Conditions: Coronavirus Infection
Keywords: COVID-19 SARS-CoV-2
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 190
Healthy volunteers: no

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.

Detailed description:

Arms:
arm 1: 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). arm 2: 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).

Interventions: intervention 1: Selinexor intervention 2: Placebo
Intervention descriptions: intervention 1: Participants will receive 20 mg of selinexor. intervention 2: Participants will receive 20 mg of placebo matched to selinexor.

Protocol document:
Prot_000.pdf: 
Cli nical St u d y Pr ot oc ol: X P O R T -C o V -1 0 0 1  
Seli ne x or  
Versi o n 6 . 0 
 
0 8 Ma y 2 0 2 0  
C o nfi de ntial  
 
Pa ge 1 of 7 4  
C LI NI C A L S T U D Y P R O T O C O L  
X P O R T -C o V - 1 0 0 1 
A P h ase 2 R a n d o mi ze d Si n gle - Bli n d St u d y t o E v al u ate t he Acti vit y a n d S afet y of L o w D ose 
Or al Seli ne x or ( K P T -3 3 0) i n P atie nts wit h Se vere C O VI D - 1 9 I nfecti o n  
(X P O R T- C o V- 1 0 0 1)  
St u d y N u m ber:  
X P O R T -C o V -1 0 0 1  
St u d y P h ase:  
P hase 2  
I n vesti g ati o n al Pr o d uct: 
Sel i ne x or (X P O VI O ® , K P T -3 3 0 ) 
I n dic ati o n: 
Se vere C O VI D -1 9   
E u dr a C T N u m ber:  
I N D N u m ber 
2 0 2 0 -0 0 1 4 1 1 -2 5  
 
S p o ns or:  
Kar y o p har m T hera pe utics I nc.  
8 5 Wells A ve n ue  
Ne wt o n, M A 0 2 4 5 9 U S A  
Tel. + ( 6 1 7) 6 5 8 -0 6 0 0  
Pr ot oc ol D ate a n d 
Versi o n:  
2 7 Marc h 2 0 2 0, Versi o n 1. 0 ( Ori gi nal)  
0 5 A pril 2 0 2 0, Versi o n 2. 0 ( A me n d me nt 1)  
0 7 A pril 2 0 2 0, Versi o n 3. 0 ( A me n d me nt 2 - c o u ntr y s pecific U S)  
0 9 A pril 2 0 2 0, Versi o n 4. 0  ( A me n d me nt 3 - c o u ntr y s pecific U S)  
1 1 A pril 2 0 2 0, Versi o n 4. 0 ( A me n d me nt 4 - Gl o bal)  
1 5 A pril 2 0 2 0, Versi o n 4. 0 U K (c o u ntr y s pecific U nite d Ki n g d o m)  
1 8 A pril 2 0 2 0, Versi o n 4. 0 D E (c o u ntr y s pecific Ger ma n y)  
1 8 A pril 2 0 2 0, Versi o n 4. 0 I L (c o u ntr y s pecific Israel) 
0 2 Ma y 2 0 2 0, Versi o n 5. 0 (c o u ntr y s pecific U S)  
0 4 Ma y 2 0 2 0, Versi o n 1. 1 (c o u ntr y s pecific Ital y)  
0 8 Ma y 2 0 2 0, Versi o n 6. 0  (c o u ntr y s pecific U S) 
C O N D U C T  
I n acc or da nce wit h t he et hical pri nci ples t hat ori gi nate fr o m t he Declarati o n of Helsi n ki a n d t hat are 
c o nsiste nt wit h I nter nati o nal C o u ncil f or Har m o nisati o n (I C H) g ui deli nes o n G o o d Cli nical Practice 
( G C P) a n d re g ulat or y re q uire me nts as a p plica ble. 
C O N F I D E N TI A L I N F O R M A TI O N 
T his d oc u me nt is t he s ole pr o pert y of Kar y o p har m T hera pe utics I nc. ( Kar y o p har m). T his d oc u me nt a n d 
all i nf or mati o n c o ntai ne d herei n has t o be c o nsi dere d a n d treate d as strictl y c o nfi de ntial. T his d oc u me nt 
will be use d o nl y f or t he discl os ure herei n pr o vi de d. N o discl os ure or p u blicati o n will be ma de wit h o ut 
t he pri or writte n c o nse nt of Kar y o p har m. 
 
 
C CI


Cli nical St u d y Pr ot oc ol: X P O R T -C o V -1 0 0 1  
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Pa ge 2 of 7 4  
P R O T O C O L A P P R O V A L SI G N A T U R E P A G E  
S P O N S O R: K A R Y O P H A R M T H E R A P E U TI C S I N C.  
I ha ve rea d a n d u n dersta n d t he c o nte nts of t his cli nical pr ot oc ol f or St u d y X P O R T -C o V - 1 0 0 1 
date d 0 8 Ma y  2 0 2 0 a n d a gree t o meet all o bli gati o ns of Kar y o p har m T hera pe utics I nc., as 
detaile d i n all a p plica ble re g ulati o ns a n d g ui deli nes. I n a d diti o n, I will i nf or m t he Pri nci pal 
I n vesti gat or a n d all ot her I n vesti gat ors of all rele va nt i nf or mati o n t hat bec o mes a vaila ble d uri n g 
t he c o n d uct of t his St u d y. 
A p pr o ve d B y:  
 
 
 M D 
 
K ar y o p h ar m T her a pe utics I nc.  
 
 
 
D ate  
 
 
 
 P h D 
 
K ar y o p h ar m T her a pe utics I nc.  
 
 
 
D ate  
 
 
 
 
P P D
P P D
P P D
P P D


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INVESTIGATOR’S AGREEMENT 
 
I have read and understand the contents of this clinical protocol for Study XPORT-CoV-1001 
dated 08 May 2020 and will adhere to the study requirements as presented, including all 
statements regarding confidentiality. In addition, I will conduct the Study in accordance with 
current Good Clinical Practice, ICH E6, and applicable FDA regulatory requirements. 
 
 
________________________________________________________________________ 
Printed Name of Investigator 
 
________________________________________________________________________ 
Signature of Investigator 
 
________________________________________________________________________ 
Institution 
 
__________________________________________ 
Date 
 
 
 


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TABLE OF CONTENTS 
PROTOCOL APPROVAL SIGNATURE PAGE ...........................................................................2 
SPONSOR: KARYOPHARM THERAPEUTICS INC. .................................................................2 
INVESTIGATOR’S AGREEMENT ...............................................................................................3 
LIST OF TABLES ...........................................................................................................................8 
LIST OF FIGURES .........................................................................................................................8 
LIST OF ABBREVIATIONS ..........................................................................................................9 
SYNOPSIS 13 
SCHEDULE OF ASSESSMENTS ................................................................................................22 
1. 
INTRODUCTION ......................................................................................................25 
1.1. 
Study Rationale ...........................................................................................................25 
1.2. 
Background on COVID-19 .........................................................................................25 
1.2.1. 
Viral Shedding and Transmission ...............................................................................26 
1.2.2. 
Cytokine Levels and Outcomes ..................................................................................26 
1.3. 
Selinexor .....................................................................................................................26 
1.4. 
Benefit/Risk Assessment ............................................................................................30 
2. 
OBJECTIVES AND ENDPOINTS ............................................................................31 
3. 
STUDY DESIGN .......................................................................................................34 
3.1. 
Overall Design ............................................................................................................34 
3.2. 
Scientific Rationale for Study Design ........................................................................35 
3.3. 
Justification for Dose ..................................................................................................35 
3.4. 
End of Study Definition ..............................................................................................35 
4. 
STUDY POPULATION .............................................................................................36 
4.1. 
Inclusion Criteria ........................................................................................................36 
4.2. 
Exclusion Criteria .......................................................................................................36 
4.3. 
Screen Failures ............................................................................................................37 
4.4. 
Randomization/Stratification ......................................................................................37 
5. 
STUDY TREATMENT ..............................................................................................39 
5.1. 
Study Treatment Administered ...................................................................................39 
5.2. 
Dosing and Administration of Selinexor/Placebo ......................................................39 
5.2.1. 
Labeling ......................................................................................................................39 
5.2.2. 
Dispensing Directions .................................................................................................39 
5.2.3. 
Dosing Information .....................................................................................................39 


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5.3. 
Missed or Vomited Doses of Selinexor ......................................................................40 
5.3.1. 
Missed Doses of Selinexor .........................................................................................40 
5.3.2. 
Vomited Doses of Selinexor .......................................................................................40 
5.4. 
Preparation/Handling/Storage/Accountability ............................................................40 
5.5. 
Study Treatment Compliance .....................................................................................41 
5.6. 
Concomitant Medication ............................................................................................41 
5.6.1. 
Recommended Concomitant Treatments ....................................................................41 
5.6.2. 
Prohibited/Permitted Concomitant Medications .........................................................41 
5.7. 
Dose Modifications .....................................................................................................41 
6. 
DISCONTINUATION OF STUDY TREATMENT AND PATIENT 
DISCONTINUATION/WITHDRAWAL ..................................................................44 
6.1. 
Discontinuation of Study Treatment ...........................................................................44 
6.2. 
Patient Discontinuation/Withdrawal from the Study ..................................................44 
6.3. 
Lost to Follow up ........................................................................................................44 
6.4. 
Blinding ......................................................................................................................45 
6.5. 
Early Termination of the Study ..................................................................................45 
6.6. 
End of Study ...............................................................................................................45 
7. 
STUDY ASSESSMENTS AND PROCEDURES ......................................................46 
7.1. 
Baseline Assessments .................................................................................................46 
7.1.1. 
Demographics .............................................................................................................46 
7.1.2. 
Medical History ..........................................................................................................46 
7.1.3. 
Disease History ...........................................................................................................46 
7.2. 
Efficacy Assessments .................................................................................................46 
7.3. 
Safety Assessments .....................................................................................................46 
7.3.1. 
Physical Examinations ................................................................................................46 
7.3.2. 
Ordinal Score ..............................................................................................................47 
7.3.3. 
Electrocardiograms .....................................................................................................47 
7.3.4. 
Clinical Safety Laboratory Assessments ....................................................................48 
7.3.5. 
Adverse Events and Serious Adverse Events .............................................................48 
7.4. 
Pharmacokinetic Assessments ....................................................................................49 
7.5. 
Cytokine Assessments ................................................................................................49 
7.6. 
Leukocyte Phenotyping ..............................................................................................49 
7.7. 
Viral  Assessments ......................................................................................................49 


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8. 
ADVERSE EVENTS ..................................................................................................50 
8.1. 
Information on Reporting Adverse Events .................................................................50 
8.1.1. 
Definitions ..................................................................................................................50 
8.1.2. 
Recording of Adverse Events .....................................................................................51 
8.1.3. 
Adverse Event Causality .............................................................................................52 
8.2. 
Serious Adverse Events ..............................................................................................53 
8.3. 
Procedures for Handling Special Situations ...............................................................54 
8.3.1. 
Pregnancy and Breastfeeding .....................................................................................54 
8.3.2. 
Abuse, Misuse, Medication Errors and Overdose ......................................................55 
9. 
STATISTICAL CONSIDERATIONS .......................................................................57 
9.1. 
General Considerations ...............................................................................................57 
9.1.1. 
Procedures for Handling Missing Data .......................................................................57 
9.2. 
Sample Size Determination ........................................................................................57 
9.3. 
Populations for Analyses ............................................................................................57 
9.4. 
Statistical Analyses .....................................................................................................57 
9.4.1. 
Efficacy Analyses .......................................................................................................57 
9.4.2. 
Safety Analyses ..........................................................................................................58 
9.4.3. 
Pharmacokinetic Analysis ..........................................................................................59 
9.4.4. 
Pharmacodynamic Analysis ........................................................................................59 
9.4.5. 
Viral Analysis .............................................................................................................59 
9.5. 
Criteria for Stopping the Study ...................................................................................59 
9.6. 
Interim Analyses .........................................................................................................60 
10. 
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS ..................................................................................................61 
10.1. 
Ethical and Administrative Obligations ......................................................................61 
10.1.1. 
Regulatory and Ethical Considerations ......................................................................61 
10.1.2. 
Responsibilities of the Investigator and Good Clinical Practice ................................61 
10.2. 
Financial Disclosure ...................................................................................................61 
10.3. 
Informed Consent Process ..........................................................................................61 
10.4. 
Data Collection and Management ..............................................................................63 
10.4.1. 
Data Confidentiality ....................................................................................................63 
10.4.2. 
Site Monitoring ...........................................................................................................63 
10.4.3. 
Data Collection ...........................................................................................................64 


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10.4.4. 
Database Management and Quality Control ...............................................................64 
10.5. 
Data Safety Monitoring Committee ............................................................................64 
10.6. 
Dissemination of Clinical Study Data ........................................................................65 
10.7. 
Source Documents ......................................................................................................65 
10.8. 
Study and Site Closure ................................................................................................66 
10.9. 
Publication Policy .......................................................................................................66 
11. 
REFERENCES ...........................................................................................................67 
APPENDIX 1. SELINEXOR AS A THERAPEUTIC STRATEGY FOR SEPSIS ...................70 
APPENDIX 2. SAFETY AND TOLERABILITY OF SELINEXOR 20-MG DOSE ................72 
APPENDIX 3. STRONG CYP3A INHIBITORS AND INDUCERS ........................................74 
 


Cli nical St u d y Pr ot oc ol: X P O R T -C o V -1 0 0 1  
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Pa ge 8 of 7 4  
  
 
 
LI S T O F T A B L E S  
Ta ble 1:  
Sc he d ule of Assess me nts f or a d mitte d patie nts o nl y  .................................................. 2 2 
Ta ble  2: 
Sc he d ule of Assess me nt P ost - Disc har ge Peri o d f or O ut patie nts O nl y  ...................... 2 4 
Ta ble  3:  
St u d y Treat me nt A d mi nistere d  ................................................................................... 3 9 
Ta ble  4: 
Seli ne x or D ose M o dificati o n Ste ps f or A d verse Reacti o ns  ....................................... 4 1 
Ta ble  5: 
Seli ne x or D osa ge M o dificati o n f or A d verse Reacti o ns ............................................. 4 2  
Ta ble  6: 
Cli nical Safet y La b orat or y Tests  ................................................................................ 4 8 
Ta ble 7:  
A d verse E ve nt ( A E) Pr ofile of L o w D ose ( ≤2 0 m g) Seli ne x or fr o m P hase 1 
St u dies i n Patie nts wit h A d va nce d Refract or y He mat ol o gic a n d S oli d T u m or 
Mali g na ncies . .............................................................................................................. 7 3 
 LI S T O F FI G U R E S  
Fi g ure 1:  
Seli ne x or I n hi bits I n Vitr o S A R S - C o V 2 Viral Pr o pa gati o n ....................................... 2 7 
Fi g ure 2:  Se psis M o del f or Seli ne x or.  ........................................................................................ 2 9 
Fi g ure 3:  Effect of Seli ne x or i n E n d ot o xi n ( L P S)- I n d uce d Se psis a n d Deat h i n Mice. ............ 7 0 
 
 
C CI


Cli nical St u d y Pr ot oc ol: X P O R T -C o V -1 0 0 1  
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Pa ge 9 of 7 4  
LI S T O F A B B R E VI A TI O N S  
T he f oll o wi n g a b bre viati o ns are use d i n t his st u d y pr ot oc ol.  
A b bre vi ati o n  
Defi niti o n  
A B G  
arterial b l o o d g as 
A E  
a d verse e ve nt  
A L T  
ala ni ne tra nsa mi nase  
A MI  
ac ute m y ocar dial i nfarcti o n  
A S T  
as partate tra nsa mi nase  
A T  
all-treat 
A T C  
A nat o mical T hera pe utic C he mical  
A U C  
area u n der t he ti me -c o nce ntrati o n c ur ve 
B U N  
bl o o d urea nitr o ge n  
C A D  
cor o nar y arter y disease  
Cr C L 
creati ni ne cleara nce  
C D 
cl uster of differe ntiati o n  
C F R  
C o de of Fe deral Re g ulati o ns  
C H F  
co n gesti ve heart fail ure  
CI 
c o nfi de nce i nter val  
C O P D  
c hr o nic o bstr ucti ve p ul m o nar y disease  
C O VI D -1 9  
c or o na vir us disease 2 0 1 9  
C ma x  
ma xi m u m plas ma c o nce ntrati o n  
C M H 
C oc hra n -Ma ntel -Hae nszel  
C CI
C CI


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C R O 
c o ntract researc h or ga nizati o n  
C R P 
C- reacti ve pr otei n 
C tr o u g h 
tr o u g h plas ma c o nce ntrati o n 
C R M 1 
c hr o m os o me re gi o n mai nte na nce 1 (als o calle d e x p orti n 1)  
D R  
deat h rate  
D S M B  
Data Safet y M o nit ori n g B oar d  
e C R F 
electr o nic case re p ort f or m  
E C G 
E lectr ocar di o gra m 
E D C  
electr o nic data ca pt ure  
E C M O 
e xtrac or p oreal me m bra ne o x y ge nati o n  
F D A  
F o o d a n d Dr u g A d mi nistrati o n  
G- C S F 
gra n ul oc yte -c ol o n y sti m ulati n g fact or  
G C P  
g o o d cli nical practice  
h C G 
h u ma n c h ori o nic g o na d otr o pi n  
HI P A A  
Healt h I ns ura nce P orta bilit y a n d Acc o u nta bilit y Act  
I A 
i nteri m a nal ysis 
I C F 
i nf or me d c o nse nt f or m 
I E C 
I n de pe n de nt E t hics C o m mittee  
I L 
Interle u ki n  
I R B 
I nstit uti o nal R e vie w B oar d  
I κ B  
i n hi bit or of n uclear fact or-ka p pa b ( nf -κ b)  
I N Fγ 
i nterfer o n-γ 
I P 
i n vesti gati o nal pr o d uct 
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ITT 
intent-to-treat 
LPM 
liters per minute 
MCP-1 
monocyte chemoattractant protein 1 
MIF-1α 
macrophage inflammatory protein 1α 
MM 
multiple myeloma 
MODS 
multiple organ dysfunction syndrome 
MW 
molecular weight 
NCI CTCAE 
National Cancer Institute Common Terminology Criteria for Adverse Events 
NES 
nuclear export sequence 
NF-κB 
nuclear factor κb 
NG 
Nasogastric 
NHBE 
normal human bronchial epithelial 
NSAID 
nonsteroidal anti-inflammatory drugs 
OSI 
Ordinal Scale for Clinical Improvement   
PEG 
percutaneous endoscopic gastrostomy 
PFS 
progression-free survival 
PHI 
protected health information 
PPARγ 
peroxisome proliferator-activated receptor γ 
PR 
partial response 
QoD 
every other day 
RNA 
ribonucleic acid 
RNP 
Ribonucleoprotein 
RRMM 
relapsed/refractory multiple myeloma 
RSV 
respiratory syncytial virus 


Cli nical St u d y Pr ot oc ol: X P O R T -C o V -1 0 0 1  
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Pa ge 1 2  of 7 4  
R X R α  
reti n oi d x rece pt or al p ha  
S A E  
seri o us a d verse e ve nt 
S A P  
Statistical A n al ysis P la n 
S A R S - C o V 
Se vere ac ute res pirat or y s y n dr o me c or o na vir us  
SI N E  
selecti ve i n hi bit or of n uclear e x p ort 
S o A 
sc he d ule of assess me nts 
S o C  
sta n dar d of care 
T E A E  
treat me nt-e mer ge nt a d verse e ve nt  
T N F α  
t u m or necr osis fact or-α  
T T CI  
ti me t o cli nical i m pr o ve me nt 
U L N  
u p per li mit of n or mal  
v R N P  
viral ri b o n ucle o pr otei n  
W H O  
W orl d Healt h Or ga nizati o n  
X P O 1  
e x p orti n 1 (als o calle d C R M 1) 
 
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SYNOPSIS 
Sponsor: 
Karyopharm Therapeutics Inc. 
Investigational Product: 
Selinexor (XPOVIO®, KPT-330) 
Study Phase: 
Phase 2 
Title of Study: 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 
Protocol Number: XPORT-CoV-1001 
Study Name: XPORT-CoV-1001 
Study Location:  
Approximately 40 international sites are planned. 
Study Rationale:  
Coronavirus disease 2019 (COVID-19) is caused by the single stranded RNA virus severe acute 
respiratory syndrome coronavirus 2 (SARS-CoV2) and can be accompanied by a marked inflammatory 
response, which is believed to be severely detrimental to the patient and associated with multi-organ 
dysfunction, respiratory failure and death (Lai 2020). Both the SARS-CoV2 lifecycle and pro-
inflammatory transcription factors require functional host nuclear export mediated by exportin 1 (XPO1, 
also called CRM1, OMIM 602559). XPO1 was recently identified as a “hub” host protein for SARS-
CoV viral propagation (Zhou 2020). Inhibition of XPO1 by the selective inhibitor of nuclear export 
(SINE) compound selinexor could induce both anti-viral and anti-inflammatory activities. 
Selinexor (XPOVIO®, KPT-330) is a potent, oral, slowly reversible covalent SINE compound that 
specifically inhibits XPO1. XPO1 mediates the nuclear export of proteins and ribonucleoprotein (RNP) 
complexes carrying a leucine-rich nuclear export sequence (NES) (Behrens 2017). Over 200 XPO1 
cargo proteins have been identified including proteins with regulatory roles in the inflammatory 
response and many viral proteins including SARS-CoV proteins. In a recent study, selinexor was shown 
to potently inhibit SARS-CoV2 viral propagation in Vero cells with IC50 and IC90 of <10nM and 100nM, 
respectively. 
Selinexor received accelerated approval from the FDA in July 2019 in combination with dexamethasone 
as a treatment for patients with advanced multiple myeloma (MM). The approved dose of selinexor for 
advanced MM is 160 mg per week (80 mg PO twice weekly). Over 3000 patients with a variety of 
advanced cancers have received selinexor alone or in combination with other anti-neoplastic agents in 
clinical studies; nearly 1000 patients have received the agent commercially. The most common side 
effects at these high doses, namely nausea, emesis, anorexia, low sodium and low platelets are dose 
dependent and reversible (Gavriatopoulou 2020).  
Selinexor was initially evaluated in two Phase 1 dose escalation studies in patients with advanced 
heavily pretreated hematologic (KCP- 330-001) and solid tumors (KCP- 330-002). These patients had 
multiple lines of prior chemotherapy and were severely immunocompromised frail patients with heavily 
pre-treated relapsed refractory hematologic and solid tumors.  Selinexor at doses of ≤12 mg/m2 (~20 mg) 
demonstrated target engagement in patients’ tumor biopsies as assessed by nuclear localization of XPO1 
cargoes such as IκB and FOXO1 (pre- and 2-4 weeks post-treatment biopsies) (Razak 2016; 
Karyopharm Data on File). Durable anti-tumor activity was observed in patients with both advanced 
hematological and solid tumors was observed at doses of ≤12 mg/m2, despite the fact that these patients 
had advanced, heavily pretreated neoplasms that were refractory to available anti-cancer agents 
(Kuruvilla 2017; Garzon 2017; Razak 2016). 
At a dose ≤12 mg/m2 (~20 mg) in the first 2 weeks, the 5 most common non-hematologic adverse events 
(AEs) were low grade (Grade 1 and 2) nausea, decreased appetite, fatigue, vomiting and dysgeusia, that 


