Trial Outcomes & Findings for Evaluation of Activity and Safety of Oral Selinexor in Participants With Severe COVID-19 Infection (NCT NCT04349098)

Last Updated: 2023-01-20

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

190 participants

Primary outcome timeframe

Baseline up to Day 14

Results posted on

2023-01-20

Participant Flow

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.

A total of 190 participants were enrolled and randomized, of which 188 participants received study treatment in this study.

Participant milestones

Participant milestones
Measure	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).	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).
Overall Study STARTED	103	87
Overall Study Treated	102	86
Overall Study COMPLETED	65	61
Overall Study NOT COMPLETED	38	26

Reasons for withdrawal

Reasons for withdrawal
Measure	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).	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).
Overall Study Death	16	8
Overall Study Lost to Follow-up	11	8
Overall Study Withdrawal by Subject	8	5
Overall Study Other	3	5

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Selinexor 20 mg n=103 Participants 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).	Placebo n=87 Participants 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).	Total n=190 Participants Total of all reporting groups
Age, Continuous	56.5 Years STANDARD_DEVIATION 16.12 • n=5 Participants	56.5 Years STANDARD_DEVIATION 14.64 • n=7 Participants	56.5 Years STANDARD_DEVIATION 15.42 • n=5 Participants
Sex: Female, Male Female	43 Participants n=5 Participants	39 Participants n=7 Participants	82 Participants n=5 Participants
Sex: Female, Male Male	60 Participants n=5 Participants	48 Participants n=7 Participants	108 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	41 Participants n=5 Participants	32 Participants n=7 Participants	73 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	59 Participants n=5 Participants	53 Participants n=7 Participants	112 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	3 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	6 Participants n=5 Participants	4 Participants n=7 Participants	10 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Black or African American	23 Participants n=5 Participants	24 Participants n=7 Participants	47 Participants n=5 Participants
Race (NIH/OMB) White	44 Participants n=5 Participants	34 Participants n=7 Participants	78 Participants n=5 Participants
Race (NIH/OMB) More than one race	19 Participants n=5 Participants	14 Participants n=7 Participants	33 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	9 Participants n=5 Participants	11 Participants n=7 Participants	20 Participants n=5 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Selinexor 20 mg n=66 Participants 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).	Placebo n=51 Participants 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).
Percentage of Participants With At-least a 2-Point Improvement in Ordinal Scale	60.6 Percentage of participants Interval 47.8 to 72.4	60.8 Percentage of participants Interval 46.1 to 74.2

SECONDARY outcome

Timeframe: Baseline up to Day 7

Population: PV 1-6 population included participants randomized into the study under protocol versions 1-6.

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.

Outcome measures

Outcome measures
Measure	Selinexor 20 mg n=103 Participants 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).	Placebo n=87 Participants 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).
Percentage of Participants With at Least a 2-Point Improvement in the Ordinal Scale up to Day 7	30.1 Percentage of participants Interval 21.5 to 39.9	32.2 Percentage of participants Interval 22.6 to 43.1

SECONDARY outcome

Timeframe: Baseline up to Day 7 and 14

Population: PV 1-6 population included participants randomized into the study under protocol versions 1-6.

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.

Outcome measures

Outcome measures
Measure	Selinexor 20 mg n=103 Participants 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).	Placebo n=87 Participants 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).
Percentage of Participants With at Least a 1-Point Improvement in the Ordinal Scale Day 7	51.5 Percentage of participants Interval 41.4 to 61.4	50.6 Percentage of participants Interval 39.6 to 61.5
Percentage of Participants With at Least a 1-Point Improvement in the Ordinal Scale Day 14	72.8 Percentage of participants Interval 63.2 to 81.1	72.4 Percentage of participants Interval 61.8 to 81.5

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Selinexor 20 mg n=66 Participants 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).	Placebo n=51 Participants 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).
Time to Clinical Improvement of 2-points Using Ordinal Scale (TTCI-2)	10.0 Days Interval 8.0 to 14.0	10.0 Days Interval 8.0 to 14.0

SECONDARY outcome

Timeframe: 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.

