Clinical trial NCT05305989
Conditions: Chronic Graft-versus-host-disease
Sponsor: Kadmon, a Sanofi Company
Start date: 2022-02-23; Completion date: 2024-06-06
Enrollment: 23 participants; Allocation: NON_RANDOMIZED; Intervention model: PARALLEL

Brief summary:
Extended Treatment and Follow-up of Subjects Treated with Belumosudil in Study KD025-208 or Study KD025-213

Detailed description:
This is a Phase 2, open-label, long-term treatment and follow-up study in subjects with cGVHD who have been previously treated with belumosudil in Study KD025-208 or Study KD025-213. Subjects will not be screened. Subjects who have signed the informed consent form will be enrolled in Study KD025-217 if they have met 1 of the following conditions:

* Actively receiving belumosudil or in long-term follow-up (LTFU) in Study KD025-208 or Study KD025-213
* Enrolled in the Companion Study as specified in Study KD025-213 Amendment 2 and received at least 6 months of treatment or is in LTFU

Approximately 20 Study Centers will participate with approximately 70 subjects participating overall.

Arms: arm 1: The assigned arm is per the previous study KD025-213 or study KD025-208 arm 2: The assigned arm is per the previous study KD025-213 or study KD025-208 arm 3: The assigned arm is per the previous study KD025-213 or study KD025-208
Interventions: intervention 1: Belumosudil 200 mg QD intervention 2: Belumosudil 200 mg BID intervention 3: Belumosudil 400 mg QD
Intervention descriptions: intervention 1: Belumosudil is an orally available Rho-associated protein kinase-2 (ROCK2) selective inhibitor. intervention 2: Belumosudil is an orally available Rho-associated protein kinase-2 (ROCK2) selective inhibitor. intervention 3: Belumosudil is an orally available Rho-associated protein kinase-2 (ROCK2) selective inhibitor.

Protocol documents:
Prot_000.pdf: 
C o nfi de nti alit y St ate me nt  
T he i nf or mati o n c o ntai ne d her ei n is c o nfi de ntial a n d t he pr o prietar y pr o pert y of Ka d m o n C or p orati o n 
a n d a n y u na ut h orize d use or discl os ure of s uc h i nf or mati o n wit h o ut t he pri or writte n a ut h orizati o n of 
Ka d m o n C or p orati o n is e x pressl y pr o hi bite d.  
C LI NI C A L  S T U D Y P R O T O C O L  
E xte n de d Tre at me nt a n d F oll o w -u p of S u bjects Tre ate d wit h Bel u m os u dil i n  
St u d y K D 0 2 5 -2 0 8 or St u d y K D 0 2 5 -2 1 3  
P r ot oc ol N u m ber:  
K D 0 2 5 -2 1 7  
St u d y Dr u g:  
Bel u m os u dil  (f or merl y K D 0 2 5) 
I N D N u m ber: 
I N D 1 2 5 8 9 0 
P h ase : 
2  
S p o ns or:  
Ka d m o n C or p orati o n , L L C 
4 5 0 East 2 9t h Street  
Ne w Y or k, N Y 1 0 0 1 6  
Ori gi n al  P r ot oc ol:  
2 6  J uly  2 0 2 1  
A me n d me nt 1:  
0 1 Se pte m ber  2 0 2 1  
V V- C LI N- 0 6 3 8 9 9 6 1. 0
          N C T: N C T 0 5 3 0 5 9 8 9


B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
I N D 1 2 5 8 9 0 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 2  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
Pr o ce d ures i n C ase of E mer ge nc y  
 
Seri o us A d verse E ve nts  
A n y  s eri o us a d verse e v e nt ( S A E) * occ urri n g i n a s u bject w hile recei vi n g st u d y dr u g or wit hi n 
2 8  da ys  of recei vi n g t heir last d ose of st u d y dr u g, e ve n t h o u g h t he e v e nt ma y n ot a p pear t o be 
st u d y dr u g relate d, m ust be pr o m ptl y re p orte d (wit hi n 2 4 h o urs ) b y tele p h o ne, e-mail,  or telefa x 
t o t he S p o ns or  ( or desi g n ee).   
E mer ge nc y C o nt a ct I nf or m ati o n:  
F or me dic al q uesti o ns c o nt act t he m e dic al m o nit or , 
: 
E mail:
 
P h o ne: 
 
F or S A E re p orti n g, se n d t he S A E f or m, pre g n a nc y f or m or f oll o w -u p wit hi n 2 4  h o urs of 
bec o mi n g a w are t o:  
Ka d m o n P har mac o vi gila nce  
 
or  
Fa x: 
S A E C RI T E RI A  
* A S A E is a n y u nt o war d me dical occ urre nce t hat at a n y d ose res ults i n a n y of t he f oll o wi n g o utc o mes, 
re gar dless of relati o ns hi p t o st u d y dr u g (see Secti o n 7. 3. 1 , Seri o us A d verse E ve nts, f or a d diti o nal 
i nf or mati o n): 
•  
Deat h  
•  
Life -t hreate ni n g a d verse dr u g e ve nt 
•  
I n patie nt h os pitalizati o n or pr ol o n gati o n of e xisti n g h os pitalizati o n 
•  
A persiste nt or si g nifica nt disa bilit y/ i nca pacit y  
•  
A c o n ge nital a n o mal y/ birt h defect  
•  
A n i m p orta nt me dical e ve nt t hat ma y j e o par dize t he s u bj ect a n d ma y re q uire me dical or 
s ur gical i nter ve nti o n t o pre ve nt o ne of t he o utc o mes liste d a b o ve. 
 
 
V V- C LI N- 0 6 3 8 9 9 6 1. 0


B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
I N D 1 2 5 8 9 0 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 3  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
S P O N S O R A P P R O V A L SI G N A T U R E  P A G E   
 
I h a ve rea d a n d a p pr o ve t his pr ot oc ol. M y si g nat ur e, i n c o nj u ncti o n wit h t he si g nat ur e of t he 
I n v esti gat or, c o nfir ms t h e a gree me nt of b ot h parties t hat t he cli nical st u d y will be c o n d ucte d i n 
acc or da nce wit h t he pr ot oc ol a n d all a p plica ble l a ws a n d re g ulati o ns i ncl u di n g, b ut n ot li mite d 
t o, t he I nter nati o nal C o nfere nce o n Har m o nizati o n G ui deli ne f or G o o d Cli nical Practice ( G C P) 
E 6 ( R 2) , a n d t he et hical pri nci ples t hat ha ve t heir ori gi ns i n t he Declarati o n of Helsi n ki. 
 
 
 
 
 
Date of Si g nat ure  
E x ec uti ve Me dical Direct or, Cli nical a n d Re g ulat or y 
De vel o p me nt  
 
( D D M M M Y Y Y Y) 
Ka d m o n C or p orati o n, L L C  
 
 
 
 
V V- C LI N- 0 6 3 8 9 9 6 1. 0


B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
Ka d m o n C or p orati o n  
P a ge 4  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
I N V E S TI G A T O R SI G N A T UR E P A G E  
I h a ve rea d a n d a p pr o ve t his pr ot oc ol. M y si g nat ur e, i n c o nj u ncti o n wit h t he si g nat ur e of t he 
S p o ns or , c o nfir ms t he a gree me nt of b ot h p arties t hat t he cli nical st u d y will be c o n d ucte d i n 
acc or da nce wit h t he pr ot oc ol a n d all a p plica ble l a ws a n d re g ulati o ns i ncl u di n g, b ut n ot li mite d 
t o, t he I nter nati o nal C o nfere nce o n Har m o nizati o n G ui deli ne f or G o o d Cli nical Practice ( G C P) 
E 6 ( R 2 ), t he C o de of Fe d eral Re g ulati o ns ( C F R), a n d t he et hical pri n ci ples t hat ha ve t heir ori gi ns 
i n t he Declarati o n of Helsi n ki. 
N ot hi n g i n t his d oc u me nt is i nte n de d t o li mit t he a ut h orit y of a p h ysici a n t o pr o vi de e mer ge nc y 
me dical ca re u n der a p pli ca ble re g ulati o ns.  
I n v esti gat or Si g nat ure 
Date of Si g nat ure  
( D D M M M Y Y Y Y) 
Na me of I n v esti gat or ( pl ease pri nt)  
V V- C LI N- 0 6 3 8 9 9 6 1. 0


B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 5  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
S Y N O P SI S   
St u d y Title  
E xte n de d Treat me nt a n d F oll o w -u p of S u bj ects Treate d wit h Bel u m os u dil i n 
St u d y K D 0 2 5 -2 0 8 or St u d y K D 0 2 5 -2 1 3  
Cli nic al P h ase  
2  
St u d y B ac k gr o u n d  
C hr o nic graft -vers us -h ost dise ase (c G V H D) re mai ns a maj or c o m plicati o n of 
all o ge neic he mat o p oietic cell tra ns pla ntati o n ( H C T) occ urri n g i n a p pr o xi matel y 
5 0 % of tra ns pla nt reci pie nts a n d i n v ol vi n g m ulti ple or ga ns. P atie nts wit h 
c G V H D re q uire pr ol o n ge d i m m u n os u p pressi ve treat me nt f or a n a vera ge of 2 t o 
3 years fr o m t he i nitial dia g n osis, wit h 1 0 % of t h ose s ur v i vi n g f or at least 
7  years still re q uiri n g i m m u n os u p pressi ve treat me nt at t hat ti me a n d be y o n d.  
T here re mai ns s u bsta ntial u n met me dical nee d f or t hera pies wit h i m pr o ve d 
t olera bilit y a n d effecti ve ness f or a d ults a n d a d olesce nts wit h c G V H D.  
B el u m os u dil ( pre vi o usl y  k n o w n as K D 0 2 5) is a n orall y a vaila ble R h o -ass ociate d 
c oile d -c oil ki nase 2 ( R O C K 2) selecti ve i n hi bit or t hat has bee n s h o w n t o be 
acti ve a n d well -t olerate d i n c G V H D.  St u d y K D 0 2 5-2 0 8 e nr olle d s u bj ects wit h 
acti ve c G V H D w h o ha d pre vi o usl y recei ve d n o  m ore t ha n 3 pri or li nes of 
treat me nt.  St u d y K D 0 2 5-2 1 3 e nr olle d s u bj ects w h o ha d pre vi o usl y recei ve d 2  t o 
5  pri or li nes of treat me nt.  O ver t w o -t hir ds of c G V H D patie nts treate d wit h 
bel u m os u dil i n t hese 2  trials a c hie ve d cli nical res p o nses.  
I n b ot h St u d y K D 0 2 5 -2 0 8 a n d St u d y K D 0 2 5 -2 1 3, s u bj ects were treate d wit h 
bel u m os u dil u ntil c G V H D pr o gressi o n or u nacce pta ble t o xicit y.  Se veral 
s u bj ects re mai n o n acti ve treat me nt.   
T his st u d y will pr o vi de e xte n de d  treat me nt a n d f oll o w-u p f or t hese s u bj ects 
utilizi n g t he sa me d ose a n d treat me nt sc he d ule of bel u m os u dil t hat eac h s u bj ect 
was recei vi n g i n St u d y K D 0 2 5 -2 0 8 or St u d y K D 0 2 5 -2 1 3.  
St u d y O bjecti ve  
T he o bj ecti ve of t his st u d y is t o e val uate l o n g -ter m safet y a n d efficac y of 
bel u m os u dil i n s u bj ects wit h c G V H D w h o ha ve pre vi o usl y bee n treate d wit h 
bel u m os u dil .  
St u d y  Desi g n  
T his will b e a P hase 2, o pe n -la bel, l o n g-ter m treat me nt a n d f oll o w-u p st u d y i n 
s u bj ects wit h c G V H D w h o ha ve bee n pre vi o usl y treate d wit h bel u m os u dil i n 
St u d y K D 0 2 5 -2 0 8 or i n St u d y K D 0 2 5 -2 1 3.  
S u bj ects will n ot be scree ne d.  
S u bj ects w h o ha ve si g ne d t he  i nf or me d c o nse nt f or m will be e nr olle d i n 
St u d y  K D 0 2 5 -2 1 7 if t he y ha ve met 1 of t he f oll o wi n g c o n diti o ns:  
•  
Acti vel y recei vi n g bel u m os u dil or i n l o n g -ter m f oll o w-u p ( L T F U) i n 
St u d y  K D 0 2 5 -2 0 8  or St u d y K D 0 2 5 -2 1 3  
•  
E nr olle d i n t he C o m pa ni o n St u d y as s pecifie d i n St u d y K D 0 2 5 -2 1 3 
A me n d me nt 2 a n d recei ve d at least 6 m o nt hs of treat me nt or is i n L T F U  
After si g ni n g t he I C F, at Baseli ne , s u bj ects will u n der g o effi cac y assess me nts b y 
Cli nicia n -re p orte d  Gl o bal c G V H D Acti vit y Assess me nt, res p o nse assess me nt, 
p ul m o nar y f u ncti o n tests, Lee S y m pt o m Scale ( L S S) sc ore, a n d d oc u me ntati o n 
of c ortic oster oi d d osa ge a n d/ or ot her t hera pies f or c G V H D.  S u bj ects will 
u n der g o safet y assess me nts i ncl u di n g s y m pt o m -directe d  p h ysica l e xa mi nati o n 
( P E), vital si g ns, wei g ht, hei g ht, Kar n ofs k y P erf or ma nce St at us  ( K P S) sc ore, 
he mat ol o g y a n d cli nical c he mistr y la b orat or y testi n g, pre g na nc y testi n g, 1 2 -lea d 
electr ocar di o gra m ( E C G ), d oc u me nti n g c o nc o mita nt me dicati o ns, a n d 
m o nit ori n g f or a d verse e ve nts ( A Es ).  S u bj ects will c o nti n ue o n t heir sa me 
V V- C LI N- 0 6 3 8 9 9 6 1. 0


B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 6  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
d osi n g re gi me n as t he y recei ve d i n St u d y K D 0 2 5 -2 0 8 or St u d y  K D 0 2 5 -2 1 3: 
bel u m os u dil 2 0 0 m g o nce dail y ( Q D ), 2 0 0 m g t wice dail y (BI D ), or 4 0 0 m g Q D.  
If t he I n vesti gat or re d uce d t he d ose, i.e., a s ubject recei ve d a re d uce d d ose of 
bel u m os u dil i n eit her St u d y  K D 0 2 5 -2 0 8 or St u d y K D 0 2 5 -2 1 3, t he s u bj ect w o ul d 
c o nti n ue t o recei ve t hat sa me re d uce d d ose treat me nt wit h bel u m os u dil 
t hr o u g h o ut St u d y K D 0 2 5-2 1 7  or u ntil t he A E  t hat le d t o t he t e m p orar y d ose 
re ducti o n ha d  res ol ve d, i n w hi c h t he d ose treat me nt ca n res u me at t he ori gi nal 
d ose at t he discreti o n of t he I n vesti gat or.   S u bj ects will be gi ve n a st u d y dr u g 
diar y t o rec or d dail y d osi n g.  S u bj ects ma y be a d mi nistere d t he first d ose eit her 
i n t he cli nic or self-a d mi nistere d at h o me.  
At 3 m o nt hs after Baseli ne  a n d e ver y 3 m o nt hs t hereafter ( ± 1 4 da ys), s u bj ects 
will re p ort t o t he cli nic f or t he sa me efficac y a n d safet y assess me nts a n d 
dis pe nsi n g of bel u m os u dil  as Baseli ne .  T he st u d y dr u g diaries f or t he past 
3  m o nt hs will be c ollecte d, a n d ne w st u d y dr u g diaries dis pe nse d.  A n y 
re mai ni n g bel u m os u dil will be c ollecte d. 
S u bj ects ma y recei ve bel u m os u dil  i n St u d y  K D 0 2 5 -2 1 7 f or u p t o a n a d diti o nal 
2  years , at t he discreti o n of t he In vesti gat or (a n d wit h g ui da nce fr o m t he me dical 
m o nit or) , be y o n d w hat t he y ha d recei ve d i n St u d y K D 0 2 5-2 0 8 or St u d y  K D 0 2 5 -
2 1 3 .  S u bj ects will be treate d wit h bel u m os u dil u ntil c G V H D pr o gressi o n or 
u nacce pta ble t o xicit y.  
S u bj ects will ret ur n t o t he cli nic f or a 2 8 -da y F oll o w -u p Visit  2 8 ( ± 7 da ys) at 
2 8  da ys after t he last d ose of st u d y dr u g.  After t he 2 8 -da y  F oll o w -U p  Visit has 
bee n c o m plete d, s u bj ects will ha ve L T F U  a p pr o xi matel y e ver y 3  m o nt hs u ntil a 
fail ure-free s ur vi val ( F F S) e ve nt occ urs.   T his L T F U assess me nt wi ll occ ur b y 
s u bj ects bei n g  c o ntacte d b y tel e p h o ne, e -mail, or p ostal mail t o c o nfir m s ur vi val 
stat us, a n y i nitiati o n of ne w s yste mic c G V H D t hera pies, a n d rela pse of 
u n derl yi n g disease.  Alter nati vel y, t his i nf or mati o n ma y be o btai ne d fr o m t he 
s u bj ect’s me dical rec or ds. 
N u m ber of St u d y Ce nters  
A p pr o xi matel y 2 0  
N u m ber of S u bjects  
A p pr o xi matel y 7 0  
A p pr o xi m ate D ur ati o n of 
S u bject P artici p ati o n  
S u bj ects ma y recei ve bel u m os u dil  u p t o a n a d diti o nal 2 years  be y o n d w hat t he y 
ha d recei ve d i n St u d y K D 0 2 5 -2 0 8 or St u d y K D 0 2 5 -2 1 3 , at t he discreti o n of t he 
In vesti gat or a n d wit h g ui da nc e fr o m t he me dical m o nit or.  
S u bj ects will be treate d wit h bel u m os u dil u ntil c G V H D pr o gressi o n or 
u nacce pta ble t o xicit y.  
S u bj ects will ret ur n t o t he cli nic f or a 2 8 -da y F oll o w -u p Visit at 2 8 da ys 
( ± 7  da ys) after  t he last d ose of st u d y dr u g.  S u bj ects will ha ve L T F U  
a p pr o xi matel y e ver y 3 m o nt hs u ntil a F F S e ve nt occ urs .  Aft er t he 2 8-da y 
F oll o w -u p Visit has bee n c o m plete d, s u bj ects will be c o ntacte d a p pr o xi matel y 
e ver y 3 m o nt hs b y tele p h o ne, e -mail, or p ostal mail t o c o nfir m s ur vi val stat us, 
a n y i nitiati o n of ne w s yste mic c G V H D t hera pies, a n d rela pse of u n derl yi n g 
disease.   
St u d y Tre at me nt  
B el u m os u dil will be a d mi nistere d orall y at t he sa me d ose t he s u bj ect recei ve d i n 
St u d y K D 0 2 5 -2 0 8 or i n St u d y K D 0 2 5 -2 1 3.  
S u bj ects will be pr o vi de d wit h a n a de q uate s u p pl y of bel u m os u dil.  St u d y dr u g 
acc o u nti n g will be perf or me d at eac h visit.  
Criteri a f or I ncl usi o n a n d 
E xcl usi o n  
I ncl usi o n Criteri a: 
1.  S u bj ects m ust ha ve bee n treat e d wit h bel u m os u dil f or at least 1 of t he 
f oll o wi n g: 
V V- C LI N- 0 6 3 8 9 9 6 1. 0


B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 7  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
a. 
Acti vel y r ecei v i n g bel u m os u dil o n St u d y  K D 0 2 5 -2 0 8  or 
St u d y  K D 0 2 5 -2 1 3  (e xcl u di n g a d ults i n t he C o m pa ni o n St u d y 
a n d e xcl u di n g a d olesce nts e nr olle d u n der K D 0 2 5 -2 1 3 
A me n d me nt 2 [0 1  J u ne 2 0 2 0]). 
b.  Is i n L o n g -ter m F oll o w -u p ( L F T U) o n St u d y K D 0 2 5 -2 0 8  or 
St u d y  K D 0 2 5 -2 1 3 .  L o n g-ter m F oll o w -u p  will be defi ne d as 
t he peri o d after e n di n g treat me nt wit h bel u m os u dil a n d u ntil a 
F F S e ve nt occ urs.  
c. 
A d ult e nr olle d i n t he C o m pa ni o n St u d y u n der K D 0 2 5 -2 1 3 
A me n d me nt 2 ( 0 1  J u ne 2 0 2 0) a n d has recei ve d at least 
6  m o nt hs of treat me nt of bel u m os u dil or is i n L T F U  
2.  Fe male s u bj ects of c hil d beari n g p ote ntial ha ve a ne gati ve pre g na nc y test 
at e nr oll me nt. Fe males of c hil d beari n g p ote ntial are defi ne d as se x uall y 
mat ure fe males wit h o ut pri or h ysterect o m y or w h o ha ve ha d a n y  
e vi de nce of me nses i n t he past 1 2 m o nt hs. H o we ver, fe males w h o ha ve 
bee n a me n orr heic f or 1 2 or m ore m o nt hs are still c o nsi dere d t o be of 
c hil d beari n g p ote ntial if t he a me n orr hea is p ossi bl y d ue t o pri or 
c he m ot hera p y, a nti -estr o ge ns, or o varia n s u p pressi o n . 
3.  Se x uall y acti ve fe males of c hil d beari n g p ote ntial e nr olle d i n t he st u d y 
m ust a gree t o use 2  f or ms of a cce pte d met h o ds of c o ntrace pti o n d uri n g 
t he c o urse of t he st u d y a n d f or 3 m o nt hs after t heir last d ose of st u d y 
dr u g. Effecti ve birt h c o ntr ol i ncl u des:  
a. 
I ntra uteri ne de vice pl us 1 barrier met h o d 
b.  Sta ble d oses of h or m o nal c o ntrace pti o n f or at least 3 m o nt hs 
(e. g., oral, i nj ecta ble, i m pla nt, tra ns der mal) pl us 1  barrier 
met h o d  
c. 
2  barrier met h o ds.  Effecti ve barrier met h o ds are male or 
fe male c o n d o ms, dia p hra g ms, a n d s per mici des (crea ms or gels 
t hat c o ntai n a c he mical t o kill s per m) or 
d.  A vasect o mize d part ner  
4.  F or male s u bj ects w h o are se x uall y acti ve a n d w h o are part ners of 
fe males of c hil d beari n g p ote ntial: a gree me nt t o use 2  f or ms of 
c o ntrace pti o n a n d t o n ot d o n at e s per m d uri n g t he treat me nt p eri o d a n d 
f or at least 3 m o nt hs after t he l ast d ose of st u d y dr u g. 
5.  S u bj ect ( or t he s u bj ect’s le gall y a ut h orize d re prese ntati ve) is a ble t o 
pr o vi de writte n i nf or me d c o ns e nt pri or t o t he perf or ma nce of a n y st u d y -
s pecific pr oced ures.  
6.  It is i n t he best i nterest of t he s u bj ect t o partici pate i n t he st u d y. 
 
E xcl usi o n Criteri a  
1.  Fe male s u bj ect w h o is pre g na nt or breastfee di n g  
2.  S u bj ect c o nsi dere d u nli kel y t o a d here t o treat me nt a n d/ or f oll o w 
pr ot oc ol i n t he o pi ni o n of t he I n vesti gat or  
Effic ac y F oll o w -u p 
V ari a bles  
 
•  
D urati o n of Res p o nse s (D O R ):  Res p o nse  is defi ne d b y t he 2 0 1 4 
Nati o nal I nstit utes of Healt h ( NI H) C o nse ns us De vel o p me nt Pr oj ect o n 
cli nical trials i n c G V H D a n d are assesse d b y i n vesti gat ors  
•  
C ha n ge i n Lee S y m pt o m Scal e Sc ore ( L S S)  
•  
Ti me t o Ne xt Treat me nt  ( T T N T) 
•  
F F S  
•  
O verall S ur vi val ( O S)  
V V- C LI N- 0 6 3 8 9 9 6 1. 0


B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 8  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
•  
P erce nta ge of s u bj ects w h o ha ve a best res p o nse of P R a n d perce nta ge 
of s u bj ects w h o ha ve a best res p o nse of C R  
•  
Res p o nse b y i n di vi d ual or ga n  
•  
C ha n ge i n cortic oster oi d d ose  
•  
C ha n ge i n c G V H D Gl o bal Se verit y Rati n g base d o n t he 
Cli nicia n -re p orte d Gl o bal c G V H D Acti vit y Assess me nt  
S afet y F oll o w -u p V ari a bles  
Safet y assess me nts will be perf or me d at re g ular i nter vals a n d will i ncl u de A Es, 
Gra d e ≥ 3 A Es, seri o us a d vers e e ve nts (S A Es ), P Es, vital si g n meas ure me nts, 
cli nical la b orat or y e val uati o ns, a n d E C Gs.  Reas o ns f or treat me nt 
disc o nti n uati o n will be d oc u me nte d.   
T he A E re p orti n g peri o d f or a s u bj ect e nr olle d i n t he st u d y will be gi n w he n t he 
s u bj ect si g ns t he i nf or me d c o nse nt a n d is c o nti n ue d t hr o u g h t he 2 8-da y F oll o w -
u p Visit at 2 8 da ys  ( ± 7 da ys) after t heir last d ose st u d y  dr u g.  
St atistic al A n al ysis  
A n i nteri m a nal ysis will be perf or me d w he n all patie nts ha ve c o m plete d at least 
3  years of treat me nt wit h bel u m os u dil or wit h dre w earlier ( n ot i ncl usi ve of t he 
c o m pa ni o n st u d y s u bj ects).   
 
St u d y S u bjects  
De m o gra p hic (e. g., ge n der, a ge, a n d race) a n d Baseli ne  c har acteristics will be 
s u m marize d.   
 
Effic ac y A n al yses:  
T he efficac y e n d p oi nt a nal yses i ncl u de  
•  
D O R  
•  
C ha n ge i n L S S  
•  
T T N T  
•  
F F S  
•  
O S  
•  
P r o p orti o n of s u bj ects wit h a C R a n d pr o p orti o n wit h a P R 
•  
Res p o nse b y i n di vi d ual or ga n  
•  
C ha n ge i n c ortic oster oi d use  
•  
C ha n ge i n c G V H D gl o bal se verit y rati n g base d o n t he 
Cli nicia n -re p orte d Gl o bal c G V H D Acti vit y Assess me nt.  
 
S afet y A n al yses:  
Safet y a nal yses will be perf or me d o n all s u bj ects w h o recei ve at least 1  d ose of 
bel u m os u dil . 
A d verse e ve nts  will be c o de d usi n g t he Me dical Dicti o nar y of Re g ulat or y 
Acti vities ( Me d D R A v ersi o n 2 4 . 0 or greater).  T he n u m ber a n d perce nta ges of 
s u bj ects e x perie nci n g treat me nt-e mer ge nt A Es will be ta b ul ate d b y S yste m  
O r ga n C lass a n d P referre d T er m ( P T).  T he n u m ber of e ve nts b y P T  will als o be 
s u m marize d.  T a b ulati o n b y ma xi m u m se verit y a n d relati o ns h i p t o treat me nt will 
als o be i ncl u de d b y treat me nt gr o u p.  S u m mar y s u bj ect listi n g will be pr o vi de d 
f or S A Es, A Es res ulti n g i n st u d y disc o nti n uati o n, a n d deat hs. 
T he A Es, S A Es, relate d A Es, relate d S A Es, Gra de ≥ 3 A Es, relate d Gra de ≥ 3 
A Es, deat hs, a n d A E s lea di n g t o wit h dra wal a n d treat me nt disc o nti n uati o n will 
be s u m marize d.  
V V- C LI N- 0 6 3 8 9 9 6 1. 0


B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
Ka d m o n C or p orati o n  
P a ge 9  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
La b orat or y res ults  a n d i nci de nce of la b orat or y a b n or malities  will be s u m marize d 
b y treat me nt gr o u p.   T he w orst o n -st u d y gra de d uri n g t he treat me nt peri o d will 
be s u m marize d. T he i nci de nce of G ra de ≥ 3 la b orat or y a b n or malities u n der 
treat me nt a n d s hifts i n t o xicit y gra di n g fr o m Baseli ne  t o hi g hest gra de 
p ost -baseli ne will be dis pla ye d.  
Vital si g n meas ure me nts a n d E C Gs will be s u m marize d b y treat me nt gr o u p at 
eac h sc he d ule d ti me p oi nt usi n g descri pti ve statistics a n d i ncl u de d i n data 
listi n gs.  
V V- C LI N- 0 6 3 8 9 9 6 1. 0


B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 1 0  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
T A B L E  O F C O N T E N T S  
C LI NI C A L S T U D Y P R O T O C O L  ............................................................................................................... 1  
S P O N S O R A P P R O V A L SI G N A T U R E P A G E  ........................................................................................... 3  
I N V E S TI G A T O R SI G N A T U R E P A G E ...................................................................................................... 4  
S Y N O P SI S  .................................................................................................................................................... 5  
T A B L E O F C O N T E N T S  ............................................................................................................................ 1 0  
LI S T O F T A B L E S  ...................................................................................................................................... 1 3  
LI S T O F FI G U R E S  .................................................................................................................................... 1 4  
LI S T O F A B B R E VI A TI O N S  ..................................................................................................................... 1 5  
1  
I N T R O D U C TI O N ................................................................................................................................ 1 7  
1. 1  
C hr o nic Graft -vers us -H ost Disease  ............................................................................................ 1 7  
1. 2  
R h o -Ass ociate d Pr otei n Ki nases ................................................................................................. 1 7  
1. 3  
N o n -cli nical Bac k gr o u n d of Bel u m os u dil  .................................................................................. 1 8  
1. 4  
Cli nical Bac k gr o u n d of Bel u m os u dil  ......................................................................................... 1 9  
1. 4. 1  St u d y K D 0 2 5 -2 0 8  ....................................................................................................................... 1 9  
1. 4. 2  St u d y K D 0 2 5 -2 1 3  ....................................................................................................................... 2 4  
1. 5  
St u d y Rati o nale  ........................................................................................................................... 2 9  
1. 6  
S u m mar y of  K n o w n a n d P ote ntial Ris ks a n d Be nefits t o H u ma n S u bj ects  ............................... 3 0  
2  
S T U D Y O BJ E C TI V E S  ........................................................................................................................ 3 1  
3  
I N V E S TI G A TI O N A L P L A N .............................................................................................................. 3 2  
3. 1  
St u d y Desi g n ............................................................................................................................... 3 2  
3. 2  
Esti mate d St u d y D urati o n  ........................................................................................................... 3 3  
4  
S T U D Y P O P U L A TI O N  ....................................................................................................................... 3 4  
4. 1  
N u m ber of S u bjects  .................................................................................................................... 3 4  
4. 2  
St u d y Ce nters  .............................................................................................................................. 3 4  
4. 3  
I ncl usi o n Criteria ........................................................................................................................ 3 4  
4. 4  
E xcl usi o n Criteria  ....................................................................................................................... 3 5  
4. 5  
Scree ni n g  .................................................................................................................................... 3 5  
4. 6  
Wit h dra wal Criteria  .................................................................................................................... 3 5  
4. 7  
Re place me nts  .............................................................................................................................. 3 6  
4. 8  
Treat me nt Di sc o nti n uati o n ......................................................................................................... 3 6  
5  
S T U D Y T R E A T M E N T  ....................................................................................................................... 3 7  
V V- C LI N- 0 6 3 8 9 9 6 1. 0


B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 1 1  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
5. 1  
I n vesti gati o nal Pr o d uct ............................................................................................................... 3 7  
5. 2  
D osa ge a n d A d mi nistrati o n  ........................................................................................................ 3 7  
5. 3  
Treat me nt Assi g n me nt  ................................................................................................................ 3 7  
5. 4  
Bli n di n g  ...................................................................................................................................... 3 8  
5. 5  
Treat me nt C o m pli a nce ............................................................................................................... 3 8  
5. 6  
Misse d D oses  .............................................................................................................................. 3 8  
5. 7  
Pr o d uct Acc o u nta bilit y  ............................................................................................................... 3 9  
5. 8  
C o nc o mita nt Me dicati o ns a n d Pr oce d ures  ................................................................................. 3 9  
5. 8. 1  C ortic oster oi ds  ............................................................................................................................ 3 9  
5. 8. 2  S yste mic c G V H D T hera pies ....................................................................................................... 3 9  
5. 8. 3  T o pical / Or ga n S pecific T hera pies f or c G V H D  ........................................................................ 3 9  
5. 8. 4  C Y P 3 A 4 I n d ucers  ...................................................................................................................... 3 9  
5. 8. 5  Dr u gs Pr ol o n gi n g t he Q Tc I nter val  ............................................................................................ 4 0  
5. 8. 6  Pr o hi bite d C o nc o mita nt Me dicati o ns  ......................................................................................... 4 0  
5. 9  
Treat me nt of O ver d ose  ............................................................................................................... 4 0  
5. 1 0  
D ose M o dificati o n G ui deli nes  .................................................................................................... 4 0  
6  
S T U D Y A S S E S S M E N T S A N D P R O C E D U R E S  ............................................................................... 4 2  
6. 1  
Sc he d ule of Assess me nts  ............................................................................................................ 4 2  
6. 2  
St u d y Visits ................................................................................................................................. 4 2  
6. 2. 1  Scree ni n g  .................................................................................................................................... 4 2  
6. 2. 2  Baseli ne Visit  .............................................................................................................................. 4 2  
6. 2. 3  M o nt h 3 Visit a n d E ver y 3 M o nt h Visits T hereafter ( ± 1 4 da ys)  ............................................... 4 3  
6. 2. 4  2 8 Da y F oll o w -U p Visit  ............................................................................................................. 4 4  
6. 2. 5  L o n g -ter m F oll o w-u p  ................................................................................................................. 4 5  
6. 2. 6  U nsc he d ule d Visit  ....................................................................................................................... 4 5  
6. 3  
Effica c y E n d p oi nts ..................................................................................................................... 4 5  
6. 4  
Safet y E n d p oi nts  ......................................................................................................................... 4 6  
7  
S A F E T Y  ............................................................................................................................................... 4 8  
7. 1  
Safet y Para meters  ....................................................................................................................... 4 8  
7. 2  
A d verse E ve nt Defi niti o n  ........................................................................................................... 4 8  
7. 3  
E val uati n g A d verse E ve nts  ......................................................................................................... 4 8  
7. 3. 1  Seri o us A d verse E ve nts  .............................................................................................................. 4 9  
7. 3. 2  Pr ot oc ol -Relate d A d verse E ve nts  ............................................................................................... 5 0  
7. 3. 3  Relati o ns hi p t o St u d y Dr u g  ........................................................................................................ 5 0  
7. 3. 4  Rec or di n g A d verse E ve nts  ......................................................................................................... 5 0  
V V- C LI N- 0 6 3 8 9 9 6 1. 0


