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

A Phase 2 Randomized Single-Blind Study to Evaluate the Activity and Safety of Low Dose Oral Selinexor (KPT-330) in Patients With Severe COVID-19 Infection

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.

Study Overview

• Status: Completed
• Conditions: Coronavirus Infection
• Intervention / Treatment: Drug: Selinexor; Other: Placebo

• Study Type: Interventional
• Enrollment (Actual): 190
• Phase: Phase 2

Contacts and Locations

Study Locations

• Austria
  • Vienna, Austria
    • Hospital Hietzing, 2. Medical department - Center for Diagnosis and Therapy of Rheumatic Diseases
• France
  • Bordeaux, France, 33076
    • CHU Bordeaux
  • Lyon, France, 69004
    • CHU Lyon
  • Nantes, France, 44093
    • CHU Nantes
• Israel
  • Jerusalem, Israel
    • Hadassah MC
  • Petah Tiqva, Israel
    • Hasharon Medical Center
  • Tel HaShomer, Israel
    • Sheba Medical Center
• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall d'Hebron
  • Salamanca, Spain, 37007
    • Servicio de Medicina Interna, Hospital Universitario de Salamanca, Universidad de Salamanca
• United Kingdom
  • Kent, United Kingdom, BR6 8ND
    • Princess Royal University Hospital
  • London, United Kingdom, SE5 9RS
    • Kings College Hospital
  • London, United Kingdom, SW3 6JJ
    • The Royal Marsden Hospital
  • Plymouth, United Kingdom, PL6 5FP
    • University Hospitals Plymouth NHS Trust
• United States
  • California
    • Los Angeles, California, United States, 90095
      • UCLA
    • Oakland, California, United States, 94612
      • Kaiser Permanente Oakland
    • Sacramento, California, United States, 95817
      • UC Davis Health
    • Sacramento, California, United States, 95825
      • Kaiser Permanente Sacramento
    • San Francisco, California, United States, 94115
      • Kaiser Permanente San Francisco
  • Florida
    • Miami, Florida, United States, 33176
      • Miami Cancer Institute at Baptist Health
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University
  • Illinois
    • Oak Lawn, Illinois, United States, 60453
      • Advocate Christ Medical Center
  • Kansas
    • Kansas City, Kansas, United States, 64113
      • University of Kansas Medical Center
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • Norton Healthcare
  • Massachusetts
    • Boston, Massachusetts, United States, 02118
      • Boston Medical Center
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Karmanos
    • Farmington Hills, Michigan, United States, 48336
      • Michigan Center of Medical Research
    • Royal Oak, Michigan, United States, 48073
      • Michigan Center of Medical Research
  • New York
    • New York, New York, United States, 10065
      • Weill Cornell Medical College
    • New York, New York, United States, 10032
      • Columbia University
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Levine Cancer Institute-Atrium Health University City
  • Pennsylvania
    • Allentown, Pennsylvania, United States, 18103
      • Lehigh Valley Hospital
  • Texas
    • Dallas, Texas, United States, 75201
      • Baylor Scott & White Dallas
  • Washington
    • Tacoma, Washington, United States, 98405
      • MultiCare Institute for Research & Innovation (Puget Sound)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With At-least a 2-Point Improvement in Ordinal Scale	Ordinal Scale 2-Point improvement was defined as percentage of participants with at least a 2-points improvement (increase from baseline) by Day 14. Baseline score was defined as the last score measured before first dosing. The 8-point ordinal scale ranges from 1 to 8: where 1= death, 2= hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3= hospitalized, on non-invasive ventilation or high flow oxygen devices; 4= hospitalized, requiring supplemental oxygen; 5= hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (coronavirus disease 2019 [COVID-19] related or otherwise); 6= hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7= not hospitalized, limitation on activities and/or requiring home oxygen; 8= not hospitalized, no limitations on activities.	Baseline up to Day 14