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Page 14 of 74 
was manageable with supportive care. Hematologic AEs included only thrombo-cytopenia, and the 
Grade 3 and 4 events (1 each) were observed in patients with refractory hematologic cancers (acute 
leukemia and MM) (Appendix 2). There were no clinically significant changes in serum chemistries. 
Nearly all of the adverse events were reversible and responded to supportive care.  Finally, there were no 
clinically significant drug-drug interactions at these low doses, nor were any observed at much higher 
doses. Based on these results, the dose of 20 mg three times per week (60 mg per week) used here is 
anticipated to be well tolerated based on two phase 1 clinical studies (and detailed in Appendix 2) and to 
confer both anti-viral and anti-inflammatory activity as described below. 
A variety of viruses produce proteins that require nuclear export to carry out their functions. SARS-
CoV2 proteins, including nucleoprotein (N), protein 9b, Orf6 and potentially spike (S) and envelop (E) 
proteins, utilize XPO1 to properly function. Amongst >100 interacting host proteins, XPO1 and three 
other “hub” proteins have the highest number of functional connections with SARS-CoV proteins (Zhou 
2020). Inhibition of XPO1 by the natural product XPO1 inhibitor leptomycin B results in apoptosis of 
the SARS-CoV-infected host cells and might prevent SARS-CoV inhibition of innate immunity as well 
as the marked viral-induced pro-inflammatory effects that lead to COVID-19 (Jorquera 2018). SINE 
compounds, including selinexor and the closely related analog verdinexor, block XPO1 in a fashion 
similar to that of leptomycin B, are taken orally and have been shown to be tolerated in humans. 
Recently, selinexor was ranked 18 out of >400 drugs screened for ability to regulate SARS-CoV gene 
expression. The ability of selinexor to inhibit SARS-CoV2 viral propagation was evaluated in vero cells 
using two approaches: (a) prophylactic (pre-treatment) of cells with selinexor prior to infection and (b) 
concurrent treatment with selinexor at the time of infection (co-incubation). Pretreatment or co-
incubation of selinexor resulted in significant inhibition of viral propagation with IC50 of ~10 nM and 
the IC90 of ~100 nM.  The cytokine profile observed in COVID-19 corelates with disease severity and is 
characterized by increased interleukin (IL)-2, IL-7, granulocyte-colony stimulating factor (G-CSF), 
interferon-γ (INFγ) inducible protein 10, monocyte chemoattractant protein 1 (MCP-1), macrophage 
inflammatory protein 1α (MIF-1α), and tumor necrosis factor-α (TNFα) (Huang 2020). In 150 cases in 
Wuhan, China, independent predictors of fatality included elevated IL-6 levels (p<0.0001) (Ruan 2020). 
Host cell factors are required for the replication of all viruses. However, pharmacological manipulation 
of host cell factors, as a means of inhibiting viral replication, has not yet been realized. Preclinical data 
demonstrate that verdinexor and other SINE compounds have activity against >20 viruses, including the 
single stranded RNA viruses respiratory syncytial virus (RSV) and influenza, along with other common 
causes of respiratory infection. Specifically, verdinexor disrupts the viral replication cycle by inhibiting 
the interaction of viral ribonucleoproteins (vRNP) with the XPO1 nuclear export protein. 
Additionally, SINE compounds reduce inflammation through inhibition of the NF-κB pathway and 
nuclear retention and activation of anti-inflammatory targets such as IκB, RXRα, and PPARγ (Tajiri 
2016; Kashyap 2016; Widman 2018). This leads to reductions in cytokines including IL-1, IL-6 and, 
TNFα.  In a model that is relavant to severe COVID-19 with respiratory insufficiency, selinexor was 
evaluated in a mouse model of sepsis and ARDS utilizing an intraperitoneal injection of a lethal dose of 
bacterial endotoxin (LPS). In this sepsis model, selinexor given via oral gavage administered 30 minutes 
after the lethal dose of endotoxin treatment increased survival at a dose of ≥15 mg/m2 (Wu 2018). 
Influenza and SARS-CoV infection induce marked host inflammatory responses, and there are 
predictive animal models of influenza infection. We have therefore investigated the effect of XPO1 
blockade by verdinexor and related SINE compounds on infection, replication, pathology and mortality 
in animal and in vitro models of influenza (Perwitasari 2016). Treatment with verdinexor leads to 
marked nuclear accumulation of vRNP and inhibition of influenza replication. Broad-spectrum anti-
influenza activity with nanomolar potency was observed with verdinexor against a variety 
of both influenza A and B strains in vitro (Perwitasari 2016). In vivo, oral treatment with verdinexor 
showed anti-influenza activity in mouse and ferret models of influenza infection. Verdinexor reduced 
viral burden in the lung, inhibited pro-inflammatory cytokine induction and reduced virus-associated 


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lung pathology and pulmonary inflammation in infected animals. Verdinexor was also effective in 
delaying mortality and improving survival in mice challenged with a lethal infection of influenza virus, 
even when given 4 days after the initiation of infection (Perwitasari 2016). Given the similarities in the 
inflammatory processes associated with SARS-CoV and influenza viruses, these results suggest that 
such beneficial effects may also be observed with SINE compounds in patients with COVID-19. 
Selinexor (MW 443.3) and verdinexor (MW 442.3) are closely related molecules that differ by one 
atom. They have similar chemical, pharmacological, and pharmacokinetic properties including similar 
oral bioavailability. Both are potent (Ki < 10 nM) and highly selective inhibitors of XPO1. Both 
compounds form slowly reversible covalent bonds with cysteine-528 of XPO1 leading to its inactivation, 
and both are orally bioavailable compounds with no known drug-drug interactions (Appendix 2). 
Selinexor has been most intensively studied in cell lines and preclinical models of neoplastic diseases, 
whereas verdinexor has been studied most intensively in viral and autoimmune disorders. Selinexor is 
approved for treatment in patients with advanced refractory MM at a high dose of 160 mg per week. 
Lower doses of selinexor are active in a variety of other cancers and in combination with other anti-
cancer agents.  Existing pharmacokinetic and pharmacodynamic data support the use of selinexor in 
viral infections at the low dose of 20 mg three times per week. This dose of selinexor is well-tolerated 
and is not associated with significant cytopenias or any changes in liver function or sodium levels.  
Given the urgency of the COVID-19 pandemic and drug product availability including a commercial 
supply of selinexor tablets, this study will be initiated with selinexor.  As described above, there are no 
known chemical, pharmacological, or toxicological distinctions between the two agents that would favor 
verdinexor at this time given the emergent SARS-CoV2 pandemic. Based on the pharmacokinetics of 
selinexor and verdinexor, low doses (e.g., 20 mg per dose) of these agents are anticipated to deliver 
sufficient drug to confer both anti-viral and anti-inflammatory activity in patients with viral infections, 
including the SARS-CoV2 virus. 
Hypothesis: Oral selinexor + standard of care (SoC) will expedite the recovery, suppress the viral load, 
shorten the hospitalization and reduce morbidity and mortality in patients with severe COVID-19 
compared to placebo + SoC. 
Objectives and Endpoints: Low dose oral selinexor (20 mg on QoD each week) + SoC will expedite 
the clinical recovery, suppress the viral load, shorten the hospitalization and reduce morbidity and 
mortality in patients with severe COVID-19 compared to placebo + SoC. 
Objectives 
Endpoints 
Primary Objectives 
Day 14 Ordinal Scale Improvement (OSI) 
Proportion of patients with at least a 2 point 
improvement (increase) in the Ordinal Scale from 
baselineto Day 14. 
The Ordinal Scale is an assessment of the clinical 
status at the first assessment on each day of 
hospitalization. 
The scale is as follows:  
1. Death;  
2. Hospitalized, on invasive mechanical 
ventilation or extracorporeal membrane 
oxygenation (ECMO);  


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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.  
Key Secondary Objectives  
To evaluate improvement in clinical 
measures across the 2 treatment arms 
• 
Time to recovery defined as improvement from 
baseline score of 3 to ≥4 or from a baseline score 
of 4 to ≥5 
• 
Proportion of patients with at least a 2 point 
improvement (increase) in the Ordinal Scale from 
baseline to Day 7. 
• 
Proportion of patients with at least a 1 point 
improvement (increase) in the Ordinal Scale from 
baseline to Day 7 
• 
Proportion of patients with at least a 1 point 
improvement (increase) in the Ordinal Scale from 
baseline to Day 14. 
• 
Time to an improvement of 2 point using WHO 
Ordinal Scale Improvement (TTCI-2) 
• 
Time to clinical improvement (TTCI-1): defined as 
the time from randomization to an improvement of 
1 point on the Ordinal Scale 
• 
Overall death rate on Day 28 
• 
Rate of mechanical ventilation 
Additional Secondary Objectives  
To evaluate improvement in additional 
clinical measures across the 2 treatment 
arms  
• 
Overall Survival 
• 
Overall death rate on Day 14 
• 
Rate of ICU admission 
• 
Length of hospitalization 
• 
Length of ICU stay 


Cli nical St u d y Pr ot oc ol: X P O R T -C o V -1 0 0 1  
Seli ne x or  
Versi o n 6 . 0 
 
0 8 Ma y 2 0 2 0  
C o nfi de ntial  
 
Pa ge 1 7  of 7 4  
•  
D urati o n of mec ha nical ve ntilati o n  
•  
Pa O 2: Fi O2 a n d/ or o x y ge nati o n i n de x o ver ti me  
T o deter mi ne t he a nti -i nfla m mat or y a n d 
i m m u ne effect of seli ne x or 
•  
Re d ucti o n of C -reacti ve pr otei n ( C R P)  
•  
Re d ucti o n i n ferriti n le vels  
•  
L D H  
•  
Meas ure c ha n ges  fr o m baseli ne of bl o o d plas ma 
c yt o ki nes: I L-1 β, I L -1 R α, I L -2, I L -4, I L -5, I L -6, 
I L-7, I L -8, I L -9, I L -1 0, I F Nγ, I P 1 0, T N F α   
T o assess safet y a n d t olera bilit y of seli ne x or 
[ti me fra me: u p t o 2 8 da ys]  
•  
Listi n g a n d d oc u me ntati o n of fre q ue nc y a n d 
se verit y of a d verse effects  
T o c haracterize seli ne x or p har mac o ki netics  
•  
Seli ne x or P K para meters, ma xi m u m plas ma 
c o nce ntrati o n ( C ma x ) a n d tr o u g h c o nce ntrati o n 
( Ctr o u g h), if feasi ble  
E x pl or at or y E n d p oi nts  
 
O ver all St u d y Desi g n:   
T his is a ra n d o mize d p hase 2 si n gle-bli n de d st u d y of l o w d ose seli ne x or versus  place b o t o e val uate t he 
acti vit y a n d safet y , as well as re d ucti o n i n m ortalit y i n patie nts wit h se vere C O VI D -1 9.  
T he st u d y p o p ulati o n will c o nsist of h os pitalize d patie nts ≥1 8  y ears ol d wit h C O VI D -1 9 . 
T he e nr oll me nt will be stratifie d b y : 
•  
Use of c o nc o mita nt t hera pies: a n a nti -viral (e. g. , re m desi vir) or a n  a nti-i nfla mm at or y  (e. g. 
h y dr o x y c hl or o q ui ne , bi ol o gics tar geti n g e. g., I L-6 or I L - 1). N ote: aceta mi n o p he n a n d  
n o nster oi dal a nti -i nfla m mat or y dr u gs ( N S AI Ds ) will n ot c o nstit ute a nti -i nfla m mat or y a ge nts f or 
t he p ur p oses of stratificati o n.  
•  
Hi g h Ris k C o m or bi dities : A ge > 7 5 , B MI > 3 0 ,  ca ncer patie nts o n c he m ot hera p y, patie nts wit h 
car diac ( C A D, A MI, C H F) or  p ul m o nar y ( C O P D, e m p h yse ma)  disease   dia betes, h y perte nsi o n ). 
Stratificati o n will be base d o n n u m ber of hi g h ris k c o m or bi dities:  (1  vs   ≥2  vs  0)  
A d ose of 2 0 -m g seli ne x or or matc hi n g place b o will be a d mi nistere d orall y o n Da ys 1, 3, a n d 5 of eac h 
wee k f or u p t o 2 wee ks. If t he patie nt is t olerati n g t hera p y a n d cli nicall y be nefitti n g (i.e., n ot meeti n g 
C CI


Cli nical St u d y Pr ot oc ol: X P O R T -C o V -1 0 0 1  
Seli ne x or  
Versi o n 6 . 0 
 
0 8 Ma y 2 0 2 0  
C o nfi de ntial  
 
Pa ge 1 8  of 7 4  
a n y of t he criteria f or st o p pi n g t hera p y liste d bel o w), d osi n g ca n c o nti n ue f or a n a d diti o nal 2 wee ks ( o n 
Da ys 1 5, 1 7, 1 9, 2 2, 2 4, a n d 2 6).  
Patie nts w h o ac hie ve A N Y of t he f oll o wi n g criteria will be c o nsi dere d as ha vi n g cli nical be nefit f or t he 
p ur p ose of c o nti n ui n g d osi n g f or a n a d diti o nal 2 wee ks.  
1.  P atie nts w h o re mai ns h os pitalize d a n d: 
a. Has n ot ha d a seli ne x or -relate d Gra de 4 A E or seli ne x or-relate d seri o us A E ( S A E)  
A N D  
b.  Has n ot ha d > 1 p oi nt  or di nal sc ore re d ucti o n ( w orse ni n g)  
O R  
c. Has 2 p oi nt  re d ucti o n ( w orse ni n g) i n or di nal sc ore wit h a ≥2 0 % a bs ol ute re d ucti o n i n 
Fi O 2 fr o m pea k o x y ge n re q uire me nt  
2.  Patie nts disc har ge d fr o m t h e h os pital bef ore Da y 2 8 m ust meet t he f oll o wi n g criteria i n or der t o 
c o nti n ue o n seli ne x or:  
a. Platelet c o u nt > 7 5, 0 0 0/ m m 3 a n d 
b.  Ne utr o p hil c o u nt > 1, 0 0 0/ m m 3 a n d 
c. Ser u m s o di u m > 1 3 0  m m ol/ L a n d  
d.  N o Gra de ≥3 na usea or v o miti n g a n d  
e. N o  Gra de 4 A Es c o nsi dere d t o be relate d t o seli ne x or   a n d 
f. I m pr o ve d or di nal sc ore fr o m baseli ne A N D 
g.  P ositi ve S A R S -C o V 2 b y F D A a p pr o ve d la b orat or y test at disc har ge  
N u m ber of P atie nts ( pl a n ne d):  
A p pr o xi matel y 3 0 0 patie nts will be e nr olle d o verall as f oll o ws:  
a. ~ 5 0 patie nts i n Pr ot oc ol versi o n ≤5. 0  
b.  T he I T T p o p ulati o n will i ncl u de 2 4 7 patie nts t hat will be e nr olle d  i n Pr ot oc ol Versi o n 6 a n d will 
be ra n d o mize d t o seline x or or place b o  i n a 
 rati o 
St u d y P o p ul ati o n: P atie nts m ust  f ulfill criteri a t o be eli gi ble f or e nr oll me nt i n t he st u d y 
Eli gi ble p atie nts are a d ults ≥1 8  y ears of a ge a d mitte d t o t he h os pital wit h c o nfir me d S A R S -C o V 2  
i nfecti o n. All patie nts or  t heir pr o xies m ust  pr o vi de si g ne d writte n  or ver bal  i nf or me d c o nse nt. T he 
I nf or me d C o nse nt F or m (I C F) a n d t he pr ocess t o o btai n t he i nf or me d c o nse nt will c o m pl y wit h all l ocal 
la ws, re g ulati o ns, a n d g ui da nce. 
I ncl usi o n Criteri a:  
Patie nts are eli gi ble t o be i ncl u de d i n t he st u d y o nl y if t he y meet all t he f oll o wi n g criteria:  
1.  A ge ≥1 8 y ears  
2.  C o nfir me d l a b orat or y dia g n osis of  S A R S -C o V 2 b y sta n dar d F D A -a p pr o ve d R T -P C R assa y or 
e q ui vale nt F D A-a p pr o ve d testi n g (l ocal la bs)  wit hi n 7 da ys of e nr oll me nt  
3.  C urre ntl y h os pitalize d  
4.  I nf or me d c o nse nt  
C CI


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5. Has symptoms of severe COVID-19 as demonstrated by: 
a. At least 1 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 
AND 
b. 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 LPM oxygen by nasal 
canula, non-rebreather/Ventimask (or similar device) or high flow nasal canula in order to 
maintain SaO2 ≥92%,  PaO2/FiO2 <300 mm/hg. Patients with COPD or chronic lung disease 
must demonstrate evidence of increased oxygen needs above baseline. 
6. Elevated CRP > 2 x ULN 
7. Concurrent anti-viral and/or anti-inflammatory agents (e.g., biologics, hydroxychloroquine) are 
permitted. If in the physician’s judgement, it is in the best interest of the patient to use anti-viral 
or anti-inflammatory treatments, these treatments are to be documented in the patient’s chart and 
entered in the electronic case report form.  
Note: Patients who may have received plasma convalescent therapy > 48 hours prior to 
enrollment with no clinical improvement and who still meet criteria for severe COVID-19 may 
enroll.  On study plasma convalescent therapy is not permitted.  
8. Patient who receive plasma convalescent therapy within 48 hours  may be permitted to enroll 
based on discussion with sponsor.Female patients of childbearing potential must have a negative 
serum pregnancy test at Screening. Female patients of childbearing potential and fertile male 
patients must use highly effective methods of contraception throughout the study and for 3 
months following the last dose of study treatment. Highly effective methods of contraception are 
listed in Section 8.3.1. 
Exclusion Criteria:  
1. Evidence of critical COVID-19 based on: 
a. 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) 
b. Septic shock  (defined by investigator assessment or requires vasopressors) 
c. Multiple organ dysfunction/failure 
2. In the opinion of the investigator, unlikely to survive for at least 48 hours from screening.  
3. Inadequate hematologic parameters as indicated by the following labs: 
a. Patients with severe neutropenia (ANC <1000 x 109/L) or 
b. Thrombocytopenia (e.g., platelets <100,000 per microliter of blood) 
4. Inadequate renal and liver function as indicated by the following labs: 
a. Creatinine clearance (CrCL) <20 mL/min using the formula of Cockcroft and Gault. 
b. Aspartate transaminase (AST) or alanine transaminase (ALT) > 5 x upper limit of normal  
5. Hyponatremia defined as sodium less than 130 mEq/L 
6. Unable to take oral medication when inform consent is obtained. 
7. Patients with a legal guardian or who are incarcerated.  


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8. Patients taking strong CYP3A inhibitors or inducers. A list of prohibited strong CYP3A 
inhibitors and inducers is provided in Appendix 3. 
9. Pregnant and breastfeeding women. 
Study Treatment/Treatment Groups, Dose, and Mode of Administration:  
A dose of 20 mg selinexor or matching placebo will be administered orally on Days 1, 3, and 5 of each 
week for up to 2 weeks. If the patient is tolerating therapy and clinically benefitting, as defined below, 
dosing can continue for an additional 2 weeks (on Days 15, 17, 19, 22, 24, and 26). 
Duration of Treatment and Follow-up: 
Patients will receive study treatment for up to 14 days. 
Dosing can continue for an additional 2 weeks if ANY of the following criteria are met: 
1. Patients who remain hospitalized must meet the following criteria to continue selinexor therapy: 
a. has not had a selinexor-related Grade 4 Advese Event (AE) or selinexor-related Serious 
AE (SAE) AND 
b. has not had >1 point ordinal score reduction (worsening) OR  
c. has 2 point reduction (worsening) in ordinal score with a ≥20% absolute reduction in 
FiO2 from peak oxygen requirement 
2. Patients discharged from the hospital before Day 28 must meet the following criteria to continue 
selinexor therapy: 
a. Platelet count > 75,000/mm3 and 
b. Neutrophil count >1,000/mm3 and 
c. Serum sodium > 130 mmol/L and 
d. No Grade ≥3 nausea or vomiting and 
e. No Grade 4 AEs related to selinexor, and 
f.  Improved ordinal score from baseline AND 
g. Positive SARS-CoV2 by FDA approved laboratory test at discharge 
Note: patients discharged from the hospital who remain on selinexor must continue to have 
twice weekly serum chemistry and complete blood counts as long as treatment is continued. 
Therapy will be stopped if any of the events defined below occur prior to 28 days: 
• 
Patient withdraws consent to continue study treatment. 
• 
Worsening clinical condition defined as at least 5 days of intubation/ECMO with no 
evidence of clinical improvement.  Patients who are clinically stable based on oxygen 
requirements on mechanical ventilation will be permitted to remain on study. 
• 
Grade ≥3 nausea or vomiting despite optimal antiemetic therapy. 
• 
Progression of renal dysfunction requiring dialysis. 
• 
Grade 4 AEs related to selinexor 
 


Cli nical St u d y Pr ot oc ol: X P O R T -C o V -1 0 0 1  
Seli ne x or  
Versi o n 6 . 0 
 
0 8 Ma y 2 0 2 0  
C o nfi de ntial  
 
Pa ge 2 1  of 7 4  
St atistic al  Met h o ds:  
S a m ple Size C alc ul ati o n a n d St atistic al P o wer:  
A p pr o xi matel y 2 4 7 patie nts
 
 
A n al ysis P o p ul ati o ns:  
T he i nte nt -t o-treat (I T T) p o p ulati o n will c o nsist of all patie nts w h o are ra n d o mize d i n t he st u d y wit h 
c o nfir me d S A R S -C o V 2 i nfecti o n  u n der p r ot oc ol v ersi o n 6. 0 a n d a b o ve, re gar dless of w het her or n ot 
t he y recei ve st u d y treat me nt.  
T he all -treat ( A T) p o p ulati o n will c o nsist of all patie nts w h o t o o k at least o ne d ose of st u d y treat me nt o n 
t his st u d y a n d ha ve c o nfir me d S A R S -C o V 2 i nfecti o n .  
Effic ac y A n al yses:  
T he differe nce of t he pri mar y e n d p oi nt (Da y 1 4 O SI ) bet wee n treat me nt ar ms will be calc ulate d wit h a 
9 5 % c o nfi de nce i nter val ( CI). C o m paris o n of O SI rates bet wee n t he 2 treat me nt ar ms will be perf or me d 
usi n g t he C oc hra n -Ma ntel -Hae nszel ( C M H) test stratifie d b y t he ra n d o mizati o n stratificati o n fact ors. 
T he C M H esti mate of t he o d ds rati o a n d its 9 5 % CI a n d t he p -val ue f or testi n g t he treat me nt differe nce 
will be re p orte d.  
A nal yses of ot her efficac y e n d p oi nts will be s pe cifie d i n Secti o n 9. 4. 1  a n d t he S A P. 
S afet y A n al yses:  
Safet y a nal yses will be base d o n t he re p orte d A Es a n d ot her safet y i nf or mati o n, s uc h as 1 2 -lea d 
electr ocar di o gra m ( E C G), cli nical la b orat or y assess me nts  i ncl u di n g he mat ol o g y, ser u m c he mistr y, vital 
si g ns a n d p h ysical e xa mi nati o n. 
Safet y a nal yses will be perf or me d usi n g t he A T p o p ulati o n.  
 
C CI


Cli nical St u d y Pr ot oc ol: X P O R T -C o V -1 0 0 1    
  
  
  
  
  
  
  
  
  
 
Seli ne x or  
Versi o n 6 . 0                                                                                                                                                                                                              0 8 Ma y 2 0 2 0  
C o nfi de ntial  
 
  
  
 
Pa ge 2 2  of 7 4  
S C H E D U L E O F  A S S E S S M E N T S   
T a ble 1 :  
Sc he d ule of Assess me nts  f or a d mitte d p atie nts o nl y  
Acti vit y/ Assess me nt  
Scree ni n g 
D osi n g Peri o d  
 
E n d- of -
Tre at me nt 
H os pit al 
Disc h ar ge 
S afet y 
F oll o w-
U p / E n d 
of St u d y i 
 
D -2 t o 
D 1  
D 1  
± 1 d a y  
D 3  
± 1  d a y  
D 5  
± 1  d a y  
D 8  
± 1  d a y  
D 1 0  
± 1  d a y  
D 1 2  
± 1  d a y  
D 1 5  
± 1  d a y  
D 1 9  
± 1  d a y  
D 2 2  
± 1  d a y  
D 2 6  
± 1  d a y  
D 1 4/ 2 8 a 
 
 
I nf or me d C o nse ntb 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
I ncl usi o n/ E xcl usi o n 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
De m o gra p hics 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Me dical hist or y  
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Disease Hist or y  
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Vital si g ns  c 
X 
T wice dail y d uri n g H os pital Sta y  
 
 
C o m plete P h ysical 
E xa m  
X 
 
 
 
 
 
 
 
 
 
 
 
X 
 
Pre g na nc y testi n g  
(p er site g ui d eli ne) 
X 
 
 
 
 
 
 
 
 
 
 
X 
 
 
Or di nal Sc ore d 
X 
Dail y a n d t he da y after disc har ge  
X 
 
1 2 -lea d E C Ge 
X 
As cli nicall y i n dicate d  
 
 
A B G ( Arterial Bl o o d 
Gas) l 
X 
As cli nicall y i n dicate d  
 
 
C B C wit h differe ntial 
X 
X 
X 
X 
X 
 
X 
X 
X 
X 
X 
 
X 
 
P T. a P T T , I N R 
X 
X 
X 
X 
X 
 
X 
X 
 
X 
X 
 
 
 
C o m plete ser u m 
c he mistr y 
X 
X 
X 
X 
X 
 
X 
X 
X 
X 
X 
 
X 
 
C- reacti ve pr otei n, 
Ferriti n, L D H f 
X 
X 
X 
X 
X 
 
X 
X 
X 
X 
X 
 
 
 
C CI


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Selinexor 
Version 6.0                                                                                                                                                                                                              08 May 2020 
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Page 23 of 74 
a 
Patients will remain on therapy for up to 14 days (or 28 days based on treating physician discretion) 
b 
Refer to Section 10.1 for Informed Consent 
c 
Vital signs include respiratory rate, temperature, and oxygen saturation It is recommended to measure SpO2 in the same position for each patient throughout the duration of the study  
d 
Ordinal Score (Section 7.3.2) will be assessed at first assessment of day 
e 
For patients who had an ECG during the hospitalization, the ECG does not need to be repeated. Results of this most recent ECG should entered into the eCRF 
 
f 
Required study and should be performed unless hospital SOP does not permit or if not feasible, to be performed locally as available. Once 2 negative viral assessments are documented testing can be 
stopped. 
g 
Day 12 or Day 15 
h 
Blood samples (~ 2mL) for selinexor PK will be collected at 4 ± 1 hr, 24 ± 4 hrs post selinexor dose on Day 1 and predose on Day 3 and Day 5. Details for PK sample collection and processing can 
be found in the Laboratory Manual. 
i 
This visit will occur 30 (+2) days post end of treatment and may be performed as either a telephone call or an in-clinic visit. Only follow up on SAEs will be reported.  
j 
In order to minimize nausea, all patients should receive ondansetron 8 mg or equivalent unless contraindicated, starting on Day 1 before the first dose of selinexor and continued 2-3 times daily 
thereafter, as needed. Alternative antiemetic agents may be used if the patient does not tolerate or has inadequate antiemetic effect with 5-HT3 antagonists.    
k 
It is recommended that patients are dosed with study drug within 12 hours of consent 
l    If feasible. 
 
