Back to resultsSafety and Efficacy of Ruxolitinib for COVID-19
Primary Purpose
COVID-19
Status
Withdrawn
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Ruxolitinib
Sponsored by
About this trial
This is an interventional treatment trial for COVID-19 focused on measuring JAK inhibitor, SARS-CoV-2, inflammation, cytokine release syndrome
Eligibility 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)
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Ruxolitinib
Arm Description
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.
Outcomes
Primary Outcome Measures
Phase 2: Cumulative incidence of Grade 3 and 4 adverse events (AEs)
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.
Phase 2: Cumulative incidence of serious adverse events (SAEs)
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.
Phase 2: Changes in white blood cell count (CBC) through 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.
Phase 2: Changes in hemoglobin through Day 15
Phase 2: Changes in platelets through Day 15
Phase 2: Changes in creatinine through Day 15
Phase 2: Changes in glucose through Day 15
Phase 2: Changes in prothrombin time (PT) through Day 15
Phase 2: Changes in total bilirubin through Day 15
Phase 2: Changes in ALT through Day 15
Phase 2: Changes in AST through Day 15
Phase 2: Changes in white blood cell count (CBC) through End of Study (EOS)
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.
Phase 2: Changes in hemoglobin through End of Study (EOS)
Phase 2: Changes in platelets through End of Study (EOS)
Phase 2: Changes in creatinine through End of Study (EOS)
Phase 2: Changes in glucose through End of Study (EOS)
Phase 2: Changes in prothrombin time (PT) though End of Study (EOS)
Phase 2: Changes in total bilirubin through End of Study (EOS)
Phase 2: Changes in ALT through End of Study (EOS)
Phase 2: Changes in AST through End of Study (EOS)
Phase 3: Percentage of patients reporting each severity on an 8-point ordinal scale at 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:
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
Secondary Outcome Measures
Phase 2: Change in the 8-point ordinal scale
Phase 2: Change in National Early Warning Score (NEWS)
Phase 3: Change in the 8-point ordinal scale
Phase 3: Change in National Early Warning Score (NEWS)
Phase 3: Time to an improvement of one category using the 8-point ordinal scale
Phase 3: Time to an improvement of two categories using the 8-point ordinal scale
Phase 3: Time to discharge or to a NEWS ≤2 and maintained for 24 hours, whichever occurs first
Phase 3: Cumulative incidence of Grade 3 and 4 adverse events (AEs)
Phase 3: Cumulative incidence of serious adverse events (SAEs)
Phase 3: Duration of hospitalization
Phase 3: Duration of new oxygen use
Phase 3: Duration of new ventilator or ECMO use
Phase 3: Incidence of discontinuation or temporary suspension of drug for any reason
Phase 3: Incidence of new oxygen use
Phase 3: Incidence of new ventilator use
Phase 3: Number of oxygen free days
Phase 3: Number of ventilator or ECMO free days
Phase 3: 14 day mortality rate
Phase 3: 28 day mortality rate
Phase 3: Changes in white blood cell count (CBC) through Day 15
Phase 3: Changes in hemoglobin through Day 15
Phase 3: Changes in platelets through Day 15
Phase 3: Changes in creatinine through Day 15
Phase 3: Changes in glucose through Day 15
Phase 3: Changes in prothrombin time (PT) through Day 15
Phase 3: Changes in total bilirubin through Day 15
Phase 3: Changes in ALT through Day 15
Phase 3: Changes in AST through Day 15
Phase 3: Changes in white blood cell count (CBC) through End of Study (EOS)
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.
