PRE-VENT Study in Hospitalized Patients With Severe COVID-19 With or Without Cancer

Inclusion Criteria:

Hospitalized or will be hospitalized prior to randomization for the treatment of severe COVID-19 with SARS-CoV-2 infection confirmed by either a) a positive reverse transcriptase polymerase chain reaction (RT PCR) or b) an antigen-based test from any respiratory, nasopharyngeal, saliva, blood, or stool specimen at Screening or documented within 1 week prior to the start of Screening (Severe COVID-19 is defined as confirmed disease in patients who are hospitalized with hypoxia [SpO2 ≤93% on room air], respiratory rate >30, PaO2/FiO2 <300, but do not require IMV).
Age ≥ 18 years
Platelet count ≥ 50,000/µL
If fertile, willing to use effective birth control methods during the study
Provision of informed consent within 96 hours after hospitalization

Exclusion Criteria:

In the opinion of the investigator, progression to death is imminent and inevitable within the next 24 hours, irrespective of the provision of treatments
Currently intubated or intubated between screening and randomization
Suspected active uncontrolled bacterial, fungal, viral, or other infection (besides COVID 19)
Prior allogenic hematopoietic stem cell transplantation
Active lung cancer or history of lung cancer within the past 12 months
Any active grade 2 or higher hemorrhage
Any active gastrointestinal or metabolic condition that could interfere with absorption of oral medication
Uncontrolled intercurrent illness that, in the judgment of the treating physician, would limit compliance with study requirements
Known seropositivity for human immunodeficiency virus with cluster of differentiation 4 (CD4) count < 200/mm3 within 3 months prior to randomization
Pregnant or breastfeeding, or positive pregnancy test in a pre-dose examination
Concurrent enrollment in another interventional trial (investigational COVID-19 antiviral studies are permitted)
Serum creatinine > 2.5 mg/dL
Total bilirubin > 4× the upper limit of normal
QT corrected by the Fridericia method (QTcF) prolongation > 480 msec
Known history of New York Heart Association Class II, III, or IV congestive heart failure prior to hospital admission
Known allergic reaction to any Janus kinase 2 (JAK2) inhibitor
Exposure to any JAK2 inhibitor within 28 days
Currently receiving a strong CYP3A4 inhibitor or strong P450 inducer (Appendix 1 and Appendix 2, respectively) and unable to stop the medication prior to the first dose of study drug and throughout the duration of study drug administration
Treatment with cytoreductive chemotherapy administered within 14 days prior to randomization
Administration of an IL 1 or IL 6 blocking immunomodulatory agent (such as tocilizumab, canakinumab, sarilumab, anakinra) within 48 hours prior to randomization
Currently receiving therapeutic anticoagulation or anti platelet medication and unable to stop the medication prior to randomization. Prophylactic anticoagulation therapy or aspirin (≤ 100mg) are permitted.
Unable to ingest capsules or tablets at randomization