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

Outcome measures

Outcome measures
Measure	Selinexor 20 mg n=66 Participants 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).	Placebo n=51 Participants 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).
Overall Death Rate	15.2 Percentage of participants Interval 7.5 to 26.1	3.9 Percentage of participants Interval 0.5 to 13.5

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Selinexor 20 mg n=66 Participants 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).	Placebo n=51 Participants 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).
Rate of Mechanical Ventilation (RMV)	13.6 Percentage of participants Interval 6.4 to 24.3	11.8 Percentage of participants Interval 4.4 to 23.9

SECONDARY outcome

Timeframe: Baseline up to Day 28

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

Outcome measures

Outcome measures
Measure	Selinexor 20 mg n=66 Participants 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).	Placebo n=51 Participants 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).
Rate of Intensive Care Unit (ICU) Admission	48.5 Percentage of participants Interval 36.0 to 61.1	41.2 Percentage of participants Interval 27.6 to 55.8

SECONDARY outcome

Timeframe: Baseline up to Day 67

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

Outcome measures

Outcome measures
Measure	Selinexor 20 mg n=66 Participants 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).	Placebo n=51 Participants 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).
Length of Hospitalization	9.0 Days Interval 3.0 to 39.0	9.0 Days Interval 3.0 to 67.0

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Selinexor 20 mg n=103 Participants 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).	Placebo n=87 Participants 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).
Change From Baseline in C-reactive Protein (CRP) Levels Change at Day 12	-86.9158 milligram per liter (mg/L) Standard Deviation 123.54705	-93.2744 milligram per liter (mg/L) Standard Deviation 131.56709
Change From Baseline in C-reactive Protein (CRP) Levels Change at Day 15	-87.9800 milligram per liter (mg/L) Standard Deviation 121.19999	-98.7940 milligram per liter (mg/L) Standard Deviation 87.65276
Change From Baseline in C-reactive Protein (CRP) Levels Change at Day 3	-47.9660 milligram per liter (mg/L) Standard Deviation 99.06082	-42.9658 milligram per liter (mg/L) Standard Deviation 89.09341
Change From Baseline in C-reactive Protein (CRP) Levels Change at Day 5	-74.4735 milligram per liter (mg/L) Standard Deviation 114.52388	-68.6191 milligram per liter (mg/L) Standard Deviation 108.19671
Change From Baseline in C-reactive Protein (CRP) Levels Change at Day 8	-83.3460 milligram per liter (mg/L) Standard Deviation 93.83500	-74.4669 milligram per liter (mg/L) Standard Deviation 117.66505
Change From Baseline in C-reactive Protein (CRP) Levels Change at Day 19	-66.2143 milligram per liter (mg/L) Standard Deviation 86.55049	-124.3233 milligram per liter (mg/L) Standard Deviation 102.04161
Change From Baseline in C-reactive Protein (CRP) Levels Change at Day 22	-90.7100 milligram per liter (mg/L) Standard Deviation 149.25579	-47.5620 milligram per liter (mg/L) Standard Deviation 171.49171
Change From Baseline in C-reactive Protein (CRP) Levels Change at Day 26	-37.2800 milligram per liter (mg/L) Standard Deviation 141.41390	-129.5020 milligram per liter (mg/L) Standard Deviation 46.26178

