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

Primary Purpose

Coronavirus Infection

Status

Completed

Phase

Phase 2

Locations

International

Study Type

Interventional

Intervention

Selinexor

Placebo

About this trial

This is an interventional treatment trial for Coronavirus Infection focused on measuring COVID-19, SARS-CoV-2

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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.

Sites / Locations

UCLA
Kaiser Permanente Oakland
UC Davis Health
Kaiser Permanente Sacramento
Kaiser Permanente San Francisco
Miami Cancer Institute at Baptist Health
Emory University
Advocate Christ Medical Center
University of Kansas Medical Center
Norton Healthcare
Boston Medical Center
Karmanos
Michigan Center of Medical Research
Michigan Center of Medical Research
Columbia University
Weill Cornell Medical College
Levine Cancer Institute-Atrium Health University City
Lehigh Valley Hospital
Baylor Scott & White Dallas
MultiCare Institute for Research & Innovation (Puget Sound)
Hospital Hietzing, 2. Medical department - Center for Diagnosis and Therapy of Rheumatic Diseases
CHU Bordeaux
CHU Lyon
CHU Nantes
Hadassah MC
Hasharon Medical Center
Sheba Medical Center
Hospital Universitari Vall d'Hebron
Servicio de Medicina Interna, Hospital Universitario de Salamanca, Universidad de Salamanca
Princess Royal University Hospital
Kings College Hospital
The Royal Marsden Hospital
University Hospitals Plymouth NHS Trust

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Selinexor 20 mg

Placebo

Arm 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).

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).

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

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.

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.

Overall Death Rate

Overall death rate was defined as the percentage of participants who died on or before 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.

Rate of Intensive Care Unit (ICU) Admission

The rate of ICU admission was defined as the percentage of participants with ICU admissions.

Length of Hospitalization

Length of hospitalization (days) was defined as (first hospital discharge date - date of randomization + 1).

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.

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.

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.

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.

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.

Full Information

NCT ID

NCT04349098

First Posted

April 14, 2020

Last Updated

January 19, 2023

Sponsor

Karyopharm Therapeutics Inc

1. Study Identification

Unique Protocol Identification Number

NCT04349098

Brief Title

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

Acronym

Coronavirus

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

January 2023

Overall Recruitment Status

Completed

Study Start Date

April 17, 2020 (Actual)

Primary Completion Date

October 5, 2020 (Actual)

Study Completion Date

October 5, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Karyopharm Therapeutics Inc

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Coronavirus Infection

Keywords

COVID-19, SARS-CoV-2

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

Participant

Allocation

Randomized

Enrollment

190 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Selinexor 20 mg

Arm Type

Experimental

Arm Description

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Intervention Type

Drug

Intervention Name(s)

Selinexor

Other Intervention Name(s)

KPT-330, XPOVIO

Intervention Description

Participants will receive 20 mg of selinexor.

Intervention Type

Other

Intervention Name(s)

Placebo

Intervention Description

Participants will receive 20 mg of placebo matched to selinexor.

Primary Outcome Measure Information:

Title

Percentage of Participants With At-least a 2-Point Improvement in Ordinal Scale

Description

Time Frame

Baseline up to Day 14

Secondary Outcome Measure Information:

Title

Percentage of Participants With at Least a 2-Point Improvement in the Ordinal Scale up to Day 7

Description

Time Frame

Baseline up to Day 7

Title

Percentage of Participants With at Least a 1-Point Improvement in the Ordinal Scale

Description

Time Frame

Baseline up to Day 7 and 14

Title

Time to Clinical Improvement of 2-points Using Ordinal Scale (TTCI-2)

Description

Time Frame

Baseline up to Day 28

Title

Overall Death Rate

Description

Overall death rate was defined as the percentage of participants who died on or before Day 28.

Time Frame

Baseline up to Day 28

Title

Rate of Mechanical Ventilation (RMV)

Description

The rate of RMV was defined as the percentage of participants who ever used invasive mechanical ventilation or ECMO during the hospital stay.

Time Frame

Baseline up to Day 28

Title

Rate of Intensive Care Unit (ICU) Admission

Description

The rate of ICU admission was defined as the percentage of participants with ICU admissions.

Time Frame

Baseline up to Day 28

Title

Length of Hospitalization

Description

Length of hospitalization (days) was defined as (first hospital discharge date - date of randomization + 1).

Time Frame

Baseline up to Day 67

Title

Change From Baseline in C-reactive Protein (CRP) Levels

Description

Time Frame

Baseline, Day 3, 5, 8, 12, 15, 19, 22 and 26

Title

Change From Baseline in Ferritin Levels

Description

Time Frame

Baseline, Day 3, 5, 8, 12, 15, 19, 22 and 26

Title

Change From Baseline in Lactate Dehydrogenase (LDH) Levels

Description

Time Frame

Baseline, Day 3, 5, 8, 12, 15, 19, 22 and 26

Title

Changes From Baseline in Blood Plasma Cytokines Levels-Interleukin-6 (IL-6)

Description

Time Frame

Baseline, Day 3, 5, 8, 12, 15, 22 and 26

Title

Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs

Description

Time Frame

From start of study drug administration up to Day 58

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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.

