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

Karyopharm Therapeutics

Status and phase: Completed; Phase 2

Conditions: Coronavirus Infection

Treatments: Drug: Selinexor; Other: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT04349098

2020-001411-25 (EudraCT Number)

XPORT-CoV-1001

Details and patient eligibility

About

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.

Enrollment: 190 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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190 participants in 2 patient groups, including a placebo group

Selinexor 20 mg

Experimental group

Description:

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).

Treatment:

Drug: Selinexor

Placebo

Placebo Comparator group

Description:

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).

Treatment:

Other: Placebo