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

The main purpose of this study is to evaluate the activity of low dose oral selinexor (KPT-330) and to evaluate the clinical recovery, the viral load, length of hospitalization and the rate of morbidity and mortality in participants with severe COVID-19 compared to placebo. The study had 2 arms and evaluated selinexor 20 mg + standard of care (SoC) and placebo + SoC. As the treatment for COVID-19 is rapidly evolving, the SoC varied over time and across regions of the world.


Eligibility Criteria:
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.