Ruxolitinib to Combat COVID-19
Primary Purpose
COVID-19
Status
Withdrawn
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Ruxolitinib
Peripheral blood draw
Sponsored by
About this trial
This is an interventional treatment trial for COVID-19
Eligibility Criteria
Inclusion Criteria:
A diagnosis of advanced COVID-19 as defined by both of the following:
- A positive test for SARS-CoV-2 RNA detected by RT-PCR collected from the upper respiratory tract (nasopharyngeal and oropharyngeal swab) and, if possible, the lower respiratory tract (sputum, tracheal aspirate, or bronchoalveolar lavage), analyzed by a CLIA certified lab
Critical disease manifested by any of the following:
- Chest imaging (CT or chest X-ray permitted) with ≥ 50% lung involvement
- Respiratory failure requiring invasive mechanical ventilation or supplementary oxygen with FiO2 ≥ 50%
- Shock (defined as mean arterial pressure ≤ 65 mmHg unresponsive to 25ml/kg isotonic intravenous fluid resuscitation and/or requiring vasopressor support
Cardiac dysfunction defined by:
- New global systolic dysfunction with ejection fraction ≤ 40%
- Takotsubo cardiomyopathy
- New onset supraventricular or ventricular arrhythmias
- Plasma troponin I ≥ 0.10 ng/mL in someone without previously documented troponin elevation beyond that level
Elevated plasma NT-proBNP in someone without documented prior elevation
- If Age < 50, NT-proBNP > 450 pg/ml
- If Age 50-74, NT-proBNP > 900 pg/ml
- If Age ≥ 74, NT-proBNP > 1800 pg/ml
- Receipt of investigational or off-label agents for COVID-19 (prior or ongoing) does not exclude eligibility.
- Patients who have received autologous or allogeneic stem cell transplant are eligible at the discretion of the investigators.
- 18 years of age or older at the time of study registration
Adequate hematologic function defined as:
- absolute neutrophil count ≥ 1000/mm3
- platelet count ≥ 50,000/mm3 without growth factor or transfusion support for 7 days prior to screening
- Creatinine clearance ≥ 15 mL/minute or receiving renal replacement therapy
- Women of childbearing potential (defined as women with regular menses, women with amenorrhea, women with irregular cycles, women using a contraceptive method that precludes withdrawal bleeding, or women who have had a tubal ligation) are required to have a negative pregnancy test and use two forms of acceptable contraception, including one barrier method, during participation in the study treatment period.
- Male patients (if engaging in reproductive sex with a women of childbearing potential) are required to use two forms of acceptable contraception, including one barrier method, during participation in the study and throughout the evaluation period.
- Able to understand and willing to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable)
Exclusion Criteria:
- Known allergy or intolerance to ruxolitinib or another JAK inhibitor.
- Known or suspected active viral (including HIV, hepatitis B, and hepatitis C), bacterial, mycobacterial, or fungal infection other than COVID-19. Virologic testing not required unless infection is suspected.
- Pregnant and/or breastfeeding.
- Any uncontrolled intercurrent illness that would put the patient at greater risk or limit compliance with study requirements in the opinion of the investigator.
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Ruxolitinib
Arm Description
-Ruxolitinib is an oral medication that will be given twice daily (BID). Dosing on Days 1 through 3 will be 5 mg BID; dosing on Days 4 through 10 will be 10 mg BID.
Outcomes
Primary Outcome Measures
Overall survival
Secondary Outcome Measures
Length of hospital stay
Length of ICU stay
Duration of ventilator use
Duration of vasopressors use
Duration on renal replacement therapy
Viral kinetics as measured by virologic failure
-Defined as increase in viral load of >0.5 log on two consecutive days, or >1 log increase in one day, not in keeping with any baseline trend of rising viral loads during the pre-treatment viral testing
Number of adverse events as measured by CTCAE v. 5.0
Proportion of participants with detectable virus
Proportion of participants with detectable virus
Proportion of participants with detectable virus
Proportion of participants with detectable virus
Full Information
NCT ID
NCT04354714
First Posted
April 16, 2020
Last Updated
May 19, 2020
Sponsor
Washington University School of Medicine
Collaborators
Incyte Corporation
1. Study Identification
Unique Protocol Identification Number
NCT04354714
Brief Title
Ruxolitinib to Combat COVID-19
Official Title
A Pilot Study of Ruxolitinib to Combat COVID-19
Study Type
Interventional
2. Study Status
Record Verification Date
May 2020
Overall Recruitment Status
Withdrawn
Why Stopped
Could not make FDA required changes
Study Start Date
June 30, 2020 (Anticipated)
Primary Completion Date
July 31, 2021 (Anticipated)
Study Completion Date
December 31, 2021 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Washington University School of Medicine
Collaborators
Incyte Corporation
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
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The investigators hypothesize that JAK 1/2 inhibition with ruxolitinib, an FDA approved treatment for intermediate or high-risk myelofibrosis, could have a similar effect in patients with severe COVID-19, quelling the immune-hyperactivation, allowing for clearance of the virus and reversal of the disease manifestations.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
COVID-19
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Ruxolitinib
Arm Type
Experimental
Arm Description
-Ruxolitinib is an oral medication that will be given twice daily (BID). Dosing on Days 1 through 3 will be 5 mg BID; dosing on Days 4 through 10 will be 10 mg BID.