B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 1 2  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
7. 3. 5  Seri o us A d verse E ve nt Re p orti n g  ............................................................................................... 5 0  
7. 3. 5. 1  
Ti mefra me f or Re p orti n g  ..................................................................................................... 5 0  
7. 3. 5. 2  
S A E I nf or mati o n t o be Pr o vi de d b y t he I n vesti gat or  ........................................................... 5 1  
7. 3. 5. 3  
Pre g na nc y  ............................................................................................................................. 5 2  
7. 3. 5. 4  
Re g ulat or y Re p orti n g  ........................................................................................................... 5 3  
7. 4  
Ot her Safet y C o nsi derati o ns  ....................................................................................................... 5 3  
7. 4. 1  La b orat or y Data  .......................................................................................................................... 5 3  
7. 4. 2  F oll o w -U p of A d verse E ve nts  .................................................................................................... 5 4  
8  
S T U D Y S T O P PI N G R U L E S  ............................................................................................................... 5 5  
9  
S T A TI S TI C A L C O N SI D E R A TI O N S  ................................................................................................. 5 6  
9. 1  
H y p ot hesis  .................................................................................................................................. 5 6  
9. 2  
Sa m ple Size a n d P o wer Calc ulati o n  ........................................................................................... 5 6  
9. 3  
A nal ysis P o p ulati o ns  .................................................................................................................. 5 6  
9. 4  
S u b gr o u p A nal yses  ..................................................................................................................... 5 6  
9. 5  
Data A nal ysis  .............................................................................................................................. 5 6  
9. 6  
I nteri m A nal ysis ......................................................................................................................... 5 6  
9. 7  
Efficac y A nal yses  ....................................................................................................................... 5 6  
9. 8  
E x pl orat or y A nal yses  ................................................................................................................. 5 6  
9. 9  
Safet y A nal yses  .......................................................................................................................... 5 7  
9. 1 0  
P har mac o ki netic A nal yses  .......................................................................................................... 5 7  
9. 1 1  
P har mac o d y na mic A nal yses  ....................................................................................................... 5 7  
1 0  D A T A Q U A LI T Y A S S U R A N C E  ....................................................................................................... 5 8  
1 1  R E G U L A T O R Y O B LI G A TI O N S & C O M P LI A N C E S T A T E M E N T  ............................................... 5 9  
1 2  E T HI C A L A S P E C T S  ........................................................................................................................... 6 0  
1 2. 1  
L ocal Re g ulati o ns  ....................................................................................................................... 6 0  
1 2. 2  
I nf or me d C o nse nt ....................................................................................................................... 6 0  
1 2. 3  
Researc h Et hics C o m mittees  ...................................................................................................... 6 1  
1 2. 4  
F ut ure Use of S u bject Sa m ples  ................................................................................................... 6 1  
1 3  C O N DI TI O N S F O R M O DI F YI N G T H E P R O T O C O L  ...................................................................... 6 2  
1 4  C O N DI TI O N S F O R T E R MI N A TI N G T H E S T U D Y  ......................................................................... 6 3  
1 5  S T U D Y D O C U M E N T A TI O N, C R F S, A N D R E C O R D K E E PI N G  ................................................... 6 4  
1 5. 1  
I n vesti gat or’s Files a n d Rete nti o n of D oc u me nts ....................................................................... 6 4  
1 5. 2  
S o urce D oc u me nts a n d Bac k gr o u n d Data  .................................................................................. 6 4  
V V- C LI N- 0 6 3 8 9 9 6 1. 0


B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 1 3  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
1 5. 3  
A u dits a n d I ns pecti o ns  ................................................................................................................ 6 5  
1 5. 4  
Electr o nic Case Re p ort F or ms  .................................................................................................... 6 5  
1 6  M O NI T O RI N G O F T H E S T U D Y  ....................................................................................................... 6 6  
1 7  C O N FI D E N TI A LI T Y O F T RI A L D O C U M E N T S A N D S U BJ E C T R E C O R D S  ............................... 6 7  
1 8  P U B LI C A TI O N O F D A T A A N D P R O T E C TI O N O F T R A D E S E C R E T S  ....................................... 6 8  
1 9  R E F E R E N C E S  ..................................................................................................................................... 6 9  
A p pe n di x  A: Sc he d ule of Assess me nts  ...................................................................................................... 7 2  
A p pe n di x  B: Cli nicia n -re p orte d Gl o bal c G V H D Acti vit y Assess me nt ...................................................... 7 4  
A p pe n di x  C: c G V H D Res p o nse Assess me nt  .............................................................................................. 7 8  
A p pe n di x  D: Lee c G V H D S y m pt o m Sc ore  ................................................................................................ 7 9  
A p pe n di x  E: Kar n ofs k y Perf or ma nce Scale  ............................................................................................... 8 0  
A p pe n di x  F: E q uati o ns t o Pre dict Gl o mer ular Filtrati o n Rate ( M D R D -4)  ................................................. 8 1  
A p pe n di x  G: Deter mi ni n g Relati o ns hi p of A Es t o St u d y Dr u g  .................................................................. 8 2  
A p pe n di x  H: Dr u gs t hat I n d uce C Y P 3 A 4  ................................................................................................... 8 4  
A p pe n di x  I: Dr u gs T hat I n d uce a n d I n hi bit C Y P 1 A 2 ................................................................................ 8 5  
A p pe n di x  J: Dr u gs T hat Pr ol o n g Q T c ........................................................................................................ 8 6  
A p pe n di x  K: Pre d nis o ne D ose E q ui vale nts  ................................................................................................ 8 7  
 
L I S T O F T A B L E S  
T a ble 1.  
Pri mar y Efficac y E n d p oi nt Res ults fr o m St u d y K D 0 2 5 -2 0 8  ............................................ 2 2  
T a ble 2.  
Safet y Res ults fr o m St u d y K D 0 2 5 -2 0 8  ............................................................................ 2 3  
T a ble 3.  
Pri mar y Efficac y E n d p oi nt Res ults fr o m St u d y K D 0 2 5 -2 1 3  ............................................ 2 7  
T a ble 4.  
Safet y Res ults fr o m St u d y K D 0 2 5 -2 1 3  ............................................................................ 2 8  
T a ble 5.  
G ui deli nes f or t he Ma na ge me nt of T E A Es wit h Bel u m os u dil Treat me nt  ........................ 4 0  
T a ble 6.  
Bel u m os u dil D ose Decre me nts  ......................................................................................... 4 1  
T a ble 7.  
Sc he d ule of Assess me nts  .................................................................................................. 7 2  
T a ble 8.  
E xa m ples of Cli nical I n d ucers o f C Y P 3 A 4 ...................................................................... 8 4  
T a ble 9.  
E xa m ples of Cli nical I n d ucers/I n hi bit ors of C Y P 1 A 2  ..................................................... 8 5  
T a ble 1 0.  
E xa m ples of Dr u gs t hat Pr ol o n g Q T c  ............................................................................... 8 6  
V V- C LI N- 0 6 3 8 9 9 6 1. 0


B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 1 4  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
 
L I S T O F FI G U R E S  
N o t a ble of fi g ures e ntries f o u n d.  
 
V V- C LI N- 0 6 3 8 9 9 6 1. 0


B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 1 5  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
LI S T O F A B B R E VI A TI O N S   
A E  
A d verse e ve nts  
B A/ B E  
Bi oa vaila bilit y/ Bi oe q ui v ale nce  
BI D  
T wice dail y  
CI  
C o nfi de nce i nter val  
C ma x  
Ma xi m u m c o nce ntrati o n o n c o nce ntr ati o n -ti me c ur ve 
C NI  
Calci ne uri n i n hi bit or  
C R  
C o m plete res p o nse  
C S R  
Cli nical St u d y Re p ort  
C T C A E  
C o m m o n Ter mi n ol o g y Criteria f or A d verse E v e nts  
c G V H D  
C hr o nic graft -v ers us -h ost disease  
D O R  
D urati o n of res p o ns e  
E C G  
Electr ocar di o gra m  
E C P  
E xtrac or p oreal p h ot o p heresis  
e C R F 
Electr o nic case re p ort f or m  
E O S  
E n d -of -St u d y  
E O T  
E n d -of -Treat me nt  
F D A  
F o o d a n d Dr u g A d mi nistrati o n  
F F S  
Fail ure -free s ur vi val 
G C P  
G o o d Cli nical Practice  
GI  
Gastr oi ntesti nal  
H C T  
He mat o p oietic cell tr a ns pla ntati o n  
I B 
I n v esti gat or’s Br oc h ure 
I C F 
I nf or me d C o nse nt F or m 
I E C 
I n d e pe n de nt Et hics C o m mittee 
I L 
I nterle u ki n 
I N D 
I n v esti gati o nal Ne w Dr u g 
I R B 
I nstit uti o nal Re vie w B oar d 
K P S  
Kar n ofs k y Perf or ma n ce Scale  
L R  
Lac k of res p o nse  
L S S  
Lee c G V H D S y m pt o m Scale  
L T F U  
L o n g -t er m F oll o w-u p  
Me d D R A  
Me dical Dicti o nar y of Re g ul at or y Acti vities  
M H C  
Maj or H ist oc o m pati bilit y C o m ple x  
mI T T  
M o difie d I nte nt -t o-Treat P o p ulati o n  
NI H  
Nati o nal I nstit ute s of Healt h  
V V- C LI N- 0 6 3 8 9 9 6 1. 0


B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 1 6  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
O S  
O verall s ur vi val  
P E  
P h ysical e x a mi nati o n  
P K  
P har mac o ki netic  
P R  
Partial res p o nse  
P T  
Preferre d Ter m  
Pt R  
P oi nt re d ucti o n  
Q D  
O nce dail y  
R O C K  
R h o -ass ociate d c oile d -c oil ki nases  
S A E  
Seri o us a d verse e ve nt  
T E A E  
Treat me nt -e mer ge nt a d verse e v e nt  
T F H  
T f ollic ular hel per  
T H 1 7  
T hel per cell 1 7  
T T N T  
Ti me t o ne xt treat me nt  
V V- C LI N- 0 6 3 8 9 9 6 1. 0


B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 1 7  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
1  I N T R O D U C TI O N  
1. 1  C hr o nic Gr aft -v ers us -H ost Dise ase   
C hr o nic graft vers us h ost disease (c G V H D) re m ai ns a maj or c o m plicati o n of all o ge neic 
he mat o p oietic cell tra ns pla ntati o n ( H C T) i n v ol vi n g m ulti ple or ga ns a n d occ urri n g i n u p t o 
7 0 %  of tra ns pla nt r eci pie nt s de pe n di n g u p o n d o n or a n d tra ns pla nt c haracteristic s.1  M ultice nter 
a n d re gistr y data s h o w a c u m ulati ve i nci de nce of 3 0 % t o 5 0 %. 2 ,3  Patie nts wit h c G V H D re q uire 
pr ol o n ge d i m m u n os u p pressi ve treat me nt f or a n a vera ge of 2 t o 3 years fr o m t he i nitial dia g n osis, 
wit h 1 0 % of t h ose s ur vi vi n g  f or at least 7 years still re q uiri n g i m m u n os u p pressi ve treat me nt at 
t hat ti me a n d be y o n d.4  
Gl uc oc ortic oi ds, wit h or wit h o ut calci ne uri n i n hi bit or s ( C NIs), re mai n t he sta n dar d i nitial 
treat me nt, b ut are ass ociate d wit h si g nifica nt si de effects a n d u nsatisfact or y o utc o mes, 
partic ularl y f or patie nts wit h hi g h -ris k feat ures of c G V H D.5 
Base d u p o n d ata fr o m St u d y K D 0 2 5 -2 1 3, t he F o o d a n d Dr u g A d mi nistrati o n ( F D A) a p pr o ve d 
R E Z U R O C K ( b el u m os u dil)  f or t he treat me nt of a d ult a n d pe diatric patie nts 1 2 years a n d ol d er 
wit h c G V H D  after fail ure of at least 2  pri or li nes of s yste mic t hera p y  (Secti o n  1. 4. 2 ).6  T his is t he 
sec o n d F D A a p pr o ve d dr u g i n dicat e d s pecifi call y f or patie nts wit h c G V H D. 
T he first F D A a p pr o ve d c G V H D t hera p y is I br uti ni b (I M B R U VI C A) f or t he treat me nt of a d ult 
patie nts wit h c G V H D aft er fail ure of o ne or m ore li nes of s yste mic t hera p y base d u p o n data fr o m 
a n o pe n-la b el st u d y ( St u d y 1 1 2 9; N C T 0 2 1 9 5 8 6 9) of 4 2 s u bjects wit h c G V H D w h o ha d faile d 
first-li ne c ortic oster oi d t h era p y a n d re q uir e d a d diti o nal t hera p y.7 
1. 2  R h o -A ss oci ate d P r otei n  K i n ases  
R h o -ass ociate d c oile d -c oil ki nases ( R O C Ks) pla y a ce ntr al r ole i n t he c o ntr ol of acti n 
c yt os kel et o n asse m bl y a n d cell ular f u ncti o ns, s uc h as pr oliferati o n, a d hesi o n, mi grati o n a n d 
p ha g o c yt osis. 8 ,9 ,1 0 ,1 1 T w o is of or ms of R O C K ha ve bee n i de ntifie d, R O C K 1 a n d R O C K 2, w hic h  
are acti vate d b y R h o G T Pases a n d pr o m ote acti n -m y osi n me diate d c o ntractile f orce ge nerati o n 
via seri ne -t hr e o ni ne ph os p h or ylati o n o f n u m er o us d o w nstrea m tar gets.  D uri n g t he i m m u ne 
res p o nse, R O C K si g nali n g is critic al i n t he c o or di nati o n a n d bala nci n g of T-cell -me diate d 
i m m u ne res p o nses, i ncl u di n g cell ular m o ve me nt, T-cell rece pt or ( T C R) si g nali n g a n d t h e 
ac q uisiti o n of t he a p pr o priat e T-cell effect or pr o gra m. 1 2 ,1 3    H o we ver, o nl y t he R O C K 2 is of or m 
was s h o w n t o be p h ysi ol o gic all y acti vate d i n C D 4 + T cells u n der T h el per 1 7 ( T H 1 7) s ke wi n g, 
lea di n g t o i ncreas e d secreti o n of i nterle u ki n- (I L-)1 7 a n d I L -2 1 i n b ot h mice a n d h u ma ns. 1 4 ,1 5  
V V- C LI N- 0 6 3 8 9 9 6 1. 0


B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 1 8  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
M ore o ver, tar get e d R O C K 2 i n hi biti o n effecti vel y decrease d I L -1 7 pr o d u cti o n i n vi v o a n d 
a meli orate d t he s p o nta n e o us de vel o p me nt of art hritis, dia betes a n d l u p us i n mice.1 5  A d diti o nall y, 
R h o -ass ociate d pr otei n ki nase ( R O C K ) acti vit y was i ncrease d i n p atie nts wit h r he u mat oi d 
art hritis  a n d s yste mic l u p us er yt h e mat os us.1 4 ,1 6 ,1 7  T he s pecific i n hi biti o n of R O C K 2 t heref ore 
has be e n e x a mi ne d f or its p ote ntial as a t hera p y f or a ut oi m m u ne dis or ders.  
1. 3  N o n -cli nic al B ac k gr o u n d of Bel u m os u dil   
Bel u m os u dil  is a n orall y a vaila ble R O C K 2 selecti ve i n hi bit or.  Data fr o m a P hase  1 cli nical trial 
de m o nstrate d  t hat oral a d mi nistrati o n of bel u m os u dil  to healt h y h u ma n s u bj ects d o w n -re g ulates 
t he a bilit y of T cells t o secrete I L-2 1 a n d I L -1 7, b ut n ot i nterfer o n - i n r es p o nse t o T C R 
sti m ulati o n e x vi v o.  Treat me nt wit h bel u m os u dil als o pr o m otes t he s u p pressi ve f u ncti o n of 
re g ulat or y T cells t hr o u g h u p-re g ulati o n of S T A T 5 p h os p h or ylati o n a n d p ositi ve re g ul ati o n of 
F o x p 3 e x pressi o n .1 8 
C hr o nic G V H D re mai ns a maj or c o m plicati o n f oll o wi n g all o ge n eic b o ne m arr o w 
tra ns pla ntati o n. 1 9  T he u n derl yi n g p at h o ge nesis of G V H D is si milar t o a ut oi m m u ne attac k i n a 
n u m ber of res p ects, i ncl u di n g a c o ntri b ut or y r ole of pr o -i nfla m mat or y T H 1 7 a n d T f ollic ular 
hel per ( T F H) cells a n d a pr otecti ve r ole of T  re g ul at or y cells.2 0  I n a d diti o n, t he a berra nt 
acti vati o n of i m m u ne cel ls lea ds t o i ncreas e d secreti o n of tra nsf or mi n g gr o wt h fact or- w hic h 
pr o m otes fi br o blast acti v ati o n, c olla ge n pr o d ucti o n , a n d de vel o p me nt of tiss ue fi br osis .2 1  
Bel u m os u d il effecti vel y a meli orates c G V H D i n m ulti ple m o dels: a f ull maj or hist oc o m pati bilit y 
c o m ple x (M H C )-mis matc h m o del of br o nc hi olitis o blitera ns s y n dr o me t hat i n v ol ve d a wi de 
s pectr u m of tar get or ga ns i ncl u di n g l u n g a n d li ver 2 2 as well as a mi n or M H C -mis matc h m o del of 
scler o der m at o us G V H D. 2 3  Treat me nt wit h bel u m os u dil  res ulte d i n n or malizati o n of pat h o ge nic 
p ul m o nar y f u ncti o n, w hi c h c orrelates wit h a mar ke d re d ucti o n of a nti b o d y a n d c olla ge n 
de p ositi o n i n t he l u n gs of treate d mice t o le vels c o m para ble t o n o n -c G V H D c o ntr ols. 2 4  S plee ns 
of mice treate d wit h bel u m os u dil ha d decrease d fre q ue nc y of T F H a n d i ncrease d fre q ue n c y of T 
f ollic ular re g ulat or y cells, acc o m pa ni e d b y a re d ucti o n i n S T A T 3 a n d c o nc urre nt i ncrease i n 
S T A T 5 p h os p h or ylati o n. To get her t hese d ata hi g hli g ht t he p ote ntial of tar gete d R O C K 2 
i n hi biti o n f or c G V H D t h era p y. 
R efer t o t he Bel u m os u dil  I n v esti gat or’s Br oc h ure (I B)  f or m or e detaile d i nf or mati o n. 
V V- C LI N- 0 6 3 8 9 9 6 1. 0


B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 1 9  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
1. 4  Cli nic al B ac k gr o u n d of Bel u m os u dil   
Bel u m os u dil  was well t olerate d i n P hase  1 st u dies of healt h y v ol u nteers at si n gle d oses u p t o 
1 0 0 0  m g, a n d wit h r e peat d oses u p t o 5 0 0  m g t wice dail y ( BI D ) f or 2 8 da ys. 
A d mi nistrati o n of bel u m os u dil  2 0 0  m g ta blet s i n t he fe d state res ulte d i n an a p pr o xi mate 2 -f ol d 
i ncreas e d e x p os ure i n ter ms of ma xi m u m c o nce ntrati o n ( C ma x ) a n d area u n der t he c o n ce ntr ati o n -
ti me c ur ve (A U C ) w he n c o m pare d t o t he fas te d st ate.  P har mac o ki n etic  ( P K) a nal yses s h o w e d 
t hat bel u m os u dil  a d mi nistere d as a 2 0 0  m g t a blet i n t he fe d state  was ra pi dl y a bs or be d wit h a  
me dia n  ti me of ma xi m u m c o nce ntrati o n of a p pr o xi matel y 3  h o urs.  Eli mi nati o n half -life is 
a p pr o xi matel y 7 h o urs .  Varia bilit y i n e x p os ure relate d para m eters C ma x  a n d A U C was re d uce d 
w he n bel u m os u dil  was a d mi nistere d i n t he fe d state w he n c o m pare d t o t he faste d state.  
Bel u m os u dil  s h o ul d be ta ke n wit h f o o d. 
Data fr o m St u d y K D 0 2 5 -2 0 8  a n d St u d y K D 0 2 5 -2 1 3  i n s u bjects wit h c G V H D are s u m marize d i n 
S ecti o n 1. 4. 1  a n d Secti o n  1. 4. 2 , res pecti vel y. 
R efer t o t he Bel u m os u dil  I B f or m ore d etaile d i nf or mati o n. 
1. 4. 1  
St u d y K D 0 2 5 -2 0 8   
Details of t he o bjecti ve, desi g n, efficac y res ults, a n d safet y res ults are a v aila ble i n t he 
St u d y  K D 0 2 5 -2 0 8 C li nic al S t u d y R e p ort ( C S R) , 0 7 J ul y 2 0 2 0 a n d are s u m marize d bel o w.  
O bjecti ves:  
T he pri mar y o bje cti ves of St u d y K D 0 2 5 -2 0 8 were t o e val uate t he acti vit y of bel u m os u dil i n 
s u bjects wit h ster oi d-de p e n de nt c G V H D a n d acti v e disease i n ter ms of p artial res p o nse ( P R) a n d 
c o m plete res p o nse ( C R) ; a n d safet y a n d t olera bilit y of bel u m os u dil i n s u bjects wit h c G V H D. 
I n cl usi o n/ E x cl usi o n Criteria: 
T he maj or i ncl usi o n criteria were: ( 1) mal e  a n d fe male s u bjects ≥ 1 8 years of a ge wit h all o ge n eic 
b o ne marr o w tra ns pla nt or H C T ; ( 2) recei vi n g gl u c oc ortic oi d t hera p y a n d calci ne uri n t hera p y or 
gl uc o c ortic oi d t hera p y al o n g f or c G V H D; ( 3) p ersiste nt acti ve c G V H D ma nifestati o ns ; 
( 4) ≤ 3  pri or li nes of treat me nt f or c G V H D; a n d ( 5) Kar n ofs k y Perf or m a nce Scale  ( K P S) sc ore 
>  4 0.  Details of i ncl usi o n criteria are pr ovi de d i n t he K D 0 2 5 -2 0 8 Pr ot oc ol, Secti o n 7. 2 . 
V V- C LI N- 0 6 3 8 9 9 6 1. 0


B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 2 0  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
T he  maj or e x cl usi o n criteria were: ( 1) recei vi n g a n i n vesti gati o nal G V H D treat me nt wit hi n 
2 8  da ys of st u d y e ntr y; ( 2) ac ute G V H D; ( 3) ta ki n g ot her i m m u n os u p pressa nt dr u gs f or G V H D 
i ncl u di n g ma m malia n  tar get of ra p a m yci n ( m T O R) i n hi bit ors; a n d ( 4) ta ki n g a n y m e dicati o n 
k n o w n t o be a m o derate or str o n g i n hi bit or of t he C Y P 3 A 4  is oz y me or a n y dr u gs k n o w n t o b e 
m o derate or str o n g C Y P 3 A 4 i n hi bit ors.  Details of e x cl usi o n criteria are pr o vi de d i n t he 
K D 0 2 5 -2 0 8 Pr ot oc ol, Secti o n  7. 2 . 
St u d y Desi g n  
St u d y K D 0 2 5 -2 0 8 w as a P hase 2a, o pe n -l a bel, d os e-escalati o n, safet y, t olera bilit y, a n d acti vit y 
st u d y of bel u m os u dil i n s u bjects wit h c G V H D.  A p pr o xi matel y 4 8 s u bjects were t o be e nr olle d t o 
recei v e oral b el u m os u dil i n 3 c o h orts, eac h c o h ort c o nsisti n g of 1 6 s u bject s ( 1: 1: 1 fas hi o n): 
b el u m os u dil 2 0 0 m g Q D ( C o h ort 1); b el u m os u dil 2 0 0 m g BI D ( C o h ort 2); a n d b el u m os u dil 4 0 0 
m g Q D ( C o h ort 3).  Bel u m os u dil was t o be a d mi nistere d i n 2 8 -da y c ycles u ntil disease 
pr o gressi o n or u nacce pta ble t o xicit y.  
Efficac y assess me nts i ncl u de d usi n g t he criteria of 2 0 1 4 NI H C o nse ns us De vel o p me nt Pr oject o n 
Cli nical Trials i n c G V H D  res p o nse ( C R, P R, or lac k of res p o nse [u nc ha n ge d, mi x e d, or 
pr o gressi o n ]), c G V H D se verit y (cli nical-re p orte d) a n d s y m pt o m (s u bject-re p orte d), a n d Lee 
c G V H D S y m pt o m Scale ( L S S).  
Safet y assess me nts i ncl u d e d p h ysi cal e xa mi nati o ns ( P Es); vital si g n meas ure me nts; bl o o d 
sa m ple c ollecti o n f or he mat ol o g y a n d c he mistr y; uri nal ysis; electr ocar di o gra ms  ( E C Gs); a d v erse 
e ve nt (A E ) assess me nts; c o nc o mita nt me dicati o n assess me nts ; a n d pre g n a nc y t esti n g f or fe m ales 
of c hil d beari n g p ote ntial.  
A F oll o w -u p Safet y Visit occ urre d 2 8 da ys ( ± 7 d a ys) after t h e last d ose of st u d y dr u g.  
S u bjects were c o ntacte d a p pr o xi matel y e ver y 8 wee ks via tele p h o n e, e mail, or p ostal mail t o 
c o nfir m s ur vi val stat us a n d t he i nitiati o n of a n y a nti-ca ncer treat me nt or a n y c h a n ges i n treat me nt 
of c G V H D . 
Dis p ositi o n of S u bjects  
O verall, 6 4 s u bjects w ere scree n e d f or t h e st u d y  of w h o m 5 4 were i n cl u de d i n t he m o difie d 
I nte nt-t o-Treat ( mI T T ) P o p ulati o n: 1 7 s u bjects i n C o h ort 1, 1 6 s u bjects i n C o h ort 2, a n d 
2 1  s u bjects i n C o h ort 3.  As of t he c ut-off date f or t his a nal ysis ( 1 9 Fe br uar y 2 0 2 0), 4 7 ( 8 7. 0 %) 
s u bjects ha ve disc o nti n ue d treat me nt a n d 7 ( 1 3. 0 %) s u bjects re mai n o n tr eat me nt wit h 
V V- C LI N- 0 6 3 8 9 9 6 1. 0


B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 2 1  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
bel u m os u dil.  T he m ost f re q ue nt r eas o n f or treat m e nt disc o nti n uati o n was disease pr o gressi o n 
( 2 2 [ 4 0. 7 %] s u bjects).  A t otal of 3 7 ( 6 8. 5 %) s u bjects were p artici pati n g i n t he st u d y, eit her bei n g 
acti vel y treat e d wit h bel u m os u dil or bei n g f oll o we d f or s ur vi val (i n L o n g -ter m F oll o w -U p).  
Se ve ntee n ( 3 1. 5 %) s u bjects ha ve disc o nti n ue d fr o m t he st u d y f or t he f oll o wi n g reas o ns: 
1 1  ( 2 0. 4 %) s u bjects die d, 5 ( 9. 3 %) s u bjects w ere l ost t o f oll o w-u p, a n d 1 ( 1. 9 %) s u bject 
disc o nti n ue d f or ot her reas o ns.  T he o verall me dia n f oll o w -u p d urati o n was  2 8. 8 m o nt hs: 
3 5. 9  m o nt hs f or C o h ort 1 ; 3 2. 4 m o nt hs f or C o h ort 2 ; a n d 2 4. 0 m o nt hs f or C o h ort 3.  
De m o gra p hics a n d Baseli ne C haract eristics  
O verall, s u bjects ha d a m e dia n a ge of 5 1. 5 years , were pre d o mi na ntl y male ( 3 4 [ 6 3. 0 %]) , a n d 
W hite ( 4 7 [ 8 7. 0 %]).  T hirt y -ni n e  ( 7 2. 2 %) s u bjects ha d a K P S sc ore ≥ 8 0.   M ost s u bjects ha d n o 
pre vi o us a ut ol o g o us tra ns pla nts ( 4 5 [ 8 3. 3 %] s u bjects) ; all ha d recei ve d a pre vi o us all o ge n eic 
tra ns pla nt.  T he me dia n ti me t o c G V H D dia g n osis fr o m tra ns pla nt was 7. 9  m o nt hs.  T he me di a n 
ti me fr o m c G V H D di a g n osis t o st u d y e nr oll me nt was 2 0. 0 m o nt hs. 
T he o verall me dia n n u m ber of pri or li nes of s yst e mic c G V H D t hera p y was 2. 0.   
T hirt y -fi ve ( 7 2. 9 %) s u bjects were refract or y t o t h e last s yste mic c G V H D treat me nt pri or t o 
e nr oll me nt i n t he st u d y.   All s u bjects ha d recei ve d c o nc o mita nt c ortic oster oi d me dicati o n at st u d y 
i nitiati o n; ot her c o m m o n c o nc o mita nt me dicati o ns recei v e d at Baseli ne  were C NI ( 2 3  s u bjects, 
4 2. 6 %), a n d e xtrac or p oreal p h ot o p h eresis (E C P ; 1 2 s u bjects, 2 2. 2 %).  
Efficac y  
T he p ri mar y efficac y e n d p oi nts are pres e nte d i n  Ta ble 1 .   
T he O R R was 6 4. 8 % ( 9 5 %  c o nfi de n ce i nter val [ CI ]: 5 0. 6 %, 7 7. 3 %) acr oss all 3 c o h orts:  
6 4. 7 %  ( 9 5 % CI: 3 8. 3 %, 8 5. 8 %) i n C o h ort 1 ; 6 8. 8 % ( 9 5 % CI: 4 1. 3 %, 8 9. 0 %) i n C o h ort 2 ; a n d 
6 1. 9 % ( 9 5 % CI: 3 8. 4 %, 8 1. 9 %) i n C o h ort 3.  All res p o nses were P Rs.  T he l o wer b o u n d of t he 
9 5 % CI ar o u n d t he O R R e x cee de d 3 0 % o v erall a n d f or eac h c o h ort.  
 
 
V V- C LI N- 0 6 3 8 9 9 6 1. 0


B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 2 2  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
 
Ta ble 1 . 
Pri m ar y Effic ac y E n d p oi nt Res ults fr o m St u d y K D 0 2 5 -2 0 8  
Pri m ar y Effic ac y O utc o me s 
C o h ort 1  
2 0 0 m g Q D  
 N  =  1 7  
C o h ort 2  
2 0 0 m g BI D  
 N  =  1 6  
C o h ort 3  
4 0 0 m g Q D  
 N  =  2 1  
 
O ver all  
 N  =  5 4  
O R R  ( C R or  P R)  - n  ( %) 
1 1  ( 6 4. 7) 
1 1  ( 6 8. 8) 
1 3  ( 6 1. 9) 
3 5  ( 6 4. 8) 
9 5 %  CI of O R R  
( 3 8. 3, 8 5. 8) 
( 4 1. 3, 8 9. 0) 
( 3 8. 4, 8 1. 9) 
( 5 0. 6, 7 7. 3)  
B est res p o nse  
C R  
0  ( 0) 
0  ( 0) 
0  ( 0) 
0  ( 0) 
P R  
1 1  ( 6 4. 7) 
1 1  ( 6 8. 8) 
1 3  ( 6 1. 9) 
3 5  ( 6 4. 8) 
L R  
L R -U nc ha n ge d  
2  ( 1 1. 8) 
3  ( 1 8. 8) 
4  ( 1 9. 0) 
9  ( 1 6. 7) 
L R -Mi xe d  
3  ( 1 7. 6) 
1  ( 6. 3) 
0  ( 0) 
4  ( 7. 4) 
L R -P r o gressi o n 
1  ( 5. 9) 
0  ( 0) 
1  ( 4. 8) 
2  ( 3. 7) 
N o  res p o nse assess me nt  
0  ( 0) 
1  ( 6. 3) 
3  ( 1 4. 3) 
4  ( 7. 4) 
BI D =  t wice dail y; CI  =  c o nfi de nce  i nter val; C R  =  c o m plete res p o nse;  L R  =  Lac k  of  Res p o nse; mI T T  =  m o difie d  I nte nt-t o-Treat;  
NI H  =  Nati o nal I nstit utes  of Healt h; O R R =  O verall Res p o nse  Rate; P R  =  partial  res p o nse; Q D =  o nce  dail y.  
N ote:  mI T T P o p ulati o n . 
N ote:  T he perce nta ges were calc ulate d base d o n t he n u m ber of s u bjects i n t he mI T T P o p ulati o n  
 
Safet y  
T he me dia n d urati o n of treat me nt o verall was 8. 4 m o nt hs: 8. 5 m o nt hs f or C o h ort 1 ; 7. 5 m o nt hs 
f or C o h ort 2; a n d 9. 0 m o nt hs f or C o h ort 3.  O verall, 4 2. 6 % of s u bjects recei ve d > 1 2 m o nt hs of 
bel u m os u dil treat me nt.  T he me dia n relati ve d ose i nte nsit y was 9 8. 3 %: 9 9. 1 % f or C o h ort 1 ; 
9 6. 6 % f or C o h ort 2 ; a n d 9 9. 1 % f or C o h ort 3.  
Safet y res ults are pres e nte d i n  Ta ble 2 . 
I n t otal, 1 8 ( 3 3. 3 %) s u bjects e x perie nce d a treat me nt-e mer ge nt A E ( T E A E ) lea di n g t o 
disc o nti n ua ti o n of treat me nt: 6  ( 3 5. 3 %) s u bjects i n C o h ort 1; 5  ( 3 1. 3 %) s u bjects i n C o h ort 2; a n d 
7  ( 3 3. 3 %) s u bjects i n C o h ort 3.  T w o s u bjects disc o nti n ue d bel u m os u dil treat me nt f or A Es 
c o nsi dere d pr o ba bl y rel ate d t o bel u m os u dil: 1 s u bject i n C o h ort 1 ( hea d ac h e  a n d diarr hea ) a n d 
1  s u bject i n C o h ort 3 (fati g ue).  O verall, 1 1 s u bjects e x perie nce d a seri o us T E A E  ( S A E) t hat le d 
t o disc o nti n uati o n of treat me nt: 3 s u bjects i n C o h ort 1; 2 s u bjects i n C o h ort 2 ; a n d 6 s u bjects i n 
C o h ort 3 .  No ne of t hese seri o us S A Es  were c o nsi dere d relate d t o bel u m os u dil.   I n C o h ort 3, 
4  ( 1 9. 0 %) s u bjects e x perie nce d a S A E  t hat le d t o deat h.  Ho we v er , n o n e were c o nsi dere d relat e d 
t o bel u m os u dil .  N o s u bjects die d i n C o h orts 1 or 2 d ue t o a S A E . 
V V- C LI N- 0 6 3 8 9 9 6 1. 0


B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 2 3  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
Ta ble 2 . 
S afet y Re s ults fr o m St u d y K D 0 2 5-2 0 8  
S afet y O utc o mes  
C o h ort 1  
2 0 0 m g Q D  
N  =  1 7  
n ( %) 
C o h ort 2  
2 0 0 m g BI D  
N  =  1 6  
n ( %) 
C o h ort 3  
4 0 0 m g Q D  
N  =  2 1  
n ( %) 
 
O ver all  
N  =  5 4  
n ( %) 
S u bj ects  wit h at least 1  T E A E  
1 7  ( 1 0 0) 
1 6  ( 1 0 0) 
2 0  ( 9 5. 2) 
5 3  ( 9 8. 1) 
 
