Evaluation of Activity and Safety of Oral Selinexor in Participants With Severe COVID-19 Infection (Coronavirus)
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The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. |
| ClinicalTrials.gov Identifier: NCT04349098 |
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Recruitment Status :
Completed
First Posted : April 16, 2020
Results First Posted : November 1, 2021
Last Update Posted : November 1, 2021
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Sponsor:
Karyopharm Therapeutics Inc
Information provided by (Responsible Party):
Karyopharm Therapeutics Inc
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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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Coronavirus Infection | Drug: Selinexor Other: Placebo | Phase 2 |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 190 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Single (Participant) |
| Primary Purpose: | Treatment |
| 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 |
| Actual Study Start Date : | April 17, 2020 |
| Actual Primary Completion Date : | October 5, 2020 |
| Actual Study Completion Date : | October 5, 2020 |
Resource links provided by the National Library of Medicine
MedlinePlus related topics:
COVID-19 (Coronavirus Disease 2019)
Drug Information available for:
Selinexor
| Arm | Intervention/treatment |
|---|---|
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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).
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Drug: Selinexor
Participants will receive 20 mg of selinexor.
Other Names:
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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).
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Other: Placebo
Participants will receive 20 mg of placebo matched to selinexor. |
Primary Outcome Measures :
- Percentage of Participants With At-least a 2-Point Improvement in Ordinal Scale [ Time Frame: Baseline up to Day 14 ]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 [ Time Frame: Baseline 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 [ Time Frame: Baseline up to Day 7 and 14 ]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) [ Time Frame: Baseline up to Day 28 ]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 [ Time Frame: Baseline up to Day 28 ]Overall death rate was defined as the percentage of participants who died on or before Day 28.
- Rate of Mechanical Ventilation (RMV) [ Time Frame: Baseline up to Day 28 ]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 [ Time Frame: Baseline up to Day 28 ]The rate of ICU admission was defined as the percentage of participants with ICU admissions.
- Length of Hospitalization [ Time Frame: Baseline up to Day 67 ]Length of hospitalization (days) was defined as (first hospital discharge date - date of randomization + 1).
- Change From Baseline in C-reactive Protein (CRP) Levels [ Time Frame: Baseline, Day 3, 5, 8, 12, 15, 19, 22 and 26 ]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 [ Time Frame: Baseline, Day 3, 5, 8, 12, 15, 19, 22 and 26 ]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 [ Time Frame: Baseline, Day 3, 5, 8, 12, 15, 19, 22 and 26 ]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) [ Time Frame: Baseline, Day 3, 5, 8, 12, 15, 22 and 26 ]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 [ Time Frame: From start of study drug administration up to Day 58 ]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.
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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).
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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:
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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.
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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)
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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.
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04349098
Locations
Show 33 study locations
Sponsors and Collaborators
Karyopharm Therapeutics Inc
Investigators
| Study Director: | Dayana Michel | Karyopharm Therapeutics Inc |
Study Documents (Full-Text)
Documents provided by Karyopharm Therapeutics Inc:
Documents provided by Karyopharm Therapeutics Inc:
Study Protocol [PDF] May 8, 2020
Statistical Analysis Plan [PDF] June 19, 2020
| Responsible Party: | Karyopharm Therapeutics Inc |
| ClinicalTrials.gov Identifier: | NCT04349098 |
| Other Study ID Numbers: |
XPORT-CoV-1001 2020-001411-25 ( EudraCT Number ) |
| First Posted: | April 16, 2020 Key Record Dates |
| Results First Posted: | November 1, 2021 |
| Last Update Posted: | November 1, 2021 |
| Last Verified: | October 2021 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Undecided |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Keywords provided by Karyopharm Therapeutics Inc:
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COVID-19 SARS-CoV-2 |
Additional relevant MeSH terms:
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Infections Communicable Diseases COVID-19 Coronavirus Infections Disease Attributes Pathologic Processes Respiratory Tract Infections Pneumonia, Viral |
Pneumonia Virus Diseases Coronaviridae Infections Nidovirales Infections RNA Virus Infections Lung Diseases Respiratory Tract Diseases |