A Randomized, Double-Blind, Placebo-Controlled Dose-Ranging Study to Evaluate the Safety and Efficacy of CCX140-B in Subjects With Focal Segmental Glomerulosclerosis (FSGS)
Phase: PHASE2
Conditions: FSGS, Focal Segmental Glomerulosclerosis, Glomerulosclerosis
Sponsor: Amgen

C C X 1 4 0- B 
 
Pr ot oc ol C L 0 1 1 _ 1 4 0 
 
  
A me n d me nt 4. 0 (2 9 Oct o ber  2 0 1 8) 
C he m o Ce n tr y x, I n c. 
C O N FI D E N TI A L  
Pa ge 1  of 9 3  
P R O T O C O L 
Pr ot oc ol A me n d me nt 4 . 0 
 
St u d y Title:  A Ra n d o mize d, D o u ble- Bli n d, Place b o- C o ntr olle d D ose- Ra n gi n g 
St u d y t o E v al uate t he Safet y a n d Efficac y of C C X 1 4 0- B i n 
S u bjects wit h F ocal Se g me ntal Gl o mer ul oscler osis ( F S G S)  
Pr ot oc ol N u m ber:  C L 0 1 1 _ 1 4 0 
I n vesti gati o n al Pr o d uct: 
Selecti ve a nta g o nist of h u ma n C- C c he m o ki ne rece pt or t y pe 2 
(C C R 2)   
I n dic ati o n: F ocal Se g me nt al Gl o mer ul oscler osis  ( F S G S) 
S p o ns or:  C he m o Ce ntr y x, I n c.  
De vel o p me nt P h ase:  2  
I N D n u m ber 1 3 4 0 0 7 
E u dr a C T n u m ber  2 0 1 7- 0 0 3 0 2 1- 1 5 
S p o ns or's Res p o nsi ble 
Me dic al Officer:  
 
C he m o Ce ntr y x, I n c.  
M o u ntai n Vie w, Calif or nia 9 4 0 4 3, U S A 
S p o ns or Si g n at or y: 
 
C he m o Ce ntr y x, I n c.  
M o u ntai n Vie w, Calif or nia 9 4 0 4 3, U S A 
A p pr o v al D ate: 
1 0 N o ve m ber 2 0 1 7 
1 8 Dece m b er 2 0 1 7   A me n d me nt 1. 0  
1 8 J a n u ar y 2 0 1 8      A me n d me nt 2. 0  
1 5 Fe br u a r y 2 0 1 8    A me n d me nt 3. 0 
2 9 Oct o ber  2 0 1 8      A me n d me nt 4. 0  
C o nfi de nti al  
T he i nf or mati o n c o ntai ne d herei n is t he pr o pert y of t he S p o ns or a n d ma y n ot be re pr o d u ce d, 
p u blis he d or discl ose d t o ot hers wit h o ut writte n a ut h orizati o n of t he S p o ns or. 
T his st u d y will be c o n d u cte d acc or di n g t o t he pri n ci ples of G o o d Cli nical Practice as descri be d 
i n I nter nati o nal C o nfer e n ce o n Har m o nizati o n  g ui deli nes, i ncl u di n g t he arc hi vi n g of ess e ntial 
d oc u me nts. 

C C X 1 4 0- B 
 
Pr ot oc ol C L 0 1 1 _ 1 4 0 
 
  
A me n d me nt 4. 0 (2 9 Oct o ber  2 0 1 8) 
C he m o Ce n tr y x, I n c. 
C O N FI D E N TI A L  
Pa ge 2  of 9 3  
I N V E S TI G A T O R SI G N A T OR Y  P A G E  
 
Pr ot oc ol N u m ber:  C L 0 1 1 _ 1 4 0 
Pr ot oc ol Title:  A R a n d o mize d, D o u ble- Bli n d, Place b o- C o ntr olle d D ose -Ra n gi n g St u d y t o 
E val uate t he Saf et y a n d Efficac y of C C X 1 4 0- B i n S u bject s wit h F ocal Se g me ntal 
Gl o mer ul oscler osis ( F S G S)  
I a gree: 
•  t o ass u me res p o nsi bilit y f or t he pr o per c o n d u ct of t he st u d y at t his site. 
•  t o c o n d uct t he st u d y i n c o m plia nce wit h t his pr ot oc ol, a n y f ut ure a me n d m e nts, a n d wit h a n y 
ot her st u d y c o n d uct pr oce d ures pr o vi d e d b y C he m o Ce ntr y x, I n c. 
•  n ot t o i m ple me nt a n y de viati o ns fr o m or c ha n ges t o t he pr ot oc ol wit h o ut a gree me nt fr o m t he 
s p o ns or a n d pri or r e vie w a n d writte n a p pr o v al fr o m t he I nstit uti o nal Re vie w B oar d 
(I R B)/ Et hics C o m mittee ( E C), e x ce pt w here necessar y t o eli mi nate a n i m me diate hazar d t o 
t he s u bjects, or f or a d mi nistrati ve as pects of t he st u d y ( w here per mitte d b y all a p plica ble 
re g ulat or y r e q uire me nts). 
•  t hat I a m t h or o u g hl y fa miliar wit h t he a p pr o priate use of t he i n vesti gati o nal dr u g(s), as 
descri be d i n t his pr ot oc ol, a n d a n y ot her i nf or mati o n pr o vi de d b y t he s p o ns or i ncl u di n g, b ut 
n ot li mite d t o t he f oll o wi n g: t he c urre nt v ersi o n of t he I n v esti gat or’s Br oc h ure pre p are d b y 
C he m o Ce ntr y x, I n c. a n d a p pr o ve d pr o d u ct la bel, if a p plica ble. 
•  t hat I a m a ware of a n d will c o m pl y wit h c urre nt I C H/ F D A g o o d cli nical practices g ui deli nes 
( G C P) a n d all re g ulat or y re q uire me nts. 
•  t o e ns ure t hat all pers o ns assisti n g me wit h t he st u d y are a d e q uatel y i nf or me d a b o ut t he 
i n vesti gati o nal dr u g(s) a n d t heir st u d y-relate d d uti es a n d f u ncti o n as d escri be d i n t he 
pr ot oc ol. 
 
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Pri nci pal I n v esti gat or     
  
  
  
  
  
  
 
Date  
 
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
Pri nte d Na me  
A d dress * _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
P h o ne N u m ber * _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
* If t he a d dr ess or p h o ne n u m ber nee ds t o be c ha n ge d d uri n g t he c o urs e of t he st u d y, t his will be 
d o ne b y t h e I n vesti gat or, wit h writte n n otificati o n t o t he S p o ns or, a n d will n ot re q uire (a) 
pr ot oc ol a me n d me nt( s). 

C C X 1 4 0- B 
 
Pr ot oc ol C L 0 1 1 _ 1 4 0 
 
  
A me n d me nt 4. 0 (2 9 Oct o ber  2 0 1 8) 
C he m o Ce n tr y x, I n c. 
C O N FI D E N TI A L  
Pa ge 3  of 9 3  
S P O N S O R C O N T A C T I N F O R M A TI O N  
Pr ot oc ol N u m ber:  C L 0 1 1 _ 1 4 0 
Pr ot oc ol Title:  A R a n d o mize d, D o u ble- Bli n d, Place b o- C o ntr olle d D ose- Ra n gi n g St u d y t o 
E val uate t he Saf et y a n d Efficac y of C C X 1 4 0 -B i n S u bjects wit h F ocal Se g me ntal 
Gl o mer ul oscler osis ( F S G S)  
 
Me dical  Offi cer  
 
C he m o Ce ntr y x, I n c.  
M o u ntai n Vie w, 
Calif or nia 9 4 0 4 3, U S A 
 
 
 
Cli nical O perati o ns 
M a na ger  
 
Cl i nical O perati o ns C o ns ulta nt 
C he m o Ce ntr y x, I n c.  
M o u ntai n Vie w,  
Calif or nia 9 4 0 4 3, U S A 
 
 
 
 

C C X 1 4 0- B 
 
Pr ot oc ol C L 0 1 1 _ 1 4 0 
 
  
A me n d me nt 4. 0 (2 9 Oct o ber  2 0 1 8) 
C he m o Ce n tr y x, I n c. 
C O N FI D E N TI A L  
Pa ge 5  of 9 3  
P R O T O C O L A M E N D M E N T 4. 0 : S U M M A R Y O F C H A N G E S 
Secti o n(s)  
Ori gi n al Te xt  
Re vise d Te xt   
R ati o n ale f or C h a n ge  
TI T L E P A G E  
Pr ot oc ol A me n d me nt 3. 0  
Pr ot oc ol A me n d me nt 4. 0  
U p date d pr ot oc ol versi o n 
n u m ber a n d date  
 
N o ne  
1 9 Oct o ber  2 0 1 8  
 
Gl o bal  
Varie d  
Varie d  
C orrecte d t y p os a n d 
gra m matical err ors  
Gl o bal  
Varie d  
Varie d  
Defi ne d acr o n y ms at first 
occ urre nce t o c or rect 
pre vi o us err or or 
o missi o n  
S Y N O P SI S, 
O bj ecti ves, b ullet 2 & 
O BJ E C TI V E S, 
Secti o n  3. 1 , 
para gra p h  2 
•  T he pri mar y efficac y 
o bj ecti ve ….c ha n ge fr o m 
baseli ne i n t he uri ne pr otei n 
t o creati ni ne rati o ( U P C R). 
•  T he pr i mar y efficac y 
o bj ecti ve ….c ha n ge fr o m 
baseli ne i n t he uri ne pr otei n 
t o creati ni ne rati o ( U P C R) at 
Wee k 1 2 . 
T o clarif y t he a nal ysis of 
t he pri mar y e n d p oi nt 
S Y N O P SI S, 
O bj ecti ves,  
b ullet 1  
T he sec o n dar y 
o bj ecti ves …are:  
•  T o e val uate t he effect of 
C C X 1 4 0 -B o n … esti mate d 
gl o mer ular filtrati o n rate 
(e G F R); 
T he sec o n dar y 
o bj ecti ves …are:  
•  T o e val uate t he effect of 
C C X 1 4 0 -B o n …esti mate d 
gl o mer ular filtrati o n rate 
(e G F R) at Wee ks 1 2 a n d 2 4 ; 
T o har m o nize S y n o psis 
wit h O BJ E C TI V E S, 
Secti o n  3. 2 , b ullet 1  
S Y N O P SI S, 
O bj ecti ves & 
O BJ E C TI V E S, 
Secti o n  3. 2 ,  
b ullet 2  
N o ne  
T o e v al u ate t he effect of 
C C X 1 4 0 -B tre at me nt o n 
fr acti o n of s u bjects 
ac hie vi n g c o m plete a n d 
p arti al re n al re missi o n ( b y  
2 differe nt p arti al 
re missi o n defi niti o ns)  
A d de d a ne w sec o n dar y 
o bj ecti ve   
S Y N O P SI S , 
O bj ecti ves & 
O BJ E C TI V E S , 
Secti o n  3. 3 , 
para gra p h  3 
•  T o e x pl ore t he effect of 
C C X 1 4 0 -B o n Healt h -relate d 
Q ualit y of Life c ha n ge s 
base d o n S h ort F or m 3 6 
versi o n 2 ( S F -3 6 v 2 a n d E Q -
5 D -5 L.)  
•  T o e x pl ore t he effect of 
C C X 1 4 0 -B o n Healt h -relate d 
Q ualit y of Life c ha n ges 
base d o n a ns wers t o t he S h ort 
F or m 3 6 versi o n 2 ( S F -3 6 
v 2 ) a n d E ur o Q u alit y of 
Life -5 D o m ai ns -5 Le vels 
(E Q -5 D -5 L) q uesti o n n aires ; 
T o c larify t hat t he 
i nstr u me nts use d are 
q uesti o n naires  
S Y N O P SI S , 
Met h o d ol o g y  
para gra p h 9  
F or assess me nt of 
p har mac o ki netics, … will 
i ncl u de 
•  Si x bl o o d sa m ples 
c ollecte d o ver 6 h o urs  
F or assess me nt of 
p har mac o ki netics, … will 
i ncl u de 
•  Se ve n  bl o o d sa m p les 
c ollecte d o ver 6 h o urs  
T o har m o nize S y n o psis  
wit h Secti o n 4 of t he 
pr ot oc ol ;  baseli ne 
(ti me 0) meas ure me nt 
o mitte d fr o m S y n o psis i n 
err or 
S Y N O P SI S & 
S T U D Y 
P O P U L A TI O N, 
Secti o n  5. 2   
1 0. Fe male s u bj ects … if 
ade q uate c o ntrace pti o n is  
use d d uri n g, a n d f or at least 5 
half -li ves after last d ose … 
1 0. Fe male s u bj ects … if 
a de q uate c o ntrace pti o n is 
use d d uri n g, a n d f or at least 1 
m o nt h  after last d ose  
T o sta n dar dize t he 
re q uire d p ost-d osi n g 
d urati o n of c o ntrace pti o n  
for males a n d fe males  

C C X 1 4 0- B 
 
Pr ot oc ol C L 0 1 1 _ 1 4 0 
 
  
A me n d me nt 4. 0 (2 9 Oct o ber  2 0 1 8) 
C he m o Ce n tr y x, I n c. 
C O N FI D E N TI A L  
Pa ge 6  of 9 3  
Secti o n(s)  
Ori gi n al Te xt  
Re vise d Te xt   
R ati o n ale f or C h a n ge  
S Y N O P SI S & 
S T U D Y 
P O P U L A TI O N,  
Secti o n  5. 3  
4. S u bj ects t hat use of 
rit u xi ma b or ot her a nti-C D 2 0 
m o n ocl o nal a nti b o dies wit hi n 
2 0  wee ks pri or t o scree ni n g 
are e xcl u de d w hile s u bj ects 
t hat use d rit u xi ma b or ot her 
a nti -C D 2 0 m o n ocl o nal 
a nti b o dies pri or t o 2 0  wee k 
of scree ni n g are all o we d wit h 
c o nfir me d rec o ver y of 
C D 2 0 + B cell p o p ulati o n t o 
wit hi n n or mal ra n ge  
4. S u bj ects w h o  use d 
rit u xi ma b or ot her B- cell 
de pleti n g  m o n ocl o nal 
a nti b o dies wit hi n 2 0  wee ks 
pri or t o scree ni n g are 
e xcl u de d w hile s u bj ects w h o  
use d rit u xi ma b or ot her 
B- cell de pleti n g  m o n ocl o nal 
a nti b o dies pri or t o 2 0  wee k s 
bef ore scree ni n g are all o we d 
wit h c o nfir me d rec o ver y of 
t he B- cell p o p ul ati o n  t o 
wit hi n n or mal ra n ge at t he 
ti me of scree ni n g  
Clarif y class of restricte d 
me dicati o ns  
 
1 2. …ass ociate d wit h F S G S 
lesi o n (e. g. si n gle ki d ne y, 
s ur gical se g me ntal a n d re nal 
a blati o n …  
1 2. …ass ociate d wit h F S G S 
lesi o n (i.e. sec o n d ar y F S G S, 
s uc h as si n gle ki d ne y, 
s ur gical se g me ntal re nal 
a blati o n … d ia betic 
ne p hr o pat h y, ot hers) , or 
hist ol o gic al c oll a psi n g 
v ari a nt s u bt y pes of F S G S  
T o clarif y t hat t he 
dis or ders ass ociate d wit h 
a n F S G S lesi o n are 
c o nsi dere d sec o n dar y 
F S G S , a n d t o e xcl u de 
s u bj ects wit h c olla psi n g 
varia nts of F S G S as t hese 
patie nts d o  n ot res p o n d t o 
me dical t hera p y  
 
 
1 3. … base d o n i nterfer o n γ 
release assa y (I G R A), 
t u berc uli n p urifie d pr otei n 
deri vati ve ( P P D) s ki n test, or 
c hest ra di o gra p h y d o ne 
d uri n g  scree ni n g or wit hi n 
6 wee ks  pri or t o scree ni n g . 
1 3. … base d o n i nterfer o n γ 
release assa y (I G R A) wit hi n 
6 wee ks pri or t o scree ni n g.  
T o clarif y t hat o nl y t he 
I G R A ca n be use d t o 
e xcl u de t u berc ul osis  
 
1 4. E vi de nce of he patic 
disease …at baseli ne pri or t o 
d osi n g …  
1 4. E vi de nce of he patic 
disease …at scree ni n g…  
T o clarif y ti mi n g of 
q ualif yi n g  he patic testi n g  
 
1 8. Hist or y of alc o h ol or 
illicit dr u g a b use or of 
lit hi u m, pa mi dr o nate a n d 
i nterfer o n. 
1 8. Hist or y of alc o h ol or 
illicit dr u g a b use. 
M o ve refere nce t o 
lit hi u m, pa mi dr o nate a n d 
i nterfer o n t o e xcl usi o n 
criteri o n # 2 4 
 
2 0. K n o w n 
h y perse nsiti vit y …  
( … ma g nesi u m stearate, or 
silic o n di o xi de). 
2 0. K n o w n 
h y perse nsiti vit y …  
( … ma g nesi u m stearate, 
silic o n di o xi de or 
t artr azi ne) 
T o a d d tartrazi ne, a 
c o m p o ne nt of t he 
place b o, t o t he list of 
p ossi ble aller ge ns i n 
st u d y dr u g  
 
2 4. S u bj ects ta ki n g lit hi u m, 
or i nterfer o n; …  
2 4. S u bj ects t a ki n g lit hi u m, 
p a mi dr o n ate , or 
i nterfer o n; … 
Cite lit hi u m, pa mi dr o nate 
a n d i nterfer o n i n o nl y o ne 
e xcl usi o n criteri o n  

C C X 1 4 0- B 
 
Pr ot oc ol C L 0 1 1 _ 1 4 0 
 
  
A me n d me nt 4. 0 (2 9 Oct o ber  2 0 1 8) 
C he m o Ce n tr y x, I n c. 
C O N FI D E N TI A L  
Pa ge 7  of 9 3  
Secti o n(s)  
Ori gi n al Te xt  
Re vise d Te xt   
R ati o n ale f or C h a n ge  
S Y N O P SI S, Efficac y 
Assess me nts &  
B ullet 2 
•  Pr o p orti o n of s u bj ects 
ac hie vi n g c o m plete re nal 
re missi o n ( U P C R 0. 3 g/ g: 
e G F R n or mal or n ot le ss t ha n 
2 0 % bel o w baseli ne) … 
assesse d at W ee ks 1 2 a n d 2 4.  
•  Pr o p orti o n of s u bj ects 
ac hie vi n g c o m plete re nal 
re missi o n at Wee ks 1 2 a n d 
2 4  
C o m plete Re missi o n 
(i ncl u des all of t he 
f oll o wi n g): 
- re d ucti o n i n U P C R  t o 
< 0. 3 g/ g  
- Ser u m al b u mi n wit hi n 
n or m al r a n ge  
- F or su bjects  wit h 
a b n or m al ser u m cre ati ni ne 
le vels at b aseli ne, ret ur n t o 
n or m al le vels f or t h at a ge 
gr o u p  
- F or s u bjects wit h n or m al 
ser u m cre ati ni ne le vels at 
b aseli ne, fi n al v al ue wit hi n 
2 0 % of b aseli ne le vels  
Clarifie d t he defi niti o n of  
c o m plete re nal re missi o n  
N o ne  
…  or partial re missi o n 
( U P C R decrease d b y 5 0 % 
fr o m baseli ne; U P C R 
< 3. 5 g/ g; a n d e G F R n or mal or 
n ot less t ha n 2 0 % bel o w 
baseli ne), assesse d at 
W ee ks  1 2 a n d 2 4.  
•  Pr o p orti o n of s u bjects 
ac hie vi n g p arti al re missi o n 
at Wee ks 1 2 a n d 2 4 b y t he 
f oll o wi n g t w o differe nt 
defi niti o ns:  
- U P C R re d ucti o n of ≥5 0 % 
fr o m b aseli ne a n d  U P C R 
< 3. 5 g/ g  
- decre ase i n U P C R t o less 
t h a n 1. 5 g/ g a n d at le ast a 
4 0 % re d ucti o n i n 
pr otei n uri a fr o m b aseli ne 
assesse d  
Clarifie d t he defi niti o n of  
partial re missi o n a n d 
a d de d a sec o n d met h o d 
f or calc ulati n g partial 
re missi o n 
S Y N O P SI S , Healt h 
Relate d Q ualit y of 
Life Assess me nt  
C ha n ge fr o m baseli ne i n 
d o mai ns assesse d b y S h ort 
F or m 3 6 versi o n 2 ( S F -3 6 v 2 
a n d E Q-5 D -5 L) t hr o u g h 
W ee k 1 2 a n d W ee k 2 4  
C ha n ge fr o m baseli ne i n 
d o mai ns assesse d b y  
a ns w ers t o t he S F -3 6 v 2 a n d 
E Q- 5 D -5 L  q uesti o n n aires  
t hr o u g h W ee k 1 2 a n d 
W ee k  2 4  
T o c larify t he i nstr u me nts 
use d  
S Y N O P SI S  & 
Secti o n  8. 4  
E x pl orat or y 
P har mac o d y na mic 
Assess me nts , b ullet  5 
 
•  C ha n ge fr o m baseli n e i n … 
bi o mar kers … ma y i ncl u de 
meas ur e me nt of all or of a 
s u bset of t he f oll o wi n g: 
•  C ha n ge fr o m baseli n e i n … 
bi o mar kers … ma y i ncl u de 
meas ure me nt of:  
T o har m o nize t he 
S y n o psis wit h Secti o n  8. 4 
(err or) 
TI M E & E V E N T S 
T A B L E,  
Secti o n  7  
St u d y Sc he ma   
C ol u m n hea di n gs f or D o u ble 
Bli n d Treat me nt; St u d y 
W ee k:  
Da y 1, W ee ks 1, 2, 4, 8, 1 2, 
1 3, 1 6, 2 0, 2 4, 2 8  
A me n de d C ol u m n hea di n g 
f or D o u ble Bli n d 
Treat me nt/ Acti ve Treat me nt; 
St u d y W ee k:  
W ee ks 1, 2, 4, 8, 1 2  
Clarif y t hat W ee k 1 2 is 
t he e n d of t he D o u ble-
bli n d Treat me nt peri o d  

C C X 1 4 0- B 
 
Pr ot oc ol C L 0 1 1 _ 1 4 0 
 
  
A me n d me nt 4. 0 (2 9 Oct o ber  2 0 1 8) 
C he m o Ce n tr y x, I n c. 
C O N FI D E N TI A L  
Pa ge 8  of 9 3  
Secti o n(s)  
Ori gi n al Te xt  
Re vise d Te xt   
R ati o n ale f or C h a n ge  
 
C ol u m n hea di n gs f or O pe n -
La bel Treat me nt; St u d y 
W ee k:  
1 6, 2 0, 2 4, 2 8  
A me n de d C ol u m n hea di n g 
f or O pe n-La bel Treat me nt; 
St u d y W ee k:  
1 3, 1 6, 2 0, 2 4  
Clarif y t hat o nl y s u bj ects 
c o nti n ui n g i n t he st u d y 
will atte n d t hese visits  
 
C ol u m n hea d i n gs f or 
E xte nsi o n P hase; St u d y 
W ee k:  
1 6, 2 0, 2 4, 2 8  
A me n de d C ol u m n hea di n g 
f or E xte nsi o n P hase; St u d y 
W ee k:  
1 3, 1 6, 2 0, 2 4  
E xte nsi o n p hase o nl y f or 
t h ose s u bj ects w h o are 
c o nti n ui n g i n t he st u d y; 
Re m o ve d d u plicate 
listi n g of W ee k 1 6,  
 
C ol u m n hea di n gs f or F oll o w-
u p P hase; St u d y W ee k: 2 8  
A me n de d C ol u m n hea di n g 
f or F oll o w-u p P hase; St u d y 
W ee k:  
1 6 ,  2 8  
T o c o ns oli date listi n g of 
F oll o w -u p visit f or all 
s u bj ects  
 
N o ne  
A d de d C ol u m n hea di n g f or 
D o u ble Bli n d Treat me nt; 
St u d y Da y:   
1, 8, 1 5, 2 9, 5 7, 8 5  
A d de d a r o w t o s h o w 
b ot h t he St u d y W ee k a n d 
St u d y Da y i n t he Ti me 
a n d E ve nts T a ble  
 
N o ne  
A d de d C ol u m n hea di n g f or 
O pe n -La bel Treat me nt 
/ F oll o w-u p; St u d y Da y:   
9 2, 1 1 3, 1 4 1, 1 7 0  
A d de d a r o w t o s h o w 
b ot h t he St u d y W ee k a n d 
St u d y Da y i n t he Ti me 
a n d E ve nts T a bl e 
 
N o ne  
A d de d C ol u m n hea di n g f or 
F oll o w -u p; St u d y Da y:   
1 1 3 , 1 9 8  
A d de d a r o w t o s h o w 
b ot h t he St u d y W ee k a n d 
St u d y Da y i n t he Ti me 
a n d E ve nts T a ble  
TI M E & E V E N T S 
T A B L E,  
Secti o n  7   
N o ne  
2 4 -h o ur uri ne c ollecti o n; 
St u d y Da y:   
1, 8 5, 1 7 0  
A d de d 2 4 -h o ur uri ne 
c ollecti o n as a m ore 
acc urate s peci me n f or 
uri nar y meas ure me nts  
TI M E & E V E N T S 
T A B L E  
He mat ol o g y, Ser u m 
c he mistr y i ncl u di n g  
c oa g ulati o n pa nel a n d li pi ds 9) 
He mat ol o g y, Ser u m 
c he mistr y (c oa g ulati o n pa nel 
a n d li p i ds i ncl u de d at 
s pecifie d visits9) 
T o clarif y t he details of 
ser u m c he mistr y testi n g 
TI M E & E V E N T S 
T A B L E,  
F o ot n ote 4  
4A n y o ne of t he f oll o wi n g 
ma y be d o ne f or T B 
scree ni n g: I nterfer o n γ 
release assa y (I G R A), 
t u berc uli n p urifie d pr otei n 
deri vati ve ( P P D) s ki n test, or 
c hest ra di o gra p h y ( d o ne 
wit hi n 6 wee ks pri or t o 
Scree ni n g or d o ne d uri n g 
Scree ni n g).  
4T B scree ni n g b y  I nterfer o n 
γ release assa y (I G R A) d o ne 
wit hi n 6 wee ks pri or t o 
Scree ni n g or d o ne d uri n g 
Scree ni n g.  
T o clarif y t hat o nl y t he 
I G R A ca n be use d t o 
pr o vi de e vi de nce of 
e xcl usi o n of  t u berc ul osis  

C C X 1 4 0- B 
 
Pr ot oc ol C L 0 1 1 _ 1 4 0 
 
  
A me n d me nt 4. 0 (2 9 Oct o ber  2 0 1 8) 
C he m o Ce n tr y x, I n c. 
C O N FI D E N TI A L  
Pa ge 9  of 9 3  
Secti o n(s)  
Ori gi n al Te xt  
Re vise d Te xt   
R ati o n ale f or C h a n ge  
TI M E & E V E N T S 
T A B L E,  
F o ot n ote 5  
5P K bl o o d sa m ple will be 
c ollecte d pri or t o t he 
m or ni n g d ose o n Da ys 1 a n d 
1 5, a n d at 0. 5, 1, 2, 3, 4, a n d 
6 h o urs f oll o wi n g d osi n g. 
T he re mai ni n g P K sa m ples 
will be c ollecte d at ti me 0 
o nl y, j ust pri or t o 
a d mi nistrati o n of t he first 
dail y d ose.  
5P K bl o o d sa m ple will be 
c ollecte d o n D a ys 1 a n d 1 5 
pri or t o t he m or ni n g d ose 
(ti me 0), a n d at 0. 5, 1, 2, 3, 
4, a n d 6 h o urs f oll o wi n g 
d osi n g. P K sa m ples at all 
ot her visits  will be c ollecte d 
at ti me 0 o nl y, j ust pri or t o 
a d mi nistrati o n of t he first 
dail y d ose.  
T o clarif y t he ti mi n g of 
P K sa m ple c ollecti o n  
TI M E & E V E N T S 
T A B L E,  
F o ot n ote 9  
9 Ser u m c he mistr y  t o i ncl u de 
c oa g ulati o n pa nel ( P T, P T T 
& I N R) a n d li pi ds ( H D L, 
L D L, Tri gl yceri de s a n d T otal 
C h olester ol) at s pecifie d 
visits.  
9 Ser u m c he mistr y  at e ac h 
visit  t o i ncl u de li ver p a nel 
(t ot al, direct a n d i n direct 
bilir u bi n, L D H, A S T, 
A L T), al k ali ne 
p h os p h at ase , etc. (see 
Secti o n 8. 2. 2 ); at s pecifie d 
visits, t o i ncl u de c oa g ulati o n 
pa nel ( P T, P T T & I N R) a n d 
li pi ds ( H D L, L D L, 
Tri gl yceri des a n d T otal 
C h olester ol) as w ell  
T o clarif y t he sc he d ule 
a n d details of ser u m 
c he mistr y testi n g  
TI M E & E V E N T S 
T A B L E,  
F o ot n ote 1 0  
C o nc o mita nt me dicati o ns 
will be rec or de d f or all 
me dicati o ns ta ke n 1 2  wee ks 
p ri or t o scree ni n g. 
Gl uc oc ortic oi ds 
i m m u n os u p pressi ves a n d 
C D 2 0 + a nti b o dies will be 
rec or de d f or u p t o 6 m o nt hs 
pri or t o scree ni n g.  
C o nc o mita nt me dicati o ns 
will be rec or de d f or all 
me dicati o ns ta ke n 1 2  wee ks 
pri or t o scree ni n g. 
Gl uc oc ortic oi ds a n d  
i m m u n os up pressi ves will be 
rec or de d f or u p t o 6 m o nt hs 
pri or t o scree ni n g. If t he 
s u bject h as recei ve d pri or 
rit u xi m a b tre at me nt or 
ot her B -cell de pleti n g 
a nti b o dies, t he rit u xi m a b 
use, as w ell as a n y a v ail a ble 
uri n ar y pr otei n v al ues,  
s h o ul d be rec or de d f or u p 
t o 1 ye ar pri or t o scree ni n g . 
T o clarif y t he rec or di n g 
peri o d f or c o nc o mita nt 
me dicati o ns, a n d t o 
ca pt ure 1 year of d osi n g 
wit h rit u xi ma b or ot her 
B- cell de pleti n g 
a nti b o die s, wit h a n y 
a vaila ble uri nar y pr otei n 
val ues   
TI M E & E V E N T S 
T A B L E,  
F o ot n ote 1 1  
1 1 P K  bl o o d sa m ples will be 
c ollecte d at 2 da ys, 7 da ys 
a n d 1 4 da ys f oll o wi n g 
disc o nti n uati o n of st u d y dr u g 
t o assess eli mi nati o n. 
1 1 P K bl o o d sa m ples will be 
c ollecte d at 2 da ys, 7 da ys 
a n d 1 4 da ys f oll o wi n g t he 
l ast d ose of st u d y dr u g, as 
w ell at t he F oll o w - up Visit 
( Wee k 1 6 or Wee k 2 8) t o 
assess eli mi nati o n P K.  
T o clarif y t he eli mi nati o n 
P K sa m pli n g ti mes  
LI S T O F 
A B B R E VI A TI O N S 
A N D A C R O N Y M S  
N o ne  
M D R D  M o dific ati o n of 
Diet i n Re n al Dise ase  
O mitte d i n err or  
I N T R O D U C TI O N, 
Secti o n  2. 4   
para gra p h  2 
A ne mia (re d bl o o d cell 
[ R B C] para meter fi n di n gs, 
wit h retic ul oc yt osis), …  
…c h a n ges i n  re d bl o o d cell 
[ R B C] para meter fi n di n gs, 
wit h retic ul oc yt osis, …  
T o clarif y t he 
he mat ol o gic c ha n ges see n 
i n t he pre-cli nical st u dies  

C C X 1 4 0- B 
 
Pr ot oc ol C L 0 1 1 _ 1 4 0 
 
  
A me n d me nt 4. 0 (2 9 Oct o ber  2 0 1 8) 
C he m o Ce n tr y x, I n c. 
C O N FI D E N TI A L  
Pa ge 1 0  of 9 3  
Secti o n(s)  
Ori gi n al Te xt  
Re vise d Te xt   
R ati o n ale f or C h a n ge  
para gra p h 3  
…t he hi g hest d ose of 
C C X 1 4 0 -B was …  
…t he hi g hest d ose 
( 5 0 m g/ k g)  of C C X 1 4 0 -B 
was …  
T o i de ntif y t he hi g hest 
d ose teste d i n t he 
3 9 -wee k d o g st u d y  
para gra p h 4  
 
A ne mia fi n di n gs are li kel y 
tra nslata ble t o h u ma ns … 
T he c h a n ges i n R B C 
p ar a meter fi n di n gs  
T o clar if y t he 
he mat ol o gic c ha n ges see n 
i n t he pre-cli nical st u dies  
 
T o e ns ure earl y detecti o n of 
a ne mia …  
T o e ns ure earl y detecti o n of 
c h a n ges i n R B C 
p ar a meters …  
 
p ara gra p h 5  
… hi g her safet y mar gi n t ha n 
a ne mia …  
… hi g her safet y mar gi n t ha n 
t he c h a n ges i n R B C 
p ar a meters … 
 
 
….a n d will be e val uate d f or 
earl y s y m pt o ms …  
….a n d will be e x a mi ne d f or 
vi br ati o n -se nse deficits a n d 
e val uate d f or earl y 
s y m pt o ms … 
T o u p date descri pti o n of 
ne ur ol o gic testi n g wit h 
all rele va nt pr oce d ures  
p ara gra p h 6  
( base d o n re versi ble a ne mia) 
( base d o n re versi ble c h a n ges 
i n R B C p ar a meters) 
T o clarif y t he 
he mat ol o gic c ha n ges see n 
i n t he pre-cli nical st u dies  
S T U D Y D E SI G N, 
para gra p h 1  
F oll o wi n g t he 1 2 -wee k 
bli n de d treat me nt peri o d, 
s u bj ects will recei ve acti ve 
treat me nt … 
F oll o wi n g t he 1 2 -wee k 
bl i n de d treat me nt peri o d, t he 
st u d y will e v al u ate u p t o 
2 4  w ee ks of tre at me nt wit h 
C C X 1 4 0 -B:  all  s u bj ects w h o 
re m ai n eli gi ble  will recei ve 
acti ve treat me nt …  
T o clarif y t he t otal 
d urati o n of d osi n g  
para gra p h 2  
Ra n d o mizati o n will be 
stratifie d b y F S G S 
classi ficati o n ( pri mar y vs 
sec o n dar y) a n d … 
Ra n d o mizati o n will be 
stratifie d b y U P C R < 3. 5 g 
pr otei n/ g cre ati ni ne vers us 
U P C R ≥3. 5 g pr otei n/ g 
cre ati ni ne at b aseli ne usi n g 
t he scree ni n g U P C R a n d …  
T o har m o nize  t he 
descri pti o n of t he 
stratificati o n fact ors 
t hr o u g h o ut t he pr ot oc ol 

C C X 1 4 0- B 
 
Pr ot oc ol C L 0 1 1 _ 1 4 0 
 
  
A me n d me nt 4. 0 (2 9 Oct o ber  2 0 1 8) 
C he m o Ce n tr y x, I n c. 
C O N FI D E N TI A L  
Pa ge 1 1  of 9 3  
Secti o n(s)  
Ori gi n al Te xt  
Re vise d Te xt   
R ati o n ale f or C h a n ge  
para gra p h 5  
All s u bj ects will ta ke bli n de d 
st u d y me dicati o n i n t he 
m or ni n g a n d e ve ni n g, wit h or 
wit h o ut f o o d, f or 8 4 
c o nsec uti ve da ys. F oll o wi n g 
t he 8 4-da y bli n de d d osi n g 
peri o d, all s u bj ects will ta ke 
o pe n la bel C C X 1 4 0 -B f or a n 
a d diti o nal 8 4 da ys at t he 
hi g hest d ose u n der 
e val uati o n, c urre ntl y pla n ne d 
t o be 1 5 m g t wice dail y. If 
t he S p o ns or, wit h t he a d vice 
of t he u n bli n de d Data 
M o nit ori n g C o m mittee 
( D M C) deter mi nes t hat 1 5 
m g t wice dail y e xcee ds t he 
ma xi m u m t olerate d d ose, 
t he n t he d ose a dmi nistere d 
d uri n g t he o pe n la bel peri o d 
will be a dj uste d d o w n war d 
fr o m t he pla n ne d d ose t o t he 
hi g hest d ose t hat is still 
u n der e val uati o n. T here will 
be a 2 8 -da y f oll o w -u p peri o d 
after c o m pleti o n of treat me nt 
a n d all s u bj ects are e x pecte d 
t o ret ur n f or assess me nt of 
eli mi nati o n p hase P K at 2, 7 
a n d 1 4 da ys after ta ki n g t he 
last d ose of st u d y 
me dicati o n.  
All s u bj ects will ta ke bli n de d 
or al  st u d y me dicati o n t wice 
d ail y, 3 t a blets  i n t he 
m or ni n g a n d 3 t a blets i n t he 
e ve ni n g, wit h or wit h o ut 
f o o d, f or 1 2  w ee ks  (8 4 
c o nsec uti ve da ys ). F oll o wi n g 
t he 8 4-da y bli n de d d osi n g 
peri o d, all s u bj ects w h o 
re m ai n eli gi ble  will ta ke 
o pe n la bel C C X 1 4 0 -B f or a n 
a d diti o nal 1 2 w ee ks  (8 4 
c o nsec uti ve  da ys ) at t he 
hi g hest t oler ate d d ose u n der 
e val uati o n, c urre ntl y pla n ne d 
t o be 1 5 mg t wice dail y. T he 
decisi o n o n t he d ose f or t he 
o pe n -l a bel peri o d will be 
m a de b y  t he S p o ns or, wit h 
t he a d vice of t he u n bli n de d 
Data M o nit ori n g C o m mittee 
( D M C). After c o m pleti o n of 
tre at me nt f or w h ate ver 
re as o n, i ncl u di n g e arl y 
ter mi n ati o n, all s u bj ects ar e 
e x pecte d t o ret ur n at 2, 7, a n d 
1 4 da ys after ta ki n g t he last 
d ose of st u d y me dicati o n f or 
assess me nt of eli mi n ati o n 
p h ase P K a n d at 2 8 d a ys 
after t a ki n g t he l ast d ose of 
st u d y me dic ati o n f or P K 
a n d s afet y m o nit ori n g . 
T o clarif y t he se q ue nce of 
e ve nts.  