Phase 3: Changes in hemoglobin through End of Study (EOS)
Phase 3: Changes in platelets through End of Study (EOS)
Phase 3: Changes in creatinine through End of Study (EOS)
Phase 3: Changes in glucose through End of Study (EOS)
Phase 3: Changes in prothrombin time (PT) though End of Study (EOS)
Phase 3: Changes in total bilirubin through End of Study (EOS)
Phase 3: Changes in ALT through End of Study (EOS)
Phase 3: Changes in AST through End of Study (EOS)
Full Information
NCT ID
NCT04348071
First Posted
April 13, 2020
Last Updated
March 3, 2021
Sponsor
University of Colorado, Denver
1. Study Identification
Unique Protocol Identification Number
NCT04348071
Brief Title
Safety and Efficacy of Ruxolitinib for COVID-19
Official Title
Safety and Efficacy of Ruxolitinib for COVID-19
Study Type
Interventional
2. Study Status
Record Verification Date
March 2021
Overall Recruitment Status
Withdrawn
Why Stopped
Could not make FDA required changes
Study Start Date
July 2021 (Anticipated)
Primary Completion Date
August 2021 (Anticipated)
Study Completion Date
October 2021 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Colorado, Denver
4. Oversight
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
5. Study Description
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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
COVID-19
Keywords
JAK inhibitor, SARS-CoV-2, inflammation, cytokine release syndrome
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Single Group Assignment
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)
Allocation
N/A
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Ruxolitinib
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Ruxolitinib
Other Intervention Name(s)
Jakafi, Jakavi
Intervention Description
Participants will receive 10 mg ruxolitinib twice daily.
Primary Outcome Measure Information:
Title
Phase 2: Cumulative incidence of Grade 3 and 4 adverse events (AEs)
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.
Time Frame
Day 0 (screening) through Day 29
Title
Phase 2: Cumulative incidence of serious adverse events (SAEs)
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.
Time Frame
Day 0 (screening) through Day 29
Title
Phase 2: Changes in white blood cell count (CBC) through Day 15
Description
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.
Time Frame
Day 1 to Day 15
Title
Phase 2: Changes in hemoglobin through Day 15
Time Frame
Day 1 to Day 15
Title
Phase 2: Changes in platelets through Day 15
Time Frame
Day 1 to Day 15
Title
Phase 2: Changes in creatinine through Day 15
Time Frame
Day 1 to Day 15
Title
Phase 2: Changes in glucose through Day 15
Time Frame
Day 1 to Day 15
Title
Phase 2: Changes in prothrombin time (PT) through Day 15
Time Frame
Day 1 to Day 15
Title
Phase 2: Changes in total bilirubin through Day 15
Time Frame
Day 1 to Day 15
Title
Phase 2: Changes in ALT through Day 15
Time Frame
Day 1 to Day 15
Title
Phase 2: Changes in AST through Day 15
Time Frame
Day 1 to Day 15
Title
Phase 2: Changes in white blood cell count (CBC) through End of Study (EOS)
Description
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.
Time Frame
Day through Day 29 or hospital discharge, whichever is first
Title
Phase 2: Changes in hemoglobin through End of Study (EOS)
Time Frame
Day 1 through Day 29 or hospital discharge, whichever is first
Title
Phase 2: Changes in platelets through End of Study (EOS)
Time Frame
Day 1 through Day 29 or hospital discharge, whichever is first
Title
Phase 2: Changes in creatinine through End of Study (EOS)
Time Frame
Day 1 through Day 29 or hospital discharge, whichever is first
Title
Phase 2: Changes in glucose through End of Study (EOS)
Time Frame
Day 1 through Day 29 or hospital discharge, whichever is first
Title
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
Title
Phase 2: Changes in total bilirubin through End of Study (EOS)
Time Frame
Day 1 through Day 29 or hospital discharge, whichever is first
Title
Phase 2: Changes in ALT through End of Study (EOS)
Time Frame
Day 1 through Day 29 or hospital discharge, whichever is first
Title
Phase 2: Changes in AST through End of Study (EOS)
Time Frame
Day 1 through Day 29 or hospital discharge, whichever is first
Title
Phase 3: Percentage of patients reporting each severity on an 8-point ordinal scale at Day 15
Description
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:
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
Time Frame
Day 15
Secondary Outcome Measure Information:
Title
Phase 2: Change in the 8-point ordinal scale
Time Frame
