Evaluation of Activity and Safety of Oral Selinexor in Participants With Severe COVID-19 Infection
Purpose
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.
Condition
- Coronavirus Infection
Eligibility
- Eligible Ages
- Over 18 Years
- Eligible Genders
- All
- Accepts Healthy Volunteers
- No
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.
Study Design
- Phase
- Phase 2
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel Assignment
- Primary Purpose
- Treatment
- Masking
- Single (Participant)
Arm Groups
Arm | Description | Assigned Intervention |
---|---|---|
Experimental 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). |
|
Placebo Comparator Placebo |
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). |
|
Recruiting Locations
More Details
- NCT ID
- NCT04349098
- Status
- Completed
- Sponsor
- Karyopharm Therapeutics Inc