C C X 1 4 0- B 
 
Pr ot oc ol C L 0 1 1 _ 1 4 0 
 
  
A me n d me nt 4. 0 (2 9 Oct o ber  2 0 1 8) 
C he m o Ce n tr y x, I n c. 
C O N FI D E N TI A L  
Pa ge 1 2  of 9 3  
Secti o n(s)  
Ori gi n al Te xt  
Re vise d Te xt   
R ati o n ale f or C h a n ge  
p ara gra p h 7  
D uri n g t he treat me nt 
peri o d …  c ollecti o n of bl o o d 
a n d uri ne. S u bj ects will 
disc o nti n ue st u d y dr u g as of 
St u d y Da y 1 6 9 ( W ee k 2 4), 
a n d will ret ur n f or a f oll o w 
u p visit o n W ee k 2 8. W he n 
feasi ble, u p o n 
disc o nti n uati o n … assess me nt 
of eli mi nati o n 2, 7 a n d 1 4 
da ys after t he fi nal d ose of 
C C X 1 4 0 -B ( or place b o).  
 
D uri n g t he treat me nt 
peri o d …  c ollecti o n of bl o o d 
a n d uri ne. A 2 4 h o ur uri ne 
c ollecti o n will be d o ne t he 
d a y bef ore t he D a y 1 visit 
( b aseli ne), t he d a y bef ore 
t he Wee k 1 2 visit at t he e n d 
of d o u b le-bli n d d osi n g, a n d 
t he d a y bef ore t he Wee k 2 4 
visit at t he e n d of o pe n -
l a bel d osi n g.  S u bj ects will 
ret ur n f or a f oll o w-u p s afet y 
visit 4 w ee ks after t he l ast 
d ose of st u d y dr u g ( at 
Wee k 1 6 f or t h ose n ot 
e nteri n g t he o pe n -l a bel 
p h ase, or at W ee k 2 8  f or 
th ose w h o c o nti n ue d osi n g 
i nt o t he o pe n-l a bel p h ase). 
W he n feasi ble, u p o n 
disc o nti n uati o n … assess me nt 
of eli mi nati o n P K  at  2, 7 a n d 
1 4 da ys after t he fi nal d ose of 
st u d y dr u g (C C X 1 4 0 -B or 
place b o ). 
T o a d d a 2 4 -h o ur uri ne 
c ollecti o n  at Da y 1, 
W ee k 1 2 a n d W ee k 2 4, 
si nce t he U P C R fr o m a 
2 4 -h o ur uri ne c ollecti o n 
is c o nsi dere d m ost 
acc urate; T o clarif y t he 
se q ue nce of e ve nts 
para gra p h 8,  
b ullet 1 
… L D H a n d t otal a n d 
bilir u bi n t o assess earl y 
e vi de nce of he m ol ysis;  
 
… L D H , a n d bilir u bi n (t ot al 
a n d i n direct)  t o assess earl y 
e vi de nce of he m ol ysis;  
T o clarif y t he reas o ns f or 
bilir u bi n testi n g  
para gra p h 8,  
b ullet 4  
… A S T a n d t otal a n d direct 
bilir u bi n; t o assess …  
… A S T a n d bilir u bi n (t ot al 
a n d direct) ; t o assess 
 
Fi g ure  1   
N o n e  
2 4 -h o ur uri ne c ollecti o ns  
T o i ncl u de t he 2 4 -h o ur 
uri ne c ollecti o ns  
S T U D Y D E SI G N, 
Secti o n 4. 2. 1, T a ble  2  
Ti mi n g, Li ne 3: C o nfir me d 
wit hi n 7 2  h o urs  
Retest  wit hi n 7 2  h o urs  
T o clarif y retesti n g a n d 
st o p pi n g r ules f or li ver 
e nz y me ele vati o ns  
Res p o nse, li ne 3:  
C o nsi der Disc o nti n uati o n of 
Treat me nt  
If c o nfir me d, disc o nti n ue 
tre at me nt wit h C C X 1 4 0- B 
 
E ve nt, li ne 4:  
A L T or A S T ≥ 5 x U L N  
A L T or A S T ≥ 5 x U L N f or 
m ore t h a n 2 w ee ks  
 
Ti mi n g, li ne 4:  
C o nfir me d wit hi n 2  wee ks …  
Retest wit hi n  7 2  h o urs a n d 
t he n 2- 3 ti mes per w ee k …  
 
Res p o nse, li ne 4:  
C o nsi der Disc o nti n uati o n of 
Treat me nt  
If c o nfir me d, disc o nti n ue 
tre at me nt wit h C C X 1 4 0- B 
 
E ve nt, li ne 5:  
A L T or A S T ≥ 3 x U L N  a n d 
T otal Bilir u bi n > 2 U L N or 
I N R > 1. 5 
E ve nt, Li ne 5: A L T or A S T 
≥ 3 x U L N  a n d eit her  T otal 
Bilir u bi n > 2 U L N or I N R 
> 1. 5  
 
Ti mi n g, li ne 5:  
C o nfir me d wit hi n 7 2  h o urs …  
Retest  wit hi n 7 2  h o urs.  
 

C C X 1 4 0- B 
 
Pr ot oc ol C L 0 1 1 _ 1 4 0 
 
  
A me n d me nt 4. 0 (2 9 Oct o ber  2 0 1 8) 
C he m o Ce n tr y x, I n c. 
C O N FI D E N TI A L  
Pa ge 1 3  of 9 3  
Secti o n(s)  
Ori gi n al Te xt  
Re vise d Te xt   
R ati o n ale f or C h a n ge  
Res p o nse, li ne 5:  
C o nsi der Disc o nti n uati o n of 
Treat me nt  
If c o nfir me d, disc o nti n ue 
tre at me nt wit h C C X 1 4 0- B 
 
Ti mi n g, line 6:  
C o nfir me d wit hi n 7 2  h o urs 
( A L T, A S P, A L P, a n d T otal 
Bilir u bi n s h o ul d all be re -
teste d) 
N o ne  
 
Res p o nse, li ne 6:  
C o nsi der Disc o nti n uati o n of 
Treat me nt  
Disc o nti n ue tre at me nt wit h 
C C X 1 4 0 - B 
 
E ve nt, li ne 9:  
I ncrease i n retic ul oc yte c o u nt 
b y ≥ 2 % (a bs ol u te) fr o m 
baseli ne t hat is n ot ot her wise 
e x plai ne d  
I ncrease fr o m b aseli ne i n 
retic ul oc yte c o u nt b y 
≥ 2 u nits ( % of R B C) t hat is 
n ot ot her wise e x plai ne d  
T o clarif y t he st o p pi n g 
r ule f or a c ha n ge i n 
retic ul oc yte 
meas ure me nt, si nce t he 
perce nta ge of re d cells 
t hat are retic ul oc ytes is 
re p orte d, n ot t he a bs ol ute 
retic ul oc yte c o u nt 
S T U D Y 
P O P U L A TI O N ,   
Secti o n 5. 4  : 
C o nti n ui n g Eli gi bilit y 
Criteria  
N o ne  
S u bjects m a y e nter t he 
O pe n -L a bel E xte nsi o n if 
t he s u bject: 
•  h as n ot wit h dr a w n 
c o nse nt f or t he st u d y  
•  h as n o ne w i nfecti o ns 
t h at, i n t he j u d g me nt of t he 
i n vesti g at or, w o ul d 
precl u de a d diti o n of a ne w 
i m m u n os u p pressi ve or 
i m m u n o m o d ul at or y 
tre at me nt 
•  h as h a d n o re q uire me nt 
f or t he a d diti o n of ne w 
i m m u n os u p pressi ve 
tre at me nt d uri n g t he pri or 
1 2  w ee ks a n d n o 
a ntici p ate d re q uire me nt 
d uri n g t he ne xt 1 2  w ee ks.  
T o clarif y t he C o nti n ui n g 
Eli gi bilit y Re q uire me nts 
as state d i n t he Ti me a n d 
E ve nts T a ble, F o ot n ote 
# 6  

C C X 1 4 0- B 
 
Pr ot oc ol C L 0 1 1 _ 1 4 0 
 
  
A me n d me nt 4. 0 (2 9 Oct o ber  2 0 1 8) 
C he m o Ce n tr y x, I n c. 
C O N FI D E N TI A L  
Pa ge 1 4  of 9 3  
Secti o n(s)  
Ori gi n al Te xt  
Re vise d Te xt   
R ati o n ale f or C h a n ge  
S T U D Y 
M E DI C A TI O N/ 
T R E A T M E N T,  
Secti o n  6. 8  
C o nc o mita nt 
Me dicati o ns a n d 
Restricti o ns,  
p ara gra p h 1 
N o ne  
M e dic ati o ns t a ke n pri or t o 
e nr oll me nt will be 
rec or de d:  
•  rit u xi m a b or ot her B -cell 
de pleti n g m o n ocl o n al 
a nti b o dies f or 1 ye ar pri or 
t o scree ni n g;  
S u bjects w h o h a ve t a ke n 
rit u xi m a b or  ot her B -cell 
de pleti n g m o n ocl o n al 
a nti b o dies b ut st o p pe d 
m ore t h a n 2 0 w ee ks bef ore 
scree ni n g will be all o w e d t o 
p artici p ate if t he rec o ver y 
of t he B cell p o p ul ati o n t o 
wit hi n n or m al r a n ge is 
c o nfir me d at t he ti me of 
scree ni n g. 
•  all F S G S me dic ati o ns 
(s pecific all y 
gl uc oc ortic oi ds, 
i m m u n os u p pressi ves) f or 6 
m o nt hs pri or t o scree ni n g;  
•  all ot her me dic ati o ns, 
i ncl u di n g pl as m a t her a p y 
re gi me ns, f or 1 2 w ee ks 
pri or t o scree ni n g.  
T o s pecif y t he pre -st u d y 
ti me peri o d f or rec or di n g 
p ote ntiall y pr o hi bite d 
me dicati o n  
S T U D Y 
M E DI C A TI O N/ 
T R E A T M E N T,  
Secti o n  6. 8   
C o nc o mita nt 
Me dicati o ns a n d 
Restricti o ns,  
para gra p h 5  
S u bj ects ta ki n g lit hi u m or 
i nterfer o n are als o e xcl u de d. 
N ote t hat s u bj ects ta ki n g 
n o n -ster oi dal a nti-
i nfla m mat or y age nts 
( N S AI D S) c hr o nicall y 
(i nter mitte nt N S AI D S f or 
pai n or fe ver) are 
disc o ura ge d fr o m st u d y 
partici pati o n, b ut n ot 
e xcl u de d.  
S u bj ects ta ki n g lit hi u m, 
p a mi dr o n ate , i nterfer o n, or 
c hr o nic N S AI D S  are als o 
e xcl u de d. N ote t hat s u bj ects 
ta ki n g i nter mitte nt N S AI D S 
f or pai n or fe ver are 
disc o ura ge d fr o m st u d y 
partici pati o n, b ut are  n ot 
e xcl u de d.  
T o ali g n t he C o nc o mita nt 
Me dicati o ns secti o n wit h 
E xcl usi o n Criteri o n # 2 4  
S T U D Y 
M E DI C A TI O N/ 
T R E A T M E N T,  
Secti o n  6. 8  
C o nc o mita nt 
Me dicati o ns a n d 
Restricti o ns,  
p ara gra p h 6 
All c o nc o mita nt me dicati o ns 
ta ke n d uri n g … 
All c o nc o mita nt me dicati o ns 
i ncl u di n g m arij u a n a use (if 
a p plic a ble)  ta ke n d uri n g 
T o clarif y t hat marij ua na 
use s h o ul d be c ollecte d 
si nce it is a C Y P 3 A 4 
i n hi bit or. 
S T U D Y 
P R O C E D U R E S, 
Secti o n  7. 1   Scree ni n g 
a n d E nr oll me nt  
b ullet 2 
Rec or di n g … gl uc oc ortic oi ds, 
i m m u n os u p pressi ves a n d all 
C D 2 0 + a nti b o dies)  
Rec or di n g … gl uc oc ortic oi ds, 
a n d i m m u n os u p pressi ves  
T o s pecif y t he pre -st u d y 
ti me peri o d f or rec or di n g 
i m m u n os u p pressi ve 
me dicati o ns  

C C X 1 4 0- B 
 
Pr ot oc ol C L 0 1 1 _ 1 4 0 
 
  
A me n d me nt 4. 0 (2 9 Oct o ber  2 0 1 8) 
C he m o Ce n tr y x, I n c. 
C O N FI D E N TI A L  
Pa ge 1 5  of 9 3  
Secti o n(s)  
Ori gi n al Te xt  
Re vise d Te xt   
R ati o n ale f or C h a n ge  
S T U D Y 
P R O C E D U R E S  
Secti o n  7. 1  Scree ni n g 
a n d E nr oll me nt  
b ullet 4 
N o ne  
If t he s u bject h as recei ve d 
pri or rit u xi m a b tre at me nt  
or ot her B -cell de pleti n g 
a nti b o dies , rec or d t he 
me dic ati o n use, as w ell as 
a n y a v ail a ble uri n ar y  
pr otei n v al ues,  f or 1 ye ar 
pri or t o scree ni n g  
T o s pecif y t he pre -st u d y 
ti me peri o d f or rec or di n g 
use of rit u xi ma b or ot her 
B- cell de pleti n g 
a nti b o dies  
S T U D Y 
P R O C E D U R E S, 
Secti o n  7. 1   Scree ni n g 
a n d E nr oll me nt  
b ullet 5 
I n or der t o e x pe dite t he 
scree ni n g pr ocess, …t he 
l ocal la b orat or y f or t he 
f oll o wi n g: 
Pre g na nc y test (i n w o me n of 
c hil d beari n g p ote ntial)  
Vir ol o g y assess me nts ( HI V, 
H C V, H B V) u nless d o ne 
wit hi n 6 wee ks pri or t o 
scree ni n g 
N o ne  
T o re m o ve t he o pti o n f or 
t he use of l ocal 
la b orat ories.  All la bs are 
t o be pr ocesse d t hr o u g h 
t he Ce ntral La b orat or y 
S T U D Y 
P R O C E D U R E S, 
Secti o n  7. 1   Scree ni n g 
a n d E nr oll me nt  
b u llet 5 
- T est t o e xcl u de t u berc ul osis 
(i nterfer o n γ release assa y 
[I G R A], t u berc uli n p urifie d 
pr otei n deri vati ve [ P P D] s ki n 
test, or c hest ra di o gra p h y [ X 
ra ys or C T sca n]) if n ot d o ne 
wit hi n 6 wee ks pri or t o 
scree ni n g 
•  T est t o e xcl u de 
t u berc ul osis (i nterfer o n γ 
release assa y [I G R A] wit hi n 
6 wee ks pri or t o scree ni n g  
T o clarif y t hat o nl y t he 
I G R A ca n be use d t o 
pr o vi de e vi de nce of 
e xcl usi o n of  t u berc ul osis  
S T U D Y 
P R O C E D U R E S, 
Secti o n  7. 1   Scree ni n g 
a n d E nr oll me nt,  
 
N o ne  
•  T h e s u bject will be gi ve n 
i nstr ucti o ns a n d s u p plies 
f or t he uri ne c ollecti o ns o n 
t he d a y bef ore t he ne xt visit 
( kit f or first m or ni n g v oi d 
a n d j u g  f or 2 4-h o ur uri ne 
c ollecti o n)  
- C ollect t he first m or ni n g 
v oi d t he d a y bef ore t he first 
visit ( D a y 0) a n d p ut i n t he 
s m aller c o nt ai ner.   
- C ollect all uri ne f or 2 4 
h o urs st arti n g A F T E R t he 
first m or ni n g v oi d, 
i ncl u di n g first m or ni n g 
v oi d o n t he d a y of t he 
St u d y D a y  1 visit, i n t he  bi g 
j u g.   
- Kee p s peci me ns 
refri ger ate d u ntil t he y are 
br o u g ht t o t he site at t he 
St u d y D a y 1 visit.  
2 4 -h o ur uri ne c ollecti o n 
a d de d bef ore first st u d y 
dr u g d ose, a n d bef ore 
W ee k 1 2 a n d W ee k 2 4 
visits  

C C X 1 4 0- B 
 
Pr ot oc ol C L 0 1 1 _ 1 4 0 
 
  
A me n d me nt 4. 0 (2 9 Oct o ber  2 0 1 8) 
C he m o Ce n tr y x, I n c. 
C O N FI D E N TI A L  
Pa ge 1 6  of 9 3  
Secti o n(s)  
Ori gi n al Te xt  
Re vise d Te xt   
R ati o n ale f or C h a n ge  
S T U D Y 
P R O C E D U R E S, 
Secti o n  7. 6  & 7. 1 0   
N o ne  
•  Pr o vi d e t he s u bject wit h 
t he kit f or c ollecti o n of t he 
first m or ni n g v oi d a n d j u g 
f or t he 2 4-h o ur uri ne 
c ollecti o n 
 
 
N o ne  
•  After all st u d y 
pr oce d ures …  
- C ollect t he first m or ni n g 
v oi d t he d a y bef ore t he 
Wee k ( 1 2, 2 4) visit a n d p ut 
i n t he s m aller c o nt ai ner 
- C oll ect all uri ne f or 2 4 
h o urs st arti n g A F T E R t he 
first m or ni n g v oi d, 
i ncl u di n g first m or ni n g 
v oi d o n t he d a y of t he 
Wee k ( 1 2, 2 4) visit, i n t he 
bi g j u g.  
- Kee p s peci me ns  
refri ger ate d u ntil t he y are 
br o u g ht t o t he site f or t he 
Wee k ( 1 2, 2 4) visit.  
 
S T U D Y 
P R O C E D U R E S, 
Secti o n  7. 2  
t hr o u g h  7. 1 2  
First m or ni n g v oi d uri ne 
sa m ple … 
Pr ocess t he first m or ni n g 
v oi d uri ne sa m ple … 
T o clarif y t he pr oce d ure  
S T U D Y 
P R O C E D U R E S, 
Secti o ns  7. 2 , 7. 7 , 7. 1 1   
N o ne  
•  Pr ocess t he 2 4 -h o ur uri ne 
s a m ple c ollecti o n f or 
q u a ntit ati ve uri n al ysis, 
U P C R, U A C R, C yst ati n C, 
Uri ne M C P- 1, 
M C P -1/cre ati ni ne r ati o, 
uri ne P D assess me nt, a n d 
uri ne pr otei n e xcreti o n/ d a y  
T o clarif y t he pr oce d ure  
S T U D Y 
P R O C E D U R E S, 
Secti o n  7. 2  & 7. 4   
P K bl o o d sa m ples will b e 
c ollecte d at 0. 5, 1, … 
P K bl o o d sa m ples will be 
c ollecte d at Ti me 0 ( pre -
d ose),  0. 5, 1, …  
T o clarif y t hat a pre d ose 
sa m ple m ust be ta ke n. 
S T U D Y 
P R O C E D U R E S, 
Secti o ns  7. 2  
t hr o u g h Secti o n  7. 1 1   
N o ne  
•  Pr o vi de t he s u bject wit h 
t he kit f or c ollecti o n of t he 
first m or ni n g v oi d  
I nstr ucti o ns o mitte d i n 
err or 
 
N o ne  
•  After all st u d y 
pr oce d ures …  
- O n t he m or ni n g of t he 
ne xt visit, c ollect t he first 
m or ni n g v oi d i n t he 
c o nt ai ner pr o vi de d a n d 
refri ger ate u ntil it is 
br o u g ht t o t he st u d y ce nter  
 

C C X 1 4 0- B 
 
Pr ot oc ol C L 0 1 1 _ 1 4 0 
 
  
A me n d me nt 4. 0 (2 9 Oct o ber  2 0 1 8) 
C he m o Ce n tr y x, I n c. 
C O N FI D E N TI A L  
Pa ge 1 7  of 9 3  
Secti o n(s)  
Ori gi n al Te xt  
Re vise d Te xt   
R ati o n ale f or C h a n ge  
S T U D Y 
P R O C E D U R E S, 
Secti o n  7. 7   
N o ne  
•  Assess me nt of c o nti n ui n g 
eli gi bilit y re q uire me nts:  
- h as n ot wit h dr a w n 
c o nse nt f or t he st u d y  
- h as n o ne w i nfecti o ns  t h at 
i n t he j u d g me nt of t he 
i n vesti g at or w o ul d precl u de 
a d diti o n of a ne w 
i m m u n os u p pressi ve or 
i m m u n o m o d ul at or y 
tre at me nt 
- h as h a d n o re q uire me nt 
f or t he a d diti o n of ne w 
i m m u n os u p pressi ve 
tre at me nt d uri n g t he pri or 
1 2 w ee ks a n d n o 
a ntici p ate d re q uire me nt  
d uri n g t he ne xt 1 2 w ee ks  
Criteria f or assessi n g 
c o nti n ue d eli gi bilit y  
 
•  After all st u d y pr oce d ures 
ha ve bee n c o m plete d, t he 
s u bj ect will be re mi n de d t o: 
•  After all st u d y pr oce d ures 
ha ve bee n c o m plete d, 
disc o nti n ui n g s u bjects  will 
be re mi n de d t o:  
S pecif y pr oce d ures f or 
t h ose s u bj ects c o nti n ui n g 
i n t he st u d y a n d t h ose 
w h o are disc o nti n ui n g 
treat me nt. 
 
N o ne  
- c o me t o t he st u d y ce nter 
at 2 d a ys, 7 d a ys a n d 1 4 
d a ys after t he l ast d ose f or 
P K eli mi n ati o n a n d   
- c o me t o t he st u d y ce nter 
f or t he Wee k 1 6 f oll o w-u p 
visi t 
 
 
 
 
 
N o ne  
•  C o nti n ui n g s u bjects  will 
be re mi n de d t o:  
 
 
- C o me t o t he st u d y ce nter 
f or t he W ee k 1 3 st u d y visit, 
bef ore ta ki n g t he d ose of t he 
visit da y  
•  C o me t o t he st u d y ce nter 
f or t he W ee k 1 3 st u d y visit, 
bef ore ta ki n g t he d ose of 
st u d y dr u g 
 
S T U D Y 
P R O C E D U R E S,  Title 
of Secti o ns  7. 8   
t hr o u g h 7. 1 1   
St u d y W ee k …  
 
St u d y W ee k  … - C o nti n ui n g 
S u bjects O nl y  
T o i de ntif y visits t hat 
o nl y pertai n t o c o nti n ui n g 
s u bj ects 
S T U D Y 
P R O C E D U R E S, 
Secti o n  7 
7. 9 St u d y W ee k 1 6 ( Da y 1 1 4 
+/ - 3 da ys) - Safet y 
E val uati o n f or Disc o nti n ui n g 
S u bj ects O nl y  
N o ne  
Re m o ve d se parate 
i nstr ucti o ns f or s u bj ects 
disc o nti n ui n g at W ee k 1 6  
S T U D Y 
P R O C E D U R E S, 
Secti o n  7 ( n o w) 
- First m or ni n g v oi d uri ne 
sa m ple c ollecti o n f or U P C R 
a n d U A C R assess me nt  
N o ne  
Re m o ve d re d u n da nt 
i nstr ucti o n 

C C X 1 4 0- B 
 
Pr ot oc ol C L 0 1 1 _ 1 4 0 
 
  
A me n d me nt 4. 0 (2 9 Oct o ber  2 0 1 8) 
C he m o Ce n tr y x, I n c. 
C O N FI D E N TI A L  
Pa ge 1 8  of 9 3  
Secti o n(s)  
Ori gi n al Te xt  
Re vise d Te xt   
R ati o n ale f or C h a n ge  
S T U D Y 
P R O C E D U R E S, 
Secti o n  7. 1 2  ( n o w) 
Title  
7. 1 3 St u d y W ee k 2 8 ( Da y 
1 9 7 +/ - 3 da ys) - F oll o w U p 
visit ( See Secti o n 7. 1 4 f or 
P K eli mi nati o n g u i deli nes) 
7. 1 2 F oll o w U p visit - St u d y 
W ee k 1 6 ( D a y 1 1 4 +/ - 3 
d a ys f or disc o nti n ui n g 
s u bjects) a n d Wee k 2 8 (Da y 
1 9 7  +/ - 3 da ys  f or 
c o nti n ui n g s u bjects ) - ( See 
Secti o n 7. 1 3  f or P K 
eli mi nati o n g ui deli nes)  
C o m bi ne d i nstr ucti o ns 
f or F oll o w-u p visit at 
W ee k 1 6 f or 
disc o nti n ui n g s u bj ects 
a n d W ee k 2 8 f or 
C o nti n ui n g s u bj ects  
S T U D Y 
P R O C E D U R E S, 
Secti o n  7. 1 2   ( n o w)  
T he St u d y Wee k 2 8 visit 
s h o ul d occ ur … 
T he f oll o w -u p  visit s h o ul d 
occ ur …  
C o m bi ne d i nstr ucti o ns 
f or F oll o w-u p v isit at 
W ee k 1 6 f or 
disc o nti n ui n g s u bj ects 
a n d W ee k 2 8 f or 
C o nti n ui n g s u bj ects  
 
…sa m ples will be c ollecte d 
bef ore d ose a d mi nistrati o n 
f or ser u m 
…sa m ples will be c ollecte d 
f or ser u m 
S u bj ects are n ot o n st u d y 
dr u g at t his visit, i ncl u de d 
i n err or.   
S T U D Y 
P R O C E D U R E S, 
Secti o n  7. 1 3  ( n o w)  
p ara gra p h 1  
U p o n disc o nti n uati o n of 
treat me nt f or a n y reas o n a 
sa m ple … 
U p o n disc o nti n uati o n of 
treat me nt f or a n y reas o n, 
i ncl u di n g e n d of st u d y, a 
sa m ple …  
T o clarif y t hat 
disc o nti n uati o n of 
treat me nt i ncl u des e n d of 
st u d y 
p ara gra p h 2  
… sta n dar d of care me dical 
treat me nt will be pr o vi de d t o 
all s u bj ects as nee de d  
…sta n dar d of care me dical 
treat me nt s h o ul d be 
i m ple me nte d f or all s u bj ects 
as nee de d  
Clarif y i m ple me ntati o n of 
off -st u d y treat me nt at 
st u d y c o m pleti o n 
S T U D Y 
P R O C E D U R E S, 
Secti o n  7. 1 4   ( n o w) 
N o ne  
•  W he ne ver p ossi ble, t he 
s u bject will be as ke d t o 
c ollect all uri ne f or t he 2 4 
h o urs after t he l ast d ose of 
st u d y dr u g 
T o i ncl u de t he 2 4 -h o ur 
uri ne c ollecti o n i n t he 
earl y ter mi nati o n 
pr oce d ures, w he ne ver 
p ossi ble  
 
•  First m or ni n g v oi d uri ne 
sa m ple … 
•  If a v ail a ble, pr ocess t he 
first m or ni n g v oi d uri ne 
sa m ple… 
T o clarif y i nstr ucti o ns  
 
N o ne  
•  If a v ail a ble, pr ocess t he 
2 4 -h o ur uri ne s a m ple f or 
q u a nt it ati ve uri n al ysis, 
U P C R, U A C R, C yst ati n C, 
Uri ne M C P -1, M C P -
1/cre ati ni ne r ati o uri ne P D 
assess me nt a n d uri ne 
pr otei n e xcreti o n/ d a y  
 
S T U D Y 
A S S E S S M E N T S,  
Secti o n  8. 1. 1   
p ara gra p h 2 
Starti n g o n Da y 1, t he uri ne 
sam ples will be se nt …  
T he  uri ne sa m ples, first 
m or ni n g v oi d a n d 2 4 -h o ur 
uri ne s a m ple  will be se nt …  
All la bs will be d o ne 
t hr o u g h t he ce ntral la b f or 
u nif or mit y of res ults  

C C X 1 4 0- B 
 
Pr ot oc ol C L 0 1 1 _ 1 4 0 
 
  
A me n d me nt 4. 0 (2 9 Oct o ber  2 0 1 8) 
C he m o Ce n tr y x, I n c. 
C O N FI D E N TI A L  
Pa ge 1 9  of 9 3  
Secti o n(s)  
Ori gi n al Te xt  
Re vise d Te xt   
R ati o n ale f or C h a n ge  
 
… ( U P C R) … c o nce ntrati o n 
assesse d i n a sa m ple dra w n 
fr o m a first m or ni n g uri ne; 
… ( U P C R) … c o nce ntrati o n; 
B ot h first m or ni n g v oi d 
a n d 2 4 -h o ur uri ne 
sa m ples will be use d f or 
efficac y assess me nts  
 
 
…( U A C R) …  c o nce ntrati o n 
assesse d i n a sa m ple dra w n 
fr o m first m or ni n g v oi d; 
…( U A C R) …  c o nce ntrati o n; 
 
S T U D Y 
A S S E S S M E N T S,  
Secti o n  8. 2. 2  
b ullet 1 
…c or p usc ular v ol u me a n d 
retic ul oc yte c o u nt; 
… mea n c or p usc ular v ol u me , 
retic ul oc yte c o u nt a n d 
sc hist oc ytes; 
S pecif y t hat t he prese nce 
of sc hist oc ytes will be 
m o nit ore d t o assess 
he m ol ysis  
b ullet 2  
… li ver pa nel (t otal a n d 
direct bilir u bi n, …  
li ver pa nel (t otal, direct a n d 
i n direct bilir u bi n,  
S pecif y t hat i n direct 
bilir u bi n will be 
meas ure d t o assess 
he m ol ysis  
b ullet 4  
Vir ol o g y ( meas ure d o nl y at 
scree ni n g a n d ma y be 
meas ure d at t he l ocal 
la b orat or y): … 
Vir ol o g y ( meas ure d o nl y at 
scree ni n g): … 
All la bs will be d o ne 
t hr o u g h t he ce ntral la b f or 
u nif or mit y of res ults  
b ullet 5  
T B scree n: O nl y o ne of t he 
f oll o wi n g is nee de d: 
i nterfer o n γ release assa y 
(I G R A), t u berc uli n p urifie d 
pr otei n deri vati ve ( P P D) s ki n  
test, or c hest ra di o gra ms 
( X ra ys or C T sca n); c hest 
ra di o gra p h y d o ne wit hi n 6 
wee ks pri or t o scree ni n g is 
all o we d f or eli gi bilit y 
assess me nt. C hest 
ra di o gra p h y at s u bse q ue nt 
visits will o nl y be perf or me d 
if dee me d cli nicall y 
necessar y b y t he I n vesti gat or 
t o assess safety.  
T B scree n : O nl y i nterfer o n γ 
release assa y (I G R A) d o ne 
wit hi n 6  wee ks pri or t o 
scree ni n g is all o we d f or 
eli gi bilit y assess me nt.  
 
T o clarif y t hat o nl y t he 
I G R A ca n be use d t o 
pr o vi de e vi de nce of 
e xcl usi o n of  t u berc ul osis  
S T U D Y 
A S S E S S M E N T S,  
Secti o n  8. 4  
E x pl orat or y 
P har mac o d y na mic 
Assess me nts  
p ara gra p h 1  
Bl o o d sa m ples ( plas ma a n d 
ser u m) f or P D 
meas ure me nt …  
Bl o o d sa m ples ( plas ma a n d 
ser u m) a n d uri ne  s a m ples 
f or P D meas ure me nt … 
Refere nce t o t he uri ne 
sa m ples o mitte d i n err or 

C C X 1 4 0- B 
 
Pr ot oc ol C L 0 1 1 _ 1 4 0 
 
  
A me n d me nt 4. 0 (2 9 Oct o ber  2 0 1 8) 
C he m o Ce n tr y x, I n c. 
C O N FI D E N TI A L  
Pa ge 2 0  of 9 3  
Secti o n(s)  
Ori gi n al Te xt  
Re vise d Te xt   
R ati o n ale f or C h a n ge  
S T A TI S TI C S, 
Secti o n  9. 2. 2   
b ullet 1  
•  C ha n ge fr o m baseli ne i n 
e G F R calc ulate d b y t he C K D 
E PI c ystati n C e q uati o n as 
meas ure d b y e G F R at wee ks 
1 2 a n d 2 4.  
•  C ha n ge fr o m baseli ne i n 
e G F R calc ulate d b y t he 
C K D -E PI c ys tati n C 
e q uati o n, C K D -E PI 
Cre ati ni ne e q u ati o n, C K D -
E PI Cre ati ni ne -C yst ati n C 
e q u ati o n a n d M D R D 
Cre ati ni ne e q u ati o n  at 
wee ks 1 2 a n d 2 4.  
T o har m o nize 
Secti o n  9. 2. 2 of t he 
pr ot oc ol  wit h S y n o psis;  
met h o ds f or calc ulati n g 
e G F R o mitte d fr o m 
Secti o n 9. 2. 2 i n err or  
b ullet 2  
•  N o ne  
•  Pr o p orti o n of s u bjects 
ac hie vi n g c o m plete re n al 
re missi o n  at Wee ks 1 2 a n d 
2 4  
C o m plete Re missi o n 
(i ncl u des all of t he 
f oll o wi n g) 
- re d ucti o n i n U P C R t o 
< 0. 3 g/ g  
- Ser u m al b u mi n wit hi n 
n or m al r a n ge  
- F or s u bjects wit h 
a b n or m al ser u m cre ati ni ne 
le vels at b aseli ne, ret ur n t o 
n or m al le vels f or t h at a ge 
gr o u p  
- F or s u bjects wit h n or m al 
ser u m cre ati ni ne le vels at 
b aseli ne, fi n al v al ue wit hi n 
2 0 % of b aseli ne le vels  
T o har m o nize 
Secti o n  9. 2. 2 of t he 
pr ot oc ol  wit h S y n o psis; 
sec o n dar y e n d p oi nts were 
differ e nt i n err or; A d de d 
e n d p oi nt a n d defi niti o n of 
c o m plete re nal re missi o n    
b ullet 3  
•   Pr o p orti o n of s u bj ects 
ac hie vi n g partial re nal 
re missi o n ( U P C R 0. 3 g/ g: 
e G F R n or mal or n ot less t ha n 
2 0 % bel o w baseli ne) or 
partial re missi o n ( U P C R 
decrease d b y 5 0 % fr o m 
baseli ne; U P C R < 3. 5 g/ g; a n d 
e G F R n or mal or n ot less t ha n 
2 0 % bel o w baseli ne), 
assesse d at W ee ks 1 2 a n d 2 4.  
•  Pr o p orti o n of s u bj ects 
ac hie vi n g partial re missi o n  
b y t he f oll o wi n g t w o 
differe nt defi niti o ns  
assesse d at Wee ks  1 2 a n d 
2 4 : 
- U P C R re d ucti o n of ≥5 0 % 
fr om b aseli ne  a n d  U P C R 
< 3. 5 g/ g   
- decre ase i n U P C R t o less 
t h a n 1. 5 g/ g a n d at le ast a 
4 0 % re d ucti o n i n 
pr otei n uri a fr o m b aseli ne  
Clarifie d t he defi niti o n of  
partial re missi o n a n d 
a d de d a sec o n d met h o d 
f or calc ulati n g partial 
re missi o n 
S T A TI S TI C S,  
Secti o n  9. 2. 3  
Sec o n dar y Efficac y 
E n d p oi nts  
b ullet 6  
- Relati o ns hi p a m o n g P K, 
ser u m al b u mi n a n d U P C R; 
- Relati o ns hi p a m o n g P K, 
e G F R, ser u m al b u mi n a n d 
U P C R;  
U p date e x pl orat or y 
e n d p oi nts  
S T A TI S TI C S,  
Secti o n  9. 3. 3   
All C D 2 0 + a nti b o dies, 
gl uc oc ortic oi ds a n d …  
All B -cell de pleti n g  
a nti b o dies, gl uc oc ortic oi ds 
a n d  
Clarif y t he class of pri or 
me dicati o ns t hat ma y be 
s u m marize d se paratel y 

C C X 1 4 0- B 
 
Pr ot oc ol C L 0 1 1 _ 1 4 0 
 
  
A me n d me nt 4. 0 (2 9 Oct o ber  2 0 1 8) 
C he m o Ce n tr y x, I n c. 
C O N FI D E N TI A L  
Pa ge 2 1  of 9 3  
Secti o n(s)  
Ori gi n al Te xt  
Re vise d Te xt   
R ati o n ale f or C h a n ge  
S T A TI S TI C S,  
Secti o n  9. 3. 9   
b ullet 1  
•  Prese nce of ne p hr otic 
s y n dr o me ( yes vs. n o). 
Ne p hr otic s y n dr o me is 
defi ne d as pr otei n uria of 
at least 3. 5 gra ms/ da y i n 
ass ociati o n wit h 
h y p oal b u mi ne mia 
( < 3 g/ d L) a n d peri p heral 
e de ma  
•  U P C R < 3. 5 g pr otei n/ g 
cre ati ni ne at b aseli ne 
vers us U P C R ≥3. 5 g 
pr otei n/ g cre ati ni ne at 
b aseli ne  
T o har m o nize t he 
w or di n g of t he 
stratificati o n fact ors 
A P P E N DI C E S  
Secti o n 1 3. 1 State me nt of 
O bli gati o ns of S p o ns or, 
M o nit or, a n d Cli nical 
I n vesti gat or,  
Secti o n 1 3. 2 I nf or me d 
C o nse nt F or m  
N o ne  
Secti o n n o t nee de d i n 
pr ot oc ol  
 