 
 
 
 
Cells for Leukocyte 
Phenotypingf  
X 
X 
 
 
X 
 
Xg 
X 
 
 
 
 
 
 
Selinexor or Placebok 
 
X 
X 
X 
X 
X 
X 
(X) 
(X) 
(X) 
(X) 
 
 
 
Blood draws for 
selinexor PKh 
 
X 
X 
X 
 
 
 
 
 
 
 
 
 
 
Cytokines 
X 
 
X 
X 
X 
 
 
 
 
 
 
 
 
 
Adverse Events (any) 
X 
Recorded Throughout 
X 
 
X 
Concomitant 
Medications  
X 
Recorded Throughout 
X 
 
 
5-HT3 antagonists  
Ondansetron or 
equivalentj 
 
Daily as needed 
 
 
 
Survival Follow-up 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 


Cli nical St u d y Pr ot oc ol: X P O R T -C o V -1 0 0 1    
  
  
  
  
 
        Seli ne x or  
Versi o n 6 . 0                                                                                                                                                0 8 Ma y 2 0 2 0  
C o nfi de ntial  
 
Pa ge 2 4  of 7 4  
T a ble  2: 
Sc he d ule of Assess me nt P ost -Disc h ar ge Peri o d f or O ut p atie nts O nl y  
Acti vit y/ Assess me nt a 
Sc he d ule  
D a y 2 8  
E n d of St u d y b  
F oll o w -u p  Call  
Wee kl y  u ntil da y 2 8  
 
X 
Or di nal Sc ore  
O n Da y 7 a n d 1 4  
 
 
A d verse E ve nt  
Wee kl y  u ntil da y 2 8  
 
X 
St u d y Dr u g A d mi nistrati o n c 
D osi n g Da ys 1, 3, 5 of eac h wee k 
u ntil da y 2 8  
 
 
C B C wit h differe ntial a n d C o m plete 
Ser u m C he mistr y c 
T wice  wee kl y  u ntil 1 4 or da y 2 8  
 
 
S ur vi val F oll o w -u p  
 
X 
 
a S p o ns or Ris k Ma na ge me nt Pla n f or C o n d uct of Cli nical Trials o utli nes pr oce d ures t o be c o n d ucte d d uri n g t he C O VI D -1 9 pa n de mi c.  
b T his visit will oc c ur 3 0 ( + 2) da ys p ost e n d of treat me nt, a n d ma y be perf or me d as eit her a tele p h o ne call or a n i n cli nic vis it.  O nl y f oll o w o n 
S A Es will be re p orte d.  
c O nl y f or patie nts w h o are disc har ge d o n st u d y treat me nt  a n d w hile o n st u d y treat me nt . Decisi o n t o c o nti n ue be y o n d da y 1 4 is per pr ot oc ol 
g ui deli nes 
 
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1. 
INTRODUCTION 
1.1. 
Study Rationale 
Novel coronavirus disease (COVID-19) is caused by the single stranded RNA virus SARS-CoV2 
(Cascella 2020).  The viral lifecycle requires interaction with >100 host proteins including 
exportin 1 (XPO1, also called CRM1).  Host inflammatory response to the virus can be marked, 
and poor outcomes are associated with high levels of pro-inflammatory cytokines. Selinexor, and 
the related compound verdinexor, are highly selective and potent oral inhibitor of XPO1. In a 
recent study, selinexor was shown to potently inhibit SARS-CoV2 viral propagation in Vero 
cells with IC50 and IC90 of < 10nM and 100nM respectively (see Section 1.3).  These SINE 
compounds have been shown block the interactions of several SARS-CoV and CoV2 proteins 
with XPO1, and separately to reduce pro-inflammatory cytokine levels through anti-
inflammatory transcriptional signaling.   
Dosing verdinexor with a delay of up to 4 days in an influenza model was as efficacious as   
initiation early in infection, which aligns well with the understood incubation period of the novel 
coronavirus (Perwitasari 2016). Verdinexor demonstrated activity against over 20 viruses, 
including respiratory syncytial virus (RSV), influenza, and other common causes of viral 
respiratory infection (Jorquera 2018; Widman 2018).  
Selinexor (MW 443.3) and verdinexor (MW 442.3) are closely related molecules that differ by 
one atom. They have similar chemical, pharmacological and pharmacokinetic properties 
including oral bioavailability.  Both are potent (Ki < 10 nM) and highly selective inhibitors of 
XPO1 with no known drug-drug interactions. Selinexor is approved in the U.S. in combination 
with dexamethasone for the treatment of adult patients with relapsed refractory multiple 
myeloma (RRMM) under the brand name XPOVIO® at doses of 160 mg per week (80 mg twice 
weekly). In this Clinical Trial, selinexor will be dosed at 20 mg three times per week (60 mg per 
week total). This selinexor dose is anticipated to be well tolerated without significant cytopenias 
and to induce both anti-viral and anti-inflammatory activities. 
1.2. 
Background on COVID-19 
In December 2019, a novel coronavirus (subsequently named SARS-CoV2) was detected in 3 
patients with pneumonia connected to the cluster of acute respiratory illness cases from Wuhan, 
China. By the end of February 2020, multiple countries were experiencing sustained local 
transmission and is now a world-wide pandemic and global health crisis. 
The most commonly reported clinical symptom in laboratory-confirmed cases was fever (88%), 
dry cough (68%), fatigue (38%), sputum production (33%), dyspnea (19%), sore throat (14%), 
headache (14%) and myalgia or arthralgia (15%). Less common symptoms were diarrhea (4%) 
and vomiting (5%). About 80% of reported cases in China had mild to moderate disease 
(including non-pneumonia and pneumonia cases), 13.8% had severe disease (as defined in this 
protocol) and 6.1% were critical (respiratory failure, septic shock, and/or multiple organ 
dysfunction/failure). Current estimates suggest a median incubation period from 5 to 6 days for 
SARS-CoV2, with a range from 1 to up to 14 days. A recent modelling study confirmed that it 
remains prudent to consider the incubation period of up to 14 days.  
Robust estimates for final case fatality risk for COVID-19 are still lacking and biased due to 
incomplete outcome data and the fact that initial detections were of mostly severe cases in most 


Cli nical St u d y Pr ot oc ol: X P O R T -C o V -1 0 0 1    
  
  
  
  
 
        Seli ne x or  
Versi o n 6 . 0                                                                                                                                                0 8 Ma y 2 0 2 0  
C o nfi de ntial  
 
Pa ge 2 6  of 7 4  
setti n gs. Base d o n a lar ge dataset fr o m cases i n C hi na, t he o verall case fatalit y ris k ( C F R) a m o n g 
la b orat or y-c o nfir me d cases is c urre ntl y ~0. 7 % f or patie nts wit h s y m pt o m o nset after 1 Fe br uar y  
2 0 2 0. T he hi g hest C F R  a m o n g pe o ple occ urs o ver 8 0 years of a ge ( 4-1 5 %)  (H ua n g 2 0 2 0 ; R ua n 
2 0 2 0 ). 
1. 2. 1.  
Vir al S he d di n g  a n d Tr a ns missi o n  
O ver t he c o urse of t he i nfecti o n, t he vir us has bee n i de ntifie d i n res pirat or y tract s peci me ns 1- 2 
da ys bef ore t he o nset of s y m pt o ms a n d it ca n persist f or 7- 1 2 da ys i n m o derate cases a n d u p t o 2 
wee ks i n se vere cases. I n feces, viral R N A has bee n detecte d fr o m  da y 5 after o nset a n d u p t o 4 
t o 5 wee ks i n m o derate cases. T he vir us has bee n detecte d als o i n w h ole bl o o d, ser u m, sali va a n d 
uri ne. Pr ol o n ge d viral R N A s he d di n g has bee n re p orte d fr o m nas o p har y n geal s wa bs, u p t o 3 7 
da ys a m o n g a d ult patie nts a n d i n feces, f or m ore t ha n o ne m o nt h after i nfecti o n i n pe diatric 
patie nts. It s h o ul d be n ote d t hat viral R N A s he d di n g d oes n ot directl y e q uate wit h i nfecti vit y. 
1. 2. 2.  
C yt o ki ne Le vels a n d O utc o mes  
C yt o ki ne le vels are ass ociate d wit h C O VI D - 1 9 se verit y, c haracterize d b y i ncrease d i nterle u ki n 
(I L)-2, I L - 7, gra n ul oc yte-c ol o n y sti m ulati n g fact or ( G-C S F) , i nterfer o n-γ (I NF γ) i n d uci ble 
pr otei n 1 0, m o n oc yte c he m oattracta nt pr otei n 1 ( M C P- 1), macr o p ha ge i nfla m mat or y pr otei n 1 α, 
( MI F-1 α) a n d t u m or necr osis fact or -α ( T N F α)  (H ua n g 2 0 2 0 ). 
Pre dict ors of fatalit y of 1 5 0 c o nfir me d C O VI D - 1 9 cases i n W u ha n i ncl u de d ele vate d I L- 6 le vels 
( p < 0· 0 0 0 1) (R ua n 2 0 2 0 ). 
1. 3.  
Sel i ne x or 
Seli ne x or ( X P O VI O ® , K P T -3 3 0) is a s mall m olec ule, oral, first -i n-class, p ote nt selecti ve 
i n hi bit or of X P O 1 -me di ate d n uclear e x p ort ( SI N E). It has recei ve d accelerate d a p pr o val fr o m t he 
F D A i n J ul y 2 0 1 9 i n c o m bi nati o n wit h de xa met has o ne as a treat me nt f or patie nts 
wit h  a d va nce d m ulti ple m yel o ma  ( M M). T he a p pr o ve d d ose of seli ne x or is 8 0 m g p o t wice 
wee kl y (t otal 1 6 0 m g per wee k). M ore t ha n 3 0 0 0 patie nts wit h a d va nce d ca ncers ha ve recei ve d 
seli ne x or al o ne or i n c o m bi nati o n wit h ot her a nti-ne o plastic a ge nts i n cli nical st u dies, a n d ~ 1 0 0 0 
a d diti o nal patie nts ha ve recei ve d t he a ge nt i n t he c o m mercial setti n g . T he m ost c o m m o n si de 
effects at t hese hi g h  d oses, na mel y na usea, e mesis, a n ore xia, l o w s odi u m a n d l o w platelets are 
d ose de pe n de nt a n d re versi ble.  
T he a bilit y of seli ne x or t o i n hi bit viral pr o pa gati o n was e val uate d usi n g t w o a p pr oac hes: (a) 
pr o p h ylactic ( pre- treat me nt) of cells wit h seli ne x or pri or t o i nfecti o n a n d ( b) c o nc urre nt 
treat me nt wit h seli ne x or at t he ti me of i nfecti o n (c o-i nc u bati o n). 
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Versi o n 6 . 0                                                                                                                                                0 8 Ma y 2 0 2 0  
C o nfi de ntial  
 
Pa ge 2 7  of 7 4  
L o w d ose seli ne x or : bi ol o gic al acti vit y, effic ac y a n d s afet y i n p atie nts wit h a d v a nce d c a ncer  
Seli ne x or was i nitiall y e val uate d i n 2 P hase 1 d ose escalati o n st u dies i n patie nts wit h a d va nce d 
hea vil y pretreate d he mat ol o gic ( K C P - 3 3 0- 0 0 1) a n d s oli d t u m ors ( K C P- 3 3 0- 0 0 2). T hese 
patie nts ha d m ulti ple li nes of pri or c he m ot hera p y a n d were se verel y i m m u n oc o m pr o mise d frail 
patie nts wit h hea vil y pre -treate d rela pse d refract or y he mat ol o gic a n d s oli d t u m ors. Seli ne x or at 
d oses of ≤1 2 m g/ m 2 ( ~ 2 0 m g) de m o nstrate d tar get e n ga ge me nt i n patie nts’ t u m or bi o psies as 
assesse d b y n uclear l ocalizati o n of X P O 1 car g oes s uc h as I κ B a n d F O X O 1 ( pre- a n d 2-4 wee ks 
p ost-treat me nt bi o psies) ( Raza k 2 0 1 6 ; Kar y o p har m Data o n File). D ura ble a nti-t u m or acti vit y 
was o bser ve d i n patie nts wit h b ot h a d va nce d he mat ol o gical a n d s oli d t u m ors was o bser ve d at 
d oses of ≤1 2 m g/ m 2, des pite t he fact t hat t hese patie nts ha d a d va nce d, hea vil y pretreate d 
ne o plas ms t hat were refract or y t o a vaila ble a nti -ca ncer a ge nts ( K ur u villa 2 0 1 7 ; Garz o n 2 0 1 7 ; 
Raza k 2 0 1 6 ). 
At a d ose ≤1 2 m g/ m 2 ( ~ 2 0 m g) i n t he first 2 wee ks, t he 5 m ost c o m m o n n o n- he mat ol o gic 
a d verse e ve nts ( A Es) were l o w gra de ( Gra de 1 a n d 2) na usea, decrease d a p petite, fati g ue, 
v o miti n g a n d d ys ge usia, t hat was ma na gea ble wit h s u p p orti ve care. He mat ol o gic A Es i ncl u de d 
o nl y t hr o m b oc yt o pe nia, a n d t he Gra de 3 a n d 4 e ve nts ( 1 eac h) were o bser ve d i n patie nts wit h 
refract or y he mat ol o gic ca ncers (ac ute le u ke mia a n d m yel o ma) (A p pe n di x 2 ). T here were n o 
cli nicall y si g nifica nt c ha n ges i n ser u m c he mistries.  Nearl y all of t he a d verse e ve nts were 
re versi ble a n d res p o n de d t o s u p p orti ve care.  Fi nall y, t here were n o cli nicall y si g nifica nt dr u g-
dr u g i nteracti o ns at t hese l o w d oses, n or were a n y o bser ve d at m uc h hi g her d oses. T he C ma x  wit h 
2 0 m g seli ne x or is 1 5 9 n g/ m L ( 3 5 9 n M).  Base d o n t hese res ults, t he d ose of 2 0 m g t hree ti mes 
per wee k ( 6 0 m g per wee k) use d here is a ntici pate d t o be well t olerate d base d o n t w o p hase 1 
cli nical st u dies ( detaile d i n A p pe n di x 2 ) a n d t o c o nfer b ot h a nti-viral a n d a nti -i nfla m mat or y 
acti vit y as descri be d bel o w.   
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Activity of Selinexor and other SINE compounds in models of Inflammation and Viral 
Infection  
Selinexor (MW 443.3) and verdinexor (MW 442.3) are closely related molecules that differ by 
one atom.  They have similar chemical, pharmacological and pharmacokinetic properties. Both 
are potent (Ki < 10 nM) and highly selective inhibitors of XPO1. Both compounds form slowly 
reversible covalent bonds with cysteine-528 of XPO1 leading to its inactivation, and both are 
orally bioavailable compounds with no known drug-drug interactions. Preclinically, selinexor 
has been most intensively studied in cell lines and models of neoplastic diseases, whereas 
verdinexor has been studied most intensively in viral and autoimmune disorders (Appendix 1).  
Over 200 XPO1 cargo proteins have been identified including proteins with regulatory roles in 
inflammatory response and many viral proteins including severe acute respiratory syndrome 
coronavirus (SARS-CoV2) proteins (Zhou 2020). 
A variety of viruses produce proteins that require nuclear export to carry out their functions. 
SARS-CoV2, including nucleoprotein (N), protein 9b, Orf6, and potentially spike (S) and 
envelop (E) proteins, utilize XPO1 to properly function (Sharma 2011; Reed 2007). XPO1 and 
three other “hub” proteins have the highest number of functional connections with SARS-CoV 
proteins (Gordon 2020). Inhibition of XPO1 by the natural product XPO1 inhibitor leptomycin B 
results in apoptosis of the SARS-CoV-infected host cells and might prevent SARS-CoV 
inhibition of innate immunity as well as the marked viral-induced pro-inflammatory effects that 
lead to COVID-19. SINE compounds, including selinexor and the closely related analog 
verdinexor, block XPO1 in a fashion similar to that of leptomycin B, are taken orally and have 
been shown to be tolerated in humans. Recently, selinexor was ranked 18 out of 400 drugs 
screened for ability to regulate SARS-CoV gene expression analysis done by Califano et al 
(private communication). 
Host cell factors are required for the replication of all viruses. However, pharmacological 
manipulation of host cell factors, as a means of inhibiting viral replication, has not yet been 
realized. Preclinical data demonstrate that verdinexor and other SINE compounds have activity 
against >20 viruses, including respiratory syncytial virus (RSV), influenza and other common 
causes of respiratory infection. Specifically, verdinexor disrupts the viral replication cycle by 
inhibiting the interaction of viral ribonucleoproteins (vRNP) with the XPO1 nuclear export 
protein (Widman 2018; Perwitasari 2016; Jorquera 2018).  
Additionally, Selienxor and other SINEs inhibit cytokine release including IL-1, IL-6 and TNFα 
through inhibition of the NF-κB pathway and nuclear retention and activation of specific 
inhibitors of pro-inflammatory transcriptional factors such as IκB, RXRα, and PPARγ (Tajiri 
2016; Kashyap 2016; Widman 2018) In a model that is relavant to severe COVID-19 with 
respiratory insufficiency, selinexor was evaluated in a mouse model of sepsis and ARDS 
utilizing an intraperitoneal injection of a lethal dose of bacterial endotoxin (LPS). In this sepsis 
model, selinexor given via oral gavage administered 30 minutes after the lethal dose of 
endotoxin treatment increased survival at a dose of ≥15 mg/m2 (Wu 2018; Figure 2). In addition, 
selinexor reduced inflammatory cytokine levels in the serum including TNFa, IL-6 and HMGB1, 
while reducing the numbers of macrophages and polymorpho-nuclear neutrophils in the mouse 
peritoneal cavity. Importantly, selinexor treatment attenuated the ARDS-like lung injury 
observed in this model. Details are provided in Appendix 1. 


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Figure 2:  
Sepsis Model for Selinexor. 
Oral selinexor dosed 30 minutes after the induction of sepsis protected the mice and increased their survival (Figure 
2A). In addition, serum levels of the proinflammatory cytokines TNFa and IL-6 at 12 h post LPS challenge were 
significantly lower in selinexor treatment groups (Figure 2B). 
 
As the severity of respiratory disease in COVID-19 is associated with the levels of cytokine 
secretion in SARS-CoV infected patients, the observed reductions in cytokine levels in this 
sepsis-ARDS model, as well as the results in influenza described below, support the view that 
treatment of patients with COVID-19 (and other respiratory viruses) with selinexor could be 
beneficial.  
Influenza and SARS-CoV infections induce marked host inflammatory responses, and there are 
animal models of influenza infection available. We have therefore investigated the effect of 
XPO1 blockade by verdinexor and related SINE compounds on infection, replication, pathology 
and mortality in animal and in vitro models of influenza. Treatment with verdinexor leads to 
marked nuclear accumulation of vRNP and inhibition of influenza replication. Broad-spectrum 
anti-influenza activity with nanomolar potency was observed with verdinexor against a variety 
of both influenza A and B strains in vitro (Perwitasari 2016). Moreover, verdinexor exhibited 
anti-influenza activity in vitro in a model of viral replication in normal human bronchial 
epithelial (NHBE) cells grown in a liquid-air interface, which is a model that mimics infection of 
the respiratory airways in humans. In vivo, oral treatment with verdinexor at 10-20 mg/kg 
showed anti-influenza activity in mouse and ferret models of influenza infection. Verdinexor 
reduced viral burden in the lung, inhibited pro-inflammatory cytokine induction and reduced 
virus-associated lung pathology and pulmonary inflammation in infected animals. Verdinexor 
was also effective in delaying mortality and improving survival in mice challenged with a lethal 
infection of influenza virus, even when given 4 days after the initiation of infection. Given the 
similarities in the inflammatory processes associated with SARS-CoV and influenza viruses, 
these results suggest that such beneficial effects may also be observed in patients with COVID-
19 (Perwitasari 2016). 
Given the urgency of the COVID-19 pandemic and drug product availability including a 
commercial supply of selinexor tablets, this study will be initiated with selinexor rather than 
verdinexor.  As described above, there are no known chemical, pharmacological or toxicological 
distinctions between the two agents that would favor verdinexor at this time given the emergent 
SARS-CoV2 pandemic. Based on the pharmacokinetics of selinexor and verdinexor, low doses 
(e.g., 20 mg per dose) of these agents are anticipated to deliver sufficient drug to confer both 
anti-viral and anti-inflammatory activity in patients with viral infections, including the SARS-
CoV2 virus. 


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Hypothesis  
Low dose oral selinexor (20 mg on QoD each week) will expedite the recovery, suppress the 
viral load, shorten hospitalization, and reduce mortality in patients with severe COVID-19 
compared to standard of care. 
1.4. 
Benefit/Risk Assessment 
Blockade of XPO1 has shown anti-SARS-CoV2 activity in vitro and anti-viral effects in animal 
models as well as in influenza models. Severe influenza is associated with a pro-inflammatory 
cytokine profile similar to severe COVID-19. Based on preclinical studies, inhibition of XPO1 is 
anticipated to confer both anti-SARS-CoV2 and anti-inflammatory activity at relatively low 
doses of selinexor to be used in this study. 
Higher doses of selinexor (160 mg per week) approved for use in the treatment of advanced 
RRMM are associated with dose-dependent and generally reversible nausea, fatigue, emesis, 
anorexia, low sodium and thrombocytopenia. The lower doses of selinexor used here (60 mg per 
week) are expected to achieve the relevant pharmacological concentrations. There are no known 
clinically significant drug-drug interactions with selinexor. The protocol allows concurrent use of 
other investigational anti-viral and/or anti-inflammatory agents. 
The highly selective and potent oral XPO1 inhibitors verdinexor and selinexor have no 
pharmacologically important discernable differences. XPO1 inhibitors have activity in models of 
sepsis/ARDS, inflammation, and influenza. In a recent study selinexor demonstrated potent 
activity against SARS-CoV2 (IC50= ~10 nM). The adverse event profile of low dose selinexor 
consists of low grade, reversible and treatable symptoms (Appendix 2). 
Therefore, we believe that the opportunity to confer both anti-viral and anti-inflammatory 
activity with a novel agent targeting a host protein warrants provides a positive risk /benefit 
assessment in the treatment of severe COVID-19.  


