Coronavirus Infection
Conditions
Keywords
COVID-19, SARS-CoV-2
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.
Interventions
DRUGSelinexor
Participants will receive 20 mg of selinexor.
OTHERPlacebo
Participants will receive 20 mg of placebo matched to selinexor.
Sponsors
Karyopharm Therapeutics Inc
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With At-least a 2-Point Improvement in Ordinal Scale | 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
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With at Least a 1-Point Improvement in the Ordinal Scale | 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) | 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 | 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) | 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 | Baseline up to Day 28 | The rate of ICU admission was defined as the percentage of participants with ICU admissions. |
| Percentage of Participants With at Least a 2-Point Improvement in the Ordinal Scale up to Day 7 | 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. |
| Change From Baseline in C-reactive Protein (CRP) Levels | 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 | 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 | 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) | 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 | 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. |
| Length of Hospitalization | Baseline up to Day 67 | Length of hospitalization (days) was defined as (first hospital discharge date - date of randomization + 1). |
Countries
Austria, France, Israel, Spain, United Kingdom, United States
Participant flow
Recruitment details
This study was conducted at 20 sites in the United States of America,1 site in Austria, 3 sites in France and Israel, 2 sites in Spain, and 4 sites in the United Kingdom from 17 Apr 2020 to 05 Oct 2020.
Pre-assignment details
A total of 190 participants were enrolled and randomized, of which 188 participants received study treatment in this study.
Participants by arm
| Arm | Count |
|---|---|
| Selinexor 20 mg Participants received a single dose of Selinexor 20 milligrams (mg) tablets orally on Days 1, 3 and 5 of each week for up to 2 weeks. The participant tolerated therapy and showed clinical benefit, dosing continued for an additional 2 weeks (on Days 15, 17, 19, 22, 24, and 26). | 103 |
| Placebo Participants received a single dose of placebo matched to selinexor tablets orally on Days 1, 3 and 5 of each week for up to 2 weeks. The participant tolerated therapy and showed clinical benefit, dosing continued for an additional 2 weeks (on Days 15, 17, 19, 22, 24, and 26). | 87 |
| Total | 190 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 16 | 8 |
| Overall Study | Lost to Follow-up | 11 | 8 |
| Overall Study | Other | 3 | 5 |
| Overall Study | Withdrawal by Subject | 8 | 5 |
Baseline characteristics
| Characteristic | Placebo | Total | Selinexor 20 mg |
|---|---|---|---|
| Age, Continuous | 56.5 Years STANDARD_DEVIATION 14.64 | 56.5 Years STANDARD_DEVIATION 15.42 | 56.5 Years STANDARD_DEVIATION 16.12 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 32 Participants | 73 Participants | 41 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 53 Participants | 112 Participants | 59 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants | 5 Participants | 3 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 4 Participants | 10 Participants | 6 Participants |
| Race (NIH/OMB) Black or African American | 24 Participants | 47 Participants | 23 Participants |
| Race (NIH/OMB) More than one race | 14 Participants | 33 Participants | 19 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 11 Participants | 20 Participants | 9 Participants |
| Race (NIH/OMB) White | 34 Participants | 78 Participants | 44 Participants |
| Sex: Female, Male Female | 39 Participants | 82 Participants | 43 Participants |
| Sex: Female, Male Male | 48 Participants | 108 Participants | 60 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 16 / 102 | 8 / 86 |
| other Total, other adverse events | 69 / 102 | 45 / 86 |
| serious Total, serious adverse events | 23 / 102 | 14 / 86 |
Outcome results
Primary
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.
Time frame: Baseline up to Day 14
Population: The intent-to-treat (ITT) population included all participants who were randomized in the study with confirmed severe acute respiratory syndrome coronavirus (SARS-CoV2) infection under protocol version (PV) 6.0 and above, regardless of whether or not they receive study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Selinexor 20 mg | Percentage of Participants With At-least a 2-Point Improvement in Ordinal Scale | 60.6 Percentage of participants |
| Placebo | Percentage of Participants With At-least a 2-Point Improvement in Ordinal Scale | 60.8 Percentage of participants |
p-value: 0.67595% CI: [0.39, 1.79]Cochran-Mantel-Haenszel
Secondary
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.
