Evaluation of Activity and Safety of Oral Selinexor in Participants With Severe COVID-19 Infection
Condition: Coronavirus Infection
MeSH terms: Infections; Communicable Diseases; COVID-19; Coronavirus Infections
Intervention: Selinexor; Placebo
Intervention description: Participants will receive 20 mg of selinexor.; Participants will receive 20 mg of placebo matched to selinexor.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Participant)
Enrollment: 190.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: COVID-19; SARS-CoV-2

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.
    

Eligibility 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.