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Selinexor 20 mg n=103 Participants 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).	Placebo n=87 Participants 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).
Change From Baseline in Ferritin Levels Change at Day 5	-25.7000 microgram/liter (mcg/L) Standard Deviation 856.16619	-155.3111 microgram/liter (mcg/L) Standard Deviation 773.76777
Change From Baseline in Ferritin Levels Change at Day 3	80.8415 microgram/liter (mcg/L) Standard Deviation 759.10075	-61.9843 microgram/liter (mcg/L) Standard Deviation 542.09460
Change From Baseline in Ferritin Levels Change at Day 8	226.6113 microgram/liter (mcg/L) Standard Deviation 1673.46162	-292.2462 microgram/liter (mcg/L) Standard Deviation 738.07874
Change From Baseline in Ferritin Levels Change at Day 12	193.5793 microgram/liter (mcg/L) Standard Deviation 1203.33385	-352.5280 microgram/liter (mcg/L) Standard Deviation 741.13673
Change From Baseline in Ferritin Levels Change at Day 15	204.3900 microgram/liter (mcg/L) Standard Deviation 557.29217	-356.8429 microgram/liter (mcg/L) Standard Deviation 476.04151
Change From Baseline in Ferritin Levels Change at Day 19	-15.9333 microgram/liter (mcg/L) Standard Deviation 462.40358	-231.2374 microgram/liter (mcg/L) Standard Deviation 599.98919
Change From Baseline in Ferritin Levels Change at Day 22	-103.9900 microgram/liter (mcg/L) Standard Deviation 636.89555	-102.0000 microgram/liter (mcg/L) Standard Deviation 417.51247
Change From Baseline in Ferritin Levels Change at Day 26	-150.1167 microgram/liter (mcg/L) Standard Deviation 535.94141	-25.7500 microgram/liter (mcg/L) Standard Deviation 231.43232

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Selinexor 20 mg n=103 Participants 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).	Placebo n=87 Participants 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).
Change From Baseline in Lactate Dehydrogenase (LDH) Levels Change at Day 3	-13.86 units/liter (U/L) Standard Deviation 148.231	-11.86 units/liter (U/L) Standard Deviation 151.630
Change From Baseline in Lactate Dehydrogenase (LDH) Levels Change at Day 5	-49.12 units/liter (U/L) Standard Deviation 175.722	31.85 units/liter (U/L) Standard Deviation 326.281
Change From Baseline in Lactate Dehydrogenase (LDH) Levels Change at Day 8	-75.85 units/liter (U/L) Standard Deviation 264.840	-10.93 units/liter (U/L) Standard Deviation 166.876
Change From Baseline in Lactate Dehydrogenase (LDH) Levels Change at Day 12	-107.39 units/liter (U/L) Standard Deviation 198.092	-16.84 units/liter (U/L) Standard Deviation 232.605
Change From Baseline in Lactate Dehydrogenase (LDH) Levels Change at Day 15	-71.82 units/liter (U/L) Standard Deviation 193.543	-51.50 units/liter (U/L) Standard Deviation 148.063
Change From Baseline in Lactate Dehydrogenase (LDH) Levels Change at Day 19	-96.38 units/liter (U/L) Standard Deviation 200.164	-74.14 units/liter (U/L) Standard Deviation 114.271
Change From Baseline in Lactate Dehydrogenase (LDH) Levels Change at Day 22	-129.70 units/liter (U/L) Standard Deviation 177.454	-75.40 units/liter (U/L) Standard Deviation 43.569
Change From Baseline in Lactate Dehydrogenase (LDH) Levels Change at Day 26	-169.50 units/liter (U/L) Standard Deviation 213.481	4.50 units/liter (U/L) Standard Deviation 130.733

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Selinexor 20 mg n=103 Participants 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).	Placebo n=87 Participants 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).
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	2.046 nanograms/milliliter (ng/mL) Standard Deviation 49.0258
Changes From Baseline in Blood Plasma Cytokines Levels-Interleukin-6 (IL-6) Change at Day 5	-10.786 nanograms/milliliter (ng/mL) Standard Deviation 102.9160	-77.509 nanograms/milliliter (ng/mL) Standard Deviation 408.0085
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	183.728 nanograms/milliliter (ng/mL) Standard Deviation 662.7908
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	223.637 nanograms/milliliter (ng/mL) Standard Deviation 715.5904
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	207.625 nanograms/milliliter (ng/mL) Standard Deviation 408.5783
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	—
Changes From Baseline in Blood Plasma Cytokines Levels-Interleukin-6 (IL-6) Change at Day 26	-23.400 nanograms/milliliter (ng/mL)	—