Time frame: Baseline, Day 3, 5, 8, 12, 15, 19, 22 and 26
Population: PV 1-6 population included participants randomized into the study under protocol versions 1-6. Here, Number Analyzed signified those participants who were evaluable for this outcome measure at a specified time-point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Selinexor 20 mg | Change From Baseline in C-reactive Protein (CRP) Levels | Change at Day 3 | -47.9660 milligram per liter (mg/L) | Standard Deviation 99.06082 |
| Selinexor 20 mg | Change From Baseline in C-reactive Protein (CRP) Levels | Change at Day 15 | -87.9800 milligram per liter (mg/L) | Standard Deviation 121.19999 |
| Selinexor 20 mg | Change From Baseline in C-reactive Protein (CRP) Levels | Change at Day 8 | -83.3460 milligram per liter (mg/L) | Standard Deviation 93.835 |
| Selinexor 20 mg | Change From Baseline in C-reactive Protein (CRP) Levels | Change at Day 19 | -66.2143 milligram per liter (mg/L) | Standard Deviation 86.55049 |
| Selinexor 20 mg | Change From Baseline in C-reactive Protein (CRP) Levels | Change at Day 5 | -74.4735 milligram per liter (mg/L) | Standard Deviation 114.52388 |
| Selinexor 20 mg | Change From Baseline in C-reactive Protein (CRP) Levels | Change at Day 22 | -90.7100 milligram per liter (mg/L) | Standard Deviation 149.25579 |
| Selinexor 20 mg | Change From Baseline in C-reactive Protein (CRP) Levels | Change at Day 12 | -86.9158 milligram per liter (mg/L) | Standard Deviation 123.54705 |
| Selinexor 20 mg | Change From Baseline in C-reactive Protein (CRP) Levels | Change at Day 26 | -37.2800 milligram per liter (mg/L) | Standard Deviation 141.4139 |
| Placebo | Change From Baseline in C-reactive Protein (CRP) Levels | Change at Day 12 | -93.2744 milligram per liter (mg/L) | Standard Deviation 131.56709 |
| Placebo | Change From Baseline in C-reactive Protein (CRP) Levels | Change at Day 3 | -42.9658 milligram per liter (mg/L) | Standard Deviation 89.09341 |
| Placebo | Change From Baseline in C-reactive Protein (CRP) Levels | Change at Day 5 | -68.6191 milligram per liter (mg/L) | Standard Deviation 108.19671 |
| Placebo | Change From Baseline in C-reactive Protein (CRP) Levels | Change at Day 8 | -74.4669 milligram per liter (mg/L) | Standard Deviation 117.66505 |
| Placebo | Change From Baseline in C-reactive Protein (CRP) Levels | Change at Day 26 | -129.5020 milligram per liter (mg/L) | Standard Deviation 46.26178 |
| Placebo | Change From Baseline in C-reactive Protein (CRP) Levels | Change at Day 15 | -98.7940 milligram per liter (mg/L) | Standard Deviation 87.65276 |
| Placebo | Change From Baseline in C-reactive Protein (CRP) Levels | Change at Day 19 | -124.3233 milligram per liter (mg/L) | Standard Deviation 102.04161 |
| Placebo | Change From Baseline in C-reactive Protein (CRP) Levels | Change at Day 22 | -47.5620 milligram per liter (mg/L) | Standard Deviation 171.49171 |
Secondary
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.
