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.
- Coronavirus Infection
- Eligible Ages
- Over 18 Years
- Eligible Genders
- Accepts Healthy Volunteers
- 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: respiratory rate ≥ 30 breaths/minute (min), heart rate ≥ 125/min, SaO2 <93% on room air or requires > 2 liter (L) oxygen by NC in order maintain SaO2 ≥93%, PaO2/FiO2 <300 millimeter per mercury (mm/hg).
- Concurrent anti-viral and/or anti-inflammatory agents (e.g., biologics, hydroxychloroquine) are permitted. If in the physician's judgement, 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.
- 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) > 2.5 x upper limit of normal (ULN)
- Total bilirubin >1.5 x upper limit of normal (ULN)
- Hyponatremia defined as sodium < 135 milliequivalents per litre (mEq/L).
- Unable to take oral medication when informed consent is obtained.
- Treatment with strong CYP3A inhibitors or inducers.
- Pregnant and breastfeeding women.
- Phase 2
- Study Type
- Intervention Model
- Parallel Assignment
- Primary Purpose
- Single (Participant)
Selinexor 20 mg
|Participants will receive 20 milligram (mg) of selinexor oral tablet on Days 1, 3, and 5 of each week for up to 2 weeks (14 days). If the participant is tolerating therapy and clinically benefitting, dosing can continue for an additional 2 weeks (28 days).||
|Participants will receive 20 mg of placebo matched to selinexor oral tablet on Days 1, 3, and 5 of each week for up to 2 weeks (14 days). If the participant is tolerating therapy and clinically benefitting, dosing can continue for an additional 2 weeks (28 days).||
- Karyopharm Therapeutics Inc
Study ContactJatin Shah, Chief Medical Officer