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Selinexor 20 mg n=102 Participants 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).	Placebo n=86 Participants 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).
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs Participants with TEAEs	75 Participants	49 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs Participants with Serious TEAEs	23 Participants	14 Participants

Adverse Events

Selinexor 20 mg

Serious events: 23 serious events

Other events: 69 other events

Deaths: 16 deaths

Placebo

Serious events: 14 serious events

Other events: 45 other events

Deaths: 8 deaths

Serious adverse events

Other adverse events

Additional Information

Jatin Shah, MD

Karyopharm Therapeutics Inc

Phone: (617) 658-0600

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Selinexor 20 mg n=102 participants at risk 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).	Placebo n=86 participants at risk 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).
Cardiac disorders Atrial fibrillation	0.98% 1/102 • From start of study drug administration up to Day 58 All-treat population consisted of the subset of ITT participants who took at least one dose of study treatment on this study.	1.2% 1/86 • From start of study drug administration up to Day 58 All-treat population consisted of the subset of ITT participants who took at least one dose of study treatment on this study.
Cardiac disorders Cardiac arrest	2.0% 2/102 • From start of study drug administration up to Day 58 All-treat population consisted of the subset of ITT participants who took at least one dose of study treatment on this study.	0.00% 0/86 • From start of study drug administration up to Day 58 All-treat population consisted of the subset of ITT participants who took at least one dose of study treatment on this study.
Cardiac disorders Myocardial infarction	0.00% 0/102 • From start of study drug administration up to Day 58 All-treat population consisted of the subset of ITT participants who took at least one dose of study treatment on this study.	2.3% 2/86 • From start of study drug administration up to Day 58 All-treat population consisted of the subset of ITT participants who took at least one dose of study treatment on this study.
Cardiac disorders Cardiac failure	0.98% 1/102 • From start of study drug administration up to Day 58 All-treat population consisted of the subset of ITT participants who took at least one dose of study treatment on this study.	0.00% 0/86 • From start of study drug administration up to Day 58 All-treat population consisted of the subset of ITT participants who took at least one dose of study treatment on this study.
Cardiac disorders Long QT syndrome	0.98% 1/102 • From start of study drug administration up to Day 58 All-treat population consisted of the subset of ITT participants who took at least one dose of study treatment on this study.	0.00% 0/86 • From start of study drug administration up to Day 58 All-treat population consisted of the subset of ITT participants who took at least one dose of study treatment on this study.
Gastrointestinal disorders Intestinal ischaemia	0.00% 0/102 • From start of study drug administration up to Day 58 All-treat population consisted of the subset of ITT participants who took at least one dose of study treatment on this study.	1.2% 1/86 • From start of study drug administration up to Day 58 All-treat population consisted of the subset of ITT participants who took at least one dose of study treatment on this study.
General disorders Multiple organ dysfunction syndrome	0.00% 0/102 • From start of study drug administration up to Day 58 All-treat population consisted of the subset of ITT participants who took at least one dose of study treatment on this study.	2.3% 2/86 • From start of study drug administration up to Day 58 All-treat population consisted of the subset of ITT participants who took at least one dose of study treatment on this study.