C C X 1 4 0- B 
 
Pr ot oc ol C L 0 1 1 _ 1 4 0 
 
  
A me n d me nt 4. 0 (2 9 Oct o ber  2 0 1 8) 
C he m o Ce n tr y x, I n c. 
C O N FI D E N TI A L  
Pa ge 2 2  of 9 3  
T A B L E O F C O N T E N T S  
I N V E S TI G A T O R SI G N A T O R Y P A G E ......................................................................................... 2 
S P O N S O R C O N T A C T I N F O R M A TI O N  ....................................................................................... 3 
S P O N S O R SI G N A T U R E F O R A P P R O V A L  ................................................................................. 4 
P R O T O C O L A M E N D M E N T 4 . 0: S U M M A R Y O F C H A N G E S  ................................................... 5 
T A B L E O F C O N T E N T S  ............................................................................................................... 2 2 
1.  
S T U D Y S Y N O P SI S  ................................................................................................... 2 7 
TI M E A N D E V E N T S T A B L E ...................................................................................................... 3 7  
LI S T O F A B B R E VI A TI O N S A N D A C R O N Y M S  ...................................................................... 4 0 
2.  
I N T R O D U C TI O N ...................................................................................................... 4 2 
2. 1.  
Bac k gr o u n d I nf or mati o n  ............................................................................................. 4 2 
2. 2.  
Rati o nale f or St u d y i n F S G S: U n met Me dical Nee d  .................................................. 4 2 
2. 3.  
P ote ntial R ole of C C R 2 i n Pat h o ge n esis of F S G S ..................................................... 4 3  
2. 4.  
C C R 2 I n hi bit or C C X 1 4 0- B: N o n -Cli nical Safet y  ...................................................... 4 4 
2. 4. 1.  
C C R 2 I n hi bit or C C X 1 4 0- B: Cli nical E x perie nce  ...................................................... 4 5 
3.  
O BJ E C TI V E S  ............................................................................................................. 4 6 
3. 1.  
Pri mar y O bj ecti ve  ....................................................................................................... 4 6 
3. 2.  
Sec o n dar y O bj ecti ves  ................................................................................................. 4 6 
3. 3.  
E x pl orat or y O bjecti ves ............................................................................................... 4 6  
4.  
S T U D Y D E SI G N  ....................................................................................................... 4 7 
4. 1.  
St u d y Treat me nts  ........................................................................................................ 4 9 
4. 2.  
D ose M o dificati o n G ui deli n es .................................................................................... 5 0 
4. 2. 1.  
St o p pi n g G ui deli nes .................................................................................................... 5 0  
5.  
S T U D Y P O P U L A TI O N  ............................................................................................. 5 3 
5. 1.  
Size of t he P o p ulati o n ................................................................................................. 5 3  
5. 2.  
I n cl usi o n Criteria ........................................................................................................ 5 3 
5. 3.  
E x cl usi o n Criteria  ....................................................................................................... 5 4 
5. 4.  
C o nti n ui n g Eli gi bilit y Criteria  .................................................................................... 5 5 
5. 5.  
Re m o val of S u bjects fr o m T hera p y of Assess me nt  .................................................... 5 6 
5. 5. 1.  
S u bjects ma y be wit h dra w n fr o m t he st u d y f or t he f oll o wi n g reas o ns: ..................... 5 6  
5. 5. 2.  
S u bjects ma y disc o nti n ue st u d y dr u g treat me nt f or a n y of t he f oll o wi n g 
reas o ns: ....................................................................................................................... 5 6 
6.  
S T U D Y M E DI C A TI O N/ T R E A T M E N T  ................................................................... 5 7 

C C X 1 4 0- B 
 
Pr ot oc ol C L 0 1 1 _ 1 4 0 
 
  
A me n d me nt 4. 0 (2 9 Oct o ber  2 0 1 8) 
C he m o Ce n tr y x, I n c. 
C O N FI D E N TI A L  
Pa ge 2 3  of 9 3  
6. 1.  
Pr o d uct C haracteristics  ............................................................................................... 5 7 
6. 2.  
Ra n d o mizati o n a n d Met h o d of Treat me nt Assi g n me nt .............................................. 5 7  
6. 3.  
D oses a n d Re gi me ns ................................................................................................... 5 7  
6. 3. 1.  
I nitial 1 2 Wee k Tr eat me nt Peri o d ............................................................................... 5 7 
6. 3. 2.  
O pe n -La b el Treat me nt 1 2 Wee k Treat me nt Peri o d  .................................................... 5 8 
6. 4.  
Rati o nale f or D ose Sel ecti o n  ...................................................................................... 5 8 
6. 5.  
Dr u g S u p pl y ................................................................................................................ 6 0  
6. 5. 1.  
Pac ka gi n g a n d La b eli n g  .............................................................................................. 6 0 
6. 5. 2.  
St ora ge  ........................................................................................................................ 6 0 
6. 5. 3.  
Bli n di n g ...................................................................................................................... 6 0  
6. 6.  
Dr u g Acc o u nta bilit y ................................................................................................... 6 1  
6. 7.  
Treat me nt C o m plia nce  ................................................................................................ 6 1 
6. 8.  
C o nc o mita nt Me dicati o ns a n d Restricti o ns ................................................................ 6 1  
7.  
S T U D Y P R O C E D U R E S  ............................................................................................ 6 2 
7. 1.  
Scree ni n g a n d E nr oll me nt  ........................................................................................... 6 2 
7. 2.  
St u d y Da y 1  ................................................................................................................ 6 3 
7. 3.  
St u d y Wee k 1 ( D a y 8 +/- 1 da y) ................................................................................. 6 5  
7. 4.  
St u d y Wee k 2 ( D a y 1 5 +/- 1 da y) ............................................................................... 6 5  
7. 5.  
St u d y Wee k 4 ( D a y 2 9 +/- 3 da ys) .............................................................................. 6 6  
7. 6.  
St u d y Wee k 8 ( D a y 5 7 +/- 3 da ys) ............................................................................. 6 7  
7. 7.  
St u d y Wee k 1 2 ( D a y 8 5 +/- 3 da ys) ( See Secti o n 7. 1 3 f or P K eli mi nati o n 
g ui deli nes) ................................................................................................................... 6 8  
7. 8.  
St u d y Wee k 1 3 ( D a y 9 2 +/- 3 da ys) - C o nti n ui n g S u bjects O nl y .............................. 6 9  
7. 9.  
St u d y Wee k 1 6 ( D a y 1 1 4 +/- 3 da ys - C o nti n ui n g S u bjects O nl y .............................. 7 0  
7. 1 0.  
St u d y Wee k 2 0 ( D a y 1 4 1 +/- 3 da ys) - C o nti n ui n g s u bjects o nl y ............................... 7 1  
7. 1 1.  
St u d y Wee k 2 4 ( D a y 1 6 9 +/- 3 da ys) - C o nti n ui n g S u bjects O nl y ............................ 7 2  
7. 1 2.  
F oll o w U p visit - St u d y Wee k 1 6 ( Da y 1 1 4 +/- 3 da ys f or disc o nti n ui n g 
s u bjects) a n d Wee k 2 8 ( Da y 1 9 7 +/- 3 d a ys f or c o nti n ui n g s u bjects) - ( See 
Secti o n 7. 1 3 f or P K eli mi nati o n g ui deli nes) ............................................................... 7 3  
7. 1 3.  
P K Eli mi nati o n Visits  ................................................................................................. 7 3 
7. 1 4.  
Earl y Ter mi nati o n Visit ( See Secti o n 7. 1 4 f or P K eli mi nati o n g ui deli nes)  ............... 7 3 
8.  
S T U D Y A S S E S S M E N T S  .......................................................................................... 7 4 
8. 1.  
Efficac y Assess me nts  ................................................................................................. 7 4 

C C X 1 4 0- B 
 
Pr ot oc ol C L 0 1 1 _ 1 4 0 
 
  
A me n d me nt 4. 0 (2 9 Oct o ber  2 0 1 8) 
C he m o Ce n tr y x, I n c. 
C O N FI D E N TI A L  
Pa ge 2 4  of 9 3  
8. 1. 1.  
Uri nar y Meas ure m e nts  ................................................................................................ 7 4 
8. 1. 2.  
Esti mate d Gl o mer ular Filtrati o n Rate  ......................................................................... 7 5 
8. 1. 3.  
Ser u m Al b u mi n  ........................................................................................................... 7 5 
8. 1. 4.  
Healt h -Relate d Q ualit y of Life a n d A C T G B P N S T Assess me nts  .............................. 7 5 
8. 2.  
Safet y Assess me nts  ..................................................................................................... 7 5 
8. 2. 1.  
P h ysical E x a mi nati o ns,  Vital Si g ns, a n d E C Gs.......................................................... 7 5 
8. 2. 2.  
Cli nical Safet y La b orat or y Assess me nts  .................................................................... 7 6 
8. 2. 3.  
A d verse E v e nts  ........................................................................................................... 7 6 
8. 2. 3. 1.  
A d verse E v e nt Se verit y Assess me nt  .......................................................................... 7 7 
8. 2. 3. 2.  
Ca usalit y Assess me nt  ................................................................................................. 7 7 
8. 2. 3. 3.  
Seri o us A d verse E v e nts .............................................................................................. 7 7  
8. 2. 3. 4.  
S A Rs a n d S U S A Rs  ..................................................................................................... 7 7 
8. 2. 3. 5.  
La b orat or y A b n or malities  ........................................................................................... 7 8 
8. 2. 3. 6.  
Pre g n a ncie s ................................................................................................................. 7 8 
8. 2. 4.  
S pecial Sit uati o n Re p orti n g ........................................................................................ 7 8  
8. 2. 5.  
Seri o us A d verse E v e nt Re p orti n g ............................................................................... 7 9  
8. 3.  
P har mac o ki netic Assess me nts  .................................................................................... 8 0 
8. 4.  
E x pl orat or y P har mac o d y na mic Assess me nts  ............................................................. 8 0 
8. 5.  
St u d y C o m pleti o n a n d Wit h dra wal ............................................................................ 8 1  
9.  
S T A TI S TI C S  .............................................................................................................. 8 1 
9. 1.  
S u bject P o p ulati o ns .................................................................................................... 8 1  
9. 1. 1.  
M o difie d I nte nt -t o-Tr eat P o p ulati o n  ........................................................................... 8 1 
9. 1. 2.  
Per Pr ot oc ol P o p ulati o n .............................................................................................. 8 2  
9. 1. 3.  
Safet y P o p ulati o n ........................................................................................................ 8 2  
9. 2.  
A nal ysis E n d p oi nts ..................................................................................................... 8 2  
9. 2. 1.  
Pri mar y Efficac y E n d p oi nts ........................................................................................ 8 2  
9. 2. 2.  
Sec o n dar y Ef ficac y E n d p oi nts .................................................................................... 8 2 
9. 2. 3.  
E x pl orat or y Effi cac y E n d p oi nts ................................................................................. 8 2  
9. 2. 4.  
Safet y E n d p oi nts i ncl u de ............................................................................................ 8 3  
9. 2. 5.  
P har mac o ki netic E n d p oi nts ........................................................................................ 8 3  
9. 2. 6.  
P har mac o d y na mi c E n d p oi nts ..................................................................................... 8 3  
9. 3.  
Statistical A nal ysis Met h o d ol o g y  ............................................................................... 8 3 
9. 3. 1.  
S u bject Dis p ositi o n  ..................................................................................................... 8 4 

C C X 1 4 0- B 
 
Pr ot oc ol C L 0 1 1 _ 1 4 0 
 
  
A me n d me nt 4. 0 (2 9 Oct o ber  2 0 1 8) 
C he m o Ce n tr y x, I n c. 
C O N FI D E N TI A L  
Pa ge 2 5  of 9 3  
9. 3. 2.  
De m o gra p hics a n d Baseli ne C haract eristics  ............................................................... 8 4 
9. 3. 3.  
Pri or a n d C o nc o mita nt Me dicati o ns ........................................................................... 8 4  
9. 3. 4.  
St u d y Dr u g E x p os ure a n d C o m plia nce ....................................................................... 8 4  
9. 3. 5.  
Efficac y  A nal yses  ....................................................................................................... 8 4 
9. 3. 6.  
Safet y A nal yses  .......................................................................................................... 8 5 
9. 3. 7.  
P har mac o ki netic a n d P har mac o d y na mic M ar ker A nal ysis  ........................................ 8 5 
9. 3. 8.  
Ha n dli n g of Missi n g Dat a ........................................................................................... 8 6  
9. 3. 9.  
Stratifie d A na l ysis ...................................................................................................... 8 6 
9. 4.  
Sa m ple Size J ustificati o n  ............................................................................................ 8 6 
9. 5.  
Pr ot oc ol De viati o ns .................................................................................................... 8 6  
1 0.  
S T U D Y C O M P L E TI O N A N D  T E R M I N A TI O N ...................................................... 8 7 
1 0. 1.  
St u d y C o m pleti o n  ....................................................................................................... 8 7 
1 0. 2.  
St u d y Ter mi nati o n  ...................................................................................................... 8 7 
1 1.  
R E G U L A T O R Y A N D A D MI N I S T R A TI V E R E Q UI R E M E N T S ............................ 8 7 
1 1. 1.  
In v esti gat or Res p o nsi bilities  ....................................................................................... 8 7 
1 1. 2.  
I nstit uti o nal Re vie w B oar d or Et hics C o m mittee ....................................................... 8 7 
1 1. 3.  
I nf or me d C o nse nt ....................................................................................................... 8 8 
1 1. 4.  
Pr ot oc ol M o dificati o ns ............................................................................................... 8 8  
1 1. 5.  
Re g ulat or y D oc u me nt ati o n ......................................................................................... 8 8 
1 1. 6.  
S u bject I d e ntificati o n Re gister  ................................................................................... 8 9 
1 1. 7.  
Rec or d Rete nti o n  ........................................................................................................ 8 9 
1 1. 8.  
Case Re p ort F or m C o m pleti o n  ................................................................................... 8 9 
1 1. 9.  
M o nit ori n g .................................................................................................................. 8 9  
1 1. 1 0.  
O n -site Visits a n d A u dits ............................................................................................ 9 0 
1 1. 1 1.  
Use of I nf or mati o n a n d P u blicati o n ............................................................................ 9 0  
1 2.  
R E F E R E N C E S  ........................................................................................................... 9 1 

C C X 1 4 0- B 
 
Pr ot oc ol C L 0 1 1 _ 1 4 0 
 
  
A me n d me nt 4. 0 (2 9 Oct o ber  2 0 1 8) 
C he m o Ce n tr y x, I n c. 
C O N FI D E N TI A L  
Pa ge 2 6  of 9 3  
 
LI S T  O F T A B L E S  
Ta ble  1: 
C C X 1 4 0- B f or t he F o ur St u d y Gr o u ps  ....................................................................... 5 0 
Ta ble  2: 
D ose M o dificati o n G ui deli nes f or Si n gle S u bjects .................................................... 5 0  
 
LI S T O F FI G U R E S  
Fi g ure  1: 
St u d y Sc h e ma  ............................................................................................................. 4 9 

C C X 1 4 0- B 
 
Pr ot oc ol C L 0 1 1 _ 1 4 0 
 
  
A me n d me nt 4. 0 (2 9 Oct o ber  2 0 1 8) 
C he m o Ce n tr y x, I n c. 
C O N FI D E N TI A L  
Pa ge 2 7  of 9 3  
1.  
S T U D Y S Y N O P SI S  
N a me of S p o ns or  
C he m o Ce ntr y x, I nc.  
N a me of Acti ve I n gre die nt  
C C X 1 4 0 - B 
St u d y n u m ber   
C L 0 1 1 _ 1 4 0 
Title  
A Ra n d o mize d, D o u ble- Bli n d, Place b o- C o ntr olle d D ose- Ra n gi n g St u d y t o E val uate t he Safet y a n d 
Efficac y of C C X 1 4 0- B i n S u bj ects wit h F ocal Se g me ntal Gl o mer ul oscler osis ( F S G S)  
I n vesti g at ors 
Se veral  
St u d y ce nters  
M ulti -ce nter ; ap pr o xi matel y 4 0 sites pla n ne d i n N ort h A merica, E ur o pe, A ustralia  
St u d y peri o d  
•  
Ti me fr o m first s u bj ect first visit t o last 
visit f or assess me nt of pri mar y e n d p oi nt 
at 1 2 wee ks: a p pr o xi matel y 6 8 wee ks : 
o  4 wee ks scree ni n g  
o  5 2 wee ks recr uit me nt  
o  1 2 w ee ks t o last s u bj ect last 
visit  
 
•  
Pa rtici pati o n ti me f or eac h s u bj ect 
a p pr o xi matel y 3 2 wee ks  
o  4 wee ks scree ni n g  
o  1 2 wee ks bli n de d treat me nt 
peri o d 
o  1 2 wee k o pe n la bel treat me nt 
peri o d 
o  4 wee k f oll o w- u p 
P h ase of de vel o p me nt  
P hase 2 
Ai m  
T he ai m of t his st u d y is t o e val uate t he effect of treat me nt  wit h C C X 1 4 0- B (s o di u m salt of C C X 1 4 0), a 
selecti ve a nta g o nist of C- C c he m o ki ne rece pt or t y pe 2 ( C C R 2), i n s u bjects wit h f ocal se g me ntal 
gl o mer ul oscler osis ( F S G S).  
O bjecti ves  
•  
T he pri mar y safet y o bjecti ve of t his st u d y is t o e val uate t he safet y a n d t olera bi lit y of C C X 1 4 0-B i n 
s u bj ects wit h F S G S wit h pr otei n uria. 
•  
T he pri mar y efficac y o bjecti ve of t his st u d y is t o e val uate t he effect of C C X 1 4 0 - B treat me nt o n 
uri nar y pr otei n e xcreti o n i n s u bjects wit h F S G S , as assesse d b y c ha n ge fr o m baseli ne i n t he uri ne 

C C X 1 4 0- B 
 
Pr ot oc ol C L 0 1 1 _ 1 4 0 
 
  
A me n d me nt 4. 0 (2 9 Oct o ber  2 0 1 8) 
C he m o Ce n tr y x, I n c. 
C O N FI D E N TI A L  
Pa ge 2 8  of 9 3  
pr ote i n t o creati ni ne rati o ( U P C R) at Wee k 1 2 . 
T he sec o n dar y o bj ecti ves of t his st u d y are:  
•  
T o e val uate t he effect of C C X 1 4 0- B o n re nal f u ncti o n, as assesse d b y esti mate d gl o mer ular filtrati o n 
rate (e G F R) at Wee ks 1 2 a n d 2 4 
•  
T o e v al u ate t he effect of C C X 1 4 0- B tre at me nt o n fr acti o n of s u bjects ac hie vi n g c o m plete a n d 
p arti al re n al re missi o n ( b y 2 differe nt p arti al re missi o n defi niti o ns)  
•  
T o e val uate t he p har mac o ki netic ( P K) pr ofile of C C X 1 4 0- B i n s u bj ects wit h F S G S  
E x pl orat or y o bj ecti ves of t his st u d y are:  
•  
T o e val uat e t he effect of C C X 1 4 0- B o n uri nar y m o n o c yte c he m oattracta nt pr otei n- 1 ( M C P - 1, als o 
k n o w n as C C L 2) a n d ot her ser u m a n d uri nar y mar kers of re nal f u ncti o n a n d i nfla m mati o n; 
•  
T o e x pl ore t he effect of C C X 1 4 0- B o n le vels of bl o o d m o n oc ytes, T, B a n d N K cells, a n d ot her 
bl o o d a n d uri nar y mar kers p ote ntiall y ass ociate d wit h C C R 2 a nta g o nis m; 
•  
T o e x pl ore t he effect of C C X 1 4 0- B o n Healt h- relate d Q ualit y of Life c ha n ges base d o n a ns wers t o 
t he S h ort F or m 3 6 versi o n 2 ( S F- 3 6 v 2) a n d E ur o Q u alit y of Life -5 D o m ai ns - 5 Le vels (E Q - 5 D- 5 L) 
q uesti o n n aires ; 
•  
T o e x pl ore t he relati o ns hi ps a m o n g e x p os ure ( P K) of C C X 1 4 0 - B, ser u m al b u mi n le vel, a n d U P C R 
R ati o n ale 
F ocal se g me ntal gl o mer ul oscler osis ( F S G S) descri bes a gr o u p of dis or ders t hat s hare a c o m m o n 
hist ol o gic lesi o n c haracterize d b y scarri n g  t hat a p pears o n li g ht micr osc o p y t o occ ur i n s o me b ut n ot all 
gl o mer uli (f ocal) a n d t o affect o nl y part of t he i n v ol ve d gl o mer uli (se g me ntal) . F S G S is classifie d as 
pri mar y w he n t he eti ol o g y is n ot k n o w n, a n d as sec o n dar y w he n it occ urs i n t he prese nce of ne p hr o n 
l oss, dia betes, o besit y, h y perte nsi o n, dr u g e x p os ure, hi g h ris k ge netic varia nts, a n d ot her c o n diti o ns 
rec o g nize d t o i ncrease ris k. 
Patie nts wit h F S G S lesi o ns ma y prese nt wit h ne p hr otic s y n dr o me or wit h s u b-cli nical ele vati o ns of 
uri nar y pr otei n or ser u m creati ni ne. C urre nt g ui deli nes ( Ki d ne y Disease: I m pr o vi n g Gl o bal O utc o mes 
Practice G ui deli ne f or Gl o mer ul o ne p hritis, 2 0 1 2 ) rec o m me n d a trial of gl uc oc ortic oi ds f or patie nts wit h 
pri mar y F S G S a n d feat ures of ne p hr otic s y n dr o me, f oll o we d b y calci ne uri n i n hi bit ors if nee de d f or 
i nt olera nce or i na de q uate res p o nse t o gl uc oc ortic oi ds. N o n - ne p hr otic or sec o n dar y F S G S is treate d wit h 
o pti mal ma na ge me nt of c o - m or bi d c o n diti o ns; bl oc ka de of t he re ni n a n gi ote nsi n al d oster o ne s yste m 
( R A A S) is use d t o treat h y perte nsi o n a n d re d uce pr otei n uria w he n i n dicate d . Des pite best sta n dar d of 
care, pr o gressi o n of disease is c o m m o n; i n t he U S, t he esti mate d i nci de nce of ne wl y -rec o g nize d F S G S, 
a n d t he re p orte d i nci de nce of e n d sta ge re nal disease ( E S R D) d ue t o F S G S, are b ot h a p pr o xi matel y 
7/ milli o n/ year. T h us c urre nt t hera pies ma y be dela yi n g, b ut n ot pre ve nti n g, re nal fail ure. 
T he i nteracti o n bet wee n C C R 2 a n d M C P- 1 has e mer ge d as a p ote ntial tar get f or treat me nt of F S G S, 
base d o n ass ociati o n bet wee n le vels of uri n e M C P - 1 a n d disease acti vit y i n h u ma n, a n d o n o bser vati o ns 
i n m uri ne m o dels wit h feat ures of F S G S . 
C C X 1 4 0 - B, a n orall y a d mi nistere d selecti ve a nta g o nist of C C R 2, has e x hi bite d efficac y i n m uri ne 
m o dels of re nal da ma ge as assesse d b y si g nifica nt re d ucti o ns i n pr otei n uria, a n i m p orta nt cli nical 
e n d p oi nt f or F S G S . C C X 1 4 0-B was ass ociate d wit h a fa v ora ble safet y pr ofile w he n a d mi nistere d at 5 
m g dail y or 1 0 m g dail y f or u p t o 5 2 wee ks i n patie nts wit h dia betic ne p hr o pat h y; a tre n d t o war d greater 
re d ucti o n i n pr otei n uria c o m pare d t o place b o was see n i n b ot h acti ve treat me nt gr o u ps, a n d reac he d 
statistical si g nifica nce i n t he gr o u p treate d wit h 5 m g d ail y. 

C C X 1 4 0- B 
 
Pr ot oc ol C L 0 1 1 _ 1 4 0 
 
  
A me n d me nt 4. 0 (2 9 Oct o ber  2 0 1 8) 
C he m o Ce n tr y x, I n c. 
C O N FI D E N TI A L  
Pa ge 2 9  of 9 3  
Base d o n t he precli nical rati o nale, fa v ora ble safet y pr ofile, a n d si g nals of efficac y i n dia betic s u bjects 
wi t h mar ke d pr otei n uria, C he m o Ce ntr y x pla ns t o assess C C X 1 4 0-B i n s u bjects wit h F S G S.  
Met h o d ol o g y 
T his st u d y will e val uate t he efficac y, safet y, t olera bilit y, a n d p har mac o ki netics of u p t o 1 2  wee ks of 
treat me nt wit h eac h of t hree d ose re gi me ns of C C X 1 4 0-B o r place b o, w he n use d i n c o m bi nati o n wit h 
sta ble sta n dar d of care t hera p y i n s u bjects wit h F S G S wit h si g nifica nt pr otei n uria, assesse d as U P C R > 
1 g/ g at Scree ni n g. F oll o wi n g t he 1 2- wee k bli n de d treat me nt peri o d, s u bjects will recei ve acti ve 
treat me nt f or a n a d diti o nal 1 2 wee ks t o assess s afet y a n d d ura bilit y of effect. 
T he tar get is t o e nr oll 4 0 a d ult male or fe male s u bjects i n t his ra n d o mize d, d o u ble - bli n d, place b o-
c o ntr olle d, P hase 2 st u d y. S u bj ects will be ra n d o mize d 1: 1: 1: 1 t o o ne of f o ur treat me nt gr o u p s: 
•  
Gr o u p A: Place b o ( N = 1 0) 
•  
Gr o u p B: C C X 1 4 0- B 5 m g o nce dail y ( N = 1 0) 
•  
Gr o u p C: C C X 1 4 0- B 1 0 m g t wice dail y ( N = 1 0) 
•  
Gr o u p D: C C X 1 4 0- B 1 5 m g t wice dail y ( N = 1 0) 
Ra n d o mizati o n will be stratifie d b y U P C R < 3. 5 g pr otei n/ g creati ni ne vers us U P C R ≥3. 5 g pr otei n/ g 
creati ni ne at baseli ne a n d b y t he c urre nt use of gl uc oc ortic oi ds a n d/ or i m m u n os u p pressi ve me dicati o ns 
( yes vs  n o). 
Bli n de d st u d y me dicati o n will be ta ke n b y t he s u bjects f or 8 4 da ys, as f oll o ws:  
•  
Gr o u p A: T hree place b o ta blets, ta ke n t wice dail y;  
•  
Gr o u p B: O ne 5 m g C C X 1 4 0 - B ta blet a n d t w o place b o ta blets i n t he m or ni n g; t hree place b o 
ta blets i n t he e ve ni n g; 
•  
Gr o u p C: T w o 5 m g C C X 1 4 0- B ta blets a n d o ne place b o ta blet, ta ke n t wice dail y  
•  
Gr o u p D: T hree 5 m g C C X 1 4 0- B ta blets, ta ke n t wice dail y  
S u bj ects will be scree ne d  wit hi n a peri o d n ot t o e xcee d 2 8 da ys pri or t o St u d y Da y 1 (t he first da y of 
d osi n g). 
All s u bj ects will ta ke bli n de d st u d y me dicati o n i n t he m or ni n g a n d e ve ni n g, wit h or wit h o ut f o o d, f or 8 4 
c o nsec uti ve da ys. F oll o wi n g t he 8 4- da y bli n de d d osi n g peri o d, al l s u bjects will ta ke o pe n la bel 
C C X 1 4 0 - B f or a n a d diti o nal 8 4 da ys at t he hi g hest d ose u n der e val uati o n, c urre ntl y pla n ne d t o be 1 5 m g 
t wice dail y. If t he S p o ns or, wit h t he a d vice of t he u n bli n de d Data M o nit ori n g C o m mittee ( D M C), 
deter mi nes t hat 1 5 m g t wic e dail y e xcee d s t he ma xi m u m t olerate d d ose, t he n t he d ose a d mi nistere d 
d uri n g t he o pe n la bel peri o d will be a dj uste d d o w n war d fr o m t he pla n ne d d ose t o t he hi g hest d ose t hat is 
still u n der e val uati o n. T here will be a 2 8 - da y f oll o w- u p peri o d after c o m pleti o n of treat me nt.  
D uri n g t he treat me nt peri o d, eli gi ble s u bjects will visit t he st u d y ce nter o n St u d y Da ys 1, 8, 1 5, 2 9 
( Wee k 4), a n d Wee ks 8, 1 2 ( pri mar y e n d p oi nt), 1 3, 1 6, 2 0, a n d 2 4 f or st u d y pr oce d ures i ncl u di n g 
i nter val hist or y, p h ysical e xa mi nati o n a n d vital si g ns, E C G, st u d y q uesti o n naires, a n d c ollecti o n of 
bl o o d a n d uri ne. S u bjects will disc o nti n ue st u d y dr u g as of St u d y Da y 1 6 9 ( Wee k 2 4), a n d will ret ur n f or 
a f oll o w u p visit o n Wee k 2 8. W he n feasi ble, u p o n disc o nti n uati o n of treat me nt f or a n y reas o n a sa m ple 
of w h ole bl o o d s h o ul d be c ollecte d f or assess me nt of eli mi nati o n 2, 7 a n d 1 4 da ys after t he fi nal d ose of 
C C X 1 4 0 - B ( or place b o). 
F or assess me nt of a d verse e ve nts of s pecial i nterest, st u d y pr oce d ures will i ncl u de  

C C X 1 4 0- B 
 
Pr ot oc ol C L 0 1 1 _ 1 4 0 
 
  
A me n d me nt 4. 0 (2 9 Oct o ber  2 0 1 8) 
C he m o Ce n tr y x, I n c. 
C O N FI D E N TI A L  
Pa ge 3 0  of 9 3  
•  
C o m plete bl o o d c o u nt wit h differe ntial, m or p h ol o g y assess me nt, retic ul oc yte c o u nt, he m o gl o bi n, 
L D H a n d t otal a n d direct bilir u bi n , t o assess earl y e vi de nce of he m ol ysis; 
•  
T he A I D S C li nical T rials Gr o u p Brief Peri p heral Ne ur o pat h y Scree ni n g T o ol ( A C T G-B P N S T) , 
t o assess earl y e vi de nce of ne ur o pat h y; 
•  
M o nit ori n g f or a d verse e ve nts of i nfecti o n;  
•  
Al kali ne p h os p hatase, A L T, A S T a n d t otal a n d direct bilir u bi n; t o assess f or e vi de nce of dr u g 
i n d uce d li ver i nj ur y. 
F or assess me nt of p har mac o ki netics, st u d y pr oce d ures will i ncl u de  
•  
Se ve n  bl o o d sa m ples c ollecte d o ver 6 h o urs o n St u d y Da y 1 a n d St u d y Da y 1 5 t o assess A U C0- 6  
f oll o wi n g t he first a d mi nistrati o n of st u d y dr u g, a n d at stea d y state; 
•  
Assess me nt of C mi n  at i nter vals t o e ns ure t hat e x p os ure is wit hi n t he pr ojecte d ra n ge, wit h 
a de q uate safet y mar gi n base d o n t he N O A E L esta blis he d i n precli nical t o xic ol o g y; 
•  
U p o n disc o nti n uati o n of treat me nt f or a n y reas o n, c ollecti o n of bl o o d at 2 da ys, 7, da ys a n d 1 4 
da ys f oll o wi n g disc o nti n uati o n t o assess eli mi nati o n ki netics . 
All st u d y pr oce d ures are prese nte d i n  t he Ti me a n d E ve nts ta ble . 
S u bj ects w h o are usi n g a n a n gi ote nsi n c o n verti n g e nz y me ( A C E) i n hi bit or, a n gi ote nsi n rece pt or bl oc ker 
( A R B) or ot her bl oc ker of t he re ni n a n gi ote nsi n al d oster o ne s yste m ( R A A S), or w h o are usi n g 
gl uc oc ortic oi ds, a calci n e uri n i n hi bit or or ot her i m m u n o m o d ulat or y or i m m u n os u p pressi ve t hera p y, 
m ust be o n a sta ble d ose f or at least 4 wee ks pri or t o scree ni n g. T he d ose of t hese me dicati o ns s h o ul d be 
pla n ne d t o be ke pt c o nsta nt o ver t he c o urse of t he st u d y i n or der t o pre ve nt u n d ue i nfl ue nce of c ha n ges 
i n t hese me dicati o ns o n t he efficac y a n d safet y assess me nts, e xce pt w he n a dj ust me nt is re q uire d f or 
patie nt safet y . T he i n vesti gat or m ust als o atte m pt t o kee p d oses of ot her me dicati o ns, a n d li pi d-l o weri n g 
me dicati o ns fi xe d t hr o u g h o ut t he bli n de d st u d y peri o d i n or der t o pre ve nt u n d ue i nfl ue nce of c ha n ges i n 
t hese me dicati o ns o n t he efficac y a n d safet y assess me nts. 
S u bj ects w h o e x perie nce deteri orati n g re nal f u ncti o n base d o n a n i ncrease i n ser u m creati ni ne of at least 
5 0 % (c o nfir me d b y a r e peat meas ure me nt after 2 wee ks) w hic h is ot her wise n ot e x plai ne d (e. g., 
de h y drati o n, ne w me dicati o n), or i ncrease i n U P C R of > 3. 0 g/ g (c o nfir me d b y a re peat meas ure me nt 
after 2 wee ks) d uri n g t he 1 2 -wee k treat me nt peri o d, will e xit t he treat me nt p hase of t he st u d y a n d be 
treate d at t he discreti o n of t he treati n g p h ysicia n. All s u bj ects w h o disc o nti n ue treat me nt will re mai n i n 
t he st u d y f or f oll o w u p a n d o utc o me rec or di n g. 
A n i n de pe n de nt Data M o nit ori n g C o m mittee ( D M C) will be res p o nsi ble f or re vie wi n g u n bli n de d safet y 
data t hr o u g h o ut t he c o urse of t he st u d y.  
S u bj ects will be disc har ge d fr o m t he st u d y at t he c o m pleti o n of t he Wee k 2 8 visit. T o t he e xte nt 
p ossi ble, a n y a d verse e ve nts t hat are dee me d st u d y dr u g -relate d a n d are o n g oi n g at disc har ge will be 
f oll owe d - u p t o res ol uti o n or u ntil a deter mi nati o n is ma de t hat t he u nres ol ve d e ve nt is sta ble. 
N u m ber of S u bjects  
T he tar get n u m ber of s u bjects is 4 0. S u bjects w h o disc o nti n ue d uri n g t he first 1 4 da ys of ta ki n g st u d y 
dr u g f or reas o ns ot her t ha n a d verse e ve nts  relate d t o st u d y dr u g ma y be re place d t o e ns ure t hat s ufficie nt 
data are a vaila ble f or assess me nt of safet y, P K, a n d efficac y.  

