3: Number of oxygen free days [ Time Frame: Day 1 through Day 29 or hospital discharge, whichever is first ]
    The mean number of days patients are free from use of oxygen will be reported.

  17. Phase 3: Number of ventilator or ECMO free days [ Time Frame: Day 1 through Day 29 or hospital discharge, whichever is first ]
    The mean number of days patients are free from use of a ventilator or ECMO will be reported.

  18. Phase 3: 14 day mortality rate [ Time Frame: Day 1 through Day 15 ]
    The rate of participant death from Day 1 through Day 15 will be reported.

  19. Phase 3: 28 day mortality rate [ Time Frame: Day 1 through Day 29 ]
    The rate of participant death from Day 1 through Day 29 will be reported.

  20. Phase 3: Changes in white blood cell count (CBC) through Day 15 [ Time Frame: Day 1 to Day 15 ]
  21. Phase 3: Changes in hemoglobin through Day 15 [ Time Frame: Day 1 to Day 15 ]
  22. Phase 3: Changes in platelets through Day 15 [ Time Frame: Day 1 to Day 15 ]
  23. Phase 3: Changes in creatinine through Day 15 [ Time Frame: Day 1 to Day 15 ]
  24. Phase 3: Changes in glucose through Day 15 [ Time Frame: Day 1 to Day 15 ]
  25. Phase 3: Changes in prothrombin time (PT) through Day 15 [ Time Frame: Day 1 to Day 15 ]
  26. Phase 3: Changes in total bilirubin through Day 15 [ Time Frame: Day 1 to Day 15 ]
  27. Phase 3: Changes in ALT through Day 15 [ Time Frame: Day 1 to Day 15 ]
  28. Phase 3: Changes in AST through Day 15 [ Time Frame: Day 1 to Day 15 ]
  29. Phase 3: Changes in white blood cell count (CBC) through End of Study (EOS) [ Time Frame: Day 1 through Day 29 or hospital discharge, whichever is first ]
    Safety assessment via standard blood chemistry and metabolic panels will be performed daily as recommended by participant's physician as SOC. Mean changes from baseline to EOS will be reported.

  30. Phase 3: Changes in hemoglobin through End of Study (EOS) [ Time Frame: Day 1 through Day 29 or hospital discharge, whichever is first ]
  31. Phase 3: Changes in platelets through End of Study (EOS) [ Time Frame: Day 1 through Day 29 or hospital discharge, whichever is first ]
  32. Phase 3: Changes in creatinine through End of Study (EOS) [ Time Frame: Day 1 through Day 29 or hospital discharge, whichever is first ]
  33. Phase 3: Changes in glucose through End of Study (EOS) [ Time Frame: Day 1 through Day 29 or hospital discharge, whichever is first ]
  34. Phase 3: Changes in prothrombin time (PT) though End of Study (EOS) [ Time Frame: Day 1 through Day 29 or hospital discharge, whichever is first ]
  35. Phase 3: Changes in total bilirubin through End of Study (EOS) [ Time Frame: Day 1 through Day 29 or hospital discharge, whichever is first ]
  36. Phase 3: Changes in ALT through End of Study (EOS) [ Time Frame: Day 1 through Day 29 or hospital discharge, whichever is first ]
  37. Phase 3: Changes in AST through End of Study (EOS) [ Time Frame: Day 1 through Day 29 or hospital discharge, whichever is first ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 89 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male or female aged 18 - 89 years at time of enrollment
  • Hospitalized (or documented plan to hospitalize if patient is in the emergency department) with symptoms suggestive of COVID-19
  • Illness of any duration that meets each of the following:

    1. Evidence of pneumonia, including radiographic infiltrates by imaging (chest x-ray, CT scan, etc.) or clinical assessment (rales/crackles on exam)
    2. Requires supportive care, including non-invasive supplemental oxygen
  • Laboratory-confirmed SARS-CoV-2 infection as determined by PCR or other commercial or public health assay within 7 days of enrollment
  • Understands and agrees to comply with planned study procedures
  • Provides informed consent signed by study patient or legally acceptable representative

Exclusion Criteria:

  • Absolute lymphocyte count is less than 500 cells/mm
  • Absolute neutrophil count is less than 1000 cells/mm
  • Hemoglobin level is less than 8 g/dL
  • Estimated GFR is less than 60 mL/min/1.73 m2
  • ALT or AST is over 5 times the upper limit of normal
  • Treatment with other JAK inhibitors, OAT3 inhibitors, biologic disease-modifying anti-rheumatic drugs (DMARDs), anti-IL-6 or anti-IL-6R antibodies, or potent immunosuppressants such as azathioprine. and cyclosporine concurrently or within the past 5 days. Note: recent or concurrent treatment with hydroxychloroquine or chloroquine is allowable, as these are 'non-biologic' DMARDs with potential antiviral activity.
  • History of HIV infection and on active immunosuppressant therapy
  • Current hematological or solid organ malignancy and on active immunosuppressant therapy
  • Active tuberculosis (TB) infection or known or suspected systemic bacterial or fungal infection
  • Pregnancy or breast feeding
  • Known allergy to baricitinib
  • In the opinion of the investigator, they are unlikely to survive for >48 hours from screening
  • Any physical examination findings and/or history of any illness that, in the opinion of the investigator, might confound the results of the study or pose an additional risk to the patient by their participation in the study

Additional Exclusion Criteria for Phase 2 only:

• Invasive oxygen supplementation, including mechanical ventilation and extracorporeal membrane oxygenation (ECMO)


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04340232


Contacts
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Contact: Angela Rachubinski, PhD (720) 507-9107 bari-covid19@cuanschutz.edu
Contact: Joaquin Espinosa, PhD (720) 507-9107 bari-covid19@cuanschutz.edu

Locations
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United States, Colorado
University of Colorado, Denver
Aurora, Colorado, United States, 80045
Sponsors and Collaborators
University of Colorado, Denver
Investigators
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Principal Investigator: Joaquin Espinosa, PhD University of Colorado, Denver
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Responsible Party: University of Colorado, Denver
ClinicalTrials.gov Identifier: NCT04340232    
Other Study ID Numbers: 20-0738
First Posted: April 9, 2020    Key Record Dates
Last Update Posted: August 25, 2020
Last Verified: August 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: De-identified individual participant data will be made available for all primary outcome measures.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Clinical Study Report (CSR)
Analytic Code
Time Frame: Data will be made available upon publication in a peer-reviewed journal.
Access Criteria: Data access requests will be reviewed by the sponsor-investigator and collaborators.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by University of Colorado, Denver:
JAK inhibitor
SARS-CoV-2
inflammation
cytokine release syndrome