Ruxolitinib to Combat COVID-19

Study Overview
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Brief Summary
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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.

Official Title
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A Pilot Study of Ruxolitinib to Combat COVID-19

Conditions
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COVID-19

Intervention / Treatment
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* Drug: Ruxolitinib
* Procedure: Peripheral blood draw


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ruxolitinib<br>-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. | Drug: Ruxolitinib<br>* For patients unable to swallow pills, a ruxolitinib suspension will be administered through a nasogastric/orogastric tube<br>* Other names: Jakafi;Procedure: Peripheral blood draw<br>* -Screening, Day 2, Day 4, Day 8, Day 15, and Day 29<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival |  | Through 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Length of hospital stay |  | Through completion of follow-up (estimated to be 7 months) | 
| Length of ICU stay |  | Through completion of follow-up (estimated to be 7 months) | 
| Duration of ventilator use |  | Through completion of follow-up (estimated to be 7 months) | 
| Duration of vasopressors use |  | Through completion of follow-up (estimated to be 7 months) | 
| Duration on renal replacement therapy |  | Through completion of follow-up (estimated to be 7 months) | 
| 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 | Through completion of follow-up (estimated to be 7 months) | 
| Number of adverse events as measured by CTCAE v. 5.0 |  | Through completion of follow-up (estimated to be 7 months) | 
| Proportion of participants with detectable virus |  | Day 5 | 
| Proportion of participants with detectable virus |  | Day 10 | 
| Proportion of participants with detectable virus |  | Day 15 | 
| Proportion of participants with detectable virus |  | Day 29 |