Time frame: Baseline, Day 3, 5, 8, 12, 15, 19, 22 and 26
Population: PV 1-6 population included participants randomized into the study under protocol versions 1-6. Here, Number Analyzed signified those participants who were evaluable for this outcome measure at a specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Selinexor 20 mg | Change From Baseline in Ferritin Levels | Change at Day 3 | 80.8415 microgram/liter (mcg/L) | Standard Deviation 759.10075 |
| Selinexor 20 mg | Change From Baseline in Ferritin Levels | Change at Day 19 | -15.9333 microgram/liter (mcg/L) | Standard Deviation 462.40358 |
| Selinexor 20 mg | Change From Baseline in Ferritin Levels | Change at Day 22 | -103.9900 microgram/liter (mcg/L) | Standard Deviation 636.89555 |
| Selinexor 20 mg | Change From Baseline in Ferritin Levels | Change at Day 5 | -25.7000 microgram/liter (mcg/L) | Standard Deviation 856.16619 |
| Selinexor 20 mg | Change From Baseline in Ferritin Levels | Change at Day 8 | 226.6113 microgram/liter (mcg/L) | Standard Deviation 1673.46162 |
| Selinexor 20 mg | Change From Baseline in Ferritin Levels | Change at Day 12 | 193.5793 microgram/liter (mcg/L) | Standard Deviation 1203.33385 |
| Selinexor 20 mg | Change From Baseline in Ferritin Levels | Change at Day 15 | 204.3900 microgram/liter (mcg/L) | Standard Deviation 557.29217 |
| Selinexor 20 mg | Change From Baseline in Ferritin Levels | Change at Day 26 | -150.1167 microgram/liter (mcg/L) | Standard Deviation 535.94141 |
| Placebo | Change From Baseline in Ferritin Levels | Change at Day 26 | -25.7500 microgram/liter (mcg/L) | Standard Deviation 231.43232 |
| Placebo | Change From Baseline in Ferritin Levels | Change at Day 3 | -61.9843 microgram/liter (mcg/L) | Standard Deviation 542.0946 |
| Placebo | Change From Baseline in Ferritin Levels | Change at Day 8 | -292.2462 microgram/liter (mcg/L) | Standard Deviation 738.07874 |
| Placebo | Change From Baseline in Ferritin Levels | Change at Day 19 | -231.2374 microgram/liter (mcg/L) | Standard Deviation 599.98919 |
| Placebo | Change From Baseline in Ferritin Levels | Change at Day 15 | -356.8429 microgram/liter (mcg/L) | Standard Deviation 476.04151 |
| Placebo | Change From Baseline in Ferritin Levels | Change at Day 22 | -102.0000 microgram/liter (mcg/L) | Standard Deviation 417.51247 |
| Placebo | Change From Baseline in Ferritin Levels | Change at Day 12 | -352.5280 microgram/liter (mcg/L) | Standard Deviation 741.13673 |
| Placebo | Change From Baseline in Ferritin Levels | Change at Day 5 | -155.3111 microgram/liter (mcg/L) | Standard Deviation 773.76777 |
Secondary
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.
Time frame: Baseline, Day 3, 5, 8, 12, 15, 19, 22 and 26
Population: PV 1-6 population included participants randomized into the study under protocol versions 1-6. Here, Number Analyzed signified those participants who were evaluable for this outcome measure at a specified time-point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Selinexor 20 mg | Change From Baseline in Lactate Dehydrogenase (LDH) Levels | Change at Day 3 | -13.86 units/liter (U/L) | Standard Deviation 148.231 |
| Selinexor 20 mg | Change From Baseline in Lactate Dehydrogenase (LDH) Levels | Change at Day 5 | -49.12 units/liter (U/L) | Standard Deviation 175.722 |
| Selinexor 20 mg | Change From Baseline in Lactate Dehydrogenase (LDH) Levels | Change at Day 8 | -75.85 units/liter (U/L) | Standard Deviation 264.84 |
| Selinexor 20 mg | Change From Baseline in Lactate Dehydrogenase (LDH) Levels | Change at Day 12 | -107.39 units/liter (U/L) | Standard Deviation 198.092 |
| Selinexor 20 mg | Change From Baseline in Lactate Dehydrogenase (LDH) Levels | Change at Day 15 | -71.82 units/liter (U/L) | Standard Deviation 193.543 |
| Selinexor 20 mg | Change From Baseline in Lactate Dehydrogenase (LDH) Levels | Change at Day 19 | -96.38 units/liter (U/L) | Standard Deviation 200.164 |
| Selinexor 20 mg | Change From Baseline in Lactate Dehydrogenase (LDH) Levels | Change at Day 22 | -129.70 units/liter (U/L) | Standard Deviation 177.454 |
