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

• Status: Completed
• Trial end date: 2020-10-05
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Karyopharm Therapeutics Inc

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 <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.