Intervention Type
Drug
Intervention Name(s)
Ruxolitinib
Other Intervention Name(s)
Jakafi
Intervention Description
For patients unable to swallow pills, a ruxolitinib suspension will be administered through a nasogastric/orogastric tube
Intervention Type
Procedure
Intervention Name(s)
Peripheral blood draw
Intervention Description
-Screening, Day 2, Day 4, Day 8, Day 15, and Day 29
Primary Outcome Measure Information:
Title
Overall survival
Time Frame
Through 28 days
Secondary Outcome Measure Information:
Title
Length of hospital stay
Time Frame
Through completion of follow-up (estimated to be 7 months)
Title
Length of ICU stay
Time Frame
Through completion of follow-up (estimated to be 7 months)
Title
Duration of ventilator use
Time Frame
Through completion of follow-up (estimated to be 7 months)
Title
Duration of vasopressors use
Time Frame
Through completion of follow-up (estimated to be 7 months)
Title
Duration on renal replacement therapy
Time Frame
Through completion of follow-up (estimated to be 7 months)
Title
Viral kinetics as measured by virologic failure
Description
-Defined as increase in viral load of >0.5 log on two consecutive days, or >1 log increase in one day, not in keeping with any baseline trend of rising viral loads during the pre-treatment viral testing
Time Frame
Through completion of follow-up (estimated to be 7 months)
Title
Number of adverse events as measured by CTCAE v. 5.0
Time Frame
Through completion of follow-up (estimated to be 7 months)
Title
Proportion of participants with detectable virus
Time Frame
Day 5
Title
Proportion of participants with detectable virus
Time Frame
Day 10
Title
Proportion of participants with detectable virus
Time Frame
Day 15
Title
Proportion of participants with detectable virus
Time Frame
Day 29
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
A diagnosis of advanced COVID-19 as defined by both of the following:
A positive test for SARS-CoV-2 RNA detected by RT-PCR collected from the upper respiratory tract (nasopharyngeal and oropharyngeal swab) and, if possible, the lower respiratory tract (sputum, tracheal aspirate, or bronchoalveolar lavage), analyzed by a CLIA certified lab
Critical disease manifested by any of the following:
Chest imaging (CT or chest X-ray permitted) with ≥ 50% lung involvement
Respiratory failure requiring invasive mechanical ventilation or supplementary oxygen with FiO2 ≥ 50%
Shock (defined as mean arterial pressure ≤ 65 mmHg unresponsive to 25ml/kg isotonic intravenous fluid resuscitation and/or requiring vasopressor support
Cardiac dysfunction defined by:
New global systolic dysfunction with ejection fraction ≤ 40%
Takotsubo cardiomyopathy
New onset supraventricular or ventricular arrhythmias
Plasma troponin I ≥ 0.10 ng/mL in someone without previously documented troponin elevation beyond that level
Elevated plasma NT-proBNP in someone without documented prior elevation
If Age < 50, NT-proBNP > 450 pg/ml
If Age 50-74, NT-proBNP > 900 pg/ml
If Age ≥ 74, NT-proBNP > 1800 pg/ml
Receipt of investigational or off-label agents for COVID-19 (prior or ongoing) does not exclude eligibility.
Patients who have received autologous or allogeneic stem cell transplant are eligible at the discretion of the investigators.
18 years of age or older at the time of study registration
Adequate hematologic function defined as:
absolute neutrophil count ≥ 1000/mm3
platelet count ≥ 50,000/mm3 without growth factor or transfusion support for 7 days prior to screening
Creatinine clearance ≥ 15 mL/minute or receiving renal replacement therapy
Women of childbearing potential (defined as women with regular menses, women with amenorrhea, women with irregular cycles, women using a contraceptive method that precludes withdrawal bleeding, or women who have had a tubal ligation) are required to have a negative pregnancy test and use two forms of acceptable contraception, including one barrier method, during participation in the study treatment period.
Male patients (if engaging in reproductive sex with a women of childbearing potential) are required to use two forms of acceptable contraception, including one barrier method, during participation in the study and throughout the evaluation period.
Able to understand and willing to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable)
Exclusion Criteria:
Known allergy or intolerance to ruxolitinib or another JAK inhibitor.
Known or suspected active viral (including HIV, hepatitis B, and hepatitis C), bacterial, mycobacterial, or fungal infection other than COVID-19. Virologic testing not required unless infection is suspected.
Pregnant and/or breastfeeding.
Any uncontrolled intercurrent illness that would put the patient at greater risk or limit compliance with study requirements in the opinion of the investigator.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
John DiPersio, M.D., Ph.D.
Organizational Affiliation
Washington University School of Medicine
Official's Role
Principal Investigator
12. IPD Sharing Statement
Plan to Share IPD
No
Links:
URL
http://www.siteman.wustl.edu
Description
Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine
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Ruxolitinib to Combat COVID-19
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