S u bj ects  wit h  T E A Es b y  ma xi m u m  se verit y 
   Gra de 3:  S e vere 
8  ( 4 7. 1) 
8  ( 5 0. 0) 
6  ( 2 8. 6) 
2 2  ( 4 0. 7) 
   Gra de 4:  L ife-t hreate ni n g 
1  ( 5. 9) 
2  ( 1 2. 5) 
4  ( 1 9. 0) 
7  ( 1 3. 0) 
   Gra de 5:  F atal 
0  ( 0) 
0  ( 0) 
4  ( 1 9. 0) 
4  ( 7. 4) 
T E A Es  b y P T  occ urri n g i n  >  2 0 %  s u bjects o verall 
   U p per  res pirat or y tract i nfecti o n 
9  ( 5 2. 9) 
9  ( 5 6. 3) 
7  ( 3 3. 3) 
2 5  ( 4 6. 3) 
   Diarr hea  
6  ( 3 5. 3) 
5  ( 3 1. 3) 
7  ( 3 3. 3) 
1 8  ( 3 3. 3) 
   Na usea  
6  ( 3 5. 3) 
4  ( 2 5. 0) 
8  ( 3 8. 1) 
1 8  ( 3 3. 3) 
   Fati g ue  
6  ( 3 5. 5) 
3  ( 1 8. 8) 
9  ( 4 2. 9) 
1 8  ( 3 3. 3) 
   D ys p nea  
3  ( 1 7. 6) 
6  ( 3 7. 5) 
7  ( 3 3. 3) 
1 6  ( 2 9. 6) 
   Hea dac he  
4  ( 2 3. 5) 
3  ( 1 8. 8) 
6  ( 2 8. 6) 
1 3  ( 2 4. 1) 
   E de ma peri p heral  
3  ( 1 7. 6) 
4  ( 2 5. 0) 
6  ( 2 8. 6) 
1 3  ( 2 4. 1) 
   C o u g h  
1  ( 5. 9) 
4  ( 2 5. 0) 
7  ( 3 3. 3) 
1 2  ( 2 2. 2) 
   H y perte nsi o n  
5  ( 2 9. 4) 
2  ( 1 2. 5) 
4  ( 1 9. 0) 
1 1  ( 2 0. 4) 
 
 
 
 
 
S u bj ects  wit h ≥ 1  st u d y 
dr u g -relate d T E A E  
8  ( 4 7. 1) 
8  ( 5 0. 0) 
1 4  ( 6 6. 7) 
3 0  ( 5 5. 6) 
St u d y dr u g -relate d T E A Es b y P T  occ urri n g  i n >  1 0 % of  s u bjects o verall  
   Fati g ue  
1  ( 5. 9) 
2  ( 1 2. 5) 
3  ( 1 4. 3) 
6  ( 1 1. 1) 
   Na usea  
2  ( 1 1. 8) 
1  ( 6. 3) 
3  ( 1 4. 3) 
6  ( 1 1. 1) 
 
 
 
 
 
S u bj ects  wit h at least 1  Gra de  3  T E A E  
9  ( 5 2. 9) 
1 0  ( 6 2. 5) 
1 4  ( 6 6. 7) 
3 3  ( 6 1. 1) 
Gra de  3  T E A Es  b y P T  occ urri n g  i n  5 % of  s u bj ects o verall 
   D ys p nea  
1  ( 5. 9) 
2  ( 1 2. 5) 
4  ( 1 9. 0) 
7  ( 1 3. 0) 
   G G T  i ncrease d 
2  ( 1 1. 8) 
2  ( 1 2. 5) 
0  ( 0) 
4  ( 7. 4) 
   H y per gl yce mia  
2  ( 1 1. 8) 
0  ( 0) 
2  ( 9. 5) 
4  ( 7. 4) 
   H y p o xia  
1  ( 5. 9) 
1  ( 6. 3) 
2  ( 9. 5) 
4  ( 7. 4) 
   A ne mia  
2  ( 1 1. 8) 
1  ( 6. 3) 
0  ( 0) 
3  ( 5. 6) 
   L u n g i nfecti o n  
0  ( 0) 
1  ( 6. 3) 
2  ( 9. 5) 
3  ( 5. 6) 
S u bj ects  wit h ≥ 1  st u d y dr u g -
relate d Gra de  3  T E A E  
1  ( 5. 9) 
3  ( 1 8. 8) 
2  ( 9. 5) 
6  ( 1 1. 1) 
St u d y dr u g -relate d Gra de   3  T E A Es b y P T  occ urri n g i n  >  3 %  if s u bjects o verall 
   A L T i ncrease d 
1  ( 5. 9) 
1  ( 6. 3) 
0  ( 0) 
2  ( 3. 7) 
   A S T i ncrease d 
1  ( 5. 9) 
1  ( 6. 3) 
0  ( 0) 
2  ( 3. 7) 
 
 
 
 
 
S u bj ects  wit h at least 1  S A E  
5  ( 2 9. 4) 
6  ( 3 7. 5) 
1 2  ( 5 7. 1) 
2 3  ( 4 2. 6) 
S A Es  b y  P T occ urri n g i n  >  2 % s u bjects o verall  
   D ys p nea  
0  ( 0) 
1  ( 6. 3) 
3  ( 1 4. 3) 
4  ( 7. 4) 
   L u n g i nfecti o n  
0  ( 0) 
1  ( 6. 3) 
2  ( 9. 5) 
3  ( 5. 6) 
   H y p o xia  
0  ( 0) 
0  ( 0) 
2  ( 9. 5) 
2  ( 3. 7) 
   I nfl ue nza-li ke ill ness 
0  ( 0) 
0  ( 0) 
2  ( 9. 5) 
2  ( 3. 7) 
 
 
 
 
 
V V- C LI N- 0 6 3 8 9 9 6 1. 0


B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 2 4  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
S afet y O utc o mes  
C o h ort 1  
2 0 0 m g Q D  
N  =  1 7  
n ( %) 
C o h ort 2  
2 0 0 m g BI D  
N  =  1 6  
n ( %) 
C o h ort 3  
4 0 0 m g Q D  
N  =  2 1  
n ( %) 
 
O ver all  
N  =  5 4  
n ( %) 
S u bj ects wit h T E A E lea di n g t o d ose 
disc o nti n uati o n  
6 ( 3 5. 3)  
5 ( 3 1. 3)  
7 ( 3 3. 3)  
1 8 ( 3 3. 3)  
 
 
 
 
 
S u bj ects wit h a st u d y dr u g -relate d T E A E 
lea di n g t o d ose disc o nti n uati o n 
2 ( 1 1. 8)  
0  
1 ( 4. 8)  
3 ( 5. 6)  
 
 
 
 
 
S u bj ects wit h T E A E lea di n g t o deat h  
0  
0  
4 ( 1 9. 0)  
4 ( 7. 4)  
A L T  =  ala ni ne a mi n otra nsferase; A S T  =  as partate a mi n otra nsferase;  BI D =  t wice dail y; G G T =  ga m ma  gl uta m yl tra nsferase ; 
Me d D R A  =  Me dical  Dicti o nar y f or Re g ulat or y  Acti vities; P T  =  preferr e d  ter m; Q D  =  o nce  dail y;  S A E = seri o us 
(treat me nt-e mer ge nt a d verse e ve nt); T E A E = treat me nt-e mer ge nt a d verse  e ve nt. 
N ote:  Safet y P o p ulati o n  
 
 
C o ncl usi o ns  
I n t his hea vil y pre-tr eate d p o p ulati o n wit h acti ve c G V H D, b el u m os u dil de m o nstrate d cli nical 
acti vit y a n d a treat me nt effect at all 3 d ose le vels wit h c o nsiste nt res p o nse rates o verall as well as 
i n s u b gr o u p p o p ulati o ns.  N ot o nl y di d bel u m os u dil s h o w hi g h perce nta ge of o verall res p o nse, 
b ut t he res p o nses were cli nicall y mea ni n gf ul, d ura ble, a n d ass ociat e d wit h i m pr o ve me nt i n 
meas ures of s y m pt o m sc ore a n d re d ucti o n i n c orti c oster oi d d ose.   Wit h a me dia n f oll o w -u p 
d urati o n of 2 9 m o nt hs, t hese res ults s u g gest a fa v ora ble be n efit/ris k pr ofile wit h bel u m os u dil f or 
t he treat me nt of s u bje cts wit h c G V H D after 1 t o 3 li nes of pri or t hera p y. 
1. 4. 2  
St u d y K D 0 2 5 -2 1 3   
Details of t he o bjecti ve, desi g n, efficac y res ults, a n d safet y res ults are a v aila ble i n t he 
St u d y  K D 0 2 5 -2 1 3 C S R , 1 6 J ul y 2 0 2 0 , a n d are s u m marize d bel o w. 
O bjecti ves  
T he o bjecti ve of St u d y K D 0 2 5 -2 1 3 was t o e v al uat e t he efficac y a n d safet y of bel u m os u dil at 
d ose le vels of 2 0 0 m g Q D  a n d 2 0 0 m g BI D i n s u bjects wit h c G V H D w h o ha d pre vi o usl y bee n 
treate d wit h at least 2 pri or li nes of s yst e mic t hera p y. 
I n cl usi o n/ E x cl usi o n Criteria 
T he maj or i ncl usi o n criteria were: ( 1) ≥ 1 2 years of a ge w h o ha d all o ge nei c H C T ; ( 2) pre vi o usl y 
recei v e d at least 2 a n d n ot m ore t ha n 5 li nes of s yste mic t hera p y f or c G V H D; ( 3) recei ve d 
V V- C LI N- 0 6 3 8 9 9 6 1. 0


B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 2 5  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
gl uc o c ortic oi d t hera p y wit h a sta ble d ose of t he 2 wee ks pri or t o scree ni n g; a n d ( 4) ha d p ersiste nt 
c G V H D ma nifestati o ns s uc h t hat s yste mic t h era p y was i n dicate d.  Details of i n cl usi o n criteria 
are pr o vi d e d i n t he K D 0 2 5 -2 1 3 Pr ot oc ol, Secti o n 4. 3 . 
T he maj or e x cl usi o n criteria were: ( 1) n ot bee n o n a sta ble d ose/re gi me n of s yste mic c G V H D 
treat me nts f or at least 2 wee ks pri or t o scree ni n g; ( 2) hist ol o gic rela pse of t he u n derl yi n g ca n cer 
or p ost -tra ns pla nt l y m p h o pr oliferati ve dise ase at t he ti me of scree ni n g; a n d (3 ) 3 0 c urre nt 
treat me nts wit h i br uti ni b ( pri or treat me nt wit h i br uti ni b was per mitte d wit h a was h o ut of 
≥ 2 8  da ys pri or t o ra n d o mizati o n ).  Details of e x cl usi o n criteria are pr o vi d e d i n t he 
St u d y  K D 0 2 5 -2 1 3 Pr ot oc ol, Secti o n  4. 4 . 
St u d y Desi g n  
St u d y K D 0 2 5 -2 1 3 w as a n o pe n -la bel, r a n d o mize d, m ultice nter st u d y i n s u bjects ≥ 1 2 years of 
a ge wit h c G V H D w h o ha d pre vi o usl y b ee n treate d wit h ≥ 2 pri or li nes of s yste mic t hera p y.  
I n t he ori gi nal pr ot oc ol, after a 2-wee k s cree ni n g p eri o d, 1 2 6 s u bjects wit h acti ve c G V H D were 
t o be ra n d o mize d i n a 1: 1 fas hi o n t o recei ve 1 of 2 treat me nt re gi me ns wit h bel u m os u dil:  
•  Ar m A:  Bel u m os u dil 2 0 0 m g Q D  
•  Ar m B:  Bel u m os u dil 2 0 0 m g BI D  
H o we ver, wit h A me n d m e nt 2, t he sa m ple siz e was i ncrease d wit h 2 0 a d diti o nal a d olesce nt 
s u bjects a n d 2 0 a d ult s u bjects i nt o a site -s pecific C o m pa ni o n St ud y t o c oll ect bi os peci me ns.  
T hese a d diti o nal 4 0 s u bjects were als o be ra n d o mize d  i n a 1: 1  fas hi o n t o Ar m A or Ar m B.  
Ra n d o mizati o n was stratifie d acc or di n g t o pri or c G V H D treat me nt wit h i br uti ni b ( Yes/ N o) a n d 
se vere c G V H D at Baseli ne  ( Yes/ N o). 
S u bjects r ecei v ed  2 8 -da y treat me nt c ycl es u ntil cli nicall y si g nifica nt pr o gressi o n of c G V H D.  
S u bjects w h o di d n ot ac hie ve d a res p o nse after 1 2 c ycles of b el u m os u dil were wit h dra w n if , i n 
t he I n v esti gat or’s j u d g me nt, t here was n o e vi de nce of cli nical be nefit.  After treat me nt was 
st o p pe d, s u bjects ha d a 4 -wee k F oll o w -u p V isit. 
T he pri mar y e n d p oi nt w as t he O R R, wit h res p o nses as defi ne d b y t he 2 0 1 4 NI H C o nse ns us 
De vel o p me nt Pr oject o n cli nical trials i n c G V H D.  
V V- C LI N- 0 6 3 8 9 9 6 1. 0


B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 2 6  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
Dis p ositi o n of S u bjects  
O verall, 1 3 2 s u bjects recei ve d at least 1 d ose of bel u m os u dil: 6 6 s u bjects i n Ar m A a n d 
6 6  s u bjects i n Ar m B. 
As of t he c ut off date , 1 9 Fe br uar y 2 0 2 0, t he me di a n f oll o w -u p d urati o n was 7. 9  m o nt hs: 
8. 0  m o nt hs f or Ar m A a n d 7. 9 m o nt hs f or Ar m B.  I n t otal, 6 2 ( 4 7. 0 %) s u bj ects ha d  disc o nti n ue d 
fr o m treat me nt; 7 0 ( 5 3. 0 %) re mai n o n tr eat me nt wit h bel u m os u dil.  T he m ost fre q ue nt reas o ns 
f or treat me nt disc o nti n uati o n were pr o gressi o n of c G V H D ( 1 6 [ 1 2. 1 %] s u bjects) a n d wit h dra wal 
b y s u bject ( 1 4 [ 1 0. 6 %]).  A t otal of 1 1 9 ( 9 0. 2 %) s u bjects  partici pate d  i n t he st u d y, eit her acti vel y 
treate d wit h bel u m os u dil or f oll o we d f or s ur vi val.  T hirtee n ( 9. 8 %) s u bjects ha d  disc o nti n ue d 
fr o m t he st u d y: 8 ( 6. 1 %) s u bjects die d; 3  ( 2. 3 %) s u bjects wit h dre w; 1 ( 0. 8 %) s u bject l ost t o 
f oll o w-u p ; a n d 1 ( 0. 8 %) s u bject  f or w hic h d ata was missi n g. 
De m o gra p hic a n d Baseli ne C haracteristics  
O verall, s u bjects ha d a m e dia n a ge of 5 5. 5 years a n d were pre d o mi na ntl y male ( 7 5 [ 5 6. 8 %] 
s u bjects), W hite ( 1 1 2 [ 8 4. 8 %] s u bjects), a n d n ot His pa nic or Lati n o ( 1 1 0 [ 8 3. 3 %] s u bjects).   I n 
t otal, 1 0 3 ( 7 8. 0 %) s u bjects ha d a K P S  ≥ 8 0.  
All s u bjects ha d recei ve d a pre vi o us all o ge n eic tra ns pla nt.  T he m ost fre q ue nt i n dicati o n s f or t he 
m ost rece nt tra ns pla nt r ecei ve d b y s u bjects i ncl u d e d ac ute m yel o ge n o us le u ke mia ( 5 3 [ 4 0. 2 %] 
s u bjects), ac ute l y m p h o blastic le u ke mia ( 1 9 [ 1 4. 4 %] s u bjects), ot her ( 1 8 [ 1 3. 6 %] s u bjects), a n d 
m yel o d ys plastic  s y n dr o me ( 1 3 [ 9. 8 %] s u bjects).  T he maj orit y of s u bjects ha d pri or ac ute G V H D  
( 9 3 [ 7 0. 5 %] s u bjects): 4 2 ( 6 3. 6 %) s u bjects i n Ar m A a n d 5 1 ( 7 7. 3 %) s u bjects i n Ar m  B.  T h e 
me dia n ti me t o c G V H D dia g n osis fr o m t he m ost rece nt tra ns pl a nt was 6. 8 m o nt hs.  T he me dia n 
ti me fr o m c G V H D di a g n osis t o st u d y e nr oll me nt was 2 8. 9 m o nt hs: 2 5. 2 m o nt hs i n Ar m A a n d 
3 0. 2  m o nt hs i n Ar m B.   T he o verall me dia n n u m ber of pri or li nes of s yst e mic c G V H D t hera p y 
was 3. 0  f or Ar m A a n d 4. 0 f or Ar m B.  O verall , 7 9 ( 7 2. 5 %) s u bjects wit h k n o w n stat us were 
refract or y t o t he last s yst e mic c G V H D treat me nt pri or t o e nr oll me nt i n t he st u d y (sta ble dise ase 
or pr o gressi ve dise ase ): 4 5 ( 8 0. 4 %) s u bjects i n Ar m A a n d 3 4 ( 6 4. 2 %) s u bj ects i n Ar m B.   All 
s u bjects were t a ki n g a c o nc o mita nt c G V H D me di cati o n, m ost fre q ue ntl y pre d nis o ne 
( 1 2 8 [ 9 7. 0 %] s u bjects), tacr oli m us ( 4 8 [ 3 6. 4 %] s u bjects), E C P  ( 4 1 [ 3 1. 1 %] s u bjects), a n d 
sir oli m us ( 3 6 [ 2 7. 3 %] s u bjects). 
Efficac y  
T he pri mar y efficac y e n d p oi nt, O R R, is prese nte d i n  Ta ble 3 . 
V V- C LI N- 0 6 3 8 9 9 6 1. 0


B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 2 7  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
At t he c ut off date, 6  m o nt hs after t he last s u bject first visit, t he O R R wit h bel u m os u dil w as 
7 3. 5 % ( 9 5 % CI: 6 5. 1 %, 8 0. 8 %): 7 2. 7 % ( 9 5 % CI: 6 0. 4 %, 8 3. 0 %) i n Ar m A a n d 7 4. 2 % ( 9 5 % CI: 
6 2. 0 %, 8 4. 2 %) i n Ar m  B.  Acr oss b ot h ar ms, 4 ( 3. 0 %) s u bjects a c hie ve d C R a n d 9 3 ( 7 0. 5 %) 
s u bjects ac hie v e d P R.  Res p o nse rates b et wee n t he 2 ar ms were n ot n oticea bl y d iffere nt. 
Ta ble 3 . 
Pri m ar y Effic ac y E n d p oi nt  Res ults fr o m St u d y K D 0 2 5 -2 1 3  
Res p o nse R ate  
Ar m A  
2 0 0 m g  Q D  
N  =  6 6  
Ar m B 
2 0 0 m g  BI D  
N  =  6 6  
O ver all  
N = 1 3 2  
O R R ( C R  or  P R)  - n ( %) 
4 8 ( 7 2. 7) 
4 9 ( 7 4. 2) 
9 7 ( 7 3. 5) 
C R  
3 ( 4. 5) 
1  ( 1. 5) 
4 ( 3. 0) 
P R  
4 5  ( 6 8. 2) 
4 8  ( 7 2. 7) 
9 3  ( 7 0. 5) 
E xact met h o d  
9 5 %  CI of O R R  
( 6 0. 4, 8 3. 0) 
( 6 2. 0, 8 4. 2) 
( 6 5. 1, 8 0. 8) 
BI D = t wice dail y; CI  =  c o nfi de nce i nter val;  C R  = c o m plete res p o nse;  mI T T =  m o difie d I nte nt -t o-Treat;  O R R  = O verall  
Res p o nse Rate; P R = partial res p o nse;  Q D = o nce dail y  
N ote: mI T T P o p ulati o n  
N ote: 2 -si de d, e xact CI was cal c ulate d usi n g t he Cl o p per-P ears o n met h o d.  
N ote: R es ults b ase d o n c ut off dat a date 1 9 Fe br uar y 2 0 2 0.  
 
Safet y  
T he me dia n d urati o n of treat me nt  i n eac h ar m was 6 . 7 m o nt hs.  O verall, 6. 1 % of  s u bjects 
recei v e d > 1 2 m o nt hs of bel u m os u dil treat me nt.  T he me dia n relati ve d ose i nte nsit y ( R DI) was 
9 9. 7 %.   O verall , 1 1 0 ( 8 3. 3 %) s u bjects ha d a n R DI > 9 5 %: 5 4 ( 8 1. 8 %) s u bj ects i n Ar m A a n d 5 6 
( 8 4. 8 %) s u bjects i n Ar m B. 
Safet y res ults are pres e nte d i n Ta ble 4 .  
I n t otal, 1 3 0 ( 9 8. 5 %) s u bjects e x perie nce d ≥ 1 T E A E : 6 5 ( 9 8. 5 %) s u bjects i n Ar m A a n d 
6 5  ( 9 8. 5 %) s u bjects i n Ar m B.  T hirt y -fi ve ( 2 6. 5 %) s u bjects e x perie nce d ≥ 1 T E A E t hat le d t o 
d ose i nterr u pti o n: 1 9 ( 2 8. 8 %) s u bjects i n Ar m A a n d 1 6  ( 2 4. 2 %) s u bjects i n Ar m B.  T he m ost 
fre q ue nt T E A E t hat le d t o d ose i nterr u pti o n b y P T was p ne u m o nia ( 7 [ 5. 3 %] s u bjects): 
4  ( 6. 1 %) s u bjects i n Ar m A an d 3 ( 4. 5 %) s u bjects i n Ar m B.  Fi ve ( 3. 8 %) s u bjects e x perie nce d 
≥ 1 T E A E t hat le d t o d ose re d ucti o n: 2 ( 3. 0 %) s u bjects i n Ar m  A a n d 3 ( 4. 5 %) s u bjects i n 
Ar m  B.  
Fi ve s u bjects e x perie n ce d a S A E  t hat le d t o treat me nt disc o nti n uati o n: 4 s u bjects i n Ar m A 
(cell ulitis; as pirati o n; se ptic s h oc k; m ulti ple or ga n d ysf u ncti o n s y n dr o m e) a n d 1 s u bject i n 
Ar m  B (s e psis a n d micr oa n gi o p at hic he m ol ytic a n e mia).  
V V- C LI N- 0 6 3 8 9 9 6 1. 0


B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 2 8  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
Fi ve s u bjects die d wit hi n 2 8 da ys of st u d y tr eat me nt.  F o ur s u bjects die d i n Ar m A d ue t o 
he m ot h ora x; as pirati o n a n d res pirat or y fail ure; se ptic s h oc k, m ulti ple or ga n d ysf u ncti o n 
s y n dr o me; a n d rec urre nt ac ute m yel oi d le u ke mia.  O ne s u bject die d i n Ar m B d ue t o car diac 
arrest.  T h e A E  of m ulti ple or ga n d ysf u ncti o n s y n dr o me was c o nsi d ere d  relate d t o bel u m os u dil.  
All ot her A E s t hat le d t o deat h were n ot c o nsi dere d relate d t o bel u m os u dil. 
Ta ble 4 . 
S afet y Res ults fr o m St u d y K D 0 2 5 -2 1 3  
S afet y O utc o mes  
Ar m A  
2 0 0 m g Q D  
N = 6 6  
n ( %)  
Ar m B  
2 0 0 m g BI D  
N = 6 6  
n ( %)  
O ver all  
N = 1 3 2  
n ( %)  
S u bj ects wit h  at least 1 T E A E  
6 5 ( 9 8. 5)  
6 5 ( 9 8. 5)  
1 3 0 ( 9 8. 5)  
S u bj ects wit h T E A Es b y ma xi m u m se verit y  
Gra de 1: Mil d  
5 ( 7. 6)  
4 ( 6. 1)  
9 ( 6. 8)  
Gra de 2: M o derate  
2 5 ( 3 7. 9)  
3 1 ( 4 7. 0)  
5 6 ( 4 2. 4)  
Gra de 3:  S e vere 
2 9  ( 4 3. 9) 
2 6  ( 3 9. 4) 
5 5  ( 4 1. 7) 
Gra de 4: L ife-t hreate ni n g 
2 ( 3. 0) 
3  ( 4. 5) 
5  ( 3. 8) 
Gra de 5: F atal 
4 ( 6. 1) 
1  ( 1. 5) 
5  ( 3. 8) 
T E A Es  b y  P T occ urri n g i n >  2 0 %  s u bjects o verall 
Fati g ue  
2 6  ( 3 9. 4) 
1 6 ( 2 4. 2) 
4 2 ( 3 1. 8) 
Diarr hea  
2 0  ( 3 0. 3) 
1 8  ( 2 7. 3) 
3 8  ( 2 8. 8) 
Na usea  
1 7 ( 2 5. 8) 
1 7  ( 2 5. 8) 
3 4  ( 2 5. 8) 
C o u g h  
1 9 ( 2 8. 8) 
1 3  ( 1 9. 7) 
3 2  ( 2 4. 2) 
D ys p nea  
2 0 ( 3 0. 3) 
1 1  ( 1 6. 7) 
3 1  ( 2 3. 5) 
U p per  res pirat or y tract i nfecti o n 
1 4  ( 2 1. 2) 
1 6  ( 2 4. 2) 
3 0  ( 2 2. 7) 
E de ma  peri p heral  
1 7  ( 2 5. 8) 
1 1  ( 1 6. 7) 
2 8  ( 2 1. 2) 
 
 
 
 
S u bj ects wit h at least 1  st u d y dr u g-relate d T E A E  
4 7  ( 7 1. 2) 
3 6  ( 5 4. 5) 
8 3  ( 6 2. 9) 
St u d y dr u g -relate d T E A Es b y P T occ urri n g i n >  1 0 % of  s u bjects o verall  
Fati g ue  
1 4  ( 2 1. 2) 
1 1 ( 1 6. 7) 
2 5 ( 1 8. 9) 
Na usea  
8  ( 1 2. 1) 
7  ( 1 0. 6) 
1 5  ( 1 1. 4) 
 
 
 
 
S u bj ects wit h at least 1  Gra de  3  T E A E  
3 5 ( 5 3. 0) 
3 0  ( 4 5. 5) 
6 5  ( 4 9. 2) 
Gra de  3  T E A Es b y  P T occ urri n g  i n  5 % of s u bjects o verall  
P ne u m o nia  
5  ( 7. 6) 
5 ( 7. 6) 
1 0  ( 7. 6) 
H y perte nsi o n  
3  ( 4. 5) 
4 ( 6. 1) 
7 ( 5. 3) 
S u bj ects wit h at least 1  st u d y dr u g -relate d Gra de  3  T E A E  
1 1  ( 1 6. 7) 
9  ( 1 3. 6) 
2 0  ( 1 5. 2) 
St u d y  dr u g -relate d Gra de 3  T E A Es  b y P T  occ urri n g i n  >  1 % of  s u bjects o verall 
Fati g ue  
0  ( 0) 
2  ( 3. 0) 
2  ( 1. 5) 
G G T  i ncrease d 
2 ( 3. 0) 
0  ( 0) 
2  ( 1. 5) 
Hea dac he  
0  ( 0) 
2  ( 3. 0) 
2  ( 1. 5) 
H y perte nsi o n  
0  ( 0) 
2 ( 3. 0) 
2 ( 1. 5) 
Na usea  
1  ( 1. 5) 
1 ( 1. 5) 
2 ( 1. 5) 
 
 
 
 
S u bj ects  wit h at least 1 S A E  
2 7  ( 4 0. 9) 
1 8  ( 2 7. 3) 
4 5  ( 3 4. 1) 
S A E s b y  P T occ urri n g i n >  2 % s u bjects o verall  
P ne u m o nia  
6  ( 9. 1) 
4 ( 6. 1) 
1 0  ( 7. 6) 
V V- C LI N- 0 6 3 8 9 9 6 1. 0


B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 2 9  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
S afet y O utc o mes  
Ar m A  
2 0 0 m g Q D  
N = 6 6  
n ( %)  
Ar m B  
2 0 0 m g BI D  
N = 6 6  
n ( %)  
O ver all  
N = 1 3 2  
n ( %)  
P yre xia  
4  ( 6. 1) 
0 ( 0) 
4 ( 3. 0) 
D ys p nea  
1  ( 1. 5) 
2 ( 3. 0) 
3 ( 2. 3) 
L u n g i nfecti o n  
1  ( 1. 5) 
2 ( 3. 0) 
3 ( 2. 3) 
Se psis  
2  ( 3. 0) 
1  ( 1. 5) 
3  ( 2. 3) 
S u bj ects wit h at least 1  st u d y dr u g -relate d seri o us S A E  
6  ( 9. 1) 
1  ( 1. 5) 
7  ( 5. 3) 
 
 
 
 
S u bj ects wit h T E A E lea di n g t o  d ose disc o nti n uati o n  
1 4  ( 2 1. 2) 
9  ( 1 3. 6) 
2 3  ( 1 7. 4) 
S u bj ects wit h st u d y  dr u g -relate d T E A E lea di n g t o  d ose  
disc o nti n uati o n  
 
8  ( 1 2. 1) 
 
5  ( 7. 6) 
 
1 3  ( 9. 8) 
S u bj ects wit h T E A E lea di n g t o deat h  
4  ( 6. 1) 
1 ( 1. 5) 
5 ( 3. 8) 
BI D  = t wice dail y;  c G V H D = graft vers us  h ost  disease;  G G T  =  ga m ma  gl uta m yl tra nsferase; Me d D R A  = Me dical  Dicti o nar y  
f or Re g ulat or y  Acti vities; P T =  preferre d  ter m; Q D = o nce dail y;  S A E = seri o us (treat me nt -e mer ge nt) a d verse e ve nt; T E A E = 
treat me nt-e mer ge nt a d verse  e ve nt. 
N ote s: 
1. Safet y P o p ulati o n  
2. Me d D R A versi o n 2 0. 0.  
3. Defi nitel y relate d, pr o ba bl y relate d, a n d p ossi bl y relate d were all c o nsi dere d as relate d t o bel u m os u dil.  
4. A  s u bject wit h m ulti ple e ve nts wit hi n a cate g or y was c o u nte d o nl y o nce i n t h at cate g or y.  
5. A s u bject wit h m ulti ple c o n diti o ns wit hi n a P T was c o u nte d o nl y o nce f or t h at P T.  
6. T he res ults prese nte d are base d o n t h e data c ut -off date of 1 9 Fe br uar y 2 0 2 0.  
 
C o ncl usi o ns  
Bel u m os u dil at 2 0 0 m g Q D a n d 2 0 0 m g BI D de m o nstrate d cli nicall y m ea ni n gf ul res p o nses i n a 
p o p ulati o n of s u bjects wit h a d va nce d, h ea vil y pre -treate d c G V H D.  T he O R R f or t he mI T T 
P o p ulati o n was 7 3. 5 % ( 9 5 % CI: 6 5. 1, 8 0. 8): 7 2. 7 % ( 9 5 % CI: 6 0. 4, 8 3. 0) i n Ar m A ( Q D) a n d 
7 4. 2 % ( 9 5 % CI: 6 2. 0, 8 4. 2) i n Ar m B ( BI D).  T he p oi nt esti mates a n d 9 5 % CIs all e x cee d e d 
8 0. 8 %.  Res p o nses were d ura ble.  T h ese fi n di n gs were s u p p orte d b y s u b gr o u p a nal yses, a n d b y 
sec o n dar y a n d e x pl orat or y e n d p oi nts.  W hile t he O R R was si milar wit h b ot h d ose le vels, t here 
was a greater  res p o nse wit h BI D d osi n g i n or ga ns s uc h as t he s ki n a n d e ye, a n d a tre n d t o w ar ds a 
l o n ger D O R wit h BI D d osi n g.  T hes e res ults s u g gest a fa v ora bl e be nefit/ris k pr ofile f or b ot h 
d ose le vels.  
1. 5  St u d y R ati o n ale   
St u d y K D 0 2 5 -2 1 7 is a n e xte nsi o n st u d y of s u bjects e nr olle d a n d treate d i n St u d y K D 0 2 5 -2 0 8 
a n d St u d y K D 0 2 5 -2 1 3 . 
M ost s u bjects i n b ot h  St u d y K D 0 2 5 -2 0 8 a n d St u d y K D 0 2 5 -2 1 3  were tr eate d wit h b el u m os u dil at 
2 0 0 m g Q D or 2 0 0 m g BI D a n d ha d si milar i ncl usi o n/e x cl usi o n criteria.  
V V- C LI N- 0 6 3 8 9 9 6 1. 0


B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 3 0  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
St u d y K D 0 2 5 -2 1 7 will b e  a n e xte nsi o n st u d y t o assess t he l o n g -t er m safet y a n d efficac y of t hese 
s u bjects treate d wit h bel u m os u dil, t he b ul k of w h o m were tr eate d wit h 2 0 0 m g Q D or 2 0 0 m g 
BI D, b ut als o s o me treate d wit h 4 0 0 m g Q D.   
1. 6  
S u m m ar y of K n o w n a n d P ote nti al Ris ks a n d Be nefits t o H u m a n S u bjects   
All p ossi ble si de effects r elate d t o bel u m os u dil  are n ot k n o w n ; the B el u m os u dil  I B c o ntai ns data 
o n ris ks ass ociate d wit h t his st u d y dr u g.   
S u bjects ma y recei ve a cli nical be nefit fr o m b el u m os u dil  w hile  s o me s u bjects ma y pr o gress.   
T his st u d y is i nte n de d t o assess t he l o n g -ter m cli ni cal be nefits a n d ris ks of bel u m os u dil f or t he 
treat me nt of c G V H D.  
 
 
V V- C LI N- 0 6 3 8 9 9 6 1. 0


B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 3 1  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
2  S T U D Y O B J E C TI V E S   
T he o bjecti ve of t his st u d y is t o e val uat e l o n g -ter m safet y a n d effi cac y of bel u m os u dil i n s u bjects 
wit h c G V H D w h o h a ve pre vi o usl y b ee n treate d w it h bel u m os u dil i n St u d y K D 0 2 5-2 0 8 or 
St u d y  K D 0 2 5 -2 1 3.  
 