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With at Least a 2-Point Improvement in the Ordinal Scale up to Day 7	Ordinal Scale 2-points improvement was defined as percentage of participants with at least a 2-points improvement (increase from baseline) by Day 7. Baseline score was defined as the last score measured before first dosing. The 8-point ordinal scale ranges from 1 to 8: where, 1= death, 2= hospitalized, on invasive mechanical ventilation or ECMO; 3= hospitalized, on non-invasive ventilation or high flow oxygen devices; 4= hospitalized, requiring supplemental oxygen; 5= hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6= hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7= not hospitalized, limitation on activities and/or requiring home oxygen; 8= not hospitalized, no limitations on activities.	Baseline up to Day 7
Percentage of Participants With at Least a 1-Point Improvement in the Ordinal Scale	Ordinal Scale 1-point improvement was defined as percentage of participants with at least 1-point improvement (increase from baseline) by Day 7 and 14. Baseline score was defined as the last score measured before first dosing. The 8-point ordinal scale ranges from 1 to 8: where 1= death, 2= hospitalized, on invasive mechanical ventilation or ECMO; 3= hospitalized, on non-invasive ventilation or high flow oxygen devices; 4= hospitalized, requiring supplemental oxygen; 5= hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6= hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7= not hospitalized, limitation on activities and/or requiring home oxygen; 8= not hospitalized, no limitations on activities.	Baseline up to Day 7 and 14
Time to Clinical Improvement of 2-points Using Ordinal Scale (TTCI-2)	TTCI-2 was defined as the time from randomization to an improvement of 2-points using 8-points Ordinal Scale. The 8-point ordinal scale ranges from 1 to 8: where 1= death, 2= hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3= hospitalized, on non-invasive ventilation or high flow oxygen devices; 4= hospitalized, requiring supplemental oxygen; 5= hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (coronavirus disease 2019 [COVID-19] related or otherwise); 6= hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7= not hospitalized, limitation on activities and/or requiring home oxygen; 8= not hospitalized, no limitations on activities.	Baseline up to Day 28
Overall Death Rate	Overall death rate was defined as the percentage of participants who died on or before Day 28.	Baseline up to Day 28
Rate of Mechanical Ventilation (RMV)	The rate of RMV was defined as the percentage of participants who ever used invasive mechanical ventilation or ECMO during the hospital stay.	Baseline up to Day 28
Rate of Intensive Care Unit (ICU) Admission	The rate of ICU admission was defined as the percentage of participants with ICU admissions.	Baseline up to Day 28
Length of Hospitalization	Length of hospitalization (days) was defined as (first hospital discharge date - date of randomization + 1).	Baseline up to Day 67
Change From Baseline in C-reactive Protein (CRP) Levels	The anti-inflammatory and immune effects of selinexor were assessed by CRP levels. Baseline was defined as the most recent non-missing measurement prior to the first administration of study treatment. Change from Baseline at the indicated time points was calculated as the value at the indicated time points minus the value at Baseline.	Baseline, Day 3, 5, 8, 12, 15, 19, 22 and 26
Change From Baseline in Ferritin Levels	The anti-inflammatory and immune effects of selinexor were assessed by ferritin levels. Baseline was defined as the most recent non-missing measurement prior to the first administration of study treatment. Change from Baseline at the indicated time points was calculated as the value at the indicated time points minus the value at Baseline.	Baseline, Day 3, 5, 8, 12, 15, 19, 22 and 26
Change From Baseline in Lactate Dehydrogenase (LDH) Levels	The anti-inflammatory and immune effects of selinexor were assessed by LDH levels. Baseline was defined as the most recent non-missing measurement prior to the first administration of study treatment. Change from Baseline at the indicated time points was calculated as the value at the indicated time points minus the value at Baseline.	Baseline, Day 3, 5, 8, 12, 15, 19, 22 and 26
Changes From Baseline in Blood Plasma Cytokines Levels-Interleukin-6 (IL-6)	The anti-inflammatory and immune effects of selinexor were assessed by blood plasma cytokines like IL-6. Baseline was defined as the most recent non-missing measurement prior to the first administration of study treatment. Change from Baseline at the indicated time points was calculated as the value at the indicated time points minus the value at Baseline.	Baseline, Day 3, 5, 8, 12, 15, 22 and 26
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs	Adverse events are defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of study treatment, whether or not considered related to the study treatment. Serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. TEAEs are defined as those AEs that develop or worsen after the first dose of study drug. TEAEs included both Serious and non-serious TEAEs.	From start of study drug administration up to Day 58

Collaborators and Investigators

• Sponsor: Karyopharm Therapeutics Inc
• Investigators: Study Director: Dayana Michel, Karyopharm Therapeutics Inc

Study record dates

Study Major Dates

• Study Start (Actual): April 17, 2020
• Primary Completion (Actual): October 5, 2020
• Study Completion (Actual): October 5, 2020

Study Registration Dates

• First Submitted: April 14, 2020
• First Submitted That Met QC Criteria: April 14, 2020
• First Posted (Actual): April 16, 2020

Study Record Updates

• Last Update Posted (Actual): January 20, 2023
• Last Update Submitted That Met QC Criteria: January 19, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Keywords: SARS-CoV-2; COVID-19
• Additional Relevant MeSH Terms: Pathologic Processes; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; Disease Attributes; COVID-19; Coronavirus Infections; Infections; Communicable Diseases
• Other Study ID Numbers: XPORT-CoV-1001; 2020-001411-25 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No