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2. 
OBJECTIVES AND ENDPOINTS 
Objectives 
Endpoints 
Primary Objectives 
Day 14 Ordinal Scale improvement 
Proportion of patients with at least a 2 point 
improvement (increase in the Ordinal Scale from 
baseline to Day 14. The Ordinal Score is an 
assessment of the clinical status at the first 
assessment on each day of hospitalization.  
The scale is as follows:  
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 (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.  
Key Secondary Objectives  
To evaluate improvement in clinical 
measures across the 2 treatment arms 
• Time to recovery defined as improvement 
from baseline score of 3 to ≥4 or from a 
baseline score of 4 to ≥5 
• Proportion of patients with at least a 2 point 
improvement (increase) in the Ordinal Scale 
from baseline to Day 7. 


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• Proportion of patients with at least a 1 point 
improvement (increase) in the Ordinal Scale 
from baseline to Day 7 
• Proportion of patients with at least a 1 point 
improvement (increase) in the Ordinal Scale 
from baseline to Day 14. 
• Time to an improvement of 2 point using 
WHO Ordinal Scale Improvement (TTCI-2) 
• Time to clinical improvement (TTCI-1): 
defined as the time from randomization to 
an improvement of 1 point on the Ordinal 
Scale 
• Overall Death Rate on Day 28 
• Rate of mechanical ventilation 
Additional Secondary Objectives  
To evaluate improvement in additional 
clinical measures across the 2 treatment 
arms  
• Overall Survival 
• Overall death rate on Day 14 
• Rate of ICU admission 
• Length of hospitalization 
• Length of ICU stay 
• Duration of mechanical ventilation 
• PaO2:FiO2 and/or oxygenation index over 
time 
To determine the anti-inflammatory and 
immune effect of selinexor 
• Reduction of C-reactive protein (CRP)  
• Reduction in ferritin levels  
• LDH 
• Measure changes from baseline of blood 
plasma cytokines: IL-1β, IL-1Rα, IL-2, IL-4, 
IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IFNγ, 
IP10, TNFα   
To assess safety and tolerability of 
selinexor [time frame: up to 28 days] 
• Listing and documentation of frequency and 
severity of adverse effects  


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T o c haracterize seli ne x or 
p har mac o ki netics 
•  Seli ne x or P K para meters, ma xi m u m plas ma 
c o nce ntrati o n ( C ma x ) a n d tr o u g h 
c o nce ntrati o n ( C tr o u g h), if feasi ble  
E x pl or at or y E n d p oi nts  
 
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3. 
STUDY DESIGN 
3.1. 
Overall Design 
This is a randomized phase 2, single-blinded study of low dose selinexor versus placebo to 
evaluate the activity in patients with severe COVID-19.  
The study has 2 arms and will evaluate selinexor 20 mg + standard of care (SoC) and placebo + 
SoC. As the treatment for COVID-19 is rapidly evolving, the SoC will vary over time and across 
regions of the world. Therefore, SoC  may include antibiotics (e.g., azithromycin), anti-malarial 
(e.g., hydroxychloroquine), or antivirals (e.g., remdesivir), and other agents (e.g., anti-IL-6 
antibodies) to be per the institution at each site. The randomization and stratification will 
minimize any influence in the variability of SoC. 
The study population will consist of hospitalized patients ≥18 years old with COVID-19. 
The enrollment will be stratified based on criteria in Section 4.4: 
Enrollment will be paused for evaluation of safety and efficacy after the enrollment of the first 
40 patients and the first meeting of the DSMB will occur within the first week of enrolling the 
40th patient.  No further patients will be enrolled until the completion of this DSMB review and 
the safety and efficacy data from the first 40 patients will be shared with the FDA prior to 
resuming enrollment. 
A dose of 20 mg selinexor or matching placebo will be administered orally on Days 1, 3, and 5 
of each week for up to 2 weeks. If the patient is tolerating therapy and clinically benefitting (i.e., 
not meeting any of the criteria for stopping therapy listed below), dosing can continue for an 
additional 2 weeks (on Days 15, 17, 19, 22, 24, and 26).  It is recommended that patients are 
dosed with study drug within 12 hours of providing consent. 
Patients who achieve ANY of the following criteria will be considered as having clinical benefit 
for the purpose of continuing dosing for an additional 2 weeks. 
1. Patient remains hospitalized and: 
a. Has not had a selinexor-related Grade 4 AE or selinexor-related serious AE (SAE)  
AND 
b. Has not had >1 point ordinal score reduction (worsening)  
OR  
c. Has 2 point reduction (worsening) in ordinal score with a ≥20% absolute 
reduction in FiO2 from peak oxygen requirement 
2. Patients discharged from the hospital before Day 28 must meet the following criteria in 
order to continue on selinexor: 
a. Platelet count >75,000/mm3 and 
b. Neutrophil count >1,000/mm3 and 
c. Serum sodium >130 mmol/L and 
d. No Grade ≥3 nausea or vomiting and 


Cli nical St u d y Pr ot oc ol: X P O R T -C o V -1 0 0 1    
  
  
  
  
 
        Seli ne x or  
Versi o n 6 . 0                                                                                                                                                0 8 Ma y 2 0 2 0  
C o nfi de ntial  
 
Pa ge 3 5  of 7 4  
e. N o  Gra de 4 A Es c o nsi dere d t o be relate d t o seli ne x or a n d  
f. I m pr o ve d or di nal sc ore fr o m baseli ne a n d 
g.  P ositi ve S A R S - C o V 2 b y F D A a p pr o ve d la b orat or y test at disc har ge 
3. 2.  
Scie ntific R ati o n ale f or St u d y Desi g n  
C O VI D - 1 9 is ca use d b y t he si n gle stra n de d R N A vir us S A R S- C o V 2 a n d ca n be acc o m pa nie d b y 
a mar ke d i nfla m mat or y res p o nse, w hic h is belie ve d t o be se verel y deter mi na ntal t o t he patie nt 
a n d ass ociate d wit h  res pirat or y failure a n d deat h.  B ot h t he S A R S- C o V 2 lifec ycle a n d pr o-
i nfla m mat or y tra nscri pti o n fact ors re q uire f u ncti o nal h ost n uclear e x p ort me diate d b y X P O 1. 
X P O 1 was rece ntl y i de ntifie d as a “ h u b” h ost pr otei n f or S R A S -C o V viral pr o pa gati o n  a n d 
seli ne x or has s h o w n marke d i n hi biti o n of viral re plicati o n i n vitr o  wit h a n I C 9 0 of ~ 1 0 0 n M. 
I n hi biti o n of X P O 1 b y t he SI N E seli ne x or c o ul d i n d uce b ot h a nti-viral a n d a nti -i nfla m mat or y 
acti vit y. 
3. 3.  
J ustific ati o n f or D ose  
3. 4.  
E n d of St u d y  Defi niti o n  
E n d of St u d y will occ ur w he n t he last patie nt has c o m plete d t he 3 0- da y Safet y f oll o w u p peri o d 
(after t heir last d ose of st u d y treat me nt), has wit h dra w n c o nse nt or has die d, w hic he ver c o mes 
first.   
C CI


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4. 
STUDY POPULATION 
Eligible patients are adults ≥18 years of age, admitted to the hospital, confirmed laboratory 
diagnosis of SARS-CoV2 infection. All patients, their proxies must provide signed written or 
verbal informed consent. The Informed Consent Form (ICF) and the process to obtain the 
informed consent will comply with all local laws, regulations, and guidance. 
4.1. 
Inclusion Criteria 
Patients are eligible to be included in the study only if they meet all the following criteria: 
1. Age ≥18 years 
2. Confirmed laboratory diagnosis of SARS-CoV2 by standard FDA-approved RT-qPCR 
assay or equivalent FDA-approved testing (local labs) within 7 days of enrollment. 
3. Currently hospitalized. 
4. Informed consent. 
5. Has symptoms of severe COVID-19 as demonstrated by: 
a. 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. 
b. 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 LPM 
oxygen by nasal canula, non-rebreather/Ventimask (or similar device) or high flow 
nasal canula in order to maintain SaO2 ≥92%, PaO2/FiO2 <300 mm/hg. Patients with 
COPD or chronic lung disease must demonstrate evidence of increased oxygen needs 
above baseline. 
6. Elevated CRP > 2 x ULN 
7. Concurrent anti-viral and/or anti-inflammatory agents (e.g., biologics, 
hydroxychloroquine) are permitted. If in the physician’s judgement, it is in the best 
interest of the patient to use anti-viral or anti-inflammatory treatments, these treatments 
are to be documented in the patient’s chart and entered in the electronic case report form.  
Note: Patients who may have received plasma convalescent therapy > 48 hours prior to 
enrollment with no clinical improvement and who still meet criteria for severe COVID-
19 may enroll.  On study plasma convalescent therapy is not permitted.  
Patient who receive plasma convalescent therapy within 48 hours may be permitted to 
enroll based on discussion with sponsor. 
8. Female patients of childbearing potential must have a negative serum pregnancy test at 
Screening. Female patients of childbearing potential and fertile male patients must use 
highly effective methods of contraception throughout the study and for 3 months 
following the last dose of study treatment. Highly effective methods of contraception are 
listed in Section 8.3.1. 
4.2. 
Exclusion Criteria  
Patients are excluded from the study if any of the following criteria apply: 


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1. Evidence of critical COVID-19 based on: 
a. 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) 
b. Septic shock (defined byinvestigator assessment or requires vasopressor) 
c. Multiple organ dysfunction/failure 
2. In the opinion of the investigator, unlikely to survive for at least 48 hours from screening  
3. Inadequate hematologic parameters as indicated by the following labs: 
a. Patients with severe neutropenia (ANC <1000 x 109/L) or 
b. Thrombocytopenia (e.g., platelets <100,000 per microliter of blood) 
4. Inadequate renal and liver function as indicated by the following labs: 
a. Creatinine clearance (CrCL) <20 mL/min using the formula of Cockcroft and Gault. 
b. Aspartate transaminase (AST) or alanine transaminase (ALT) > 5 x upper limit of 
normal (ULN) 
5. Hyponatremia defined as sodium < 130 mEq/L 
6. Unable to take oral medication when informed consent is obtained. 
7. Patients with a legal guardian or who are incarcerated.  
8. Treatment with strong CYP3A inhibitors or inducers. A list of strong CYP3A inhibitors 
and inducers is provided in Appendix 3. 
9. Pregnant and breastfeeding women. 
4.3. 
Screen Failures 
Screen failures are defined as patients who consent to participate in the clinical study but are not 
subsequently randomized for treatment in the study. Minimal information is required for these 
patients including demographics, screen failure details, eligibility criteria, and any serious 
adverse event (SAE) not related to COVID-19. 
Individuals who do not meet the criteria for participation in this study (screen failure) may be 
rescreened. Rescreened patients should be assigned the same patient number as for the initial 
screening. 
4.4. 
Randomization/Stratification  
Randomization will be performed prior to dosing. 
Randomization will be stratified based on the following stratification factors and will maintain 
the 2:1 allocation between treatment arms (selinexor vs placebo) within each of the stratification 
categories: 
• Use of concomitant therapies: an anti-viral (e.g., remdesivir) or an anti-inflammatory 
(e.g. hydroxychloroquine, biologics targeting e.g., IL-6 or IL-1).   


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Note: acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDs) will not 
constitute anti-inflammatory agents for the purposes of stratification.  
• High Risk Comorbidities: Age > 75, BMI> 30, cancer patients on chemotherapy, 
patients with cardiac (CAD, AMI, CHF) or pulmonary (COPD, emphysema) disease,  
diabetes, hypertension. Stratification will be based on number of high risk 
comorbidities: (1  vs  ≥2  vs  0) 


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5. 
STUDY TREATMENT 
5.1. 
Study Treatment Administered 
Table 3:  
Study Treatment Administered 
Treatment Name 
Selinexor (XPOVIO®, KPT-330) / Placebo 
Type  
Drug 
Dose Formulation 
Tablet 
Unit Dose Strength 
20 mg 
Dosage Level 
20 mg, single dose 
Route of Administration 
Oral 
A dose of 20 mg selinexor or matching placebo will be administered orally on Days 1, 3, and 5 
of each week for up to 2 weeks. If the patient is tolerating therapy and clinically benefitting 
(defined below), dosing can continue for an additional 2 weeks (on Days 15, 17, 19, 22, 24, and 
26). 
5.2. 
Dosing and Administration of Selinexor/Placebo 
5.2.1. 
Labeling 
Medication labels for each blister pack of selinexor and matching placebo tablets will be in the 
local language and comply with the legal requirements of each country. They will include 
storage conditions for the drug and the kit identification number, with a space to record the 
patient ID number after the IMP is assigned. 
5.2.2. 
Dispensing Directions 
The Investigator or responsible site personnel must instruct the patient or caregiver to take the 
study treatment as per protocol. Study treatment will be dispensed to the patient by authorized 
site personnel only. Additional dispensing instructions will be provided in the Pharmacy Manual. 
5.2.3. 
Dosing Information 
Study treatment tablets should be taken orally with at least 120 mL (4 ounces) of water. Study 
treatment can be taken with or without food. In order to avoid contact with skin, tablets must be 
swallowed whole and should not be crushed. 
Eligible patients must be able to take oral medication when informed consent is obtained. If a 
patient is later intubated or unable to take oral medication during treatment, it is permissible to 
use selinexor suspension prepared as below: 
A suspension of selinexor and/or placebo can be prepared by the site pharmacy from selinexor 
tablets, water, and the commercial suspension agent Ora-Blend®.  The pharmacy should place 
one 20 mg active or placebo tablet in a bottle (amber if available) and add 3 mL of water to 
disintegrate the tablet, then add 9 mL of Orablend® suspending agent. Gentle swirling or 


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inversion of the capped bottle will mix the suspension and suspend selinexor for dosing.  The 
resulting suspension should be dosed within 4 hours.  Administer the suspension to the patients 
using an oral dosing syringe via a nasogastric (NG) or percutaneous endoscopic gastrostomy 
(PEG) feeding tube. Rinse the bottle, syringe and tube with 40 mL to 110 mL of saline and dose 
the saline rinse to the patient to ensure complete delivery of the selinexor/placebo dose. 
Handling Precaution:  Selinexor tablets are coated for easy handling. Do not break, cut, or crush 
selinexor tablets because of increased risk of dermatologic toxicity (e.g., rash) from exposure to 
the active ingredient in the tablets.  
Handling Precaution: The tablets quickly disintegrate in water (<10 min) without being crushed. 
Please wear gloves when handling the suspension to prevent unintended exposure to the active 
ingredient. The site pharmacy should consult the pharmacy manual for full instructions on 
preparing and handling the suspension and for alternative suspending agents should Ora-Blend® 
be unavailable. 
5.3. 
Missed or Vomited Doses of Selinexor 
5.3.1. 
Missed Doses of Selinexor 
Missed selinexor doses should be managed as follows: 
• 
If a dose was missed, the dose should be taken the next day.  Subsequent doses must 
respect the required 48 hour interval planned schedule. All missed and delayed doses 
should be documented 
• 
If a dose must be skipped (e.g., due to recommendation of treating physician), the 
next dose will be taken as per schedule. All missed and delayed doses should be 
documented. 
5.3.2. 
Vomited Doses of Selinexor 
If a dose is vomited ≤1 hour after ingestion and an intact tablet is seen, it will be replaced. If 
vomiting occurs more than 1 hour after dosing, it will be considered a complete dose. 
5.4. 
Preparation/Handling/Storage/Accountability 
• The Investigator or designee must confirm appropriate temperature conditions have 
been maintained during transit for all study treatment received and any discrepancies 
are reported and resolved before use of the study treatment. 
• Only patients randomized in the study may receive study treatment and only 
authorized site staff may supply or administer study treatment. All study treatment 
must be stored in a secure, environmentally controlled, and monitored (manual or 
automated) area in accordance with the labeled storage conditions with access limited 
to the Investigator and authorized site staff. 
• The Investigator, institution, or the head of the medical institution (where applicable) 
is responsible for study treatment accountability, reconciliation, and record 
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• Further guidance and information for the final disposition of unused study treatment 
are provided in the Pharmacy Manual. 
5.5. 
Study Treatment Compliance 
Administration of study treatment will be documented at each timepoint specified in the SoA. 
Deviation(s) from the prescribed dosage regimen should be recorded in the eCRF. 
5.6. 
Concomitant Medication 
5.6.1. 
Recommended Concomitant Treatments  
Provide prophylactic concomitant treatment with a 5-HT3 antagonist and/or other anti-emetic 
agents prior to and during treatment with selinexor. 
Ensure that patients are maintaining adequate fluid status and administer intravenous hydration 
as clinically warranted during the study treatment. 
5.6.2. 
Prohibited/Permitted Concomitant Medications 
If in the physician’s judgement, it is in the best interest of the patient to use anti-viral or anti-
inflammatory treatments, these treatments are to be documented in the patient’s chart and entered 
in the electronic case report form. Use of these treatments should be carefully considered as they 
could potentially confound data interpretation. 
The use of strong CYP3A inhibitors or inducers while on selinexor treatment is not permitted.  
Selinexor should be interrupted during the use of these agents.  See Appendix 3 for a list of 
strong CYP3A inhibitors and inducers. 
5.7. 
Dose Modifications 
Each dose modification or treatment delay must be documented, including the respective reason.  
The reason for dose modification should be directly related to a selinexor-associated AE, and not 
due to disease symptom/sign or to other medications. 
For all Grade ≥3 hematological or non-hematological AEs that are NOT selinexor related, after 
consultation with the Medical Monitor and at the discretion of the Investigator, selinexor dosing 
may be maintained. 
Selinexor should be discontinued for all selinexor-related life-threatening (Grade 4) AEs. 
Table 4 summarizes the selinexor dose levels; Table 5 describes supportive care and dose 
adjustment guidelines. Deviations from the guidelines are permitted after discussion between the 
Sponsor and the treating physician. 
Table 4: 
Selinexor Dose Modification Steps for Adverse Reactions 
Recommended Starting Dosage 
First Reduction 
20 mg 
Days 1, 3 and 5 of each week  
(60 mg total per week) 
20 mg 
Days 1 and 3 weekly 
(40 mg total per week) 
 


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Table 5: 
Selinexor Dosage Modification for Adverse Reactions  
Adverse Reactiona 
Occurrence 
Action 
Hematologic Adverse Reactions 
Thrombocytopenia 
Platelet count 25,000 to 
less than 50,000/mcL  
Any 
• Reduce selinexor by 1 dose level (see Table 4). 
Platelet count 25,000 to 
less than 50,000/mcL with 
concurrent G3 bleeding 
Any 
• Interrupt selinexor and provide appropriate supportive 
care. 
• Restart selinexor after bleeding has resolved at 1 dose 
level lower (see Table 4). 
Platelet count less than 
25,000/mcL 
Any 
 
• Interrupt selinexor and provide appropriate supportive 
care. 
• Monitor until platelet count returns to at least 
50,000/mcL. 
• Restart selinexor at 1 dose level lower (see Table 4). 
Neutropenia 
Absolute neutrophil count 
of 0.5 to 1.0 x 109/L with 
fever 
Any 
• Interrupt selinexor and provide provide appropriate 
supportive care. 
• Monitor until neutrophil counts return to 1.0 x 109/L or 
higher. 
• Restart selinexor at 1 dose level lower (see Table 4). 
Absolute neutrophil count 
less than 0.5 x 109/L  
Any 
• Interrupt selinexor and provide appropriate supportive 
care. 
• Monitor until neutrophil counts return to 1.0 x 109/L or 
higher. 
• Restart selinexor at 1 dose level lower (see Table 4). 
Anemia 
Hemoglobin less than 8.0 
g/dL 
Any 
• Reduce selinexor by 1 dose level (see Table 4). 
• Administer blood transfusions and/or other treatments 
per clinical guidelines. 
Life-threatening 
consequences 
Any 
• Interrupt selinexor and administer appropriate care with 
blood transfusions and/or other treatments per clinical 
guidelines. 
• Monitor until patient stabilizes and hemoglobin is >8.0 
g/dL. 
• Restart selinexor at 1 dose level lower (see Table 4). 
Non-Hematologic Adverse Reactions 
Hyponatremia 
Sodium level 130 mmol/L 
or less not due to disease 
or fluid status 
Any 
• Interrupt selinexor and provide appropriate supportive 
care. 
• Monitor until sodium levels return to 130 mmol/L or 
higher.  


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Adverse Reactiona 
Occurrence 
Action 
• Restart selinexor at 1 dose level lower (see Table 4). 
Nausea and Vomiting 
Grade 1 or 2 nausea (oral 
intake decreased without 
significant weight loss, 
dehydration or 
malnutrition) 
OR Grade 1 or 2 vomiting 
(5 or fewer episodes per 
day) 
Any 
• Maintain selinexor and initiate additional anti-nausea 
medications. 
Grade 3 nausea 
(inadequate oral caloric or 
fluid intake)  
OR Grade 3 or higher 
vomiting (6 or more 
episodes per day) 
Any 
• Interrupt selinexor.  
• Monitor until nausea or vomiting has resolved to Grade 
2 or lower or baseline.  
• Initiate additional anti-nausea medications for Grade 2 
or lower. 
• Restart selinexor at 1 dose level lower (see Table 4) 
Diarrhea 
Grade 2 (increase of 4 to 6 
stools per day over 
baseline) 
1st  
• Maintain selinexor and institute supportive care. 
 
 
2nd and 
subsequent 
• Reduce selinexor by 1 dose level (see Table 4). 
• Institute supportive care. 
Grade 3 or higher 
(increase of 7 stools or 
more per day over 
baseline; hospitalization 
indicated) 
Any 
 
• Interrupt selinexor and institute supportive care. 
• Monitor until diarrhea resolves to Grade 2 or lower. 
• Restart selinexor at 1 dose level lower (see Table 4).  
Weight Loss and Anorexia 
Weight loss of 10% to less 
than 20%  
OR anorexia associated 
with significant weight 
loss or malnutrition not 
due to intensive care status 
Any 
• Interrupt selinexor and institute supportive care. 
• Monitor until weight returns to more than 90% of 
baseline weight. 
• Restart selinexor at 1 dose level lower (see Table 4). 
Other Adverse Reactions 
Grade 3 or 4 non-
hematologic reactions 
Any 
• Interrupt selinexor. 
• Monitor until resolved to Grade 2 or lower, restart 
selinexor at 1 dose level lower (see Table 4).  
Life-threatening 
hematological and non-
hematological (Grade 4) 
AEs related to selinexor 
Any 
• Discontinue selinexor 
a National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0. Only 
adverse reactions to selinexor should lead to dose adjustments. 


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6. 
DISCONTINUATION OF STUDY TREATMENT AND PATIENT 
DISCONTINUATION/WITHDRAWAL 
6.1. 
Discontinuation of Study Treatment 
In rare instances, it may be necessary for a patient to permanently discontinue study treatment. If 
study treatment is permanently discontinued, the patient will remain in the study to be evaluated 
for overall mortality. See the SoA for data to be collected at the time of discontinuation of study 
treatment. 
Selinexor should be discontinued for all selinexor-related life-threatening (Grade 4) AEs. 
6.2. 
Patient Discontinuation/Withdrawal from the Study 
A patient may withdraw from the study at any time at his/her own request or may be withdrawn 
at any time at the discretion of the Investigator for safety, behavioral, compliance, or 
administrative reasons. Waivers for eligibility criteria for enrollment will not be permitted. The 
criteria given below are reasons the investigator must consider for removal of patients from 
study.  
The Investigator must determine the primary reason for a patient’s discontinuation of study 
treatment/withdrawal from the study and record this information on the electronic case report 
form (eCRF). 
The Investigator may remove a patient from study treatment for any of the following reasons: 
• Unacceptable AEs or toxicity that cannot be managed by supportive care 
• Significant deviations from inclusion/exclusion criteria 
• Missed / unscheduled / off-schedule / incomplete / incorrect assessments that result in 
patients being put at risk 
• Any other medically appropriate reason or significant protocol violation, in the 
opinion of the Investigator. 
The Investigator must remove a patient from study treatment for any of the following reasons: 
• Patient withdraws consent to continue study treatment. 
• Worsening clinical condition defined as at least 5 days of intubation/ECMO with no 
evidence of clinical improvement.  Patients who are clinically stable based on oxygen 
requirements on mechanical ventilation will be permitted to remain on study. 
• Grade ≥3 nausea or vomiting despite optimal antiemetic therapy. 
• Progression of renal dysfunction requiring dialysis. 
• Grade 4 AEs related to selinexor. 
6.3. 
Lost to Follow up 
A patient will be considered lost to follow-up if he/she unable to be contacted by the study site. 