 
 
V V- C LI N- 0 6 3 8 9 9 6 1. 0


B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 3 2  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
3  I N V E S TI G A TI O N A L P L A N  
3. 1  St u d y Desi g n   
T his wil l be a P hase 2, o pe n -la bel, e xte n de d  treat me nt a n d f oll o w-u p st u d y i n s u bjects wit h 
c G V H D w h o ha ve b ee n pre vi o usl y tr eate d wit h b el u m os u dil i n St u d y K D 0 2 5 -2 0 8 (see 
Secti o n  1. 4. 1 ) or i n St u d y K D 0 2 5-2 1 3 (see Secti o n  1. 4. 2 ). 
S u bjects will n ot be scree ne d.  
S u bjects w h o ha ve si g n e d t he I C F will be e nr olle d i n St u d y K D 0 2 5-2 1 7 if t he y h a ve met a n y of 
t he f oll o wi n g c o n diti o ns: 
•  Acti vel y recei vi n g b el u m os u dil  i n St u d y K D 0 2 5-2 0 8  or i n St u d y K D 0 2 5 -2 1 3  (e x cl u di n g 
a d ults i n t he C o m pa ni o n St u d y a n d e x cl u di n g a d olesce nts e nr olle d u n d er K D 0 2 5 -2 1 3 
A me n d me nt 2 [0 1J u ne 2 0 2 0 ]) 
•  Is i n l o n g-ter m f oll o w-u p  ( L F T U) o n St u d y K D 0 2 5 -2 0 8 or St u d y K D 0 2 5 -2 1 3.  
L o n g -t er m f oll o w-u p  will be defi ne d as t h e peri o d after e n di n g tr eat me nt wit h 
bel u m os u dil a n d u ntil a n F F S e v e nt occ urs.  
•  A d ult e nr olle d i n t he C o m pa ni o n St u d y as s pecifi e d i n St u d y K D 0 2 5 -2 1 3 A me n d me nt 2 
( 0 1 J u ne 2 0 2 0) a n d recei ve d at least 6 m o nt hs of treat me nt or is i n L T F U  
After si g ni n g t he I C F, at Baseli ne , s u bjects will u n der g o efficac y ass ess me nts b y 
Cli nicia n -re p orte d Gl o b al c G V H D Acti vit y Assess me nt, res p o nse assess m e nt, p ul m o nar y 
f u ncti o n tests ( P F Ts), Lee S y m pt o m Scale ( L S S) sc ore, a n d d o c u me ntati o n of c ortic oster oi d 
d osa ge a n d/ or ot her t hera pies f or c G V H D.  
S u bjects will u n der g o s afet y assess me nts i ncl u di n g s y m pt o m -direct e d  P E, vital si g ns, wei g ht,  
hei g ht,  K P S, he mat ol o g y a n d cli nical c he mistr y la b orat or y testi n g,  pre g n a n c y t esti n g, 1 2lea d 
E C G, d oc u me nti n g c o nc o mita nt me dicati o ns, a n d m o nit ori n g f or A Es.  S u bjects will c o nti n ue o n 
t heir sa me d osi n g re gi me n t he y recei ve d i n St u d y K D 0 2 5-2 0 8 or St u d y  K D 0 2 5 -2 1 3 : bel u m os u dil 
2 0 0 m g Q D, 2 0 0 m g BI D, or 4 0 0 m g Q D.  If t he I n vesti gat or re d uce d t he s u bject’s d ose  of 
bel u m os u dil i n eit her St u d y  K D 0 2 5 -2 0 8 or St u d y K D 0 2 5 -2 1 3, t he s u bject will  c o nti n ue t o 
recei v e t hat sa me re d uce d d ose treat me nt wit h bel u m os u dil t hr o u g h o ut St u d y K D 0 2 5-2 1 7  or 
u ntil t he A E  t hat le d t o t he te m p orar y d os e re d u cti o n has res ol ve d, i n w hic h case t he d os e 
treat me nt ca n res u me at t he ori gi n al d ose at t he discreti o n of the I n v esti gat or .  S u bjects will be 
V V- C LI N- 0 6 3 8 9 9 6 1. 0


B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 3 3  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
gi ve n a st u d y dr u g diar y t o rec or d dail y d osi n g.  S u bjects ma y b e a d mi nistere d t he first d ose 
eit her i n t he cli nic or self -a d mi nistere d at h o me.  
At 3 m o nt hs after Baseli ne  a n d e v er y 3 m o nt hs t hereafter ( ± 1 4 da ys), s u bj ec ts will re p ort t o t he 
cli nic f or t he sa me efficac y a n d safet y assess me nts a n d dis pe nsi n g of bel u m os u dil  at Baseli ne .  
( Hei g ht is o nl y re q uire d at Bas eli ne .)  T h e st u d y dr u g diaries f or t he past 3 m o nt hs will be 
c ollecte d, a n d n e w st u d y dr u g diaries dis pe ns e d.  A n y re mai ni n g bel u m os u dil will be c ollecte d.  
S u bjects ma y recei ve bel u m os u dil o n St u d y K D 0 2 5 -2 1 7 f or u p t o a n a d diti o nal 2 years , at t he 
discreti o n of t he I n v esti gat or (a n d wit h g ui da nce fr o m t he me dical m o nit or),  be y o n d w hat t he y 
ha d recei ve d i n St u d y K D 0 2 5 -2 0 8 or St u d y K D 0 2 5 -2 1 3,  c G V H D pr o gressi o n , or u nacce pta ble 
t o xicit y. 
Efficac y a n d s afet y e n d p oi nts are descri be d i n Secti o n  6. 3  a n d Secti o n  6. 4 , res pecti vel y. 
S u bjects will ret ur n t o t he cli nic f or a  2 8 -da y  F oll o w -u p Visit at 2 8 da ys ( ± 7 da ys) after t he last 
d ose of st u d y dr u g.  S u bjects will ha ve L F T U  a p pr o xi matel y e ver y 3 m o nt hs u ntil a n  F F S e ve nt 
occ urs .  After t h e 2 8-da y F oll o w -u p Visit has bee n c o m plete d, s u bjects will be c o ntact e d 
a p pr o xi matel y e ver y 3 m o nt hs b y tele p h o ne, e -mail, or p ostal mail t o c o nfir m s ur vi val stat us, 
a n y i nitiati o n of ne w s yst e mic c G V H D t hera pies, a n d rela ps e of u n derl yi n g disease.  
Alter nati vel y, t his i nf or m ati o n ma y b e o btai ne d fr o m t he s u bject ’s me dical rec or ds.  T he 
Sc he d ule of Assess me nts is prese nte d i n  A p pe n di x  A: Sc he d ule of Assess me nts . 
3. 2  Esti m ate d St u d y D ur ati o n   
S u bjects ma y recei ve bel u m os u dil  f or 2 years at t he discreti o n of t he In vesti gat or a n d wit h 
g ui da n ce fr o m t he me dic al m o nit or.  
S u bjects will be treate d wit h bel u m os u dil u ntil c G V H D pr o gressi o n or u n acce pta ble t o xicit y.  
S u bjects will ret ur n t o t he cli nic f or a 2 8 -da y F oll o w -u p Visit ( ± 7 da ys) after t he last d ose of 
st u d y dr u g.  S u bjects will ha ve l o n g -ter m f oll o w-u p a p pr o xi matel y e ver y 3 m o nt hs u ntil a n F F S  
e ve nt occ urs .  After t he 2 8-da y F oll o w -u p Visit has bee n c o m plete d, s u bjects will be c o ntacte d 
a p pr o xi matel y e ver y 3 m o nt hs b y tele p h o ne, e -mail, or p ostal mail t o c o nfir m s ur vi val stat us,  
a n y i nitiati o n of ne w s yst e mic c G V H D t hera pies, a n d rela ps e of u n derl yi n g disease  (see 
Secti o n  3. 1 ).  Alter n ati vel y, t his i nf or mati o n ma y be o btai ne d fr o m t he s u bj ect’s me dical rec or ds. 
 
 
V V- C LI N- 0 6 3 8 9 9 6 1. 0


B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 3 4  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
4  S T U D Y P O P U L A TI O N   
4. 1  N u m ber of S u bjects   
A p pr o xi matel y 7 0 s u bj ects  ma y be e nr olle d . 
4. 2  St u d y Ce nters   
T his st u d y will be c o n d u cte d at a p pr o xi matel y 2 0  sites. 
4. 3  I ncl usi o n Criteri a  
1.  S u bjects m ust ha ve bee n treate d wit h bel u m os u dil f or at least 1 of t h e f oll o wi n g  criteria: 
a. Acti vel y recei vi n g b el u m os u dil o n St u d y K D 0 2 5 -2 0 8  or o n St u d y K D 0 2 5 -2 1 3  
(e x cl u di n g a d ults i n t he C o m pa ni o n St u d y a n d e x cl u di n g a d ol esce nts e nr olle d 
u n der K D 0 2 5 -2 1 3 A me n d me nt 2 [0 1  J u ne 2 0 2 0]) 
b.  Is i n L T F U  o n St u d y K D 0 2 5 -2 0 8  or o n K D 0 2 5 -2 1 3 .  L o n g-t er m F oll o w -u p will 
be defi ne d as t he peri o d after e n di n g tr eat me nt wit h bel u m os u d il a n d u ntil a n F F S 
e ve nt occ urs.  
c. A d ult e nr olle d i n t he C o m pa ni o n St u d y u n d er K D 0 2 5 -2 1 3 A me n d m e nt 2 
( 0 1 J u ne 2 0 2 0) w h o has recei ve d at least 6 m o nt hs of treat me nt of b el u m os u dil or 
is i n l o n g-ter m f oll o w-u p  
2.  Fe male s u bjects of c hil d beari n g p ote ntial ha v e a ne gati ve pre g n a nc y test at e nr oll me nt. 
Fe males of c hil d beari n g p ote ntial are defi ne d as s e x uall y m at ure fe males wit h o ut pri or 
h ysterect o m y or w h o h a v e ha d a n y e vi de nce of me nses i n t he past 1 2  m o nt hs.  H o we ver, 
fe males w h o h a ve bee n a me n orr heic f or 1 2 or more m o nt hs are still c o nsi dere d t o be of 
c hil d beari n g p ote ntial if t he a me n orr hea is p ossi bl y d ue t o pri or c he m ot hera p y, 
a nti-estr o ge ns, or o v aria n s u p pressi o n.  
3.  Se x uall y acti ve fe m ales of c hil d beari n g p ote ntial e nr olle d i n t he st u d y m ust a gree t o use 
2  f orms of acce pte d m et h o ds of c o ntrace pti o n d uri n g t he c o urse of t he st u d y a n d f or 
3  m o nt hs after t heir last d ose of st u d y dr u g. Effecti ve birt h c o ntr ol i ncl u des:  
a. I ntr a uteri ne d e vice pl us 1 barrier m et h o d 
b.  Sta ble d oses of h or m o nal c o ntrace pti o n f or at least 3 m o nt hs (e. g., oral, i njecta ble, 
i m pla nt, tra ns der mal) pl us 1  barrier m et h o d  
V V- C LI N- 0 6 3 8 9 9 6 1. 0


B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 3 5  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
c. 2  barrier m et h o ds.  Effecti ve barrier met h o ds are male or fe m ale c o n d o ms, 
dia p hra g ms, a n d s per mici des (crea ms or gels t hat c o ntai n a c h e mical t o kill 
s per m) or 
d.  A vasect o miz e d part ne r 
4.  F or male s u bjects w h o are se x uall y acti ve a n d w h o are part ners of fe mal es of c hil d beari n g 
p ote ntial: a gree me nt t o use 2  f or ms of c o ntr ace pti o n a n d t o n ot d o nate s per m d uri n g t he 
treat me nt peri o d a n d f or at least 3 m o nt hs after t h e last d ose of st u d y dr u g. 
5.  S u bject ( or t he s u bject ’s l e gall y a ut h orize d re prese ntati ve) is a ble t o pr o vi de writte n 
i nf or me d c o nse nt pri or t o t he perf or m a nce of a n y st u d y-s pecific pr oce d ures. 
6.  It is i n t he best i nterest of t he s u bject t o partici pate i n t he st u d y. 
4. 4  E xcl usi o n Criteri a   
1.  Fe male s u bject w h o is pre g n a nt or breastfee di n g  
2.  S u bject c o nsi dere d u nli k el y t o a d here t o treat me nt a n d/ or f oll o w pr ot oc ol i n t he o pi ni o n of 
t he In v esti gat or  
4. 5  Scree ni n g   
N o scree ni n g will be perf or me d i n t his st u d y.  S u bjects w h o meet t he i ncl usi o n /e xcl usi o n criteria 
will be i ncl u de d o nce t he I C F is si g ne d.  
4. 6  Wit h dr a w al Criteri a   
S u bjects will recei ve b el u m os u dil treat me nt u ntil cli nicall y si g nifica nt pr o gressi o n of c G V H D 
( defi ne d as pr o gressi o n re q uiri n g a d diti o n of ne w s yste mic t hera p y f or c G V H D), hist ol o gic 
rec urre nce of u n derl yi n g mali g na n c y, u nacce pta bl e t o xicit y, I n vesti gat or d ecisi o n, s u bject 
prefere nce/ wit h dra w al of c o nse nt, l oss t o f oll o w -u p, S p o ns or  decisi o n, or deat h ( w hic he ver 
occ urs first).  
S u bjects w h o e x perie nce c G V H D pr o gressi o n as d efi ne d b y NI H criteria b u t f or w h o m n o ne w 
s yste mic t hera p y is pla n n e d ma y c o nti n ue t o recei ve bel u m os u dil a n d be assesse d a gai n at t heir 
ne xt visit .  If pr o gressi o n per NI H criteri a is n ot c o nfir me d or n o ne w s yst e mic t hera p y is 
pla n ne d, s u bjects ma y c o nti n ue o n bel u m os u dil at t he In v esti gat or ’s discreti o n u ntil s u bjects 
f ulfill at least 1 criteri o n re q uiri n g disc o nti n uati o n of st u d y dr u g. 
V V- C LI N- 0 6 3 8 9 9 6 1. 0


B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 3 6  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
Bel u m os u dil ma y b e t a pere d aft er a s ustai ne d res p o nse f or 6 m o nt hs a n d cessati o n of all ot her 
i m m u n os u p pressa nts f or at least 3 m o nt hs.  T he ta peri n g s c he d ule f or bel u m os u dil is descri be d 
i n D osa ge a n d A d mi nistrati o n  5. 2 . 
S u bjects ma y be wit h dra w n fr o m st u d y tr eat me nt at a n y ti me b y t h e I n vesti gat or or t he S p o ns or  
if it is c o nsi dere d detri me ntal f or t he s u bject t o c o nti n ue i n t he st u d y.  T h e reas o n f or wit h drawal 
will  be ca pt ure d i n t he e C R F.  
S u bjects ha ve t he ri g ht t o wit h dra w fr o m t he st u d y at a n y ti me a n d f or a n y reas o n wit h o ut 
prej u dice t o t heir f ut ure me dical care b y t he p h ysi cia n or at t he i nstit uti o n.  If t he s u bject wis hes 
t o v ol u ntaril y wit h dra w fr o m the st u d y, t he p h ysicia n will c o ns ult wit h t he s u bject re gar di n g 
pr oce d ures f or s afe wit h dra wal.  E v er y eff ort s h o ul d be ma de t o ha ve s uc h s u bjects atte n d 
pr ot oc ol visits i ncl u di n g t he 2 8 -da y F oll o w -u p V isit.  R eas o ns f or wit h dra wal of c o nse nt will be 
ca pt ure d i n t he e C R F.  S u bject data u p t o wit h dra wal of c o nse nt will be i n cl u de d i n t he a nal ysis 
of t he st u d y, a n d w h ere p er mitte d, p u blicl y a v aila ble data ca n be i ncl u de d after wit h dra wal of 
c o nse nt.  
4. 7  Re pl ace me nts   
N o s u bjects will be re pla ce d i n t his st u d y.  
4. 8  Tre at me nt Disc o nti n u ati o n   
Reas o ns f or disc o nti n uati o n of treat me nt wit h bel u m os u dil i ncl u de : 
•  Cli nicall y si g nifica nt c G V H D pr o gressi o n re q uiri n g a d diti o n of s yste mic t hera p y  
•  Pr o gressi o n of u n derl yi n g diseas e  as d efi ne d b y esta blis he d disease s pecific criteri a  
•  A n A E t hat re q uires per ma ne nt disc o nti n uati o n of st u d y dr u g  
•  I n v esti gat or decisi o n  
•  Vol u nta r y disc o nti n uati o n / wit h dra wal fr o m st u d y b y s u bject  (su bject ma y re mai n eli gi ble 
f or f oll o w-u p ) 
•  N o nc o m plia nce t o pr ot oc ol  
•  S u bject l ost t o f oll o w -u p  
•  Ter mi nati o n of t he st u d y b y S p o ns or  
•  S u bject deat h  
 
V V- C LI N- 0 6 3 8 9 9 6 1. 0


B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 3 7  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
5  S T U D Y T R E A T M E N T   
5. 1  I n vesti g ati o n al Pr o d uct  
Bel u m os u dil ( 2-( 3-( 4-( 1 H-i n daz ol-5 -yl a mi n o) q ui naz oli n -2 -yl) p he n o x y) -N -is o pr o p yl aceta mi de-
met ha ne s ulf o nic aci d salt ), pre vi o usl y  k n o w n as  K D 0 2 5 , is a n orall y a v aila ble R O C K 2 selecti ve 
i n hi bit or.  B el u m os u dil  will be pr o vi de d as 2 0 0  m g ta blets.  
5. 2  D os a ge a n d A d mi nistr ati o n   
S u bjects will be treate d wit h t he sa me d osa ge of bel u m os u dil as t he y were assi g ne d i n 
St u d y  K D 0 2 5 -2 0 8 or  St u d y K D 0 2 5 -2 1 3:  
•  St u d y K D 0 2 5 -2 0 8:  bel u m os u dil 2 0 0 m g Q D, bel u m os u dil 2 0 0 m g BI D , or bel u m os u dil 
4 0 0 m g Q D  
•  St u d y K D 0 2 5 -2 1 3:  bel u m os u dil 2 0 0 m g Q D or bel u m os u dil 2 0 0 m g  BI D  
 
Bel u m os u dil will be ta pere d aft er a s ustai ne d res p o nse f or 6 m o nt hs a n d cessati o n of all ot her 
i m m u n os u p pressa nts f or at least 3 m o nt hs.  Ta peri n g is als o e x pecte d if s u bjects wit h dra w f or 
reas o ns ot her t h a n c G V H D pr o gressi o n or a d verse e ve nts.  T he ta peri n g sc h e d ule f or 
bel u m os u dil is as f oll o ws:  
 
•  2 0 0 m g Q D → 2 0 0 m g Q O D f or 1 m o nt h → Disc o nti n ue  
•  2 0 0 m g BI D  → 2 0 0 m g Q D  f or 1 m o nt h →2 0 0 m g Q O D f or 1 m o nt h → Disc o nti n ue  
•  4 0 0 m g Q D  → 2 0 0 m g Q D  f or 1 m o nt h →2 0 0 m g Q O D f or 1 m o nt h → Disc o nti n ue  
 
5. 3  Tre at me nt Assi g n me nt   
S u bjects will c o nti n ue t o recei v e t he sa me d os a ge of bel u m os u dil ( 2 0 0 m g Q D, 2 0 0 m g BI D, or 
4 0 0 m g Q D) as t he y w ere assi g n e d i n St u d y K D 0 2 5 -2 0 8 or St u d y K D 0 2 5 -2 1 3.   If t he 
I n v esti gat or re d u ce d t he d ose of bel u m os u dil i n eit her St u d y K D 0 2 5-2 0 8 or St u d y K D 0 2 5 -2 1 3, 
t he s u bject will  c o nti n ue t o recei ve t h at sa me re d u ce d d ose tr eat me nt wit h bel u m os u dil t hr o u g h 
St u d y K D 0 2 5 -2 1 7  or u ntil t he A E  t hat le d t o t he te m p orar y d os e red u cti o n has res ol ve d , i n w hic h 
t he d ose treat me nt ca n res u me at t he ori gi nal d ose at t he discreti o n of t he I n vesti gat or. 
V V- C LI N- 0 6 3 8 9 9 6 1. 0


B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 3 8  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
5. 4  Bli n di n g   
T his will be a n o pe n -la bel st u d y.  N o s u bjects will be bli n de d. 
5. 5  Tre at me nt C o m pli a nce   
S u bjects will be gi ve n a st u d y dr u g diar y t o rec or d t he details of eac h d ose of st u d y dr u g.  
5. 6  Misse d D oses   
S u bjects s h o ul d ma ke e v er y eff ort t o ta ke t h e st u d y dr u g at t he sa me sc h e d ule d ti me dail y wit h 
t heir m or ni n g/e v e ni n g meal or wit hi n 5 mi n utes of c o m pleti n g t he m eal.  I n t he e ve nt t hat t he 
s u bject misses t he pla n ne d d ose of st u d y dr u g, t he pr ot oc ol  bel o w  s h o ul d be f oll o we d: 
F or s u bjects r ecei vi n g st u d y dr u g o n a Q D d osi n g sc he d ule:  
•  If less t ha n 1 2 h o urs of ti me ha ve el a pse d after t he sc he d ule d d ose, t he dr u g s h o ul d be 
ta ke n. T he s u bject s h o ul d t he n res u me t he re g ular pla n ne d dail y d osi n g s c h e d ule t he 
f oll o wi n g da y. 
•  If m ore t ha n 1 2 h o urs of ti me ha ve ela pse d after t he sc he d ule d d os e, t he dr u g s h o ul d be 
s ki p pe d f or t hat da y. T he s u bject s h o ul d t he n res u me t he re g ular pla n ne d d osi n g sc he d ul e 
t he f oll o wi n g da y. 
F or  s u bjects r ecei vi n g st u d y dr u g o n a BI D d osi n g sc h e d ule:  
•  If less t ha n 6 h o urs of ti me ha ve el a pse d after t he sc he d ule d d ose, t he dr u g s h o ul d be 
ta ke n. T he s u bject s h o ul d t he n res u me t he re g ular pla n ne d d osi n g s c he d ule. 
•  If m ore t ha n 6 h o urs of ti me ha ve el apse d after t he sc he d ule d d ose, t he d os e s h o ul d be 
s ki p pe d a n d t he s u bject s h o ul d res u me d osi n g wit h t he ne xt t he re g ular pla n ne d d ose.    
If t he s u bject s ki ps m ore t ha n 7 c o nsec uti ve d a ys of dr u g, t he s u bject s h o ul d be disc o nti n ue d 
fr o m t he st u d y u nless a p pr o ve d b y t he me dical m o nit or a n d I n vesti gat or. 
I n t he e ve nt of v o miti n g, t he s u bject s h o ul d re p ort t he A E a n d s h o ul d n ot ta ke a d diti o nal d oses of 
st u d y dr u g t o c o m pe ns ate. 
V V- C LI N- 0 6 3 8 9 9 6 1. 0


B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 3 9  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
5. 7  Pr o d uct Acc o u nt a bilit y   
I n acc or da n ce wit h re g ul at or y re q uir e me nts, st u d y sites m ust d oc u me nt t he a m o u nt of 
bel u m os u dil  recei ve d fr o m a n d ret ur ne d t o t he S p o ns or , t he a m o u nts of bel u m os u dil dis pe nse d t o 
st u d y s u bjects, a n d t he a m o u nt ret ur ne d b y st u d y s u bjects.  Pr o d uct acc o u nta bilit y rec or ds m ust 
be mai ntai ne d t hr o u g h o ut t he c o urse of t he st u d y .  
5. 8  C o nc o mit a nt Me dic ati o ns a n d Pr oce d ures   
All c o nc o mita nt me dicati o ns i ncl u di n g dietar y/ h er bal/ o ver t he c o u nter s u p ple me nts ta ke n d uri n g 
t he st u d y a n d rele v a nt pr oce d ures will be rec or de d.   I nitiati o n of ne w s yst e mic c G V H D t hera p y 
will be c o nsi dere d a ne w li ne of treat me nt a n d a bel u m os u dil  treat me nt fail ure. 
5. 8. 1  
C ortic ost er oi ds   
C ortic oster oi d d ose data will be c ollecte d t hr o u g h o ut t he st u d y.  C ortic oster oi ds ma y b e ta pere d 
at t he discreti o n of t he I n vesti gat or. 
Tra nsie nt i ncreas es i n c ortic oster oi d d os i n g ( n ot e x cee di n g 1 m g/ k g/ da y pre d nis o ne e q ui vale nt , 
see A p p e n di x  K : Pre d nis o ne D ose E q ui vale nts ) are per mitte d f or t he treat m e nt of c G V H D flare, 
b ut t he d ose m ust be re d uce d wit hi n 6  wee ks.  If t he d ose re m ai ns ele vate d f or m ore t ha n 6  
wee ks,  t his will be c o nsi dere d a b el u m os u dil treat me nt fail ure. 
5. 8. 2  
S yste mic c G V H D T her a pies   
S u bjects ma y be recei vi n g t he sta n d ar d of care s yste mic c G V H D t h era pies s uc h as C NIs  
(tacr oli m us, c ycl os p ori ne), sir oli m us, m yc o p he n ol ate m ofetil , met h otre x ate, rit ux i ma b, or E CP.  
C ha n ges i n d os es of dr u gs t o mai ntai n t hera pe utic le vels are n ot c o nsi dere d as a c ha n ge i n 
d ose/sc he d ule.  
5. 8. 3  
T o pic al / Or g a n S pecific T her a pies f or c G V H D   
Use of t o pical/ or ga n s p ecific t hera pies f or c G V H D is per mitte d  b ut m ust be d oc u me nte d.  
5. 8. 4  
C Y P  3 A 4 I n d ucers   
Use of str o n g C Y P 3 A 4 i n d ucers  decreases bel u m os u dil e x p os ure  (A p pe n di x  H : Dr u gs t hat 
I n d u ce C Y P 3 A 4). 
V V- C LI N- 0 6 3 8 9 9 6 1. 0


B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 4 0  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
5. 8. 5  
Dr u gs Pr ol o n gi n g t he Q Tc I nter v al   
Dr u gs t hat pr ol o n g Q T/ Q Tc s h o ul d be use d wit h ca uti o n (A p pe n di x  J: Dr u gs T h at Pr ol o n g Q Tc ). 
5. 8. 6  
Pr o hi bite d  C o nc o mit a nt Me dic ati o ns   
Treat me nt wit h i n vesti gati o nal s yste mic i m m u n os u p pressa nt dr u gs f or c G V H D (i ncl u di n g 
r u x oliti ni b) is pr o hi bite d. 
5. 9  Tre at me nt o f O ver d ose   
D oses of bel u m os u dil  c o nsi dere d t o re prese nt a n o ver d ose ha v e n ot bee n d efi ne d.  I n cli nical 
st u dies of bel u m os u dil  i n healt h y v ol u nteers, re peat d osi n g of 5 0 0 m g BI D f or 2 8 da ys was 
ge n erall y w el l-t olerate d.  T here are n o k n o w n a nti d otes t o bel u m os u dil ; n o s pecific treat me nt is 
rec o m me n de d i n t he e ve nt of a s us pecte d o ver d ose.  T he tr eati n g I n vesti gat or s h o ul d e m pl o y 
cli nical j u d g me nt i n ma n a gi n g s u bjects wit h s us pecte d o ver d ose.   O ver d ose s h o ul d be re p orte d 
as a n A E (Secti o n  7. 2 ) re gar dless of w h et her  t here are a n y ot h er ass o ciate d A E s.  
5. 1 0  D ose M o dific ati o n G ui deli nes   
A n y cli nicall y si g nifica nt t o xicit y will necessitate c o nsi derati o n of eit her a pa use or cessati o n of 
t hera p y.  G ui deli nes f or ma na ge me nt of tr eat me nt -e mer ge nt t o xicities i n s u bjects recei vi n g 
bel u m os u dil  are o utli ne d i n  Ta ble 5 .  W he n d ose re d ucti o n is necessar y, t he d ose s h o ul d be 
decrease d as s h o w n i n Ta ble 6 . 
Ta ble 5 . 
G ui deli nes f or t he M a n a ge me nt of T E A Es wit h Bel u m os u dil Tre at me nt  
T o xicit y  
Rec o m me n de d Acti o n  
Gra d e 4 or ga n t o xicities 
c o nsi dere d at least 
p ossi bl y relate d t o 
bel u m os u dil  
•  
Disc o nti n ue bel u m os u dil  
Gra d e ≥ 3 L F Ts ( A S T, 
A L T or t otal bilir u bi n) 
re gar dless of attri b uti o n 
t o bel u m os u dil  
•  
H ol d bel u m os u dil  d osi n g u ntil res ol uti o n t o Gra de 1 or bel o w le vels  
•  
C o nsi der res u mi n g bel u m o s u dil.  If res u mi n g, t he n res u me at 1  d ose 
decre me nt  
•  
If t o xicit y rec urs, disc o nti n ue bel u m os u dil  
Ot her Gra d e ≥3 
cli nicall y si g nifica nt 
t o xicities c o nsi dere d at 
least p ossi bl y relate d t o 
bel u m os u dil   
•  
H ol d bel u m os u dil  d osi n g u ntil t o xicit y has res ol ve d t o Gra de 1 or bel o w 
t he n c o nsi der res u mi n g bel u m os u dil . If res u mi n g, t he n res u me at 1  d ose 
decre me nt  
•  
If t o xicit y rec urs, h ol d d ose as a b o ve t he n c o nsi der res u mi n g bel u m os u dil  
at o ne d ose decre me nt  
A L T = ala ni n e a mi n otra nsferase; A S T = as partate a mi n otra nsfer ase; e C R F = electr o nic case re p ort f or m; L F T = li ver f u ncti o n 
test; T E A E = treat me nt-e mer ge nt a d verse e ve nt  
 
V V- C LI N- 0 6 3 8 9 9 6 1. 0


B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 4 1  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
D ose i nterr u pti o n f or u p t o 1 4 da ys f or t o xicit y m a na ge me nt is per mitte d.  S u bjects re q uiri n g 
pa uses of m ore t h a n 1 4  d a ys will be disc o nti n ue d fr o m t he st u d y  u nless a p pr o ve d b y t he m e dical 
m o nit or. 
Ta ble 6 . 
Bel u m os u dil D ose Decre me nts  
Bel u m os u dil D ose  
D ose Re d ucti o n  
4 0 0 m g Q D  
2 0 0 m g Q D  
2 0 0  m g BI D  
2 0 0  m g Q D  
2 0 0  m g Q D  
2 0 0  m g Q O D  
BI D = t wice dail y; Q D =  o nce dail y; Q O D = o nce e ver y ot h er da y  
 
If t he re d u ce d d os e of bel u m os u dil is t olerate d f or 1 m o nt h , t he d ose ma y b e escal ate d t o t he 
pre vi o us d ose.  
 