General disorders Systemic inflammatory response syndrome	0.98% 1/102 • From start of study drug administration up to Day 58 All-treat population consisted of the subset of ITT participants who took at least one dose of study treatment on this study.	0.00% 0/86 • From start of study drug administration up to Day 58 All-treat population consisted of the subset of ITT participants who took at least one dose of study treatment on this study.
Infections and infestations COVID-19	0.00% 0/102 • From start of study drug administration up to Day 58 All-treat population consisted of the subset of ITT participants who took at least one dose of study treatment on this study.	2.3% 2/86 • From start of study drug administration up to Day 58 All-treat population consisted of the subset of ITT participants who took at least one dose of study treatment on this study.
Infections and infestations Pneumonia	0.98% 1/102 • From start of study drug administration up to Day 58 All-treat population consisted of the subset of ITT participants who took at least one dose of study treatment on this study.	1.2% 1/86 • From start of study drug administration up to Day 58 All-treat population consisted of the subset of ITT participants who took at least one dose of study treatment on this study.
Infections and infestations Sepsis	0.00% 0/102 • From start of study drug administration up to Day 58 All-treat population consisted of the subset of ITT participants who took at least one dose of study treatment on this study.	1.2% 1/86 • From start of study drug administration up to Day 58 All-treat population consisted of the subset of ITT participants who took at least one dose of study treatment on this study.
Infections and infestations Viral myocarditis	0.98% 1/102 • From start of study drug administration up to Day 58 All-treat population consisted of the subset of ITT participants who took at least one dose of study treatment on this study.	0.00% 0/86 • From start of study drug administration up to Day 58 All-treat population consisted of the subset of ITT participants who took at least one dose of study treatment on this study.
Injury, poisoning and procedural complications Procedural pneumothorax	0.98% 1/102 • From start of study drug administration up to Day 58 All-treat population consisted of the subset of ITT participants who took at least one dose of study treatment on this study.	0.00% 0/86 • From start of study drug administration up to Day 58 All-treat population consisted of the subset of ITT participants who took at least one dose of study treatment on this study.
Metabolism and nutrition disorders Metabolic acidosis	0.00% 0/102 • From start of study drug administration up to Day 58 All-treat population consisted of the subset of ITT participants who took at least one dose of study treatment on this study.	1.2% 1/86 • From start of study drug administration up to Day 58 All-treat population consisted of the subset of ITT participants who took at least one dose of study treatment on this study.
Nervous system disorders Cerebrovascular accident	0.00% 0/102 • From start of study drug administration up to Day 58 All-treat population consisted of the subset of ITT participants who took at least one dose of study treatment on this study.	1.2% 1/86 • From start of study drug administration up to Day 58 All-treat population consisted of the subset of ITT participants who took at least one dose of study treatment on this study.
Psychiatric disorders Catatonia	0.98% 1/102 • From start of study drug administration up to Day 58 All-treat population consisted of the subset of ITT participants who took at least one dose of study treatment on this study.	0.00% 0/86 • From start of study drug administration up to Day 58 All-treat population consisted of the subset of ITT participants who took at least one dose of study treatment on this study.
Blood and lymphatic system disorders Iron deficiency anaemia	0.98% 1/102 • From start of study drug administration up to Day 58 All-treat population consisted of the subset of ITT participants who took at least one dose of study treatment on this study.	0.00% 0/86 • From start of study drug administration up to Day 58 All-treat population consisted of the subset of ITT participants who took at least one dose of study treatment on this study.
