COVID-19 XPORT-CoV-1001

Low dose oral selinexor (20 mg on QoD each week) will expedite the clinical recovery, suppress the viral load, shorten the hospitalization and reduce morbidity and mortality in patients with severe Covid-19 compared to standard of care.

Time to Clinical Improvement (TTCI):

• Absence of fever: oral temperature <38°C x 24 hours without antipyretics (acetaminophen) AND one of the following:
  • Respiratory rate ≤24/minute OR
  • Oxygen saturation ≥94% on room air OR
  • Hospital discharge

Mortality

• All-cause mortality by Day 28 after randomization

1. Age ≥18 years
2. Clinically suspected and subsequently confirmed; or laboratory diagnosis confirming patient is positive for SARS-CoV-2 nucleic acid by RT-PCR (by local labs)
3. Currently hospitalized and consented within the first 48 hours of hospitalization
4. Informed consent provided as above
5. Has symptoms of severe Covid-19 as demonstrated by:
   
   a. Respiratory rate ≥24 breaths/minute OR
   
   b. Pulse Oxygen Saturation (SpO2) ≤94% without oxygen supplementation, OR
   
   c. PaO2/FiO2 (fraction of inspired oxygen) ≤300 mm Hg
6. Concurrent anti-virals and/or anti-inflammatory agents are permitted at baseline for patients entering the study
7. Female patients of childbearing potential must have a negative serum pregnancy test at Screening. Female patients of childbearing potential and fertile male patients who are sexually active with a female of childbearing potential must use highly effective methods of contraception throughout the study and for 1 week following the last dose of study treatment. Highly effective methods of contraception are listed in Section 8.3.1.

1. Evidence of critical Covid-19 based on:
   
   a. Mechanical ventilation (invasive or non-invasive) or ECMO or hemofiltration required
   
   b. Shock
2. In the opinion of the investigator, unlikely to survive for at least 48 hours from screening or anticipate mechanical ventilation within 48 hours
3. Inadequate renal and liver function as indicated by the following labs:
   
   a. Creatinine clearance (CCL) <20 mL/min
   
   b. Aspartate transaminase (AST) or alanine transaminase (ALT) >5 x upper limit of normal (ULN)
4. Unable to take oral medication

Oral 20 mg selinexor administered on Days 1, 3, 5, 8, 10, 12. If the patient is tolerating therapy well and clinically benefitting, dosing can continue for additional 2 weeks on Days 15, 17, 19, 22, 24, 26 in the hospital (or weekly on Days 8, 15, and 22 as an outpatient).