V V- C LI N- 0 6 3 8 9 9 6 1. 0


B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 4 2  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
6  S T U D Y A S S E S S M E N T S A N D P R O C E D U R E S   
6. 1  Sc he d ule of Assess me nts   
T he efficac y a n d safet y assess me nts f or t his st u d y are prese nte d i n A p pe n di x  A: Sc he d ule of 
Assess me nts . 
6. 2  St u d y Visits   
6. 2. 1  
Scree ni n g   
T his st u d y will  ha ve n o f or mal scree ni n g.  
S u bjects w h o meet all i ncl usi o n/e x cl usi o n criteria a n d si g n t he I C F will be e nr olle d i n t he st u d y.  
6. 2. 2  
B aseli ne  Visit   
S u bjects will be e val uate d t o deter m i ne if t he y meet all i ncl usi o n/e xcl usi o n criteria.  T h os e 
si g ni n g t he I C F will be e nr olle d i n t he st u d y.  
N ote:  If t he s u bject w as i n L T F U  i n St u d y  K D 0 2 5 -2 0 8 or i n St u d y  K D 0 2 5 -2 1 3, t he  s u bject will 
o nl y ha v e L T F U assess m e nts perf or m e d o nce a p pr o xi matel y e v er y 3 m o nt hs  (Secti o n  6. 2. 5 ).   
Bel u m os u dil  will be a d mi nistere d as f oll o ws:  
•  S u bject recei v es sa me d os e of bel u m os u dil as assi g ne d i n St u d y K D 0 2 5 -2 0 8 or i n 
St u d y  K D 0 2 5 -2 1 3, as a p pr o priate.  T h e first d ose ma y b e ta ke n at h o me or i n t he cli nic.  
•  Dis pe nse a st u d y dr u g di ar y t o t he s u bject  
T he f oll o wi n g d ata will n ee d t o be ca pt ure d fr o m St u d y K D 0 2 5 -2 0 8 or St u d y K D 0 2 5 -2 1 3:  
•  T he d osi n g gr o u p t o w hic h t he s u bject was assi g n e d or ra n d o mize d  
•  Cli nicia n -re p orte d Gl o b al c G V H D Acti vit y A ssess me nt fr o m Da y 1 
•  A n y o n g oi n g  A E s 
T he f oll o wi n g efficac y assess me nts will be perf or me d : 
•  Cli nicia n -re p orte d Gl o b al c G V H D Acti vit y A ssess me nt 
V V- C LI N- 0 6 3 8 9 9 6 1. 0


B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 4 3  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
•  Res p o nse assess me nt .  ( N ote: all res p o nses will b e  assesse d wit h r es pect t o C ycle 1 Da y 1 
of St u d y  K D 0 2 5 -2 0 8 or St u d y K D 0 2 5 -2 1 3 .) 
•  P F T  (f or s u bj ects wit h l u n g c G V H D or w he n l u n g c G V H D is s us pecte d) 
•  L S S  
•  Use of c ortic oster oi d d os a ge  
•  Use of ot her c G V H D t hera pies  
T he f oll o wi n g s afet y assess me nts will be perf or m e d:  
•  S y m pt o m -dir ecte d P E  
•  Vital si g ns  
•  Wei g ht a n d hei g ht  
•  K P S  
•  He mat ol o g y l a b testi n g  
•  Cli nical c he mistr y la b testi n g  
•  1 2 -lea d E C G 
•  Uri ne pre g n a nc y test ( a n y p ositi ve res ults will be c o nfir me d wit h se r u m testi n g) 
•  Use of c o n c o mita nt me dicati o ns  
•  A Es  
6. 2. 3  
M o nt h 3 Visit  a n d E ver y 3 M o nt h Visits T here after  ( ± 1 4 d a ys)  
T hree m o nt hs ( ± 1 4 da ys) after Baseli ne , s u bjects will ha ve t he f ollo wi n g 
pr oce d ures/assess me nts:  
•  C ollecti o n of a n y re mai ni n g bel u m os u dil fr o m s u bject  
•  Dis pe nsi n g bel u m os u dil me dicati o n at t he sa me d ose.  D oses  ma y be t a ke n at h o me or i n 
t he cli nic. 
•  C ollecti o n of st u d y dr u g diar y  
•  Dis pe nsi n g ne w st u d y dr u g diar y  
•  Cli nicia n -rep orte d Gl o b al c G V H D Acti vit y assess me nt  
V V- C LI N- 0 6 3 8 9 9 6 1. 0


B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 4 4  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
•  Res p o nse assess me nt  
•  P F T *  
•  L S S  
•  Use of c ortic oster oi d d os a ge  
•  Use of ot her c G V H D t hera pies  
•  S y m pt o m -dir ecte d P E  
•  Vital si g ns  
•  Wei g ht  
•  K P S  
•  He mat ol o g y l a b testi n g  
•  Cli nical c he mistr y la b testi n g  
•  1 2 -lea d E C G 
•  Uri ne pre g n a nc y test  (a n y p ositi ve res ults will be c o nfir me d wit h ser u m testi n g) 
•  Use of c o n c o mita nt me dicati o ns  
•  A Es  
* W he n perf or mi n g P F T , t he sa me e q ui p me nt a n d tester s h o ul d be use d d uri n g t he c o urse of t he 
st u d y w he n p ossi ble.  T h e P F Ts s h o ul d be c o n d u cte d i n acc or da nce wi t h st u d y g ui deli nes a n d t h e 
A merica n T h oracic S ociet y/ E ur o pea n Res pirat or y S ociet y sta n dar dizati o n of l u n g f u ncti o n 
testi n g. 
6. 2. 4  
2 8 D a y F oll o w -U p Visit   
T h is 2 8 -da y F oll o w -u p V isit (±  7 da ys) will be 2 8 da ys after t h e last d ose of bel u m os u dil.  
S u bjects will ha ve t he f oll o wi n g assess me nts a n d pr oce d ures:  
•  C ollecti o n of a n y re mai ni n g bel u m os u dil fr o m s u bject  
•  C ollecti o n of st u d y dr u g diar y  
•  Use of c ortic oster oi d d os a ge  
•  Use of ot her c G V H D t h era pies  
V V- C LI N- 0 6 3 8 9 9 6 1. 0


B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 4 5  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
•  S y m pt o m -dir ecte d P E  
•  Vital si g ns  
•  Wei g ht  
•  K P S  
•  He mat ol o g y l a b testi n g  
•  Cli nical c he mistr y la b testi n g  
•  1 2 -lea d E C G 
•  Uri ne pre g n a nc y test ( a n y p ositi ve res ults will be c o nfir me d wit h ser u m testi n g)  
•  Use of c o n c o mita nt me dicati o ns  
•  A Es  
6. 2. 5  
L o n g -ter m F oll o w -u p   
L o n g -ter m F oll o w-u p will start at Bas eli ne f or e nr olle d s u bjects w h o ha ve bee n per m a ne ntl y 
disc o nti n ue d fr o m bel u m os u dil i n St u d y K D 0 2 5 -2 0 8 or i n St u d y K D 0 2 5 -2 1 3 w here t he y ha ve 
n ot yet ha d a n F F S  e ve nt.  T he L T F U  will occ ur a fter t he 2 8-da y F oll o w -u p Visit has bee n 
c o m plete d f or e nr olle d s u bjects w h o  were acti vel y d os e d wit h bel u m os u dil at Baseli ne.   
S u bjects will ha ve L T F U  a p pr o xi matel y e ver y 3 m o nt hs u ntil a n F F S  e ve nt occ urs.  T his L T F U 
assess me nt will occ ur b y s u bjects bei n g c o ntact e d b y tele p h o n e, e -m ail, or p ostal mail t o c o nfir m 
s ur vi val stat us, a n y i nitiati o n of ne w s yst e mic c G V H D t hera pies, a n d rela pse of u n derl yi n g 
disease.  Alter nati vel y, t his  i nf or mati o n ma y be o btai ne d fr o m t he s u bject’s me dical rec or ds. 
6. 2. 6  
U nsc he d ule d Visit   
T he assess me nts a n d pr oce d ures p erf or me d at a n y u nsc he d ule d visit will de pe n d o n t he cli nical 
ju d g me nt of t he I n vesti gat or . 
6. 3  Effic ac y  E n d p oi nts   
T he efficac y e n d p oi nts of t his st u d y will be:  
•  D urati o n of Res p o nse  (D O R )  
•  C ha n ge i n L S S  (A p p e n di x  D: Lee c G V H D S y m pt o m Sc ore ) 
V V- C LI N- 0 6 3 8 9 9 6 1. 0


B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 4 6  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
•  Ti me t o Ne xt Treat me nt  ( T T N T):  defi ne d as t he ti me fr o m t he first d ose of bel u m os u dil 
t o t he start of a d diti o nal s yste mic c G V H D t h era p y 
•  F F S:   defi n e d a s t he a bs e nce of c G V H D tr eat me nt c ha n ge, n o n-rela ps e m ortalit y, a n d 
rec urre nt mali g na nc y  
•  O verall S ur vi val ( O S):  d efi ne d as t he ti me fr o m first d ose of bel u m os u dil t o t he date of 
deat h d ue t o a n y ca use  
•  Perce nta ge of s u bjects w h o ha ve a b est res p o nse of C R  a n d perce nta ge  of s u bjects w h o 
ha ve a b est res p o nse of P R  
•  Res p o nse b y in di vi d ual o r ga n 
•  C ha n ge i n cortic oster oi d d ose:  t he c ha n ge i n pre d nis o ne e q ui vale nt d ose of 
c ortic oster oi ds ( m g/ k g/ da y) d uri n g t he st u d y   
•  C ha n ge i n c G V H D Gl o b al Se verit y R ati n g usi n g t he Cli nicia n-re p ort e d Gl o bal c G V H D 
Acti vit y Ass ess me nt  (A p pe n di x  B: Cli nicia n -re p orted Gl o bal c G V H D Acti vit y 
Assess me nt ) 
6. 4  S afet y  E n d p oi nts   
T he f oll o w -u p safet y e n d p oi nts of t his st u d y will b e o btai ne d at r e g ular i nter vals a n d will 
i ncl u de: 
•  A Es  
•  Gra de ≥ 3 A Es  
•  S A Es  
•  Deat hs  
•  P Es  
•  Vital si g ns  
•  Cli nical la b orat or y e val u ati o ns  
o  He mat ol o gi c:  w hite bl o o d cell c o u nt wit h differe ntial, re d bl o o d cell c o u nt, 
he m o gl o bi n, he mat o crit, platelet c o u nt, a n d mea n c or p usc ular v ol u me  
o  Ser u m c he mistr y:  al b u mi n, al kali ne p h os p hatase, A L T, A S T, bl o o d urea 
nitr o ge n , Ca, Cl, C O2, creati ni ne/ gl o mer ular filtratio n rate  (A p pe n di x  F : 
V V- C LI N- 0 6 3 8 9 9 6 1. 0


B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 4 7  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
E q uati o ns t o Pre dict Gl o mer ular Filtrati o n Rate ( M D R D -4) , creati ni ne 
p h os p h o ki nase , t otal a n d direct bilir u bi n, ga m ma gl uta m yl transferas e, 
gl o b uli n, gl u c ose, lact ate de h y dr o ge nas e, M g, P, K, Na, t otal pr otei n, a n d uric 
aci d  
o  Pre g n a nc y testi n g: uri ne pre g na nc y t ests will be d o ne i n fe males of 
c hil d beari n g p ote ntial.  P ositi ve uri ne res ults will  be c o nfir me d wit h ser u m 
testi n g.  If preg na n c y is c o nfir me d wit h ser u m testi n g, bel u m os u dil will be 
disc o nti n ue d . 
•  E C Gs  
T he A E re p orti n g peri o d f or a s u bject e nr olle d i n t he st u d y will be gi n w he n t he s u bject si g ns t he 
I C F a n d c o nti n ues  t hr o u g h t he 2 8-da y F oll o w -u p Visit, i.e., 2 8 da ys after t he l ast d ose of 
bel u m os u dil.  
 
 
V V- C LI N- 0 6 3 8 9 9 6 1. 0


B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 4 8  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
7  S A F E T Y   
7. 1  S afet y P ar a meters   
T he C o m m o n Ter mi n ol o g y Criteria f or A d verse E ve nts versi o n 4. 0 3  (C T C A E v 4. 0 3 ) will be 
use d f or classif yi n g la b orat or y res ults a n d gra di n g  A Es .  S u bjects will be m o nit ore d t hr o u g h o ut 
t he treat me nt a n d f oll o w-u p peri o d f or occ urre nce of A E s (ac ute, dela ye d, a n d/or c u m ulati ve) as 
well as f or c h a n ges i n cli nical stat us, vital si g n meas ure me nts, a n d la b orat or y d ata.  Safet y 
para meters t o be meas ure d/assesse d i ncl u de vital si g n meas ure me nts ; P E ; he mat ol o g y  a n d ser u m 
c he mistr y  res ults; a n d E C G  rec or di n gs. 
7. 2  A d verse E ve nt  D efi niti o n   
A n A E is defi n e d as a n y u nt o war d me dical o cc urre nce i n a cli nical trial s u bject ass ociate d wit h 
t he use of a dr u g, w het her or n ot c o nsi dere d dr u g-relate d.  A n A E  ca n b e a n u nfa v ora bl e a n d 
u ni nte n de d si g n (e .g ., a n a b n or mal la b orat or y val u e fi n di n g), a s y m pt o m, or a disease te m p orall y 
ass ociate d wit h t he use of a dr u g, wit h o ut j u d g m e nt as t o ca usalit y.  A n A E ca n aris e fr o m use of 
t he dr u g (e.g ., us e i n c o m bi nati o n wit h a n ot her dr u g) a n d fr o m a n y r o ute of a d mi nistrati o n, 
f or m ulati o n or d ose, i ncl u di n g a n o v er d ose.  A n A E als o i ncl u des, b ut is n ot li mite d t o, a n y 
cli nicall y si g nifica nt w orse ni n g of a pre -e xisti n g c o n diti o n.   E x a m ples i ncl u de:  
•  A n y si g n, s y m pt o m, p h ysi cal fi n di n g, or l a b orat or y res ult t hat has w orse n e d i n nat ure, 
se verit y or fre q ue n c y c o m pare d t o Baseli ne  
•  Reacti o ns fr o m a n i n vesti gati o nal pr o d u ct i ncl u di n g t h ose o cc urri n g as a res ult of a n 
o ver d ose, a b us e of t he st u d y dr u g, wit h dra wal p h e n o me na, se nsiti vit y or t o xicit y  
•  C o nc urre nt ill ness t hat w as n ot prese nt or w orse ns i n nat ure, se verit y, or fre q ue nc y 
c o m pare d t o Baseli ne   
•  I nj ur y or acci de nt a n d/ or 
•  E x acer bati o n of a pre -e xisti n g c o n diti o n  
F or t he p ur p os e of dat a c ollecti o n, all u nt o war d e v e nts t hat occ u r after i nf or me d c o nse nt t hr o u g h 
t he 2 8-da y F oll o w -u p Visit  are t o be rec or de d o n e C R Fs b y t he i n vesti gati o nal site.   
7. 3  E v al u ati n g A d verse E ve nts   
T he I n vesti gat or will det er mi ne t he seri o us n ess, i nte nsit y, a n d ca us alit y of A E s bas e d o n t he 
defi niti o ns t hat f oll o w.  
V V- C LI N- 0 6 3 8 9 9 6 1. 0


B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 4 9  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
7. 3. 1  
Seri o us A d verse E ve nts   
T he S p o ns or  or desi g nee m ust be n otifie d wit hi n 2 4 h o urs.  
T he S A E defi niti o n a n d re p orti n g re q uire m e nts will be i n  acc or da nce wit h Title 2 1 Part C o de of 
Fe deral Re g ulati o ns ( C F R ) 3 1 2. 3 2 a n d t he G ui da nce f or I n d ustr y a n d I n v esti gat ors Safet y 
Re p orti n g Re q uir e me nts f or I n vesti gati o nal N e w Dr u g (I N Ds) a n d 
Bi oa vaila bilit y /Bi oe q ui v ale nce  St u dies  ( B A/ B E). 
S A E: A n a d verse e v e nt is c o nsi dere d "seri o us" if, i n t he vie w of eit her t he I n vesti gat or or 
S p o ns or , it res ults i n a n y of t he f oll o wi n g o ut c o mes: 
•  Deat h:   T his i ncl u des a n y deat h t hat occ urs w hile t he s u bject is “o n st u d y ” as well as a n y 
deat h t hat occ urs wit hi n 2 8 da ys after st u d y dr u g disc o nti n uati o n .  N ote:  Deat h is a n 
o utc o me of a n A E, n ot a n A E i n itself.  T he e ve nt(s) t hat ca use d d eat h ( e. g., ill nes s, 
acci de nt) is t he S A E.  D eat h d ue t o a n y ot her ca us e(s) m ust als o be re p orte d as a n 
o utc o me of t he re p orta bl e S A E.  
•  Lif e -t hreate ni n g A E :  A n A E or s us pecte d a d verse reacti o n is c o nsi dere d 
“life-t hreate ni n g” if, i n t h e vie w of eit her t he I n v esti gat or or S p o ns or , its occ urre n ce 
places t he s u bje ct at i m me diate ris k of deat h.   It d oes n ot i ncl u de a n A E or s us pecte d 
a d verse reacti o n t hat, ha d it occ urre d i n a m ore se v ere f or m, mi g ht ha ve ca use d deat h .  
•  I n p atie nt h os pitalizati o n or pr ol o n gati o n of e xisti n g h os pitalizati o n:  T he I n vesti gat or 
s h o ul d n ot re p ort h os pitalizati o n or pr ol o n gati o n of h os pitalizati o n i n t he f oll o wi n g 
sit uati o ns: ( 1) hos pitaliz ati o n or pr ol o n gati o n of h os pitalizati o n is nee de d f or a pr oce d ure 
re q uire d b y t he pr ot oc ol; ( 2) h os pitalizati o n o r pr ol o n gati o n of h os pitalizati o n is part of 
r o uti ne pr oce d ure f oll o w e d b y st u d y ce nter; or ( 3) h os pitalizati o n f or s ur ve y visits or 
a n n ual p h ysicals.  N ote: a  h os pitalizati o n pla n ne d bef ore t h e start of t he st u d y f or a 
pre -e xisti n g c o n diti o n w hic h has n ot  w orse n e d d o es n ot c o u nt as a n S A E .  
•  Persiste nt or si g nifica nt i nca pacit y or s u bsta ntial disr u pti o n of t he a bilit y t o c o n d uct 
n or mal life f u ncti o ns  
•  C o n ge nital a n o mal y/ birt h defect  
•  I m p ort a nt me dical e v e nt:  A n e ve nt t hat ma y n ot res ult i n deat h, be life -t hr eate ni n g, or 
re q uire h os pitaliz ati o n ma y b e c o nsi dere d seri o us w he n, base d u p o n a p pr o priate me dical 
j u d g me nt, it ma y je o par diz e t he s u bject a n d ma y re q uire me dical or s ur gical i nter ve nti o n 
t o pre ve nt o ne  of t h e o utc o mes liste d i n t his defi niti o n.  
V V- C LI N- 0 6 3 8 9 9 6 1. 0


B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 5 0  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
7. 3. 2  
Pr ot oc ol -R el ate d A d ve rse E ve nts   
A d verse e ve nts  t hat are n ot st u d y dr u g relate d ma y ne vert heless b e c o nsi dere d b y t h e 
I n v esti gat or or t he m e di cal m o nit or t o be relate d t o t he c o n d uct of  t he cli nical st u d y, i.e., t he 
e ve nt ma y be relate d t o t he fact t hat a s u bject is p artici pati n g i n t he st u d y.  F or e x a m ple, a 
pr ot oc ol -relat e d A E  m a y be a n e v e nt t hat occ urs d uri n g a was h o ut peri o d or t hat is relate d t o a 
pr oce d ure re q uire d b y t h e pr ot oc ol . 
7. 3. 3  
Rel ati o ns hi p t o St u d y Dr u g   
T he I n vesti gat or will atte m pt t o assess t he relati o ns hi p of t he e ve nt  t o st u d y dr u g usi n g a 5-p oi nt 
scale (n ot relate d, u nli kel y-relate d, p ossi bl y rel ate d, pr o ba bl y relat e d, or defi nitel y relate d; 
(A p pe n di x  G : Deter mi ni n g Relati o ns hi p of  A Es t o St u d y Dr u g ). 
7. 3. 4  
Rec or d i n g A d verse E ve nts  
All A E s a n d S A Es  are t o be acc uratel y rec or de d o n t he A d verse E ve nt p a ge of t he s u bject ’s 
e C R F d uri n g t he s u bject’s partici pati o n i n t he st u d y.  T he se verit y of eac h A E  will be gra de d 
usi n g t he C T C A E v 4. 0 3  scale.  T h e date of o ns et as well as t he e n d d ate of t he e ve nt als o s h o ul d 
be rec or de d  or t h e e ve nt s h o ul d be e ntere d as “o n g oi n g ”.  I n a d diti o n, t he met h o d use d t o treat 
t he A E  a n d t h e o utc o me o f t he A E  als o will be n ote d.  I n t he e v e nt t hat t he gra de of a n A E  
w orse ns , a n e n d date s h o ul d be e ntere d t o t he i niti al A E a n d a ne w A E e ntere d wit h t he u p date d 
gra de a n d d ate of o ns et.  T he I n vesti gat or will ass ess t he relati o ns hi p of t he e ve nt t o st u d y dr u g.    
N ote: All S A Es als o are t o be e ntere d o nt o a n S A E f or m a n d se nt t o t he S p o ns or  or desi g nee  
wit hi n 2 4 h o urs . 
7. 3. 5  
Seri o us A d verse E ve nt Re p orti n g   
7. 3. 5. 1  
Ti mefr a me  f or Re p orti n g  
A n y d eat h, S A E , or  pre g na nc y  (i ncl u di n g pre g na n c y of a part ner) e x perie n ce d b y a s u bject w hile 
recei vi n g or wit hi n 2 8 da ys of recei vi n g st u d y dr u g, re gar dl ess of rel ati o ns hi p t o  st u d y dr u g, 
i ncl u di n g f oll o w-u p i nf or mati o n,  or a n y S A E t h at occ urs m ore t h a n 2 8 da ys after recei vi n g st u d y 
dr u g, a n d is belie ve d t o b e st u d y dr u g -rel ate d, m ust be pr o m ptl y re p orte d ( wit hi n 2 4 h o urs of t he 
I n v esti gat or bec o mi n g a ware of t he e v e nt) b y e -ma il t o t he S p o ns or  ( or desi g nee). 
S A E F or m o r Pre g n a nc y F or m (i niti al re p ort or f oll o w-u p re p ort) m ust be se nt 
wit hi n 2 4 h o urs  of bec o mi n g a w are t o:  cli nic al S A Ere p orti n g @ K a d m o n.c o m . 
V V- C LI N- 0 6 3 8 9 9 6 1. 0


B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 5 1  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
A d diti o nall y, t he I n vesti gat or will be a ble t o c o ntact t he m e dical m o nit or at all ti mes .  Refer t o 
s p o ns or a n d C R O c o ntact list f or u p t o date c o ntact i nf or mati o n. 
7. 3. 5. 2  
S A E I nf or m ati o n t o be Pr o vi de d b y t he I n vesti g at or  
T he S A Es  f or all e nr olle d s u bjects m ust be rec or de d o n t he S A E f or m  ( d uri n g st u d y 
partici pati o n) .  T his re q uire me nt i ncl u des all S A Es t hat occ ur after i nf or me d c o nse nt a n d t hr o u g h 
t he 2 8-da y F oll o w -u p Visit at 2 8  da ys after last d os e of st u d y dr u g .  In a d diti o n, a n y S A Es t hat 
are ass esse d as at least p ossi bl y relate d t o st u d y dr u g  b y t h e I n vesti gat or, e ve n if t he S A E occ urs 
m ore t ha n 2 8 da ys after t he last d ose of st u d y dr u g , m ust be re p orte d t o t he Ka d m o n 
P har mac o vi gila nce ( or d esi g nee)  as descri b e d bel o w:  
Re p ort S A Es o n a n S A E f or m wit hi n 2 4 h o urs of bec o mi n g a w are t o:  
cli nic al S A Ere p orti n g @ K a d m o n.c o m . 
A d diti o n all y, t he I n vesti g at or will be a ble t o c o nt act t he me dic al m o nit or at all ti mes at:  
A. Wo olf re y @ me d p ace. c o m . 
T he mi ni m u m i nf or mati o n re q uire d f or S A E re p orti n g i ncl u des i de ntit y of I n vesti gat or, site 
n u m ber, s u bject n u m ber, a n e ve nt des cri pti o n, S A E ter m(s), o nset dat e, reas o n w h y t he e ve nt is 
c o nsi dere d t o  be s eri o us ( i.e., t he seri o us ness criteria), a n d t he I n v esti gat or’s assess me nt of t he 
relati o ns hi p of t he e ve nt t o st u d y dr u g .  A d diti o nal S A E i nf or mati o n i ncl u di n g me dicati o ns or 
ot her t hera p e utic meas ures use d t o treat t he e ve nt, acti o n ta ke n wit h t he st u d y dr u g  d u e t o t he 
e ve nt, a n d t he o utc o m e/r es ol uti o n of t he e ve nt will be rec or de d o n t he S A E f or m .  F or ms f or 
re p orti n g S A E will be pr o vi de d t o t he st u d y sites. 
W he n re p orti n g S A E, t he f oll o wi n g a d diti o nal p oi nts s h o ul d be n ote d:  
•  W he n t he dia g n osis of a n S A E is k n o w n or s us pecte d, t he I n vesti gat or s h o ul d re p ort t he 
dia g n osis or s y n dr o m e as t he pri mar y S A E ter m, r at her t ha n as si g ns or s y m pt o ms . Si g ns 
a n d s y m pt o ms ma y t he n be descri b e d i n t he e ve nt descri pti o n .  F or e x a m ple, d ys p nea 
s h o ul d n ot be use d as a n S A E ter m if t he dia g n osis w hic h ca use d t h e d ys p n ea is k n o w n t o 
be m ali g n a nt p le ural eff usi o n.   
•  Deat h s h o ul d n ot be re p orte d as a n S A E b ut as a n o utc o me of a s pecific S A E, u nless t he 
e ve nt prece di n g t he deat h is u n k n o w n .  I n t he e x ce pti o nal case w here t he e ve nts lea di n g 
V V- C LI N- 0 6 3 8 9 9 6 1. 0


B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 5 2  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
t o deat h are u n k n o w n, t he n d eat h ma y b e use d as a n e ve nt ter m .  If a n a ut o ps y was 
perf or me d, t h e a ut o ps y re p or t s h o ul d be pr o vi de d.  
W hile m ost h os pitaliz ati o ns necessitate re p orti n g a n S A E, s o me h os pitalizati o ns d o n ot re q uire 
S A E re p orti n g: ( 1) ele cti ve or pre vi o usl y sc h e d ule d s ur ger y (e.g ., a pre vi o usl y sc he d ul e d ve ntral 
her nia re pair ); ( 2) pr oce d ures f or pre-existi n g c o n diti o ns t hat ha ve n ot w orse ne d aft er i nitiati o n 
of treat me nt ; ( 3) pre-s p ecifie d st u d y hos pitalizati o ns f or o bser vati o n ; a n d ( 4) eve nts t hat res ult i n 
e mer ge n c y r o o m sta ys of less t ha n 2 4 h o urs a n d t h at d o n ot re q uire a d missi o n. 
H o we ver, S A E s m ust be re p orte d f or a n y s ur gical or pr oce d ural c o m plicati o n res ulti n g i n 
pr ol o n gati o n of t h e h os pitaliz ati o n.  
I n all cases, t he I n vesti gat or s h o ul d c o nti n ue t o m o nit or t he cli nical sit uati o n a n d re p ort all 
material facts relati n g t o t he pr o gressi o n or o ut c o me of t he S A E as a f oll o w -u p i n t he sa me 
ti mefra me a n d ma n ner as t he i nitial S A E re p ort.  F urt her m ore, t he I n vesti gat or ma y b e re q uir e d 
t o pr o vi de s u p ple me ntar y i nf or mati o n as re q u este d b y t he Ka d m o n P har mac o vi gila nce or 
desi g nee.  
Re p ort f oll o w -u p S A E i n f or m ati o n wit hi n 2 4 h o urs of bec o mi n g a w are t o: 
cli nic al S A Ere p orti n g @ K a d m o n.c o m . 
7. 3. 5. 3  
Pre g n a nc y   
Pre g n a ncies o cc urri n g i n s u bject s e nr olle d i n a st u d y or i n a fe mal e part ner of a male st u d y 
partici pa nt m ust be re p orte d a n d f oll o we d t o o utc o me.  If a fe male s u bject i na d verte ntl y bec o mes 
pre g na nt w hile o n st u d y treat me nt, t he s u bject will i m me diatel y be re m o ve d fr o m t he st u d y.  A n y 
pr e g na nci es of fe male st u d y s u bjects a n d part ners of male st u d y s u bject t hat occ ur wit hi n 
1 2 0  da ys f oll o wi n g t he l ast d ose of st u d y tr eat me nt m ust be ca pt ure d i n t he e C R F.  
T he I n vesti gat or s h o ul d c o m plete t he initial Pre g n a nc y  Re p ort  F or m a n d f or war d it t o t he 
S p o ns or ( or desi g nee) wit hi n 2 4 h o urs of bec o mi n g a ware of t he pre g na n c y as descri be d i n 
Secti o n  7. 3. 5. 1  of t he pr ot oc ol.  If t here is a n ass ociate d seri o us o utc o me, t h e n b ot h t he initial 
Pre g n a nc y R e p ort F or m a n d S A E Re p ort F or m s h o ul d be c o m plete d.  
T he site will f oll o w -u p wit h t he s u bject at least m o nt hl y a n d d oc u m e nt t he s u bject ’s stat us u ntil 
t he pre g na n c y has bee n c o m plete d or ter mi nate d.  T he In vesti gat or will ma ke e ver y eff ort t o 
o btai n per missi o n t o f oll o w t he o utc o me of t he pre g n a nc y a n d re p ort t he c o n diti o n of t he fet us or 
ne w b or n t o t he S p o ns or .  T he Pre g na n c y Re p ort  F or m s h o ul d be u p date d a n d s u b mitte d t o t he 
V V- C LI N- 0 6 3 8 9 9 6 1. 0


B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 5 3  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
S p o ns or  wit hi n 2 4 h o urs of bec o mi n g a ware of t he pre g na nc y o ut c o me.  If a n S A E occ urre d, 
t he n t he S A E Re p ort F or m m ust be c o m plete d a n d s u b mitte d as well. 
I n t he e ve nt t he pre g na n c y o utc o me o cc urs f oll o wi n g t he e n d of t he st u d y a n d data base l oc k, t h e 
I n v esti gat or will re p ort t he pre g na n c y o utc o me t o t he S p o ns or ( or desi g nee) wit hi n 2 4 h o urs after 
t he o utc o me of t he pre g n a nc y is k n o w n t o t he I n v esti gat or i n acc or da nce wit h t he pr oce d ure f or 
re p orti n g S A Es (Secti o n  7. 3. 5. 1 ). 
Pre g n a nc y al o n e is n ot re gar de d as a n A E u nless t here is a p ossi bilit y t hat t he st u d y dr u g m a y 
ha ve i nterfere d wit h t he effecti ve ness of a c o ntrace pti ve me dicati o n.   Electi ve a b orti o ns wit h o ut 
c o m plicati o ns s h o ul d n ot be c o nsi dere d A Es u nless t he y were t h era p e utic a b orti o ns b ut s h o ul d be 
re p orte d t o t he S p o ns or.  H os pitalizati o n f or n or mal deli ver y of a healt h y n e w b or n s h o ul d n ot be 
c o nsi dere d a n S A E.  Pre g na n c y is n ot c o nsi dere d a n S A E u nles s t here is a n ass ociate d seri o us 
o utc o me. S p o nta ne o us a b orti o ns s h o ul d al wa ys b e re p ort e d as S A Es.  
A n y S A E t hat o cc urs d uri n g pre g n a nc y m ust be rec or de d o n t he S A E Re p ort F or m (e .g ., 
mater nal seri o us c o m plicati o ns, t hera pe utic a b orti o n, ect o pic pre g n a nc y, still birt h, ne o natal 
deat h, c o n ge nital a n o mal y, birt h defect) a n d re p ort e d wit hi n 2 4 h o urs i n acc or da nce wit h t he 
pr oce d ure f or re p orti n g S A Es.  
T he Pre g na n c y Re p ort F or m  a n d a n y relate d S A E Re p ort F or ms m ust be re p orte d t o t he S p o ns or 
as o utli ne d f or S A Es i n Secti o n  7. 3. 5. 2 . 
7. 3. 5. 4  
Re g ul at or y Re p orti n g   
Ka d m o n P har mac o vi gila nce ( or d esi g n ee) will s u b mit S A E s t hat meet t he criteria f or e x pe dite d 
re p orti n g t o t he Re g ulat or y A ut h orities i n acc or da nce wit h l ocal r e g ulati o ns g o ver ni n g s afet y 
re p orti n g.  Re p orti n g of S A E s b y t he I n v esti gat or t o his or her I R B/I E C will be d o ne i n 
acc or d a nce wit h t he sta n dar d o perati n g pr oce d ures a n d p olicies of t he I R B /I E C.  A de q u ate 
d oc u me ntati o n m ust be mai ntai ne d s h o wi n g t hat t he I R B /I E C was pr o perl y n otifie d.  
7. 4  Ot her S afet y C o nsi der ati o ns   
7. 4. 1  
L a b or at or y D at a   
All la b orat or y data o bt ai ne d d uri n g t he c o urse of t he st u d y  s h o ul d be re vie we d.  A n y a b n or mal 
val ue t hat lea ds t o a c ha n ge i n s u bje ct ma na ge m e nt ( e.g ., d os e re d ucti o n or dela y, re q uire me nt 
f or a d diti o nal me dicati o n or m o nit ori n g) or is c o nsi dere d t o be of cli nical si g nifica nce b y t h e 
V V- C LI N- 0 6 3 8 9 9 6 1. 0


B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 5 4  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
I n v esti gat or s h o ul d be re p orte d as a n A E a n d/or S A E  as a p pr o priate, u nless t his val ue is 
c o nsiste nt wit h t he s u bject ’s prese nt disease state or is c o nsiste nt wit h val ues o btai ne d bef ore  
e ntr y i nt o t he st u d y.  
La b orat or y res ults will be classifie d usi n g t he C T C A E v 4. 0 3 . 
7. 4. 2  
F oll o w -U p of A d verse E ve nts   
All  S A E s a n d T E A Es  (i n cl u di n g cli nicall y si g nifica nt a b n or mal la b orat or y val ues t hat meet t hese 
criteria) will be f oll o we d u ntil eit her res ol uti o n of t he e ve nt or d eter mi nati o n b y t he I n vesti gat or 
t hat t he e ve nt has bec o m e sta ble or irre versi ble.  T he stat us of all ot her c o nti n ui n g A Es will be 
d oc u me nte d as of 2 8 d a ys after last d ose of st u d y dr u g .   
 
V V- C LI N- 0 6 3 8 9 9 6 1. 0


B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 5 5  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
8  S T U D Y S T O P PI N G R U L E S   
T here are n o st o p pi n g r ul es f or t his st u d y.  
 
 
V V- C LI N- 0 6 3 8 9 9 6 1. 0


B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 5 6  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
9  S T A TI S TI C A L C O N SI D E R A TI O N S   
9. 1  H y p ot hesis   
T his will be a l o n g -ter m f oll o w-u p st u d y of t h e efficac y a n d safet y of s u bjects treate d wit h 
bel u m os u dil i n St u d y K D 0 2 5 -2 0 8 a n d St u d y K D 0 2 5 -2 1 3.  N o f or mal h y p ot hesis will be  use d.  
9. 2  S a m ple Size  a n d P o w er C alc ul ati o n   
N o f or mal p o wer calc ulati o n will be  perf or me d t o deter mi ne t he st u d y sa m ple size.  
9. 3  A n al ysis P o p ul ati o ns   
T he p o p ulati o ns f or  efficac y a n d safet y a n al ys es will be t he  F ull A nal ysis S et c o nsist i n g of all 
s u bjects e nr olle d i n t he st u d y. 
T here are 3  tr eat me nt gr o u ps f or t his st u d y: bel u m os u dil 2 0 0 m g Q D, 2 0 0 m g BI D, a n d 4 0 0 m g 
Q D.  Eac h s u bject ’s treat me nt gr o u p is det er mi ne d b y t heir ori gi n all y assi g ne d d osi n g c o h ort 
(St u d y K D 0 2 5 -2 0 8) or ra n d o mize d ar m (St u d y K D 0 2 5 -2 1 3).  
9. 4  S u b gr o u p A n al yses   
N o s u b gr o u p a nal ysis will be c o n d ucte d.  
9. 5  D at a A n al ysis   
All pre -s pecifie d a n al ys es will be descri be d i n a Statistical A nal ysis Pla n.  
9. 6  I nteri m A n al ysis  
A n i nteri m a nal ys is will be perf or me d w he n all s u bjects ha ve c o m plet e d at least 3 years of 
treat me nt wit h bel u m os u dil or wit h dre w earlier ( n ot i ncl usi ve of t he c o m pa ni o n st u d y s u bjects). 
9. 7  Effic ac y A n al yses   
T he f oll o w -u p efficac y e n d p oi nts i n t his st u d y are descri be d i n Secti o n  6. 3 . 
9. 8  E x pl or at or y A n al yses   
N o e x pl orat or y a nal yses will be c o n d ucte d.  
V V- C LI N- 0 6 3 8 9 9 6 1. 0


B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 5 7  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
9. 9  S afet y A n al yses   
Safet y a nal yses will be perf or me d o n all s u bjects w h o recei ve at least o ne d ose of bel u m os u dil.   
A d verse e ve nt s will be c o de d usi n g t he M e dical Dicti o nar y of Re g ulat or y Acti vities ( Me d D R A ) 
( Versi o n 24 . 0 or greater).  T he n u m ber a n d perce nt a ges of s u bjects e x perie nci n g T E A Es will be 
ta b ulate d b y S yste m Or ga n Class a n d Preferre d Ter m ( P T) .  T he n u m b er of e ve nts b y P T  will 
als o be s u m marize d.  Ta b ulati o n b y ma xi m u m se verit y a n d rel ati o ns hi p t o treat me nt will als o b e 
i ncl u de d b y tr eat me nt gr o u p. 
S u m mar y s u bject listi n g will be pr o vi de d f or S A Es, A Es res ulti n g i n st u d y disc o nti n uati o n, a n d 
deat hs.  
A d verse e ve nts, S A Es, relate d A Es, r elate d S A Es, Gra de ≥ 3 A Es, relate d Gra de ≥ 3 A Es, a n d 
A Es lea di n g t o wit h dra w al a n d t reat me nt disc o nti n uati o n, a n d deat hs will be s u m marize d.  
La b orat or y res ults will be s u m mariz e d b y tr eat me nt gr o u p , inci de nce of la b orat or y 
a b n or malities , a n d w orst o n -st u d y gra de d uri n g t h e treat me nt peri o d will be s u m marize d. T he 
i nci de nce of Gra d e ≥ 3 la b orat or y a b n or malities u n der treat me nt a n d s hifts i n t o xicit y gra di n g 
fr o m Bas eli ne  t o hi g h est gra de p ost-bas eli ne will be dis pla ye d.  
Vital si g n meas ur e me nts a n d E C Gs will be s u m marize d b y treat me nt gr o u p at eac h s c he d ule d 
ti me p oi nt usi n g descri pti ve statistics a n d i ncl u de d i n data listi n gs.  
9. 1 0  P h ar m a c o ki netic A n al yses   
N o P K assess me nts f or a nal ysis will be perf or me d i n t his st u d y.  
9. 1 1  P h ar m a c o d y n a mi c A n al yses   
N o p har mac o d y na mic assess me nts f or a nal ysis will be perf or me d i n t his st u d y.  
 