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6.4. 
Blinding 
The site investigators and patients are blinded to treatment assignment during the conduct of the 
study. All study staff will be blinded to the treatment assignments and study drug will be 
administered in a blinded manner.  
Unblinding of treatment assignments should be undertaken for safety reasons when it is essential 
for effective treatment of the patient. 
Unblinding is performed using the IRT. When the investigator contacts the IRT to unblind a 
patient, he/she must provide the requested patient identifying information and confirm the 
necessity to unblind the patient. The Investigator will then receive details of the drug treatment 
for the specified patient. 
The entire study population will be unblinded at the end of the study and the unblinding 
information will be shared with each study site. 
6.5. 
Early Termination of the Study 
The study may be terminated at the sole discretion of the Sponsor for any reason, including 
medical or ethical reasons affecting the continued performance of the study, or difficulties in the 
recruitment of patients. If this occurs, the Sponsor will notify independent ethics committees 
(IECs), institutional review boards (IRBs), Investigators, and regulatory authorities.  
6.6. 
End of Study 
End of Study will occur when the last patient has completed the 30-day Safety follow up period 
(after their last dose of study treatment), has withdrawn consent or has died, whichever comes 
first.  


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7. 
STUDY ASSESSMENTS AND PROCEDURES 
• Study procedures and their timing are summarized in the SOA.  
• Immediate safety concerns should be discussed with the Sponsor immediately upon 
occurrence or awareness to determine if the patient should continue or discontinue 
study treatment. 
• Procedures conducted as part of the patient’s routine clinical management (e.g., blood 
count) and obtained prior to signing of the informed consent form (ICF) may be 
utilized for screening or baseline purposes provided the procedures met the protocol-
specified criteria and were performed within the time frame defined in the SOA. 
• Please reference the Karyopharm Risk Management Plan for Conduct of Clinical 
Trials During the COVID-19 Pandemic as the document may address procedures 
being performed as a part of this clinical trial. 
7.1. 
Baseline Assessments 
7.1.1. 
Demographics 
Patient demographics (including date of birth, sex, ethnicity, and race) will be collected. 
7.1.2. 
Medical History 
The medical history will include co-infections, baseline symptoms as well as active medical 
conditions. Data from standard-of-care procedures will be part of the patient's medical history 
and may be used for study purposes. 
In addition, the smoking history of the patient will be recorded. 
7.1.3. 
Disease History 
The disease history will include collection of COVID-19 symptom onset date as well as date and 
time of admission to hospital and reason for admission (COVID-diagnosis/COVID associated 
complication or Concomitant Illness). 
7.2. 
Efficacy Assessments 
Study procedures and their timing are summarized in the SOA. 
7.3. 
Safety Assessments 
Planned time points for all safety assessments are provided in the SOA. 
7.3.1. 
Physical Examinations  
The physical examination will be performed according to the standards at each institution. 
Complete physical examination, including vital signs, will be performed in the screening visit 
and if possible, at the End of Study visit. Suspected selinexor associated symptom-directed 
physical exam should be performed at any time directed by the clinical need as directed by the 
investigator.  


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Vital signs will include: 
• Body temperature (°C or °F) 
• Systolic and diastolic blood pressure and pulse rate 
• Respiratory Rate  
• Oxygen Saturation 
− If patient requires respiratory assistance, then type of assistance, start and end date 
as well as reason for removal of mechanical ventilation will be documented in the 
eCRF. 
Clinically relevant findings made after the start of study treatment, which meet the definition of 
an AE, must be recorded on the AE eCRF. 
7.3.2. 
Ordinal Score 
The Ordinal score is a composite measure of clinical improvement and/or survival, assessed on a 
daily basis.  
The severity rating is on a 8-point ordinal scale: 
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 
(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. 
7.3.3. 
Electrocardiograms 
Standard 12-lead ECGs will be performed at the time points specified in the SoA.  
The Investigator will interpret the ECG using 1 of the following categories: normal, abnormal 
but not clinically significant, or abnormal and clinically significant.  
The time the ECG was performed, and the following parameters will be recorded in the eCRF: 
heart rate, PR interval, QT interval, QRS interval, and QT corrected using either Bazett’s or 
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7.3.4. 
Clinical Safety Laboratory Assessments 
Clinical laboratory tests (detailed in Table 6) will be performed by the sites’ local laboratories. In 
addition, laboratory tests will be collected and analyzed at times specified on the SoA. More 
frequent assessments may be performed if clinically indicated. 
Table 6: 
Clinical Safety Laboratory Tests 
Hematology 
Hemoglobin 
Leukocytes (with differential) 
Neutrophils 
Hematocrit 
Platelet count 
Monocytes 
Basophils 
Lymphocytes 
Eosinophils 
Serum Chemistry 
Sodium 
Creatinine 
ALT 
Potassium 
Glucose 
AST 
Albumin 
Calcium 
Alkaline phosphatase 
Bicarbonate 
Phosphate 
Total bilirubin 
BUN/Urea 
LDH 
Total protein 
Coagulation  
PT 
aPTT 
INR 
Blood samples will be analyzed at each study center by a certified laboratory. The Investigator or 
designee will review the laboratory report after receipt of the results and assess the clinical 
significance of all abnormal values. Results should be reviewed prior to dosing and appropriate 
action taken for any clinically significant abnormal values.  
At any time during the study, abnormal laboratory values which are clinically relevant 
(e.g., require dose modification and/or interruption of study treatment, lead to clinical symptoms 
or signs or require therapeutic intervention), must be documented in the eCRF.  
If any abnormal laboratory value or test result constitutes a selinexor related AE, then these must 
be recorded on the AE eCRF. Values will be documented on the laboratory report until 
stabilized, or the laboratory value returns to a clinically acceptable range (regardless of 
relationship to study treatment) or baseline. Any laboratory value that remains abnormal at the 
End of Study visit that is considered clinically significant will be followed according to accepted 
medical standards for up to 30 days or until resolution of the abnormality or return to baseline 
levels. Toxicity will be assessed using the NCI CTCAE, v. 5.0. 
Karyopharm must be provided with a copy of the laboratory certification and normal ranges for 
each parameter measured. In addition, if at any time a patient has laboratory parameters obtained 
from a different outside laboratory, Karyopharm must be provided with a copy of the 
certification and normal ranges for that laboratory. 
7.3.5. 
Adverse Events and Serious Adverse Events 
Detailed information related to the collection and reporting of AEs and SAEs in Section 8. 


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T he I n vesti gat or a n d a n y q ualifie d desi g nees are res p o nsi ble f or detecti n g, d oc u me nti n g, a n d 
rec or di n g e ve nts t hat meet t he defi niti o n of a n A E or S A E a n d re mai n res p o nsi ble f or f oll o wi n g 
u p A Es t hat are seri o us, c o nsi dere d relate d t o st u d y treat me nt or st u d y pr oce d ures, or t hat ca use d 
t he patie nt t o disc o nti n ue st u d y dr u g (see Secti o n 6 ). 
7. 3. 5. 1.  
Pre g n a nc y Testi n g  
Pre g na nc y testi n g will be perf or me d o nl y f or fe males of c hil d beari n g p ote ntial. A ne gati ve ser u m 
h C G pre g na nc y test m ust be o btai ne d at Scree ni n g ( wit hi n 2 da ys bef ore st u d y treat me nt 
a d mi nistrati o n) a n d at t he e n d of treat me nt. Pre g na nc y testi n g ma y be perf or me d if cli nicall y 
i n dicate d d uri n g t he st u d y. 
7. 4.  
P h ar m ac o ki netic Assess me nts  
P har mac o ki netic ( P K) assess me nt will be perf or me d o n a s u bset of patie nts. Bl o o d dra ws f or P K 
a nal ysis of a p pr o xi matel y 2. 0 m L will be c ollecte d  f or t he meas ure me nt of plas ma 
c o nce ntrati o ns of seli ne x or  at 4 ± 1 hr, 2 4 ± 4 hr p ost d ose o n Da y 1 a n d pre d ose o n Da ys 3 a n d 
5. I nstr ucti o ns f or t he c ollecti o n a n d ha n dli n g of bi ol o gical sa m ples are pr o vi de d i n t he 
La b orat or y Ma n ual. T he act ual date a n d ti me ( 2 4- h o ur cl oc k ti me) of eac h sa m ple a n d seli ne x or 
d ose will be  rec or de d.  
If a patie nt e x perie nces e mesis wit hi n  t he first h o ur of seli ne x or d osi n g, n o P K sa m ples will be 
c ollecte d f or t hat d ose.  
Plas ma P K sa m ples will be s hi p pe d t o a bi oa nal ytical la b orat or y f or a nal ysis. Details f or 
c ollecti o n a n d pr ocessi n g of P K sa m ples ca n be f o u n d i n t he La b orat or y Ma n ual. Plas ma 
sa m ples will be a nal yze d via a vali date d hi g h- perf or ma nce li q ui d c hr o mat o gra p h y/ta n de m mass 
s pectr o metr y ( H P L C/ M S- M S) met h o d f or plas ma seli ne x or. 
7. 5.  
C yt o ki ne Asses sme nts  
Bl o o d dra ws f or c yt o ki ne a nal ysis of a p pr o xi matel y 2. 5 m L will be c ollecte d acc or di n g t o t he 
Sc he d ule of Assess me nts Ta ble . We will be testi n g c yt o ki nes a n d ot her plas ma pr otei ns a n d 
c o m pare t heir le vels t o assess t he efficac y of seli ne x or i n t he re d ucti o n of c yt o ki nes k n o w n t o be 
ele vate d i n C O VI D - 1 9 patie nts. E xact details o n t he c ollecti o n, pre parati o n, st ora ge a n d deli ver y 
o f t he sa m pl es will be i ncl u de d i n t he Cli nical Pr ot oc ol La b ma n ual. 
7. 6.  
Le u k oc yte P he n ot y pi n g  
F or  Le u k oc yte P he n ot y pi n g, bl o o d will be c ollecte d acc or di n g t o t he Sc he d ule of Assess me nts 
Ta ble . E xact details o n t he c ollecti o n, pre parati o n, st ora ge a n d deli ver y of t he sa m ples will be 
i ncl u de d i n t he Cli nical Pr ot oc ol La b ma n ual. 
7. 7.  
Vir al  Assess me nts  
C CI


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8. 
ADVERSE EVENTS 
8.1. 
Information on Reporting Adverse Events 
8.1.1. 
Definitions 
• Adverse event (AE): Any untoward medical occurrence in a patient or clinical 
investigation subject 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.  
• Life-threatening adverse event or life-threatening suspected adverse reaction: An 
adverse event or suspected adverse reaction is considered "life-threatening" if, in the 
view of either the investigator or sponsor, its occurrence places the patient or subject 
at immediate risk of death. It does not include an adverse event or suspected adverse 
reaction that, had it occurred in a more severe form, might have caused death. 
• Treatment-emergent adverse event (TEAE): Any event that was not present prior to 
the initiation of study treatment or any event already present that worsens in either 
intensity or frequency following exposure to study treatment.  
• Serious adverse event (SAE): Any untoward medical occurrence that, at any dose, 
results in death; is life threatening (ie, an event in which the patient was at risk of 
death at the time of the event; it does not refer to an event that hypothetically might 
have caused death if it were more severe); requires inpatient hospitalization or 
prolongation of existing hospitalization; results in persistent or significant 
disability/incapacity; or is a congenital anomaly/birth defect. Important medical 
events that may not result in death, be life-threatening, or require hospitalization may 
be considered serious when, based upon appropriate medical judgment, they may 
jeopardize the patient or subject and may require medical or surgical intervention to 
prevent one of the outcomes listed in this definition. Examples of such medical events 
include allergic bronchospasm requiring intensive treatment in an emergency room or 
at home, blood dyscrasias or convulsions that do not result in inpatient 
hospitalization, or the development of drug dependency or drug abuse. (See 
Section 8.2.1.3 for additional information about SAE reporting.)  
• Suspected adverse reaction: Any adverse event for which there is a reasonable 
possibility that the drug caused the adverse event. For the purposes of IND safety 
reporting, "reasonable possibility" means there is evidence to suggest a causal 
relationship between the drug and the adverse event. Suspected adverse reaction 
implies a lesser degree of certainty about causality than adverse reaction, which 
means any adverse event caused by a drug. 
• Unexpected adverse event or unexpected suspected adverse reaction: An adverse 
event or suspected adverse reaction is considered "unexpected" if it is not listed in the 
investigator brochure or is not listed at the specificity or severity that has been 
observed; or, if an investigator brochure is not required or available, is not consistent 


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with the risk information described in the general investigational plan or elsewhere in 
the current application, as amended. For example, under this definition, hepatic 
necrosis would be unexpected (by virtue of greater severity) if the investigator 
brochure referred only to elevated hepatic enzymes or hepatitis. Similarly, cerebral 
thromboembolism and cerebral vasculitis would be unexpected (by virtue of greater 
specificity) if the investigator brochure listed only cerebral vascular accidents. 
"Unexpected," as used in this definition, also refers to adverse events or suspected 
adverse reactions that are mentioned in the investigator brochure as occurring with a 
class of drugs or as anticipated from the pharmacological properties of the drug, but 
are not but are not specifically mentioned as occurring with the particular drug under 
investigation. 
8.1.2. 
Recording of Adverse Events 
All AEs that begin or worsen after the patient has provided informed consent will be recorded. 
Those AEs that occur prior to study dosing, can be captured in the patient’s baseline conditions, 
however if any of these AEs are considered, serious, these are to be reported both to 
Pharmacovigilance and documented in the eCRF AE log. For events that are considered by the 
Investigator to be related to the study drug, the monitoring of the AE should be continued 
through the end of the study, for at least 30 days following last dose of study drug (if the end of 
the study is within 30 days of the last dose of study drug), or until the AE has resolved.  
Investigators should use medical judgment in determining whether a particular symptom or sign 
is considered to be a part of COVID-19 infection clinical course or not and report them or not as 
AEs according to such determination. When a clear determination cannot be made by the 
investigators, a sign or symptom should be reported as AEs. All deaths irrespective of cause of 
death including due to COVID-19 during the study should be reported to the Sponsor using an 
SAE form. 
Adverse events (including laboratory abnormalities that constitute AEs) should be described 
using a diagnosis whenever possible, rather than individual underlying signs and symptoms. 
When a clear diagnosis cannot be identified, each sign or symptom should be recorded as a 
separate AE. 
The Investigator should ask the patient non-leading questions to determine if any AEs have 
occurred during the study, since the last study visit. Adverse events may also be recorded when 
they are volunteered by the patient, or through physical examination, laboratory tests, or other 
clinical assessments. 
An AE should be followed until its resolution or until it is judged to be permanent, and 
assessment should be made at each visit (or more frequently, if necessary) of any changes in 
severity of the event, the suspected relationship to the study treatment, the interventions required 
to treat the event, and the outcome. 
8.1.2.1. 
Laboratory Test Abnormalities 
Laboratory abnormalities that constitute an AE in their own right (i.e., are considered to be 
clinically significant, induce clinical signs or symptoms, require concomitant therapy, or require 
changes in study treatment), should be recorded on the Adverse Events eCRF. Whenever 


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possible, a diagnosis, rather than a symptom should be provided (e.g., anemia instead of low 
hemoglobin).  
Laboratory abnormalities that meet the criteria for an AE should be followed until they have 
returned to baseline levels (as measured during the Screening visit) or an adequate explanation of 
the abnormality is identified. When an abnormal laboratory or test result corresponds to a 
sign/symptom of an already reported AE, it is not necessary to separately record the 
laboratory/test result as an additional event. 
A laboratory abnormality that does not meet the definition of an AE should not be reported as an 
AE. A Grade 3 or 4 event (considered to be severe per NCI CTCAE, v. 5.0) does not 
automatically indicate an SAE unless it meets the definition of serious as defined in Section 8.1 
and/or as per the opinion of the Investigator. A laboratory abnormality that results in a dose 
being held or modified would, by definition, be an AE and must be recorded as such in the 
eCRF. 
8.1.2.2. 
Adverse Event Severity 
The term “severe” is used to describe the intensity of an AE; the event itself could be of 
relatively minor clinical significance (e.g., ‘severe’ headache). This is not the same as a “serious” 
AE. 
The severity of the AE will be graded by the Investigator according to the NCI CTCAE Grading 
Scale, v. 5.0 (the NCI CTCAE files can be accessed online at the following URL: 
http://evs.nci.nih.gov/ftp1/CTCAE/About.html).  
If there is not a specific NCI CTCAE grading scale for an AE, the severity will be characterized 
as mild, moderate, severe, or life-threatening, according to the following definitions: 
• Grade 1 (mild) events are usually transient in nature and do not interfere with the 
patient’s daily activities. 
• Grade 2 (moderate) events introduce a low level of inconvenience or concern to the 
patient and may interfere with daily activities. 
• Grade 3 (severe) events interrupt the patient’s usual daily activities. 
• Grade 4 events are those that are considered to be life-threatening. 
8.1.3. 
Adverse Event Causality 
The Investigator will make a judgment regarding the relationship of the AE to study treatment, as 
defined below. 
• Not related: These events will lack a strong temporal relationship of the event to the 
study treatment, making a causal relationship not reasonably possible.  Exposure to 
other drugs, therapeutic interventions, or underlying conditions may provide a 
sufficient explanation for the event. 
• Related: There is a temporal relationship of the event to the study treatment making a 
definitive relationship, and the event is more likely explained by exposure to the 
study treatment than by any other drugs, therapeutic interventions, or underlying 
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8.2. 
Serious Adverse Events 
See Section 8.1 for the definition of an SAE. Please note that SAEs that occur at any time 
between the signing of the Informed Consent Form up to the first dose of study treatment must 
be reported (in addition to SAEs that occur after the first dose of study treatment). 
8.2.1.1. 
Events that Do Not Meet the Definition of a Serious Adverse Event 
Patients are hospitalized as part of the study. If patients are kept in hospital due to a social reason 
or an administrative reason after they are considered to be discharged, these events will not be 
considered an SAE. Any other elective hospitalizations to simplify trial treatment or trial 
procedures or other medical procedures are not considered SAEs 
Any sudden explained or unexplained death should be reported as an SAE. Death due to 
COVID-19 should be reported to the Karyopharm PV department using a SAE form.  
8.2.1.2. 
Recording of Serious Adverse Events 
It is the responsibility of the Investigator to record and document all SAEs occurring from the 
time when the ICF is signed until at least 30 days after the patient has stopped study treatment. 
All SAEs must be reported on the designated Sponsor’s SAE Report Form in addition to being 
recorded in the eCRF. The original SAE report form must be retained in the Investigator’s site 
file. 
All applicable sections of the SAE Report Form must be completed in order to provide a 
clinically thorough report. The Investigator must assess and record the relationship of each SAE 
to study treatment and complete the form in English. 
See ICH E2A (Clinical Safety Data Management: Definitions and Standards for Expedited 
Reporting, Attachment 1) for key data elements that are required for expedited reporting. 
8.2.1.3. 
Reporting of Serious Adverse Events 
Every SAE, regardless of the causal relationship to the study treatment, occurring after the 
patient has signed informed consent, until at least 30 days after the patient has stopped study 
treatment, must be reported to the Karyopharm Pharmacovigilance Department with the 
timeframe not to exceed 24 hours of the Investigator becoming aware of the event. The 
investigational site personnel must use the SAE Report Form provided by Karyopharm for 
reporting any SAE to the Karyopharm Pharmacovigilance Department. 
Upon completion, the SAE Report Form must be immediately emailed or faxed to: 
Pharmacovigilance Department 
Karyopharm Therapeutics Inc. 
Email: pharmacovigilance@karyopharm.com 
Fax: 
+1-617-334-7617 (USA) 
+49-89-9218-5650 (Germany) 
Any SAE observed after the 30-day follow-up period should only be reported to Karyopharm if 
the Investigator suspects that the SAE has a causal relationship to the study treatment. Recurrent 
episodes, complications, or progression of the initial SAE must be reported, as follow-up to the 
original episode, within 24 hours of the Investigator receiving the follow-up information.  


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An SAE should be followed until its resolution or until it is judged to be permanent. An 
assessment should be made at each study visit (or more frequently, if necessary) of any changes 
in severity of the event, the suspected relationship to the study treatment, the interventions 
required to treat the event, and the outcome of the event. 
8.2.1.4. 
Suspected Unexpected Serious Adverse Reactions 
Suspected unexpected serious adverse reactions (SUSARs) are SAEs that are unexpected and 
judged by the Investigator or Karyopharm to be related to the study treatment administered. All 
SUSARs will be collected and reported to the competent authorities and relevant ethics 
committees in accordance with the FDA’s “Safety Reporting Requirements for Investigational 
New Drugs and Bioanalytical/Bioequivalence Studies” or as per national regulatory requirements 
in participating countries. 
If required by local regulations, the Investigator is responsible for notifying his/her IRB or local 
ethics committee of all SAEs. 
8.3. 
Procedures for Handling Special Situations 
8.3.1. 
Pregnancy and Breastfeeding 
Note: Pregnancy per se is not considered to be an AE; however, it is discussed here because of 
the importance of reporting pregnancies that occur during studies and because a medical 
occurrence observed in the mother or fetus/newborn would be classified as an AE. 
Female patients of childbearing potential and fertile male patients will be informed as to the 
potential risk of conception while participating in this study and will be advised that they must 
use highly effective contraception listed below (i.e., results in a low failure rate when used 
consistently and correctly) during the dosing period and for a period of at least 3 months after the 
end of treatment. 
Highly effective methods include: 
• Combined (estrogen and progestogen containing) hormonal contraception associated 
with inhibition of ovulation: 
− Oral 
− Intravaginal 
− Transdermal 
• Progestogen-only hormonal contraception associated with inhibition of ovulation: 
− Oral 
− Injectable 
− Implantable 
• Intrauterine device 
• Intrauterine hormone-releasing system 
• Bilateral tubal occlusion 


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• Vasectomized partner 
• Sexual abstinence 
If a patient is confirmed pregnant during the study, study drug administration must be 
discontinued immediately. The Investigator must immediately notify the Sponsor’s Medical 
Monitor of the event and record the pregnancy on the Pregnancy Form (provided by 
Karyopharm). The initial information regarding a pregnancy must be forwarded to Karyopharm’s 
Pharmacovigilance by email or fax within 24 hours of first knowledge of its occurrence.  
The pregnancy should be followed up to determine the outcome, including any spontaneous or 
voluntary termination, details of the birth, and any birth defects, congenital abnormalities, or 
maternal and/or newborn complications.  
All pregnancies occurring within 3 months after the patient’s last dose of study drug must be 
reported to Karyopharm, regardless of whether the patient received selinexor or other study 
drugs, withdraws from the study, or the study is completed. Patients should be instructed to 
inform the Investigator regarding any pregnancies.  
Any SAE that occurs during pregnancy must be recorded on the SAE report form (e.g. maternal 
serious complications, therapeutic abortion, ectopic pregnancy, stillbirth, neonatal death, 
congenital anomaly, or birth defect) and reported within 24 hours in accordance with the 
procedure for reporting SAEs (described in Section 8.2.1.3 ). 
A pregnancy in a female partner of a male patient must be reported to Karyopharm within 24 
hours of learning of its occurrence. Pregnancies in female partners should only be followed if the 
male patient is being treated with a selinexor-containing regimen. Consent to report information 
regarding these pregnancy outcomes should be obtained from the female partner. 
It is not known whether selinexor passes into the breast milk. Mothers should not breastfeed 
while being treated with selinexor-containing regimen. 
8.3.2. 
Abuse, Misuse, Medication Errors and Overdose 
All incidences of abuse, misuse, medication errors and overdose are to be reported to 
Karyopharm Pharmacovigilance on an SAE report form to pharmacovigilance 
@karyopharm.com, regardless of whether or not there is an associated AE or SAE. 
8.3.2.1. 
Overdose 
An overdose is a deliberate or accidental administration of any study treatment to a study patient, 
at a dose greater than that which was assigned to that patient per the study protocol. If an 
overdose occurs, the Investigator and Karyopharm should be notified immediately, and the 
patient should be observed closely for AEs. Resulting symptoms should be treated, as 
appropriate, and the incident of overdose and related AEs and/or treatment should be 
documented in the patient’s medical record and in the eCRF. Information regarding the overdose 
is to be recorded on an SAE report form and sent to Karyopharm Pharmacovigilance, regardless 
of whether or not an AE or SAE has occurred due to the overdose. If the overdose is associated 
with an SAE, the SAE report form must be submitted to Karyopharm Pharmacovigilance within 
24 hours of awareness. If there is no AE or SAE, the report must be submitted as soon as 
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Doses of selinexor of up to 160 mg per week (80 mg twice weekly, the approved dose in 
RRMM) and weekly doses of up to 100 mg have been given to patients with advanced cancers 
with adequate tolerability.  No specific antidotes for overdose are known at this time. 
8.3.2.2. 
Abuse, Misuse, or Medication Error 
Abuse is the persistent or sporadic, intentional excessive use of the study treatment which is 
accompanied by harmful physical or psychological effects.  
A medication error is any preventable incident that may cause or lead to inappropriate study 
treatment use or patient harm while the study treatment is in the control of the health care 
professionals or patients. Such incident may be due to health care professional practice, product 
labeling, packaging and preparation, procedures for administration, and systems, including the 
following: prescribing, order communication, nomenclature, compounding, dispensing, 
distribution, administration, education, monitoring, and use. 
All occurrences of abuse, misuse, or medication error with any study treatment are to be 
recorded on an SAE report form and sent to Karyopharm Pharmacovigilance, regardless of 
whether or not an AE or SAE has occurred due to the abuse, misuse, or medication error. If the 
abuse, misuse, or medication error is associated with an SAE, the SAE report form must be 
submitted to Karyopharm Pharmacovigilance within 24 hours of awareness. If there is no AE or 
SAE, the report must be submitted within 24 hours of awareness. 


