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

ArmDescriptionAssigned 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).
  • Drug: Selinexor
    Participants will receive 20 mg of selinexor.
    Other names:
    • KPT-330
    • XPOVIO
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).
  • Other: Placebo
    Participants will receive 20 mg of placebo matched to selinexor.

More Details

Status
Completed
Sponsor
Karyopharm Therapeutics Inc

Study Contact