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

• Sponsor: Karyopharm Therapeutics Inc (Industry)
• Overall Status: Completed
• CT.gov ID: NCT04349098
• Collaborator: (none)
• Enrollment: 190
• Locations: 33
• Arms: 2
• Actual Duration (Months): 5.6
• Patients Per Site: 5.8
• Patients Per Site Per Month: 1

Study Details

Study Description

Brief Summary

The main purpose of this study is to evaluate the activity of low dose oral selinexor (KPT-330) and to evaluate the clinical recovery, the viral load, length of hospitalization and the rate of morbidity and mortality in participants with severe COVID-19 compared to placebo. The study had 2 arms and evaluated selinexor 20 mg + standard of care (SoC) and placebo + SoC. As the treatment for COVID-19 is rapidly evolving, the SoC varied over time and across regions of the world.

Condition or Disease	Intervention/Treatment	Phase
Coronavirus Infection	Drug: Selinexor; Other: Placebo	Phase 2

Study Design

• Study Type: Interventional
• 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: Apr 17, 2020
• Actual Primary Completion Date: Oct 5, 2020
• Actual Study Completion Date: Oct 5, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Selinexor 20 mg Participants will receive 20 milligram (mg) of selinexor oral tablet on Days 1, 3, and 5 of each week for up to 2 weeks (14 days). If the participant is tolerating therapy and clinically benefitting, dosing can continue for an additional 2 weeks (28 days).	Drug: Selinexor; Participants will receive 20 mg of selinexor.; Other Names: KPT-330 XPOVIO
Placebo Comparator: Placebo Participants will receive 20 mg of placebo matched to selinexor oral tablet on Days 1, 3, and 5 of each week for up to 2 weeks (14 days). If the participant is tolerating therapy and clinically benefitting, dosing can continue for an additional 2 weeks (28 days).	Other: Placebo; Participants will receive 20 mg of placebo matched to selinexor.

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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.

2. 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.

3. 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.

4. 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.

5. 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.

6. 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.

7. Length of Hospitalization [Baseline up to Day 67]

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

8. 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.

9. 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.

10. 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.

11. 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.

12. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts 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.

Contacts and Locations

Locations

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

Sponsors and Collaborators

• Karyopharm Therapeutics Inc

Investigators

• Study Director: Dayana Michel, Karyopharm Therapeutics Inc

Study Documents (Full-Text)

• Study Protocol - May 8, 2020
• Statistical Analysis Plan - Jun 19, 2020

More Information

Publications

None provided.

• Responsible Party: Karyopharm Therapeutics Inc
• ClinicalTrials.gov Identifier: NCT04349098
• Other Study ID Numbers: XPORT-CoV-1001; 2020-001411-25
• First Posted: Apr 16, 2020
• Last Update Posted: Nov 1, 2021
• Last Verified: Oct 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Undecided
• 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: COVID-19; SARS-CoV-2
• Additional relevant MeSH terms: Infections; Communicable Diseases; COVID-19; Coronavirus Infections

Study Results

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

Arm/Group Title	Selinexor 20 mg	Placebo
Arm/Group Description	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).	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).
Period Title: Overall Study
STARTED	103	87
Treated	102	86
COMPLETED	65	61
NOT COMPLETED	38	26

Baseline Characteristics

Arm/Group Title	Selinexor 20 mg	Placebo	Total
Arm/Group Description	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).	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 of all reporting groups
Overall Participants	103	87	190
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	56.5 (16.12)	56.5 (14.64)	56.5 (15.42)
Sex: Female, Male (Count of Participants)
Female	43 41.7%	39 44.8%	82 43.2%
Male	60 58.3%	48 55.2%	108 56.8%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	41 39.8%	32 36.8%	73 38.4%
Not Hispanic or Latino	59 57.3%	53 60.9%	112 58.9%
Unknown or Not Reported	3 2.9%	2 2.3%	5 2.6%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	6 5.8%	4 4.6%	10 5.3%
Native Hawaiian or Other Pacific Islander	2 1.9%	0 0%	2 1.1%
Black or African American	23 22.3%	24 27.6%	47 24.7%
White	44 42.7%	34 39.1%	78 41.1%
More than one race	19 18.4%	14 16.1%	33 17.4%
Unknown or Not Reported	9 8.7%	11 12.6%	20 10.5%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

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/Group Title	Selinexor 20 mg	Placebo
Arm/Group Description	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).	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).
Measure Participants	66	51
Number (95% Confidence Interval) [Percentage of participants]	60.6 58.8%	60.8 69.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Selinexor 20 mg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.6750
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.84
	Confidence Interval	(2-Sided) 95%; 0.39 to 1.79
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Selinexor 20 mg	Placebo
Arm/Group Description	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).	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).
Measure Participants	103	87
Number (95% Confidence Interval) [Percentage of participants]	30.1 29.2%	32.2 37%

3. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Selinexor 20 mg	Placebo
Arm/Group Description	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).	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).
Measure Participants	103	87
Day 7	51.5 50%	50.6 58.2%
Day 14	72.8 70.7%	72.4 83.2%

4. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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/Group Title	Selinexor 20 mg	Placebo
Arm/Group Description	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).	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).
Measure Participants	66	51
Median (95% Confidence Interval) [Days]	10.0	10.0

5. Secondary Outcome

Title	Overall Death Rate
Description	Overall death rate was defined as the percentage of participants who died on or before Day 28.
Time Frame	Baseline up to Day 28

Outcome Measure Data

Analysis Population Description

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/Group Title	Selinexor 20 mg	Placebo
Arm/Group Description	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).	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).
Measure Participants	66	51
Number (95% Confidence Interval) [Percentage of participants]	15.2 14.8%	3.9 4.5%

6. Secondary Outcome

Title	Rate of Mechanical Ventilation (RMV)
Description	The rate of RMV was defined as the percentage of participants who ever used invasive mechanical ventilation or ECMO during the hospital stay.
Time Frame	Baseline up to Day 28

Outcome Measure Data

Analysis Population Description

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/Group Title	Selinexor 20 mg	Placebo
Arm/Group Description	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).	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).
Measure Participants	66	51
Number (95% Confidence Interval) [Percentage of participants]	13.6 13.2%	11.8 13.6%

7. Secondary Outcome

Title	Rate of Intensive Care Unit (ICU) Admission
Description	The rate of ICU admission was defined as the percentage of participants with ICU admissions.
Time Frame	Baseline up to Day 28

Outcome Measure Data

Analysis Population Description

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/Group Title	Selinexor 20 mg	Placebo
Arm/Group Description	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).	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).
Measure Participants	66	51
Number (95% Confidence Interval) [Percentage of participants]	48.5 47.1%	41.2 47.4%

8. Secondary Outcome

Title	Length of Hospitalization
Description	Length of hospitalization (days) was defined as (first hospital discharge date - date of randomization + 1).
Time Frame	Baseline up to Day 67

Outcome Measure Data

Analysis Population Description

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/Group Title	Selinexor 20 mg	Placebo
Arm/Group Description	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).	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).
Measure Participants	66	51
Median (Full Range) [Days]	9.0	9.0

9. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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/Group Title	Selinexor 20 mg	Placebo
Arm/Group Description	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).	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).
Measure Participants	103	87
Change at Day 3	-47.9660 (99.06082)	-42.9658 (89.09341)
Change at Day 5	-74.4735 (114.52388)	-68.6191 (108.19671)
Change at Day 8	-83.3460 (93.83500)	-74.4669 (117.66505)
Change at Day 12	-86.9158 (123.54705)	-93.2744 (131.56709)
Change at Day 15	-87.9800 (121.19999)	-98.7940 (87.65276)
Change at Day 19	-66.2143 (86.55049)	-124.3233 (102.04161)
Change at Day 22	-90.7100 (149.25579)	-47.5620 (171.49171)
Change at Day 26	-37.2800 (141.41390)	-129.5020 (46.26178)

10. Secondary Outcome

Title	Change From Baseline in Ferritin Levels
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Selinexor 20 mg	Placebo
Arm/Group Description	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).	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).
Measure Participants	103	87
Change at Day 3	80.8415 (759.10075)	-61.9843 (542.09460)
Change at Day 5	-25.7000 (856.16619)	-155.3111 (773.76777)
Change at Day 8	226.6113 (1673.46162)	-292.2462 (738.07874)
Change at Day 12	193.5793 (1203.33385)	-352.5280 (741.13673)
Change at Day 15	204.3900 (557.29217)	-356.8429 (476.04151)
Change at Day 19	-15.9333 (462.40358)	-231.2374 (599.98919)
Change at Day 22	-103.9900 (636.89555)	-102.0000 (417.51247)
Change at Day 26	-150.1167 (535.94141)	-25.7500 (231.43232)

11. Secondary Outcome

Title	Change From Baseline in Lactate Dehydrogenase (LDH) Levels
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Selinexor 20 mg	Placebo
Arm/Group Description	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).	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).
Measure Participants	103	87
Change at Day 3	-13.86 (148.231)	-11.86 (151.630)
Change at Day 5	-49.12 (175.722)	31.85 (326.281)
Change at Day 8	-75.85 (264.840)	-10.93 (166.876)
Change at Day 12	-107.39 (198.092)	-16.84 (232.605)
Change at Day 15	-71.82 (193.543)	-51.50 (148.063)
Change at Day 19	-96.38 (200.164)	-74.14 (114.271)
Change at Day 22	-129.70 (177.454)	-75.40 (43.569)
Change at Day 26	-169.50 (213.481)	4.50 (130.733)

12. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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/Group Title	Selinexor 20 mg	Placebo
Arm/Group Description	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).	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).
Measure Participants	103	87
Change at Day 3	-19.931 (51.2072)	2.046 (49.0258)
Change at Day 5	-10.786 (102.9160)	-77.509 (408.0085)
Change at Day 8	-13.909 (161.6803)	183.728 (662.7908)
Change at Day 12	276.289 (1541.3692)	223.637 (715.5904)
Change at Day 15	-34.850 (28.6357)	207.625 (408.5783)
Change at Day 22	-8.600 (11.8072)
Change at Day 26	-23.400

13. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

All-treat population consisted of the subset of ITT participants who took at least one dose of study treatment on this study.