C C X 1 4 0- B 
 
Pr ot oc ol C L 0 1 1 _ 1 4 0 
 
  
A me n d me nt 4. 0 (2 9 Oct o ber  2 0 1 8) 
C he m o Ce n tr y x, I n c. 
C O N FI D E N TI A L  
Pa ge 3 1  of 9 3  
M a i n Criteri a f or I ncl usi o n 
1.  Male or fe male s u bjects a ge d 1 8 - 7 5 years i ncl usi ve 
2.   Uri nar y t otal pr otei n:creati ni ne rati o  ( U P C R) ≥ 1 g pr otei n/ g creati ni ne at scree ni n g ( or U P C R 
at 1 1 3 m g/ m m ol). 
3.  Dia g n osis of F S G S base d o n at least o ne of t he f oll o wi n g:  
o  Re nal bi o ps y de m o nstrati n g t he F S G S lesi o n  a n d c haracteristic cli nical prese ntati o n a n d 
c o urse 
o  H i g h ris k ge netic varia nt a n d c haracteristic cli nical prese ntati o n  a n d c o urse 
4.  Dia g n osis of o ne of t he f oll o wi n g s u bt y pes of F S G S: 
o  Pri mar y F S G S base d o n c haracteristic hist o pat h ol o g y, me dical hist or y, a n d cli nical 
c o urse , or 
o  F S G S sec o n dar y t o a ge netic varia nt ass ociate d wit h i ncrease d  ris k or se verit y, w hic h 
ma y i ncl u de N P H S 1, N P H S 2, W T- 1, L A M B 2, C D 2 A P, T R P C 6, A C T N 4 or I N F 2 
5.  Esti mate d gl o mer ular filtrati o n rate (e G F R) > 3 0 m L/ mi n/ 1. 7 3 m 2, wit h e G F R calc ulate d usi n g 
t he C hr o nic Ki d ne y Disease E pi de mi ol o g y C olla b orati o n ( C K D- E PI) e q uati o n ( usi n g creati ni ne 
or c ystati n C) 
6.  T he t y pical bl o o d press ure of t he patie nt s h o ul d be cli nicall y sta ble pri or t o e nr oll me nt a n d n ot 
e xcee d 1 4 5/ 9 5 m m H g. 
7.  If usi n g R A A S bl oc kers, d ose m ust be sta ble f or a mi ni m u m of 4 wee ks pri or t o Scree ni n g, a n d 
pr ojecte d t o re mai n sta ble t hr o u g h St u d y Wee k 1 2, u nless a dj ust me nt is re q uire d f or 
ma na ge me nt of h y perte nsi o n. 
8.  If usi n g i m m u n os u p pressi ve or i m m u n o m o d ulat or y t hera p y, d ose m ust be sta ble f or a mi ni m u m 
of 4 wee ks pri or t o Scree ni n g, a n d pr ojecte d t o re mai n sta ble t hr o u g h St u d y Wee k 1 2 
9.  If usi n g gl uc oc ortic oi ds, d ose m ust be sta ble f or a mi ni m u m of 4 wee ks pri or t o Scree ni n g a n d 
pr ojecte d t o re mai n sta ble t hr o u g h St u d y Wee k 1 2 
1 0.  Fe male s u bjects of c hil d beari n g p ote ntial ma y partici pate if a de q uate c o ntrace pti o n is use d 
d uri n g, a n d f or at least 1 m o nt h  after last d ose of st u d y dr u g. Male s u bjects wit h part ners of 
c hil d beari n g p ote ntial ma y partici pate i n t he st u d y if t he y ha d a vasect o m y at least 6 m o nt hs 
pri or t o ra n d o mizati o n or if a de q uate c o ntrace pti o n is use d d uri n g, a n d f or at least o ne m o nt h 
after t he last d ose of st u d y dr u g. A de q uate c o ntrace pti o n is defi ne d as res ulti n g i n a fail ure rate 
of less t ha n 1 % per year (c o m bi ne d estr o ge n a n d pr o gest o ge n [ oral, i ntra va gi nal, or 
tra ns der mal], or pr o gest o ge n- o nl y h or m o nal c o ntrace pti o n ( oral, i njecta ble, or i m pla nta ble), 
i ntra-uteri ne de vice, i ntra - uteri ne h or m o ne releasi n g s yste m, bilateral t u bal occl usi o n, 
vasect o mize d part ner, or se x ual a bsti ne nce). I n a d diti o n, a barrier met h o d (i.e. cer vical ca p, 
dia p hra g m or c o n d o m) m ust b e use d d uri n g i nterc o urse bet wee n a male s u bject a n d a fe male of 
c hil d- beari n g p ote ntial. 
1 1.  Willi n g a n d a ble t o gi ve writte n I nf or me d C o nse nt a n d t o c o m pl y wit h t he re q uire me nts of t he 
st u d y pr ot oc ol 
1 2.  J u d ge d t o be ot her wise fit f or t he st u d y b y t he I n vesti gator, base d o n me dical hist or y, p h ysical 

C C X 1 4 0- B 
 
Pr ot oc ol C L 0 1 1 _ 1 4 0 
 
  
A me n d me nt 4. 0 (2 9 Oct o ber  2 0 1 8) 
C he m o Ce n tr y x, I n c. 
C O N FI D E N TI A L  
Pa ge 3 2  of 9 3  
e xa mi nati o n, a n d cli nical la b orat or y assess me nts. S u bjects wit h cli nical la b orat or y val ues t hat 
are o utsi de of n or mal li mits ( ot her t ha n t h ose s pecifie d i n t he E xcl usi o n Criteria) a n d/ or wit h 
ot her a b n or mal cli nical fi n di n gs t hat are j u d ge d b y t he I n vesti gat or n ot t o be of cli nical 
si g nifica nce, ma y be e ntere d i nt o t he st u d y. 
M ai n Criteri a f or E xcl usi o n  
1.  Pre g na nt or n ursi n g 
2.  Hist or y of or ga n tra ns pla ntati o n, i ncl u di n g re nal tra ns pla ntati o n 
3.  C urre ntl y o n a n or ga n tra ns pla nt waiti n g list or t here’s a reas o na ble p ossi bilit y of getti n g a n 
or ga n tra ns pla nt wit hi n 6 m o nt hs of scree ni n g 
4.  S u bj ects w h o  use d rit u xi ma b or ot her B- cell de pleti n g  m o n ocl o nal a nti b o dies wit hi n 2 0 wee ks 
pri or t o scree ni n g are e xcl u de d w hile s u bjects t hat use d rit u xi ma b or ot her B- cell de pleti n g  
m o n ocl o nal a nti b o dies pri or t o 2 0  wee k s of scree ni n g are all o we d wit h c o nfir me d rec o ver y of 
t he B-cell p o p ulati o n t o wit hi n n or mal ra n ge at t he ti me of scree ni n g  
5.  Plas ma p heresis wit hi n 1 2 wee ks pri or t o scree ni n g  
6.  B o d y mass i n de x ( B MI ) ≥4 0  
7.  Partici pate d i n a n y cli nical st u d y of a n i n vesti gati o nal pr o d uct wit hi n 1 2 wee ks pri or t o 
scree ni n g, or wit hi n 5 half-li ves after ta ki n g t he last d ose of i n vesti gati o nal pr o d uct  
8.  C urre ntl y o n dial ysis or li kel y t o re q uire dial ysis d uri n g t he pr ojecte d bli n de d treat me nt peri o d 
of 1 2 wee ks  
9.  Hist or y or prese nce of a n y f or m of ca ncer wit hi n t he 5 years pri or t o scree ni n g, wit h t he 
e xce pti o n of e xcise d basal cell or s q ua m o us cell carci n o ma of t he s ki n, or carci n o ma i n sit u s uc h 
as cer vical or breast carci n o ma  i n sit u t hat has bee n e xcise d or resecte d c o m pletel y a n d is 
wit h o ut e vi de nce of l ocal rec urre nce or metastasis  
1 0.  P ositi ve H B V, H C V, or HI V viral scree ni n g test. S u bjects w h o ha ve recei ve d hi g hl y effecti ve 
t hera p y f or H C V de m o nstrate d t o ha ve ne gati ve viral titers f or at least 6 m o nt hs f oll o wi n g 
disc o nti n uati o n of treat me nt, will be c o nsi dere d t o ha ve a ne gati ve H C V scree ni n g test  
1 1.  Re nal disease ass ociate d wit h dis or ders ot her t ha n F S G S (e. g. l u p us ne p hritis, C 3 
gl o mer ul o pat h y, pr oliferati ve gl o mer ul o ne p hritis, I g A ne p hr o pat h y, refl u x ne p hr o pat h y, s ur gical 
se g me ntal re nal a blati o n, sic kle cell disease) t hat is acti ve, or has si g nifica nt ris k of pr o gressi n g 
d uri n g t he c o urse of t he st u d y 
1 2.  Dis or ders ot her t ha n t h ose liste d i n I ncl usi o n Criteri o n 4 t hat are ass ocia te d wit h F S G S lesi o n 
(i.e.. sec o n d ar y F S G S s uc h as si n gle ki d ne y, sur gical se g me ntal re nal a blati o n , sic kle cell 
disease, dia betic ne p hr o pat h y , ot hers), or hist ol o gic al c oll a psi n g v ari a nt s u bt y pes of F S G S  
1 3.  E vi de nce of t u berc ul osis base d o n i nterfer o n γ rele ase assa y (I G R A ) wit hi n 6 wee ks pri or t o 
scree ni n g 
1 4.  E vi de nce of he patic disease; A S T, A L T, al kali ne p h os p hatase > 3 x U L N, or t otal bilir u bi n > 2 x 
U L N or I N R > 1. 5 x U L N at scree ni n g wit h t he e xce pti o n t hat is olate d I N R ele vati o n i n t he 
a bse nce of ot her si g ni fica nt li ver e nz y me a b n or malities is e x plai ne d b y a ntic oa g ula nt t hera p y, 

C C X 1 4 0- B 
 
Pr ot oc ol C L 0 1 1 _ 1 4 0 
 
  
A me n d me nt 4. 0 (2 9 Oct o ber  2 0 1 8) 
C he m o Ce n tr y x, I n c. 
C O N FI D E N TI A L  
Pa ge 3 3  of 9 3  
(e. g. warfari n).  
1 5.  Cli nicall y si g nifica nt peri p heral ne ur o pat h y.  
1 6.  He mat ol o gic a b n or malities as f oll o ws: H b <  8 g/ d L, platelets <  5 0, 0 0 0, A N C < 1 0 0 0  cells/ μ L) at 
baseli ne  
1 7.  Cli nicall y si g n ifica nt a b n or mal E C G d uri n g scree ni n g, e. g., Q T c F greater t ha n 4 5 0 msec  
1 8.  Hist or y of alc o h ol or illicit dr u g a b use . Recreati o nal use of ca n na bis is n ot e xcl u de d w here le gal.  
1 9.  Hist or y of gastr oi ntesti nal c o n diti o ns t hat ma y i nterfere wit h st u d y me dicati o n c o m p lia nce, e. g., 
se vere gastr o paresis, wit h re g ur gitati o n of f o o d or oral me dicati o n 
2 0.  K n o w n h y perse nsiti vit y t o C C X 1 4 0- B or i nacti ve i n gre die nts of t he C C X 1 4 0 -B ta blets 
(i ncl u di n g micr ocr ystalli ne cell ul ose, starc h, cr os p o vi d o ne, ma g nesi u m stearate, silic o n dio xi de , 
or t artr azi ne ) 
2 1.  Hist or y or prese nce of s yste mic dis or der ot her t ha n F S G S t hat re q uires, or is e x pecte d t o re q uire, 
s yste mic gl uc oc ortic oi ds or i m m u ne m o d ulat ors d uri n g t he st u d y; t o pical or i n hale d 
gl uc oc ortic oi ds a n d i m m u n e m o d ulat ors are n ot e xcl u d e d 
2 2.  Hist or y or prese nce of a n y me dical c o n diti o n or disease w hic h, i n t he o pi ni o n of t he 
I n vesti gat or, ma y place t he s u bj ect at u nacce pta ble ris k f or st u d y partici pati o n 
2 3.  S u bj ects ta ki n g str o n g C Y P 3 A 4 i n d ucers (e. g., p he n yt oi n, rifa m pici n, car ba maze pi ne, St. J o h n’s 
W ort)  or str o n g C Y P 3 A 4 i n hi bit ors (e. g., b oce pre vir, clarit hr o m yci n, c o ni va pta n, gra pefr uit 
j uice, i n di na vir, itrac o naz ole, ket oc o naz ole, l o pi na vir/rit o na vir, mi befra dil, nefaz o d o ne, 
nelfi na vir, p osac o naz ole, rit o na vir, sa q ui na vir, tela pre vir, teli t hr o m yci n, a n d v oric o naz ole) 
wit hi n t w o wee ks pri or t o scree ni n g 
2 4.  S u bj ects ta ki n g lit hi u m , p a mi dr o n ate, or i nterfer o n; s u bj ects ta ki n g n o n -ster oi dal a nti-
i nfla m mat or y a ge nts ( N S AI D S) c hr o nicall y (i nter mitte nt, i.e., occasi o nal N S AI D S f or pai n or 
fe ver is disc oura ge d, b ut is n ot e xcl u de d)  
Test P r o d uct  
St u d y dr u g will be a d mi nistere d as 3 ta blets t wice dail y ( 5 m g C C X 1 4 0- B ta blets, matc he d place b o, or 
c o m bi nati o n) f or u p t o 1 2 wee ks i n a d o u ble- bli n d ma n ner. 
C C X 1 4 0- B will be a d mi nistere d as  u p t o 3 ta blets ( 5  m g eac h) t wice dail y d uri n g st u d y wee ks 1 3 
t hr o u g h 2 4 i n a n o pe n-la bel ma n ner. 
St u d y dr u g will be s u p plie d t o t he st u d y ce nter i n plastic b ottles, eac h b ottle c o ntai ni n g 3 0 ta blets. 
D uri n g t he bli n de d p orti o n of t he st u d y, st u d y dr u g will be s u p plie d t o t he s u bject i n kits, eac h kit 
c o ntai ni n g 3 b ottles la bele d wit h a yell o w ba n d f or use i n t he m or ni n g a n d 3 b ottles la bele d wit h a bl ue 
ba n d f or use i n t he e ve ni n g. Eac h b ottle will be als o la bele d wit h a disti n g uis hi n g n u m ber. S u bj ects will 
be i nstr ucte d t o  ta ke o ne ta blet fr o m eac h of t he t hree yell o w b ottles i n t he m or ni n g, a n d o ne ta blet fr o m 
eac h of t he t hree bl ue b ottles i n t he e ve ni n g a n d t o mai ntai n a d osi n g diar y. 

C C X 1 4 0- B 
 
Pr ot oc ol C L 0 1 1 _ 1 4 0 
 
  
A me n d me nt 4. 0 (2 9 Oct o ber  2 0 1 8) 
C he m o Ce n tr y x, I n c. 
C O N FI D E N TI A L  
Pa ge 3 4  of 9 3  
D ur ati o n of Tre at me nt a n d O bser v ati o n 
S u bj ects will be scree ne d wit hi n a peri o d n ot t o  e xcee d 2 8 da ys pri or t o St u d y Da y 1 (t he first da y of 
d osi n g). 
T he place b o -c o ntr olle d treat me nt peri o d t hr o u g h t he pri mar y safet y, P K a n d efficac y e n d p oi nts is 8 4 
da ys ( 1 2 wee ks). T he t otal treat me nt peri o d is 2 4 wee ks. T he safet y f ol l o w u p peri o d is 4 we e ks. 
T o t he e xte nt p ossi ble, a n y a d verse e ve nts t hat are dee me d st u d y dr u g- relate d a n d are o n g oi n g at 
disc har ge will be f oll o we d t hr o u g h res ol uti o n or u ntil a deter mi nati o n is ma de t hat t he u nres ol ve d e ve nt 
is sta ble. 
S af et y a n d Ot her Assess me nts  
Safet y w ill be e val uate d b y peri o dic p h ysical e xa mi nati o ns a n d b o d y s yste m re vie ws, assess me nts of 
vital si g ns, r o uti ne cli nical la b orat or y tests (i ncl u di n g bl o o d c he mistr y, he mat ol o g y, a n d uri nal ysis), 
electr ocar di o gra p hic ( E C G) m o nit ori n g, a n d m o nit ori n g of a d ve rse e ve nts a n d c o nc o mita nt me dicati o ns. 
T he A C T G -B P N S T will be use d at eac h sc he d ule d visit t o assess earl y e vi de nce of ne ur o pat h y.  
P h ar m ac o ki netic Assess me nts  
C o nce ntrati o ns of C C X 1 4 0 will be deter mi ne d i n plas ma fr o m 4. 0- m L bl o o d sa m ples c ollecte d i n 
K 2E D T A t u bes acc or di n g t o t he Ti me a n d E ve nts Ta ble . T he f oll o wi n g para meters will be deter mi ne d, 
w here p ossi ble:  
C ma x  
Ma xi m u m plas ma c o nce ntrati o n  
T ma x  
Ti me of ma xi m u m plas ma c o nce ntrati o n  
A U C 0- 6 
Area u n der t he plas ma c o nce ntrati o n -ti me c ur ve fr o m Ti me 0 to H o ur 6 o n Da y 1 a n d Da y 
1 5 
C mi n        Tr o u g h le vel plas ma c o nce ntrati o ns at p ost-Da y 1 visits  ot her t ha n Da y 1 5  
T he relati o ns hi p bet wee n P K a n d ser u m al b u mi n a n d bet wee n P K a n d U P C R will be e x pl ore d w here 
p ossi ble. 
Effic ac y Assess me nts  
Efficac y will be  e val uate d b y assess me nt of uri ne pr otei n:creati n i ne rati o ( U P C R), uri ne 
al b u mi n:creati ni ne rati o ( U A C R)  a n d esti mate d gl o mer ular filtrati o n rate (e G F R)  
T he pri mar y efficac y e n d p oi nt is: 
•  
C ha n ge fr o m baseli ne i n uri ne pr otei n:creati ni ne rati o ( U P C R) 
Sec o n da r y e n d p oi nts i ncl u de: 
•  
C ha n ge fr o m baseli ne i n e G F R calc ulate d b y t he C K D -E PI c ystati n C e q uati o n, C K D -E PI 
Creati ni ne e q uati o n, C K D -E PI Creati ni ne -C ystati n C e q uati o n a n d M D R D Creati ni ne e q uati o n at 
Wee ks 1 2 a n d 2 4 
•  
Pr o p orti o n of s u bjects ac hie vi n g c o m plete re nal re missi o n at Wee ks 1 2 a n d 2 4 
C o m plete Re missi o n (i ncl u des all of t he f oll o wi n g):  
- 
Re d ucti o n i n U P C R t o < 0. 3 g/ g 
- 
Ser u m al b u mi n wit hi n  n or m al r a n ge  
- 
F or s u bjects wit h a b n or m al ser u m cre ati ni ne le vels at  b aseli ne , ret ur n t o n or m al le vels f or 
t h at a ge gr ou p  

C C X 1 4 0- B 
 
Pr ot oc ol C L 0 1 1 _ 1 4 0 
 
  
A me n d me nt 4. 0 (2 9 Oct o ber  2 0 1 8) 
C he m o Ce n tr y x, I n c. 
C O N FI D E N TI A L  
Pa ge 3 5  of 9 3  
- 
F or s u bjects wit h n or m al ser u m cre ati ni ne le vels at b aseli ne, fi n al v al ue wit hi n 2 0 % of 
b aseli ne le vels  
•  
P r o p orti o n of s u bjects ac hie vi n g  p arti al re missi o n at Wee ks 1 2 a n d 2 4 b y t he f oll o wi n g t w o 
differe nt defi niti o ns:  
- 
U P C R re d ucti o n of ≥ 5 0 % f r o m b aseli ne  a n d U P C R < 3. 5 g / g 
- 
decre ase i n U P C R t o  less t h a n 1. 5 g/ g a n d at le ast a 4 0 % re d ucti o n i n pr otei n uri a fr o m 
b aseli ne  
He alt h Rel ate d Q u alit y of Lif e Assess me nt  
C ha n ge fr o m baseli ne i n d o mai ns assesse d b y a ns wers t o t he  S F - 3 6 v 2 a n d E Q-5 D - 5 L q uesti o n n aires  
t hr o u g h Wee k 1 2 a n d Wee k 2 4  
E x pl or at or y P h ar m ac o d y n a mic Assess me nts  
Bl o o d ( plas ma a n d ser u m) a n d uri ne sa m ples will be c ollecte d acc or di n g t o t he Ti me a n d  E ve nts Ta ble  
f or P D bi o mar ker meas ure me nts.  
E x pl orat or y assess me nts m a y i ncl u de: 
•  
Pr ofile of F S G S relate d ge ne m utati o ns;  
•  
C ha n ge fr o m baseli ne i n uri nar y M C P- 1:creati ni ne rati o;  
•  
C ha n ge fr o m baseli ne i n  uri nar y al b u mi n t o creati ni ne rati o (U A C R ) 
•  
C ha n ge fr o m baseli ne i n bl o o d m o n oc ytes, T, B a n d N K cells 
•  
C ha n ge fr o m baseli ne i n ot her uri nar y a n d bl o o d e x pl orat or y bi o mar kers  p ote ntiall y ass ociate d wit h 
acti vit y of F S G S or i n hi biti o n of t he C C R 2 / M C P-1 pat h wa ys. T hese ma y i ncl u de meas ure me nt of : 
- Tra nsf or mi n g gr o wt h fact or-beta ( T G F -β), c o n necti ve tiss ue gr o wt h fact or ( C T G F), N -
acet yl gl uc osa mi ne ( N A G), β 2 micr o gl o b uli n, a di p o necti n, C -reacti ve pr otei n ( C R P), c ystati n C, 
s y na pt o p o di n, ne utr o p hil gelati nase-ass ociate d li p ocali n ( N G A L), li ver -fatt y aci d- bi n di n g 
pr otei n ( L F A B P), ki d ne y i nj ur y m olec ule- 1 ( KI M - 1), i ntact P T H, le pti n, resisti n, c he meri n, 
reti n ol bi n di n g pr otei n 4 ( R B P- 4), M C P-1, I L -1 β, I L - 6, s u P A R, s u C D 1 6 3, mi R - 1 9 3a, C L C F- 1 
a n d T N F -α.  
St atistic al Met h o ds  
A Statistical A nal ysis Pla n ( S A P) will be de vel o pe d se paratel y pri or t o t he data base l oc k a n d u n bli n di n g. 
T his S A P will  pr o vi de detail of t he data s u m mar y a n d a nal ysis s pecificati o ns. W he n differe nce s e xist 
bet wee n t he S A P a n d t he pr ot oc ol s pecifie d statistical met h o ds, t he S A P will s u perse de t he pr ot oc ol.  
De m o gr a p hics a n d B aseli ne C h ar acteristics 
All baseli ne s u bject c har acteristics , de m o gra p hics, a n d pri or/ c o nc o mita nt me dicati o ns will be liste d b y 
s u bj ect a n d s u m marize d b y treat me nt gr o u p a n d o verall. 
S afety A n alysis  
All s u bj ects w h o are ra n d o mize d a n d recei ve d at least o ne d ose of st u d y me dicati o n will be i ncl u de d i n 
t he safet y p o p ulati o n. 
Safet y e n d p oi nts i ncl u de:  
•  
S u bj ect i nci de nce of treat me nt -e mer ge nt a d verse e ve nts, a d verse e ve nts lea di n g t o st u d y wit h dra wal, 
a n d seri o us a d verse e ve nts;  
•  
C ha n ge fr o m baseli ne a n d s hifts fr o m baseli ne i n all safet y la b orat or y para meters;  
•  
C ha n ge fr o m baseli ne i n vital si g ns;  
•  
C ha n ge fr o m baseli ne i n sc ore o n t he A C T G - B P N S T  

C C X 1 4 0- B 
 
Pr ot oc ol C L 0 1 1 _ 1 4 0 
 
  
A me n d me nt 4. 0 (2 9 Oct o ber  2 0 1 8) 
C he m o Ce n tr y x, I n c. 
C O N FI D E N TI A L  
Pa ge 3 6  of 9 3  
•  
Cli nicall y si g nifica nt a b n or mal E C G fi n di n gs  
•  
P h ysical e xa mi nati o ns  
Treat me nt -e mer ge nt a d verse e ve nts ( T E A E) will be s u m marize d f or eac h treat me nt gr o u p b y Me d D R A 
S yste m Or ga n Class ( S O C) a n d preferre d ter m ( P T), b y relate d ness a n d ma xi m u m se verit y. Treat me nt -
e mer ge nt seri o us a d verse e ve nts ( T E S A E) a n d T E A E lea di n g t o st u d y wit h dra wal will be se paratel y 
liste d a n d ma y be s u m marize d if warra nte d b y t he s u bject i nci de nces. 
V ital si g ns a n d la b orat or y test res ults, a n d t heir c ha n ges fr o m baseli ne will be s u m marize d b y treat me nt 
gr o u p a n d visit. A b n or mal la b orat or y val ues will be fla g ge d i n t he data listi n g. S hift ta bles will be 
ge nerate d b y st u d y visit.  
I n di vi d ual E C G fi n di n gs a n d c ha n ge fr o m baseli ne i n E C G fi n di n gs will be liste d b y treat me nt gr o u p, 
s u bj ect, a n d st u d y visit, a n d s u m marize d b y treat me nt gr o u p a n d visit. 
Fi n di n gs fr o m p h ysical e xa mi nati o ns will be liste d. 
P h ar m ac o ki netic A n alysis  
I n di vi d ual plas ma c o nce ntrati o ns of C C X 1 4 0 will be liste d, pl otte d, a n d s u m marize d descri pti vel y a n d 
gra p hicall y f or s u bj ects recei vi n g C C X 1 4 0 - B. T he f oll o wi n g para meters will be deter mi ne d f or 
C C X 1 4 0:  
C ma x  
Ma xi m u m plas ma c o nce ntrati o n  
tma x  
Ti me of ma xi m u m plas ma c o nce ntrati o n  
A U C 0- 6 
Are a u n der t he plas ma c o nce ntrati o n -ti me c ur ve fr o m Ti me 0 t o Ti me 6 
S u m mar y statistics f or stea d y state tr o u g h plas ma c o nce ntrati o ns will als o be perf or me d. 
T he relati o ns hi p bet wee n P K para meters a n d re nal f u ncti o n base d o n e G F R, U P C R a n d ser u m al b u mi n 
will be e val uate d. T he data ma y als o be use d t o e val uate t he P K/ P D rela ti o ns hi p of C C X 1 4 0-B 
treat me nt. 
Effic acy A n alysis  
S u m mar y statistics will be calc ulate d f or eac h of t he efficac y para meters. F or cate g orical e n d p oi nts, 
n u m bers a n d perce nta ges will be calc ul ate d. F or c o nti n u o us varia bles, n u m bers, mea ns, me dia ns, ra n ges, 
a n d sta n dar d de viati o ns will be calc ulate d. P oi nt esti mates a n d c orres p o n di n g 9 0 % c o nfi de nce i nter vals 
will be esti mate d f or t he differe nce bet wee n C C X 1 4 0 - B a n d place b o gr o u ps. 
Beca use of t he  relati vel y s mall size of t he st u d y, i nfere ntial statistical a nal yses ma y n ot be a p pr o priate. 
W here p ossi ble, c ha n ge fr o m baseli ne t o Da y 8 5 a n d fr o m Da y 8 5 t o Da y 1 6 9 i n U P C R will be a nal yze d 
usi n g t he mi xe d- effects m o del f or re peate d meas ures ( M M R M), wit h treat me nt gr o u p, visit, a n d 
treat me nt- b y-visit as fact ors a n d baseli ne U P C R a n d a ge as c o variates. T he bet wee n gr o u p c o m paris o n 
will be c o m p ute d usi n g t he si m ple c o ntrast fr o m t he m o del. A nal ysis of c o varia nce ( A N C O V A) wit h 
last o bser vati o n carrie d f or war d ( L O C F) f or missi n g data will als o be use d f or se nsiti vit y a nal ysis. T he 
M M R M a n d A N C O V A a nal yses will als o be a p plie d t o t he e G F R e n d p oi nt.  
Pr o p orti o n of s u bjects ac hie vi n g partial res p o nse will be calc ulate d f or eac h treat me nt gr o u p. T he 
bet wee n gr o u p c o m paris o n will be carrie d o ut  usi n g t he Fis her’s e xact test.  
T he e x pl orat or y e n d p oi nts will be a nal yze d usi n g M M R M m o del or A N C O V A as descri be d f or t he 
pri mar y efficac y e n d p oi nt a nal ysis.  

C C X 1 4 0- B 
 
Pr ot oc ol C L 0 1 1 _ 1 4 0 
 
 
A me n d me nt 4. 0 ( 2 9 Oct o ber  2 0 1 8) 
C he m o Ce ntr y x, I n c . 
C O N FI D E N TI A L  
Pa ge 3 7  of 9 3  
TI M E A N D E V E N T S T A B L E  
Assess me nts  
Scree ni n g  
D o u ble -Bli n d Tre at me n t1 
O pe n -L a bel Tre at me nt  
F oll o w -U p  
V ari a ble  
 
 
I niti al St u d y P h ase 
E xte nsi o n P h ase  
Eli mi n ati o n  
D a ys  
≤ 2 8 d a ys  
1 
8 
1 5  
2 9  
5 7  
8 5 7 
9 2  
1 1 3  
1 4 1  
1 7 0  
 
1 1 3 7 & 1 9 8  
 
2, 7 & 1 4 
d a ys p ost 
fi n al d ose 
Wee ks  
≤4 w ee ks  
 
1 
2 
4 
8 
1 2 7 
1 3  
1 6  
2 0  
2 4  
1 6 7 & 2 8  
 
I nf or me d c o nse nt 
X 
 
 
 
 
 
 
 
 
 
 
 
 
De m o gra p hics, me dical 
hist or y, pri or me dicati o ns  
X  
 
 
 
 
 
 
 
 
 
 
 
 
HI V, H B V, H C V testi n g  
X 
 
 
 
 
 
 
 
 
 
 
 
 
Scree ni n g f or t u berc ul osis 4 
X  
 
 
 
 
 
 
 
 
 
 
 
 
Re nal nee dle bi o ps y f or F S G S 
c o nfir mati o n (if n ot d o ne 
pre vi o usl y a n d if dia g n osis n ot 
base d o n ge netic i nf or mati o n)  
X  
 
 
 
 
 
 
 
 
 
 
 
 
E nr oll me nt, Stratificati o n a n d 
Ra n d o mizati o n  
 
X  
 
 
 
 
 
 
 
 
 
 
 
P h ysical  e xa mi nati o n 2 
X 
X 3 
X 
X 
X 
X  
X 
X 
X 
X 
X 
X 
 
Vital si g ns  
X  
X 3 
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
 
1 2 -lea d E C G 
X  
X  
 
 
 
 
X  
X  
 
 
X  
X  
 
Ser u m pre g na nc y test f or 
w o me n of c hil d beari n g 
p ote ntial  
X 
X 
 
 
X 
 
X 
 
X 
X 
X 
X 
 
He mat ol o g y, Ser u m c he mistr y 
(c oa g ulati o n pa nel a n d li pi ds 
i ncl u ded at s pecifie d visits 9) 
X 
X 3, 9 
X 9 
X 
X 9 
X 
X 9 
X 9 
X 9 
X 
X 9 
X 9 
 
W h ole bl o o d f or D N A  
 
X  
 
 
 
 
 
 
 
 
 
 
 
L y m p h oc yte s u bset 8 
X  
X  
X  
X  
X  
 
X  
 
X  
 
X  
X  
 
Uri nal ysis  
X  
X 3 
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
 

C C X 1 4 0- B 
 
Pr ot oc ol C L 0 1 1 _ 1 4 0 
 
 
A me n d me nt 4. 0 ( 2 9 Oct o ber  2 0 1 8) 
C he m o Ce ntr y x, I n c . 
C O N FI D E N TI A L  
Pa ge 3 8  of 9 3  
Assess me nts  
Scree ni n g  
D o u ble -Bli n d Tre at me n t1 
O pe n -L a bel Tre at me nt  
F oll o w -U p  
V ari a ble  
 
 
I niti al St u d y P h ase 
E xte nsi o n P h ase  
Eli mi n ati o n  
D a ys  
≤ 2 8 d a ys  
1 
8 
1 5  
2 9  
5 7  
8 5 7 
9 2  
1 1 3  
1 4 1  
1 7 0  
 
1 1 3 7 & 1 9 8  
 
2, 7 & 1 4 
d a ys p ost 
fi n al d ose 
Wee ks  
≤4 w ee ks  
 
1 
2 
4 
8 
1 2 7 
1 3  
1 6  
2 0  
2 4  
1 6 7 & 2 8  
 
First m or ni n g v oi d f or uri ne 
pr otei n a n d creati ni ne assa ys 
( U P C R, U A C R a n d C ystati n 
C assess me nt)  
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
2 4 -h o ur uri ne c ollecti o n  
 
X 
 
 
 
 
X 
 
 
 
X 
 
 
A C T G Brief P eri p heral 
Ne ur o pat h y Scree ni n g T o ol  
X 
X 3 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
S F -3 6 v 2 & E Q -5 D -5 L  
 
X 3 
 
 
X 
 
X 
 
X 
 
X 
X 
 
C C X 1 4 0 -B/ Place b o 
dis pe nsi n g  
 
X 
 
 
X 
X 
 
 
 
 
 
 
 
C C X 1 4 0 -B/ Place b o d o u ble -
bli n d d osi n g  
 
X
→ 
→ 
→ 
→ 
→ 
 
 
 
 
 
 
 
C C X 1 4 0 -B O pe n la bel 
dis pe nsi n g  
 
 
 
 
 
 
X 
 
X 
X 
 
 
 
C C X 1 4 0 -B O pe n la bel 
d osi n g 6 
 
 
 
 
 
 
X
→ 
→ 
→ 
→ 
→ 
 
 
C C X 1 4 0 -B acc o u nta bilit y  
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
Plas ma M C P -1  
 
X 3 
X  
X  
X  
 
X  
X  
X  
 
X  
X  
 
P D plas ma/ser u m sa m ple 
c ollecti o n  
 
X 3 
X  
X  
X  
 
X  
X  
X  
 
X  
X  
 
Uri ne M C P 1 -1,  
M C P -1/ Creati ni ne  
 
X 3 
X  
X  
X  
 
X  
X  
X  
 
X  
X  
 
P D uri ne sa m ple c ollecti o n  
 
X 3 
X 
X 
X 
 
X 
X 
X 
 
X 
X 
 
P K plas ma sa m ple c ollecti o n  
 
X 3, 5 
X  
X 5 
X  
X  
X  
X  
X  
X  
X  
X 1 1 
X 1 1 
 

C C X 1 4 0- B 
 
Pr ot oc ol C L 0 1 1 _ 1 4 0 
 
 
A me n d me nt 4. 0 ( 2 9 Oct o ber  2 0 1 8) 
C he m o Ce ntr y x, I n c . 
C O N FI D E N TI A L  
Pa ge 3 9  of 9 3  
Assess me nts  
Scree ni n g  
D o u ble -Bli n d Tre at me n t1 
O pe n -L a bel Tre at me nt  
F oll o w -U p  
V ari a ble  
 
 
I niti al St u d y P h ase 
E xte nsi o n P h ase  
Eli mi n ati o n  
D a ys  
≤ 2 8 d a ys  
1 
8 
1 5  
2 9  
5 7  
8 5 7 
9 2  
1 1 3  
1 4 1  
1 7 0  
 
1 1 3 7 & 1 9 8  
 
2, 7 & 1 4 
d a ys p ost 
fi n al d ose 
Wee ks  
≤4 w ee ks  
 
1 
2 
4 
8 
1 2 7 
1 3  
1 6  
2 0  
2 4  
1 6 7 & 2 8  
 
C o nc o mita nt me dicati o ns  
X 1 0 
X 
X 
X  
X 
X 
X 
X 
X 
X 
X 
X 
 
A d verse e ve nt assess me nt  
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
1W ee k 1 a n d 2 visits m ust occ ur wit h a ± 1 da y wi n d o w. W ee k 4 t hr o u g h W ee k 2 8 visits ma y occ ur wit hi n a ± 3 da y wi n d o w.  
2P h ysical e xa mi nati o n will i ncl u de b o d y wei g ht meas ure me nts. Hei g ht will o nl y be meas ur e d at Scree ni n g. F ull p h ysical e xa mi nati o n will be perf or me d at 
Scree ni n g  a n d Da y 1 . At all ot her visits, li mite d , p h ysical e xa mi nati o n will be perf or me d directe d b y re vie w of s yste ms, l a b orat or y fi n di n gs a n d I n vesti gat or 
discreti o n.  
3T hese pr oce d ures m ust  be perf or me d bef ore ta ki n g t he first d ose of C C X 1 4 0 -B o n Da y 1; i n a d diti o n, C B C a n d bilir u bi n will be assesse d at 2 a n d 6 h o urs 
f oll o wi n g d osi n g i n bl o o d t o be dra w n at t he sa me ti me as t he P K sa m ple 
4T B scree ni n g  b y  I nterfer o n γ release assa y (I G R A) d o ne wit hi n 6 wee ks pri or t o Scree ni n g or d o ne d uri n g Scree ni n g.  
5P K bl o o d sa m ple will be c ollecte d o n D a ys 1 a n d 1 5  pri or t o t he m or ni n g d ose (ti me 0), a n d at 0. 5, 1, 2, 3, 4, a n d 6 h o urs f oll o wi n g d osi n g. P K sa m ples at a ll 
ot her visits  will be c ollecte d at ti me 0 o nl y, j ust pri or t o a d mi nistrati o n of t he first dail y d ose.  
6 Eli gi ble s u bj ects ma y e nter a n O pe n -La bel E xte nsi o n at t he hi g hest safe d ose of C C X 1 4 0 -B. T he mi ni m u m eli gi bilit y r e q uire me nts f or t he O pe n -La b el 
E xt e nsi o n i ncl u de n o wit h dra wal of s u bj ect c o nse nt a n d n o ne w i nfecti o ns t hat i n t he j u d g me nt of t he i n vesti gat or w o ul d precl u de a d diti o n of a ne w 
i m m u n os u p pressi ve or i m m u n o m o d ulat or y treat me nt, n o re q uire me nt f or a d diti o n of ne w i m m u n os u p pressi ve treat me nt d uri n g t he pri or 1 2 wee ks a n d n o 
a ntici pate d re q uire me nt d uri n g t he ne xt 1 2 wee ks.  
7T he W ee k 1 6 visit is a safet y f oll o w u p visit f or  s u bj ects st o p pi n g st u d y dr u g at W ee k 1 2, a n d n ot g oi n g o nt o t he O pe n-La bel E xte nsi o n. F or t h ose g oi n g o n t he 
O pe n -La bel E xte nsi o n, W ee k 1 6 is a re g ularl y sc he d ule d st u d y visit.  
8W h ole bl o o d f or a nal ysis of a bs ol ute c o u nt of T -cells, B -cells a n d Nat ural Killer Cells  
9 Ser u m c he mistr y  at e ac h visit  t o i ncl u de li ver p a nel (t ot al, direct a n d i n direct bilir u bi n, L D H, A S T, A L T), al k ali n e p h os p h at ase, etc. (see Secti o n 8. 2. 2 ); 
at s pecifie d visits, t o i ncl u de c oa g ulati o n pa nel ( P T, P T T & I N R) a n d li pi ds ( H D L, L D L, Tri gl yceri des a n d T otal C h olester ol) as w ell  
1 0 C o nc o mita nt me dicati o ns will be rec or de d f or all me dicati o ns ta ke n 1 2 wee ks pri or t o scree ni n g. Gl uc oc ortic oi ds a n d  i m m u n os u p pressi ves will be re c or de d 
f or u p t o 6 m o nt hs pri or t o scree ni n g. If t he s u bject h as recei ve d pri or rit u xi m a b tre at me nt or ot her B- cell de pleti n g a nti b o dies, t he me dic ati o n use, as  
w ell as a n y a v ail a ble u ri n ar y pr otei n v al ues,  s h o ul d be re c or de d f or u p t o 1 ye ar pri or t o scree ni n g .  
1 1 P K bl o o d sa m ples will be c ollecte d at 2 da ys, 7 da ys a n d 1 4 da ys f oll o wi n g t he l ast d os e of st u d y dr u g , as w ell at t he F oll o w-u p Visit ( Wee k 1 6 or Wee k 2 8)  
t o assess eli mi nati o n. 
 

