evaluation of activity and safety of oral selinexor in participants with severe covid-19 infection

Conditions: Coronavirus Infection

Summary: 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 \ 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.

Keywords: covid-19 sars-cov-2