Arm/Group Title	Selinexor 20 mg	Placebo
Arm/Group Description	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).	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).
Measure Participants	102	86
Participants with TEAEs	75 72.8%	49 56.3%
Participants with Serious TEAEs	23 22.3%	14 16.1%

Adverse Events

Time Frame	From start of study drug administration up to Day 58
Adverse Event Reporting Description	All-treat population consisted of the subset of ITT participants who took at least one dose of study treatment on this study.
Arm/Group Title	Selinexor 20 mg		Placebo
Arm/Group Description	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).		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).
All Cause Mortality
	Selinexor 20 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	16/102 (15.7%)		8/86 (9.3%)
Serious Adverse Events
	Selinexor 20 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	23/102 (22.5%)		14/86 (16.3%)
Blood and lymphatic system disorders
Iron deficiency anaemia	1/102 (1%)		0/86 (0%)
Cardiac disorders
Atrial fibrillation	1/102 (1%)		1/86 (1.2%)
Cardiac arrest	2/102 (2%)		0/86 (0%)
Myocardial infarction	0/102 (0%)		2/86 (2.3%)
Cardiac failure	1/102 (1%)		0/86 (0%)
Long QT syndrome	1/102 (1%)		0/86 (0%)
Gastrointestinal disorders
Intestinal ischaemia	0/102 (0%)		1/86 (1.2%)
General disorders
Multiple organ dysfunction syndrome	0/102 (0%)		2/86 (2.3%)
Systemic inflammatory response syndrome	1/102 (1%)		0/86 (0%)
Infections and infestations
COVID-19	0/102 (0%)		2/86 (2.3%)
Pneumonia	1/102 (1%)		1/86 (1.2%)
Sepsis	0/102 (0%)		1/86 (1.2%)
Viral myocarditis	1/102 (1%)		0/86 (0%)
Injury, poisoning and procedural complications
Procedural pneumothorax	1/102 (1%)		0/86 (0%)
Metabolism and nutrition disorders
Metabolic acidosis	0/102 (0%)		1/86 (1.2%)
Nervous system disorders
Cerebrovascular accident	0/102 (0%)		1/86 (1.2%)
Psychiatric disorders
Catatonia	1/102 (1%)		0/86 (0%)
Renal and urinary disorders
Acute kidney injury	2/102 (2%)		1/86 (1.2%)
Renal failure	1/102 (1%)		0/86 (0%)
Respiratory, thoracic and mediastinal disorders
Respiratory failure	6/102 (5.9%)		2/86 (2.3%)
Pulmonary embolism	4/102 (3.9%)		2/86 (2.3%)
Acute respiratory failure	2/102 (2%)		2/86 (2.3%)
Pneumothorax	2/102 (2%)		0/86 (0%)
Hypoxia	1/102 (1%)		0/86 (0%)
Pneumonia aspiration	0/102 (0%)		1/86 (1.2%)
Respiratory distress	0/102 (0%)		1/86 (1.2%)
Other (Not Including Serious) Adverse Events
	Selinexor 20 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	69/102 (67.6%)		45/86 (52.3%)
Blood and lymphatic system disorders
Anaemia	9/102 (8.8%)		1/86 (1.2%)
Lymphopenia	5/102 (4.9%)		2/86 (2.3%)
Leukopenia	5/102 (4.9%)		1/86 (1.2%)
Gastrointestinal disorders
Constipation	14/102 (13.7%)		9/86 (10.5%)
Nausea	13/102 (12.7%)		6/86 (7%)
Diarrhoea	10/102 (9.8%)		4/86 (4.7%)
Infections and infestations
COVID-19	5/102 (4.9%)		0/86 (0%)
Investigations
Aspartate aminotransferase increased	9/102 (8.8%)		7/86 (8.1%)
Alanine aminotransferase increased	8/102 (7.8%)		4/86 (4.7%)
Metabolism and nutrition disorders
Hyponatraemia	24/102 (23.5%)		5/86 (5.8%)
Hyperglycaemia	7/102 (6.9%)		3/86 (3.5%)
Hypoalbuminaemia	4/102 (3.9%)		5/86 (5.8%)
Hypokalaemia	5/102 (4.9%)		3/86 (3.5%)
Hypophosphataemia	5/102 (4.9%)		0/86 (0%)
Respiratory, thoracic and mediastinal disorders
Hypoxia	6/102 (5.9%)		2/86 (2.3%)
Vascular disorders
Hypotension	3/102 (2.9%)		5/86 (5.8%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.