C C X 1 4 0- B 
 
Pr ot oc ol C L 0 1 1 _ 1 4 0 
 
  
A me n d me nt 4. 0 (2 9 Oct o ber  2 0 1 8) 
C he m o Ce ntr y x, I n c . 
C O N FI D E N TI A L  
Pa ge 4 0  of 9 3  
LI S T O F A B B R E VI A TI O N S A N D A C R O N Y M S  
A C T G -B P N S T  
Ai ds Cli nical Trial Gr o u p - Brief Peri p heral Ne ur o pat h y Scree ni n g T o ol 
A C E  
A n gi ote nsi n C o n verti n g E nz y m e 
A D M E  
A bs or pti o n, Distri b uti o n, Meta b olis m a n d E x creti o n 
A N C O V A  
A nal ysis of c o vari a nce  
A R B  
a n giote nsi n r ece pt or II bl oc ker 
A U C  
area u n d er t he c ur ve  
A U C 0- 6 
area u n d er t he c ur ve, fr o m ti me of d osi n g t o 6 h o urs p ost- d ose 
BI D  
t w o d oses per da y; als o re prese nt e d as b.i. d. 
C C L 2  
C C C he m o ki ne Li ga n d 2 (als o k n o w n as M C P- 1), mai n c he m o ki ne f or 
C C R 2  
C C R 2  
C C C he m o ki ne Rece pt or 2 
C C X 1 4 0- B 
s o di u m salt of C C X 1 4 0 
C K D -E PI  
c hr o nic ki d ne y disease e pi de mi ol o g y c olla b orati o n 
C mi n  
mi ni m u m plas ma c o nce ntrati o n  
C ma x  
ma xi m u m ( ma xi mal) plas ma c o nce ntrati o n  
C Y P  
c yt o c hr o me P 4 5 0 
D M C  
Data M o nit ori n g C o m mittee  
D N  
Dia betic ne p hr o p at h y  
E C G  
Electr ocar di o gra m  
e G F R  
Esti mate d gl o mer ular filtrati o n rate  
E S R D  
E n d State Re nal Disease  
E S R F  
E n d Sta ge Re n al Fail ure  
F D A  
F o o d a n d Dr u g A d mi nistrati o n 
F S G S  
F ocal Se g me nt al Gl o mer ul oscler osis  
GI  
Gastr oi ntesti nal  
G L P  
G o o d La b orat or y Practices  
G M P  
G o o d Ma n ufact uri n g Practice 
H B V  
He patitis B vir us  
H C V  
He patitis C vir us  
h E R G  
p otassi u m c ha n nel e nc o d e d b y t h e h u ma n et her-à- g o g o relate d ge n e  

C C X 1 4 0- B 
 
Pr ot oc ol C L 0 1 1 _ 1 4 0 
 
  
A me n d me nt 4. 0 (2 9 Oct o ber  2 0 1 8) 
C he m o Ce ntr y x, I n c . 
C O N FI D E N TI A L  
Pa ge 4 1  of 9 3  
HI V  
H u ma n i m m u n o deficie nc y vir us 
I C H 
I nter nati o nal C o nfere nce o n Har m o nizati o n 
I g G 
I m m u n o gl o b uli n G 
I g M 
I m m u n o gl o b uli n M 
I G R A 
I nterfer o n Ga m ma Rel ease Assa y 
I M P 
I n v esti gati o nal me dici nal pr o d uct 
I N D 
I n v esti gati o nal Ne w Dr u g A p plicati o n 
I N R 
I nter nati o nal N or m alizati o n Rati o 
K DI G O  
Ki d ne y Disease I m pr o vi n g Gl o bal O ut c o mes 
L O C F  
Last o bser va ti o n carrie d f or war d 
M C P - 1 
m o n oc yte c he m oattracta nt pr otei n 1, als o k n o w n as C C L 2 
M D R D  
M o dific ati o n of Diet i n Re n al Dise ase  
mI T T  
M o difie d I nte nt  t o treat 
M M R M  
Mi x e d -effects m o del f or re peat e d meas ures  
N O A E L  
n o- o bser ve d-a d verse- effect le vel  
N O E L  
n o- o bser ve d -effect le v el  
P K  
p har mac o ki netic(s) 
P O  
oral ( per os); als o re prese nte d as “ p. o.” 
P R  
Partial re missi o n  
Q D  
o ne d ose per d a y; als o re prese nte d as “ q. d.” 
R A A S  
Re ni n -a n gi ote nsi n -al d oster o ne s yste m  
R B C  
re d bl o o d cell(s) 
S A E  
Seri o us a d verse e ve nt  
t1/ 2 
half -life 
T 2 D M  
t y pe 2 dia b etes mellit us 
T E A E  
Treat me nt e mer ge nt a d v erse e ve nt  
T ma x  
ti me of ma xi mal c o nce ntrati o n 
U A C R  
uri nar y al b u mi n:creati ni ne rati o  
U A E R  
uri nar y al b u mi n e x creti o n rate  
U L N  
U p per Li mit of N or mal  
U P C R  
Uri nar y pr otei n : creati ni n e rati o  
μ M  
Micr o m olar  

C C X 1 4 0- B 
 
Pr ot oc ol C L 0 1 1 _ 1 4 0 
 
  
A me n d me nt 4. 0 (2 9 Oct o ber  2 0 1 8) 
C he m o Ce ntr y x, I n c . 
C O N FI D E N TI A L  
Pa ge 4 2  of 9 3  
2.  
I N T R O D U C TI O N 
2. 1.  
B ac k gr o u n d I nf or m ati o n  
C C X 1 4 0- B is a n orall y a d mi nistere d, selecti ve a nt a g o nist of C- C c h e m o ki ne rece pt or t y pe 2 
( C C R 2) t hat has de m o nstrate d efficac y f or re d u cti o n of pr otei n uria i n a P hase 2 st u d y i n patie nts 
wit h dia betic ne p hr o pat h y a n d is c urre ntl y i n de v el o p me nt f or treat me nt of patie nts wit h f ocal 
se g me nt al gl o mer ul oscler osis ( F S G S). 
2. 2.  
R ati o n ale f or St u d y  i n F S G S: U n met Me dic al Nee d 
F ocal se g m e ntal gl o mer ul oscler osis ( F S G S) des cri bes a gr o u p of dis or d ers t hat prese n t cli nicall y 
wit h pr otei n uria a n d pr o gressi ve re n al i ns ufficie n c y a n d s h are a c o m m o n hist ol o gic lesi o n 
c haracterize d b y scarri n g  t hat a p pears o n li g ht micr osc o p y t o occ ur i n s o me b ut n ot all gl o mer uli 
(f ocal) a n d t o affect o nl y part of t he i n v ol ve d gl o m er uli (se g me ntal). F S G S is classifie d as 
pri mar y w he n  t he eti ol o g y is n ot k n o w n, a n d as sec o n dar y w h e n it occ urs i n t he prese n ce of 
ne p hr o n l oss, dia betes, o besit y, h y perte nsi o n, dr u g e x p os ure, hi g h -ris k ge n etic varia nts a n d ot h er 
c o n diti o ns rec o g nize d t o i nc reas e ris k. Se veral ge n etic varia nts ha v e bee n i de ntifie d t hat i m pact 
t he str uct ure or f u ncti o n of p o d oc ytes, a n d i ncreas e t he ris k or se v erit y of F S G S (C he n et al, 
2 0 1 5 ). F S G S ma y pres e nt wit h ne p hr otic s y n dr o m e or wit h s u b-cli nical el e vati o ns of uri nar y 
pr otei n or ser u m creati ni ne. 
S u p p orti ve ma na ge me nt f or F S G S i ncl u des re ni n-a n gi ote nsi n al d oster o ne s yste m i n hi bit ors 
( R A A S) bl oc kers f or ma na ge me nt of pr ot ei n uria a n d h y p erte nsi o n w h e n i n dicate d , a n d stati ns 
f or ma na ge me nt of d ysli pi de mia. F or patie nts prese nti n g wit h pri mar y F S G S a n d pr otei n uria, 
gl uc o c ortic oi ds at d oses e q ui vale nt t o 0. 3 t o 1. 5 m g/ k g/ d pre d nis o ne f or d urati o ns of 4 t o 2 4 
m o nt hs ha ve bee n r e p ort e d t o ac hie v e c o m plete or partial re missi o n i n 2 8 % t o 7 4 % of patie nts 
(K or bet et al., 1 9 9 4 ; Ba nf i et al., 1 9 9 1; Cattra n a n d Ra o, 1 9 9 8 ; R y del et al., 1 9 9 5 ; Gi ps o n et al., 
2 0 1 6 ; Cattra n et al., 2 0 0 8 ). Li mitati o ns of c urre nt treat me nt i ncl u de i na d e q u ate res p o nse i n a 
si g nifica nt pr o p orti o n of patie nts, fre q ue nt rec urre nce of disease i n res p o n d ers, a n d pr o gressi o n 
of re nal i ns uffi cie nc y i n m ost patie nts o ver ti me.  T he m ost i nf or mati ve p u blis he d data o n rate of 
pr o gressi o n deri v es fr o m t he T or o nt o Gl o mer ul o n e p hritis Re gistr y ( Cattra n et al, 2 0 0 8 ). A m o n g 
3 7 0 patie nts wit h F S G S, t he esti m at e d gl o mer ul ar filtr ati o n r ate (e G F R ) decli ne d b y 5 t o 1 8 
g/ ml/ 1. 7 5 m 2/ year i n t he s u bset wit h ne p hr otic le vel pr otei n uria. A m o n g pati e nts wit h hi g h le vels 
of pr otei n uria at t he ti me of prese ntati o n, 5 0 % pr o gresse d t o e n d-st a ge re n al dise ase (E S R D ) 
wit hi n 3 t o 8 years ( D’ A gat i, 2 0 1 1). I n t he U S, t he esti mate d i nci de nce of ne wl y -rec o g nize d 
F S G S, a n d t he re p orte d i nci de nce E S R D d ue t o F S G S, are b ot h a p pr o xi matel y 7/ milli o n/ year 
(Si m et al., 2 0 1 6 ). T h us c urre nt t her a pies ma y be d ela yi n g b ut n ot pre ve nti n g, re nal fail ure 
(Tr o ya n o v et al., 2 0 0 5 ). 
A d diti o nal li mitati o ns of c urre nt t hera p y i ncl u de si g nifica nt m or bi dit y a n d pre mat ure m ort alit y 
ascri ba ble t o t he n e ur ol o gic, met a b olic a n d b o ne t o xicit y ass oci ate d wit h hi g h d ose 
gl uc o c ortic oi ds, re n al t o xicit y ass oci ate d wit h calci ne uri n i n hi bit ors, a n d t o i m m u n os u p pressi o n. 
T here is a n ee d f or t her a pe utic a p pr oac hes t hat i n d uce a n d mai ntai n res p o nse i n a greater 
pr o p orti o n of s u bjects wit h less t o xicit y. 

C C X 1 4 0- B 
 
Pr ot oc ol C L 0 1 1 _ 1 4 0 
 
  
A me n d me nt 4. 0 (2 9 Oct o ber  2 0 1 8) 
C he m o Ce ntr y x, I n c . 
C O N FI D E N TI A L  
Pa ge 4 3  of 9 3  
2. 3.  
P ote nti al R ole  of C C R 2  i n P at h o ge nesis of F S G S  
A p ote ntial r ole f or C C R 2 i n t he pat h o ge nesis of F S G S is s u p p orte d b y cli nical a n d 
hist o pat h ol o gic o bser v ati o ns i n s u bjects wit h re nal disease, a n d fi n di n gs wit h i n vitr o st u dies a n d 
i n viv o m o use m o dels of F S G S. 
C C R 2 is a maj or dri ver of m o n oc yt e mi grati o n a n d acti vati o n, a n d has bee n s h o w n t o me diate 
re nal i nterstitial i nfla m mati o n a n d t u b ular atr o p h y i n c hr o nic re nal diseases b y recr uiti n g 
m o n oc yt es t o t he re nal i nterstiti u m ( Ya da v et al; 2 0 1 0 ). I ncrease d uri nar y l e vels of M C P- 1, t he 
li ga n d f or C C R 2, is ass ociate d wit h i ncrease d i nterstitial macr o p ha ge i nfiltrati o n i n s u bjects wit h 
c hr o nic ki d ne y disease ( Ear dle y et al, 2 0 0 6 ) a n d wit h i ncrease d d e gree of pr otei n uria i n c hil dre n 
wit h F S G S ( Wasile ws ka, et al, 2 0 1 1 ). T here is a w ell-c haracterize d D N A p ol y m or p his m ( M C P 1 
2 5 1 8 A/ G) t hat has bee n as s ociate d wit h ele v ate d M C P- 1 le vels a n d greater ris k f or de v el o p me nt 
of re nal f ail ure i n F S G S, as well as i n I g A n e p hr o pat h y, dia b etic ne p hr o p at h y a n d l u p us n e p hritis 
(Bes b as et al, 2 0 1 5 ). 
I n vitr o e x peri me nts s u p p ort a r ole f or t he C C R 2/ M C P- 1 pat h wa y i n t he p ur p orte d diseas e 
accelerati o n r ole ascri b e d t o pr otei n uria. S pecificall y, it is re p orte d t hat t u b ular e pit helial cells 
releas e M C P- 1 ( C C L 2) w he n e x p ose d t o ser u m pr otei ns o n t he a pical si de (B urt o n et al, 1 9 9 9 ). 
I n vi v o, tar geti n g t he M C P-1/ C C R 2 s yste m  i n precli nical m o dels of c hr o nic ki d ne y dise ase  
(C K D ) de m o nstrat es be n efit. M C P -1 deficie nt mice are resista nt t o t he de v el o p me nt of 
al b u mi n uria f oll o wi n g di a betes i n d ucti o n b y stre pt oz ot oci n a n d t his pr otecti ve p he n ot y p e is 
mar ke d b y a lac k of m o n oc yt e r ecr uit me nt i nt o t he gl o mer uli ( C h o w et al., 2 0 0 6 ). M C P- 1 
deficie nc y als o pre v e nts dia betic d b/ d b  mice fr o m de vel o pi n g al b u mi n uria (C h o w et al., 2 0 0 7 ). 
P har mac ol o gical tr eat me nt wit h a C C R 2 a nta g o nist pre ve nts t he o nset of al b u mi n uria i n d b/ d b  
mice a n d t his  be nefit c orr elates wit h a lac k of m o n oc yt e recr uit me nt t o t he gl o mer uli a n d 
a meli orati o n of hist ol o gi cal da ma ge ( Ka n g et al., 2 0 1 0 ). C he m o Ce ntr y x c o n d ucte d a n e xte nsi ve 
series of pr ecli nical efficac y st u dies wit h C C X 1 4 0- B a n d s urr o gat e C C R 2 a nta g o nists. E fficac y 
was o bser v e d i n m o use m o dels of dia betic, n o n- dia betic ne p hr o p at h y a n d i n m o dels wit h feat ures 
of F S G S i n d uce d b y partial ne p hrect o m y or b y e x p os ure t o A dria m yci n ( A D R). Ra pi d a n d 
si g nifica nt r e d ucti o n i n pr otei n uria as ass esse d b y meas ure me nts of uri nar y al b u mi n e x creti o n 
rate ( U A E R) a n d uri n ar y al b u mi n:creati ni ne rati o ( U A C R) was o bser v e d i n all a ni mal m o dels, 
t he re d ucti o n i n pr otei n uria are s ustai ne d t hr o u g h o ut t he d urati o n of t he st u dies. Hist ol o gical 
para meters were als o i m pr o ve d b y treat me nt wit h C C R 2 i n hi bit ors a n d i n c o m bi nati o n wit h 
R A A S bl oc ka de. T hes e hist ol o gical para meters i n cl u de re d u ce d gl o mer ul ar h y pertr o p h y, 
mesa n gi al e x pa nsi o n, gl o mer ular scler osis, a n d i ncrease d t u b ular a n d gl o mer ular i nte grit y. I n 
a d diti o n, hist o pat h ol o g y re veals pr eser v ati o n of gl o mer ular arc hitect ure a n d rest orati o n of 
n or mal t u b ular a p peara n ce wit h C C R 2 bl oc ka de i n t he 5/ 6 ne p hrect o m y m o use m o del. T he 
prese nce of i ntra- gl o mer ular C C R 2 p ositi ve cells has bee n de m o nstrate d i n t he a ni mal m o dels  
(P C 0 6 8 4 _ 1 4 0 ). M ore o ver, re nal pr ot ecti ve effects are ass o ciate d wit h C C R 2 i n hi biti o n i n t he 
F S G S m o dels. N ota bl y, t he n u m ber of p o d o c yt es per gl o mer ul us is si g nifica ntl y hi g her wit h 
C C R 2 i n hi bit or t hera p y t ha n i n ve hicle- treate d matc he d c o ntr ols (See I n vesti gat or’s Br o c h ure ). 
E x vi v o , e vi de nce f or a r ole f or C C R 2 i n F S G S i n h u ma ns c o mes fr o m u n p u blis he d st u dies 
c o n d ucte d b y C he m o Ce ntr y x. E x pressi o n of C C R 2 pr otei n was assess e d usi n g 
i m m u n o hist oc he mistr y met h o ds i n re nal bi o psies fr o m n or mal ki d ne y a n d fr o m s u bjects wit h 

C C X 1 4 0- B 
 
Pr ot oc ol C L 0 1 1 _ 1 4 0 
 
  
A me n d me nt 4. 0 (2 9 Oct o ber  2 0 1 8) 
C he m o Ce ntr y x, I n c . 
C O N FI D E N TI A L  
Pa ge 4 4  of 9 3  
pri ma r y F S G S. B ot h s h o we d e x pressi o n of C C R 2 i n cells i m plicate d i n pat h o ge n esis, i ncl u di n g 
parietal e pit helial cells, t u b ular e pit helial cells a n d i nfiltrati n g macr o p ha ges . 
Differ e nce i n e x pressi o n bet wee n h ealt h y a n d disease d ki d ne y w as o bser ve d i n t he t u b ula r 
e pit heli u m, c o nsiste nt wit h pri or data s h o wi n g t hat pr otei n uria i n d uces C C L 2 ( M C P - 1, t he li ga n d 
f or C C R 2) e x pressi o n i n t u b ules (B urt o n et al; 1 9 9 9 ). 
Fi nall y, s u p p ort deri ves fr o m t he de m o nstrati o n t hat C C X 1 4 0- B was ass oci ate d wit h cli nicall y 
mea ni n gf ul re d u cti o n i n pr otei n uria i n a P hase 2 st u d y i n s u bjects wit h dia betic ne p hr o pat h y (de 
Zee u w, et al., 2 0 1 5 ), as s u m marize d i n Secti o n  2. 4. 1 . T he pat h o ge nic mec ha nis ms t hat c o ntri b ute 
t o pr otei n uria a n d pr o gressi ve re nal d ysf u n cti o n i n dia betic ne p hr o p at h y are s hare d, at least i n 
part, wit h mec ha nis ms i n F S G S ( J effers o n et al., 2 0 0 8). S pecificall y, a d ecrease i n p o d oc yte 
n u m ber has bee n s h o w n i n s u bjects wit h b ot h t y pe I a n d t y p e II dia betes mellit us, re d uce d 
p o d oc yt e n u m ber ma y pr ece d e t he o nset of cli nicall y detecta ble al b u mi n uri a a n d/ or pr otei n uri a 
b y se v eral years, f o ot pr o cess efface me nt is o bser v e d, a n d e x peri me ntal a n d cli nical st u dies ha ve 
s h o w n a direct c orr elati o n bet wee n t he m a g nit u de of pr otei n uria a n d t he e xte nt of efface m e nt a n d 
decrease i n p o d oc yt e n u m ber. F urt h er, as i n F S G S, i ncrease d gl o mer ul ar pr otei n uria lea ds t o 
e n ha nce d t u b ular cell u pta ke of pr ot ei n, lea di n g t o c o m ple me nt acti vati o n, t u b ul oi nterstitial 
i nfla m mati o n a n d releas e of fi br o ge nic gr o wt h fact ors a n d i nfla m mat or y c yt o ki nes. 
T hese o bser v ati o ns s u p p ort t he rati o nale t hat sel ecti ve C C R 2 i n hi biti o n wit h C C X 1 4 0- B ma y 
pr o vi de t hera p e utic be n efit i n s u bjects wit h F S G S. 
2. 4.  
C C R 2 I n hi bit or C C X 1 4 0 - B: N o n-Cli nic al S afet y  
T he n o ncli nical saf et y of C C X 1 4 0- B was st u die d i n vitr o a n d i n vi v o i n mice, rats, d o gs a n d 
C y n o m ol g us m o n ke ys. T he n o ncli nical t o xicit y st u dies wit h C C X 1 4 0- B w ere s u p ple me nt e d wit h 
safet y p har m ac ol o g y st u dies i ncl u di n g be h a vi oral a n d a ut o n o mic ne ur o n al f u ncti o n testi n g, 
p ul m o nar y a n d car di o vas c ular f u n cti o n e val uati o ns i n c o nsci o us rats a n d d o gs, a n d i n cl u de d a n 
i n vitr o p otassi u m c ha n nel h E R G assa y. T here w ere n o a d verse fi n di n gs attri b uta ble t o 
C C X 1 4 0- B i n a n y of t he or ga n s yste ms st u die d. I n a d diti o n st u dies of t he effects of C C X 1 4 0- B 
o n t he i m m u ne s yste m ( T cell de pe n d e nt a nti b o d y pr o d ucti o n) were als o c o n d ucte d a n d di d n ot 
i de ntif y a n y s afet y c o ncer ns. C C X 1 4 0- B was n ot ge n ot o xic i n vitr o or i n viv o, a n d was n ot 
p h ot ot o xic i n vitr o. 
I n re peat- d ose t o xicit y st u dies ( u p t o 2 6 wee ks i n rats a n d 3 9 wee ks i n d o gs) t w o a d vers e 
n o ncli nical fi n di n gs of c o ncer n w ere re veale d: c h a n ges  i n re d bl o o d cell [ R B C] para meter 
fi n di n gs, wit h retic ul oc yt osis, w hic h was o bser v e d acr oss all s pecies st u die d , a n d peri p heral a x o n 
ne ur o pat h y w h ic h was o bser ve d o nl y i n d o gs. 
I n t hes e re p eat d ose n o n cli nical st u dies, t here was clear e vi de nce of ra pi d rec o ver y of t h e R B C 
fi n di n gs a n d retic ul oc yt osis i n t he a bse nce of dr u g. I n t he 3 9- wee k d o g st u d y, t he hi g hest d ose 
( 5 0 m g/ k g) of C C X 1 4 0-B was ass ociate d wit h sli g ht  t o mil d ne ur o nal cell c ha n ges ( b ase d o n 
t h or o u g h hist ol o gi cal e x a mi nati o ns), b ut t hese were n ot dee me d t o be of li kel y cli nical rele v a nce 
b y t he hist o pat h ol o gist a n d i n dee d t here were n o cli nical c orrelates o bser v e d. C essati o n of acti ve 
da ma ge ( d ecr ease d i m m u ne cell i nfiltrates) was n ote d , h o we ver rec o ver y w as i nc o m plete. Off-
tar get bi n di n g assa ys, i n viv o i m m u ne mec ha nis m, a n d i m m u n o hist oc he mistr y e v al uati o ns di d 
n ot re veal a m ec ha nis m f or t he ne ur o p at h y fi n di n gs i n d o gs, b ut ma y r ule o ut direct C C R 2 
recept or i n hi biti o n. I n i n vitr o assess me nts, t here were n o u ni q u e meta b olites t o d o gs. H o w e ver, 

C C X 1 4 0- B 
 
Pr ot oc ol C L 0 1 1 _ 1 4 0 
 
  
A me n d me nt 4. 0 (2 9 Oct o ber  2 0 1 8) 
C he m o Ce ntr y x, I n c . 
C O N FI D E N TI A L  
Pa ge 4 5  of 9 3  
i n d o gs t her e is a hi g h er perce nt a ge of free C C X 1 4 0 i n plas ma w hic h is u ni q ue a m o n g st u die d 
s pecies, i ncl u di n g h u ma ns. T he ne ur o n al fi n di n gs a p peari n g o nl y i n d o gs s u g gests s pecies 
s pecificit y, h o we v er t he mec ha nis m is u n k n o w n, a n d a t hres h ol d effect of free dr u g 
c o nce ntr ati o n ca n n ot be r ule d o ut. 
T he c h a n ges  i n R B C p ar a met er fi n di n gs are li kel y tra nslat a ble t o h u ma ns, b ut are m o nit ora ble, 
re versi ble, a n d t her e was a n acce pta ble s afet y mar gi n acr oss all s peci es (see bel o w). T o e ns ure 
earl y detecti o n of c h a n ges i n R B C  p ar a meters  i n t he P hase 2 cli nical trial, bl o o d sa m ples will 
be dra w n at baseli ne, at 6 h o urs f oll o wi n g a d mi nistrati o n of t he first d ose, at St u d y D a ys 8, 1 5 
a n d 2 9, t he n at e v er y 4 w ee k i nter vals 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 
assess me nt of c o m plete bl o o d c o u nt, retic ul oc yte c o u nt a n d bilir u bi n. 
Ne ur o pat h y fi n di n gs i n d o gs are li kel y s peci es-s pecific wit h a hi g her s afet y mar gi n t ha n t he 
c h a n ges  i n R B C p ar a meters, h o we ver re v ersi bilit y was i nc o m plete a n d t he mec ha nis m is 
u n k n o w n. S u bjects i n t he P hase 2 st u d y will be m o nit ore d f or a d v erse e ve nts relate d t o t he 
ner v o us s yst e m, a n d will be e x a mi ne d f or vi br ati o n- se nse deficits a n d e val uated f or earl y 
s y m pt o ms usi n g a q u esti o n naire vali date d f or earl y det ecti o n of peri p heral ne ur o pat h y i n st u dies 
of patie nts wit h HI V i nfecti o n.  
T he N O A E L i n t he 2 6- w ee k rat st u dies of 1 5 m g/ k g/ da y ( b ase d o n re versi ble c h a n ges i n R B C 
p ar a meters ) w as ass ociate d wit h s yste mic A U C 0- 2 4 t otal plas ma e x p os ures t o C C X 1 4 0 of 4 6 4. 6 
a n d 4 9 3. 7 µ g• hr/ m L, f or males a n d fe m ales, res p ecti vel y. T h us, f or d ose es calati o n i n h u ma n 
s u bjects, e x p os ures t o C C X 1 4 0 s h o ul d n ot e x cee d t otal plas ma A U C 0- 2 4 e x p os ures of 
4 6 5 µ g• hr/ m L, or t otal Cma x  c o nce ntrati o ns of 3 2 µ g/ m L.  
Res ults fr o m all t he safet y a n d t o xic ol o g y st u dies s u p p ort re peat e d d osi n g of C C X 1 4 0- B t o 
h u ma ns u p t o pre dicte d e x p os ure parit y wit h t he 2 6- wee k rat N O A E L le vels. T he N O A E L i n t he 
2 6- wee k rat st u d y was ass ociate d wit h s yste mic e x p os ure t o C C X 1 4 0 w hic h was a p pr o xi matel y 
3- t o 4-f ol d t he pre di cte d h u ma n e x p os ure wit h a 1 5 m g t wice d ail y ( b.i. d.) d ose of C C X 1 4 0- B.  
2. 4. 1.  
C C R 2 I n hi bit or C C X 1 4 0 -B: Cli nic al E x perie nce  
C C X 1 4 0- B is a n orall y a d mi nistere d, selecti ve s m all m olec ule i n hi bit or of t he c he m o ki ne 
rece pt or k n o w n as C C R 2. T o date it has n ot bee n a d mi nistere d i n s u bjects wit h bi o ps y- pr o v e n 
F S G S.  
C C X 1 4 0- B has bee n assesse d i n 4 P hase 1 cli nical trials i n healt h y v ol u nteers, o ne P hase 2 trial 
i n s u bjects wit h dia betes, a n d t w o Phase 2 trials i n s u bjects wit h dia betic ne p hr o pat h y. A ta b ular 
s u m mar y of cli nical st u dies c o n d ucte d wit h C C X 1 4 0- B a n d s u b mitte d t o I N D 1 1 4 4 6 9 are 
pr o vi de d i n t he I n vesti gat or’s Br o c h ure. 
Efficac y  fi n di n gs i n st u d y C L 0 0 5 _ 1 4 0 i n patie nts wit h dia betic ne p hro pat h y a n d pr otei n uria 
pr o vi de s u p p ort f or e x pl ori n g C C X 1 4 0- B i n F S G S. I n t hat tri al, 1 9 2 s u bjects wit h dia betic 
ne p hr o pat h y r ecei v e d u ni nterr u pte d d osi n g f or u p t o 5 2 wee ks wit h place b o, 5 m g dail y of 
C C X 1 4 0- B or 1 0 m g dail y of C C X 1 4 0- B. C o m pare d t o place b o, C C X 1 4 0- B was ass ociate d wit h 
gr eater re d u cti o n i n al b u mi n uria. S pecificall y, c h a n ges fr o m bas eli ne i n t he rati o of uri nar y 
al b u mi n t o creati ni ne ( U A C R) a vera ge d - 2 % i n t h e place b o gr o u p ( 9 5 % CI - 1 1 % t o + 9 %), - 1 8 % 
i n t he C C X 1 4 0-B 5  m g gr o u p ( 9 5 % CI - 2 6 % t o - 8 %), a n d - 1 1 % i n t he C C X 1 4 0- B 1 0 m g gr o u p 
( 9 5 % CI - 2 0 % t o -1 %). T he decr eas e i n U A C R was o bser ve d at t he earliest meas ure d ti me p oi nt 
( Da y 1 5) a n d reac he d a ma xi m u m decrease b y t h e Da y 8 5 visit (de Zee u w et al., 2 0 1 5 ). 

C C X 1 4 0- B 
 
Pr ot oc ol C L 0 1 1 _ 1 4 0 
 
  
A me n d me nt 4. 0 (2 9 Oct o ber  2 0 1 8) 
C he m o Ce ntr y x, I n c . 
C O N FI D E N TI A L  
Pa ge 4 6  of 9 3  
Of n ote, s u bjects e nteri n g t he st u d y w ere stratifie d base d o n t he le vel of pr otei n uria at baseli ne. 
I n a pre-s pecifi e d s u bset a nal ysis, t he great est perce nta ge i m pr o v e me nt i n U A C R fr o m baseli ne 
was o bser v e d i n s u bjects w h o prese nte d wit h t he hi g hest bas eli ne U A C R ( 8 0 1- 3 0 0 0 m g/ g) a n d 
e G F R  of at least 6 0 m L/ mi n/ 1. 7 3 m2. I n t his s u bset mea n c ha n ges i n U A C R fr o m baseli ne w ere 
+ 4 5 % i n t he place b o gr o u p ( 9 5 % CI - 6 % t o + 1 2 1 %, n = 8), - 2 3 % i n t he C C X 1 4 0- B 5 m g gr o u p 
( 9 5 % CI - 5 5 % t o + 3 2 %, n = 5; p = 0. 0 3 vs c o ntr ol), a n d - 3 9 % i n t he C C X 1 4 0-B 1 0 m g gr o u p 
( 9 5 % CI - 6 1 % t o - 7 %; n = 8; p = 0. 0 0 4 vs c o ntr ol). 
W he n ta ke n t o get her wit h res ults fr o m t he pre- cli nical st u dies , a n d a fa v ora ble cli nical safet y 
pr ofile  (see I n vesti gat or’s Br oc h ure), t h ese o bser v ati o ns f urt her s u p p ort e v al uati o n of C C X 1 4 0-B 
i n hi g hl y pr otei n uric r e nal diseases, i ncl u di n g F S G S. 
3.  
O B J E C TI V E S 
3. 1.  
Pri m ar y O bjecti ve  
T he pri mar y safet y o bjecti ve of t his st u d y is t o e v al uate t he safet y a n d t olera bilit y of C C X 1 4 0- B 
i n s u bjects wit h F S G S wit h pr otei n uria. 
T he pri mar y efficac y o bj ecti ve of t his st u d y is t o e val uate t he effect of C C X 1 4 0- B treat me nt o n 
uri nar y pr otei n e x cr eti o n i n s u bjects wit h F S G S , as assesse d b y c h a n ge fr o m baseli ne i n t he uri ne 
pr otei n t o creati ni ne rati o ( U P C R)  at Wee k 1 2. 
3. 2.  
Sec o n d ar y O bjecti ves  
•  T o e val uate t he eff ect of C C X 1 4 0 - B o n re n al f u ncti o n, as assesse d b y esti mate d 
gl o mer ular filtrati o n rat e (e G F R)  usi n g t he C K D - E PI C ystati n C e q uati o n, C K D-E PI 
(c hr o nic ki d ne y dise ase e pi de mi ol o g y c oll a b or ati o n) Creati ni ne e q uati o n, C K D-E PI 
Creati ni ne - C yst ati n C e q uati o n a n d M D R D ( M o dific ati o n of Diet i n Re n al Dise ase) 
Creati ni ne e q uati o n ass esse d at Wee ks 1 2 a n d 2 4 
•  T o e v al u ate t he eff ect of C C X 1 4 0 -B tre at me nt o n fr acti o n of s u bjects ac hie vi n g 
c o m plete a n d p arti al re n al re missi o n  ( b y 2 differe nt p arti al re missi o n defi niti o ns) 
•  T o e val uate t he p h ar mac o ki netic s ( P K) pr ofile of C C X 1 4 0-B i n s u bjects wit h F S G S 
3. 3.  
E x pl or at or y O bjecti ves  
T o e val uate t he eff ect of C C X 1 4 0 - B o n uri nar y m o n oc yt e c he m o attracta nt pr otei n -1 ( M C P -1) 
a n d ot her ser u m a n d uri n ar y mar k ers of re nal f u n cti o n a n d i nfla m mati o n; 
T o e x pl ore t he eff ect of C C X 1 4 0 - B o n le vels of bl o o d m o n oc ytes, T, B a n d N K cells, a n d ot her 
bl o o d a n d uri nar y mar k ers p ote ntiall y ass ociat e d wit h C C R 2 a nta g o nis m; 
T o e x pl ore t he eff ect of C C X 1 4 0- B o n Healt h- rel ate d Q ualit y of Life c ha n ges b ase d o n S h ort 
F or m 3 6 versi o n 2 ( S F- 3 6 v 2) a n d E ur o Q u alit y of Life- 5 D o m ai ns- 5 Le v els (E Q - 5 D-5 L ) 
q uesti o n n aires ; 
T o e x pl ore t he relati o ns hi ps a m o n g e x p os ure ( P K) of C C X 1 4 0- B, ser u m al b u mi n le vel, a n d 
U P C R . 

C C X 1 4 0- B 
 
Pr ot oc ol C L 0 1 1 _ 1 4 0 
 
  
A me n d me nt 4. 0 (2 9 Oct o ber  2 0 1 8) 
C he m o Ce ntr y x, I n c . 
C O N FI D E N TI A L  
Pa ge 4 7  of 9 3  
4.  
S T U D Y D E SI G N  
T his st u d y will e val uate t he effi cac y, s afet y, t olera bilit y, a n d  p har mac o ki netics of u p t o 1 2 wee ks 
of treat me nt wit h eac h of t hree d ose r e gi me ns of C C X 1 4 0- B or place b o, w he n use d i n 
c o m bi nati o n wit h sta ble sta n dar d of care t hera p y i n s u bjects wit h F S G S wit h si g nifica nt 
pr otei n uria, assess e d as U P C R > 1 g/ g at Scree ni n g . F oll o wi n g t he 1 2- wee k bli n de d treat me nt 
peri o d, t he st u d y will e v al u ate up t o 2 4 w ee ks of tre at me nt wit h C C X 1 4 0 -B: all  s u bjects w h o 
re m ai n eli gi ble will recei ve acti ve treat me nt f or a n a d diti o nal 1 2 wee ks t o assess safet y a n d 
d ura bilit y of eff ect.  
T he ta r get is t o e nr oll 4 0 male or fe m ale s u bjects i n t his ra n d o mize d, d o u ble- bli n d, place b o-
c o ntr olle d, P hase 2 st u d y. Ra n d o mizati o n will be stratifie d b y U P C R < 3. 5 g pr otei n/ g 
cre ati ni ne vers us  U P C R ≥3. 5 g pr otei n/ g cre ati ni ne at b aseli ne  usi n g t he scree ni n g 
U P C R a n d b y t he us e of gl uc o c ortic oi ds a n d/ or i m m u n os u p pressi ve me dicati o ns ( yes, n o). 
S u bjects will be ra n d o mize d 1: 1: 1: 1 t o o ne of f o ur treat me nt gr o u ps: 
•  Gr o u p A: Place b o ( N = 1 0) 
•  Gr o u p B: C C X 1 4 0- B 5 m g o nce dail y ( N = 1 0)  
•  Gr o u p C: C C X 1 4 0- B 1 0 m g t wice d ail y ( N = 1 0)  
•  Gr o u p D: C C X 1 4 0- B 1 5 m g t wice d ail y ( N = 1 0)  
St u d y m e dicati o n will be ta ke n b y t he s u bjects f or 8 4 da ys, as f oll o ws: 
•  Gr o u p A: T hree place b o ta blets, ta ke n t wice d ail y; 
•  Gr o u p B: O n e 5 m g C C X 1 4 0- B ta bl et a n d t w o pl ace b o ta bl ets i n t he m or ni n g; t hree 
plac e b o ta blets i n t he e v e ni n g; 
•  Gr o u p C: T w o 5 m g C C X 1 4 0- B ta bl ets a n d o ne place b o ta blet, ta k e n t wice dail y  
•  Gr o u p D: T hree 5 m g C C X 1 4 0- B ta blets, ta k e n t wice dail y  
All s u bjects will ta ke bli n de d or al  st u d y me di cati o n t wice d ail y, 3 t a blets  i n t he m or ni n g a n d 
3 t a blets i n t he e ve ni n g, wit h or wit h o ut f o o d, f or 1 2 w ee ks  (8 4 c o nsec uti v e da ys ). F oll o wi n g 
t he 8 4- da y bli n de d d osi n g peri o d, all s u bjects w h o re m ai n eli gi ble  will ta ke o pe n la bel 
C C X 1 4 0- B f or a n a d diti o nal 1 2 w ee ks ( 8 4 c o nsec uti ve da ys ) at t he hi g hest toler ate d  d ose u n der 
e val uati o n , c urre ntl y pla n ne d t o be 1 5 m g t wi ce d ail y. T he decisi o n o n t he d ose f or t he 
o p e n-l a bel peri o d will be m a de b y t he S p o ns or, wit h t he a d vice of t he u n bli n de d Data 
M o nit ori n g C o m mittee ( D M C) . After  c o m pleti o n of tre at me nt f or w h ate ver re as o n, 
i ncl u di n g e arl y ter mi n ati o n, all s u bjects are e x pecte d t o ret ur n at 2, 7 a n d 1 4 da ys after t a ki n g 
t he last d ose of st u d y m e dicati o n f or assess me nt of eli mi n ati o n p h ase P K a n d 2 8 d a ys after 
t a ki n g t he l ast d ose of st u d y me dic ati o n f or P K a n d s afet y m o nit o ri n g. 
T he scree ni n g peri o d will be u p t o 2 8 da ys. All p ote ntial st u d y s u bjects m ust si g n writte n 
i nf or me d c o nse nt bef ore a n y st u d y scree ni n g pr oce d ures. Dia g n osis of F S G S will be c o nfir me d 
base d o n cli nical j u d g me nt s u p p orte d b y a hist orical or c urre nt re n al bi o ps y wit h c haracteristic 
feat ur es a n d/ or pr ese nce of hi g h -ris k ge netic v aria nts. Ot her scree ni n g pr oce d ures i ncl u de 
c ollecti o n of de m o gr a p hic a n d me dical hist or y, p h ysical e x a mi nati o n a n d vital si g ns, 1 2- lea d 

