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

Karyopharm Therapeutics Inc190 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

SINGLE

Enrollment

190

Conditions

Coronavirus Infection

Interventions

SelinexorDRUG

Participants will receive 20 mg of selinexor.

PlaceboOTHER

Participants will receive 20 mg of placebo matched to selinexor.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Locations (33)

Outcomes

Primary Outcomes

Percentage of Participants With At-least a 2-Point Improvement in Ordinal Scale

Ordinal Scale 2-Point improvement was defined as percentage of participants with at least a 2-points improvement (increase from baseline) by Day 14. Baseline score was defined as the last score measured before first dosing. The 8-point ordinal scale ranges from 1 to 8: where 1= death, 2= hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3= hospitalized, on non-invasive ventilation or high flow oxygen devices; 4= hospitalized, requiring supplemental oxygen; 5= hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (coronavirus disease 2019 \[COVID-19\] related or otherwise); 6= hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7= not hospitalized, limitation on activities and/or requiring home oxygen; 8= not hospitalized, no limitations on activities.

Time frame: Baseline up to Day 14

Secondary Outcomes

Percentage of Participants With at Least a 2-Point Improvement in the Ordinal Scale up to Day 7

Ordinal Scale 2-points improvement was defined as percentage of participants with at least a 2-points improvement (increase from baseline) by Day 7. Baseline score was defined as the last score measured before first dosing. The 8-point ordinal scale ranges from 1 to 8: where, 1= death, 2= hospitalized, on invasive mechanical ventilation or ECMO; 3= hospitalized, on non-invasive ventilation or high flow oxygen devices; 4= hospitalized, requiring supplemental oxygen; 5= hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6= hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7= not hospitalized, limitation on activities and/or requiring home oxygen; 8= not hospitalized, no limitations on activities.

Time frame: Baseline up to Day 7

Percentage of Participants With at Least a 1-Point Improvement in the Ordinal Scale

Ordinal Scale 1-point improvement was defined as percentage of participants with at least 1-point improvement (increase from baseline) by Day 7 and 14. Baseline score was defined as the last score measured before first dosing. The 8-point ordinal scale ranges from 1 to 8: where 1= death, 2= hospitalized, on invasive mechanical ventilation or ECMO; 3= hospitalized, on non-invasive ventilation or high flow oxygen devices; 4= hospitalized, requiring supplemental oxygen; 5= hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6= hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7= not hospitalized, limitation on activities and/or requiring home oxygen; 8= not hospitalized, no limitations on activities.

Data from ClinicalTrials.gov

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