 
 
V V- C LI N- 0 6 3 8 9 9 6 1. 0


B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 5 8  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
1 0  D A T A Q U A LI T Y  A S S U R A N C E   
Acc urate a n d relia ble dat a c ollecti o n will be e ns ure d b y v erificati o n a n d cr oss-c hec ki n g of t h e 
e C R Fs a gai nst t he I n vesti gat or’s rec or ds b y t he st u d y m o nit or (s o urce d oc u me nt verificati o n) 
a n d b y t h e mai nte na n ce of a dr u g – dis pe nsi n g l o g b y t he I n v esti gat or.  C ollecte d data will be 
e ntere d i nt o a c o m p uter data base a n d s u bject t o electr o nic a n d ma n ual q ualit y ass ura nce 
pr oce d ures.  
 
 
 
V V- C LI N- 0 6 3 8 9 9 6 1. 0


B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 5 9  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
1 1  R E G U L A T O R Y O B LI G A TI O N S  & C O M P LI A N C E S T A T E M E N T   
T his st u d y will be c o n d u cte d i n c o m plia nce wit h G C P, i ncl u di n g I nter nati o nal C o nfere n ce o n 
Har m o nisati o n of Tec h ni cal Re q uire me nts f or Re gistrati o n of P har m ace uti cals f or H u ma n Use, 
a n d i n ge neral, c o nsiste nt wit h t he m ost rece nt versi o n of t he Declarati o n  of Helsi n ki.  I n 
a d diti o n, t he I n v esti gat or will a gree  t o a d here t o all a p plica ble l ocal la ws a n d re g ulat or y 
re q uire me nts r ele va nt t o t he use of ne w t h era p e utic a ge nts i n t he c o u ntri es i n v ol ve d. 
T he st u d y will  be c o n d ucte d i n c o m plia nce wit h t he pr ot oc ol.  
Freel y gi v e n writte n i nf or me d c o nse nt m ust be o btai ne d fr o m e ver y s u bject bef ore p artici pati o n 
i n t his cli nical trial.  T he ri g hts, safet y, a n d well -b ei n g of partici pati n g s u bj ects are t he m ost 
i m p orta nt c o nsi derati o ns a n d s h o ul d pre vail o ver i nterests of scie nce a n d s o ciet y. 
St u d y p ers o n nel i n v ol ve d i n c o n d ucti n g t his trial will be q ualifie d b y e d ucati o n, trai ni n g, a n d 
e x perie nce t o perf or m t h eir res pecti ve tas k(s).  T his trial will n ot use t he ser vices of st u d y 
pers o n nel w here sa n cti o ns ha ve bee n i n v o k e d  or w here t here has b ee n sci e ntific misc o n d uct of 
fra u d (e. g., l oss of me dic al lice ns ure, d e bar me nt). 
 
 
 
 
V V- C LI N- 0 6 3 8 9 9 6 1. 0


B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 6 0  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
1 2  E T HI C A L A S P E C T S   
1 2. 1  L oc al Re g ul ati o ns   
T he st u d y m ust f ull y a d h ere t o t he pri n ci ples o utli ne d i n “G ui deli ne f or G o o d Cli nical Practice ” 
I C H E 6( R 2) I nte grate d A d de n d u m t o I C H E 6( R 1) ( Marc h 2 0 1 8), a n d i n ge n eral, be c o n d ucte d i n 
a ma n ner c o nsiste nt wit h t he  m ost rece nt versi o n of t he Decl arati o n of Helsi n ki .  T he 
I n v esti gat or will e ns ure t hat t he c o n d uct of t he st u d y c o m plies wit h t he basi c pri nci ples of G C P 
as o utli ne d i n t he c urre nt versi o n of 2 1  C F R, S u b part  D, Part  3 1 2, “Res p o nsi bilities of S p o ns ors 
a n d I n vesti gat ors”, Part  5 0, “Pr otecti o n of H u ma n S u bjects ”, a n d Part 5 6, “I nstit uti o nal Re vie w 
B oar ds ”, or a p plica ble l o cal e q ui vale nt . 
1 2. 2  I nf or me d C o nse nt  
Sa m ple I C Fs  will be s u p plie d  t o eac h site. 
It is t he res p o nsi bilit y of t he I n v esti gat or, or a pers o n desi g n ate d b y t he I n v esti gat or, t o o btai n 
writte n i nf or me d c o ns e nt fr o m eac h s u bject ( or t h e s u bject ’s le gall y a ut h orize d re prese ntati ve) 
partici pati n g i n t his st u d y after a de q uat e e x pla nati o n of t he ai ms, met h o ds, a ntici pate d be nefits, 
a n d p ote ntial hazar ds of t he st u d y  i n acc or da nce wit h a p plica ble fe d eral a n d state re g ulati o ns.  I n 
t he case w h ere t he s u bject is u na ble t o rea d, a n i m partial wit ness s h o ul d be prese nt d uri n g t he 
e ntire i nf or me d c o nse nt disc ussi o n.  After t he s u bject has orall y c o ns e nte d t o partici pati o n i n t he 
trial, t he wit ness’ si g nat ure o n t he f or m will attest t hat t he i nf or mati o n i n t he c o nse nt f or m was 
acc uratel y e x plai ne d a n d u n derst o o d .  A c o p y of t h e I C F  m ust be  pr o vi de d t o t he s u bject or t o t he 
s u bject’s le gall y a ut h orize d re prese ntati ve.  If a p plica ble, it will be pr o vi de d i n a certifie d 
tra nslati o n of t he l ocal la n g ua ge. 
T he e C R F f or t his st u d y c o ntai ns a secti o n f or d oc u me nti n g i nf or me d s u bject c o nse nt, a n d this 
m ust be c o m plete d a p pr o priatel y .  Si g n e d I C Fs  m ust re mai n i n eac h s u bject ’s st u d y file a n d b e 
a vaila ble f or verific ati o n b y st u d y m o nit ors at a n y ti me .  If ne w safet y i nf or mati o n res ults i n 
c ha n ges i n t he ris k/ be n efit assess me nt, t he I C F s h o ul d be re vie we d a n d u p date d as necessar y.  
All s u bjects (i ncl u di n g t h ose alrea d y bei n g treate d) s h o ul d be i nf or me d of t he ne w i nf or m ati o n, 
s h o ul d be gi ve n a c o p y of t he re vise d f or m, a n d s h o ul d gi ve t heir c o nse nt t o c o nti n ue i n t he 
st u d y. 
V V- C LI N- 0 6 3 8 9 9 6 1. 0


B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 6 1  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
1 2. 3  Rese arc h Et hics C o m mittees   
Pri or t o t he i nitiati o n of t he st u d y, t he pr ot oc ol a n d ass ociate d d oc u me ntati o n m ust be gi ve n a fa v ora ble 
o pi ni o n a n d/ or a p pr o val b y a n Et hic C o m mittee a n d/ or a n I nstit uti o nal Re v ie w B oar d.  A c o p y of t his 
writte n a p pr o val a n d a n y c orres p o n de nce wit h t he E C/I R B will be pr o vi de d t o t he S p o ns or . 
1 2. 4  F ut ure Use of S u bject S a m ples   
A ll of t he bl o o d c o m p o ne nts o btai ne d d uri n g t his st u d y ma y be re q uire d f or t he tests t hat are p art 
of t he cli nical trial .   
 
 
V V- C LI N- 0 6 3 8 9 9 6 1. 0


B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 6 2  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
1 3  C O N DI TI O N S F O R M O DI F YI N G T H E P R O T O C O L   
Pr ot oc ol m o dificati o ns will be re vie we d a n d a p pr o ve d b y Ka d m o n C or p orati o n  re prese nt ati ves. 
All pr ot oc ol m o dificati o ns m ust be s u b mitte d t o t he I R B/I E C f or i nf or mati o n a n d a p pr o val i n 
acc or da nce wit h l ocal re q uire me nts, a n d t o re g ulat or y a ge ncies if re q uir e d.  A p pr o val m ust be 
o btai ne d bef ore a n y c ha n ges ca n be i m ple me nt e d, e x ce pt f or c ha n ges necessar y t o eli mi nate a n 
i m me diate hazar d t o st u d y s u bjects, or w he n t he c ha n ge i n v ol ves o nl y l o gistical or a d mi nistrati ve 
as pects of t he tri al (e. g., c ha n ge i n m o nit or, c ha n ge of tele p h o ne n u m b er).  
 
 
V V- C LI N- 0 6 3 8 9 9 6 1. 0


B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 6 3  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
1 4  C O N DI TI O N S F O R T E R MI N A TI N G T H E S T U D Y   
Ka d m o n C or p orati o n has t he ri g ht t o ter mi nate t h e st u d y at a n y ti me .  I n t er mi nati n g t he st u d y, 
Ka d m o n C or p orati o n a n d t he I n v esti gat or will e ns ure t hat a de q u ate c o nsi d erati o n is gi ve n t o t he 
pr otecti o n of t he s u bjects ’ i nterests. 
 
 
 
V V- C LI N- 0 6 3 8 9 9 6 1. 0


B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 6 4  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
1 5  S T U D Y D O C U M E N T A TI O N , C R F S , A N D R E C O R D K E E PI N G   
1 5. 1  In vesti g at or’s Files a n d Rete nti o n of D oc u me nts   
T he I n vesti gat or m ust mai ntai n a de q uate a n d acc urate rec or ds t o e n a ble t h e c o n d uct of t he st u d y 
t o be f ull y d oc u m e nte d a n d t he st u dy data t o b e s u bse q ue ntl y v erifie d .  T hese d oc u me nts s h o ul d 
be classifie d i nt o 2  se parate cat e g ories:  I n vesti gat or’s S t u d y F iles a n d S u bject C li nical S o urce 
d oc u me nts.  
T he I n vesti gat or’s st u d y file will c o ntai n t he pr ot oc ol a n d pr ot oc ol a me n d m e nts, e C R Fs, q uer y 
f or ms, I R B/I E C, a n d g o v er n me ntal a p pr o val wit h c orres p o n d e nce, s a m ple I C F, dr u g rec or ds, 
staff c urric ul u m vitae, a ut h orizati o n f or ms, a n d ot her a p pr o priate d oc u m e nts a n d 
c orres p o n d e nce.  
S u bject cli nical s o urce d oc u me nts ( us uall y pre d efi ne d b y t he pr oject t o rec or d ke y efficac y a n d 
safet y para meters i n de pe n de nt of t he e C R Fs) ma y i ncl u de s u bject h os pital/cli nic rec or ds, 
p h ysicia n ’s a n d n urs e’s n otes, a p p oi nt me nt b o o k, ori gi nal la b orat or y re p orts, E C G, 
electr oe n ce p h al o gra m, X -ra y, pat h ol o g y a n d s pecial assess me nt re p orts, si g ne d I C Fs, c o ns ulta nt 
letters, a n d s u bject scree ni n g a n d e nr oll me nt l o gs .  T he I n vesti gat or m ust k ee p t hese d o c u me nts 
o n file f or at least 2  years f oll o wi n g t he mar keti n g a p plicati o n a p pr o val d ate f or t he st u d y dr u g 
a n d f or t he i n di cati o n bei n g i n vesti gate d or f or 2  years after t he i n v esti gati o n is disc o nti n ue d a n d 
t he F D A is n otifie d .  After t hat peri o d of ti me, t he d oc u me nts ma y b e destr o ye d s u bject t o l ocal 
re g ulati o ns wit h pri or writte n per missi o n fr o m Ka d m o n C or p orati o n .  If t he I n vesti gat or wa nts t o 
assi g n t he st u d y rec or ds t o a n ot her part y or m o ve t he m t o a n ot her l ocati o n, Ka d m o n C or p orati o n  
m ust be n otifie d i n a d va n ce.  
If t he I n vesti gat or ca n n ot g uara nte e t he arc hi vi n g re q uire me nt at t he st u d y site f or a n y or all of 
t he d oc u ments, s pecial arra n ge me nts m ust be ma d e bet wee n t he I n vesti gat or a n d Ka d m o n 
C or p orati o n  t o st ore t hes e i n a seale d c o ntai ner o utsi de of t he st u d y site s o t hat t he y ca n b e 
ret ur ne d seale d t o t he I n v esti gat or i n case of a re g ulat or y a u dit.  W he n s o urce d oc u me nts are 
re q uire d f or t he c o nti n ue d care of t he s u bject, a p pr o priate c o pi es s h o ul d be ma de f or st ori n g 
o utsi de of t he st u d y site.  
1 5. 2  S o urce D oc u me nts a n d B ac k gr o u n d D at a   
U p o n re q uest, t he I n vesti gat or will s u p pl y Ka d m o n C or p orati o n  wit h a n y re q uire d bac k gr o u n d 
data fr o m t he st u d y d oc u me ntati o n or cli nic rec or ds . I n case of s peci al pr o ble ms or g o v er n me ntal 
V V- C LI N- 0 6 3 8 9 9 6 1. 0


B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 6 5  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
q ueries or re q uests f or a u dit i ns pecti o ns, it is als o necessar y t o h a ve access t o t he c o m plete st u d y 
rec or ds, pr o vi de d t hat s u bject c o nfi de ntialit y is pr otecte d. 
1 5. 3  A u dits a n d I ns pecti o ns   
T he I n vesti gat or s h o ul d u n dersta n d t hat s o urce d oc u me nts f or t his st u d y s h o ul d be ma de 
a vaila ble t o a p pr o priatel y q ualifie d pers o n nel fr o m t he Ka d m o n C or p orati o n  Q ualit y Ass ura n ce 
U nit ( or desi g nee), or t o healt h a ut h orit y i ns p ect ors after a p pr o priate n otifi cati o n .  T he 
verificati o n of t he e C R F data m ust be b y direc t i ns pecti o n of s o urce d oc u me nts. 
1 5. 4  Electr o nic C ase Re p ort F or ms   
Cli nical trial data f or t his st u d y will be ca pt ure d o n e C R F s.  T he I n v esti gat or will a gree t o 
pr o vi de all i nf or mati o n re q ueste d o n t he e C R F i n a n acc urate m a n ner acc or di n g t o i nstr ucti o ns 
pr o vi de d.  Electr o nic C R Fs are desi g ne d f or c o m p uter pr ocessi n g a n d a nal ysis.  T he I n vesti gat or 
s h o ul d e ns ure t he acc urac y, c o m plete ness, a n d ti meli ness of t he data re p orte d t o Ka d m o n  
C or p orati o n  ( or desi g nee) i n t he e C R F a n d i n all r e q uire d re p orts. 
A n e C R F is re q uir e d t o be s u b mitte d f or e ver y s u bject w h o pr o vi des i nf or m e d c o nse nt.  T his 
i ncl u des s u b missi o n of retrie va ble data o n s u bj ects w h o wit h dra w bef ore c o m pleti o n of t he 
st u d y.  T he  e C R Fs m ust be re vie we d f or c o m plete ness a n d acc urac y, a n d el ectr o nicall y si g ne d 
w here  i n dicate d, b y t he Pri nci pal I n vesti gat or or a ut h orize d dele gate fr o m t he st u d y staff.  If a 
s u bject st o ps treat me nt or ter mi nates fr o m t he st u d y, t he dates a n d reaso ns m ust be n ote d o n t he 
e C R F. 
 
 
 
V V- C LI N- 0 6 3 8 9 9 6 1. 0


B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 6 6  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
1 6  M O NI T O RI N G O F T H E S T U D Y   
It is u n derst o o d t hat t he res p o nsi ble Ka d m o n C or p orati o n  m o nit or ( or desi g nee) will c o ntact a n d 
visit t he I n vesti gat or re g ularl y a n d will be all o we d o n re q uest t o i ns pect t h e vari o us rec or ds of 
t he trial (e C R Fs a n d ot her perti ne nt data) pr o vi de d t hat s u bject c o nfi de ntialit y is mai ntai ne d i n 
acc or da nce wit h l ocal re q uire me nts.  
It will be t he st u d y m o nit or ’s res p o nsi bilit y t o i ns p ect t he e C R Fs at re g ular i nter vals t hr o u g h o ut 
t he st u d y, t o v erif y t he a d here nce t o t he pr ot oc ol a n d t he c o m plete ness, c o nsiste nc y, a n d acc urac y 
of t he data bei n g e ntere d o n t he m .  T he st u d y m o nit or s h o ul d ha ve access t o la b orat or y test 
re p orts a n d ot her s u bject rec or ds n ee de d t o v erif y t he e ntries o n t he e C R F.  T he I n vesti gat or ( or 
desi g nee) m ust a gree t o c o o perate wit h t he m o nit or t o e ns ure t hat a n y pr o bl e ms detecte d i n t he 
c o urse of t hes e m o nit ori n g visits are res ol ve d.  
 
 
V V- C LI N- 0 6 3 8 9 9 6 1. 0


B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 6 7  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
1 7  C O N FI D E N TI A LI T Y O F T RI A L D O C U M E N T S A N D S U B J E C T R E C O R D S   
T he I n vesti gat or m ust e ns ure t hat s u bjects ’ a n o n y mit y will be mai ntai ne d a n d t hat t heir i de ntities 
are pr ot ecte d fr o m u na ut h orize d parties .  O n e C R Fs or ot her d oc u me nts s u b mitte d t o Ka d m o n 
C or p orati o n , s u bjects s h o ul d be i de ntifie d b y a n i d e ntificati o n c o de a n d n ot b y t heir n a mes.  T he 
s u bjects’ pers o nal i nf or m ati o n s h o ul d be re dacte d o n all s o urce d oc u m e nts pri or t o s u b missi o n t o 
Ka d m o n C or p orati o n  (or desi g nee) .  T h e I n v esti gat or s h o ul d kee p a s u bject e nr oll me nt l o g 
s h o wi n g c o d es, na mes, a n d a d dresses.  T he I n v esti gat or s h o ul d mai ntai n d oc u me nts n ot f or 
s u b missi o n t o Ka d m o n C or p orati o n  (e.g ., s u bjects’ writte n c o nse nt f or ms) i n strict c o nfi de nce.  
 
 
V V- C LI N- 0 6 3 8 9 9 6 1. 0


B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 6 8  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
1 8  P U B LI C A TI O N O F D A T A A N D P R O T E C TI O N O F T R A D E S E C R E T S   
T he res ults of t his st u d y ma y b e p u blis he d or pres e nte d at scie ntific meeti n gs .  T h e I n vesti gat or 
a grees t o s u b mit all ma n uscri pts or a bstracts t o Ka d m o n C or p orati o n  f or re vie w at least 3 0 da ys 
bef ore s u b missi o n .  T his all o ws Ka d m o n C or p orati o n  t o pr otect pr o prietar y i nf or mati o n a n d t o 
pr o vi de c o m me nts base d o n i nf or mati o n fr o m ot her st u dies t hat ma y n ot yet be a vaila ble t o t he 
I n v esti gat or. 
I n t he e ve nt t hat K a d m o n C or p orati o n  c o or di nates a p u blicati o n or pres e ntati o n of st u d y res ults 
fr o m all st u d y sites, t he p artici pati o n of I n vesti gat or or ot her re pres e ntati ves of st u d y site as a 
na me d a ut h or s hall be d eter mi ne d i n acc or da nce  wit h Ka d m o n C or p orati o n  p olic y a n d ge nerall y 
acce pte d sta n dar ds f or a ut h ors hi p.  
 
V V- C LI N- 0 6 3 8 9 9 6 1. 0


B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 6 9  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
1 9  R E F E R E N C E S   
1.  Lee SJ.  Classificati o n s yste ms f or c hr o nic graft -vers us -h ost disease.  Bl o o d. 2 0 1 7; 1 2 9( 1): 3 0 -3 7  
2.  Arai S, Ar ora M, Wa n g T, et al. I ncreasi n g i nci de nce of c hr o nic graft -vers us -h ost disease i n 
all o ge neic tra ns pla ntati o n: a re p ort fr o m t he Ce nter f or I nter nati o nal Bl o o d a n d Marr o w Tra ns pla nt 
Researc h. Bi ol Bl o o d Marr o w Tra ns pla nt. 2 0 1 5; 2 1( 2) : 2 6 6-2 7 4  
3.  Ar ora M, C utler C S, Ja gasia M H, et al. Late ac ute a n d c hr o nic graft -vers us -h ost disease after 
all o ge neic he mat o p oietic cell tra ns pla ntati o n. Bi ol Bl o o d Marr o w Tra ns pla nt. 2 0 1 6; 2 2( 3): 4 4 9 -4 5 5.  
4.  Fl o wers M E, Marti n PJ.  H o w we treat c hr o nic graft -vers u s-h ost disease.  Bl o o d. 2 0 1 5; 1 2 5( 4): 
6 0 6 -6 1 5  
5.  Gar nett C et al. Treat me nt a n d ma na ge me nt of graft -vers us -h ost disease: i m pr o vi n g res p o nse a n d 
s ur vi val. T her A d v He mat ol. 2 0 1 3; 4 6( 6): 3 6 6 -3 7 8  
6.  Rez ur oc k ( Bel u m os u dil) Prescri bi n g I nf or mati o n 
htt ps:// w w w.access data.f da. g o v/ dr u gsatf da _ d ocs/la bel/ 2 0 2 1/ 2 1 4 7 8 3s 0 0 0l bl. p df   Accesse d 
2 2  J ul 2 0 2 1  
7.  I br uti ni b Prescri bi n g I nf or mati o n 
htt ps:// w w w.access data.f da. g o v/ dr u gsatf da _ d ocs/la bel/ 2 0 1 7/ 2 0 5 5 5 2s 0 2 0l bl. p df  accesse d 
2 8  Mar  2 0 1 8   
8.  It o h, K et al. A n esse ntial part f or R h o -ass ociate d ki nas e i n t he tra nscell ular i n vasi o n of t u m or cells. 
Nat ure M e d. 1 9 9 9;5 , 2 2 1-2 2 5 . d oi: 1 0. 1 0 3 8/ 5 5 8 7.  
9.  Ols o n, M F , Sa hai, E. T he acti n c yt os kelet o n i n ca ncer cell m otilit y. Cli n E x p Metastasis . 
2 0 0 9; 2 6 :2 7 3 -2 8 7 . d oi: 1 0. 1 0 0 7/s 1 0 5 8 5 -0 0 8 -9 1 7 4 -2.  
1 0.  Rie nt o K , Ri dle y AJ.  R oc ks: m ultif u ncti o nal ki nases i n cell be ha vi o ur. Nat Re v M ol Cell Bi ol . 
2 0 0 3; 4, 4 4 6 -4 5 6 . d oi: 1 0. 1 0 3 8/ nr m 1 1 2 8.  
1 1.  Sc h ofiel d A V , Ber nar d O. R h o -ass ociate d c oile d -c oil ki nase ( R O C K) si g nali n g a n d disease. Crit Re v 
Bi oc he m M ol Bi ol . 2 0 1 3; 4 8 : 3 0 1 -3 1 6, d oi: 1 0. 3 1 0 9/ 1 0 4 0 9 2 3 8. 2 0 1 3. 7 8 6 6 7 1.  
1 2.  Li Y. et al. P h os p h or ylate d E R M is res p o nsi ble f or i ncrease d T cell p olarizati o n, a d hesi o n, a n d 
mi grati o n i n patie nts wit h s yste mic l u p us er yt he mat os us. J o ur nal of Im m u n . 2 0 0 7;1 7 8, 1 9 3 8 -1 9 4 7.  
1 3.  T y b ule wicz V L , He n ders o n R B. R h o fa mil y G T Pases a n d t heir re g ulat ors i n l y m p h oc ytes. Nat Re v 
I m m u n ol. 2 0 0 9;9 : 6 3 0 -6 4 4, d oi: 1 0. 1 0 3 8/ nri 2 6 0 6.  
1 4.  R oz o C et al. Tar geti n g t he R h o A -R O C K pat h wa y t o re verse T -cell d ysf u ncti o n i n S L E. A n n R he u m 
Dis . 2 0 1 6;7 6 : 7 4 0 -7 4 7 . d oi: 1 0. 1 1 3 6/a n nr he u m dis -2 0 1 6 -2 0 9 8 5 0.  
V V- C LI N- 0 6 3 8 9 9 6 1. 0


B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 7 0  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
1 5.  Bi s was P S et al. P h os p h or ylati o n of I R F 4 b y R O C K 2 re g ulates I L -1 7 a n d I L -2 1 pr o d ucti o n a n d t he 
de vel o p me nt of a ut oi m m u nit y i n mice. J Cli n I n vest. 2 0 1 0;1 2 0 :3 2 8 0 -3 2 9 5 . d oi: 1 0. 1 1 7 2/J CI 4 2 8 5 6.  
1 6.  He Y et al. A ntii nfla m mat or y effect of R h o ki nase bl oc ka de via i n hi biti o n of N F-ka p pa B acti vati o n i n 
r he u mat oi d art hritis. Art hritis R he u m . 2 0 0 8;5 8 : 3 3 6 6 -3 3 7 6 . d oi: 1 0. 1 0 0 2/art. 2 3 9 8 6.  
1 7.  Is gr o J et al. E n ha nce d r h o-ass ociate d pr otei n ki nase acti vati o n i n patie nts wit h s yste mic l u p us 
er yt he mat os us. Art hritis R he u m . 2 0 1 3;6 5 :1 5 9 2 -1 6 0 2 . d oi: 1 0. 1 0 0 2/art. 3 7 9 3 4.  
1 8.  Za ni n -Z h or o v A et al. Selecti ve oral R O C K 2 i n hi bit or d o w n -re g ulates I L-2 1 a n d I L -1 7 secreti o n i n 
h u ma n T cells via S T A T 3 -de pe n de nt mec ha nis m. Pr oc Natl Aca d Sci U S A . 2 0 1 4;1 1 1 :1 6 8 1 4 -1 6 8 1 9 . 
d oi: 1 0. 1 0 7 3/ p nas. 1 4 1 4 1 8 9 1 1 1.  
1 9.  Lee SJ et al. Se verit y of c hr o nic graft -vers us -h ost disease: ass ociati o n wit h treat me nt -relate d 
m ortalit y a n d rela pse. Bl o o d . 2 0 0 2;1 0 0 :4 0 6 -4 1 4.  
2 0.  Mac D o nal d K P, Blazar B R , Hill G R. C yt o ki ne me diat ors of c hr o nic graft-vers us -h ost disease. J  Cli n 
I n vest. 2 0 1 7;1 2 7, 2 4 5 2 -2 4 6 3 . d oi: 1 0. 1 1 7 2/J CI 9 0 5 9 3.  
2 1.  Ba n o vic T et al. T G F -beta i n all o ge neic ste m cell tra ns pla ntati o n: frie n d or f oe? Bl o o d . 
2 0 0 5; 1 0 6 :2 2 0 6 -2 2 1 4 . d oi: 1 0. 1 1 8 2/ bl o o d -2 0 0 5 -0 1 -0 0 6 2.  
2 2.  Sri ni vasa n M et al. D o n or B -cell all oa nti b o d y de p ositi o n a n d ger mi nal ce nter f or ma ti o n are re q uire d 
f or t he de vel o p me nt of m uri ne c hr o nic G V H D a n d br o nc hi olitis o blitera ns. Bl o o d. 
2 0 1 2; 1 1 9 :1 5 7 0 -1 5 8 0 . d oi: 1 0. 1 1 8 2/ bl o o d -2 0 1 1 -0 7 -3 6 4 4 1 4.  
2 3.  Ra d oj cic V et al. S T A T 3 si g nali n g i n C D 4 + T cells is critical f or t he pat h o ge nesis of c hr o nic 
scler o der mat o us graft -vers us -h ost disease i n a m uri ne m o del. J Im m u n ol  2 0 1 0; 1 8 4 :7 6 4 -7 7 4 . 
d oi: 1 0. 4 0 4 9/ji m m u n ol. 0 9 0 3 0 0 6.  
2 4.  Fl y n n R et al. T ar gete d R h o -ass ociate d ki nase 2 ( R O C K 2) i n hi biti o n decreases cli nical a n d i m m u ne 
pat h ol o g y of m uri ne a n d h u ma n c hr o nic G V H D t hr o u g h  Stat 3 -de pe n de nt mec ha nis m. Bl o o d . 2 0 1 6, 
d oi: 1 0. 1 1 8 2/ bl o o d -2 0 1 5 -1 0 -6 7 8 7 0 6 ( 2 0 1 6).  
2 5.  Lee SJ, W olff D, Kit k o C, et al. Meas uri n g T hera pe utic Res p o nse i n C hr o nic Graft -vers us -H ost 
Disease. Nati o nal I nstit utes of Healt h C o nse ns us De vel o p me nt Pr oject o n Criteria f or Cli nical Trials 
i n C hr o nic Graft-vers us -H ost Disease: I V. T he 2 0 1 4 Res p o nse Criteria W or ki n g Gr o u p Re p ort. Bi ol 
Bl o o d Marr o w Tra ns pla nt. 2 0 1 5; 2 1: 9 8 4 – 9 9 9.  
2 6.  Ja gasia M H et al, Nati o nal I nstit utes of Healt h C o nse ns us De vel o p me nt Pr oject o n Criteria f or 
Cli n ical Trials i n C hr o nic Graft-vers us -H ost Disease: I. T he 2 0 1 4 Dia g n osis a n d Sta gi n g W or ki n g 
Gr o u p re p ort. Bi ol Bl o o d Marr o w Tra ns pla nt. 2 0 1 5; 2 1: 3 8 9 – 4 0 1 . 
V V- C LI N- 0 6 3 8 9 9 6 1. 0


B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 7 1  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
2 7.  Lee S, C o o k E F, S oiffer R et al. De vel o p me nt a n d vali dati o n of a scale t o meas ure s y m pt o ms of 
c hr o nic graft-vers us -h ost disease. Bi ol Bl o o d Marr o w Tra ns pla nt . 2 0 0 2; 8: 4 4 4-4 5 2.  
2 8.  Kar n ofs k y D A, B urc he nal J H. 1 9 4 9. T he Cli nical E val uati o n of C he m ot hera pe utic A ge nts i n Ca ncer. 
I n E val uati o n of C he m ot hera pe utic A ge nts: S y m p osi u m Hel d at t he Ne w Y or k Aca de m y of 
Me d ici ne, Mac Le o, e d. ( Ne w Y or k, C ol u m bia U ni versit y Press), p. 1 9 1-2 0 5.  
2 9.  Le ve y A S, C ores h J, Gree ne T, Ste ve ns L A, Z ha n g Y L, He n dri kse n S, K use k J W, va n Le nte F, 
C hr o nic Ki d ne y Disease E pi de mi ol o g y C olla b orati o n. Usi n g sta n dar dize d ser u m creati ni ne val ues i n 
t he m o dificati o n of diet i n re nal disease st u d y e q uati o n f or esti mati n g gl o mer ular filtrati o n rate. A n n 
I nter n Me d. 2 0 0 6 A u g 1 5; 1 4 5( 4): 2 4 7-5 4.  
3 0.  C o bert B 2 0 1 2. C o bert’s Ma n ual of Dr u g Safet y a n d P har mac o vi gila nce ( 2 n d e d.) Massac h usetts: 
J o nes a n d Barlett Lear ni n g, L L C.  
3 1.  F D A. Dr u g De vel o p me nt a n d Dr u g I nteracti o ns, T a ble of S u bstrates, I n hi bit ors a n d I n d ucers 
htt ps:// w w w.f da. g o v/ dr u gs/ de vel o p me nta p pr o val pr ocess/ de vel o p me ntres o urces/ dr u gi nteracti o nsla beli
n g/ uc m 0 9 3 6 6 4. ht m .  Accesse d 2 5 J u n 2 0 21.  
3 2.  Cre di ble Me ds  2 0 2 0: htt ps://cre di ble me ds. or g/ p dft e m p/ p df/ C o m bi ne d List. p df   Accesse d 
1 1  Ma y  2 0 2 0 . 
3 3.  Li u D, A h met A, War d L, Kris h na m o ort h y P, Ma n delc or n E D, Lei g h R, Br o w n JP, C o he n A, Ki m H. 
A practical g ui de t o t he m o nit ori n g a n d ma na ge me nt of t he c o m plicati o ns of s yste mic c ortic oster oi d 
t hera p y. Aller g y Ast h ma Cli n I m m u n ol. 2 0 1 3 A u g; 9( 1): 3 0.  
 
V V- C LI N- 0 6 3 8 9 9 6 1. 0


B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 7 2  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
A p pe n di x  A: Sc he d ule of Assess me nts   
Ta ble 7 . 
Sc he d ule of Assess me nts  
Assess me nt  
Tre at me nt Peri o d  
F oll o w -U p Peri o d  
Assess me nt  
B aseli ne a 
M o nt h 3 a n d  
E ver y 3 M o nt hs T here after  
2 8 -d a y F oll o w -u p Visit  
 (2 8 D a ys fr o m L ast D ose)  
Wi n d o w  
 
± 1 4 d a ys  
± 7 d a ys  
E val uate I/ E Criteria  
X  
 
 
Si g n I C F  
X  
 
 
St u d y K D 0 2 5 -2 0 8 or 
St u d y  K D 0 2 5 -2 1 3 Hist or y b 
X  
 
 
E F FI C A C Y A S S E S S M E N T S  
Cli nicia n -re p orte d Gl o bal 
c G V H D Acti vit y 
Assess me nt  
X  
X  
 
Res p o nse Assess me nt   
X  
X  
 
P F T c 
X  
X  
 
L S S  
X  
X  
 
D oc u me nt C ortic oster oi d 
D osa ge  
Data t o be c ollecte d fr o m t he date t he I C F is si g ne d u ntil 2 8 da ys after t he last d ose 
of st u d y dr u g  
D oc u me nt Ot her c G V H D 
T hera pies  
Data t o be c ollecte d fr o m t he date t he I C F is si g ne d u ntil 2 8 da ys after t he last d ose 
of st u d y dr u g  
S A F E T Y A S S E S S M E N T S  
S y m pt o m -directe d P E  
X  
X  
X  
Vital Si g ns d 
X  
X  
X  
W ei g ht  
X  
X  
X  
Hei g ht  
X  
 
 
K P S  
X  
X  
X  
He mat ol o g y  
X  
X  
X  
Cli nical C he mistr y  
X  
X  
X  
1 2 -lea d E C G 
X  
X  
X  
Pre g na nc y T est ( Uri ne) e 
X  
X  
X  
C o nc o mita nt Me dicati o ns 
a n d Pr oce d ures  
Data t o be c ollecte d fr o m t he date t he I C F is si g ne d u ntil 2 8 da ys after t he last d ose 
of st u d y dr u g  
A Es  
A Es t o be c ollecte d fr o m t he date t he I C F is si g ne d u ntil 2 8 da ys after t he last d ose 
of st u d y dr u g  
B E L U M O S U DI L  
St u d y Dr u g A d mi nistrati o n f 
X  
X  
 
Dis pe nse St u d y Dr u g Diar y  
X  
X  
 
C ollect St u d y Dr u g Diar y  
 
X  
X  
A E = a d verse e ve nt; BI D = t wice dail y; c G V H D = c hr o nic graft -vers us -h ost disease; D L C O = diff use ca pacit y of car b o n 
m o n o xi d e;  E C G = electr o car di o gra p h; F E V 1 = f orce d e x pirat or y v ol u me i n 1 sec o n d; F V C = f orce d vital ca pacit y; H b = 
he m o gl o bi n; I C F = i nf or me d c o nse nt f or m; I/ E = i n cl usi o n/e xcl usi o n criteria; K P S = Kar n ofs k y P erfor ma nce Stat us; L S S = Lee 
S y m pt o m Scale sc ore; L T F U = l o n g -ter m f oll o w-u p; P E = p h ysical e xa mi n ati o n; P F T = p ul m o nar y f u ncti o n test ; Q D = o nce 
dail y; R V = resi d ual v ol u me; T L C = t otal l u n g ca pacit y  
a. E val u ati o n of i n cl usi o n/e xcl usi o n criteria a n d si g ni n g of I C F d o n ot necessaril y ha ve t o occ ur o n t he sa me da y as efficac y a n d 
safet y assess me nts.  H o we ver, t h e I C F m ust b e si g ne d bef ore a n y st u d y pr oce d ures b e gi n.  
b. At Baseli ne, t h e f oll o wi n g assess me nts n ee d t o be d oc u me nte d fr o m t h e K D 0 2 5 -2 0 8 or K D 0 2 5 -2 1 3 st u dies: d osi n g gr o u p t o 
w hic h t h e s u bject was assi g ne d or ra n d o mize d, Cli nicia n -re p orte d Gl o bal c G V H D Acti vit y Assess m e nt fr o m C ycle 1 Da y 1, a n d 
o n g oi n g A E s. 
c. P ul m o nar y f u ncti o n tests are t o be c o n d ucte d f or s u bjects wit h l u n g c G V H D or w he n c G V H D is s us pecte d a n d i n cl u de: F E V 1, 
F V C, D L C O  (c orrecte d f or H b), R V, a n d T L C . 
V V- C LI N- 0 6 3 8 9 9 6 1. 0


B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 7 3  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
d . Vital si g n meas ure me nts i ncl u de sitti n g bl o o d press ure a n d heart rate (aft er 5 mi n utes of rest); res pirat or y rate; a n d 
te m per at ure.  
e. Fe mal es of c hil d beari n g p ote ntial m ust h a ve a ne gati ve uri n e pre g na nc y test.  P ositi ve res ults are t o be c o nfir me d wit h ser u m 
testi n g. 
f. S u bjects will recei ve t h e sa me d ose of bel u m os u dil as t h e y were assi g ne d a n d recei ve d d uri n g St u d y K D 0 2 5-2 0 8 or 
St u d y  K D 0 2 5 -2 1 3 ( i.e., bel u m os u dil 2 0 0 m g Q D, 2 0 0 m g BI D, or 4 0 0 m g Q D).  First d ose ma y be ta ke n at h o me or i n t h e cli nic.  
 