| Selinexor 20 mg | Change From Baseline in Lactate Dehydrogenase (LDH) Levels | Change at Day 26 | -169.50 units/liter (U/L) | Standard Deviation 213.481 |
| Placebo | Change From Baseline in Lactate Dehydrogenase (LDH) Levels | Change at Day 26 | 4.50 units/liter (U/L) | Standard Deviation 130.733 |
| Placebo | Change From Baseline in Lactate Dehydrogenase (LDH) Levels | Change at Day 3 | -11.86 units/liter (U/L) | Standard Deviation 151.63 |
| Placebo | Change From Baseline in Lactate Dehydrogenase (LDH) Levels | Change at Day 15 | -51.50 units/liter (U/L) | Standard Deviation 148.063 |
| Placebo | Change From Baseline in Lactate Dehydrogenase (LDH) Levels | Change at Day 5 | 31.85 units/liter (U/L) | Standard Deviation 326.281 |
| Placebo | Change From Baseline in Lactate Dehydrogenase (LDH) Levels | Change at Day 22 | -75.40 units/liter (U/L) | Standard Deviation 43.569 |
| Placebo | Change From Baseline in Lactate Dehydrogenase (LDH) Levels | Change at Day 8 | -10.93 units/liter (U/L) | Standard Deviation 166.876 |
| Placebo | Change From Baseline in Lactate Dehydrogenase (LDH) Levels | Change at Day 19 | -74.14 units/liter (U/L) | Standard Deviation 114.271 |
| Placebo | Change From Baseline in Lactate Dehydrogenase (LDH) Levels | Change at Day 12 | -16.84 units/liter (U/L) | Standard Deviation 232.605 |
Secondary
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.
Time frame: Baseline, Day 3, 5, 8, 12, 15, 22 and 26
Population: PV 1-6 population included participants randomized into the study under protocol versions 1-6. Here, Overall Number of participants analyzed included all participants with baseline data and Number Analyzed signified those participants who were evaluable for this outcome measure at a specified time-point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Selinexor 20 mg | Changes From Baseline in Blood Plasma Cytokines Levels-Interleukin-6 (IL-6) | Change at Day 26 | -23.400 nanograms/milliliter (ng/mL) | — |
| Selinexor 20 mg | Changes From Baseline in Blood Plasma Cytokines Levels-Interleukin-6 (IL-6) | Change at Day 8 | -13.909 nanograms/milliliter (ng/mL) | Standard Deviation 161.6803 |
| Selinexor 20 mg | Changes From Baseline in Blood Plasma Cytokines Levels-Interleukin-6 (IL-6) | Change at Day 12 | 276.289 nanograms/milliliter (ng/mL) | Standard Deviation 1541.3692 |
| Selinexor 20 mg | Changes From Baseline in Blood Plasma Cytokines Levels-Interleukin-6 (IL-6) | Change at Day 15 | -34.850 nanograms/milliliter (ng/mL) | Standard Deviation 28.6357 |
| Selinexor 20 mg | Changes From Baseline in Blood Plasma Cytokines Levels-Interleukin-6 (IL-6) | Change at Day 22 | -8.600 nanograms/milliliter (ng/mL) | Standard Deviation 11.8072 |
| Selinexor 20 mg | Changes From Baseline in Blood Plasma Cytokines Levels-Interleukin-6 (IL-6) | Change at Day 3 | -19.931 nanograms/milliliter (ng/mL) | Standard Deviation 51.2072 |
| Selinexor 20 mg | Changes From Baseline in Blood Plasma Cytokines Levels-Interleukin-6 (IL-6) | Change at Day 5 | -10.786 nanograms/milliliter (ng/mL) | Standard Deviation 102.916 |
| Placebo | Changes From Baseline in Blood Plasma Cytokines Levels-Interleukin-6 (IL-6) | Change at Day 3 | 2.046 nanograms/milliliter (ng/mL) | Standard Deviation 49.0258 |
| Placebo | Changes From Baseline in Blood Plasma Cytokines Levels-Interleukin-6 (IL-6) | Change at Day 15 | 207.625 nanograms/milliliter (ng/mL) | Standard Deviation 408.5783 |
| Placebo | Changes From Baseline in Blood Plasma Cytokines Levels-Interleukin-6 (IL-6) | Change at Day 5 | -77.509 nanograms/milliliter (ng/mL) | Standard Deviation 408.0085 |
| Placebo | Changes From Baseline in Blood Plasma Cytokines Levels-Interleukin-6 (IL-6) | Change at Day 12 | 223.637 nanograms/milliliter (ng/mL) | Standard Deviation 715.5904 |
| Placebo | Changes From Baseline in Blood Plasma Cytokines Levels-Interleukin-6 (IL-6) | Change at Day 8 | 183.728 nanograms/milliliter (ng/mL) | Standard Deviation 662.7908 |
Secondary
Length of Hospitalization
Length of hospitalization (days) was defined as (first hospital discharge date - date of randomization + 1).