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9.  
S T A TI S TI C A L C O N SI D E R A TI O N S  
A statistical a nal ysis pla n ( S A P) will be fi nalize d pri or t o data base l oc k. A n y c ha n ges fr o m t he 
statistical a nal yses descri be d i n t his d oc u me nt will be descri be d i n t he S A P, a n d a n y de viati o n 
fr o m t he fi nal S A P will be descri be d i n t he fi nal re p ort. 
9. 1.  
Ge ner al C o nsi der ati o ns  
Ta b ulati o ns will be pr o d uce d f or a p pr o priate de m o gra p hic, baseli ne, efficac y, a n d safet y 
para meters.  
F or cate g orical varia bles, s u m mar y ta b ulati o ns of t he n u m ber a n d perce nta ge of patie nts wit hi n 
eac h cate g or y ( wit h a cate g or y f or missi n g data) of t he para meter will be prese nte d.  
F or c o nti n u o us varia bles, t he n u m ber of patie nts, mea n, me dia n, sta n dar d de viati o n, mi ni m u m, 
a n d ma xi m u m val ues will be prese nte d. 
9. 1. 1.  
Pr oce d ures f or H a n dli n g Missi n g D at a  
F or A Es, missi n g dates will n ot be i m p ute d; h o we ver, if partial dates are a vaila ble, t he y will be 
use d t o assess if t he  A E occ urre d d uri n g t he treat me nt peri o d. Missi n g se verities of A Es will n ot 
be i m p ute d a n d will be c o nsi dere d missi n g i n a n y ta b ulati o ns of A E se verit y. If a n A E is missi n g 
a res p o nse t o t he q uesti o n re gar di n g relati o ns hi p t o treat me nt, t he e ve nt will be c o nsi dere d t o be 
relate d. 
9. 2.  
S a m ple Size Deter mi n ati o n  
A p pr o xi matel y 2 4 7 patie nts
 
 
9. 3.  
P o p ul ati o ns f or A n al yses 
T he i nte nt- t o-treat (I T T) p o p ulati o n will c o nsist of all patie nts w h o are ra n d o mize d i n t he st u d y 
wit h c o nfir me d S A R S- C o V 2 i nfecti o n u n der pr ot oc ol versi o n 6. 0 a n d a b o ve , re gar dless of 
w het her or n ot t he y recei ve st u d y treat me nt.  
T he all -treat ( A T) p o p ulati o n will c o nsist of all patie nts w h o t o o k at least o ne d ose of st u d y 
treat me nt o n t his st u d y a n d ha ve c o nfir me d S A R S- C o V 2 i nfecti o n.  
9. 4.  
St atistic al A n al yses  
S u m mar y ta b ulati o ns will be pr o vi de d f or dis p ositi o n, de m o gra p hic, baseli ne, efficac y, a n d 
safet y data as n ote d i n t he f oll o wi n g secti o ns.  
T his secti o n is a s u m mar y of t he pla n ne d statistical a nal yses of t he pri mar y a n d sec o n dar y 
e n d p oi nts. 
9. 4. 1.  
Effic ac y A n al yses 
Efficac y a nal yses will be perf or me d i n I T T p o p ulati o n. If t he pri mar y e n d p oi nt, ( Da y 1 4 O SI) , is 
si g nifica nt, t he 4 ke y sec o n dar y e n d p oi nts will be se q ue ntiall y teste d i n t he or der liste d bel o w. If 
C CI


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any null hypothesis is not rejected in this sequence of tests, formal sequential testing will be 
stopped and the analyses of any endpoints thereafter will be nominal only.   
• 
Time to recovery defined as improvement from baseline score of 3 to ≥4 or from a 
baseline score of 4 to ≥5 
• 
Proportion of patients with at least a 2 point improvement (increase) in the Ordinal Scale 
from baseline to Day 7. 
• 
Proportion of patients with at least a 1 point improvement (increase) in the Ordinal Scale 
from baseline to Day 7 
• 
Proportion of patients with at least a 1 point improvement (increase) in the Ordinal Scale 
from baseline to Day 14. 
• 
Time to an improvement of 2 point using WHO Ordinal Scale Improvement (TTCI-2) 
• 
Time to clinical improvement (TTCI-1): defined as the time from randomization to an 
improvement of 1 point on the Ordinal Scale 
• 
Overall Death rate on Day 28 (DR) 
• 
Rate of mechanical ventilation (RMV) 
The difference in binary endpoints between treatment arms will be calculated with a 95% 
confidence interval (CI). Comparison of the these  endpoints between the 2 treatment arms will 
be performed using the Cochran-Mantel-Haenszel (CMH) test stratified by the randomization 
stratification factors. The CMH estimate of the odds ratio and its 95% CI and the p-value for 
testing the treatment difference will be reported. 
The analysis of time to event endpoints will be performed by treatment arm based on a log-rank 
test. The median will be estimated with a 95% CI for each treatment arm using the Kaplan-Meier 
method. Hazard ratios with the associated 95% CI will be estimated by a stratified Cox 
proportional hazards model, using Efron’s method of tie handling, with treatment as the factor. 
The strata will be the same stratification factors used for randomization. 
Analyses of all other secondary endpoints will be nominal only. Details will be specified in the 
SAP.  
9.4.2. 
Safety Analyses 
Safety analyses will be based on the reported AEs and other clinical information. 
Safety analyses will be performed in AT population.  
The safety and tolerability of selinexor will be evaluated by means of drug-related AE reports, 
physical examinations, and laboratory safety evaluations. The grading of the severity of the AEs 
will be done according to CTCAE, v.5.0. Investigators will provide their assessment as either the 
AE is related or not related to study drug.  
Treatment-emergent AEs, SAEs, AEs of at least Grade 3 in severity, related AEs, and AEs 
leading to withdrawal of treatment will be summarized by cohort and in the overall safety 
population. Treatment-emergent AEs will be those that start or worsen on or after the first day of 
study treatment, through 30 days after last dose. Related AEs will be those with an Investigator 
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9.4.3. 
Pharmacokinetic Analysis 
Plasma samples will be analyzed via a validated HPLC/MS-MS method for plasma selinexor 
concentration. Selinexor Cmax and Ctrough data will be summarized. Selinexor concentration data 
might also be analyzed using a population PK modeling approach if deemed necessary. Details 
of the population PK analysis, including software, post-processing and statistical analysis, will 
be outlined in a separate Data Analysis Plan to be completed prior to database lock. 
9.4.4. 
Pharmacodynamic Analysis 
Plasma proteins will be assessed and quantified by immunoassays and multiplex assays when 
possible in a central lab. 
9.4.5. 
Viral Analysis 
Viral testing will be assessed and quantified. 
9.5. 
Criteria for Stopping the Study 
The criteria to halt the study will depend on the number of patients enrolled at the time of the 
analysis as described below:   
A. If the overall number of patients enrolled is ≤60 patients, the study will be halted if any 1 of 
the following conditions are met at an IA or Data Safety Monitoring Board (DSMB) meeting: 
1. The absolute difference in the death rate in the treatment arm versus the control arm is 
>30%  
2. The absolute difference in the need for invasive ventilation in the treatment arm versus 
the control arm is >30% 
3. The absolute difference in the rate of Grade 3 or 4 nausea or vomiting in the treatment 
arm versus the control arm is >20% 
B. If the overall number of patients enrolled is >60 patients, the study will be halted if any 1 of 
the following conditions are met at an IA or DSMB meeting: 
1. The absolute difference in the death rate in the treatment arm versus the control arm is 
>20%  
2. The absolute difference in the need for invasive ventilation in the treatment arm versus 
the control arm is >20% 
3. The absolute difference in the rate of Grade 3 or 4 nausea or vomiting in the treatment 
arm versus the control arm is >20% 
C. If the overall number of patients enrolled is >120 patients, the study will be halted if any 1 of 
the following conditions are met at an IA or DSMB meeting: 
1. The absolute difference in the death rate in the treatment arm versus the control arm is 
>10%  
2. The absolute difference in the need for invasive ventilation in the treatment arm versus 
the control arm is >10% 


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3. The absolute difference in the rate of Grade 3 or 4 nausea or vomiting in the treatment 
arm versus the control arm is >10% 
In addition, each IA includes a futility analysis which will determine if there is no significant 
improvement in the ordinal score in the treatment arm compared with the control arm. 
9.6. 
Interim Analyses  
The first IA occurs 14 days after approximately 74 patients are randomized. This IA is for futility 
only. The futility boundary p-value will be calculated using the Lan DeMets spending function 
with the O’Brien-Fleming type of boundary based on the actual number of patients who have 
completed 14 days on study at the time of the IA. 
The second IA happens 14 days after approximately 124 patients are randomized. This IA is for 
futility and sample size reestimation. An unblinded sample size re-estimation (SSR), is planned 
to be performed at this IA. The unblinded SSR will be based on the method of conditional power 
(CP). It is defined as the probability to detect a statistically significant difference for the primary 
endpoint at the end of study given the current data observed at this IA, assuming this interim 
trend continues. The CP will be calculated for the primary endpoint at this IA using East 
software with CHW method (Cui 1999).  
The odds ratio and associated p-value will be obtained for the primary endpoint OSI between 
two arms based on the observed data at this IA, then the CP will be calculated using East. The 
calculated CP will be assigned to one of the 3 zones:  
1. favorable (CP ≥80%)  
2. promising (30% ≤ CP <80%)  
3. unfavorable (CP<30%)  
The original planned total sample size of approximately 247 patients will be increased to achieve 
the targeted power of 80%, up to a maximum of 371 patients when the conditional power is in 
the promising zone. If the CP is <30%, the trial may be stopped for futility (non-binding). 
Otherwise, if the CP is ≥80% the total sample size will remain at 247 patients, and the trial 
continues as planned. 
 
If the trial is not stopped at IAs and sample size is not changed based on the second IA, 
enrollment will continue until approximately 247 patients are enrolled, the final analysis will 
happen when all enrolled patients have had the chance to have the Day 14 OSI assessed. 
At the interim analyses, primary efficacy outcome and selected safety outcomes will be reviewed 
by the Data Safety Monitoring Board (DSMB) to determine if the trial will be stopped for 
futility, adjust the sample size, or continue as planned. 


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10. 
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS 
10.1. 
Ethical and Administrative Obligations 
10.1.1. 
Regulatory and Ethical Considerations 
This clinical study was designed and shall be implemented and reported in accordance with the 
International Conference on Harmonisation (ICH) Harmonized Tripartite Guidelines for Good 
Clinical Practice, with applicable local regulations (including European Directive 2001/20/EC 
and US Code of Federal Regulations (CFR) Title 21), and with the ethical principles that 
originate from the Declaration of Helsinki. 
The protocol and the proposed ICF(s) must be reviewed and approved by a properly constituted 
IRB/IEC before study start. Prior to study start, the Investigator is required to sign a protocol 
signature page confirming his/her agreement to conduct the study in accordance with these 
documents and all of the instructions and procedures found in this protocol and to give access to 
all relevant data and records to Karyopharm monitors, auditors, designated agents of 
Karyopharm, IRBs/IECs, and regulatory authorities as required. 
Any amendments to the protocol will require IRB/IEC approval before implementation of 
changes made to the study design, except for changes necessary to eliminate an immediate 
hazard to study patients. 
10.1.2. 
Responsibilities of the Investigator and Good Clinical Practice 
The Investigator will be responsible for the following: 
• Providing written summaries of the status of the study to the IRB/IEC annually or 
more frequently in accordance with the requirements, policies, and procedures 
established by the IRB/IEC 
• Notifying the IRB/IEC of SAEs or other significant safety findings as required by 
IRB/IEC procedures 
• Providing oversight of the conduct of the study at the site and adherence to 
requirements of 21 CFR, ICH guidelines, the IRB/IEC, European regulation 536/2014 
for clinical studies (if applicable), and all other applicable local regulations 
10.2. 
Financial Disclosure 
Investigators and sub-investigators will provide the sponsor with sufficient, accurate financial 
information as requested to allow the sponsor to submit complete and accurate financial 
certification or disclosure statements to the appropriate regulatory authorities. Investigators are 
responsible for providing information on financial interests during the course of the study and for 
1 year after completion of the study. 
10.3. 
Informed Consent Process 
The Informed Consent Form (ICF) and the process to obtain the informed consent will comply 
with all local laws, regulations, and guidance. Karyopharm will provide to Investigators, in a 
separate document, proposed ICFs that are considered appropriate for this study and comply with 


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the ICH GCP guidelines and regulatory requirements. Any changes to the ICFs suggested by the 
Investigator must be agreed to by Karyopharm before submission to the IRB/IEC, and a copy of 
the approved version(s) must be provided to the Karyopharm after IRB/IEC approval. 
All patients, proxies or legal guardians must provide signed written or verbal informed consent 
as follows:  
• In a COVID-19 clinical trial, informed consent may be verbal in the presence of 
another hospital employee and/or a patient representative. In this case informed 
consent will be documented in the patient’s chart and informed consent will be 
obtained per usual practice when the patient or patient’s representative is able to 
provide after contamination concerns are no longer an issue.  
• In a COVID-19 clinical trial, if a patient is in an emergency situation informed 
consent will be obtained consistent with 21 CFR 50.24.  
Females of childbearing potential should be informed that taking the study drug may involve 
unknown risks to the fetus if pregnancy were to occur during the study and agree that in order to 
participate in the study they must adhere to the contraception requirement for the duration of the 
study and for 3 months after the last dose. If there is any question that the patient will not reliably 
comply, they should not be entered in the study. 
• The investigator or his/her representative will explain the nature of the study to the 
patient or his/her legally authorized representative or proxy and answer all questions 
regarding the study. 
• Patients must be informed that their participation is voluntary. Patients or their legally 
authorized representative will be required to sign a statement of informed consent that 
meets the requirements of 21 CFR 50, local regulations, ICH guidelines, Health 
Insurance Portability and Accountability Act (HIPAA) requirements, where 
applicable, and the IRB/IEC or study center. 
• The medical record must include a statement that written informed consent was 
obtained before the patient was enrolled in the study and the date the written consent 
was obtained. The authorized person obtaining the informed consent must also sign 
the ICF. 
• Patients must be re-consented to the most current version of the ICF(s) during their 
participation in the study. 
• A copy of the ICF(s) must be provided to the patient or the patient’s legally 
authorized representative. 
Males should be informed that taking the study drug may lead to reductions in sperm counts, 
including marked reductions. Recovery from this may take weeks or months and may not be 
complete and the effects on sperm during recovery are not known.   In order to participate in the 
study, males must adhere to the contraception requirement for the duration of the study and for 3 
months after the last dose. If there is any question that the patient will not reliably comply, they 
should not be entered in the study. 


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10.4. 
Data Collection and Management 
10.4.1. 
Data Confidentiality 
Patients will be assigned a unique identifier by the Karyopharm. Signed ICFs and patient 
enrollment logs must be kept strictly confidential to enable patient identification at the site. 
Any patient records or datasets that are transferred to Karyopharm will contain the identifier 
only; patient names or any information which would make the patient identifiable will not be 
transferred. 
Information about study patients will be kept confidential and managed under the applicable 
laws and regulations. Those regulations require a signed patient authorization informing the 
patient of the following: 
• What protected health information (PHI) will be collected from patients in this study  
• Who will have access to that information and why.  
• Who will use or disclose that information.  
• The rights of a research patient to revoke their authorization for use of their PHI.  
In the event that a patient revokes authorization to collect or use PHI, the Investigator, by 
regulation, retains the ability to use all information collected prior to the revocation of patient 
authorization. For patients that have revoked authorization to collect or use PHI, attempts should 
be made to obtain permission to collect follow-up safety information (e.g., has the patient 
experienced any new or worsened AEs) at the end of their scheduled study period. 
The data collection system for this study uses built-in security features to encrypt all data for 
transmission in both directions, preventing unauthorized access to confidential patient 
information. Access to the system will be controlled by a sequence of individually assigned user 
identification codes and passwords, made available only to authorized personnel who have 
completed prerequisite training. 
10.4.2. 
Site Monitoring 
Before site activation, Karyopharm personnel (or designated contract research organization 
[CRO]) will review the protocol and applicable study documents with the Investigators and their 
staff (e.g., at a site initiation visit). During the study, the monitor must have access to the source 
documents to check the completeness of patient records, accuracy of entries on the CRFs, 
adherence to the protocol and to Good Clinical Practice (GCP), progress of enrollment, and to 
ensure that study treatment is being stored, dispensed, and accounted for according to 
specifications. Key study personnel must be available to assist the monitor during these visits. 
Remote study monitoring could be used, more details will be provided in the study-specific 
monitoring plan. 
The Investigator must maintain source documents for each patient in the study, consisting of case 
and visit notes (hospital or clinic medical records) containing demographic and medical 
information, laboratory data, ECGs, and the results of any other tests or assessments. All 
information recorded on CRFs must be traceable to source documents in the patient's file. The 
Investigator must also keep the original signed ICF (a signed copy is given to the patient). 


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The Investigator must give the monitor access to all relevant source documents to confirm their 
consistency with the CRF entries. Karyopharm monitoring standards require full verification for 
the presence of informed consent, adherence to the inclusion/exclusion criteria and 
documentation of SAEs. Additional checks of the consistency of the source data with the CRFs 
are performed according to the study-specific monitoring plan. 
10.4.3. 
Data Collection 
This study will utilize electronic data capture (EDC), the designated clinical site staff will enter 
the data required by the protocol into the eCRF. The eCRFs will be constructed using fully 
validated secure web-enabled software that conforms to 21 CFR Part 11 requirements. Clinical 
site staff will not be given access to the EDC system until they have been trained. Automatic 
validation programs check for data discrepancies in the eCRFs and allow modification or 
verification of the entered data by the Investigator staff. Any missing data must be explained. An 
audit trail will be maintained by the eCRF system 
The Investigator is responsible for assuring that the data entered into the eCRF is complete and 
accurate, and that entry and updates are performed in a timely manner. 
Concomitant treatments and prior medications entered into the database will be coded using the 
WHO Drug Reference List, which employs the Anatomical Therapeutic Chemical (ATC) 
classification system. Medical history/current medical conditions and AEs will be coded using 
the MedDRA terminology. 
10.4.4. 
Database Management and Quality Control 
Karyopharm personnel (or designated CRO) will review the eCRF data entered by 
investigational staff for completeness and accuracy. Electronic data queries stating the nature of 
the problem and requesting clarification will be created for discrepancies and missing values and 
sent to the investigational site via the electronic data capture (EDC) system. Designated 
Investigator site staff are required to respond promptly to queries and to make any necessary 
changes to the data. 
At the conclusion of the study, after discrepancies and missing values have been completed and 
the data have been verified to be complete and accurate, the database will be declared locked.  
For EDC studies, after database lock, the Investigator will receive a CD-ROM or paper copies of 
the patient data for archiving at the investigational site. 
10.5. 
Data Safety Monitoring Committee  
At the interim analyses, primary efficacy outcome and/or safety outcomes will be reviewed by 
the DSMB to determine if the trial will be stopped for futility or efficacy or continue as planned 
(Section 9.5). The DSMB will meet at least three times during the course of the study. 
Enrollment will be paused for evaluation of safety and efficacy after the enrollment of the first 
40 patients and the first meeting of the DSMB will occur within the first week of enrolling the 
40th patient.  No further patients will be enrolled until the completion of this DSMB review and 
the safety and efficacy data from the first 40 patients will be shared with the FDA prior to 
resuming enrollment. The remaining DSMB meetings are planned to evaluate the data from the 
IA. The DSMB may also meet at other times during the study as needed.  


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The independent DSMB will be composed of at least 3 members who are independent of 
Karyopharm and the study.  The DSMB will meet to evaluate safety and efficacy, to ensure the 
appropriate benefit risk profile for patients enrolled in the study and to review any SAEs that 
occur during the study. The DSMB will be provided with all reports of AEs including SAEs 
regardless of Investigator causality assessments. 
Details on how the DSMB will review safety and response data are provided in the DSMB 
Charter. The DSMB review will include, but not be limited to, evaluations of duration of therapy 
and all cause and AE-related dose reductions, interruptions, and discontinuations. At the interim 
analyses, primary efficacy outcome and selected safety outcomes will be reviewed by the DSMB 
to determine if the trial will be stopped for futility or efficacy or continue as planned.  
10.6. 
Dissemination of Clinical Study Data 
Results from the study (including demographics, baseline characteristics, primary and secondary 
endpoints) will be posted in a publicly accessible database (such as www.clinicaltrials.gov or 
EudraCT) in accordance with applicable laws, regulations, and/or guidelines.  
In addition, upon study completion and finalization of the clinical study report, the results of this 
study may be submitted for publication in a peer-reviewed journal or presented at a 
scientific/biomedical conference. 
10.7. 
Source Documents 
Each participating site will maintain appropriate medical and research records for this study, in 
compliance with Section 4.9 of the ICH E6 GCP, and regulatory and institutional requirements 
for the protection of confidentiality of subjects. As part of participating in a Karyopharm-
sponsored study, each site will permit authorized representatives of Karyopharm and regulatory 
agencies to examine (and when required by applicable law, to copy) clinical records for the 
purposes of quality assurance reviews, audits and evaluation of the study safety and progress. 
Source data are all information, original records of clinical findings, observations, or other 
activities in a clinical study necessary for the reconstruction and evaluation of the study. 
Examples of these original documents and data records include, but are not limited to, hospital 
records, clinical and office charts, laboratory notes, memoranda, patients’ diaries or evaluation 
checklists, pharmacy dispensing records, recorded data from automated instruments, copies or 
transcriptions certified after verification as being accurate and complete, microfiches, 
photographic negatives, microfilm or magnetic media, x-rays, and patient files and records kept 
at the pharmacy, at the laboratories, and medico-technical departments involved in the clinical 
study. 
The Investigator/institution should maintain the study documents as specified in Essential 
Documents for the Conduct of a Clinical Trial (ICH E6 Section 8) and as required by applicable 
regulations and/or guidelines. The Investigator/institution should take measures to prevent 
accidental or premature destruction of these documents. 
Essential documents (written and electronic) should be retained for a period of not less than 
fifteen (15) years from the completion of the clinical study unless Karyopharm provides written 
permission to dispose of them or, requires their retention for an additional period of time because 
of applicable laws, regulations and/or guidelines. 


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10.8. 
Study and Site Closure 
The Sponsor or designee reserves the right to close the study site or terminate the study at any 
time for any reason at the sole discretion of the Sponsor. Study sites will be closed upon study 
completion. A study site is considered closed when all required documents and study supplies 
have been collected and a study-site closure visit has been performed. 
The Investigator may initiate study-site closure at any time, provided there is reasonable cause 
and sufficient notice is given in advance of the intended termination. 
Reasons for the early closure of a study site by the Sponsor or Investigator may include but are 
not limited to: 
• Failure of the Investigator to comply with the protocol, the requirements of the 
IRB/IEC or local health authorities, the Sponsor's procedures, or GCP guidelines 
• Inadequate recruitment of patients by the Investigator 
• Discontinuation of further study treatment development 
10.9. 
Publication Policy 
• The results of this study may be published or presented at scientific meetings. If this 
is foreseen, the investigator agrees to submit all manuscripts or abstracts to the 
sponsor before submission. This allows the sponsor to protect proprietary information 
and to provide comments. 
• The sponsor will comply with the requirements for publication of study results. In 
accordance with standard editorial and ethical practice, the sponsor will generally 
support publication of multicenter studies only in their entirety and not as individual 
site data. In this case, a coordinating investigator will be designated by mutual 
agreement. 
• Authorship will be determined by mutual agreement and in line with International 
Committee of Medical Journal Editors authorship requirements. 