C C X 1 4 0- B 
 
Pr ot oc ol C L 0 1 1 _ 1 4 0 
 
  
A me n d me nt 4. 0 (2 9 Oct o ber  2 0 1 8) 
C he m o Ce ntr y x, I n c . 
C O N FI D E N TI A L  
Pa ge 4 8  of 9 3  
E C G, ser u m c he mistr y i n cl u di n g ser u m al b u mi n a n d creati n i ne, h e mat ol o g y, uri nal ysis i ncl u di n g 
assess me nt of uri nar y pr otei n:creati ni ne rati o ( U P C R) a n d uri nar y al b u mi n:creati ni ne rati o 
( U A C R) i n a sa m ple fr o m a first m or ni n g v oi d, viral a n d T B s cree ni n g, pre g n a nc y testi n g f or all 
fe male s u bjects of c hil d b eari n g p ote ntial, a n d rec or di n g of c o nc o mita nt me dicati o n use. F or 
s u bjects wit h o ut pri or bi o ps y t o c o nfir m dia g n osis, nee dle bi o ps y ma y be c o m plete d d uri n g t he 
scree ni n g p eri o d. F or s u bjects wit h o ut ge n etic scree ni n g f or ris k alleles ass ociate d wit h F S G S, 
ge n etic testi n g m a y be d o ne d uri n g t he scree ni n g p eri o d. 
D uri n g t h e treat me nt p eri o d, eli gi ble s u bjects will visit t he st u d y ce nter o n St u d y Da ys 1, 8, 1 5, 
2 9 ( Wee k 4), a n d Wee ks 8, 1 2 ( pri mar y e n d p oi nt) , 1 3, 1 6, 2 0, a n d 2 4 f or st u d y pr o ce d ures 
i ncl u di n g i nter val hist or y, p h ysical e x a mi nati o n a n d vital si g ns, E C G, st u d y q uesti o n naires, a n d 
c ollecti o n of bl o o d a n d uri ne. A 2 4 h o ur uri ne c ollecti o n will be d o ne t he d a y be f ore t he D a y 
1 visit ( b aseli ne) , t he d a y bef ore t he Wee k 1 2 visit at t he e n d of d o u ble -bli n d d osi n g , a n d 
t he d a y bef ore t he Wee k 2 4 visit at t he e n d of o pe n -l a bel d osi n g. S u bjects will ret ur n f or a 
f oll o w- u p s af et y visit 4 w ee ks after t he l ast d ose of st u d y dr u g ( at Wee k 1 6 f or t h ose n ot 
e nteri n g t he o pe n -l a bel p h ase, or at  Wee k 2 8  f or t h ose w h o c o nti n ue d osi n g i nt o t he o pe n-
l a bel p h ase). W he n feasi ble, u p o n disc o nti n uati o n of treat me nt f or a n y reas o n, a sa m ple of 
w h ole bl o o d s h o ul d be c ollecte d f or assess me nt of eli mi nati o n P K at  2, 7 a n d 1 4 da ys aft er t he 
fi nal d ose of st u d y dr u g (C C X 1 4 0- B or place b o). 
F or ass ess me nt of a d vers e e ve nts of s p ecial i nterest, st u d y pr oce d ures will i ncl u de 
•  C o m plete bl o o d c o u nt wit h differe ntial, m or p h ol o g y ass ess me nt, retic ul oc ytes c o u nt, 
he m o gl o bi n, L D H , a n d bilir u bi n (t ot al a n d i n direct) t o assess earl y e vi de n ce of 
he m ol ysis; 
•  T he AI D S Cli nical Trials Gr o u p Brief Peri p h eral Ne ur o pat h y Scree ni n g T o ol Brief 
Peri p heral N e ur o pat h y S cree ni n g T o ol ( A C T G-B P N S T)  t o assess earl y e vi de nce of 
ne ur o pat h y; 
•  M o nit ori n g f or a d vers e e ve nts of i nfecti o n; 
•  Al kal i ne p h os p hatase, A L T, A S T a n d bilir u bi n  (t ot al a n d direct); t o assess f or e vi de nce 
of dr u g i n d uce d li ver i nj ur y. 
F or ass ess me nt of p har m ac o ki netics, st u d y pr oce d ures will i ncl u de 
•  Se ve n bl o o d sa m ples c ollecte d o ver 6 h o urs o n St u d y D a y 1 a n d at stea d y state (St u d y 
Da y 1 5 , or wit hi n 2 wee ks t hereaft er) t o ass ess A U C0- 6  f oll o wi n g t he first a d mi nistrati o n 
of st u d y dr u g, a n d at stea d y state; 
•  Assess me nt of C mi n  at i nter vals t o e ns ure t hat e x p os ure is wit hi n t he pr oject e d ra n ge, 
wit h a de q uate safet y mar gi n base d o n t he N O A E L esta blis he d i n precli nical t o xic ol o g y; 
•  U p o n disc o nti n uati o n of treat me nt f or a n y reas o n, c ollecti o n of bl o o d at 2 da ys, 7 d a ys 
a n d 1 4 da ys f oll o wi n g disc o nti n uati o n t o assess eli mi nati o n.  
All st u d y pr oce d ures are prese nte d i n t he Ti me a n d E ve n ts ta ble. 
S u bjects w h o are usi n g a n a n gi ote nsi n c o n v erti n g e nz y me ( A C E) i n hi bit or, a n gi ote nsi n rece pt or 
bl oc ker ( A R B) or ot h er bl oc ker of t he re ni n a n gi ot e nsi n al d oster o ne s yste m ( R A A S), or w h o are 
usi n g gl uc oc ortic oi ds, a calci ne uri n i n hi bit or or ot her i m m u n o m o d ulat or y or i m m u n os u p pressi ve 

C C X 1 4 0- B 
 
Pr ot oc ol C L 0 1 1 _ 1 4 0 
 
  
A me n d me nt 4. 0 (2 9 Oct o ber  2 0 1 8) 
C he m o Ce ntr y x, I n c . 
C O N FI D E N TI A L  
Pa ge 5 0  of 9 3  
T a ble 1: 
C C X 1 4 0 -B f or t he F o ur  St u d y Gr o u ps  
 
1 2 w ee ks  
Gr o u p  
5 m g  
C C X 1 4 0 -B Q D  
1 0 m g 
C C X 1 4 0 -B BI D  
1 5 m g  
C C X 1 4 0 -B BI D  
Pl ace b o  
M or ni n g 
d ose 
1 x 5 m g ta blet +  
2 place b o ta b lets 
orall y  
2 x 5 m g ta blets +  
1 place b o ta blet 
orall y  
3 x 5 m g ta blets 
orall y  
3 place b o ta blets 
orall y  
E ve ni n g 
d ose 
3 place b o ta blets 
orall y  
2 x 5 m g ta blets +  
1 place b o ta blet 
orall y  
3 x 5 m g ta blets 
orall y  
3 place b o ta blets 
orall y  
4. 2.  
D ose M o dific ati o n G u i deli nes 
T he D M C will be res p o nsi ble f or re vie wi n g s afet y data t hr o u g h o ut t he c o urse of t he st u d y. I n t he 
e ve nt t he D M C has a str o n g i n dicati o n t hat t here are si g nifi ca nt d ose-relat e d a d verse e ve nts t he 
D M C ca n ma ke t he rec o m me n dati o n t o disc o nti n ue e nr oll me nt t o t he affecte d ar m a n d t o ste p-
d o w n all s u bjects t o t he ne xt l o wer d ose ar m. I n a d diti o n t o t he pla n ne d data re vie ws, t he D M C 
c harter will i ncl u de pre -s pecifie d r ul es t hat tri g ger a n A d H oc re vie w of dat a b y u n - bli n de d 
treat me nt gr o u p. 
S u bjects parti ci pati n g i n t he O pe n- La bel E xte nsi o n will be s witc he d o ver t o t he hi g hest safest  
d ose of t he C C X 1 4 0- B. 
4. 2. 1.  
St o p pi n g G ui deli nes  
A n i n de pe n de nt D ata M o nit ori n g C o m mittee ( D M C) will be res p o nsi ble f or re vie wi n g safet y 
data t hr o u g h o ut t he c o urs e of t he st u d y. A m o n g ot her res p o nsi bilities, t he D M C is tas ke d wit h 
i m ple me nti n g d ose m o dificati o n g ui d eli nes t o ass ure t he safet y of all st u d y partici pa nts. 
G ui deli nes will be defi ne d f or st o p pi n g t he st u d y, halti n g e nr oll me nt or h alti n g treat me nt base d 
o n safet y e v e nts occ urri n g i n m ore t ha n 1 s u bj ect. Ge neral d ose m o dificati o n g ui deli nes f or 
i n di vi d uals are pr o vi de d bel o w. 
T a ble 2: 
D ose M o dific ati o n G ui deli nes for Si n gle S u bjects  
Assess me nt  
E ve nt  
Ti mi n g  
Res p o nse  
Ser u m Creati ni ne 
5 0 % i ncrease fr o m 
baseli ne val ue  
If c o nfir me d b y re peat 
meas ure me nt after 
2 wee ks  
Disc o nti n ue treat me nt 
wit h C C X 1 4 0- B 
Uri ne Pr otei n: Creati ni ne 
rati o ( U P C R) 
If baseli ne U P C R < 6. 0 
g/ g a n i ncrease of > 3. 0 
g/ g; if U P C R ≥ 6. 0 g/ g 
a n i ncrease of 5 0 % 
If c o nfir me d by re peat 
meas ure me nt after 
2 wee ks  
Disc o nti n ue treat me nt 
wit h C C X 1 4 0- B 

C C X 1 4 0- B 
 
Pr ot oc ol C L 0 1 1 _ 1 4 0 
 
  
A me n d me nt 4. 0 (2 9 Oct o ber  2 0 1 8) 
C he m o Ce ntr y x, I n c . 
C O N FI D E N TI A L  
Pa ge 5 1  of 9 3  
Assess me nt  
E ve nt  
Ti mi n g  
Res p o nse  
A L T, A S T  
A L T or A S T ≥ 8 x U L N  Retest  wit hi n 7 2 h o urs 
( A L T, A S P, A L P a n d 
T otal Bilir u bi n s h o ul d 
all be re-teste d) 
If c o nfir me d, 
di sc o nti n ue tre at me nt 
wit h C C X 1 4 0 - B  
A L T, A S T  
A L T or A S T ≥ 5 x U L N 
f or m ore t h a n 2 wee ks 
Retest  wit hi n 7 2 h o urs 
a n d t he n  2-3 ti mes per  
wee k ( A L T, A S P, A L P 
a n d T otal Bilir u bi n 
s h o ul d all be re-teste d) 
If c o nfir me d, 
di sc o nti n ue tre at me nt 
wit h C C X 1 4 0 - B  
A L T, A S T, T otal 
Bilir u bi n  a n d I N R  
A L T or A S T ≥ 3 x U L N  
a n d eit her T otal 
Bilir u bi n > 2 U L N or 
I N R > 1. 5 
Retest  wit hi n 7 2 h o urs 
( A L T, A S P, A L P, T otal 
Bilir u bi n a n d I N R 
s h o ul d all be re-teste d) 
If c o nfir me d, 
di sc o nti n ue tre at me nt 
wit h C C X 1 4 0 - B  
A L T, A S T  
A L T or A S T ≥ 3 x U L N 
wit h t he a p peara nce of 
fati g ue, na usea, 
v o miti n g, ri g ht u p per 
q ua dra nt pai n or 
te n der ness, fe ver, ras h 
a n d / or e osi n o p hilia 
( > 5 %) 
 
Disc o nti n ue tre at me nt 
wit h C C X 1 4 0 - B  
L D H  
L D H ≥ 2 ti mes u p per 
li mit of n or mal, a n d 
c o nfir me d t o n ot be 
relate d t o s peci me n 
ha n dli n g  
Halt treat me nt t he n 
reassess after 2 wee ks  
If wit hi n n or mal ra n ge, 
c o nti n ue t o treat at 
re d uce d d ose, defi ne d as 
t he ne xt l o wer d ose. 
Ot her wise, c o ntact 
Me dical M o nit or t o 
disc uss ne xt ste ps  
A ne mia  
He m o gl o bi n re d uce d 
fr o m baseli ne b y 
≥ 2 g/ d L a n d dee me d 
cli nicall y si g nifica nt b y 
t he PI 
Ha lt treat me nt t he n 
reassess after 2 wee ks  
If n or mal, c o nti n ue t o 
treat at re d uce d d ose, 
defi ne d as ne xt l o wer 
d ose. Ot her wise, c o ntact 
Me dical M o nit or t o 
disc uss ne xt ste ps  
Retic ul oc yte C o u nt  
I ncrease fr o m b aseli ne 
i n retic ul oc yte c o u nt b y 
≥ 2 u nits ( % of R B C ) 
t hat is n ot ot her wise 
e x plai ne d 
Halt treat me nt t he n 
reassess after 2 wee ks  
If wit hi n n or mal ra n ge 
f or t he he mat ocrit, 
c o nti n ue t o treat at 
re d uce d d ose, defi ne d as 
ne xt l o wer d ose. 
Ot her wise, c o ntact 
Me dical M o nit or t o 
disc uss ne xt ste ps  

C C X 1 4 0- B 
 
Pr ot oc ol C L 0 1 1 _ 1 4 0 
 
  
A me n d me nt 4. 0 (2 9 Oct o ber  2 0 1 8) 
C he m o Ce ntr y x, I n c . 
C O N FI D E N TI A L  
Pa ge 5 2  of 9 3  
Assess me nt  
E ve nt  
Ti mi n g  
Res p o nse  
Peri p heral N e ur o pat h y 
≥ m o derate s y m pt o ms 
li miti n g (li miti n g 
i nstr u me ntal acti vities 
of dail y li vi n g) or 
as y m pt o matic ( base d o n 
dia g n ostic e val uati o n 
o nl y) a n d dee me d 
cli nicall y si g nifica nt b y 
t he PI 
Halt treat me nt t he n 
reassess after 2 wee ks  
C o ntact Me dical 
M o nit or t o disc uss ne xt 
ste ps 
Ot her Cli nicall y 
Si g nifica nt E ve nts  
A n y a d verse e ve nts 
assesse d as m o derate, 
relate d t o st u d y dr u g, 
a n d cli nicall y si g nifica nt 
Halt treat me nt t he n 
reassess after 2 wee ks  
C o ntact Me dical 
M o nit or t o disc uss ne xt 
ste ps 

C C X 1 4 0- B 
 
Pr ot oc ol C L 0 1 1 _ 1 4 0 
 
  
A me n d me nt 4. 0 (2 9 Oct o ber  2 0 1 8) 
C he m o Ce ntr y x, I n c . 
C O N FI D E N TI A L  
Pa ge 5 3  of 9 3  
5.  
S T U D Y P O P U L A TI O N  
5. 1.  
Size of t h e P o p ul ati o n  
A p pr o xi matel y 4 0 m ale or fe male a d ult s u bjects wit h pri mar y or ge netic F S G S  (see Secti o n 5. 2 ; 
f or ge netic v aria nts) will be e nr olle d i n  t his st u d y. S u bjects w h o disc o nti n ue d uri n g t he first 
1 4 da ys o f ta ki n g st u d y dr u g f or r eas o ns ot her t h a n a d verse e ve nts relate d t o st u d y dr u g ma y b e 
re place d t o e ns ure t h at s ufficie nt data are a vaila ble f or assess me nt of s afet y, P K a n d efficac y. 
5. 2.  
I ncl usi o n Criteri a 
S u bject s m ust meet all t he f oll o wi n g i ncl usi o n criteria t o e nter t he st u d y: 
1.  Male or fe m ale s u bjects a ge d 1 8 - 7 5 years i ncl usi ve. 
2.  Uri nar y t otal pr otei n:creati ni ne rati o ( U P C R) ≥ 1 g pr otei n/ g creati ni ne at scree ni n g ( or 
U P C R at 1 1 3 m g/ m m ol) . 
3.  Dia g n osis of F S G S base d o n at least o ne of t he f oll o wi n g: 
•  Re nal bi o ps y de m o nstr ati n g t he F S G S lesi o n a n d c haract eristic cli nical pres e ntati o n a n d 
c o urse 
•  Hi g h ris k ge n etic vari a nt a n d c haracteristic cli nical prese ntati o n a n d c o urse  
4.  Dia g n osis of o n e of t he f oll o wi n g s u bt y p es of F S G S: 
•  Pri mar y F S G S base d o n c haracteristic hist o pat h ol o g y, me dical hist or y a n d cli nical 
c o urse, or 
•  F S G S sec o n dar y t o a ge n etic varia nt ass o ciate d wit h i ncrease d ris k or se verit y, w hic h 
ma y i ncl u d e N P H S 1, N P H S 2, W T- 1, L A M B 2, C D 2 A P, T R P C 6, A C T N 4 or I N F 2 
5.  Esti mate d gl o mer ular filtrati o n rate (e G F R) > 3 0 m L/ mi n/ 1. 7 3 m2, wit h e G F R calc ulate d 
usi n g t he C hr o nic Ki d ne y D isease E pi de mi ol o g y C olla b orati o n ( C K D _ E PI) e q uati o n ( usi n g 
creati ni ne or c ystati n C)  
6.  T he t y pical bl o o d press ur e of t he patie nt s h o ul d be cli nicall y sta ble pri or t o e nr oll me nt a n d 
n ot e x cee d 1 4 5/ 9 5 m m H g. 
7.  If usi n g R A A S bl oc k ers, d ose m ust be sta ble f or a mi ni m u m of 4 wee ks pri or t o Scree ni n g, 
a n d pr ojecte d t o re mai n sta ble t hr o u g h St u d y Wee k 1 2, u nless a dj ust me nt is re q uire d f or 
ma na ge me nt of h y p erte nsi o n .  
8.  If usi n g i m m u n os u p pressi ve or i m m u n o m o d ulat or y t hera p y, d ose m ust be sta ble f or a 
mi ni m u m of 4 wee ks pri or t o Scree ni n g, a n d pr ojecte d t o re m ai n sta ble t hr o u g h St u d y Wee k 
1 2. 
9.  If usi n g gl u c oc ortic oi ds, d ose m ust be sta ble f or a mi ni m u m of 4 wee ks pri or t o Scree ni n g 
a n d pr ojecte d t o re mai n sta ble t hr o u g h St u d y Wee k 1 2. 
1 0.  Fe male s u bjects of c hil d beari n g p ote ntial ma y partici pate if a de q u ate c o ntrace pti o n is use d 
d uri n g, a n d f or at least 1 m o nt h  after last d ose of st u d y dr u g. Mal e s u bjects wit h part ners of 

C C X 1 4 0- B 
 
Pr ot oc ol C L 0 1 1 _ 1 4 0 
 
  
A me n d me nt 4. 0 (2 9 Oct o ber  2 0 1 8) 
C he m o Ce ntr y x, I n c . 
C O N FI D E N TI A L  
Pa ge 5 4  of 9 3  
c hil d beari n g p ote ntial ma y partici pate i n t he st u d y if t he y h a d a vas ect o m y at least 6 m o nt hs 
pri or t o ra n d o mizati o n or if a de q uate c o ntrace pti o n is use d d uri n g, a n d f or a t least o ne m o nt h 
after t he l ast d ose of st u d y dr u g. A de q uat e c o ntrace pti o n is defi ne d as res ulti n g i n a fail ure 
rate of less t ha n 1 % per year ( c o m bi ne d estr o ge n a n d pr o gest o ge n [ oral, i ntra va gi nal, or 
tra ns der mal], or pr o gest o ge n- o nl y h or m o nal c o ntrace pti o n ( oral, i njecta ble, or i m pla nta ble), 
i ntra-uteri ne d e vice, i ntra - uteri ne h or m o ne releasi n g s yste m, bilateral t u bal occl usi o n, 
vasect o mize d part ner, or se x ual a bsti ne nce) . I n a d diti o n, a barrier met h o d (i.e. cer vical ca p, 
dia p hra g m or c o n d o m) m ust be use d d uri n g i nterc o urse bet wee n a mal e s u bject a n d a fe male 
of c hil d- beari n g p ot e ntial. 
1 1.  Willi n g a n d a ble t o gi ve writte n I nf or me d C o nse nt a n d t o c o m pl y wit h t he re q uire me nts of 
t he st u d y pr ot oc ol. 
1 2.  J u d ge d t o be ot her wise fit f or t he st u d y b y t he I n v esti gat or, b ase d o n me dical hist or y, 
p h ysical e x a mi nati o n, a n d cli nical la b orat or y assess me nts. S u bject s wit h cli nical la b orat or y 
val ues t hat ar e o utsi de of n or mal li mits ( ot her t ha n t h ose s pecifie d i n t he E x cl usi o n Criteria) 
a n d/ or wit h ot her a b n or m al cli nical fi n di n gs t hat are j u d ge d b y t he I n vesti gat or n ot t o be of 
cli nical si g nifica nce, m a y be e nter e d i nt o t he st u d y. 
5. 3.  
E xcl usi o n Criteri a  
1.  Pre g n a nt or n ursi n g. 
2.  Hist or y of or ga n tr a ns pla ntati o n, i ncl u di n g re n al tra ns pla ntati o n. 
3.  C urre ntl y o n a n or ga n tr a ns pla nt waiti n g li st or t here’s a reas o n a ble p ossi bilit y of getti n g a n 
or ga n tra ns pla nt wit hi n 6 m o nt hs of scree ni n g 
4.  S u bjects w h o  used  rit u xi ma b or ot her B- cell de pleti n g  m o n ocl o nal a nti b o dies wit hi n 
2 0 wee ks pri or t o scree ni n g are e x cl u de d w hile s u bjects w h o  use d rit u xi ma b  or ot her B- cell 
de pleti n g  m o n ocl o nal a nti b o dies pri or t o 2 0 wee ks bef ore  scree ni n g are all o we d wit h 
c o nfir me d r ec o ver y of t h e B-cell p o p ulati o n t o wit hi n n or mal ra n ge at t he ti me of scree ni n g  
5.  Plas ma p heresis wit hi n 1 2 wee ks pri or t o scree ni n g. 
6.  B o d y Mass I n d e x ( B MI ) ≥4 0 
7.  Partici pat e d i n a n y cli nical st u d y of a n i n vesti gati o nal pr o d uct wit hi n 1 2 wee ks pri or t o 
scree ni n g or wit hi n 5 half-li ves after ta ki n g t he last d ose of i n vesti gati o nal pr o d uct. 
8.  C urre ntl y o n dial ysis or li kel y t o re q uire dial ysis d uri n g t he pr ojecte d bli n d e d treat me nt 
peri o d of 1 2 wee ks. 
9.  Hist or y or prese n ce of a n y f or m of ca n cer wit hi n t he 5 years pri or t o scree ni n g, wit h t he 
e x ce pti o n of e x cise d basal cell or s q ua m o us cell carci n o ma of t h e s ki n, or carci n o ma i n sit u 
s uc h as cer vical or breast carci n o ma i n sit u t hat has bee n e x cise d or resecte d c o m pletel y a n d 
is wit h o ut e vi de nce of l o cal rec urr e nce or metastasis. 
1 0.  P ositi ve H B V, H C V, or HI V viral scree ni n g test. S u bject s w h o ha ve recei v e d hi g hl y 
effecti ve t her a p y f or H C V de m o nstrate d t o ha v e ne gati ve vira l titers f or at least 6 m o nt hs 
f oll o wi n g disc o nti n uati o n of treat me nt, will be c o nsi dere d t o ha ve a ne gati ve H C V scree ni n g 
test. 

C C X 1 4 0- B 
 
Pr ot oc ol C L 0 1 1 _ 1 4 0 
 
  
A me n d me nt 4. 0 (2 9 Oct o ber  2 0 1 8) 
C he m o Ce ntr y x, I n c . 
C O N FI D E N TI A L  
Pa ge 5 5  of 9 3  
1 1.  Re nal disease ass o ciate d wit h dis or ders ot her t ha n F S G S (e. g. l u p us ne p hritis, C 3 
gl o mer ul o pat h y, pr olifer ati ve gl o mer ul o ne p hritis, I g A ne p hr o p at h y, refl u x ne p hr o pat h y, 
s ur gical se g me ntal r e nal a blati o n, sic kle cell disease) t hat is acti ve, or h as a si g nifica nt ris k of 
pr o gressi n g d uri n g t he c o urse of t he st u d y 
1 2.  Dis or ders ot her t h a n t h ose liste d i n I n cl usi o n Criteria 4 t hat are ass ociate d wit h F S G S lesi o n 
(i.e. sec o n d ar y F S G S, s uc h as si n gle ki d ne y, s ur gical se g me ntal re nal a bl ati o n, sic kle cell 
disease, dia betic n e p hr o p at h y , ot hers), or hist ol o gic al c oll a psi n g v ari a nt s u bt y pes of F S G S  
1 3.  E vi de nce of t u b erc ul osis base d o n i nterfer o n γ release assa y (I G R A) wit hi n 6 wee ks pri or t o 
scree ni n g. 
1 4.  E vi de nce of h e patic disease; A S T, A L T, al kali ne p h os p hatase > 3 x U L N , or t otal bilir u bi n > 
2 x U L N or I N R >  1. 5 x U L N at scree ni n g wit h t he e x ce pti o n t hat is olate d I N R ele vati o n i n 
t he a bse nce of ot her si g nifica nt li ver e nz y m e a b n or malities is e x plai ne d b y a ntic oa g ula nt 
t hera p y, ( e. g. warfari n).  
1 5.  Cli nicall y si g nifica nt peri p heral ne ur o pat h y. 
1 6.  He mat ol o gi c a b n or maliti es as f oll o ws: H b < 8 g/ d L, platel ets < 5 0, 0 0 0, A N C < 1 0 0 0 cells/ µ L) 
at baseli ne. 
1 7.  Cli nicall y s i g nifica nt a b n or mal E C G d uri n g s cree ni n g, e. g., Q Tc F greater t ha n 4 5 0 msec.  
1 8.  Hist or y of alc o h ol or illicit dr u g a b us e. Recreati o n al use of ca n na bis is n ot e x cl u de d w here 
le gal. 
1 9.  Hist or y of gastr oi ntesti nal c o n diti o ns t hat ma y i nterfere wit h st u d y me di cati o n c o m plia nce, 
e. g., s e ver e gastr o p aresis, wit h re g ur gitati o n  of f o o d or oral me dicati o n. 
2 0.  K n o w n h y p erse nsiti vit y t o C C X 1 4 0- B or i nacti ve i n gre di e nts of t he C C X 1 4 0- B ta blets 
(i ncl u di n g micr o cr ystalli ne cell ul ose, starc h, cr os p o vi d o ne, ma g n esi u m stearate, silico n 
di o xi de or t artr azi ne ). 
2 1.  Hist or y or prese n ce of s yste mic dis or der ot her t ha n F S G S t hat re q uires, or is e x pecte d t o 
re q uire, s yste mic gl uc o c ortic oi ds or i m m u ne m o d ulat ors d uri n g t he st u d y; t o pical or i n hale d 
gl uc o c ortic oi ds a n d i m m u ne m o d ulat ors are n ot e x cl u de d. 
2 2.  Hist or y or prese n ce of a n y me dical c o n diti o n or disease w hic h, i n t he o pi ni o n of t he 
I n v esti gat or, ma y place t he s u bject at u nacce pt a ble ris k f or st u d y partici p ati o n. 
2 3.  S u bjects ta ki n g str o n g C Y P 3 A 4 i n d ucers (e. g., p h e n yt oi n, rifa m pici n, car b a maze pi ne, St. 
J o h n’s W ort) or str o n g C Y P 3 A 4 i n hi bit ors (e. g., b oce pre vir, clarit hr o m yci n, c o ni va pta n, 
gr a pefr uit j uice, i n di na vir, itrac o naz ole, ket oc o naz ole, l o pi na vir/rit o na vir, mi befra dil, 
nefaz o d o ne, nelfi n a vir, p osac o naz ole, rit o na vir, sa q ui na vir, tela pre vir, t elit hr o m yci n, a n d 
v oric o naz ole) wit hi n t w o wee ks pri or t o scree ni n g. 
2 4.  S u bjects ta ki n g lit hi u m , p a mi dr o n ate , or i nterfer o n; s u bjects ta ki n g n o n-ster oi dal a nti-
i nfla m mat or y a ge nts ( N S AI D S) c hr o ni call y (i nter mitte nt, i.e. occasi o nal N S AI D S f or pai n or 
fe ver is disc o ura ge d, b ut is n ot e x cl u de d). 
5. 4.  
C o nti n ui n g Eli gi bilit y Criteri a  
S u bjects m a y e nter t he O pe n -L a bel E xte nsi o n if t he s u bject:  

C C X 1 4 0- B 
 
Pr ot oc ol C L 0 1 1 _ 1 4 0 
 
  
A me n d me nt 4. 0 (2 9 Oct o ber  2 0 1 8) 
C he m o Ce ntr y x, I n c . 
C O N FI D E N TI A L  
Pa ge 5 6  of 9 3  
•  h as n ot wit h dr a w n c o nse nt f or t he st u d y  
•  h as n o ne w i nf ecti o ns t h at, i n t he j u d g me nt of t he i n vesti g at or, w o ul d precl u de 
a d di ti o n of a ne w i m m u n os u p pressi ve or i m m u n o m o d ul at or y tre at me nt 
•  h as h a d n o re q uire me nt f or t he a d diti o n of ne w i m m u n os u p pressi ve tre at me nt 
d uri n g t he pri or 1 2 w ee ks a n d n o a ntici p ate d re q uire me nt d uri n g t he ne xt 1 2 w ee ks.  
5. 5.  
Re m o v al of S u bject s fr o m T her a p y of Assess me nt  
I n v esti gat ors m ust clearl y disti n g uis h bet w ee n st u d y dr u g treat me nt disc o nti n uati o n a n d st u d y 
wit h dra wal. S u bject s w h o disc o nti n ue st u d y dr u g treat me nt or w h o i nitiate me dicati o n c ha n ges 
(i ncl u di n g t h ose pr o hi bit e d b y t h e pr ot oc ol) will n ot be aut o maticall y wit h dra w n fr o m t he st u d y, 
b ut all eff orts m ust be ma de t o c o nti n ue t o f oll o w t he s u bjects f or all re g ularl y s c he d ule d visits.  
T he Me dical M o nit or s h o ul d be c o ntacte d t o d eter mi ne h o w t o a d dress t he s pecific sit uati o n. 
I n v esti gat ors m ust ta ke a p pr o priate meas ures t o m a ke s ure t h at s u bject s are m oti vate d t o c o m pl y 
wit h all re q uire me nts of t he pr ot oc ol i n or der t o mi ni mize t he a m o u nt of missi n g data. S u bject s 
w h o disc o nti n ue st u d y tr eat me nt earl y or i nitiate me dicati o n c ha n ges (i ncl u di n g t h ose pr o hi bite d 
b y t he pr ot oc ol) s h o ul d c o nti n ue t o be f oll o we d f or all re g ularl y s c he d ule d visits f or safet y a n d 
efficac y ass ess me nts.  I n v esti gat ors a n d t heir staff m ust ta ke meas ures t o acti vel y mai ntai n 
c o ntact wit h t heir s u bjects i n t he st u d y, s uc h as tel e p h o ne calls, te xts, or e mails bet wee n visits, 
a n d offers f or tr a ns p ortati o n s u p p ort t o visit t he st u d y site.  
5. 5. 1.  
S u bject s m a y be wit h dr a w n fr o m t he st u d y f or t he f oll o wi n g re as o ns: 
1.  S u bject  wit h dra wal of c o nse nt t o c o ntri b ute a d diti o nal o utc o me i nf or mati o n; 
2.  S u bject  n o n-c o m plia nce wit h d osi n g or diar y c o m pleti o n; 
3.  L oss t o f oll o w- u p; 
4.  S p o ns or’s decisi o n t o ter mi nate t he st u d y. 
5. 5. 2.  
S u bject s m a y disc o nti n ue st u d y dr u g tre at me nt  f or a n y of t he f oll o wi n g re as o ns: 
1.  S u bject  wit h dra wal of c o nse nt ; 
2.  T he I n vesti gat or ma y dis c o nti n ue s t u d y dr u g treat me nt if, i n his/ her cli nical j u d g me nt, it is i n 
t he best i nterest of t he s u bject; 
3.  T he S p o ns or ma y re q u est disc o nti n uati o n of st u d y dr u g treat me nt f or safet y reas o ns or n o n-
c o m plia nce wit h treat me nt ; 
4.  T he S p o ns or ma y re q u est disc o nti n uati o n of st u d y dr u g treat me nt d ue t o n e w or i ncrease d 
gl uc o c ortic oi d/i m m u n os u p pressa nt treat me nt. 
I n t he e ve nt of earl y wit h dra wal fr o m t he st u d y , t h e tests a n d e val u ati o ns liste d f or t he Earl y 
Ter mi nati o n visit  i n Secti o n 7. 1 4  will be perf or me d , w he ne ver p ossi ble. Data c ollecte d at t his 
visit will be desi g nate d as a n “ Earl y T er mi nati o n” visit  i n t he E D C. T he S p o ns or s h o ul d be 
n otifie d of all st u d y dr u g treat me nt a n d st u d y wit h dra wals i n a ti mel y ma n n er. 
If t he I n vesti gator c o nsi d ers a c h a n ge i n bac k gr o u n d treat me nt f or F S G S , t his s h o ul d be 
disc usse d wit h t he Me dical M o nit or, a n d decisi o n ma de re gar di n g disc o nti n uati o n of bli n de d 

C C X 1 4 0- B 
 
Pr ot oc ol C L 0 1 1 _ 1 4 0 
 
  
A me n d me nt 4. 0 (2 9 Oct o ber  2 0 1 8) 
C he m o Ce ntr y x, I n c . 
C O N FI D E N TI A L  
Pa ge 5 7  of 9 3  
st u d y dr u g. I n d e pe n d e nt of c o nti n uati o n or disc o nti n uati o n of st u d y dr u g, s u bjects s h o ul d 
c o nti n ue i n t he st u d y f or assess me nt of o utc o me. 
6.  
S T U D Y M E DI C A TI O N/ T R E A T M E N T  
6. 1.  
Pr o d uct C h ar acteristics  
T he i n vesti gati o nal me dici nal pr o d ucts (I M P ) are oral fil m c oate d ta blets c o ntai ni n g 5 m g of 
C C X 1 4 0- B a n d matc hi n g place b os. T he t a blets are ma n ufact ure d u n der c urre nt g o o d 
ma n ufact uri n g pr actice. T he cli nical trial materi al is pac ka ge d i n hi g h de nsit y p ol yet h yl e ne 
( H D P E) b ottles c o ntai ni n g 3 0 ta blets of eit her place b o or acti ve. T hese b ottl es will be pac ka ge d 
i n kits t o a d mi nister t o s u bjects i n a bli n de d fas hi on; place b o, 5 m g o nce d ail y, 1 0 m g t wi ce 
dail y, a n d 1 5 m g t wice d ail y.  
D uri n g t h e bli n de d p orti o n of t he st u d y, st u d y dr u g will be s u p plie d t o eac h s u bject i n kits. Eac h 
kit c o ntai ns 3 b ottles la bele d wit h a yell o w ba n d f or use i n t he m or ni n g a n d 3 b ottles la bele d wit h 
a bl ue ba n d f or use i n t he e ve ni n g. Eac h b ottle will be als o la bele d wit h a disti n g uis hi n g n u m ber. 
S u bjects will be i nstr ucte d t o ta ke o ne ta blet fr o m eac h of t h e t hree yell o w ba n de d b ottles i n t he 
m or ni n g, a n d o n e ta blet fr o m eac h of t he t hree bl ue ba n de d b ottles i n t he e v e ni n g. 
D uri n g t h e o pe n la bel p h ase of t he st u d y C C X 1 4 0- B will be a d mi nistere d as u p t o 3 ta blets ( 5 m g 
eac h) t wi ce dail y, de p e n di n g o n deter mi nati o n of t he hi g h est safest d ose. D uri n g st u d y wee ks 1 3 
t hr o u g h 2 4, disti ncti o n b et wee n m or ni n g a n d e ve ni n g d oses a n d b ottles are n ot re q uire d si nce 
eac h b ottle will  c o ntai n acti ve st u d y me dicati o n at t he sa me d ose. T heref ore t he b ottles dis pe nse d 
f or t his p hase of t he st u d y will neit her i ncl u d e yell o w or bl ue mar ki n gs or disti nct n u m bers. 
6. 2.  
R a n d o miz ati o n a n d Met h o d of Tre at me nt Assi g n me nt  
Eli gi ble s u bjects will be e nr olle d a n d stratifi e d base d o n t w o stratificati o n fact ors: U P C R < 3. 5 g 
pr otei n/ g creati ni ne at baseli ne vers us U P C R ≥3. 5 g pr otei n/ g creati ni ne at baseli ne , a n d o n 
gl uc o c ortic oi d/i m m u n os u p pressi ves or n o gl uc o c ortic oi d/ i m m u n os u p pressi ves, a n d ra n d o mize d 
t o o ne of t he f o ur tr eat me nt gr o u ps i n a rati o of 1: 1: 1: 1; plac e b o: 5 m g C C X 1 4 0- B Q D: 1 0 m g 
C C X 1 4 0- B BI D:  1 5 m g C C X 1 4 0-B BI D.  Ra n d o mizati o n will be perf or me d ce ntrall y via a n 
i nteracti ve r es p o nse tec h n ol o g y (I R T) s yst e m a n d mi ni mizati o n al g orit h m, usi n g t he 
stratificati o n fact ors. I n or der t o pr otect t he bli n di n g, t he ra n d o mizati o n sc he d ule will n ot be 
accessi ble t o  st u d y pers o n nel w h o ha ve c o ntact wit h st u d y ce nters or w h o are i n v ol ve d i n data 
ma na ge me nt a n d a nal ysis.  
6. 3.  
D oses a n d Re gi me ns  
Treat me nts f or eac h gr o u p are s h o w n i n  T a ble  1. S u bject s will recei v e o ne of t he f oll o wi n g d os e 
re gi me ns: 5 m g C C X 1 4 0- B o nce dail y, 1 0 m g C C X 1 4 0-B t wice dail y,  1 5 m g C C X 1 4 0-B t wi ce 
dail y, or mat c hi n g pl ace b o. 
6. 3. 1.  
I niti al 1 2 Wee k Tre at me nt P eri o d  
St u d y dr u g a n d place b o will be ta ke n as f oll o ws b y st u d y s u bjects: 
5 m g C C X 1 4 0- B ( Q D):  