Renal and urinary disorders Acute kidney injury	2.0% 2/102 • From start of study drug administration up to Day 58 All-treat population consisted of the subset of ITT participants who took at least one dose of study treatment on this study.	1.2% 1/86 • From start of study drug administration up to Day 58 All-treat population consisted of the subset of ITT participants who took at least one dose of study treatment on this study.
Renal and urinary disorders Renal failure	0.98% 1/102 • From start of study drug administration up to Day 58 All-treat population consisted of the subset of ITT participants who took at least one dose of study treatment on this study.	0.00% 0/86 • From start of study drug administration up to Day 58 All-treat population consisted of the subset of ITT participants who took at least one dose of study treatment on this study.
Respiratory, thoracic and mediastinal disorders Respiratory failure	5.9% 6/102 • From start of study drug administration up to Day 58 All-treat population consisted of the subset of ITT participants who took at least one dose of study treatment on this study.	2.3% 2/86 • From start of study drug administration up to Day 58 All-treat population consisted of the subset of ITT participants who took at least one dose of study treatment on this study.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	3.9% 4/102 • From start of study drug administration up to Day 58 All-treat population consisted of the subset of ITT participants who took at least one dose of study treatment on this study.	2.3% 2/86 • From start of study drug administration up to Day 58 All-treat population consisted of the subset of ITT participants who took at least one dose of study treatment on this study.
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	2.0% 2/102 • From start of study drug administration up to Day 58 All-treat population consisted of the subset of ITT participants who took at least one dose of study treatment on this study.	2.3% 2/86 • From start of study drug administration up to Day 58 All-treat population consisted of the subset of ITT participants who took at least one dose of study treatment on this study.
Respiratory, thoracic and mediastinal disorders Pneumothorax	2.0% 2/102 • From start of study drug administration up to Day 58 All-treat population consisted of the subset of ITT participants who took at least one dose of study treatment on this study.	0.00% 0/86 • From start of study drug administration up to Day 58 All-treat population consisted of the subset of ITT participants who took at least one dose of study treatment on this study.
Respiratory, thoracic and mediastinal disorders Hypoxia	0.98% 1/102 • From start of study drug administration up to Day 58 All-treat population consisted of the subset of ITT participants who took at least one dose of study treatment on this study.	0.00% 0/86 • From start of study drug administration up to Day 58 All-treat population consisted of the subset of ITT participants who took at least one dose of study treatment on this study.
Respiratory, thoracic and mediastinal disorders Pneumonia aspiration	0.00% 0/102 • From start of study drug administration up to Day 58 All-treat population consisted of the subset of ITT participants who took at least one dose of study treatment on this study.	1.2% 1/86 • From start of study drug administration up to Day 58 All-treat population consisted of the subset of ITT participants who took at least one dose of study treatment on this study.
Respiratory, thoracic and mediastinal disorders Respiratory distress	0.00% 0/102 • From start of study drug administration up to Day 58 All-treat population consisted of the subset of ITT participants who took at least one dose of study treatment on this study.	1.2% 1/86 • From start of study drug administration up to Day 58 All-treat population consisted of the subset of ITT participants who took at least one dose of study treatment on this study.

