Evaluation of Activity and Safety of Oral Selinexor in Participants With Severe COVID-19 Infection

Inclusion Criteria

• Confirmed laboratory diagnosis of SARS-CoV2 by standard FDA-approved reverse transcription polymerase chain reaction (RT-PCR) assay or equivalent FDA-approved testing (local labs).
• Currently hospitalized.
• Informed consent provided as above (it is recommended that participants are dosed with study drug within 12 hours of consent).
• Has symptoms of severe COVID-19 as demonstrated by:
• At least one of the following: fever, cough, sore throat, malaise, headache, muscle pain, shortness of breath at rest or with exertion, confusion, or symptoms of severe lower respiratory symptoms including dyspnea at rest or respiratory distress.
• Clinical signs indicative of lower respiratory infection with COVID-19, with at least one of the following: SaO2 <92% on room air in last 12 hours or requires > 4 liters per minute (LPM) oxygen by nasal canula, non-rebreather/Ventimask or high flow nasal canula in order maintain SaO2 ≥92%, PaO2/FiO2 <300 millimeter per mercury (mm/hg).
• Elevated C-reactive protein (CRP) > 2 x upper limit of normal (ULN).
• Concurrent anti-viral and/or anti-inflammatory agents (e.g., biologics, hydroxychloroquine) are permitted. If in the physician's judgment, it is in the best interest of the participant to use anti-viral or anti-inflammatory treatments, these treatments are to be documented in the participant's chart and entered in the electronic case report form.
• Female participants of childbearing potential must have a negative serum pregnancy test at Screening. Female participants of childbearing potential and fertile male participants must use highly effective methods of contraception throughout the study and for 3 months following the last dose of study treatment.

Exclusion Criteria

• Evidence of critical COVID-19 based on:
• Respiratory failure (defined by endotracheal intubation and mechanical ventilation, oxygen delivered by noninvasive positive pressure ventilation, or clinical diagnosis of respiratory failure in setting of resource limitations)
• Septic shock (defined by Systolic blood pressure [BP] < 90 mm Hg, or Diastolic BP < 60 mm Hg)
• Multiple organ dysfunction/failure
• In the opinion of the investigator, unlikely to survive for at least 48 hours from screening or anticipate mechanical ventilation within 48 hours.
• Inadequate hematologic parameters as indicated by the following labs:
• Participants with severe neutropenia (ANC <1000 x 10^9/L) or
• Thrombocytopenia (e.g., platelets <100,000 per microliter of blood)
• Inadequate renal and liver function as indicated by the following labs:
• Creatinine clearance (CrCL) <20 mL/min using the formula of Cockcroft and Gault
• Aspartate transaminase (AST) or alanine transaminase (ALT) > 5 x ULN
• Hyponatremia defined as sodium < 135 milliequivalents per liter (mEq/L).
• Unable to take oral medication when informed consent is obtained.
• Participants with a legal guardian or who are incarcerated.
• Treatment with strong CYP3A inhibitors or inducers.
• Pregnant and breastfeeding women.