Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Safety and Efficacy of Ruxolitinib 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: NCT04348071
Recruitment Status : Not yet recruiting
First Posted : April 15, 2020
Last Update Posted : May 6, 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 ruxolitinib 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). Ruxolitinib is FDA-approved for the treatment of myelofibrosis, polycythemia vera, and graft-versus-host disease. This study intends to define the impact of ruxolitinib 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: Ruxolitinib 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 ruxolitinib. Study participants will receive 10 mg twice daily of ruxolitinib for 14 days and will be followed for up to 29 days.

Layout table for study information
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 ruxolitinib.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Safety and Efficacy of Ruxolitinib for COVID-19
Estimated Study Start Date : June 2020
Estimated Primary Completion Date : August 2020
Estimated Study Completion Date : October 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Ruxolitinib
This study is an Adaptive Phase 2/3 trial designed to test the safety (Phase 2) and efficacy (Phase 2 and 3) of ruxolitinib to treat COVID-19. Phase 2 consists of a single-arm, open-label assignment of 20 participants receiving 10 mg ruxolitinib twice daily for 14 days. Phase 3 consists of a single-arm, open-label assignment of 60 additional participants receiving ruxolitinib 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: Ruxolitinib
Participants will receive 10 mg ruxolitinib twice daily.
Other Names:
  • Jakafi
  • Jakavi




Primary Outcome Measures :
  1. Phase 2: 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.

  2. Phase 2: 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.

  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 ]
  2. Phase 2: Change in National Early Warning Score (NEWS) [ Time Frame: Day 1 through Day 29 or hospital discharge, whichever is first ]
  3. Phase 3: Change in the 8-point ordinal scale [ Time Frame: Day 1 to Day 29 ]
  4. Phase 3: Change in National Early Warning Score (NEWS) [ Time Frame: Day 1 to Day 29 or hospital discharge, whichever is first ]
  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 ]
  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 ]
  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 ]
  8. Phase 3: Cumulative incidence of Grade 3 and 4 adverse events (AEs) [ Time Frame: Day 0 (screening) through Day 29 ]
  9. Phase 3: Cumulative incidence of serious adverse events (SAEs) [ Time Frame: Day 0 (screening) through Day 29 ]
  10. Phase 3: Duration of hospitalization [ Time Frame: Day 1 through Day 29 or hospital discharge, whichever is first ]
  11. Phase 3: Duration of new oxygen use [ Time Frame: Day 1 through Day 29 or hospital discharge, whichever is first ]
  12. Phase 3: Duration of new ventilator or ECMO use [ Time Frame: Day 1 to Day 29 or hospital discharge, whichever is first ]
  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 ]
  14. Phase 3: Incidence of new oxygen use [ Time Frame: Day 1 to Day 29 or hospital discharge, whichever is first ]
  15. Phase 3: Incidence of new ventilator use [ Time Frame: Day 1 to Day 29 or hospital discharge, whichever is first ]
  16. Phase 3: Number of oxygen free days [ Time Frame: Day 1 through Day 29 or hospital discharge, whichever is first ]
  17. Phase 3: Number of ventilator or ECMO free days [ Time Frame: Day 1 through Day 29 or hospital discharge, whichever is first ]
  18. Phase 3: 14 day mortality rate [ Time Frame: Day 1 through Day 15 ]
  19. Phase 3: 28 day mortality rate [ Time Frame: Day 1 through Day 29 ]
  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.


Layout table for eligibility information
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
  • lllness of any duration that meets each of the following:
  • Evidence of pneumonia, including radiographic infiltrates by imaging (chest x-ray, CT scan, etc.) or clinical assessment (rales/crackles on exam)
  • 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 platelet counts are less than 75 x 10^9/L
  • Absolute neutrophil count is less than 0.5 x 10^9/L
  • Hemoglobin is less than 8 g/dL
  • Severe renal impairment defined by serum creatinine greater than 2 mg/dL or CrCl less than 30 mL/min
  • Treatment with other JAK inhibitors, strong CYP3A4 inhibitors, biologic disease-modifying anti-rheumatic drugs (DMARDs, including 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 ruxolitinib
  • 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): NCT04348071


Contacts
Layout table for location contacts
Contact: Angela Rachubinski, PhD ‪(720) 515-2868 rux-covid19@cuanschutz.edu
Contact: Joaquin M Espinosa, PhD ‪(720) 515-2868

Sponsors and Collaborators
University of Colorado, Denver
Investigators
Layout table for investigator information
Principal Investigator: Joaquin Espinosa, PhD University of Colorado, Denver
Layout table for additonal information
Responsible Party: University of Colorado, Denver
ClinicalTrials.gov Identifier: NCT04348071    
Other Study ID Numbers: 20-0869
First Posted: April 15, 2020    Key Record Dates
Last Update Posted: May 6, 2020
Last Verified: May 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.

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by University of Colorado, Denver:
JAK inhibitor
SARS-CoV-2
inflammation
cytokine release syndrome