Day 1 to Day 29
Title
Phase 2: Change in National Early Warning Score (NEWS)
Time Frame
Day 1 through Day 29 or hospital discharge, whichever is first
Title
Phase 3: Change in the 8-point ordinal scale
Time Frame
Day 1 to Day 29
Title
Phase 3: Change in National Early Warning Score (NEWS)
Time Frame
Day 1 to Day 29 or hospital discharge, whichever is first
Title
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
Title
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
Title
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
Title
Phase 3: Cumulative incidence of Grade 3 and 4 adverse events (AEs)
Time Frame
Day 0 (screening) through Day 29
Title
Phase 3: Cumulative incidence of serious adverse events (SAEs)
Time Frame
Day 0 (screening) through Day 29
Title
Phase 3: Duration of hospitalization
Time Frame
Day 1 through Day 29 or hospital discharge, whichever is first
Title
Phase 3: Duration of new oxygen use
Time Frame
Day 1 through Day 29 or hospital discharge, whichever is first
Title
Phase 3: Duration of new ventilator or ECMO use
Time Frame
Day 1 to Day 29 or hospital discharge, whichever is first
Title
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
Title
Phase 3: Incidence of new oxygen use
Time Frame
Day 1 to Day 29 or hospital discharge, whichever is first
Title
Phase 3: Incidence of new ventilator use
Time Frame
Day 1 to Day 29 or hospital discharge, whichever is first
Title
Phase 3: Number of oxygen free days
Time Frame
Day 1 through Day 29 or hospital discharge, whichever is first
Title
Phase 3: Number of ventilator or ECMO free days
Time Frame
Day 1 through Day 29 or hospital discharge, whichever is first
Title
Phase 3: 14 day mortality rate
Time Frame
Day 1 through Day 15
Title
Phase 3: 28 day mortality rate
Time Frame
Day 1 through Day 29
Title
Phase 3: Changes in white blood cell count (CBC) through Day 15
Time Frame
Day 1 to Day 15
Title
Phase 3: Changes in hemoglobin through Day 15
Time Frame
Day 1 to Day 15
Title
Phase 3: Changes in platelets through Day 15
Time Frame
Day 1 to Day 15
Title
Phase 3: Changes in creatinine through Day 15
Time Frame
Day 1 to Day 15
Title
Phase 3: Changes in glucose through Day 15
Time Frame
Day 1 to Day 15
Title
Phase 3: Changes in prothrombin time (PT) through Day 15
Time Frame
Day 1 to Day 15
Title
Phase 3: Changes in total bilirubin through Day 15
Time Frame
Day 1 to Day 15
Title
Phase 3: Changes in ALT through Day 15
Time Frame
Day 1 to Day 15
Title
Phase 3: Changes in AST through Day 15
Time Frame
Day 1 to Day 15
Title
Phase 3: Changes in white blood cell count (CBC) through End of Study (EOS)
Description
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.
Time Frame
Day 1 through Day 29 or hospital discharge, whichever is first
Title
Phase 3: Changes in hemoglobin through End of Study (EOS)
Time Frame
Day 1 through Day 29 or hospital discharge, whichever is first
Title
Phase 3: Changes in platelets through End of Study (EOS)
Time Frame
Day 1 through Day 29 or hospital discharge, whichever is first
Title
Phase 3: Changes in creatinine through End of Study (EOS)
Time Frame
Day 1 through Day 29 or hospital discharge, whichever is first
Title
Phase 3: Changes in glucose through End of Study (EOS)
Time Frame
Day 1 through Day 29 or hospital discharge, whichever is first
Title
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
Title
Phase 3: Changes in total bilirubin through End of Study (EOS)
Time Frame
Day 1 through Day 29 or hospital discharge, whichever is first
Title
Phase 3: Changes in ALT through End of Study (EOS)
Time Frame
Day 1 through Day 29 or hospital discharge, whichever is first
Title
Phase 3: Changes in AST through End of Study (EOS)
Time Frame
Day 1 through Day 29 or hospital discharge, whichever is first
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
89 Years
Accepts Healthy Volunteers
No
Eligibility 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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Joaquin Espinosa, PhD
Organizational Affiliation
University of Colorado, Denver
Official's Role
Principal Investigator
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
De-identified individual participant data will be made available for all primary outcome measures.
IPD Sharing Time Frame
Data will be made available upon publication in a peer-reviewed journal.
IPD Sharing Access Criteria
Data access requests will be reviewed by the sponsor-investigator and collaborators.
Learn more about this trial
Safety and Efficacy of Ruxolitinib for COVID-19
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