Measure	Selinexor 20 mg n=102 participants at risk 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).	Placebo n=86 participants at risk 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).
Blood and lymphatic system disorders Anaemia	8.8% 9/102 • From start of study drug administration up to Day 58 All-treat population consisted of the subset of ITT participants who took at least one dose of study treatment on this study.	1.2% 1/86 • From start of study drug administration up to Day 58 All-treat population consisted of the subset of ITT participants who took at least one dose of study treatment on this study.
Blood and lymphatic system disorders Lymphopenia	4.9% 5/102 • From start of study drug administration up to Day 58 All-treat population consisted of the subset of ITT participants who took at least one dose of study treatment on this study.	2.3% 2/86 • From start of study drug administration up to Day 58 All-treat population consisted of the subset of ITT participants who took at least one dose of study treatment on this study.
Blood and lymphatic system disorders Leukopenia	4.9% 5/102 • From start of study drug administration up to Day 58 All-treat population consisted of the subset of ITT participants who took at least one dose of study treatment on this study.	1.2% 1/86 • From start of study drug administration up to Day 58 All-treat population consisted of the subset of ITT participants who took at least one dose of study treatment on this study.
Gastrointestinal disorders Constipation	13.7% 14/102 • From start of study drug administration up to Day 58 All-treat population consisted of the subset of ITT participants who took at least one dose of study treatment on this study.	10.5% 9/86 • From start of study drug administration up to Day 58 All-treat population consisted of the subset of ITT participants who took at least one dose of study treatment on this study.
Gastrointestinal disorders Nausea	12.7% 13/102 • From start of study drug administration up to Day 58 All-treat population consisted of the subset of ITT participants who took at least one dose of study treatment on this study.	7.0% 6/86 • From start of study drug administration up to Day 58 All-treat population consisted of the subset of ITT participants who took at least one dose of study treatment on this study.
Gastrointestinal disorders Diarrhoea	9.8% 10/102 • From start of study drug administration up to Day 58 All-treat population consisted of the subset of ITT participants who took at least one dose of study treatment on this study.	4.7% 4/86 • From start of study drug administration up to Day 58 All-treat population consisted of the subset of ITT participants who took at least one dose of study treatment on this study.
Infections and infestations COVID-19	4.9% 5/102 • From start of study drug administration up to Day 58 All-treat population consisted of the subset of ITT participants who took at least one dose of study treatment on this study.	0.00% 0/86 • From start of study drug administration up to Day 58 All-treat population consisted of the subset of ITT participants who took at least one dose of study treatment on this study.
Investigations Aspartate aminotransferase increased	8.8% 9/102 • From start of study drug administration up to Day 58 All-treat population consisted of the subset of ITT participants who took at least one dose of study treatment on this study.	8.1% 7/86 • From start of study drug administration up to Day 58 All-treat population consisted of the subset of ITT participants who took at least one dose of study treatment on this study.
Investigations Alanine aminotransferase increased	7.8% 8/102 • From start of study drug administration up to Day 58 All-treat population consisted of the subset of ITT participants who took at least one dose of study treatment on this study.	4.7% 4/86 • From start of study drug administration up to Day 58 All-treat population consisted of the subset of ITT participants who took at least one dose of study treatment on this study.
Metabolism and nutrition disorders Hyponatraemia	23.5% 24/102 • From start of study drug administration up to Day 58 All-treat population consisted of the subset of ITT participants who took at least one dose of study treatment on this study.	5.8% 5/86 • From start of study drug administration up to Day 58 All-treat population consisted of the subset of ITT participants who took at least one dose of study treatment on this study.
Metabolism and nutrition disorders Hyperglycaemia	6.9% 7/102 • From start of study drug administration up to Day 58 All-treat population consisted of the subset of ITT participants who took at least one dose of study treatment on this study.	3.5% 3/86 • From start of study drug administration up to Day 58 All-treat population consisted of the subset of ITT participants who took at least one dose of study treatment on this study.
Metabolism and nutrition disorders Hypoalbuminaemia	3.9% 4/102 • From start of study drug administration up to Day 58 All-treat population consisted of the subset of ITT participants who took at least one dose of study treatment on this study.	5.8% 5/86 • From start of study drug administration up to Day 58 All-treat population consisted of the subset of ITT participants who took at least one dose of study treatment on this study.
Metabolism and nutrition disorders Hypokalaemia	4.9% 5/102 • From start of study drug administration up to Day 58 All-treat population consisted of the subset of ITT participants who took at least one dose of study treatment on this study.	3.5% 3/86 • From start of study drug administration up to Day 58 All-treat population consisted of the subset of ITT participants who took at least one dose of study treatment on this study.
Metabolism and nutrition disorders Hypophosphataemia	4.9% 5/102 • From start of study drug administration up to Day 58 All-treat population consisted of the subset of ITT participants who took at least one dose of study treatment on this study.	0.00% 0/86 • From start of study drug administration up to Day 58 All-treat population consisted of the subset of ITT participants who took at least one dose of study treatment on this study.
Respiratory, thoracic and mediastinal disorders Hypoxia	5.9% 6/102 • From start of study drug administration up to Day 58 All-treat population consisted of the subset of ITT participants who took at least one dose of study treatment on this study.	2.3% 2/86 • From start of study drug administration up to Day 58 All-treat population consisted of the subset of ITT participants who took at least one dose of study treatment on this study.
Vascular disorders Hypotension	2.9% 3/102 • From start of study drug administration up to Day 58 All-treat population consisted of the subset of ITT participants who took at least one dose of study treatment on this study.	5.8% 5/86 • From start of study drug administration up to Day 58 All-treat population consisted of the subset of ITT participants who took at least one dose of study treatment on this study.