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K. Lal. 2011. “SARS-CoV 9b Protein Diffuses into Nucleus, Undergoes Active Crm1 
Mediated Nucleocytoplasmic Export and Triggers Apoptosis When Retained in the 
Nucleus.” Edited by Patricia V. Aguilar. PLoS ONE 6 (5): e19436. 
https://doi.org/10.1371/journal.pone.0019436. 
Sun et al., (2013) Nuclear export inhibition through covalent conjugation and hydrolysis of  
Leptomycin B by CRM1. Proc Natl Acad Sci U S A. 2013 Jan 22; 110(4): 1303–1308.  
DOI:10.1073/pnas.1217203110 
Tai YT, Landesman,Y, Acharya C, et al., (2014) CRM1 inhibition induces tumor cell 
cytotoxicity and impairs osteoclastogenesis in multiple myeloma: molecular mechanisms 
and therapeutic implications. Leukemia. 2014; 28:155-65. 
Tajiri, Naoki, Ike De La Peña, Sandra A. Acosta, Yuji Kaneko, Sharon Tamir, Yosef 
Landesman, Robert Carlson, Sharon Shacham, and Cesar V. Borlongan. 2016. “A Nuclear 
Attack on Traumatic Brain Injury: Sequestration of Cell Death in the Nucleus.” CNS 
Neuroscience and Therapeutics 22 (4): 306–15. https://doi.org/10.1111/cns.12501. 
Tamir et al., (2016) Verdinexor, a Clinical-Stage Selective Inhibitor of Nuclear Export (SINE™) 
Compound, Demonstrates a Wide Therapeutic Window and Low Susceptibility to 
Resistance Development in Mouse Models of Influenza A. International Society for 
Influenza and other Respiratory Virus Diseases, Aug 24–28, 2016; Chicago, IL. 
Widman, Douglas G., Savanna Gornisiewicz, Sharon Shacham, and Sharon Tamir. 2018. “In 
Vitro Toxicity and Efficacy of Verdinexor, an Exportin 1 Inhibitor, on Opportunistic 
Viruses Affecting Immunocompromised Individuals.” PLoS ONE 13 (10). 
https://doi.org/10.1371/journal.pone.0200043. 
Wu, Ming, Huan Gui, Zongtai Feng, Hua Xu, Gang Li, Mei Li, Ting Chen, et al. 2018. “KPT-
330, a Potent and Selective CRM1 Inhibitor, Exhibits Anti-Inflammation Effects and 
Protection against Sepsis.” Biochemical and Biophysical Research Communications 503 
(3): 1773–79. https://doi.org/10.1016/j.bbrc.2018.07.112. 


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Zhou, Yadi, Yuan Hou, Jiayu Shen, Yin Huang, William Martin, and Feixiong Cheng. 2020. 
Network-Based Drug Repurposing for Human Coronavirus. MedRxiv. Cold Spring Harbor 
Laboratory Press. https://doi.org/10.1101/2020.02.03.20020263. 


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APPENDIX 2. SAFETY AND TOLERABILITY OF SELINEXOR 20-MG 
DOSE 
Please see the safety data available for the 20mg dose of selinexor (Table 7) These data were 
generated in two phase 1 studies evaluating escalating doses of selinexor in patients with heavily 
pretreated, progressive, relapsed refractory hematological malignancies and solid tumors.  
• Study KCP-330-001: A Phase 1 Study of the Pharmacokinetics and Pharmacodynamics of 
Escalating Doses of the Selective Inhibitor of Nuclear Export (SINE) KPT-330 in Patients 
with Advanced Hematological Malignancies; NCT01607892  
• Study KCP- 330-002: A Phase 1 Study of the Pharmacokinetics and Pharmacodynamics of 
Escalating Doses of the Selective Inhibitor of Nuclear Export (SINE) KPT-330 in Patients 
with Advanced or Metastatic Solid Tumor Malignancies; NCT01607905.  
A summary of the findings from these studies are as follows: Twenty-five patients received a 
dose of ≤12 mg/m2 (~20 mg) from two Phase 1 dose escalation studies in patients with advanced 
heavily pretreated hematologic (KCP- 330-001) and solid tumors (KCP- 330-002) and were 
included in the analysis. These patients had multiple lines of prior chemotherapy and were 
severely immunocompromised frail patients with heavily pre-treated relapsed refractory 
hematologic and solid tumors.   
At a dose ≤12 mg/m2 (≤ ~20 mg) in the first 2 weeks, the 5 most common non-hematologic 
adverse events (AEs) were low grade (Grade 1 and 2) nausea, decreased appetite, fatigue, 
vomiting and dysgeusia, that was manageable with supportive care. Hematologic AEs included 
only thrombocytopenia (Table 7) and the Grade 3 and 4 events (1 each) were observed in 
patients with refractory hematologic cancers (acute leukemia and myeloma). Note there were no 
grade 5 (death) events. There were no clinically significant changes in serum chemistries.  
Nearly all of the adverse events were reversible and responded to supportive care.  Finally, there 
were no clinically significant drug-drug interactions at these low doses, nor were any observed at 
much higher doses. 
As these patients have refractory cancers that have progressed on available therapies, they will 
generally have more medical problems than the majority of the patients entering the proposed 
COVID-19 study, and therefore this represents a ‘worst case’ scenario. 
 
Conclusion.  Based on the data presented here, the highly selective and potent oral XPO1 
inhibitors verdinexor and selinexor have no clinically important discernable differences, 
both have activity in models of sepsis, inflammation and influenza, and the adverse event 
profile of low dose selinexor consists of low grade, reversible and treatable symptoms. 
 
 


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Table 7:  
Adverse Event (AE) Profile of Low Dose (≤20 mg) Selinexor from Phase 1 
Studies in Patients with Advanced Refractory Hematologic and Solid Tumor 
Malignancies. 
 
 
 


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APPENDIX 3. STRONG CYP3A INHIBITORS AND INDUCERS 
 
Type 
Example Medications 
Strong CYP3A inducers 
Apalutamide, avasimibe, carbamazepine, enzalutamide, 
ivosidenib, lumacaftor, mitotane, phenobarbital, phenytoin, 
rifampin, rifapentine, St John's Wort extract 
Strong CYP3A inhibitors  
VIEKIRA pak, indinavior/RIT, tipranavir/RIT,  ritonavir, 
cobicistat (GS-9350), ketoconazole, indinavir, troleandomycin, 
telaprevir, danoprevir / RIT, elvitegravir / RIT, saquinavir / RIT, 
lopinavir / RIT, itraconazole, voriconazole, mifepristone, 
mibefradil, clarithromycin, posaconazole, telithromycin, grapefruit 
juice DS, ceritinib, conivaptan, nefazodone, nelfinavir, aquinavir, 
ribociclib, idelalisib , boceprevir 
 
Note: This is based on Metabolism and Transport Drug Interaction Database 
(https://www.druginteractioninfo.org/), and is not an exhaustive list.  For an updated FDA list, 
see the following link: https://www.fda.gov/drugs/drug-interactions-labeling/drug-development-
and-drug-interactions-table-substrates-inhibitors-and-inducers#cypEnzymes.   
 

SAP_001.pdf: 
Study XPORT-CoV-1001 
 
Karyopharm Therapeutics, Inc. 
Statistical Analysis Plan 
 
Version 1.0 
1 
 
STATISTICAL ANALYSIS PLAN 
 
Study Name: XPORT-CoV-1001 
 
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  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Confidentiality Statement 
This statistical analysis plan contains confidential information and is the proprietary 
property of Karyopharm Therapeutics, Inc. It may not be copied or made available for 
review by an unauthorized person or firm without the prior written authorization of 
Karyopharm Therapeutics, Inc. 
 
 
 
Protocol Number: 
XPORT-CoV-1001 
Protocol Date and Version: 
19 June 2020, Version 7.0 
Phase: 
Phase II 
Sponsor: 
Karyopharm Therapeutics, Inc 
Analysis Plan Date: 
19 June 2020 
Analysis Plan Version: 
Version 1.0 


Study XPORT-CoV-1001 
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SPONSOR SIGNATURE PAGE 
Protocol 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 
Protocol Number: 
XPORT-CoV-1001 
Sponsor:  
Karyopharm Therapeutics, Inc 
By signing this document, I acknowledge that I have read the document and approve of 
the planned statistical analyses described herein. I agree that the planned statistical 
analyses are appropriate for this study, are in accordance with the study objectives, and 
are consistent with the statistical methodology described in the protocol and all 
applicable regulatory guidance and guidelines.  
Author (Trial Lead Statistician): 
 PhD 
Karyopharm Therapeutics Inc. 
Signature: 
Date: 
Approver: 
PhD 
Karyopharm Therapeutics Inc. 
Signature:
Date: 
MD 
Karyopharm Therapeutics Inc. 
Signature: 
Date:  
PPD
PPD
PPD
PPD
PPD
PPD
P
P
PPD
PPD
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DOCUMENT HISTORY 
Version 
Date 
Author(s) 
Brief Summary of Changes 
1.0 
June 19, 2020 
Original version. 
 
 
 
 
 
 
 
 
 
 
 
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TABLE OF CONTENTS 
ABBREVIATIONS ............................................................................................................7 
1. 
INTRODUCTION..................................................................................................9 
2. 
STUDY DESIGN ..................................................................................................10 
2.1 
Overview of Study Design ................................................................................10 
2.2 
Sample Size and Power Considerations ............................................................10 
2.3 
Interim Analyses ...............................................................................................11 
3. 
STUDY OBJECTIVES AND ENDPOINTS ......................................................12 
4. 
GENERAL STATISTICAL METHODS AND DATA HANDLING 
CONVENTION ....................................................................................................16 
4.1 
General Statistical Methods ..............................................................................16 
4.2 
Definition of Study Days ..................................................................................16 
4.3 
Definition of Baseline .......................................................................................16 
4.4 
Missing Data Handling Rules ...........................................................................16 
4.4.1 Handling of Missing/partial Dates for Adverse Events or Concomitant 
Medications ................................................................................................16 
4.4.2 Handling of Missing or Partial Birth Date for Calculation of Age ............17 
4.4.3 Handling of Missing Severity of AEs ........................................................17 
4.4.4 Handling of Missing Assessment of Relationship of AEs to Study 
Treatment ...................................................................................................17 
4.5 
Visit Windows ...................................................................................................17 
5. 
STATISTICAL ANALYSIS POPULATION ....................................................20 
5.1 
Intent-to-Treat (ITT) Population .......................................................................20 
5.2 
Efficacy evaluable (EE) Population ..................................................................20 
5.3 
All-Treat (AT) Population.................................................................................20 
5.4 
The Proof of Concept Population ......................................................................20 
5.5 
Application of Analysis Population ..................................................................20 
6. 
PATIENT SUMMARY .......................................................................................22 
6.1 
Patients Disposition ...........................................................................................22 
6.2 
Demographic and Baseline Characteristics .......................................................22 
6.3 
Medical/Surgical History ..................................................................................22 
6.4 
Disease History .................................................................................................23 


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6.5 
Prior and Concomitant Medications..................................................................23 
6.6 
Protocol Deviations ...........................................................................................23 
6.7 
Extent of Study Treatment Exposure and Compliance .....................................23 
6.7.1 Extent of Study Treatment Exposure .........................................................23 
6.7.2 Treatment Compliance ...............................................................................24 
7. 
EFFICACY ANALYSES ....................................................................................25 
7.1 
Analyses of Primary Efficacy Endpoint ............................................................27 
7.1.1 Sensitivity Analyses ...................................................................................27 
7.1.2 Subgroup Analyses ....................................................................................28 
7.2 
Analyses of Secondary Efficacy Endpoints ......................................................28 
7.2.1 Analyses of Key Secondary Efficacy Endpoints .......................................28 
7.2.2 Analyses of Additional Secondary Endpoints ...........................................29 
7.3 
Analyses of Exploratory Endpoints ..................................................................30 
8. 
SAFETY ANALYSES .........................................................................................31 
8.1 
Adverse Events..................................................................................................31 
8.2 
Clinical Laboratory Data ...................................................................................32 
8.3 
Vital Signs .........................................................................................................33 
8.4 
Electrocardiogram (ECG) .................................................................................33 
9. 
PHARMACOKINETIC ANALYSES ................................................................33 
10. 
REFERENCES .....................................................................................................34 
 
 
 


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LIST OF TABLES 
Table 1: Study Objectives and Endpoints ................................................................ 13 
Table 2: Visit Windows for CBC with differential, Complete serum chemistry, C-
reactive protein, Ferritin and LDH. ....................................................... 17 
Table 3: Visit Windows for PT, aPTT, INR, 
 
. ........................................ 19 
Table 4: Visit Windows for Cells for Leukocyte Phenotyping................................ 19 
Table 5: Application of Populations for Summary .................................................. 21 
Table 6: Efficacy Endpoints and Definitions ........................................................... 25 
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ABBREVIATIONS 
Abbreviation 
Definition 
AE 
Adverse Event 
AT 
all-treat  
ATC 
Anatomical Therapeutic Class 
CI 
Confidence Interval 
CMH 
Cochran-Mantel-Haenszel  
COPD 
chronic obstructive pulmonary disease 
COVID-19 
Coronavirus Disease 2019 
CP 
Conditional power 
CRP 
C-Reactive Protein  
CTCAE 
Common Terminology Criteria for Adverse Events 
DR-14 
Overall death rate on Day 14  
DR-28 
Overall death rate on Day 28  
ECG 
Electrocardiogram 
eCRF 
Electronic Case Report Form 
EE 
Efficacy evaluable  
FiO2 
Fraction of Inspired Oxygen 
IA 
Interim Analysis 
ITT 
Intent-to-Treat  
ICU 
intensive care unit 
KM  
Kaplan-Meier  
LDH 
Lactate Dehydrogenase 
NSAID 
nonsteroidal anti-inflammatory drug 
PaO2 
Partial Pressure of Oxygen in Arterial Blood 
PT 
Preferred Term 
OS 
Overall survival  
OSI-14 
Day 14 Ordinal Scale improvement  
OSI-28 
Day 28 Ordinal Scale improvement  
QTcF 
QT Interval Corrected For Heart Rate Using Fridericia’s Formula 
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RMV 
Rate of mechanical ventilation  
SAP 
Statistical Analysis Plan 
SSR 
sample size re-estimation  
STD 
standard deviation  
TEAE 
Treatment Emergent Adverse Event 
TTMV 
Time to mechanical ventilation  
TTCI 
Time to Clinical Improvement  
TTR 
Time to recovery 
WHO 
World Health Organization  


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1. 
INTRODUCTION  
This statistical analysis plan describes detailed statistical methods to be used for analysis 
and data presentation for reporting the activity and safety of low dose oral selinexor (KPT-
330) in patients with severe coronavirus disease 2019 (COVID-19).  
This document has been prepared according to study protocol version 7.0 dated 18 June 
2020.  
 
 


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2. 
STUDY DESIGN 
2.1 
Overview of Study Design 
This is a randomized phase 2 single-blinded study of low dose selinexor versus placebo to 
evaluate the activity and safety, as well as reduction in mortality in patients with severe 
COVID-19.  
A dose of 20 mg selinexor or matching placebo will be administered orally on Days 1, 3, 
and 5 of each week for up to 2 weeks. If the patient is tolerating therapy and clinically 
benefitting, dosing can continue for an additional 2 weeks. 
The study population will consist of hospitalized patients ≥18 years old with COVID-19. 
The randomization under protocol version 6.0 or above will be stratified by: 
x Use of concomitant therapies  
o Use of anti-viral (e.g. remdesivir) only 
o Use of anti-inflammatory (e.g. hydroxychloroquine, biologics targeting e.g. 
IL-6 or IL-1) only 
o Use of both anti-viral and anti-inflammatory therapies 
o Use of neither anti-viral nor anti-inflammatory therapy  
x Number of high-risk comorbidities. 
o No high-risk comorbidity 
o One high-risk comorbidity 
o Two or above comorbidities 
High risk comorbidities are defined as: BMI> 30, cancer patients on chemotherapy, 
patients with cardiac (CAD, AMI, CHF) or pulmonary (COPD, emphysema) disease, 
diabetes, hypertension. 
Note: acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDs) will not 
constitute anti-inflammatory agents for the purposes of stratification. 
The study schedules are presented in Table 1 of the protocol.  
2.2 
 Sample Size and Power Considerations 
Approximately 300 patients are planned to be enrolled: 
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2.3 
Interim Analyses 
The interim analyses apply to ITT population only.  
The first IA occurs 14 days after the first 74 patients are randomized. This IA is for futility 
only (non-binding). The futility boundary p-value will be calculated using the Lan DeMets 
spending function with the O’Brien-Fleming type of boundary based on the actual number 
of patients who have completed 14 days on study at the time of the IA.  
The second IA happens 14 days after 124 patients are randomized. This IA is for futility 
and sample size re-estimation (SSR). An unblinded SSR is planned to be performed at this 
IA. The unblinded SSR will be based on the method of conditional power (CP). It is defined 
as the probability to detect a statistically significant difference for the primary endpoint at 
the end of study given the current data observed during this second IA, assuming this 
interim trend continues. The CP will be calculated for the primary endpoint at this IA using 
East software with CHW method (Cui et al., 1999).   
The odds ratio and associated p-value will be obtained for the primary efficacy endpoint 
between two treatment arms based on the observed data at this IA, then the CP will be 
calculated using East. The calculated CP will be assigned to one of the 3 zones:  
1. favorable (CP ≥80%)  
2. promising (30% ≤ CP <80%)  
3. unfavorable (CP< 30%)  
Additionally, if the 2nd interim analysis is conducted and sample size is adjusted, the CHW 
method (Cui et al., 1999) will be implemented in the primary analysis for the primary and 
key secondary efficacy endpoints to preserve the overall type I error.  
Please refer to Section 9.5 in Protocol for Criteria for Stopping the Study. 
 
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3. 
STUDY OBJECTIVES AND ENDPOINTS 
 
Study objectives and endpoints are described in Error! Reference source not found. 
below.   


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Table 1: Study Objectives and Endpoints 
Objectives 
Endpoints 
Primary Objectives 
Day 14 Ordinal Scale improvement 
Proportion of patients with at least a 2-point 
improvement (increase) in the Ordinal Scale 
from time of randomization (baseline) to Day 14. 
The Ordinal Score is an assessment of the 
clinical status at the first assessment on each day 
of hospitalization.  
The scale is as follows:  
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 (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.  
Key Secondary Objectives  
To evaluate improvement in clinical 
measures across the 2 treatment 
arms 
x Time to an improvement of 2 point using 
Ordinal Scale (TTCI-2) 
x Overall Death Rate on Day 28 
x Rate of mechanical ventilation 


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x Time to mechanical ventilation 
Additional Secondary Objectives  
To evaluate improvement in 
additional clinical measures across 
the 2 treatment arms  
x Time to recovery defined as improvement 
from baseline score of 3 to ≥4 or from a 
baseline score of 4 to ≥5 
x Proportion of patients with at least a 2 point 
improvement (increase) in the Ordinal Scale 
from baseline to Day 7. 
x Proportion of patients with at least a 1 point 
improvement (increase) in the Ordinal Scale 
from baseline to Day 7 
x Proportion of patients with at least a 1 point 
improvement (increase) in the Ordinal Scale 
from baseline to Day 14. 
x Time to an improvement of  1 point on the 
Ordinal Scale (TTCI-1) 
x Overall Survival 
x Overall death rate on Day 14 
x Rate of ICU admission 
x Length of hospitalization 
x Length of ICU stay 
x Duration of mechanical ventilation 
x PaO2:FiO2 and/or oxygenation index over 
time 
 
To determine the anti-inflammatory 
and immune effect of selinexor 
x Reduction of C-reactive protein (CRP)  
x Reduction in ferritin levels  
x LDH 
x Measure changes from baseline of blood 
plasma cytokines: IL-1β, IL-1Rα, IL-2, IL-
4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IFNγ, 
IP10, TNFα   
To assess safety and tolerability of 
selinexor [time frame: up to 28 days] x Listing and documentation of frequency and 
severity of adverse effects  


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To characterize selinexor 
pharmacokinetics 
x Selinexor PK parameters, maximum plasma 
concentration (Cmax) and trough 
concentration (Ctrough), if feasible  
Exploratory Endpoints  
 
 
 
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4. 
GENERAL 
STATISTICAL 
METHODS 
AND 
DATA 
HANDLING 
CONVENTION 
4.1 
General Statistical Methods 
All statistical analyses will be performed using SAS® (Version 9.4 or higher, SAS Institute 
Inc., Cary, NC, USA) 
Categorical variables will be tabulated as number of patients and percentage of total 
number of patients in the given analysis population as noted for each category (with a 
category for missing data).  Percentages will be reported to one decimal place.  
Descriptive statistics will be used to summarize continuous variables including number of 
patients, mean, standard deviation (STD), median, minimum and maximum. 
Unless otherwise stated, all analysis will be performed by treatment arm (selinexor versus 
placebo). Listing will be sorted by treatment arm, patient ID and visit whenever it is 
applicable.  
4.2 
Definition of Study Days 
Unless otherwise noted, study days of an evaluation are defined as number of days relative 
to the Study Day 1 which is defined as the date of first study treatment (selinexor or placebo 
for patients in the selinexor or placebo arm respectively), and the preceding day is Day -1, 
the day before that is Day -2, etc.  
x For assessments on/after Study Day 1, study days are calculated as  
(date of assessment – date of Study Day 1 + 1) 
x For assessments before Study Day 1, study days are calculated as  
(date of assessment – date of Study Day) 
4.3 
Definition of Baseline  
For all evaluations unless otherwise noted, baseline is defined as the most recent non-
missing measurement prior to the first administration of study treatment. Baseline can be 
the same date as first dose, given the measurement is expected prior to first dose when only 
date information is available. 
4.4 
Missing Data Handling Rules 
Unless otherwise stated, missing data will not be imputed. 
4.4.1 
Handling of Missing/partial Dates for Adverse Events or Concomitant 
Medications 
In general, the imputation should be conservative such that onset dates should be imputed 
to be as early as possible and resolution dates will be imputed to be as late as possible.  


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Impute resolution date first and then impute onset date using imputed resolution date. 
However, for categorization purpose, if the partial AE onset date information does not 
indicate whether the AE started prior to treatment or after the treatment-emergent adverse 
event (TEAE) period, the AE will be classified as treatment-emergent.   
These data imputations are for categorization purpose or calculation of AE duration, and 
will not be used in listings. In data listings, an ongoing flag will be identified from the 
eCRF AE page. 
Refer to the Karyopharm Biostatistics and Statistical Programming Rule Book version 1.0 
for details on imputation methods. 
4.4.2 
Handling of Missing or Partial Birth Date for Calculation of Age 
Refer to the Karyopharm Biostatistics and Statistical Programming Rule Book version 1.0 
for details on imputation methods. 
4.4.3 
Handling of Missing Severity of AEs 
If the severity is missing for one of the treatment-emergent occurrences of an AE, the 
maximal severity on the remaining occurrences with the same PT and same patient will be 
considered. If the severity is missing for all the occurrences or the PT is missing, a 
“missing” category will be added in the summary table. 
4.4.4 
Handling of Missing Assessment of Relationship of AEs to Study Treatment 
If the assessment of the relationship to study treatment is missing, then the relationship to 
study treatment in the frequency tables is considered as related. 
4.5 
Visit Windows 
For safety data that are summarized/plotted by time points, non-missing assessments from 
all scheduled and unscheduled visits will be mapped to the nearest visit. Analysis visit 
windows for clinical laboratory parameters are defined in Table 2 to Table 4. If there are 2 
or more assessments mapped to the same analysis visit for a patient, the assessment that is 
closest to the target visit day will be used for analysis. If there are 2 or more assessments 
mapped to the same analysis visit with the same distance from the target visit day, then 
select the latest one for the analysis. Visit windows definitions will be described in analysis 
data specifications. 
Table 2: Visit Windows for CBC with differential, Complete serum chemistry, C-
reactive protein, Ferritin and LDH. 
Analysis Visit Name 
Target Visit Day 
Study Day Range in Window 


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Baseline 
Day 1 
Prior to first dosing (prior to or on 
Day 1 if exact dosing time is not 
available) 
Day 3 
Day 3 
Day 2 to 3 
Day 5 
Day 5 
Day 4 to 6 
Day 8 
Day 8 
Day 7 to 9 
Day 12 
Day 12 
Day 10 to 13 
Day 15 
Day 15 
Day 14 to 16 
Day 19 
Day 19 
Day 17 to 20 
Day 22 
Day 22 
Day 21 to 23 
Day 26 
Day 26 
Day 24 or later 
NOTE: Day 1 is the date of first selinexor or placebo. Analysis visit and visit window 
may change for certain parameters depending on the data availability. 
 