C C X 1 4 0- B 
 
Pr ot oc ol C L 0 1 1 _ 1 4 0 
 
  
A me n d me nt 4. 0 (2 9 Oct o ber  2 0 1 8) 
C he m o Ce ntr y x, I n c . 
C O N FI D E N TI A L  
Pa ge 5 8  of 9 3  
•  O ne 5 m g C C X 1 4 0- B a n d t w o matc hi n g place b o t a blets i n t he m or ni n g d os e, a n d t hree 
matc hi n g place b o ta blets i n t he e ve ni n g d ose; d oses s h o ul d be a p pr o xi matel y 1 0- 1 2 h o urs 
a part a n d ta k e n  dail y f or 1 2 wee ks ( 8 4 d a ys).  
1 0 m g C C X 1 4 0- B ( BI D):  
•  T w o 5 m g C C X 1 4 0- B a n d o ne matc hi n g place b o ta blets i n t he m or ni n g d os e, a n d t w o 5 
m g C C X 1 4 0- B a n d o ne matc hi n g place b o ta blets i n t he e ve ni n g d ose, d oses s h o ul d be 
a p pr o xi matel y 1 0- 1 2 h o urs a part a n d t a ke n dail y f or 1 2 wee ks ( 8 4 da ys). 
1 5 m g C C X 1 4 0- B ( BI D):  
•  T hree 5 m g C C X 1 4 0- B ta blets i n t he m or ni n g d os e, a n d t hree 5 m g C C X 1 4 0- B ta blets i n 
t he e ve ni n g d ose, d oses s h o ul d be a p pr o xi matel y 1 0- 1 2 h o urs a part a n d ta k e n dail y f or 1 2 
wee ks ( 8 4 d a ys). 
Place b o:  
•  T hree mat c hi n g pl ace b o t a blets  i n t he m or ni n g a n d t hree matc hi n g place b o  t a blets i n t he 
e ve ni n g, a p pr o xi matel y 1 0- 1 2 h o urs after t he m or ni n g d ose, d ail y f or 1 2 wee ks ( 8 4 da ys).  
( T he place b o ta blets will be i de ntical i n a p peara n ce t o t he C C X 1 4 0-B ta blets). 
6. 3. 2.  
O pe n -L a bel Tre at me nt 1 2 Wee k Tre at me nt Peri o d  
( O nl y a p plica ble t o s u bjects w h o are eli gi ble a n d willi n g t o partici pate i n t he O pe n -La bel 
E xte nsi o n, after Wee k 1 2). 
St u d y dr u g will be ta ke n as f oll o ws b y st u d y s u bjects:  
O pe n La bel D ose: 
T he d ose f or t h e o pe n la b el p hase of t his st u d y is pla n ne d t o be 1 5 m g t wice dail y. If, d uri n g t he 
c o urse of t he st u d y, t he S p o ns or, t o get h er wit h t he i n de pe n de nt Dat a M o nit ori n g C o m mittee 
deter mi nes t hat 1 5 m g t wice dail y is e x cee ds t he ma xi mall y t olerat e d d ose, t he o pe n la bel d ose 
will be a dj uste d d o w n war d. 
6. 4.  
R ati o n ale f or D ose Selecti o n  
T he t hree  acti ve tr eat me nt  d oses pr o p ose d f or t he st u d y are 5 m g a d mi nistere d dail y, 1 0 m g 
a d mi nistere d t wice d ail y, a n d  1 5 m g a d mi nistere d t wice dail y.  
Fi ve ( 5) m g d ail y is selecte d as t he l o west d ose t hat was teste d a n d f o u n d t o be b ot h safe a n d t o 
be ass ociate d wit h a cli nicall y -m ea ni n gf ul t hera pe utic effect i n s u bjects wit h dia betic 
ne p hr o pat h y ( D N) i n St u d y C L 0 0 5 _ 1 4 0. A t otal of 3 3 2 s u bjects were e nr olle d i n a ra n d o mize d, 
d o u ble- bli n d, place b o- c o ntr olle d cli nical trial t o e val uate t he efficac y, safet y a n d t olera bilit y of 
5 m g C C X 1 4 0- B 5 a n d 1 0 m g C C X 1 4 0- B c o m pare d t o place b o, w h e n a d mi nistere d f or u p t o 5 2 
wee ks i n s u bject s wit h D N. T he P hase 2 trial met its pri mar y e n d p oi nt b y d e m o nstrati n g t hat 
treat me nt wit h 5 m g of C C X 1 4 0-B gi ve n orall y o n ce dail y a d d e d t o a sta n d ar d of care  ( S O C) 
re gi me n of R A A S bl oc ka de treat me nt res ulte d i n a statisticall y si g nifica nt ( p = 0. 0 1) i m pr o ve me nt 
i n U P C R, be y o n d t h at ac hie ve d wit h S O C al o ne. T he ma xi m u m treat me nt effect ( 2 4 % re d ucti o n) 
was reac he d at 1 2 wee ks, a n d s ustai ne d re d u cti o n i n al b u mi n uri a relati ve t o place b o w as 
o bser ve d o ver t he f ull year ( U A C R at eac h o n e of t he te n ti me p oi nts o ver t he 5 2- wee k treat me nt 
peri o d i n t he s u bjects w h o recei v e d 5 m g C C X 1 4 0- B c o nti n u o usl y f or 5 2 w ee ks, were bel o w 

C C X 1 4 0- B 
 
Pr ot oc ol C L 0 1 1 _ 1 4 0 
 
  
A me n d me nt 4. 0 (2 9 Oct o ber  2 0 1 8) 
C he m o Ce ntr y x, I n c . 
C O N FI D E N TI A L  
Pa ge 5 9  of 9 3  
t h ose of t he S O C al o ne gr o u p). B ot h acti ve treat me nt re gi me ns were w ell -t olerate d; n o d ose-
relate d safet y si g nals wer e re p ort e d. 
Te n ( 1 0) m g t wice d ail y is selecte d as a n i nter me di ate d ose f or e x pl orati o n of d ose res p o ns e a n d 
t o g uar d a gai nst l osi n g t h e effi caci o us d ose if 1 5 m g t wice d ail y is ass o ciate d wit h u ne x pecte d or 
i nt olera ble t o xicit y. Usi n g t he r at as t he m ore se nsiti ve s pecies base d o n e x p os ure, t he N O A E L 
i n t he 2 6- wee k rat st u d y was 1 5 m g/ k g/ da y. T h e N O A E L i n t he 1 3- w ee k a n d 2 6-wee k rat st u dies 
were ass ociate d wit h s yst e mic e x p os ures t o C C X 1 4 0 w hic h were a b o ut 9- 1 0 ti mes hi g her t ha n 
t he h u ma n e x p os ure ass o ciate d wit h a dail y 1 0 m g d ose, a n d a b o ut 4- 5 f ol d a 1 0 m g BI D d os e. 
F iftee n ( 1 5) m g t wice d ail y is select e d as t he hi g hest d ose f or t his pr ot oc ol, w hic h  is pr ojecte d t o 
pr o vi de e x p os ure at b ot h pea k a n d tr o u g h t hat is wit hi n t he safet y m ar gi ns esta blis he d i n t he 
t o xic ol o g y pr o gr a m, a n d t hat is pr ojecte d t o mai ntai n a hi g h l e vel of tar get e n ga ge me nt, as 
s u m marize d bel o w a n d d etaile d i n t he I n vesti gat or’s Br o c h ure. T h e pr ojecte d cli nical e x p os ure 
wit h 1 5 m g t wice d ail y d osi n g is 3 -f ol d bel o w t he N O A E L e x p os ure esta blis he d i n t he m ost 
se nsiti ve s pecies teste d i n t he n o ncli nical t o xicit y st u dies (rat 2 6- w ee k, P O, Q D). I n h u ma ns, 
C C X 1 4 0- B has bee n a d mi nistere d a n d was w ell t olerate d at 1 5 m g a d mi nistere d o nce dail y f or 
u p t o 1 0 da ys i n healt h y v ol u nteers, a n d at 1 0 m g a d mi nistere d o nce d ail y f or u p t o 5 2 wee ks i n 
s u bjects wit h D N. A d mi nistrati o n of 1 5 m g t wice dail y i n h u ma ns wit h o ut pr otei n uria is 
pr ojecte d t o ac hie ve a pea k c o nce ntrati o n of ~ 6 5 0 0 n g/ m L ( ~ 1 3 µ M) a n d a tr o u g h c o nce ntrati o n 
of ~ 5 5 0 0 n g/ m L ( ~ 1 1 µ M) at stea d y state. T otal e x p os ure wit h 1 5 m g t wice dail y is pr oject e d t o 
be ~ 2 -f ol d hi g her t h a n t hat ac hie v e d wit h 1 5 m g d ail y a d mi nistrati o n i n healt h y v ol u nteers a n d 
3. 0 7-f ol d hi g h er t ha n t hat o bser ve d wit h 1 0 m g dail y e x p os ure i n s u bjects wit h D N. Tr o u g h 
e x p os ure wit h 1 5 m g t wice dail y is pr oject e d t o be  2. 4-f ol d hi g her t ha n tr o u g h e x p os ure ac hie ve d 
i n D N. 
Rati o nale f or selecti o n of 1 5 m g t wice d ail y is t o e ns ure a de q u ate e x p os ure mar gi n t o a d dress:  
1.  L oss of al b u mi n- b o u n d dr u g t hr o u g h pr otei n uria; a p ost- h oc a n al ysis P K i n s u bjects of 
trial # C L 0 0 5 _ 1 4 0 w h o e ntere d i n st u d y wit h al b u mi n uria > 1 gra m i n dicate d e x p os ure 
was a p pr o xi matel y 3 0 % bel o w t he mea n f or t he treat me nt gr o u p as a w h ole 
2.  I n crease d bi n di n g c o m petiti o n fr o m e n d o ge n o us li ga n d; M C P- 1 is re p ort e d t o be 
i ncreas e d i n ser u m a n d uri ne i n s u bjects wit h F S G S 
Rati o nale f or a d mi nistrati o n of t he hi g hest d ose as a di vi de d d ose ( 1 5 m g t wice dail y), as 
o p p ose d t o a si n gle d os e ( 3 0 m g o n ce dail y) i ncl u de:  
1.  Ease of a d mi nistrati o n ( 3 ta blets t wice dail y vs 6 ta blets o nce dail y)  
2.  1 5 m g a d mi nistere d as a si n gle dail y d ose  h as pre vi o usl y bee n test e d a n d t olerate d i n 
healt h y v ol u nteers, w hile 3 0 m g has n ot bee n pre vi o usl y d ose d 
3.  1 5 m g t wice d ail y will res ult i n a l o wer C ma x  t ha n 3 0 m g o nce dail y, miti gati n g t he 
p ote ntial f or C ma x -dri ve n safet y c o n cer ns  
T o e ns ure earl y det ecti o n of d ose-r elate d safet y si g nals, t he pr o p ose d pr ot o c ol will i nc or p orate: 
1.  Fre q u e nt cli nical visits a n d safet y la b orat or y assess me n ts, i ncl u di n g s pecial atte nti o n t o 
assess me nt of earl y i n dicati o n of he m ol ysis (e. g. i ncreas e d retic ul o c yt es, i n creas e fr o m 
baseli ne i n bilir u bi n or L D H) a n d a p plicati o n of a sta n dar d healt h assess me nt a n d a 

C C X 1 4 0- B 
 
Pr ot oc ol C L 0 1 1 _ 1 4 0 
 
  
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C he m o Ce ntr y x, I n c . 
C O N FI D E N TI A L  
Pa ge 6 0  of 9 3  
q uesti o n naire t o detect s y m pt o ms of ne ur o pat h y a t re g ular i nter v als as detaile d i n t he 
Ti me a n d E ve nts Ta ble . 
2.  Safet y m o nit ori n g b y a n i n de pe n de nt D ata M o nit ori n g C o m mittee t hr o u g h o ut t he st u d y. 
6. 5.  
Dr u g S u p pl y  
6. 5. 1.  
P ac k a gi n g a n d L a beli n g 
T he i n vesti gati o nal me dici nal pr o d ucts (I M P ) are oral fil m c oate d ta blets co ntai ni n g 5 m g of 
C C X 1 4 0- B a n d matc hi n g place b os. T he t a blets are ma n ufact ure d u n der c urre nt g o o d 
ma n ufact uri n g pr actice. T he cli nical trial materi al is pac ka ge d i n hi g h de nsit y p ol yet h yl e ne 
( H D P E) b ottles c o ntai ni n g 3 0 ta blets of eit her place b o or acti ve. T heses b ottles will be pac ka ge d 
i n kits t o a d mi nister t o t he s u bjects, i n a bli n de d fas hi o n; place b o, 5 m g o n ce dail y, 1 0 m g t wice 
dail y a n d 1 5 m g t wice dail y. 
6. 5. 2.  
St or a ge 
C C X 1 4 0- B ta blets will be st ore d acc or di n g t o la b el i nstr ucti o ns. Access s h o ul d be restricte d t o 
p har mac y staff or t o t he desi g nat e d res p o nsi ble m e m ber of t he I n vesti gat or’s staff, a n d t o t he 
st u d y m o nit or. T he I n v esti gat or a grees t hat neit her s/ he n or a n y of t he st u d y staff will s u p pl y 
st u d y me dicati o n t o a n y pers o ns ot her t ha n t h ose e nr olle d i n t he st u d y. 
6. 5. 3.  
Bli n di n g  
T his st u d y is d o u ble- bli n d. Bli n di n g of t h e st u d y will be ac hie ve d b y t h e f oll o wi n g meas ures: 
T he st u d y dr u g b ottles a n d ta blet a p peara nce f or C C X 1 4 0- B a n d its matc hi n g place b o will be 
i de ntical. 
Li mite d access t o t he r a n d o mizati o n  c o de; S p o ns or pers o n nel directl y i n v ol ve d i n t he c o n d uct 
a n d m o nit ori n g of t he st u d y, st u d y site pers o n n el, st u d y s u bjects, pers o n nel res p o nsi ble f or st u d y 
m o nit ori n g, a n d bi ostatisticia ns a n d data ma n a gers i n v ol ve d i n data a nal ysis of t he st u d y will 
re mai n bli n de d t o treat m e nt assi g n me nt f or t he d urati o n of t he st u d y. 
W hile la b orat or y p ers o n n el c o n d ucti n g t he P K ass a ys will n ot be bli n de d t o treat me nt 
assi g n me nt, u n bli n de d C C X 1 4 0- B plas ma c o nce ntrati o n res ults will n ot be s hare d wit h t he st u d y 
site pers o nnel or st u d y staff w h o h a ve direct c o ntact wit h st u d y sites d uri n g t he st u d y. 
Efficac y data t hat c o ul d p ote ntiall y be u n bli n di n g, (i.e. U P C R , ser u m al b u mi n a n d C B C) data 
wit hi n t he n or mal ra n ge will n ot be ma de a vaila bl e t o st u d y site pers o n n el, st u d y s u bjects, 
pers o n nel res p o nsi ble f or st u d y m o nit ori n g, a n d bi ostatisticia ns a n d data ma na gers d uri n g t he 
st u d y u nless f or s afet y m o nit ori n g. I n vesti gat ors, h o we ver, will be pr o vi de d wit h safet y 
la b orat or y dat a re p orts, fla g gi n g a b n or mall y hi g h a n d l o w val ues t o ma ke i nf or me d decisi o ns 
re gar di n g s u bject care.  
Treat me nt assi g n me nts f or i n di vi d ual s u bjects will re mai n bli n de d t o t he st u d y tea m, 
i n vesti gat ors, a n d s u bj ects u ntil after t he st u d y d at a base has b ee n clea n e d a n d l oc ke d. Desi g nate d 
st u d y staff will be pro vi de d wit h i nstr ucti o ns re gar di n g h o w t o u n bli n d a n i n di vi d ual s u bject 
treat me nt assi g n me nt. A n i n di vi d ual s u bject treat me nt assi g n me nt ma y b e u n bli n de d o nl y i n t he 
case of a n a d v erse e ve nt t hat re q uires k n o wle d ge of t he st u d y me di cati o n recei ve d b y t h e su bject  

C C X 1 4 0- B 
 
Pr ot oc ol C L 0 1 1 _ 1 4 0 
 
  
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C he m o Ce ntr y x, I n c . 
C O N FI D E N TI A L  
Pa ge 6 1  of 9 3  
i n or der t o pr o vi de a p pr o priate treat me nt or ma na ge m e nt of t he a d v erse e v e nt. T he st u d y m o nit or 
a n d S p o ns or s h o ul d be n otifie d as s o o n as p ossi ble i n t he e ve nt t hat u n bli n di n g of a n i n di vi d ual 
s u bject’s treat me nt assi g n me nt occ urs pri or t o st u d y c o m pleti o n. 
A n e xter nal data m o nit ori n g c o m mittee ( D M C) will be c o nstit ute d pri or t o start of t he st u d y. T h e 
D M C me m bers will re vie w data p eri o dicall y o ver t he c o urse of t h e st u d y i n a n u n bli n de d 
ma n ner. T he D M C will pr o vi de rec o m me n dati o ns t o t he S p o ns or re gar di n g f urt her c o n d u ct of 
t he st u d y. T he D M C will o perate acc or di n g t o a c harter d e vel ope d pri or t o st u d y i nitiati o n.  
6. 6.  
Dr u g Acc o u nt a bilit y  
T he st u d y p h ar macist a n d I n v esti gat or m ust mai ntai n acc urate rec or ds of d ates a n d q ua ntities of 
pr o d uct(s) r ecei v e d, t o w h o m dis pe nse d ( s u bject-b y -s u bject acc o u nti n g), a n d acc o u nts of a n y 
pr o d uct acci de ntall y or d eli beratel y destr o ye d. T h e I n vesti gat or m ust retai n all u n use d a n d/ or 
e x pire d st u d y s u p plies u ntil t he st u d y m o nit or has c o nfir me d t he acc o u nt a b ilit y ( b ottle, stu d y 
me dicati o n a n d diar y rec o nciliati o n) data.  
6. 7.  
Tre at me nt C o m pli a nce  
T he C C X 1 4 0- B a n d matc hi n g  place b o ta bl ets will be self -a d mi nistere d b y partici pati n g st u d y 
s u bjects. T he m or ni n g d ose of st u d y dr u g o n Da y 1 will be ta ke n i n t he prese nce of st u d y site 
per s o n nel. S u bject s will be pr o vi de d wit h d osi n g i nstr ucti o ns at t he start of t he st u d y, a n d will be 
e nc o ura ge d b y st u d y site pers o n nel t o ta ke t he st u d y me dicati o n acc or di n g t o t he i nstr ucti o ns f or 
t he d urati o n of t he st u d y. S u bject s will be i nstr ucte d t o bri n g t he assi g n e d b ottles of st u d y 
me dicati o n t o t he site staff at eac h st u d y visit, w het her e m pt y or n ot  al o n g wit h c o m plete d 
diaries . T he st u d y dr u g dis pe nse d will be c hec ke d, a n d a ta blet c o u nt will b e d o ne fr o m Wee k 4 
t hr o u g h t he e n d of acti ve st u d y treat me nt of a n y re mai ni n g C C X 1 4 0- B or place b o ta blets. T his 
i nf or mati o n will be rec or de d a n d e ntere d i nt o t he electr o nic d ata ca pt ure (E D C ) s yste m. S u bjects 
w h o ta ke less t ha n 8 5 % of t heir pres cri be d d ose of st u d y me dicati o n ma y b e wit h dra w n fr o m 
st u d y d ue to treat me nt n o n -c o m plia nce.  
C C X 1 4 0- B plas ma c o n ce ntrati o n meas ure me nts o ver t he c o urse of t he st u d y ma y als o be use d t o 
assess s u bject c o m plia nce. A n y e ve nts of n o n-c o m plia nce t o t he pr ot oc ol will be d oc u me nte d i n 
t he st u d y r ec or ds a n d c o ul d res ult i n wit hdra wal of t he rele va nt s u bject . 
6. 8.  
C o nc o mit a nt Me dic ati o ns a n d Restricti o ns  
Me dic ati o ns t a ke n pri or t o e nr oll me nt will be rec or de d:  
•  rit u xi m a b or ot her B-cell de pleti n g m o n ocl o n al a nti b o dies  f or 1 ye ar pri or t o 
scree ni n g; 
S u bjects w h o h a ve t a ke n rit u xi m a b or o t her B-cell de pleti n g m o n ocl o n al a nti b o dies 
b ut st o p pe d m ore t h a n 2 0 w ee ks bef ore scree ni n g will be all o w e d t o p artici p ate if 
t he rec o v er y of t he B cell p o p ul ati o n t o wit hi n n or m al r a n ge is c o nfir me d at t he ti me 
of scree ni n g.  
•  all F S G S me dic ati o ns (s pecific all y gl uc oc ortic oi ds, i m m u n os u p pressi ves) f or 6 
m o nt h s pri or t o s cree ni n g;  

C C X 1 4 0- B 
 
Pr ot oc ol C L 0 1 1 _ 1 4 0 
 
  
A me n d me nt 4. 0 (2 9 Oct o ber  2 0 1 8) 
C he m o Ce ntr y x, I n c . 
C O N FI D E N TI A L  
Pa ge 6 2  of 9 3  
•  all ot her me dic ati o ns, i ncl u di n g pl as m a t her a p y re gi me ns, f or 1 2 w ee ks pri or t o 
scree ni n g. 
I n or der n ot t o disr u pt s u bject car e, t he pr ot oc ol will all o w c o nti n uati o n of treat me nt 
( bac k gr o u n d m e dicati o ns) wit h gl uc o c ortic oi ds, i m m u n os u p presa nts, calci ne uri n i n hi bit ors, or 
re ni n-a n gi ote nsi n -al d oster o ne s yste m ( R A A S)  bl o c kers . T he d os es f or t h ese bac k gr o u n d 
me dicati o ns m ust re mai n sta ble f or a mi ni m u m of 4 wee ks pri or t o scree ni n g a n d t hr o u g h t he 
treat me nt peri o d ( 2 4 wee ks)  f oll o wi n g ra n d o mizati o n, wit h t he f oll o wi n g e x ce pti o ns. A dj ust me nt 
of R A A S bl oc kers is per mitte d f or ma na ge me nt of h y p erte nsi o n. D uri n g t h e o pe n la bel p eri o d 
(after Wee k 1 2), gl uc o c ortic oi ds, i m m u n os u p presa nts, a n d calci n e uri n i n hi bit or will be all o we d 
o nl y if ess e ntial f or patie nt safet y . 
E x peri me ntal dr u gs, rit u xi ma b, a n d plas ma p heresis are n ot all o we d at a n y p oi nt d uri n g t he 
c o urse of t he st u d y. If t he In v esti gat or dee ms t hat a n y of t hese treat me nts are necessar y f o r t he 
best i nterest of a s u bject, t his s u bject w o ul d disc o nti n ue st u d y dr u g, b ut re m ai n i n t he st u d y t o 
m o nit or o utc o mes. 
C C X 1 4 0- B is pri maril y cleare d t hr o u g h C Y P 3 A 4 meta b olis m. S u bjects ta ki n g str o n g C Y P 3 A 4 
i n d ucers (e. g., p he n yt oi n, rifa m pici n, car ba maze pi ne, St. J o h n’s W ort) or str o n g C Y P 3 A 4 
i n hi bit ors (e. g., b oce pr e vir, clarit hr o m yci n, c o ni va pta n, gra pefr uit j uice, i n di na vir, itrac o naz ole, 
ket oc o naz ole, l o pi na vir/rit o na vir, mi befra dil, nefaz o d o ne, nelfi na vir, p osac o naz ole, rit o na vir, 
sa q ui na vir, tela pre vir, telit hr o m yci n, a n d v oric o naz ole) will be e x cl u de d fr o m t his cli nical trial 
si nce t hese dr u gs ma y s u bsta ntiall y i ncrease t he C C X 1 4 0-B plas ma le v els.  
S u bjects ta ki n g lit hi u m , p a mi dr o n ate , i nterfer o n, or c hr o nic N S AI D S  are als o e x cl u de d. N ote 
t hat su bje cts ta ki n g i nter mitte nt N S AI D S f or p ai n or fe ver are disc o ura ge d fr o m st u d y 
partici pati o n , b ut are  n ot e x cl u de d. 
All c o nc o mita nt me dicati o ns i nclu di n g  m arij u a n a use (if a p plic a ble) ta ke n d uri n g t he c o urse 
of t he st u d y m ust be r ec or de d metic ul o usl y o n t h e c o nc o mita nt me dicati o n pa ges of t he C R F. 
A n y i n vesti gati o nal pr o d ucts ta ke n u p t o 1 2 wee ks pri or t o scree ni n g or wit hi n 5 half- li ves after 
ta ki n g t he last d ose m ust be rec or de d o n t he c o nc o mita nt me dicati o n pa ge. 
7.  
S T U D Y P R O C E D U R E S  
7. 1.  
Scree ni n g a n d E nr oll me nt  
I nf or me d C o nse nt m ust be o btai ne d pri or t o perf or ma nce of a n y st u d y-s pecific tests or 
e val uati o ns. It is i m p orta nt t o c o m plete t he scree ni n g pr oce d ures i n t he s h ortest ti me p ossi ble t o 
all o w s u bjects t o start treat me nt. Wit hi n a peri o d n ot t o e x cee d 2 8 da ys pri or t o e nr oll me nt, 
s u bjects will u n der g o t h e f oll o wi n g e v al uati o ns t o deter mi ne t heir eli gi bilit y f or st u d y 
partici pati o n:  
•  Rec or di n g of de m o gr a p hic data a n d me dical hist or y  
•  Rec or di n g of all pri or me dicati o ns f or F S G S  (s pecificall y gl uc o c ortic oi ds a n d  
i m mu n os u p pressi ves ) f or t he 6 m o nt h peri o d pri or t o scree ni n g 
•  Rec or di n g of all  ot her pri or me dicati o ns , i ncl u di n g plas ma t hera p y re gi me n, f or t he 1 2 wee k 
peri o d pri or t o scr ee ni n g, 

C C X 1 4 0- B 
 
Pr ot oc ol C L 0 1 1 _ 1 4 0 
 
  
A me n d me nt 4. 0 (2 9 Oct o ber  2 0 1 8) 
C he m o Ce ntr y x, I n c . 
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•  If t he s u bject h as recei v e d pri or rit u xi m a b tre at me nt or ot her B -cell de pleti n g 
a nti b o dies , rec or d t he me dic ati o n use, as w ell as a n y a v ail a ble uri n ar y pr otei n v al ues, 
f or 1 ye ar pri or t o scree ni n g  
•  Test t o e x cl u de t u berc ul osis (i nterfer o n γ release assa y [I G R A] wit hi n 6 wee ks pri or t o 
scree ni n g 
•  Ser u m c he mistr y , h e mat ol o g y , c o a g ulati o n, li pi ds, l y m p h oc yte s u bsets a n d uri nal ysis tests 
(res ults fr o m tests d o ne wit hi n 7 2 h o urs pri or t o scree ni n g ma y b e use d f or eli gi bilit y 
assess me n t) 
•  Rec or di n g of r e nal bi o ps y r es ults f or F S G S c o nfir mati o n 
•  T he A C T G Brief  Peri p heral Ne ur o p at h y Scree ni n g T o ol will be a d mi nistere d  
•  Res ults fr o m tests t hat ha ve bee n p erf or m e d pri or t o scree ni n g ma y  b e use d t o deter mi ne 
st u d y eli gi bilit y if t hese t ests were p erf or me d as p art of t he practice of me dici ne a n d were 
d o ne w het her or n ot st u d y e ntr y was c o nt e m plate d, s uc h as f or dia g n osis or treat me nt of t he 
s u bject’s c o n diti o n. Res ults fr o m t he pri or tests m ust be rec or d e d i n t he E D C 
•  A first m or ni n g v oi d f or assess me nt of uri ne pr otei n a n d creati ni ne assa ys ( U P C R / U A C R 
a n d C ystati n C assess me nt)  
•  A c o m plete p h ysical e x a mi nati o n will be perf or m e d  
•  Vital si g ns ( w ei g ht, hei g ht, te m perat ure, bl o o d press ure, heart rat e) will be meas ure d after at 
least 3 mi n utes of rest 
•  A 1 2 -lea d E C G, after at least 3 mi n utes of rest, will be rec or d e d a n d assess e d f or a n y 
cli nicall y si g nifica nt a b n or malit y  
•  After all scree ni n g pr o ce d ures ha ve b ee n c o m plete d, a n d t he s u bject  s atisfies all eli gi bilit y 
criteria, t he st u d y sc h e d ule will be dis c usse d wit h t he s u bject a n d t he sc h e d ule will be 
pr o vi de d t o t he s u bject t o e ns ure c o m plia n ce wit h t he st u d y visits 
•  T he s u bject will be gi ve n i nstr ucti o ns a n d s u p plies f or t he uri ne c ollecti o ns o n t he d a y 
bef ore t he ne xt visit ( kit f or first m or ni n g v oi d an d j u g f or 2 4-h o ur uri ne c ollecti o n)  
− C ollect t he first m o r ni n g v oi d t he d a y bef ore t he first visit ( D a y 0) a n d p ut i n t he 
s m aller c o nt ai ner. 
− C ollect all uri ne f or 2 4 h o urs st arti n g A F T E R t he first m o r ni n g v oi d, i ncl u di n g first 
m o r ni n g v oi d o n t he d a y of t h e St u d y D a y 1 visit , i n t he bi g j u g. 
− Kee p s peci me ns ref ri ger ate d u ntil t he y are br o u g ht t o t he site at t he St u d y D a y 1 
visit.  
7. 2.  
St u d y D a y 1  
If eli gi ble f or t he st u d y, t he s u bject will visit t he st u d y ce nter o n Da y 1. T he f oll o wi n g 
pr oce d ur es will be perf or me d bef or e ta ki n g t he first d ose of C C X 1 4 0- B: 
•  A c o m plete p h ysical e x a mi nati o n  
•  Vital si g ns ( w ei g ht, te m p erat ur e, bl o o d press ure, h eart rate aft er at least 3 mi n utes of rest ) 

C C X 1 4 0- B 
 
Pr ot oc ol C L 0 1 1 _ 1 4 0 
 
  
A me n d me nt 4. 0 (2 9 Oct o ber  2 0 1 8) 
C he m o Ce ntr y x, I n c . 
C O N FI D E N TI A L  
Pa ge 6 4  of 9 3  
•  A 1 2 -lea d E C G, after at least 3 mi n utes of rest, will be rec or d e d a n d assess e d f or a ny 
cli nicall y si g nifica nt a b n or malit y  
•  Bl o o d sa m ples will be c ollecte d f or ser u m c he mistr y  (i ncl u di n g c oa g ulati o n pa nel a n d 
li pi ds), pre g n a nc y test  (i n w o me n of c hil d beari n g p ote ntial), he mat ol o g y, D N A, plas ma 
M C P - 1, P K , P D  (i ncl u di n g l y m p h oc yte s u bsets) a n d baseli ne meas ure me nts  
•  Pr o cess t he  first m or ni n g v oi d uri ne s a m ple c ollecti o n f or q ua ntitati ve uri nal ysis, U P C R , 
U A C R , C yst ati n C, Uri ne M C P- 1, M C P-1/creati ni ne rati o  a n d uri ne P D assess me nt  
•  Pr o cess t he 2 4 -h o ur uri ne s a m ple c ollecti o n f or q u a ntit ati ve uri n al ysis, U P C R, U A C R, 
C yst ati n C, Uri ne M C P - 1, M C P-1/cre ati ni ne r ati o uri ne P D assess me nt a n d uri ne 
pr otei n e xcreti o n/ d a y  
•  A n y pre -tr eat me nt a d v ers e e ve nts (fr o m ti me of t he scree ni n g visit) will be rec or d e d 
•  S u bject s will be as ke d t o c o m plete t he S F- 3 6 v 2 a n d E Q - 5 D-5 L  
•  S u bjects will be as ke d t o c o m plete t heir diar y eac h da y i m me diat el y after eac h d ose  
•  T he A C T G Brief Peri p heral Ne ur o p at h y Scree ni n g T o ol will be a d mi nistere d  
O nce dee me d eli gi ble , t h e f oll o wi n g pr oce d ures will be perf or me d: 
•  St u d y m e dicati o n (i n kits, c o ntai ni n g 4- wee k s u p pl y b ottles of C C X 1 4 0- B/ Place b o ), will be 
pr o vi de d t o t he s u bject wit h d osi n g i nstr ucti o ns 
•  T he s u bject  will be as ke d t o ta ke t he first d ose of C C X 1 4 0- B w hile at t he st u d y ce nter  a n d 
s h o ul d re mai n at t he st u d y ce nter f or o bser vati o n at t he PI’s discreti o n  
•  T he ti me of t he d osi n g of C C X 1 4 0- B will be rec or de d  
•  P K bl o o d sa m ples will be c ollecte d at Ti me 0 ( pre -d ose) , 0. 5, 1, 2, 3, 4, a n d 6 h o urs 
f oll o wi n g C C X 1 4 0- B or place b o d osi n g f or plas m a C C X 1 4 0 c o nce ntrati o n meas ure me nts; 
t he act ual ti me of eac h bl o o d sa m ple c ollecti o n will be rec or d e d 
•  A bl o o d sa m ple will be c ollecte d f or p h ar mac o d y na mic mar ker meas ure m e nts  
•  A n y c ha n ges i n c o nc o mita nt me dicati o n use will be rec or de d  
•  A n y p ost- d osi n g a d v erse e ve nts will be rec or de d  
•  Pr o vi de t he s u bject wi t h t he kit f or c ollecti o n of t he first m or ni n g v oi d  
•  After all st u d y pr oce d ures ha ve bee n c o m plete d, t he s u bject will be re mi n d e d t o:  
− C o me t o t he st u d y ce nt er f or t he Wee k 1  st u d y visit 
− St ore t he st u d y me dicati o ns  i n a c o ol a n d dr y place acc or di n g t o la b el i nstr ucti o ns f or t he 
d urati o n of t he st u d y 
− O n t he m or ni n g of t he ne xt visit, c ollect t he first m or ni n g v oi d i n t he c o nt ai ner 
pr o vi de d a n d ref ri ger ate u ntil it is br o u g ht t o t he st u d y ce nter  

C C X 1 4 0- B 
 
Pr ot oc ol C L 0 1 1 _ 1 4 0 
 
  
A me n d me nt 4. 0 (2 9 Oct o ber  2 0 1 8) 
C he m o Ce ntr y x, I n c . 
C O N FI D E N TI A L  
Pa ge 6 5  of 9 3  
7. 3.  
St u d y Wee k 1  ( D a y 8 +/ - 1 d a y)  
T he St u d y Wee k 1  visit s h o ul d occ u r wit hi n ± 1 da y of t he sc h e d ule d date. D uri n g t his visit, t he 
f oll o wi n g st u d y pr oce d ur es will be perf or me d: 
•  A n a b bre viat e d, s y m pt o m- directe d  p h ysical e x a mi nati o n  
•  Vital si g ns (te m perat ure, bl o o d press ure a n d h eart rate after at least 3 mi n utes of rest , w eig ht ) 
•  T he date a n d ti me of  t he last d ose of C C X 1 4 0- B or place b o  pri or t o c ollecti o n of t he P K 
sa m ple will be rec or de d 
•  Bl o o d sa m ples will be c ollecte d bef ore d ose a d mi nistrati o n f or ser u m c h e mistr y (i ncl u di n g 
c oa g ulati o n pa nel a n d li pi ds), he mat ol o g y, plas ma  M C P - 1, P K , a n d P D  (i ncl u di n g 
l y m p h oc yte s u bsets) m eas ure me nts; rec or d t he ti me of bl o o d c ollecti o n. 
•  Pr o cess t he first  m or ni n g v oi d uri ne s a m ple c ollecti o n f or q ua ntitati ve uri nal ysis, U P C R , 
U A C R  C yst ati n C, Uri ne M C P- 1 a n d M C P-1/cr eati ni ne rati o a n d uri ne P D assess me nt  
•  T he A C T G Brief  Peri p heral Ne ur o p at h y Scree ni n g T o ol will be a d mi nistere d  
•  If t he s u bject has n ot yet ta ke n t he m or ni n g d ose of C C X 1 4 0- B f or t his da y, t he s u bject will 
be as ke d t o ta ke t h e d ose 
•  A n y c ha n ges i n c o nc o mita nt me dicati o n use will be  rec or de d 
•  A n y a d vers e e ve nts will be rec or de d  
•  Dr u g acc o u nta bilit y a n d rec o nciliati o n wit h s u bject c o m plete d diaries  
•  Pr o vi de t he s u bject wit h t he kit f or c ollecti o n of t he first m or ni n g v oi d  
•  After all st u d y pr oce d ures ha ve bee n c o m plete d, t he s u bject will be re mi n d e d t o: 
− C o m plete t heir diar y eac h da y i m me diat el y after eac h d ose  
− C o me t o t he st u d y ce nt er f or t he Wee k 2 st u d y visit, bef ore ta ki n g t he d ose of t he visit 
da y 
− St ore t he st u d y me dicati o ns i n a c o ol a n d dr y place acc or di n g t o la b el i nstr ucti o n s f or the 
d urati o n of t he st u d y 
− O n t he m or ni n g of t he ne xt visit, c ollect t he first m or ni n g v oi d i n t he c o nt ai ner 
pr o vi de d a n d ref ri ger ate u ntil it is br o u g ht t o t he st u d y ce nter  
7. 4.  
St u d y Wee k 2  ( D a y 1 5 +/ - 1 d a y ) 
T he St u d y Wee k 2 visit s h o ul d occ ur wit hi n ± 1 da y o f t he sc h e d ule d date. D uri n g t his visit, t he 
f oll o wi n g st u d y pr oce d ur es will be perf or me d: 
•  A n a b bre viat e d, s y m pt o m- directe d p h ysical e x a mi nati o n  
•  Vital si g ns ( w ei g ht, te m p erat ur e, bl o o d press ure, h eart rate) after at least 3 mi n utes of rest 
•  Bl o o d sa m ples wi ll be c ollecte d f or ser u m c he mistr y, h e mat ol o g y, pl as ma M C P - 1, a n d P D 
(i ncl u di n g l y m p h oc yte s u bset) meas ure me nts 