N ote:  F oll o wi n g t h e 2 8 -da y F oll o w -u p Visit, s u bjects will ha ve L T F U b y bei n g c o ntacte d b y tele p h o ne, e -mail, or p ostal mail t o 
c o nfir m s ur vi val stat us, a n y i nitiati o n of ne w s yste mic c G V H D t h era pies, a n d rela pse of u n derl yi n g disease.   If t h e s u bject was i n 
L T F U i n St u d y K D 0 2 5 -2 0 8 or i n St u d y  K D 0 2 5 -2 1 3, t h e s u bject will o nl y ha ve L T F U assess me nts p erf or me d o nce 
a p pr o xi matel y e ver y 3 m o nt hs  (Secti o n 6. 2. 5 ).   
 
N ote:  At U nsc he d ule d Visit, s u bject s h o ul d n ot recei ve ha ve a n y re mai ni n g  bel u m os u dil c ollecte d, or ha ve st u d y diaries 
dis pe nse d or c ollecte d u nless treat me nt is st o p pe d.  
 
N ote:  T he assess me nts a n d pr oce d ures p erf or me d at a n y u nsc he d ule d visit de pe n d o n t h e cli nical j u d g me nt of t h e I n vesti gat or.  
 
 
V V- C LI N- 0 6 3 8 9 9 6 1. 0


B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 7 4  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
A p pe n di x  B: Cli nici a n -re p orte d Gl o b al c G V H D Acti vit y Assess me nt   
 
 
S C O R E 0  
S C O R E 1  
S C O R E 2  
S C O R E 3  
 
 
E S O P H A G U S  
N o es o p h a g e al 
s y m pt o ms 
Occ asi o n al d ys p h a gi a or 
o d y n o p h a gi a wit h s oli d 
f o o d or pills d uri n g t h e 
p ast w e ek  
I nt er mitt e nt d ys p h a gi a 
or o d y n o p h a gi a wit h 
s oli d f o o ds or pills, b ut 
n ot f or li q ui ds or s oft 
f o o ds, d uri n g t h e p ast 
w e ek  
Dys p h a gi a or 
o d y n o p h a gi a f or al m ost 
all or al i nt a k e, o n 
al m ost ev ery d a y of t h e 
p ast w e ek  
 
 
□ 
□ 
□ 
□ 
 
 □ A b n or m ality pr es e nt b ut ex pl ai n e d e ntir ely b y n o n -G V H D d oc u m e nt e d c a us e (s p ecify):  
  
 □ A b n or m ality t h o u g ht t o r e pr es e nt G V H D PL U S ot h er c a us es (s p ecify):  
  
 
 
S C O R E 0  
S C O R E 1  
S C O R E 2  
S C O R E 3  
 
 
U P P E R GI  
N o sy m pt o ms  
Mil d, occ asi o n al 
s y m pt o ms, wit h littl e 
r e d ucti o n i n or al i nt a k e 
d uri n g t h e p ast w e ek  
M o d er at e, i nt er mitt e nt 
s y m pt o ms, wit h s o m e 
r e d ucti o n i n or al i nt a k e 
d uri n g t h e p ast w e ek  
M or e s ev er e or 
p ersist e nt sy m pt o ms 
t hr o u g h o ut t h e d a y, 
wit h m ark e d r e d ucti o n 
i n oral i nt a k e, o n al m ost 
ev ery d a y of t h e p ast 
w e ek  
 
 
□ 
□ 
□ 
□ 
 
 □ A b n or m ality pr es e nt b ut ex pl ai n e d e ntir ely b y n o n -G V H D d oc u m e nt e d c a us e (s p ecify):  
  
 □ A b n or m ality t h o u g ht t o r e pr es e nt G V H D PL U S ot h er c a us es (s p ecify):  
  
 
 
S C O R E 0  
S C O R E 1  
S C O R E 2  
S C O R E  3  
 
 
L O W E R GI 
N o l o os e or li q ui d st o ols 
d uri n g t h e p ast w e ek  
Occ asi o n al l o os e or 
li q ui d st o ols, o n s o m e 
d ays d uri n g t h e p ast 
w e ek  
I nt er mitt e nt l o os e or 
li q ui d st o ols t hr o u g h o ut 
t h e d a y, o n al m ost 
ev ery d a y of t h e p ast 
w e ek , wit h o ut 
r e q uiri n g i nt erv e nti o n 
t o pr ev e nt or c orr ect 
v ol u m e d e pl eti o n  
V ol u mi n o us di arr h e a  
a o n al m ost ev ery d a y 
of t h e p ast w e ek, 
r e q uiri n g i nt erv e nti o n 
t o pr ev e nt or c orr ect 
v ol u m e d e pl eti o n  
 
 
□ 
□ 
□ 
□ 
 
 □ A b n or m ality pr es e nt b ut ex pl ai n e d e ntir ely b y n o n -G V H D d oc u m e nt e d c a us e (s p ecify):  
  
 □ A b n or m ality t h o u g ht t o r e pr es e nt G V H D PL U S ot h er c a us es (s p ecify):  
  
 
 
S C O R E 0  
S C O R E 1  
S C O R E 2  
S C O R E 3  
 
 
L U N G S 
N o sy m pt o ms  
Mil d s y m pt o ms 
(s h ort n ess of br e at h 
aft er cli m bi n g o n e fli g ht 
of st e ps)  
M o d er at e sy m pt o ms 
(s h ort n ess of br e at h 
aft er w alki n g o n fl at 
gr o u n d)  
S ev er e sy m pt o ms 
(s h ort n ess of br e at h at 
r est; r e q uiri n g O2) 
 
 
□ 
□ 
□ 
□ 
 
 
 
S pir o m etr y  
N ot d o n e □ 
 
F E V 1  
( % Pr e dict e d): 
 
_ _ _ _ _ _  
F E V 1  
(L): 
 
_ _ _ _ _ _  
F V C  
( % Pr e dict e d): 
 
_ _ _ _ _ _  
F V C 
(L): 
 
_ _ _ _ _ _  
 
 □ A b n or m ality pr es e nt b ut ex pl ai n e d e ntir ely b y n o n -G V H D d oc u m e nt e d c a us e (s p ecify):  
  
 □ A b n or m ality t h o u g ht t o r e pr es e nt G V H D PL U S ot h er c a us es (s p ecify):  
  
V V- C LI N- 0 6 3 8 9 9 6 1. 0


B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 7 5  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
 
 
S C O R E 0  
S C O R E 1  
S C O R E 2  
S C O R E 3  
 
 
E Y E S  
N o sy m pt o ms  
Mil d dry e y e sy m pt o ms n ot 
aff ecti n g A DL (r e q uir e m e nt of 
l u bric a nt ey e dr o ps ≤ 3 x p er 
d ay)  
M o d er at e dr y ey e sy m pt o ms 
p arti all y aff ecti n g A DL 
(r e q uiri n g l u bric a nt ey e 
dr o ps > 3 x p er d a y or 
p u nct al pl u gs).  
WI T H O U T  n e w visi o n 
i m p air m e nt d u e t o K C S 
S ev er e dry ey e 
s y m pt o ms 
si g nific a ntly 
aff ecti n g A DL 
(s p eci al e y e w e ar 
t o r eli ev e p ai n) 
O R  u n a bl e t o 
w ork b ec a us e of 
oc ul ar 
s y m pt o ms O R 
l oss of visi o n d u e 
t o K C S 
 
 
□ 
□ 
□ 
□ 
 
 □ A b n or m ality pr es e nt b ut ex pl ai n e d e ntir ely b y n o n -G V H D d oc u m e nt e d c a us e (s p ecify): 
  
 □ A b n or m ality t h o u g ht t o r e pr es e nt G V H D PL U S ot h er c a us es (s p ecify):  
  
 
 
S C O R E 0  
S C O R E 1  
S C O R E 2  
S C O R E 3  
 
 
J OI N T S 
A N D 
F A S CI A  
N o sy m pt o ms  
Mil d ti g ht n ess of ar ms or 
l e gs, n or m al or mil d 
d ecr e as e d r a n g e of m oti o n 
( R O M) A N D n ot aff ecti n g A DL 
Ti g ht n ess of ar ms or l e gs O R 
j oi nt c o ntr act ur es, eryt h e m a 
t h o u g ht d u e t o f asciitis, 
m o d er at e d ecr e as e R O M 
A N D mil d t o m o d er at e 
li mit ati o n of A DL 
C o ntr act ur es 
WI T H si g nific a nt 
d ecr e as e of 
R O M A N D 
si g nific a nt 
li mit ati o n of A DL 
( u n a bl e t o ti e 
s h o es, b utt o n 
s hirts, dr ess s elf 
etc.)  
 
 
□ 
□ 
□ 
□ 
 
 □ A b n or m ality pr es e nt b ut ex pl ai n e d e ntir ely b y n o n -G V H D d oc u m e nt e d c a us e (s p ecify):  
  
 □ A b n or m ality t h o u g ht t o r e pr es e nt G V H D PL U S ot h er c a us es (s p ecify):  
  
 
P -R O M 
Sc or e 
 
 
 
Sc or e    _ _ _ _ _  
N ot d o n e   □ 
 
 
Sc or e    _ _ _ _ _  
N ot d o n e   □ 
 
Sc or e    _ _ _ _ _  
N ot d o n e   □ 
 
Sc or e    _ _ _ _ _  
N ot d o n e   □ 
 □ A b n or m ality pr es e nt b ut ex pl ai n e d e ntir ely b y n o n -G V H D d oc u m e nt e d c a us e (s p ecify):  
  
 □ A b n or m ality t h o u g ht t o r e pr es e nt G V H D PL U S ot h er c a us es (s p ecify):  
  
 
 
 
V V- C LI N- 0 6 3 8 9 9 6 1. 0


B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 7 6  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
 
 
V V- C LI N- 0 6 3 8 9 9 6 1. 0


B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 7 7  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
 
 
S o urces:  Lee et al . 2 0 1 5(2 5 ) a n d Ja gasia et al. 2 0 1 5 (2 6 ) 
 
V V- C LI N- 0 6 3 8 9 9 6 1. 0


B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 7 8  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
A p pe n di x  C : cG V H D Res p o nse Assess me nt   
 
S o urce:  Lee et al. 2 0 1 5 (2 5 )   
V V- C LI N- 0 6 3 8 9 9 6 1. 0


B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 7 9  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
A p pe n di x  D: Lee c G V H D S y m pt o m Sc ore   
B y circli n g o ne n u m ber per li ne, please i n dicate h o w m uc h y o u ha ve bee n b ot here d b y t he f oll o wi n g 
pr o ble ms i n t he past 7 da ys: ( Lee et al. 2 0 0 2(2 7 )) 
S ki n  
N ot at all  
Sli g htl y  
M o der atel y  
Q uite a bit  
E xtre mel y  
1.  
A b n or mal s ki n c ol or  
0  
1  
2  
3  
4  
2.  
Ras hes  
0  
1  
2  
3  
4  
3.  
T hic ke ne d s ki n  
0  
1  
2  
3  
4  
4.  
S ores o n s ki n  
0  
1  
2  
3  
4  
5.  
Itc h y s ki n 
0  
1  
2  
3  
4  
E yes a n d M o ut h  
N ot at all  
Sli g htl y  
M o der atel y  
Q uite a bit  
E xtre mel y  
6.  
Dr y e yes  
0  
1  
2  
3  
4  
7.  
Nee d t o use e ye dr o ps fre q ue ntl y  
0  
1  
2  
3  
4  
8.  
Diffic ult y seei n g clearl y  
0  
1  
2  
3  
4  
9.  
Nee d t o a v oi d certai n f o o ds d ue t o 
m o ut h pai n  
0  
1  
2  
3  
4  
1 0.  
Ulcers i n m o ut h  
0  
1  
2  
3  
4  
1 1.  
Recei vi n g n utriti o n fr o m a n d 
i ntra ve n o us li ne or fee di n g t u be 
0  
1  
2  
3  
4  
Bre at hi n g  
N ot at all  
Sli g htl y  
M o der atel y  
Q uite a bit  
E xtre mel y  
1 2.  
Fr e q ue nt c o u g h  
0  
1  
2  
3  
4  
1 3.  
C ol ore d s p ut u m  
0  
1  
2  
3  
4  
1 4.  
S h ort ness of breat h wit h e xercise  
0  
1  
2  
3  
4  
1 5.  
S h ort ness of breat h at rest  
0  
1  
2  
3  
4  
1 6.  
Nee d t o use o x y ge n  
0  
1  
2  
3  
4  
E ati n g a n d Di gesti o n  
N ot at all  
Sli g htl y  
M o der atel y  
Q uite a bit  
E xtre mel y  
1 7.  
Diffic ult y s wall o wi n g s oli d f o o ds  
0  
1  
2  
3  
4  
1 8.  
Diffic ult y s wall o wi n g li q ui ds  
0  
1  
2  
3  
4  
1 9.  
V o miti n g  
0  
1  
2  
3  
4  
2 0.  
Wei g ht l oss  
0  
1  
2  
3  
4  
M uscl es a n d J oi nts  
N ot at all  
Sli g htl y  
M o der atel y  
Q uite a bit  
E xtre mel y  
2 1.  
J oi nt a n d m uscle ac hes 
0  
1  
2  
3  
4  
2 2.  
Li mite d j oi nt m o ve me nt  
0  
1  
2  
3  
4  
2 3.  
M uscle cra m ps  
0  
1  
2  
3  
4  
2 4.  
Wea k m uscle d  
0  
1  
2  
3  
4  
E ner g y  
N ot at all  
Sli g htl y  
M o der atel y  
Q uite a bit  
E xtre mel y  
2 5.  
L oss of e ner g y  
0  
1  
2  
3  
4  
2 6.  
Nee d t o slee p m ore/ta ke na ps  
0  
1  
2  
3  
4  
2 7.  
Fe vers  
0  
1  
2  
3  
4  
Me nt al a n d E m oti o n al  
N ot at all  
Sli g htl y  
M o der atel y  
Q uite a bit  
E xtre mel y  
2 8.  
De pressi o n  
0  
1  
2  
3  
4  
2 9.  
A n xiet y  
0  
1  
2  
3  
4  
3 0.  
Diffic ult y slee pi n g  
0  
1  
2  
3  
4  
 
 
V V- C LI N- 0 6 3 8 9 9 6 1. 0


B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 8 0  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
A p pe n di x  E : K ar n ofs k y Perf or m a nce Sc ale   
Sc ore  
Descri pti o n  
1 0 0  
N or mal, n o c o m plai nts, n o e vi de nce of disease  
9 0  
A ble t o carr y o n n or mal acti vit y  
8 0  
N or mal acti vit y wit h eff ort  
7 0  
Cares f or self; u na ble t o carr y o n n or mal acti vit y or t o d o acti ve w or k  
6 0  
Re q uires occasi o nal assista nce b ut is a ble t o care f or m ost nee ds  
5 0  
Re q uires c o nsi dera ble assista nce a n d fre q ue nt me dical care  
4 0  
Disa ble d; re q uires s pecial care  a n d assista nce 
3 0  
Se verel y disa ble d; h os pitalizati o n i n dicate d; deat h n ot i m mi ne nt  
2 0  
Ver y sic k; h os pitalizati o n i n dicate d; deat h n ot i m mi ne nt  
1 0  
M ori b u n d; fatal pr ocesses pr o gressi n g ra pi dl y  
Sc ores 8 0 t o 1 0 0: a ble t o carr y o n n or mal acti vit y; n o s pecial care is n ee de d 
Sc ores 5 0 t o 7 0: u na ble t o w or k; a ble t o li ve at h o me a n d care f or m ost p ers o nal nee ds; a var yi n g de gree of assista nce nee de d  
Sc ores 1 0 t o 4 0: u na ble t o care f or self; re q uires e q ui vale nt of i nstit uti o nal or h os pice care; disease ma y  be pr o gressi n g ra pi dl y  
S o urce:  Kar n ofs k y et al. 1 9 4 9 (2 8 ) 
 
 
 
V V- C LI N- 0 6 3 8 9 9 6 1. 0


B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 8 1  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
A p pe n di x  F : E q u ati o ns t o Pre dict Gl o mer ul ar Filtr ati o n R ate ( M D R D-4)   
4 -V ari a ble M o dific ati o n of Diet i n Re n al Dise ase ( M D R D -4) E q u ati o n  
Hi g h Le vel F or m ul a f or Bl ac k or Af ric a n -A meric a n M ales:  
Esti mate d G F R = 1 7 5 × ( Creati ni ne -1. 1 5 4) × ( A ge -0. 2 0 3) × 1. 2 1 2 
 
Hi g h Le vel F or m ul a f or M ales N O T Bl ac k or Af ric a n -A meric a n ( a n y ot her o pti o n):  
Esti mate d G F R = 1 7 5 × ( Creati ni ne -1. 1 5 4) × ( A ge -0. 2 0 3) 
 
Hi g h Le vel F or m ul a f or Bl ac k or Af ric a n -A meric a n F e m ales:  
Esti mate d G F R = 1 7 5 × ( Creati ni ne -1. 1 5 4) × ( A ge -0. 2 0 3) × 1. 2 1 2 × 0. 7 4 2 
 
Hi g h Le vel F or m ul a f or Fe m ales N O T Bl ac k or Afric a n -A meric a n ( a n y ot her o pti o n):  
Esti mate d G F R = 1 7 5 × ( Creati ni ne -1. 1 5 4) × ( A ge -0. 2 0 3) × 0. 7 4 2 
Le ve y et al. 2 0 0 6 (2 9 ) 
 
 
 
V V- C LI N- 0 6 3 8 9 9 6 1. 0


B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 8 2  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
A p pe n di x  G : Deter mi ni n g Rel ati o ns hi p of  A Es t o St u d y Dr u g   
1  
N O T R E L A T E D  
T his cate g or y a p plies t o t h ose A E s w hic h, after caref ul me dical c o nsi derati o n, are clearl y felt t o be d ue t o 
ex tra ne o us ca uses (e. g., disease, e n vir o n me nt, etc.) that are u nrelate d  t o t he a d mi nistrati o n of st u d y dr u g. 
2  
U N LI K E L Y R E L A T E D  ( m ust ha ve first 2) 
T his cate g or y a p plies t o t h ose A E s w hic h, after caref ul me dical c o nsi derati o n, are felt u nli kel y t o be 
relate d t o t he a d mi nistrati o n of t he st u d y dr u g.  T he relati o ns hi p of a n A E  t o t he st u d y dr u g ca n be 
c o nsi dere d u nli kel y  if: 
•  
It d oes n ot f oll o w a reas o na ble te m p oral se q ue nce fr o m a d mi nistrati o n of t he dr u g. 
•  
It c o ul d rea dil y ha ve bee n a res ult of t he s u bject’s cli nical state, e n vir o n me ntal or t ox ic fact ors, or 
ot her m o des of t hera p y a d mi nistere d t o t he s u bj ect.  
•  
It d oes n ot f oll o w a k n o w n res p o nse patter n t o t he s us pecte d dr u g. 
•  
It d oes n ot rea p pear or w orse n w he n t he dr u g is re-a d mi nistere d. 
3  
P O S SI B L Y R E L A T E D ( m ust ha ve first 2) 
T his cate g or y a p plies t o t h ose A E s w hic h, after caref ul me dical c o nsi derati o n, are felt u nli kel y t o be 
relate d t o t he a d mi nistrati o n of t he st u d y dr u g, b ut t he p ossi bilit y ca n n ot be r ule d o ut wit h certai nt y.  T he 
relati o ns hi p of a n A E  t o t he st u d y dr u g ca n be c o nsi dere d p ossi ble  if: 
•  
It f oll o ws a reas o na ble te m p oral se q ue nce fr o m a d mi nistrati o n of t he dr u g. 
•  
It c o ul d rea dil y ha ve bee n a res ult of t he s u bject’s cli nical state, e n vir o n me ntal or t ox ic fact ors, or 
ot her m o des of t hera p y a d mi nistere d t o t he s u bj ect.  
•  
It f oll o ws a k n o w n res p o nse patter n t o t he s us pecte d dr u g. 
4  
P R O B A B L Y R E L A T E D ( m ust ha ve first 3) 
T his cate g or y a p plies t o t h ose A E s w hic h, after caref ul me dical c o nsi derati o n, are felt wit h a hi g h de gree 
of certai nt y t o be relate d t o t he a d mi nistrati o n of t he st u d y dr u g.  T he relati o n s hi p of a n A E  t o t he st u d y 
dr u g ca n be c o nsi dere d pr o ba ble  if: 
•  
It f oll o ws a reas o na ble te m p oral se q ue nce fr o m a d mi nistrati o n of t he dr u g.  
•  
It c o ul d n ot be reas o na bl y ex plai ne d b y t he k n o w n c haracteristics of t he s u bject’s cli nical state, 
e n vir o n me ntal or t o x ic fact ors or ot her m o des of t hera p y a d mi nistere d t o t he s u bject.  
•  
It disa p pears or decreases u p o n cessati o n of dr u g or re d ucti o n i n d ose. * 
•  
It f oll o ws a k n o w n res p o nse patter n t o t he s us pecte d dr u g. 
V V- C LI N- 0 6 3 8 9 9 6 1. 0


B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 8 3  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
5  
D E FI NI T E L Y R E L A T E D ( m ust ha ve first 3) 
T his cate g or y a p plies t o t h ose A E s, w hic h, after caref ul me dical c o nsi derati o n, are felt t o be relate d t o t he 
a d mi nistrati o n of t he st u d y dr u g.  T he relati o ns hi p of a n A E  t o t he st u d y dr u g ca n be c o nsi dere d relate d if: 
•  
It f oll o ws a reas o na ble te m p oral se q ue nce fr o m a d mi nistrati o n of t he dr u g or dr u g le vels ha ve 
bee n esta blis he d i n b o d y fl ui ds or tiss ues.  
•  
It c o ul d n ot be reas o na bl y ex plai ne d b y t he k n o w n c haracteristics of t he s u bject’s cli nical state, 
e n vir o n me ntal or t o x ic fact ors or ot her m o des of t hera p y  a d mi nistere d t o t he s u bject.  
•  
It disa p pears or decreases u p o n cessati o n of dr u g or re d ucti o n o n d ose a n d a p pears u p o n 
rec halle n ge. * 
•  
It f oll o ws a k n o w n res p o nse patter n t o t he s us pecte d dr u g. 
* T here are e x ce pti o ns w he n a n A E  d oes n ot disa p pear u p o n disc o nti n uati o n of t he dr u g, yet dr u g 
relate d ness clearl y ex ists. 
 
S o urce:  A da pte d fr o m C o bert B 2 0 1 2 (3 0 ) 
 
 
 
V V- C LI N- 0 6 3 8 9 9 6 1. 0


B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 8 4  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
A p pe n di x  H : Dr u gs t h at I n d uce C Y P 3 A 4   
T his is n ot a c o m pre he nsi ve list, a n d all c o nc o mita nt me dicati o ns s h o ul d be e val uat e d f or 
p ossi ble i nteracti o ns wit h bel u m os u dil . 
Ta ble 8 . 
E x a m ple s of Cli nic al I n d ucers of C Y P 3 A 4  
Str o n g I n d ucer  
M o der ate I n d ucer  
We a k I n d ucer  
A pal uta mi de  
Car ba maze pi ne  
E nzal uta mi de  
Mit ota ne  
P he n yt oi n  
Rifa m pi n  
St. J o h n’s w ort  
B ose nta n  
Efa vire nz  
Etra viri ne  
P he n o bar bital  
Pri mi d o ne  
Ar m o dafi nil  
M o dafi nil  
R ufi na mi de  
 
S o urce:  F D A. Dr u g De vel o p me nt a n d Dr u g I nteracti o ns.   
htt ps:// w w w.f da. g o v/ dr u gs/ de vel o p me nta p pr o val pr ocess/ d e vel o p me ntres o urces/ dr u gi nteracti o nsla beli n g/ u c m 0 9 3 6 6 4. ht m  
Ac cess e d 2 5  J un 2 0 2 1 (3 1 ) 
 
 
V V- C LI N- 0 6 3 8 9 9 6 1. 0


B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 8 5  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
A p pe n di x  I: Dr u gs T h at I n d uce a n d I n hi bit C Y P 1 A 2   
T his is n ot a c o m pre he nsi ve list, a n d all c o nc o mita nt me dicati o ns s h o ul d be e val uate d f or p ossi ble 
i nteracti o ns wit h bel u m os u dil . 
Ta ble 9 . 
E x a m ples of C li nic al In d ucers/ In hi bit ors of C Y P 1 A 2  
 
Str o n g  
M o der ate  
We a k  
I n d ucers 
Rifa m pi n  
P he n yt oi n  
Rifa m pi n  
Rit o na vir  
S m o ki n g  
T erifl u n o mi de  
--- 
I n hi bit o rs 
Ci pr ofl o xaci n  
E n o xaci n  
Fl u v o xa mi ne  
Met h o xsale n  
Me xileti ne  
Oral c o ntrace pti ves  
Ac ycl o vir  
All o p uri n ol  
Ci meti di ne  
P e gi nterfer o n α -2a  
Pi peri ne  
Zile ut o n  
 
S o urce: F D A. Dr u g De vel o p me nt a n d Dr u g I nteracti o ns.   
htt ps:// w w w.f da. g o v/ dr u gs/ de vel o p me nta p pr o val pr ocess/ d e vel o p me ntres o urces/ dr u gi nteracti o nsla beli n g/ u c m 0 9 3 6 6 4. ht m  
Ac cess e d 2 5 J u n 2 0 2 1 (3 1 ) 
 
 
 
V V- C LI N- 0 6 3 8 9 9 6 1. 0


B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 8 6  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
A p pe n di x  J : Dr u gs T h at Pr ol o n g Q Tc   
T his is n ot a c o m pre he nsi ve list, a n d all c o nc o mita nt me dicati o ns s h o ul d be e val uat e d f or 
p ossi ble i nteracti o ns wit h bel u m os u dil . 
Ta ble 1 0 . E x a m ples of D r u gs t h at P r ol o n g Q Tc 
Ge neric N a me  
•  
Aclar u bici n  
•  
Il o peri d o ne 
•  
A mi o dar o ne  
•  
Le v ofl o xaci n  
•  
A na greli de  
•  
Le v o me pr o mazi ne  
•  
Arse nic tri o xi de  
•  
Le v o met ha d yl acetate  
•  
Aste miz ole  
•  
Le v os ul piri de  
•  
Azit hr o m yci n  
•  
Mes ori dazi ne  
•  
Be pri dil  
•  
Met ha d o ne  
•  
C hl or o q ui ne  
•  
M o xifl o xaci n  
•  
C hl or pr o mazi ne  
•  
O n da nsetr o n  
•  
Cil ostaz ol  
•  
O xali plati n  
•  
Ci pr ofl o xaci n  
•  
Pa pa veri ne H Cl  
•  
Cisa pri de  
•  
Pe nta mi di ne  
•  
Cital o pra m  
•  
Pi m ozi de  
•  
Clarit hr o m yci n  
•  
Pr o b uc ol  
•  
Dis o p yra mi de  
•  
Pr ocai na mi de  
•  
D ofetili de  
•  
Pr o p of ol  
•  
D o m peri d o ne  
•  
Q ui ni di ne  
•  
D o ne pezil  
•  
R o xit hr o m yci n  
•  
Dr o ne dar o ne  
•  
Se v ofl ura ne  
•  
Dr o peri d ol  
•  
S otal ol  
•  
Er yt hr o m yci n  
•  
S parfl o xaci n  
•  
Escital o pra m  
•  
S ul piri de  
•  
Flecai ni de  
•  
S ult o pri de  
•  
Fl uc o naz ole  
•  
T erfe na di ne  
•  
Gatifl o xaci n  
•  
T erli pressi n  
•  
Gre pafl o xaci n  
•  
T er o dili ne  
•  
Hal ofa ntri ne  
•  
T hi ori dazi ne  
•  
Hal o peri d ol  
•  
Va n deta ni b  
•  
I b o gai ne 
 
•  
I b utili de 
 
S o urce:  htt ps://cre di ble me ds. or g/ p dfte m p/ p df/ C o m bi n e d List. p df   Ac cess e d 1 1  Ma y  2 0 2 0 (3 2 ) 
V V- C LI N- 0 6 3 8 9 9 6 1. 0


B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 8 7  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
A p pe n di x  K : Pre d nis o ne D ose E q ui v ale nts   
C ha n ge i n c ortic oster oi d d oses will be a nal yze d b y usi n g pre d nis o ne d ose e q ui vale nts.  If s u bj ects are n ot 
usi n g pre d nis o ne as t he s yste mic c ortic oster oi d, t he n t he p re d nis o ne d ose e q ui vale nt will be deter mi ne d 
acc or di n g t o f oll o wi n g c o n versi o n rati os .  
O ne m g of pre d nis o ne is e q ui vale nt t o:  
•  4. 0 m g h y dr oc ortis o ne  
•  0. 8 m g Met h yl pre d nis ol o ne  
•  0. 1 5 m g De x a met has o ne  
•  1. 0 m g Pre d nis ol o ne  
•  0. 8  m g Tria mci n ol o ne  
 
S o urce:  Li u D  et al. 2 0 1 3 (3 3 )  
 
V V- C LI N- 0 6 3 8 9 9 6 1. 0

SAP_001.pdf: 
STATISTICAL ANALYSIS PLAN 
Extended Treatment and Follow-up of Subjects Treated with Belumosudil in Study KD025-208 
or Study KD025-213 
Protocol Number: 
KD025-217 
Study Drug: 
Belumosudil (KD025) 
IND Number: 
IND 125890 
Phase: 
2 
Sponsor: 
Sanofi 
55 Corporate Drive 
Bridgewater, NJ 08807 
Version 1: 
03Apr2024 
VV-CLIN-0671890 1.0
 NCT: NCT05305989


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DOCUMENT HISTORY 
Version 
Author 
Description 
V1 
Original Document 
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TABLE OF CONTENTS 
STATISTICAL ANALYSIS PLAN ................................................................................................ 1 
SIGNATURE PAGE ................................................................................................................... 2 
DOCUMENT HISTORY ............................................................................................................. 3 
TABLE OF CONTENTS ............................................................................................................. 4 
LIST OF ABBREVIATIONS ........................................................................................................ 6 
1 
INTRODUCTION .................................................................................................................. 7 
2 
STUDY SUMMARY .............................................................................................................. 7 
2.1 
Study Objectives .......................................................................................................... 7 
2.1.1 Primary objective ......................................................................................................... 7 
2.1.2 Secondary objectives................................................................................................... 7 
2.2 
Study Design ............................................................................................................... 8 
2.3 
Visit Schedule and Study Assessment ......................................................................... 9 
3 
STATISTICAL METHODS .................................................................................................... 9 
3.1 
General Methods ......................................................................................................... 9 
3.1.1 Computing Environment .............................................................................................. 9 
3.1.2 Sample Size Justification ............................................................................................. 9 
3.1.3 General Considerations ............................................................................................... 9 
3.1.4 Study Day ...................................................................................................................10 
3.1.5 Baseline .....................................................................................................................10 
3.1.6 Handling of Incomplete or Missing Data .....................................................................10 
3.2 
Analysis Populations ..................................................................................................12 
3.3 
Subject Disposition and Evaluability ...........................................................................12 
3.4 
Demographics and Baseline Characteristics ...............................................................12 
3.4.1 Demographics and Other Characteristics ...................................................................12 
3.4.2 Medical History ...........................................................................................................12 
3.5 
Concomitant Medications ...........................................................................................13 
3.6 
Treatment Exposure ...................................................................................................13 
3.7 
Definition of Efficacy Endpoints ..................................................................................13 
3.7.1 Primary Efficacy Endpoint: Overall Response Rate (ORR) .........................................13 
3.7.2 Secondary Efficacy Endpoints ....................................................................................15 
3.8 
Safety Analysis ...........................................................................................................20 
3.8.1 Adverse Events ..........................................................................................................20 
3.8.2 Clinical Laboratory Evaluation ....................................................................................21 
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3.8.3 Vital Signs ..................................................................................................................22 
3.8.4 ECG ...........................................................................................................................22 
3.9 
Pharmacokinetic Analysis ...........................................................................................23 
3.10 Pharmacodynamics Analysis ......................................................................................23 
3.11 Exploratory Objectives Analysis ..................................................................................23 
4 
APPENDIX A: Kadmon Algorithmic Response Assessments ..............................................24 
 
 
 
 
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LIST OF ABBREVIATIONS 
Abbreviation Full Term 
AE 
Adverse Event 
ALP 
Alkaline phosphatase 
ALT 
Alanine aminotransferase 
AST 
Aspartate aminotransferase 
ATC 
Anatomical therapeutic Class 
BID 
Two times a day 
BMI 
Body Mass Index 
cGVHD  
Chronic Graft Versus Host Disease 
CI 
Confidence interval 
CKD-EPI 
Chronic Kidney Disease Epidemiology Collaboration  
CM 
Concomitant Medication 
CR 
Complete Response 
CRF 
Case Report Form 
CTCAE 
Common Terminology Criteria for Adverse Events 
DOR 
Duration of Responses 
ECG  
Electrocardiogram 
FEV1 
Forced Expiratory Volume in One Second 
FFS  
Failure Free Survival 
ICF  
Informed Consent Form 
ICH 
International Conference on Harmonisation 
KPS 
Karnofsky Performance Scale 
LR 
Lack of Response 
LSS 
Lee Symptom Scale Score 
LTFU 
Long-term Follow-up 
MDRD-4 
Modification of Diet in Renal Disease 
MedDRA 
Medical Dictionary for Regulatory Activities  
NE 
Not Evaluable 
NIH  
National Institutes of Health 
OS 
Overall Survival  
PFT 
Pulmonary Function Test 
PR 
Partial Response 
PT 
Preferred Term 
QD 
Every day 
QTcF 
Corrected QT interval using Fridericia's formula 
SAP 
Statistical Analysis Plan 
SOC 
System Organ Class 
TEAE 
Treatment-emergent Adverse Event 
TTNT 
Time to Next Treatment 
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1 INTRODUCTION 
This Statistical Analysis Plan (SAP) describes data-handling and statistical procedures to be 
used for Study KD025-217 as specified in protocol (Amendment No. 1, 08 September 2021): 
Extended Treatment and Follow-up of Subjects Treated with Belumosudil in Study KD025-208 
or Study KD025-213. 
The SAP was written in accordance with the recommendations outlined in the International 
Conference on Harmonisation (ICH) E9 Guideline entitled “Guidance for Industry: Statistical 
Principles for Clinical Trials” and the most recent ICH-E3 Guideline, entitled “Guidance for 
Industry: Structure and Content of Clinical Study Reports.”  
2 STUDY SUMMARY 
2.1 
Study Objectives 
2.1.1 
Primary objective 
• 
The objective of this study is to evaluate long-term safety and efficacy of belumosudil in 
subjects with Chronic Graft Versus Host Disease (cGVHD) who have previously been 
treated with belumosudil. 
2.1.2 
Secondary objectives 
• 
Duration of Responses (DOR): Response is defined by the 2014 National Institutes of 
Health (NIH) Consensus Development Project on clinical trials in cGVHD and are 
assessed by investigators  
• 
Change in Lee Symptom Scale Score (LSS)  
• 
Time to Next Treatment (TTNT)  
• 
Failure Free Survival (FFS) 
• 
Overall Survival (OS) 
• 
Percentage of subjects who have a best response of Partial Response (PR) and 
percentage of subjects who have a best response of Complete Response (CR)  
• 
Response by individual organ  
• 
Change in corticosteroid dose  
• 
Change in cGVHD Global Severity Rating based on the Clinician-reported Global 
cGVHD Activity Assessment  
 
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2.2 
Study Design 
KD025-217 is a Phase 2, open-label, extended treatment and follow-up study in subjects with 
cGVHD who have been previously treated with belumosudil in Study KD025-208 or in Study 
KD025-213. 
Subjects who have signed the Informed Consent Form (ICF) will be enrolled in Study KD025-
217 if they have met any of the following conditions:  
• 
Actively receiving belumosudil in Study KD025-208 or in Study KD025-213 (excluding 
adults in the Companion Study and excluding adolescents enrolled under KD025-213 
Amendment 2 [01June 2020])  
• 
Is in long-term follow-up (LFTU) on Study KD025-208 or Study KD025-213. Long-term 
follow-up will be defined as the period after ending treatment with belumosudil and until 
an FFS event occurs.  
• 
Adult enrolled in the Companion Study as specified in Study KD025-213 Amendment 2 
(01 June 2020) and received at least 6 months of treatment or is in LTFU. 
After signing the ICF, at Baseline, subjects will undergo efficacy assessments by Clinician-
reported Global cGVHD Activity Assessment, response assessment, pulmonary function tests 
(PFTs), LSS score, and documentation of corticosteroid dosage and/or other therapies for 
cGVHD. 
 