 
 


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Table 3: Visit Windows for PT, aPTT, INR, 
 
. 
Analysis Visit Name 
Target Visit Day 
Study Day Range in Window 
Baseline 
Day 1 
Prior to first dosing (prior to or on 
Day 1 if exact dosing time is not 
available) 
Day 3 
Day 3 
Day 2 to 3 
Day 5 
Day 5 
Day 4 to 6 
Day 8 
Day 8 
Day 7 to 9 
Day 12 
Day 12 
Day 10 to 13 
Day 15 
Day 15 
Day 14 to 18 
Day 22 
Day 22 
Day 19 to 23 
Day 26 
Day 26 
Day 24 or later 
NOTE: Day 1 is the date of first selinexor or placebo. Analysis visit and visit window 
may change for certain parameters depending on the data availability. 
 
Table 4: Visit Windows for Cells for Leukocyte Phenotyping 
Analysis Visit Name 
Target Visit Day 
Study Day Range in Window 
Baseline 
Day 1 
Prior to or on Day 4 
Day 8 
Day 8 
Day 5 to 9/11 
Day 12/15 
Day 12 or Day 15 
Day 10/12 or later 
NOTE: Day 1 is the date of first selinexor or placebo. Analysis visit and visit window 
may change for certain parameters depending on the data availability. 
 
 
 
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5. 
STATISTICAL ANALYSIS POPULATION 
5.1 
Intent-to-Treat (ITT) Population  
The intent-to-treat (ITT) population will consist of all patients who are 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. This population will be used for 
primary analyses of efficacy. Patients will be analyzed in the treatment arm to which they 
were randomized and strata assignment at the time of randomization. 
5.2 
Efficacy evaluable (EE) Population 
The EE population is a subset of the ITT population, consisting of patients who did not 
die within 24 hours of randomization, had at least one post-baseline Ordinal Scale 
assessment, and received at least one dose of study treatment. Patients will be analyzed in 
the treatment arm to which they were randomized and strata assignment at the time of 
randomization. 
5.3 
All-Treat (AT) Population 
The all-treat (AT) population will consist of the subset of ITT patients who took at least 
one dose of study treatment on this study. Patients will be analyzed based on the actual 
treatment received. This population will be used for primary analyses of safety. 
5.4 
The Proof of Concept Population 
The Proof of Concept (PoC) Population consists of all patients who are randomized in the 
study with confirmed SARS-CoV2 infection under protocol version 1.0 to 5.0. This is a 
proof-of-concept cohort and thus will be analyzed separately. Efficacy and safety endpoints 
will be presented for descriptive purpose. Patients will be analyzed in the treatment arm to 
which they were treated. 
5.5 
Application of Analysis Population 
Unless otherwise noted, the analysis populations that will be used for summaries of each 
set of data points are provided in Table 5.   
 
 


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Table 5: Application of Populations for Summary 
  
ITT  
Population 
EE  
Population 
AT 
Population 
PoC 
Population 
Disposition 
X 
 
 
X 
 
 
 
 
 
Baseline 
Characteristics 
 
 
 
 
   Demographics 
X 
X 
X 
X 
   Medical history 
X 
 
X 
X 
   Disease history  
X 
 
X 
X 
   Prior/concomitant 
medication 
X 
X 
X 
X 
   Tobacco use 
X 
X 
X 
X 
 
 
 
Drug exposure and 
compliance 
 
X 
X 
 
 
 
Efficacy Endpoints 
 
 
 
 
   Primary efficacy 
endpoint 
X 
X 
 
X 
   Key secondary 
efficacy endpoints 
X 
X 
 
X 
   Other secondary 
endpoints 
X 
 
 
X 
 
 
 
 
 
Safety Endpoints 
 
 
 
TEAEs 
 
X 
X 
Labs 
 
X 
X 
Vital signs 
 
X 
X 
ECG 
 
X 
X 
 
 
 
 
 
 
 
 
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6. 
PATIENT SUMMARY 
6.1 
Patients Disposition  
Patients’ disposition will be tabulated by treatment arm and overall using ITT and PoC 
Population for the following categories: 
x Number of randomized patients: 
 Number of patients received at least one dose of study treatment 
 Number of patients still on-treatment 
 Number of patients with treatment discontinuation  
 Primary reasons for treatment discontinuation 
A by-patient listing of study completion information, including the reason for study 
withdrawal will be provided.   
6.2 
Demographic and Baseline Characteristics 
The demographic and baseline data will be summarized by treatment arm and overall 
including: 
x Age at screening (years) 
x Age in categories 
x Sex 
x Race.  
x Ethnicity  
x Weight at baseline (kg) 
x BMI at baseline (kg/m2) 
x Baseline use of concomitant therapies  
x Baseline comorbidities 
x Baseline comorbidities by medical history 
x Smoking History 
x Baseline cytokines (LDH, CRP, Ferritin) 
Race will be collected wherever allowed and reported for the patients for whom it is known.  
6.3 
Medical/Surgical History 
Medical history will be coded using the latest Medical Dictionary for Regulatory Activities 
(MedDRA) Version available. Summaries will be presented by System Organ Class (SOC) 
and Preferred Term (PT) with numbers and percentages by treatment arm. Each patient 
will be counted only once in each SOC or SOC/PT summary. 


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In the summary table, medical history will be sorted by alphabetic order SOC and then by 
decreasing frequency PT within each SOC. In cases of SOCs or PTs with equal frequencies, 
medical history will be sorted alphabetically. 
6.4 
Disease History 
Patients’ disease history will be summarized by treatment arm including following 
variables: 
x Days from first COVID-19 symptoms to randomization date, calculated as (date of 
randomization - date of initial onset of  COVID-19 symptoms + 1) 
x Days from admission to hospital to randomization date, calculated as (date of 
randomization - date of admission to hospital + 1) 
x Days from date of confirmed COVID-19 diagnosis to randomization date, 
calculated as (date of randomization - date of confirmed COVID-19 diagnosis + 1) 
6.5 
Prior and Concomitant Medications  
All medications will be coded using the latest WHO Drug Dictionary version available.  
Prior medications are defined as those medications started prior to the administration of 
study treatment. Concomitant medications are defined as those medications taken after first 
dose of study treatment. Hence medications started before receiving study treatment but 
continuing after will be considered as both prior and concomitant medications.   
Prior and concomitant medications will be summarized with numbers and percentages by 
ATC level 2 (therapeutic level), ATC level 4 (generic level) and standardized medication 
name separately.  A patient who takes more than one medication will be counted only once 
if these medications belong to the same extended ATC classification.  The summary tables 
will be sorted by alphabetic order ATC levels and standard medication names. 
6.6 
Protocol Deviations 
Protocol deviations will be recorded by the site staff separately from the clinical database.  
They may also be identified through programmable checks of the data. 
A by-patient listing for all major protocol deviations will be provided. 
6.7 
Extent of Study Treatment Exposure and Compliance 
6.7.1 
Extent of Study Treatment Exposure  
The extent of exposure for the study treatment will be assessed by treatment arm using the 
following variables: 


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x Duration (weeks) of exposure defined as (date of last study treatment - date of first 
study treatment + 1)  
x Duration of exposure in category (<=1 week, (1, 2] weeks, (2, 3] weeks, (3, 4] 
weeks) 
x Total dose received (mg) defined as sum of doses received 
x Average dose received (mg/week) defined as total dose received/duration of 
exposure 
x Number and percentage of patients with dose reduced w/wo dose delayed  
x Number and percentage of patients with dose delayed w/wo dose reduced 
x Number and percentage of patients with concurrent dose reduced and delayed    
x Number and percentage of patients with dose held  
x Number and percentage of patients with missed dose 
6.7.2 
Treatment Compliance 
Treatment compliance (%) will be summarized by treatment arm, calculated as  
ܜܗܜ܉ܔܖܝܕ܊܍ܚܗ܎܌ܗܛ܍ܛܜ܉ܓ܍ܖ
܂ܗܜ܉ܔܖܝܕ܊܍ܚܗ܎܌ܗܛ܍ܛܛ܋ܐ܍܌ܝܔ܍܌ ൈ૚૙૙Ǥ 
Note that the number of scheduled doses does not include doses missed due to treatment 
interruption or other reasons not related to patient choice.  
The number and percentage of patients with study treatment compliance ≥70% will be 
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7. 
EFFICACY ANALYSES 
Efficacy analyses will be primarily performed in ITT population. For primary and key 
secondary endpoints, efficacy analyses using the EE population will be considered as 
supportive for the corresponding analyses in the ITT population. Efficacy analyses in PoC 
population will be descriptive in nature. 
Please refer to Table 6 below for efficacy endpoints and the corresponding definitions. 
Table 6: Efficacy Endpoints and Definitions 
Endpoint 
Definition 
Primary Endpoint 
Day 14 Ordinal Scale 
improvement (OSI2-14) 
 
Proportion of patients with at least a 2 points 
improvement (increase) in the Ordinal Scale by Day 
14. Baseline score is defined as the last score 
measured before first dosing. The improvement is 
assessed between the baseline score and the latest 
score on or before Day 14, End of study (EoS) date, 
or database cut date, whichever occurs first. 
Key Secondary Endpoints 
Time to an improvement of 2 
points using Ordinal Scale 
(TTCI-2) 
The time from randomization to an improvement of 
2 points on the Ordinal Scale. For patients who 
didn’t achieve clinical improvement of 2 points,  
x If no death event by Day 28, they will be 
censored on the last contact date, on or 
before Day 28, EoS date, or database cut 
date, whichever occurs first.   
If they died by Day 28, they will be censored on Day 
28. 
Overall death rate on Day 28 
(DR-28) 
Proportion of patients died on or before Day 28. 
Rate of mechanical ventilation 
(RMV) 
Proportion of patients who ever used invasive 
mechanical ventilation or ECMO during the hospital 
stay. 
Time to mechanical ventilation 
(TTMV) 
Time to the first use of mechanical ventilation. For 
patients who never used mechanical ventilator, the 
censoring date is defined as the death date or last 
contact date (if no death), on or before EoS or 
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Additional Secondary Endpoints 
Time to recovery (TTR) 
Time to improvement from baseline score of 3 to ≥4 
or from a baseline score of 4 to ≥5 by Day 28. For 
patients who didn’t achieve recovery, the censoring 
rule will be the same as that in TTCI-2. 
Day 7 Ordinal Scale 2 points 
improvement (OSI2-7) 
Proportion of patients with at least a 2 points 
improvement (increase) in the Ordinal Scale from 
baseline to Day 7. The improvement is assessed 
between the baseline score and the latest score on or 
before Day 7, End of study (EoS) date, or database 
cut date, whichever occurs first. 
Day 7 Ordinal Scale 1 point 
improvement (OSI1-7) 
Proportion of patients with at least a 1 point 
improvement (increase) in the Ordinal Scale from 
baseline to Day 7. The improvement is assessed the 
same as in OSI2-7. 
 
Day 14 Ordinal Scale 1 point 
improvement (OSI1-14) 
Proportion of patients with at least a 1 point 
improvement (increase) in the Ordinal Scale from 
baseline to Day 14. The improvement is assessed the 
same as in OSI2-14. 
 
Time to an improvement of 1 
point on the Ordinal Score 
(TTCI-1) 
The time from randomization to an improvement of 
1 point on the Ordinal Scale. For patients who didn’t 
achieve clinical improvement of 1 point, the 
censoring rule will be the same as that in TTCI-2. 
Overall survival (OS) 
Time since randomization to death date, or the last 
contact date with patient status being alive, on or 
before EoS or database cut date, whichever occurs 
first. 
Overall death rate on Day 14 
(DR-14) 
Proportion of patients died on or before Day 14. 
Rate of ICU admission 
Proportion of patients with ICU admission. 
Length of hospitalization 
Length of hospital stay defined as cumulative length 
of hospital stay. 
Length of ICU stay 
Cumulative length of ICU stay. 
Duration 
of 
mechanical 
ventilation 
Cumulative number of days with invasive mechanical 
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PaO2:FiO2 and/or oxygenation 
index over time 
PaO2:FiO2 and/or oxygenation index over time. Will 
be summarized by visit using descriptive statistics. 
7.1 
Analyses of Primary Efficacy Endpoint 
The difference in OSI2-14 rates between treatment arms will be calculated with a 95% 
confidence interval (CI). Comparison between 2 treatment arms will be performed using 
the Cochran-Mantel-Haenszel (CMH) test stratified by the randomization stratification 
factors. The CMH estimate of the odds ratio and its 95% CI and the p-value for testing the 
treatment difference will be reported.  
7.1.1 
Sensitivity Analyses 
In a sensitivity analysis for OSI2-14, the assessment of 2 points improvement will be 
conducted with the baseline score defined as the last score before first dosing, or a lower 
score within 24 hours of randomization, whichever is lower.   
The classification of whether a score can be considered as within 24 hours of randomization 
will be determined based on the date and time of randomization and score assessment. If 
there is partial date/time that make it impossible to determine whether the difference is 
within 24 hours, to be conservative, the score will be considered to be outside the 24-hour 
window.  
Specifically, 
x If the date of lower score is missing, it will be categorized as “outside 24 hours”. 
x If the date of lower score is not missing, but hour is missing: 
o It will be categorized as “within 24 hours” if the lower score is measured on 
the same day of randomization. 
o It will be categorized as “outside 24 hours” if the lower score is measured 
on subsequent day of randomization. 
x If both date and hour are not missing, but minute is missing: 
o It will be categorized as “within 24 hours” if lower score is on same day or 
subsequent day of randomization and hour is earlier than the hour in 
randomization time. 
It will be categorized as “outside 24 hours” if lower score is on subsequent day of 
randomization and hour is the same or later than the hour in randomization time. 
In the ITT population, the first approximately 50 patients were randomized with an 
allocation ratio of 2:1, the other patients in the ITT population will be randomized with 
an allocation ratio of 1:1. The switch of allocation ratio was due to an administrative 
reason and independent of patient characteristics and thus is not expected to cause any 
confounding bias. In a sensitivity analysis for OSI2-14, the CMH test will be conducted 


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stratifying by the randomization stratification factors and the period for the allocation 
ratio to assess robustness of results.  
7.1.2 
Subgroup Analyses 
The following sub-group analyses will be conducted for OSI2-14 and TTCI-2. 
x By age (≤70 vs. > 70) 
x Among patients with immune compromised, have hypertension, or have 
pulmonary disease (smoking history or moderate to severe chronic obstructive 
pulmonary disease [COPD)], cardiac disease 
x By baseline use of concomitant therapies 
x By high-risk comorbidities (0 vs 1 vs ≥2) 
x By race.  
7.2 
Analyses of Secondary Efficacy Endpoints 
7.2.1 
Analyses of Key Secondary Efficacy Endpoints 
If the primary endpoint, OSI2-14, is significant in ITT population, the following key 
secondary endpoints in ITT population will be sequentially tested in the order listed below. 
If any null hypothesis is not rejected in this sequence of tests, formal sequential testing will 
be stopped and the analyses of any endpoints thereafter will be nominal only.   
 
x Time to clinical improvement (TTCI-2) 
x Overall Death rate on Day 28 (DR-28) 
x Rate of mechanical ventilation (RMV) 
x Time to mechanical ventilation (TTMV) 
 
 
For binary endpoints (DR-28, RMV), the difference in rates between treatment arms will 
be calculated with a 95% confidence interval (CI). Comparison between 2 treatment arms 
will be performed using the Cochran-Mantel-Haenszel (CMH) test stratified by the 
randomization stratification factors. The CMH estimate of the odds ratio and its 95% CI 
and the p-value for testing the treatment difference will be reported.  
For time to event endpoints (TTCI-2, TTMV), the number and percentage of patients with 
the corresponding events will be reported. Median event times with 95% CIs will be 
estimated by Kaplan-Meier (KM) method for each treatment arm. KM curves by treatment 
arms will be provided. 
The following analysis stratified on randomization strata will be performed: 
x Log-rank test stratified to compare the event times between treatment arms 


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x Hazard ratios of treatment effect with 95% CI estimated by Cox proportional 
hazards model with Efron’s method of tie handling 
Non-stratified log rank test and Cox proportional hazards model will be performed as 
sensitivity analyses. 
The Kolmogorov-type Supremum test will be conducted to assess the validity of the 
proportion hazards assumption in all fitted Cox proportional hazards models. If there is 
evidence for a violation of the proportional hazards assumption, interaction terms between 
time-dependent terms and treatment variable (selinexor vs. placebo) will be added to assess 
time-varying treatment effects.   
In sensitivity analysis for RMV, analyses will be conducted with patients who ever used 
one of the respiratory assistances as below: 
x Non-invasive positive pressure mechanical ventilation (CPAP/BiPAP) 
x High-flow nasal cannula 
x Invasive mechanical ventilation 
x Extracorporeal membrane oxygenation (ECMO) 
For TTCI-2, sensitivity analyses will be performed in the same manner as OSI2-14. 
7.2.2 
Analyses of Additional Secondary Endpoints 
For the additional secondary endpoints, binary endpoints and time to event endpoints will 
be analyzed similarly as for the key secondary endpoints, with the only exception that there 
will be no hypothesis testing. 
 
For continuous endpoints (length of hospitalization, length of ICU stay, duration of 
mechanical ventilation), summary statistics by treatment arm will be provided including 
number of patients, median, mean, standard deviation, minimum, and maximum.  
For duration of mechanical ventilation, sensitivity analyses will be performed in the same 
manner as RMV. 
For PaO2:FiO2 and/or oxygenation index over time, only descriptive statistics will be 
provided. 
7.2.2.1 
 Determination of the anti-inflammatory and immune effect of selinexor 
The following endpoints will be summarized by time. Change from baseline will also be 
summarized. The analyses will be descriptive only, no hypotheses testing will be 
performed.  
x Reduction of C-reactive protein (CRP)  
x Reduction in ferritin levels  


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x LDH 
x Measure changes from baseline of blood plasma cytokines: IL-1β, IL-1Rα, IL-2, IL-4, 
IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IFNγ, IP10, TNFα 
7.3 
Analyses of Exploratory Endpoints 
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8. 
SAFETY ANALYSES  
Safety endpoints include AEs, clinical laboratory variables, vital signs, and ECGs.  
Unless otherwise specified, all safety analysis will be performed by treatment arm 
according to the treatment the patient actually received using the AT and POC 
populations. 
8.1 
Adverse Events  
Adverse events (AEs) will be coded using the most recent version of MedDRA.  
The severity of all AEs will be graded according to the NCI CTCAE Grading Scale, v. 5.0. 
An AE with a CTCAE grade of 3 or higher is considered a severe AE. The severity of the 
AE is different from the seriousness of the AE. For AEs not covered by CTCAE, the 
severity will be characterized as “mild,” “moderate,” “severe”, “life-threatening” 
(corresponding to Grades 1 to 4). Handling rules for missing severity of AEs are described 
in Section 4.4.3. 
Treatment emergent adverse events (TEAEs) are defined as those AEs that develop or 
worsen after the first dose of study treatment and up to 30 days beyond the last dose of 
study treatment. Additionally, any AEs that occurred 30 days after the last dose of study 
treatment will also be considered as TEAE, if assessed by the Investigator as related to 
study treatment. 
AEs are classified as related or not related to study treatment. Any AEs with missing or 
unknown relationship will be considered as related to study treatment.  
All summaries of AEs described in this section will be on TEAEs. All summaries will be 
ordered by decreasing frequency of total number of patients in overall in PT within SOC 
which is sorted alphabetically. In the case of equal frequency of number of patients in PTs, 
then summaries of AEs will be sort alphabetically.  
An overall summary for AEs including number of patients who experience an TEAE will 
be provided:  
x TEAEs  
x Grade 3/4 TEAEs  
x Serious TEAEs  
x TEAEs leading to study treatment discontinuation 
x TEAEs leading to dose reduction of study treatment 
x TEAEs leading to dose interruption of study treatment 
x TEAEs leading to death  
x Treatment-related TEAEs 
x Treatment-related serious TEAEs 


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x Treatment-related TEAEs leading to study treatment discontinuation 
x Treatment-related TEAEs leading to dose reduction of study treatment 
x Treatment-related TEAEs leading to dose interruption of study treatment 
x Treatment-related TEAEs leading to death  
The following types of TEAEs will be summarized by primary SOC and PT:  
x All TEAEs  
x All TEAEs, by causality 
x All TEAEs, by maximum grade  
x Grade ≥ 3 TEAEs  
x Grade ≥ 3TEAEs, by causality 
x TEAEs leading to study treatment discontinuation 
x TEAEs leading to dose reduction of study treatment 
x TEAEs leading to dose interruption of study treatment 
x TEAEs leading to death 
x Serious TEAEs  
x Serious TEAEs, by causality 
If a SOC or PT was reported more than once for a patient, the patient would only be counted 
once in the incidence for that SOC or PT.  
For patients experiencing the same PT at multiple severities, the occurrence of the AEs 
with the greatest severity will be used in the analysis of incidence by severity.  
For patients experiencing the same PT at multiple relationship levels, the occurrence of the 
AEs with the strongest relationship to study treatment will be used in the analysis of 
incidence by relationship to study treatment. 
An overview of all death events and primary cause of death will be provided. 
The following listing will be provided:  
x All AEs 
x Serious AEs 
x AEs leading to study treatment discontinuation 
x AEs leading to dose modification (reduction, interruption) 
x Death  
8.2 
Clinical Laboratory Data 
All laboratory parameters will be normalized by converting values in original units to 
values in SI units and classified as normal, abnormal low, or abnormal high on normal 
ranges supplied by the local laboratories and upon employing standardization.  


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Observed and change from baseline of clinical laboratory data (hematology, serum 
chemistry and coagulation) will be summarized at each analysis visit by treatment arm.   
Whenever applicable, severity of selected clinical laboratory measures will be determined 
based on the CTCAE criteria. Laboratory values with CTCAE Grade ≥ 3 will be 
presented in a data listing. The worst toxicity grade in hematology and chemistry will be 
summarized by toxicity grade. Shift tables that present changes from baseline to worst 
on-study relative to CTCAE classification ranges will be presented. These shift tables 
will include results from unscheduled visits. 
8.3 
Vital Signs 
Observed and change from baseline of vital signs (including temperature, pulse rate, 
respiratory rate, systolic and diastolic blood pressure, oxygen saturation) will be 
summarized at each analysis visit by treatment arm, up to ICU admission if applicable. 
8.4 
Electrocardiogram (ECG) 
ECG will be listed only. Values of potentially clinically significant ECG (scheduled or 
unscheduled) will be flagged.  These are defined as:  
x QT, QTcF ≥ 450 msec 
x QT, QTcF increase from baseline ≥ 30 msec 
x PR ≤ 100 msec or PR ≥ 240 msec 
x QRS ≥ 140 msec 
x Heart rate ≤ 40 bmp or heart rate ≥ 120 bmp 
9. 
PHARMACOKINETIC ANALYSES 
Plasma samples will be analyzed via a validated HPLC/MS-MS method for plasma 
selinexor concentration. Selinexor Cmax and Ctrough data will be summarized. Selinexor 
concentration data might also be analyzed using a population PK modeling approach if 
deemed necessary. Details of the population PK analysis, including software, post-
processing and statistical analysis, will be outlined in a separate Data Analysis Plan to be 
completed prior to database lock. 
 
 
 


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10. 
REFERENCES 
Cui L, Hung H, Wang S. Modification of sample size in group sequential clinical trials.  
Biometrics. 1999;55:853-857. 
Lan K, DeMets D. Discrete sequential boundaries for clinical trials. Biometrika. 
1983;70:659-63.