Facility Information:

Facility Name

UCLA

City

Los Angeles

State/Province

California

ZIP/Postal Code

90095

Country

United States

Facility Name

Kaiser Permanente Oakland

City

Oakland

State/Province

California

ZIP/Postal Code

94612

Country

United States

Facility Name

UC Davis Health

City

Sacramento

State/Province

California

ZIP/Postal Code

95817

Country

United States

Facility Name

Kaiser Permanente Sacramento

City

Sacramento

State/Province

California

ZIP/Postal Code

95825

Country

United States

Facility Name

Kaiser Permanente San Francisco

City

San Francisco

State/Province

California

ZIP/Postal Code

94115

Country

United States

Facility Name

Miami Cancer Institute at Baptist Health

City

Miami

State/Province

Florida

ZIP/Postal Code

33176

Country

United States

Facility Name

Emory University

City

Atlanta

State/Province

Georgia

ZIP/Postal Code

30322

Country

United States

Facility Name

Advocate Christ Medical Center

City

Oak Lawn

State/Province

Illinois

ZIP/Postal Code

60453

Country

United States

Facility Name

University of Kansas Medical Center

City

Kansas City

State/Province

Kansas

ZIP/Postal Code

64113

Country

United States

Facility Name

Norton Healthcare

City

Louisville

State/Province

Kentucky

ZIP/Postal Code

40202

Country

United States

Facility Name

Boston Medical Center

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02118

Country

United States

Facility Name

Karmanos

City

Detroit

State/Province

Michigan

ZIP/Postal Code

48201

Country

United States

Facility Name

Michigan Center of Medical Research

City

Farmington Hills

State/Province

Michigan

ZIP/Postal Code

48336

Country

United States

Facility Name

Michigan Center of Medical Research

City

Royal Oak

State/Province

Michigan

ZIP/Postal Code

48073

Country

United States

Facility Name

Columbia University

City

New York

State/Province

New York

ZIP/Postal Code

10032

Country

United States

Facility Name

Weill Cornell Medical College

City

New York

State/Province

New York

ZIP/Postal Code

10065

Country

United States

Facility Name

Levine Cancer Institute-Atrium Health University City

City

Charlotte

State/Province

North Carolina

ZIP/Postal Code

28204

Country

United States

Facility Name

Lehigh Valley Hospital

City

Allentown

State/Province

Pennsylvania

ZIP/Postal Code

18103

Country

United States

Facility Name

Baylor Scott & White Dallas

City

Dallas

State/Province

Texas

ZIP/Postal Code

75201

Country

United States

Facility Name

MultiCare Institute for Research & Innovation (Puget Sound)

City

Tacoma

State/Province

Washington

ZIP/Postal Code

98405

Country

United States

Facility Name

Hospital Hietzing, 2. Medical department - Center for Diagnosis and Therapy of Rheumatic Diseases

City

Vienna

Country

Austria

Facility Name

CHU Bordeaux

City

Bordeaux

ZIP/Postal Code

33076

Country

France

Facility Name

CHU Lyon

City

Lyon

ZIP/Postal Code

69004

Country

France

Facility Name

CHU Nantes

City

Nantes

ZIP/Postal Code

44093

Country

France

Facility Name

Hadassah MC

City

Jerusalem

Country

Israel

Facility Name

Hasharon Medical Center

City

Petah Tiqva

Country

Israel

Facility Name

Sheba Medical Center

City

Tel HaShomer

Country

Israel

Facility Name

Hospital Universitari Vall d'Hebron

City

Barcelona

ZIP/Postal Code

08035

Country

Spain

Facility Name

Servicio de Medicina Interna, Hospital Universitario de Salamanca, Universidad de Salamanca

City

Salamanca

ZIP/Postal Code

37007

Country

Spain

Facility Name

Princess Royal University Hospital

City

Kent

ZIP/Postal Code

BR6 8ND

Country

United Kingdom

Facility Name

Kings College Hospital

City

London

ZIP/Postal Code

SE5 9RS

Country

United Kingdom

Facility Name

The Royal Marsden Hospital

City

London

ZIP/Postal Code

SW3 6JJ

Country

United Kingdom

Facility Name

University Hospitals Plymouth NHS Trust

City

Plymouth

ZIP/Postal Code

PL6 5FP

Country

United Kingdom

12. IPD Sharing Statement

Plan to Share IPD

Undecided

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

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