Time frame: Baseline up to Day 67
Population: ITT population included all participants who were randomized in the study with confirmed SARS-CoV2 infection under protocol version 6.0 and above, regardless of whether or not they receive study treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Selinexor 20 mg | Length of Hospitalization | 9.0 Days |
| Placebo | Length of Hospitalization | 9.0 Days |
Secondary
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.
Time frame: From start of study drug administration up to Day 58
Population: All-treat population consisted of the subset of ITT participants who took at least one dose of study treatment on this study.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Selinexor 20 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs | Participants with TEAEs | 75 Participants |
| Selinexor 20 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs | Participants with Serious TEAEs | 23 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs | Participants with TEAEs | 49 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs | Participants with Serious TEAEs | 14 Participants |
Secondary
Overall Death Rate
Overall death rate was defined as the percentage of participants who died on or before Day 28.
Time frame: Baseline up to Day 28
Population: ITT population included all participants who were randomized in the study with confirmed SARS-CoV2 infection under protocol version 6.0 and above, regardless of whether or not they receive study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Selinexor 20 mg | Overall Death Rate | 15.2 Percentage of participants |
| Placebo | Overall Death Rate | 3.9 Percentage of participants |
Secondary
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 frame: Baseline up to Day 7 and 14
Population: PV 1-6 population included participants randomized into the study under protocol versions 1-6.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Selinexor 20 mg | Percentage of Participants With at Least a 1-Point Improvement in the Ordinal Scale | Day 7 | 51.5 Percentage of participants |
| Selinexor 20 mg | Percentage of Participants With at Least a 1-Point Improvement in the Ordinal Scale | Day 14 | 72.8 Percentage of participants |
| Placebo | Percentage of Participants With at Least a 1-Point Improvement in the Ordinal Scale | Day 7 | 50.6 Percentage of participants |
| Placebo | Percentage of Participants With at Least a 1-Point Improvement in the Ordinal Scale | Day 14 | 72.4 Percentage of participants |
Secondary
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.
Time frame: Baseline up to Day 7
Population: PV 1-6 population included participants randomized into the study under protocol versions 1-6.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Selinexor 20 mg | Percentage of Participants With at Least a 2-Point Improvement in the Ordinal Scale up to Day 7 | 30.1 Percentage of participants |
| Placebo | Percentage of Participants With at Least a 2-Point Improvement in the Ordinal Scale up to Day 7 | 32.2 Percentage of participants |
Secondary
Rate of Intensive Care Unit (ICU) Admission
The rate of ICU admission was defined as the percentage of participants with ICU admissions.
Time frame: Baseline up to Day 28
Population: ITT population included all participants who were randomized in the study with confirmed SARS-CoV2 infection under protocol version 6.0 and above, regardless of whether or not they receive study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Selinexor 20 mg | Rate of Intensive Care Unit (ICU) Admission | 48.5 Percentage of participants |
| Placebo | Rate of Intensive Care Unit (ICU) Admission | 41.2 Percentage of participants |
Secondary
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.
Time frame: Baseline up to Day 28
Population: ITT population included all participants who were randomized in the study with confirmed SARS-CoV2 infection under protocol version 6.0 and above, regardless of whether or not they receive study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Selinexor 20 mg | Rate of Mechanical Ventilation (RMV) | 13.6 Percentage of participants |
| Placebo | Rate of Mechanical Ventilation (RMV) | 11.8 Percentage of participants |
Secondary
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.
Time frame: Baseline up to Day 28
Population: ITT Population included all participants who were randomized in the study with confirmed SARS-CoV2 infection under protocol version 6.0 and above, regardless of whether or not they receive study treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Selinexor 20 mg | Time to Clinical Improvement of 2-points Using Ordinal Scale (TTCI-2) | 10.0 Days |
| Placebo | Time to Clinical Improvement of 2-points Using Ordinal Scale (TTCI-2) | 10.0 Days |