Subjects will undergo safety assessments including symptom-directed Physical Exams (PE), 
vital signs, weight, height, Karnofsky Performance Scale (KPS), hematology and clinical 
chemistry laboratory testing, pregnancy testing, 12-lead Electrocardiogram (ECG), documenting 
concomitant medications, and monitoring for Adverse Events (AEs). Subjects will continue on 
their same dosing regimen they received in Study KD025-208 or Study KD025-213: belumosudil 
200 mg QD, 200 mg BID, or 400 mg QD. If the Investigator reduced the subject’s dose of 
belumosudil in either Study KD025-208 or Study KD025-213, the subject will continue to receive 
that same reduced dose treatment with belumosudil throughout Study KD025-217 or until the 
AE that led to the temporary dose reduction has resolved, in which case the dose treatment can 
resume at the original dose at the discretion of the Investigator. Subjects will begiven a study 
drug diary to record daily dosing. Subjects may be administered the first dose either in the clinic 
or self-administered at home.  
 
At 3 months after Baseline and every 3 months thereafter (± 14 days), subjects will report to the 
clinic for the same efficacy and safety assessments and dispensing of belumosudil at Baseline. 
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(Height is only required at Baseline.) The study drug diaries for the past 3 months will be 
collected, and new study drug diaries dispensed. Any remaining belumosudil will be collected.  
Subjects may receive belumosudil on Study KD025-217 for up to an additional 2 years, at the 
discretion of the Investigator (and with guidance from the medical monitor), beyond what they 
had received in Study KD025-208 or Study KD025-213, cGVHD progression, or unacceptable 
toxicity. 
 
Subjects will return to the clinic for a 28-day Follow-up Visit at 28 days (± 7 days) after the last 
dose of study drug. Subjects will have LFTU approximately every 3 months until an FFS event 
occurs. After the 28-day Follow-up Visit has been completed, subjects will be contacted 
approximately every 3 months by telephone, e-mail, or postal mail to confirm survival status, 
any initiation of new systemic cGVHD therapies, and relapse of underlying disease. 
Alternatively, this information may be obtained from the subject’s medical records. 
2.3 
Visit Schedule and Study Assessment 
The flow chart of visit schedule and study assessments is given in Appendix A of the KD025-
217 Protocol. 
3 STATISTICAL METHODS 
3.1 
General Methods 
3.1.1 
Computing Environment 
All statistical analyses will be performed using SAS® Version 9.4 or higher for Windows. 
3.1.2 
Sample Size Justification 
No formal power calculation will be performed to determine the study sample size.   
3.1.3 
General Considerations  
General considerations for descriptive statistics, presentation, and analysis model (for efficacy 
analysis) used for continuous and categorical data are given below.  
3.1.3.1 
Reporting of Numerical Values 
Continuous data will be described using descriptive statistics: number of observations (n), 
mean, standard deviation, median, minimum and maximum. Frequencies and percentages will 
be used for summarizing categorical data. When categorical data are presented, the percent will 
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be suppressed when the count is zero in order to draw attention to the non-zero counts. The 
denominator for all percentages, unless otherwise specified, will be the number of subjects in 
the specified analysis population or group.  
Means, medians, standard deviations, and confidence intervals will be reported to one decimal 
place more than the data reported on the case report form (CRF) or by the laboratory/vendor. 
Minimum and maximum will be reported to the same number of decimal places displayed on the 
CRF or by the laboratory/vendor. P-Values will be reported to 4 decimal places.  
3.1.4 
Study Day 
The study day for all assessments prior to the first study drug administration is calculated as the 
difference between the date of the measurement (e.g., assessment date, sample collection 
date, etc.) and the start date of study treatment. The day before the start of study treatment is 
Study Day -1.   
The study day for all post assessments after the first study drug administration is calculated as 
the difference between the date of the measurement (e.g., assessment date, sample collection 
date, etc.) and the start date of study treatment in parent study KD025-208/KD025-213, plus 
one day. The first day of study treatment is Study Day 1. 
3.1.5 
Baseline 
Baseline value for efficacy analyses is defined as the valid and last non-missing value obtained 
within 28 days prior to subject receiving the first study medication in parent study KD025-
208/KD025-213.  
Baseline value for safety analyses is defined as the “Baseline” visit from KD025-217.  
Baseline can be the day before the first study medication or on the same day as the first study 
medication if a pre-dose assessment is available. Subjects without data on a parameter before 
the first study medication will have a missing baseline for this parameter. 
3.1.6 
Handling of Incomplete or Missing Data 
Missing data will not be imputed in general and it will be reported as missing in all listings. For 
categorical variables, patients with missing data are not included in calculations of percentages 
unless otherwise specified. 
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3.1.6.1 
Missing start and end dates for AE and concomitant medication (CM)  
The assumption will be the worst or most conservative judgment when imputing AE and CM 
start and end dates. The purpose of imputing a start date is to help define whether the AE/CM 
started while taking study drug. 
For a partial or missing start date: 
• 
If the day is missing, the first day of the month will be imputed. If the missing day is the 
same as the month of first dose of study drug, then the first dose date will be imputed. 
• 
If the day and month are missing, the first day of January will be imputed. If the year is 
the same as the first dose date, then the first dose date will be imputed. 
• 
If the day is completely missing, the first dose date will be imputed. If the end date 
suggests it could have started prior to this, the first day of January of the same year as 
the end date will be imputed. 
• 
When imputing a start date, the start date will ensure that the new imputed date is 
sensible, i.e., is prior to the end date of the AE or CM. 
For a partial or missing end date: 
• 
If the day is missing, the last day of the month or the last assessment date, whichever is 
earlier, will be imputed. 
• 
If the day and month are missing, the 31st of December or the last assessment date, 
whichever is earlier, will be imputed. 
• 
If the date is completely missing, there will be a need to look at whether the AE/CM is 
still ongoing before imputing a date. If the ongoing flag is missing, then it will be 
assumed that AE is still present, or CM is still being taken (i.e., do not impute a date). If 
the AE/CM has stopped, then the last assessment date will be imputed. 
These data imputations are for categorization purpose only and will not be used in listings. 
If the assessment of the relationship of the AE to belumosudil is missing, then it will be assumed 
that the AE is related to belumosudil and the AE considered as such in the frequency tables of 
possibly related AEs. No imputation should be done at the data level. 
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3.1.6.2 
Missing event dates 
Event date will be imputed only when day is missing, and the purpose of imputing an event date 
is to most conservatively calculate time to event. If the day is missing, the first (mid, last) day of 
the month will be imputed for undesired (neutral, desired) event. If the missing day is the same 
as the month of first dose of study drug, then the first dose date will be imputed for undesired 
event. These data imputations are for time to event calculation only and will not be used in the 
listings. 
3.2 
Analysis Populations 
Full Analysis Set: The Full Analysis Set is defined as all subjects enrolled in the study. All 
safety and efficacy analyses will be performed on the Full Analysis Set.  
There are 3 treatment groups for this study: belumosudil 200 mg QD, 200 mg BID, and 400 mg 
QD. Each subject’s treatment group is determined by their originally assigned dosing cohort 
(Study KD025-208) or randomized arm (Study KD025-213). 
3.3 
Subject Disposition and Evaluability 
A disposition of safety population, the number of subjects discontinuing from treatment, and the 
primary reason for discontinuation will be summarized. This summary will also be presented by 
exposure range. 
Subject listing will be provided for the disposition of subjects who died during study.  
3.4 
Demographics and Baseline Characteristics 
3.4.1 
Demographics and Other Characteristics 
Subject demographics information will be summarized. Descriptive statistics will be provided for 
age, height, weight, body mass index (BMI) and KPS. Frequencies and percentages will be 
tabulated for gender, child bearing potential, race, and ethnicity.  
Demographics and other baseline characteristics will be summarized by treatment group in 
each population.  
3.4.2 
Medical History 
Medical history will be coded using Medical Dictionary for Regulatory Activities (MedDRA) 
Version 24.1 terminology, and summarized by Preferred Term (PT). Subject listing will be 
provided.  
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3.5 
Concomitant Medications 
Concomitant medications will be coded using the World Health Organization Drug Dictionary 
(WHODrug-Global-B3, version 202109). CM are defined as medications taken after the start of 
study treatment and during the study period, including those initiated before but ongoing at the 
start of study treatment. If a medication start date is partially or fully missing and it is unclear as 
to whether the medication is prior or concomitant, it will be assumed that the medication is 
concomitant.  
Number and percentage of incidence of CM will be summarized according to Anatomical 
Therapeutic Class (ATC) and preferred drug name.  
3.6 
Treatment Exposure 
The number of subjects will be summarized, along with descriptive summary of duration of 
treatment, exposure ranges and overall exposure.  
The duration of treatment (days) is defined as: (Date of last dose – Date of first dose) + 1. It will 
also be classified into the following exposure ranges: 0 to 6 months; > 6 to 12 months, > 12 to 
18 months, > 18 to 24 months, > 24 to 30 months, > 30 to 36 months and > 36 months.  
Overall exposure will be summarized in total patient-years, derived as Exposure in patient 
(years) = Sum of duration of treatment in days (for all patients in each dose group) / 365.25. 
3.7 
Definition of Efficacy Endpoints  
3.7.1 
Primary Efficacy Endpoint: Overall Response Rate (ORR) 
Kadmon Algorithmic Response Assessments is used in all of the overall response analyses. 
Individual organ response is assessed for Skin, Eyes, Mouth, Esophagus, Upper GI, Lower GI, 
Liver, Lungs, Joints and Fascia and Global Severity Rating by using individual scores or 
assessment results for the ten systems based on the APPENDIX A in the SAP. The overall 
response is calculated from the 9 organ (Skin, Eyes, Mouth, Esophagus, Upper GI, Lower GI, 
Liver, Lungs, and Joints and Fascia) response using the definition in the Table 2 below. 
Response is assessed with respect to the parent study baseline (Cycle 1, Day 1 (C1D1)) 
cGVHD assessment. The overall response at each assessment time point is categorized as 
Complete Response (CR), Partial Response (PR), or Lack of Response (LR), where LR 
includes the response status of unchanged, mixed, or progression as defined in Table 1.  
The ORR is defined as the proportion of subjects with a best response meeting the overall 
response criteria assessment of CR or PR at any post-baseline response assessment.  
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If a treated subject is lost to follow up without any response assessment, this subject will be 
counted as a non-responder.  
Point estimates, two-sided 95% confidence intervals (Clopper-Pearson (exact) method), by 
treatment groups will be reported. The number and percentage of subjects who have a best 
response of PR and number and percentage of subjects who have a best response of CR will 
be reported. 
In addition to ORR assessed by investigators, analyses of ORR and DOR will be repeated with 
this investigator’s assessment of overall response. 
The following will also be presented: 
Table 1 cGVHD Response Definitions 
Response  
Definition  
Complete Response (CR) 
Resolution of all manifestations of cGVHD in each organ or site  
Partial Response (PR) 
Improvement in at least one organ or site without progression in 
any other organ or site  
Lack of Response (LR) 
 
    Mixed (LR-M) *  
Complete or partial response in at least one organ accompanied 
by progression in another organ  
    Unchanged (LR-U)  
Outcomes that do not meet the criteria for complete response, 
partial response, progression or mixed response  
    Progression (LR-P)  
Progression in at least one organ or site without a response in any 
other organ or site  
 
*Considered progression for purposes of analysis  
 
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3.7.2 
Secondary Efficacy Endpoints 
3.7.2.1 
Duration of Response (DOR) 
DOR will be presented according to 5 methodologies:  
• 
The primary definition of DOR is the time from first documentation of response to the 
time of first documentation of deterioration from best response (e.g., CR to PR, or PR to 
LR).  
• 
The secondary definition of DOR is the time from first documentation of response to the 
time of first documentation of lack of response.  
• 
The tertiary definition of DOR is the time from first documentation of response to the time 
of initiation of new systemic cGVHD therapy.  
• 
The quaternary definition of DOR is the time from first documentation of response to the 
time of first documentation of lack of response (as the secondary definition) but with 
durations summed for multiple response/lack of response episodes.  
• 
The FDA definition of DOR is the time from first documentation of response to the time 
of first documentation of organ-level progression, initiation of a new cGVHD therapy, or 
death from any cause, whichever occurs first  
The DOR will be reported for early responders, and statistics will include:  
• 
Kaplan-Meier plots and descriptive statistics of DOR. The censoring rules in Table 2 will 
be applied  
• 
Landmark analyses: Number and percentage of subjects with response sustained for ≥ 
3, ≥ 6, ≥ 9, ≥ 12, ≥ 15, ≥ 18, ≥ 24, ≥ 30, ≥ 36 months  
Table 2 Censoring Rules for Duration of Response 
DOR 
Events 
Censoring 
Primary 
 
• 
Deterioration from best response  
• 
Initiation of new systemic therapy 
for cGVHD  
• 
Death  
 
• 
Last documented response 
assessment  
• 
If LR or initiation of new 
systemic therapy happens 
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Secondary 
 
• 
Documented LR  
• 
Initiation of new systemic therapy 
for cGVHD  
• 
Death  
immediately after two or 
more missed response 
assessments, the event 
date is set as 24 weeks 
after last documented 
response assessment prior 
this event  
 
Tertiary 
 
• 
Initiation of new systemic therapy 
for cGVHD  
• 
Death  
Last response assessment or long 
term follow up assessment, 
whichever is the latest and 
available  
 
Quaternary  
 
• 
Documented LR  
• 
Initiation of new systemic therapy 
for cGVHD  
• 
Death  
• 
With summation of DOR from 
multiple response episodes  
Same as censoring rules for 
primary and secondary  
FDA defined  
• 
Documentation of organ-level 
progression  
• 
Initiation of a new cGVHD 
therapy  
• 
Death 
 
• 
Last documented response 
assessment  
• 
If organ-level progression 
or initiation of new 
systemic therapy happens 
immediately after two or 
more missed response 
assessments, the event 
date is set as 24 weeks 
after last documented 
response assessment prior 
this event  
  
 
3.7.2.2 
Change in Lee Symptom Scale Score (LSS) 
The Lee cGVHD Symptom Scale consists 30 items of 7 domains: skin, eyes and mouth, 
breathing, eating and digestion, muscles and joints, energy, and mental and emotional. Each 
question is scored 0, 1, 2, 3 or 4.  
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A domain score will be calculated for each domain by taking the mean of all items completed if 
more than 50% were answered and normalizing to a 0 to 100 scale. A summary score will be 
calculated as average of all non-missing domain scores if more than 50% of them are non-
missing. A higher score indicated more bothersome symptoms. 7 points difference on the 
summary score of cGVHD symptom scale was found to be clinically meaningful. In the above 
formulas, m is the number of items have non-missing value in a domain, and n is the number of 
domains have non-missing domain scores. 
 
 
 
 
In the above formulas, m is the number of items have non-missing value in a domain, and n is 
the number of domains have non-missing domain scores. 
Analyses will include:  
• 
Both score and change-from-baseline values (summary score and domain scores) will 
be summarized as continuous variables by visit  
• 
Number and percent of subjects with a ≥7-point reduction from baseline (C1D1)  
• 
Number and percent of subjects with a ≥7- point reduction from baseline on at least 2 
consecutive post-baseline assessments. 
• 
Duration of a 7-PtR (DO7-PtR) (defined as time from documentation of the first ≥7-point 
reduction to the first documentation of less than 7-point reduction). If there are multiple 
episodes, then DO7-PtR will be measured as the sum of DO7-PtR from all episodes.   
These analyses will be performed on Full Analysis Set.  
3.7.2.3 
Time to Next Treatment (TTNT) 
The TTNT will be measured as the time from first treatment to the time of new systemic cGVHD 
treatment (which will be defined by clinical team review), censored by last response assessment 
or long term follow up assessment, whichever is the latest and available. TTNT will be analyzed 
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by the Kaplan-Meier survival method as well as the landmark analysis at 6, 12, 18, and 24 
months. 
3.7.2.4 
Failure-free-survival (FFS) 
FFS is defined as the absence of new cGVHD systemic therapy, non-relapse mortality and 
recurrent malignancy (i.e., underlying disease) and is censored by last response assessment or 
long term follow up assessment, whichever is the latest and available. Kaplan-Meier plots, 
descriptive statistics of FFS and landmark FFS at 6, 12, 18, 24, 30 and 36 months will be 
provided. In addition, analyses for the three components of FFS will also be provided. 
3.7.2.5 
Overall Survival (OS) 
OS is defined as time from first dose of belumosudil to the date of death due to any cause and 
is censored by last response assessment or long term follow up assessment, whichever is the 
latest and available. Kaplan-Meier plots, descriptive statistics of OS and landmark OS at 6, 12, 
18, 24, 30, 36 months will be provided. 
3.7.2.6 
Percentage of subjects who have a best response of PR and percentage of 
subjects who have a best response of CR  
The percentage of subjects who have a best response of PR and percentage of subjects who 
have a best response of CR will be summarized separately by treatment groups.  
3.7.2.7 
Response by individual organ 
For KD025-213 and KD025-217 organ involvement is captured in the CRF. For KD025-208, the 
database did not specifically capture baseline organ involvement. Organ involvement was 
determined as follows: 
• 
All organs, except lungs: 
o If the baseline score is > 0, the organ will be defined as Involved, unless all response 
assessments are Not Evaluable (NE) 
o If the baseline score is 0, the organ will be defined as Not Involved, unless any 
response assessment of CR or PR which triggers clinical review to confirm baseline 
involvement.  
• 
For the lungs: 
o If Forced Expiratory Volume in One Second (FEV1) ≥ 75%, the organ will be defined 
as Not Involved 
o If FEV1 < 75%, the organ will be defined as Involved, unless all responses are NE 
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The response assessment for the 9 individual organs (skin, eyes, mouth, esophagus, upper GI, 
lower GI, liver, lungs, and joints and fascia) and global severity rating is categorized into 5 
response status: CR, PR, Progression, NE, Stable. 
Number and percentage of subjects with best response of CR or PR and total (CR+PR) by 
individual organ system and global severity rating will be summarized and presented. With the 
total number of subjects in the Full Analysis Set with involvement of the given organ at baseline 
as denominator.  
 
3.7.2.8 
Change in corticosteroid dose  
Corticosteroid doses will be presented as mg/kg/day prednisone equivalent dose. Any 
corticosteroid dose increases to ≥ 0.9 mg/kg PE during the study is counted as new systemic 
cGVHD therapy.  
Descriptive statistics for the Full Analysis Set will be provided for:  
• 
Both prednisone equivalent dose and change-from-baseline values (summary score and 
domain scores) will be summarized as continuous variables by visit  
• 
Change and % change from baseline to the greatest corticosteroid dose reduction at any 
post-baseline visit  
• 
Number and % of subjects who reduced systemic corticosteroid dose at any post-
baseline visit  
• 
Number and % of subjects who ever discontinued systemic corticosteroid usage at any 
post-baseline visit  
If subjects are not using prednisone as the systemic corticosteroid, then the prednisone dose 
equivalent will be determined according to following conversion ratios2:  
1 mg prednisone is equivalent to:  
• 
4mg Hydrocortisone  
• 
0.8mg Methylprednisolone  
• 
0.15mg Dexamethasone  
• 
1mg Prednisolone  
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• 
0.8mg Triamcinolone  
3.7.2.9 
Change in cGVHD Global Severity Rating based on the Clinician-reported 
Global cGVHD Activity Assessment  
The Clinician-reported global cGVHD Activity Assessment is a 0-10 point numeric rating scale 
with a score of 0 indicating “cGVHD symptoms not at all severe” and a score of 10 being “Most 
severe cGVHD symptoms possible”. The activities are assessed on at baseline and then every 
3 months after.  
Change from baseline in cGVHD severity based on the Clinician-reported global cGVHD Activity 
Assessment will be summarized as a categorical endpoint at all scheduled assessment visits.    
 
3.8 
Safety Analysis 
Safety assessments include AEs, clinical laboratory evaluations (hematology and chemistry), 
vital sign measurements, and electrocardiograms. Unscheduled visits for safety assessments 
will not be presented in by visit summary tables but will be in listings and shift tables. All safety 
analyses will be performed using the safety population.  
3.8.1 
Adverse Events 
AEs will be coded using the MedDRA dictionary (Version 24.1 or higher). Treatment-emergent 
AEs (TEAEs) are any AEs occurring or worsening in severity after the first administration of 
study medication until 28 days after EOT. All AEs will undergo 4 sets of ratings by Investigator 
as follows:  
• 
Serious vs. non-serious [based on seriousness criteria of death, life threatening, 
hospitalization – initial or prolonged, IME, disability or permanent damage, congenital 
anomaly or birth defects, and required intervention] 
• 
Grades using the 5-point Common Terminology Criteria for Adverse Events (CTCAE 
4.03) scale (mild, moderate, severe, life-threatening, or death) 
• 
Causality assessment with respect to study drug classified as either: related (definitely 
related, related, probably related, and possibly related) or not related (unlikely related, 
not related). 
• 
The relationship of AEs to cGVHD or the underlying disease 
 
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The number (N) and percentage (%) of patients who experienced at least one TEAE will be 
summarized by dose group, including tabulation by: 
• 
System Organ Class (SOC) and PT within each SOC in decreasing total frequency 
• 
Decreasing frequency of PT 
• 
Maximum severity 
• 
Relationship to study drug 
These analyses will be repeated for serious TEAEs, events leading to dose modification, events 
leading to study drug discontinuation, events related to study drug and events related to cGVHD 
or the underlying disease.  
Subject listings will be provided for AEs, SAEs, AEs resulting in study drug discontinuation and 
deaths. Time to onset and duration of AEs will be included in listings, along with action taken 
and outcome. 
3.8.2 
Clinical Laboratory Evaluation 
The summary statistics (including number, mean, SD, median, minimum and maximum) of all 
laboratory variables and changes from baseline will be calculated for each visit or study 
assessment by treatment group.   
For parameters of white blood cell counts, neutrophils (absolute count), lymphocytes (absolute 
count), monocytes (absolute count), hemoglobin, platelets, ALP, ALT, aspartate 
aminotransaminase, gamma glutamyl transferase, total bilirubin, glomerular filtration rate, plots 
of mean/mean changes from baseline with the corresponding standard error will be displayed. 
For shift tables, laboratory results will be classified using the CTCAE 4.03. All graded laboratory 
parameters will be summarized separately for hematology and biochemistry. Corresponding 
shift tables to compare baseline to the worst post-baseline grade within the treatment period will 
be provided.   
A by patient by lab tests by visit listing will be generated for lab results with CTC grade >=3. 
The estimated glomerular filtration rate will be calculated and summarized using the 
Modification of Diet in Renal Disease (MDRD-4) and Chronic Kidney Disease Epidemiology 
Collaboration 2021 (CKD-EPI2021) methods. Below is the formula used for each respective 
method.  
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Method 
Formula  
MDRD-4 
eGFR = 175 x (SCr)-1.154 x (age)-0.203 x 0.742 [if female] x 1.212 [if Black] 
CKD-EPI2021 
eGFR = 142 x min(Scr/κ, 1)α x max(Scr/κ, 1)-1.200 x 0.9938Age x 1.012 [if 
female] 
Where:  
Scr = standardized serum creatinine in mg/dL 
κ = 0.7 (females) or 0.9 (males) 
α = -0.241 (female) or -0.302 (male) 
min(Scr/κ, 1) is the minimum of Scr/κ or 1.0 
max(Scr/κ, 1) is the maximum of Scr/κ or 1.0 
3.8.3 
Vital Signs 
Descriptive statistics for vital signs (weight, temperature, systolic and diastolic blood pressure, 
pulse rate (beats/min), and respiratory rate (breath/min)) values and the change from baseline 
will be presented by treatment group for each scheduled assessment time point. 
A by patient by visit listing will be generated for vital signs. 
3.8.4 
ECG 
Descriptive statistics for ECG parameters (i.e., heart rate, PR interval, RR interval, QRS interval, 
QT interval, and QTcF interval) at each time point will be presented for the absolute values and 
change from baseline scores (QTcF is the QT interval using Fridericia’s correction which is 
calculated by QTcF = QT/RR1/3).  
The number and percentage of subjects with observed absolute QTcF values at maximum value 
during treatment period that satisfy the following conditions will be presented by dose group: ≤ 
450 ms; > 450 to 480 ms; > 480 to 500 ms; and > 500 ms.  
The number and percentage of subjects having change from baseline QTcF at maximum value 
during treatment period that satisfy the following conditions will be presented by dose group: ≤ 0 
ms; > 0 to ≤ 30 ms; > 30 to ≤ 60 ms; and > 60 ms. 
A by patient by visit listing will be generated for ECG results. 
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3.9 
Pharmacokinetic Analysis  
No PK assessments for analysis will be performed in this study.  
3.10 
Pharmacodynamics Analysis  
No pharmacodynamic assessments for analysis will be performed in this study.  
3.11 
Exploratory Objectives Analysis  
No exploratory analyses will be conducted. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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4 APPENDIX A: Kadmon Algorithmic Response Assessments 
Baseline Organ Involvement 
Organ  
Organ Involvement  
Esophagus  
NIH Esophagus Score ≥ 1, not entirely explained by non-cGVHD 
cause  
Upper GI  
NIH Upper GI Score ≥ 1, not entirely explained by non-cGVHD cause  
Lower GI  
NIH Lower GI Score ≥ 1, not entirely explained by non-cGVHD cause  
Lungs  
FEV1 <75% predicted, not entirely explained by non-cGVHD cause  
If no PFTs available, use NIH lung score ≥ 1, not entirely explained by 
non-cGVHD cause  
Eyes  
NIH Eye Score ≥ 1, not entirely explained by non-cGVHD cause  
Joints and 
Fascia  
P-ROM Score <25 (< maximal score) or NIH Joints/Fascia Score ≥ 1, 
not entirely explained by non-cGVHD cause  
Skin  
NIH Skin Score ≥ 1, not entirely explained by non-cGVHD cause  
Mouth  
NIH Modified Oral Mucosal Rating Score ≥ 1, not entirely explained by 
non-cGVHD cause  
Liver  
Elevation > 2x ULN of one or more (ALT, ALP, Total Bilirubin), not 
entirely explained by non-cGVHD cause  
 
Response Assessments 
Organ  
Complete 
Response  
Partial 
Response  
Unchanged  
Progression  Non 
Evaluable  
Esophagus  
NIH 
Esophagus 
Score 0 after 
previous 
involvement  
Decrease in 
NIH 
Esophagus 
Score by 1 
or more 
points  
No change 
or increase 
from 0 to 1 in 
NIH 
Esophagus 
Score  
Increase in 
NIH 
Esophagus 
Score by 1 
or more 
points, 
except 0 to 1  
NIH 
esophagus 
score is Non 
evaluable  
Upper GI  
NIH Upper 
GI Score 0 
after 
previous 
involvement  
Decrease in 
NIH Upper 
GI Score by 
1 or more 
points  
No change 
or increase 
from 0 to 1 in 
NIH Upper 
GI Score  
Increase in 
Upper GI 
Score by 1 
or more 
points, 
except 0 to 1  
NIH upper GI 
score is Non 
evaluable  
Lower GI  
NIH Lower 
GI Score 0 
after 
previous 
involvement  
Decrease in 
NIH Lower 
GI Score by 
1 or more 
points  
No change 
or increase 
from 0 to 1 in 
NIH Lower 
GI Score  
Increase in 
Lower GI 
Score by 1 
or more 
points, 
except 0 to 1  
If NIH Lower 
GI score is 
Non 
evaluable  
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Lungs  
%FEV1 ≥ 
80% after 
previous 
involvement; 
or NIH Lung 
Symptom 
Score 0 after 
previous 
involvement 
if PFTs not 
available  
Increase by 
10% 
absolute 
value 
of %FEV1; 
or decrease 
in NIH Lung 
Symptom 
Score by 1 
or more 
points if 
PTSs not 
available  
Not in the 
other 
categories  
Decrease by 
10% 
absolute 
value 
of %FEV1 
and %FEV1 
< 75%; or 
increase in 
NIH Lung 
Symptom 
Score by 1 
or more 
points, 
except 0 to 1 
if PFTs not 
available  
NIH Lung 
score is Non 
evaluable 
and %FEV1 
is missing  
Eyes  
NIH Eye 
Score 0 after 
previous 
involvement  
Decrease in 
NIH Eye 
Score by 1 
or more 
points  
No change 
or increase 
from 0 to 1 in 
NIH Eye 
Score  
Increase in 
NIH Eye 
Score by 1 
or more 
points, 
except 0 to 1  
NIH eye 
score is Non 
evaluable  
Joints and 
Fascia  
NIH Joint 
and Fascia 
Score 0 and 
P-ROM 
score 25 
after 
previous 
involvement 
in at least 
one measure  
Decrease in 
NIH Joint 
and Fascia 
Score by 1 
or more 
points or 
increase in 
P-ROM 
score by 1 or 
more points 
for any site  
Not in the 
other 
categories  
Increase in 
NIH Joint 
and Fascia 
Score by 1 
or more 
points or 
decrease in 
P-ROM 
score by 1 or 
more points 
for any site  
Both in NIH 
Joint and 
Fascia and 
P-ROM 
scores are 
Non 
evaluable  
Skin  
NIH Skin 
Score 0 after 
previous 
involvement  
Decrease in 
NIH Skin 
Score from 
baseline by 1 
or more 
points  
No change 
or increase 
from 0 to 1 in 
NIH Skin 
Score  
Increase in 
NIH Skin 
Score from 
baseline by 1 
or more 
points, 
except 0 to 1  
NIH skin 
score is Non 
evaluable  
Mouth  
NIH Modified 
OMRS 0 
after 
previous 
involvement  
Decrease in 
NIH Modified 
Oral Mucosa 
Rating Score 
of 2 or more 
points  
No change in 
NIH Modified 
Oral Mucosa 
Rating Score  
Increase in 
NIH Modified 
Oral Mucosa 
Rating Score 
of 2 or more 
points  
NIH mouth 
score is Non 
evaluable  
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Liver  
Normal ALT, 
ALP and 
total bilirubin 
after 
elevation of 
one or more 
at baseline  
50% 
improvement 
in ALT, ALP, 
or total 
bilirubin 
without 
increase by 
2x ULN for 
any other 
parameters 
of ALT, ALP 
or total 
bilirubin  
Not in the 
other 
categories  
Increase by 
2x ULN for 
any one of 
ALT, ALP or 
total bilirubin  
If ALT, ALP 
and total 
bilirubin are 
missing  
Global  
GSR 0  
GSR 
decreases 
by 2 or more 
points  
Not in the 
other 
categories  
GSR 
increases by 
2 or more 
points  
Not 
applicable  
 
Organs not involved at baseline can progress according to the definitions in this Response 
Assessments table, but cannot achieve a response (PR or CR). 
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