C C X 1 4 0- B 
 
Pr ot oc ol C L 0 1 1 _ 1 4 0 
 
  
A me n d me nt 4. 0 (2 9 Oct o ber  2 0 1 8) 
C he m o Ce ntr y x, I n c . 
C O N FI D E N TI A L  
Pa ge 6 6  of 9 3  
•  P K bl o o d sa m ples will be c ollecte d at  Ti me  0 ( pre- d ose), 0. 5, 1, 2, 3, 4, a n d 6 h o urs 
f oll o wi n g C C X 1 4 0- B or place b o d osi n g f or plas m a C C X 1 4 0 c once ntrati o n meas ure me nts; 
t he act ual ti me of eac h bl o o d sa m ple c ollecti o n will be rec or d e d 
•  Pr o cess t he first  m or ni n g v oi d uri ne s a m ple c ollecti o n f or q ua ntitati ve uri nal ysis , U P C R , 
U A C R C yst ati n C, Uri ne M C P- 1, M C P -1/crea ti ni ne rati o a n d uri n e P D ass ess ment 
•  T he A C T G Brief  Peri p heral Scree ni n g T o ol will b e a d mi nistere d  
•  If t he s u bject has n ot yet ta ke n t he m or ni n g d ose of C C X 1 4 0- B f or t his da y, t he s u bject will 
be as ke d t o ta ke t h e d ose 
•  A n y c ha n ges i n c o nc o mita nt me dicati o n use will be rec or de d  
•  A n y a d vers e e ve nts will be rec or de d  
•  Dr u g acc o u nta bilit y a n d rec o nciliati o n wit h s u bject c o m plete d diaries   
•  Pr o vi de t he s u bject wit h t he kit f or c olle cti o n of t he first m or ni n g v oi d 
•  After all st u d y pr oce d ures ha ve bee n c o m plete d, t he s u bject will be re mi n d e d t o:  
− C o m ple te t heir diar y eac h da y i m me diat el y after eac h d ose 
− C o me t o t he st u d y ce nt er f or t he Wee k 4 st u d y visit, bef ore ta ki n g t he d ose of t he visit 
da y 
− St ore t he st u d y me dicati o ns i n a c o ol a n d dr y place acc or di n g t o la b el i nstr ucti o ns f or t he 
d urati o n of t he st u d y  
− O n t he m or ni n g of t he ne xt visit, c ollect t he first m or ni n g v oi d i n t he c o nt ai ner 
pr o vi de d a n d ref ri ger ate u ntil it is br o u g ht t o t he st u d y ce nter  
7. 5.  
St u d y Wee k 4 ( D a y 2 9+/ - 3 d a ys ) 
T he St u d y Wee k 4 visit s h o ul d occ ur wit hi n ± 3 da ys of t he sc h e d ule d date.  D uri n g t his visit, t he 
f oll o wi n g st u d y pr oce d ur es will be perf or me d: 
•  A n a b bre viat e d, s y m pt o m- directe d p h ysical e x a mi nati o n  
•  Vital si g ns ( w ei g ht, te m p erat ur e, bl o o d press ure, h eart rate) after at least 3 mi n utes of rest 
•  T he date a n d ti me of t he last d ose of  C C X 1 4 0- B or place b o pri or t o c ollecti o n of t he P K 
sa m ple will be rec or de d 
•  Bl o o d sa m ples will be c ollecte d bef ore d ose a d mi nistrati o n f or ser u m c h e mistr y (i ncl u di n g 
c oa g ulati o n pa nel a n d li pi ds), he mat ol o g y, ser u m pre g na nc y t est (i n w o me n of c hil d beari n g 
p ote ntial),  P K (ti me 0 o nl y), plas ma M C P - 1, a n d P D  (i ncl u di n g l y m p h oc yt e s u bset) 
meas ure me nt ; r ec or d t h e ti me of bl o o d c ollecti o n 
•  Pr o cess t he first  m or ni n g v oi d uri ne s a m ple c ollecti o n f or q ua ntitati ve uri nal ysis , U P C R , 
U A C R , C yst ati n C, Uri ne M C P- 1, M C P - 1/creati ni ne rati o a n d uri ne P D assess me nt  
•  S u bject s will be as ke d t o c o m plete t he S F- 3 6 v 2 a n d E Q- 5 D-5 L.  
•  T he A C T G Brief  Peri p heral Scree ni n g T o ol will b e a d mi nistere d  

C C X 1 4 0- B 
 
Pr ot oc ol C L 0 1 1 _ 1 4 0 
 
  
A me n d me nt 4. 0 (2 9 Oct o ber  2 0 1 8) 
C he m o Ce ntr y x, I n c . 
C O N FI D E N TI A L  
Pa ge 6 7  of 9 3  
•  If t he s u bject has n ot yet ta ke n t he m or ni n g d ose of C C X 1 4 0- B f or t his da y, t he s u bject wi ll 
be as ke d t o ta ke t h e d ose 
•  Dr u g acc o u nta bilit y a n d rec o nciliati o n wit h s u bject c o m plete d diaries  
•  A ne w kit, c o ntai ni n g 4- wee k s u p pl y b ottles of C C X 1 4 0- B/ Place b o  will be dis pe nse d 
•  A n y c ha n ges i n c o nc o mita nt me dicati o n use will be rec or de d  
•  A n y a d vers e e ve nts will be rec or de d  
•  Pr o vi de t he s u bject wit h t he kit f or c olle cti o n of t he first m or ni n g v oi d 
•  After all st u d y pr oce d ures ha ve bee n c o m plete d, t he s u bject will be re mi n d e d t o:  
− C o m plete t heir diar y eac h da y i m me diat el y after eac h d ose  
− C o me t o t he st u d y ce nt er f or t he Wee k 8 st u d y visit, bef ore ta ki n g t he d ose of t he visit 
da y 
− St ore t he st u d y me dicati o ns i n a c o ol a n d dr y place acc or di n g t o la b el i nstr ucti o ns f or t he 
d urati o n of t he st u d y 
− O n t he m or ni n g of t he ne xt visit, c ollect t he first m or ni n g v oi d i n t he c o nt ai ner 
pr o vi de d a n d ref ri ger ate u ntil it is br o u g ht t o t he st u d y ce nter  
7. 6.  
St u d y Wee k 8 ( D a y 5 7 +/ - 3 d a ys ) 
T he St u d y Wee k 8 visit s h o ul d occ ur wit hi n ± 3 da ys of t he sc h e d ule d date. D uri n g t his visit, t he 
f oll o wi n g st u d y pr oce d ur es will be perf or me d: 
•  A n a b bre viat e d, s y m pt o m- directe d p h ysical e x a mi nati o n  
•  Vital si g ns ( w ei g ht, te m p erat ure, bl o o d press ure, h eart rate aft er at least 3 mi n utes of rest) 
•  T he date a n d ti me of t he last d ose of C C X 1 4 0- B or place b o pri or t o c ollecti o n of t he P K 
sa m ple will be rec or ded 
•  Bl o o d sa m ples will be c ollecte d  bef ore d ose a d mi nistrati o n f or ser u m c h e mistr y, 
he mat ol o g y a n d P K (at ti me 0 o nl y); rec or d t h e ti me of bl o o d c ollecti o n. 
•  Pr o cess t he first  m or ni n g v oi d uri ne s a m ple c ollecti o n f or q ua ntitati ve uri nal ysis, 
U P C R ,U A C R  a n d c ystati n C assess me nt  
•  T he A C T G Brief Peri p heral Scree ni n g T o ol will b e a d mi nistere d  
•  If t he s u bject has n ot yet ta ke n t he m or ni n g d ose of C C X 1 4 0- B f or t his da y, t he s u bject 
will be as ke d t o ta ke t he d ose 
•  Dr u g acc o u nta bilit y a n d rec o nciliati o n wit h s u bject c o m p lete d diaries 
•  A ne w kit, c o ntai ni n g 4- wee k s u p pl y b ottles of C C X 1 4 0- B/ Place b o will be dis pe nse d  
•  A n y c ha n ges i n c o nc o mita nt me dicati o n use will be rec or de d  

C C X 1 4 0- B 
 
Pr ot oc ol C L 0 1 1 _ 1 4 0 
 
  
A me n d me nt 4. 0 (2 9 Oct o ber  2 0 1 8) 
C he m o Ce ntr y x, I n c . 
C O N FI D E N TI A L  
Pa ge 6 8  of 9 3  
•  A n y a d vers e e ve nts will be rec or de d  Pr o vi de t he s u bject wit h t he kit f or c ollecti o n of 
t he first m o r ni n g v oi d a n d j u g f or t he 2 4-h o ur uri ne c ollecti o n . After all st u d y 
pr oce d ur es ha ve b ee n c o m plete d, t he s u bject will be re mi n de d t o: 
− C o m plete t heir diar y eac h da y i m me diat el y after eac h d ose  
− C o me t o t he st u d y ce nt er f or t he Wee k 1 2 st u d y visit a n d bri n g c o m plet e d diaries a n d 
A L L us e d a n d u n use d c o ntai ners of st u d y me dicati o n t o t he ne xt visit 
− C ollect t he first m o r ni n g v oi d t he d a y bef ore t he Wee k 1 2  visit a n d p ut i n t he 
s m aller c o nt ai ner 
− C ollect all uri ne f or 2 4 h o urs st arti n g A F T E R t he first m o r ni n g v oi d, i nc l u di n g 
first m or ni n g v oi d o n t he d a y of t he Wee k 1 2 visit , i n t he bi g j u g 
− Kee p s peci me ns ref ri ger ate d u ntil t he y are br o u g ht t o t he site f or t he Wee k 1 2 
visit.  
7. 7.  
St u d y Wee k 1 2  ( D a y 8 5  +/ - 3 d a ys ) ( See Secti o n 7.1 3 f or P K 
eli mi n ati o n g ui deli nes)  
T he St u d y Wee k 1 2 visit s h o ul d occ ur wit hi n ± 3 da ys of t he sc h e d ule d dat e. D uri n g t his visit, 
t he f oll o wi n g st u d y pr oce d ures will be perf or me d: 
•  A n a b bre viat e d, s y m pt o m- directe d p h ysical e x a mi nati o n  
•  Vital si g ns ( w ei g ht, te m p erat ur e, bl o o d press ure, h eart rate) after at least 3 mi n utes of rest 
•  A 1 2 -lea d E C G, after at least 3 mi n utes of rest, will be rec or d e d a n d assess e d f or a n y 
cli nicall y si g nifica nt a b n or malit y  
•  T he date a n d ti me of t he last d ose of C C X 1 4 0- B or place b o pri or t o c ollecti o n of t he P K 
sa m ple will be rec or de d 
•  Bl o o d sa m ples will be c ollecte d bef ore d ose a d mi nistrati o n f or ser u m c h e mistr y (i ncl u di n g 
c oa g ulati o n pa nel a n d li pi ds), he mat ol o g y, ser u m pre g na nc y t est (i n w o me n of c hil d beari n g 
p ote ntial), P K (ti me 0 o nl y), plas ma M C P - 1, a n d P D (i ncl u di n g l y m p h oc yt e s u bset) 
meas ure me nts; r ec or d t h e ti me of bl o o d c ollecti o n  
•  Pr o cess t he first  m or ni n g v oi d uri ne s a m ple c ollecti o n f or q ua ntitati ve uri nal ysis, U P C R , 
U A C R , C yst ati n C, Uri ne M C P- 1, M C P -1/crea ti ni ne rati o a n d uri ne P D assess me nts  
•  Pr o cess t he 2 4 -h o ur uri ne s a m ple c ollecti o n f or q u a ntit ati ve uri n al ysis, U P C R, U A C R, 
C yst ati n C, Uri ne M C P - 1, M C P-1/cre ati ni ne r ati o , uri ne P D assess me nt , a n d uri ne 
pr otei n e xcreti o n/ d a y  
•  S u bjec ts will be as ke d t o c o m plete t he S F- 3 6 v 2 a n d E Q- 5 D-5 L.  
•  T he A C T G Brief Peri p heral Scree ni n g  T o ol will b e a d mi nistere d  
•  If t he s u bject has n ot yet ta ke n t he m or ni n g d ose of C C X 1 4 0- B/ place b o f or t his da y, t he 
s u bject will be as ke d t o t a ke t he d ose 
•  Dr u g acc o u nta bilit y a n d rec o nciliati o n wit h s u bject c o m plete d diaries  

C C X 1 4 0- B 
 
Pr ot oc ol C L 0 1 1 _ 1 4 0 
 
  
A me n d me nt 4. 0 (2 9 Oct o ber  2 0 1 8) 
C he m o Ce ntr y x, I n c . 
C O N FI D E N TI A L  
Pa ge 6 9  of 9 3  
•  All st u d y dr u g me dicati o n c o ntai ners m ust be ret ur ne d a n d dr u g us a ge m ust be rec o n cile d 
a gai nst t he c o m plete d diaries si nce c o nti n ui n g s u bjects will be gi v e n ne w dr u g s u p pl y of 
acti ve st u d y m e dicati o n f or o pe n la bel d osi n g. 
•  A n y c ha n ges i n c o nc o mita nt me dicati o n use will be rec or de d  
•  A n y a d vers e e ve nts will be rec or de d  
•  Assess me nt of c o nti n ui n g eli gi bilit y re q uire me nts:  
− h as n ot wit h dr a w n c o nse nt f or t he st u d y  
− h as n o ne w i nf ecti o ns t h at i n t he j u d g me nt of t he i n vesti g at or w o ul d precl u de 
a d diti o n of a ne w i m m u n os u p pressi ve or i m m u n o m o d ul at or y tre at me nt 
− h as h a d n o re q uire me nt f or t he a d diti o n of ne w i m m u n os u p pressi ve tre at me nt 
d uri n g t he pri or 1 2 w ee ks a n d n o a ntici p ate d re q uire me nt d uri n g t he ne xt 1 2 w ee ks  
•  Pr o vi de t he s u bject wit h t he kit f or c ollecti o n of t he first m or ni n g v oi d  
•  After all st u d y  pr oce d ures ha ve bee n c o m plete d, d isc o nti n ui n g s u bjects will be re mi n de d t o:  
− c o me t o t he st u d y ce nter at 2 d a ys, 7 d a ys a n d 1 4 d a ys after t he l ast d ose f or P K 
eli mi n ati o n  a n d  
− c o me t o t he st u d y ce nter f or t he Wee k 1 6 f oll o w-u p visit  
•  C o nti n ui n g s u bjects  wil l be re mi n de d t o: 
− C o m plete t heir diar y eac h da y i m me diat el y after eac h d ose 
− C o me t o t he st u d y ce nt er f or t he Wee k 1 3 st u d y visit, bef ore ta ki n g t he d os e of st u d y 
dr u g  
− o n t he m o r ni n g of t he ne xt visit, c ollect t he first m o r ni n g v oi d i n t he c o nt ai ner 
pr o vi de d a n d ref ri ger ate u ntil it is br o u g ht t o t he st u d y ce nter  
7. 8.  
St u d y Wee k 1 3 ( D a y 9 2 +/ - 3 d a ys)  - C o nti n ui n g S u bjects O nl y  
T he St u d y Wee k 1 3 visit s h o ul d occ ur wit hi n ± 3 da ys of t he sc h e d ule d dat e. D uri n g t his visit, 
t he f oll o wi n g st u d y pr oce d ures will be perf or me d: 
•  A n a b bre viat e d, s y m pt o m- directe d p h ysical e x a mi nati o n  
•  Vital si g ns ( w ei g ht, te m p erat ur e, bl o o d press ure, h eart rate) after at least 3 mi n utes of rest  
•  A 1 2 -lea d E C G, after at least 3 mi n utes of rest, will be rec or d e d a n d assess e d f or a n y 
cli nicall y s i g nifica nt a b n or malit y 
•  T he date a n d ti me of t he last d ose of C C X 1 4 0- B pri or t o c ollecti o n of t he P K sa m ple will be 
rec or d e d 
•  Bl o o d sa m ples will be c ollecte d bef ore d ose a d mi nistrati o n f or ser u m c h e mistr y (i ncl u di n g 
c oa g ulati o n pa nel a n d li pi ds), he mat ol o g y, P K meas ure me nts  (ti me 0 o nl y), plas ma M C P - 1, 
a n d P D meas ure m e nts; rec or d t he ti me of bl o o d c ollecti o n 

C C X 1 4 0- B 
 
Pr ot oc ol C L 0 1 1 _ 1 4 0 
 
  
A me n d me nt 4. 0 (2 9 Oct o ber  2 0 1 8) 
C he m o Ce ntr y x, I n c . 
C O N FI D E N TI A L  
Pa ge 7 0  of 9 3  
•  Pr o cess t he first  m or ni n g v oi d uri ne s a m ple c ollecti o n f or q ua ntitati ve uri nal ysis , U P C R , 
U A C R , C yst ati n C, Uri ne M C P- 1, M C P -1/cr eati ni ne rati o a n d uri n e P D assess me nt  
•  T he A C T G Brief Peri p heral Scree ni n g T o ol will b e a d mi nistere d  
•  If t he s u bject has n ot yet ta ke n t he m or ni n g d ose of C C X 1 4 0-B f or t his da y, t he s u bject will 
be as ke d t o ta ke t h e d ose 
•  Dr u g acc o u nta bilit y a n d rec o nciliati o n wit h s u bject c o m plet e d diaries  
•  A n y c ha n ges i n c o nc o mita nt me dicati o n use will be rec or de d  
•  A n y a d vers e e ve nts will be rec or de d  
•  Pr o vi de t he s u bject wit h t he kit f or c ollecti o n of t he first m or ni n g v oi d  
•  After all st u d y pr oce d ures ha ve bee n c o m plete d, t he s u bject will be re mi n d e d t o: 
− C o m plete t heir diar y eac h da y i m me diat el y after eac h d ose  
− C o me t o t he st u d y ce nt er f or t he Wee k 1 6 st u d y visit, bef ore ta ki n g t he d os e of t he visit 
da y 
− O n t he m or ni n g of t he ne xt visit, c ollect t he first m or ni n g v oi d i n t he c o nt ai ner 
pr o vi de d a n d ref ri ger ate u ntil it is br o u g ht t o t he st u d y ce nter  
7. 9.  
St u d y Wee k 1 6 ( D a y 1 1 4 +/ - 3 d a ys  - C o nti n ui n g S u bjects O nl y  
T he St u d y Wee k 1 6 visit s h o ul d occ ur wit hi n ± 3 da ys of t he sc h e d ule d dat e. D uri n g t his visit, 
t he f oll o wi n g st u d y pr oce d ures will be perf or me d: 
•  A n  a b bre viat e d, s y m pt o m-directe d p h ysical e x a mi nati o n  
•  Vital si g ns ( w ei g ht, te m p erat ur e, bl o o d press ure, h eart rate) after at least 3 mi n utes of rest 
•  S u bjects will be as ke d t o c o m plete t he S F - 3 6 v 2 a n d E Q- 5 D-5 L.  
•  T he A C T G Brief Peri p heral Scree ni n g T o ol will b e a d mi nistere d  
•  T he date a n d ti me of t he last d ose of C C X 1 4 0- B pri or t o c ollecti o n of t he P K sa m ple will be 
rec or d e d 
•  Bl o o d sa m ples will be c ollecte d bef ore d ose a d mi nistrati o n f or ser u m c h e mistr y (i ncl u di n g 
c oa g ulati o n pa nel a n d li pi ds), he mat ol o g y, ser u m pre g na nc y t est (i n w o me n of c hil d beari n g 
p ote ntial), P K (ti me 0 o nl y) , plas ma M C P - 1, a n d P D (i ncl u di n g l y m p h oc yt e s u bset) 
meas ure me nts; r ec or d t h e ti me of bl o o d c ollecti o n  
•  Pr o cess t he first  m or ni n g v oi d uri ne s a m ple c ollecti o n f or q ua ntitati ve uri nal ysis, U P C R , 
U A C R , C yst ati n C, Uri ne M C P- 1, M C P -1/cr eati ni ne rati o a n d uri ne P D assess me nt  
•  If t he s u bject has n ot yet ta ke n t he m or ni n g d ose of C C X 1 4 0- B f or t his da y, t he s u bject will 
be as ke d t o ta ke t h e d ose 
•  Dr u g acc o u nta bilit y a n d rec o nciliati o n wit h s u bject c o m plete d diaries  
•  A ne w 4- w ee k s u p pl y of b ottles of C C X 1 4 0- B will be dis pe nse d 

C C X 1 4 0- B 
 
Pr ot oc ol C L 0 1 1 _ 1 4 0 
 
  
A me n d me nt 4. 0 (2 9 Oct o ber  2 0 1 8) 
C he m o Ce ntr y x, I n c . 
C O N FI D E N TI A L  
Pa ge 7 1  of 9 3  
•  A n y c ha n ges i n c o nc o mita nt me dicati o n use will be rec or de d  
•  A n y a d vers e e ve nts will be rec or de d  
•  Pr o vi de t he s u bject wit h t he kit f or c ollecti o n of t he first m or ni n g v oi d  
•  After all  st u d y pr oce d ures ha ve bee n c o m plete d, t he s u bject will be re mi n d e d t o:  
− C o m plete t heir diar y eac h da y i m me diat el y after eac h d ose  
− C o me t o t he st u d y ce nt er f or t he Wee k 2 0 st u d y visit 
− St ore t he st u d y me dicati o ns i n a c o ol a n d dr y place acc or di n g t o la b el i nstr ucti o ns f or t he 
d urati o n of t he st u d y 
− O n t he m or ni n g of t he ne xt visit, c ollect t he first m or ni n g v oi d a n d refri ger ate u ntil 
it is br o u g ht t o t he st u d y ce nter 
7. 1 0.  
St u d y Wee k 2 0  ( D a y 1 4 1+/ - 3 d a ys ) - C o nti n ui n g s u bjects o nl y  
T he St u d y Wee k 2 0 visit s h o ul d occ ur wit hi n ± 3 da ys of t he sc h e d ule d dat e. D uri n g t his visit, 
t he f oll o wi n g st u d y pr oce d ures will be perf or me d: 
•  A n a b bre viat e d, s y m pt o m- directe d p h ysical e x a mi nati o n  
•  Vital si g ns ( w ei g ht, te m p erat ur e, bl o o d press ure, h eart rate) after at least 3 mi n utes of rest 
•  T he A C T G Brief Peri p heral Scree ni n g T o ol will b e a d mi nistere d  
•  Bl o o d sa m ples will be bef ore d ose a d mi nistrati o n c ollecte d f or ser u m c h e mistr y, he mat ol o g y, 
ser u m pre g na nc y test (f or w o me n of c hil d beari n g p ote ntial), P K (ti me 0 o nl y); rec or d t he 
ti me of bl o o d c ollecti o n 
•  Pr o cess t he first  m or ni n g v oi d uri ne s a m ple c ollecti o n f or q ua ntitati ve uri nal ysis, U P C R , 
U A C R  a n d c ystati n C assess me nt  
•  If t he s u bject has n ot yet ta ke n t he m or ni n g d ose of C C X 1 4 0- B f or t his da y, t he s u bject will 
be as ke d t o ta ke t h e d ose 
•  Dr u g acc o u nta bilit y a n d rec o nciliati o n wit h s u bject c o m plete d diaries  
•  A ne w 4- w ee k s u p pl y of b ottles of C C X 1 4 0- B will  be dis pe nse d 
•  A n y c ha n ges i n c o nc o mita nt me dicati o n use will be rec or de d  
•  A n y a d vers e e ve nts will be rec or de d  
•  Pr o vi de s u bject wit h c o nt ai ne r f or c ollecti o n of first m or ni n g v oi d o n t he m o r ni n g of t he 
ne xt visit a n d j u g f or t he 2 4- h o ur uri ne c ollecti o n  
•  After all st u d y pr oce d ures ha ve bee n c o m plete d, t he s u bject will be re mi n d e d t o:  
− C o m plete t heir diar y eac h da y i m me diat el y after eac h d ose  
− C o me t o t he st u d y ce nt er f or t he Wee k 24 st u d y visit 
− St ore t he st u d y me dicati o ns i n a c o ol a n d dr y place acc or di n g t o la b el i nstr ucti o ns f or t he 
d urati o n of t he st u d y 

C C X 1 4 0- B 
 
Pr ot oc ol C L 0 1 1 _ 1 4 0 
 
  
A me n d me nt 4. 0 (2 9 Oct o ber  2 0 1 8) 
C he m o Ce ntr y x, I n c . 
C O N FI D E N TI A L  
Pa ge 7 2  of 9 3  
− C ollect t he first m o r ni n g v oi d t he d a y bef ore t he Wee k 2 4  visit a n d p ut i n t he 
s m aller c o nt ainer  
− C ollect all uri ne f or 2 4 h o urs st arti n g A F T E R t he first m o r ni n g v oi d, i ncl u di n g first 
m o r ni n g v oi d o n t he d a y of t he Wee k 2 4 visit , i n t he bi g j u g. 
− Kee p s peci me ns ref ri ger ate d u ntil t he y are br o u g ht t o t he site f or t he Wee k 2 4 visit.  
7. 1 1.  
St u d y Wee k 2 4 ( D a y 16 9  +/ - 3 d a ys ) - C o nti n ui n g S u bjects O nl y  
T he St u d y Wee k 2 4 visit s h o ul d occ ur wit hi n ± 3 da ys of t he sc h e d ule d dat e. D uri n g t his visit, 
t he f oll o wi n g st u d y pr oce d ures will be perf or me d: 
•  A n a b bre viat e d, s y m pt o m- directe d p h ysical e x a mi nati o n  
•  Vital si g ns ( w ei g ht, te m p erat ur e, bl o o d press ure, h eart rate) after at least 3 mi n utes of rest 
•  1 2 Lea d E C G after at least 3 mi n utes of rest, will be rec or de d a n d assesse d f or a n y cli nicall y 
si g nifica nt a b n or malit y 
•  T he date a n d ti me of t he last d ose of C C X 1 4 0- B pri or t o  c ollecti o n of t he P K sa m ple will be 
rec or d e d 
•  Bl o o d sa m ples will be c ollecte d bef ore d ose a d mi nistrati o n f or ser u m c h e mistr y (i ncl u di n g 
c oa g ulati o n pa nel a n d li pi ds), he mat ol o g y, ser u m pre g na nc y t est (i n w o me n of c hil d beari n g 
p ote ntial), P K (ti me 0 o nl y), plas ma M C P - 1, a n d P D (i ncl u di n g l y m p h oc yt e s u bset) 
meas ure me nts;  r ec or d t h e ti me of bl o o d c ollecti o n 
•  Pr o cess t he first  m or ni n g v oi d uri ne s a m ple c ollecti o n f or q ua ntitati ve uri nal ysis, U P C R , 
U A C R , C yst ati n C, Uri ne M C P- 1, M C P -1/cr eati ni ne rati o a n d uri ne PD assess me nt  
•  Pr o cess t he 2 4 - h o ur uri ne s a m ple c ollecti o n f or q u a ntit ati ve uri n al ysis, U P C R, U A C R, 
C yst ati n C, Uri ne M C P - 1, M C P-1/cre ati ni ne r ati o uri ne P D assess me nt a n d uri ne 
pr otei n e xcreti o n/ d a y  
•  S u bjects will be as ke d t o c o m plete t he S F - 3 6 v 2 a n d E Q- 5 D-5 L. T h e A C T G Brief Peri p heral 
Scree ni n g T o ol will be a d mi nistere d  
•  If t he s u bject has n ot yet ta ke n t he m or ni n g d ose of C C X 1 4 0- B f or t his da y, t he s u bject will 
be as ke d t o ta ke t h e d ose 
•  Dr u g acc o u nta bilit y a n d rec o nciliati o n wit h s u bject c o m plete d diaries  
•  A n y c ha n ges i n c o nc o mita nt me dicati o n use will be rec or de d  
•  A n y a d vers e e ve nts will be rec or de d  
•  Pr o vi de s u bject wit h c o nt ai ner f or c ollecti o n of first m or ni n g v oi d o n t he m o r ni n g of t he 
ne xt visit 
•  After all st u d y pr oce d ures ha ve bee n c o m plete d, t he s u bject wi ll be re mi n d e d t o: 
− C o me t o t he st u d y ce nt er f or t he Wee k 2 8 f oll o w- u p visit  
− Ret ur n all use d a n d u n us e d c o ntai ners of st u d y m e dicati o n al o n g wit h c o m plete d diaries 
f or fi nal dr u g acc o u nt a bilit y 

C C X 1 4 0- B 
 
Pr ot oc ol C L 0 1 1 _ 1 4 0 
 
  
A me n d me nt 4. 0 (2 9 Oct o ber  2 0 1 8) 
C he m o Ce ntr y x, I n c . 
C O N FI D E N TI A L  
Pa ge 7 3  of 9 3  
− O n t he m or ni n g of t he ne xt visit, c ollect t he first m or ni n g v oi d a n d refri ger ate u ntil 
it is br o u g ht t o t he st u d y ce nter 
7. 1 2.  
F oll o w U p visit - St u d y Wee k  1 6 ( D a y 1 1 4 +/ - 3 d a ys  f or 
disc o nti n ui n g s u bjects) a n d Wee k  2 8 ( D a y 1 9 7  +/ - 3 d a ys  f or 
c o nti n ui n g s u bjects ) - ( See Secti o n 7.1 3 f or P K eli mi n ati o n 
g ui deli nes)  
T h e f oll o w-u p  visit s h o ul d occ ur wit hi n ± 3 da ys of t he sc he d ule d d ate. D uri n g t his visit, t he 
f oll o wi n g st u d y pr oce d ur es will be perf or me d: 
•  A n a b bre viat e d, s y m pt o m- directe d p h ysical e x a mi nati o n  
•  Vital si g ns ( w ei g ht, te m p erat ur e, bl o o d press ure, h eart rate) after at least 3 mi n utes of rest 
•  1 2 Lea d E C G after at least 3 mi n utes of rest, will be rec or de d a n d assesse d f or a n y cli nicall y 
si g nifica nt a b n or malit y 
•  Bl o o d sa m ples will be c ollecte d f or ser u m c he mistr y (i ncl u di n g c oa g ulati o n pa nel a n d 
li pi ds), he mat ol o g y, ser u m pre g n a nc y test (i n w o me n of c hil d beari n g p ot e ntial), P K (ti me 0 
o nl y), plas ma M C P - 1, a n d P D (i ncl u di n g l y m p h oc yt e s u bset) meas ure me nts; rec or d t he ti me 
of bl o o d c ollecti o n 
•  Pr o cess t he first  m or ni n g v oi d uri ne s a m ple c ollecti o n f or q ua ntitati ve uri nal ysis, UP C R , 
U A C R , C yst ati n C, Uri ne M C P- 1, M C P -1/cr eati ni ne rati o a n d uri ne P D assess me nt  
•  S u bjects will be as ke d t o c o m plete t he S F - 3 6 v 2 a n d E Q- 5 D-5 L.  
•  T he A C T G Brief Peri p heral Scree ni n g T o ol will b e a d mi nistere d  
•  A n y c ha n ges i n c o nc o mita nt me dicati o n use will be  rec or de d 
•  A n y a d vers e e ve nts will be rec or de d  
7. 1 3.  
P K Eli mi n ati o n Visits  
U p o n disc o nti n uati o n of treat me nt f or a n y reas o n , i ncl u di n g e n d of st u d y, a sa m ple of w h ole 
bl o o d s h o ul d be c ollecte d f or assess me nt of eli mi nati o n at 2, 7 a n d 1 4 da ys after disc o nti n uati o n. 
Rec or d t he ti me of bl o o d c ollecti o n. 
After all st u d y pr oce d ures ha ve bee n c o m plete d, t he s u bject will be disc har ge d fr o m t he st u d y. 
T he s u bject’s c o n diti o n will be e val uate d b y t he I n vesti gat or at t he e n d of t he cli nical trial ( Wee k 
2 8) a n d a p pr o priate sta n d ar d of care m e dical treat me nt s h o ul d be i m ple me nte d f or all s u bjects 
as nee de d.  
7. 1 4.  
E arl y Ter mi n ati o n Visit  ( See Secti o n 7. 1 4 f or P K eli mi n ati o n 
g ui deli nes)  
If a s u bject will be wit h dra w n earl y fr o m t he st u d y, t he f oll o wi n g ter mi nati o n pr oce d ures s h o ul d 
be c o m plete d w h e ne ver p ossi ble: 
•  W he ne ver p ossi ble, t he s u bject will be as ke d t o c ollect all uri ne f or t he 2 4 h o urs after 
t he l ast d ose of st u d y dr u g. 

C C X 1 4 0- B 
 
Pr ot oc ol C L 0 1 1 _ 1 4 0 
 
  
A me n d me nt 4. 0 (2 9 Oct o ber  2 0 1 8) 
C he m o Ce ntr y x, I n c . 
C O N FI D E N TI A L  
Pa ge 7 4  of 9 3  
•  A n a b bre viat e d, s y m pt o m- directe d p h ysical e x a mi nati o n  
•  Vital si g ns ( w ei g ht, te m p erat ur e, bl o o d press ure, h ea rt rate) after at least 3 mi n utes of rest 
•  Bl o o d sa m ples a n d uri n e will be c ollecte d f or s hi p me nt t o t he ce ntral la b orat or y f or ser u m 
c he mistr y, h e mat ol o g y, ser u m pre g n a nc y test (i n w o me n of c hil d beari n g p ote ntial)  a n d 
q ua ntitati ve uri nal ysis  
•  Nee d f or dial ysis will be rec or d e d  
•  If a v ail a ble, pr ocess t he first m or ni n g v oi d uri ne sa m ple c ollecti o n f or U P C R a n d U A C R 
assess me nt  
•  If a v ail a ble, pr ocess t he 2 4- h o ur uri ne s a m ple f or q u a ntit ati ve uri n al ysis, U P C R, 
U A C R, C yst ati n C, Uri ne M C P - 1, M C P-1/cre ati ni ne r ati o uri ne P D assess me nt a n d 
uri ne pr otei n e xcreti o n/ d a y  
•  1 2 Lea d E C G after at least 3 mi n utes of rest, will be rec or de d a n d assesse d f or a n y cli nicall y 
si g nifica nt a b n or malit y 
•  Dr u g acc o u nta bilit y a n d rec o nciliati o n wit h s u bject c o m plete d diaries  
•  A n y c ha n ges i n c o nc o mita nt me dicati o n use , i ncl u di n g plas ma t hera p y re gi me n, will be 
rec or d e d 
•  A n y a d vers e e ve nts will be rec or de d.  If a n a d vers e e ve nt re mai ns u nres ol v e d at t he 
c o ncl usi o n of t he st u d y, a cli nical assess me nt will be ma de b y t he I n v esti gat or a n d t he 
S p o ns or’s Me dical M o nit or t o deter mi ne w h et her c o nti n ue d f oll o w- u p of t he a d vers e e v e nt is 
warr a nte d  
•  A fi nal safet y f oll o w - u p visit will be sc he d ule d f or 4 wee ks after s u bj ect disc o nti n ues st u d y 
dr u g 
8.  
S T U D Y A S S E S S M E N T S  
8. 1.  
Effic ac y Assess me nts  
8. 1. 1.  
Uri n ar y Me as ure me nts  
Eff icac y will be e val u ate d b y ass ess me nt of uri ne pr otei n:creati ni ne rati o ( U P C R), uri ne 
alb u mi n:creati ni ne rati o ( U A C R), a n d esti mate d gl o mer ular filtrati o n rate (e G F R)  usi n g t he 
C K D -E PI C ystati n C e q u ati o n , C K D- E PI Creati ni ne e q uati o n, C K D-E PI Creati ni ne -C y stati n C 
e q uati o n a n d M D R D Creati ni ne e q uati o n assesse d at Wee ks 1 2 a n d  2 4. 
T he  uri ne sa m ples , first m o r ni n g v oi d a n d 2 4-h o ur uri ne s a m ple  will be se nt t o t he ce ntral 
la b orat or y f or a nal ysis. T he f oll o wi n g a nal yses will be perf or me d acc or di n g t o t he Ti me a n d 
E ve nts Ta ble : 
•  Uri ne pr otei n t o cr eati ni n e rati o ( U P C R): t he uri ne pr otei n creati ni ne rati o is t he rati o of t he 
uri ne pr otei n c o n ce ntrati o n t o t he uri ne creati ni ne c o nce ntrati o n 
•  
Uri ne al b u mi n t o creati ni ne rati o ( U A C R): t he uri ne al b u mi n creati ni ne rati o  is t he rati o of 
t he uri ne al b u mi n c o nce ntrati o n t o t he uri ne creati ni ne c o nce ntrati o n U ri nal ysis i ncl u di n g 

C C X 1 4 0- B 
 
Pr ot oc ol C L 0 1 1 _ 1 4 0 
 
  
A me n d me nt 4. 0 (2 9 Oct o ber  2 0 1 8) 
C he m o Ce ntr y x, I n c . 
C O N FI D E N TI A L  
Pa ge 7 5  of 9 3  
bl o o d, pr otei n, a n d nitrites; if p ositi ve f or bl o o d, pr otei n, or nitrites, a micr osc o pic assess me nt f or 
R B C casts a n d R B C c o u nt will be perf or me d; 
Micr osc o pic r e vie w is tri g gere d if a uri nar y di psti c k test is p ositi ve f or bl o o d , nitrite, or pr otei n. 
W he n micr osc o p y is perf or me d, he mat uria w ill be cate g orize d as f oll o ws: N o ne, Occasi o nal 
( Occ), 1 - 2, 3 - 5, 6 - 9, 1 0 - 1 5, 1 6 - 2 9, 3 0 - 4 9, 5 0 - 7 5, a n d > 7 5 R B Cs per hi g h p o wer fiel d. 
8. 1. 2.  
Esti m at e d Gl o mer ul ar Filtr ati o n R ate  
T he esti mate d gl o mer ular filtrati o n rate (e G F R) will be calc ulate d at all a p plica ble st u d y visits 
usi n g t he C K D -E PI Cr eati ni n e-e q uati o n (Sc h wartz GJ, et al. 2 0 1 6 , Selistre L et al 2 0 1 6 ), t he 
C K D -E PI C ystati n C  (D har ni d har k a V R, et al, 2 0 0 2 ) e q uati o n t he C K D-E PI Creati ni ne - C yst ati n 
C e q uati o n ( Ste ve ns et al ., 2 0 0 8) a n d t he M D R D Creati ni ne e q uati o n ( Le v e y et al. 1 9 9 9 , Le v e y 
et al. 2 0 0 6). 
8. 1. 3.  
Ser u m Al b u mi n  
T he ser u m al b u mi n le vel pr o vi des a n i n de x of t he de gree of pr otei n l oss. H y p oal b u mi ne mia ma y 
be see n i n s u bject s wit h s e vere pr otei n uria a n d t he ne p hr otic s y n dr o me. 
8. 1. 4.  
He alt h - Rel ate d Q u alit y of Life a n d A C T G B P N S T Assess me nts  
T he S F - 3 6 v 2 a n d E Q -5 D -5 L  a n d A C T G B P N S T will be c o m plete d b y st u d y s ubject s at visits 
s pecifie d i n t he Ti me a n d E ve nts Ta ble  t o meas ure c ha n ges fr o m baseli ne i n healt h-rel ate d 
q ualit y of life  a n d t he A C T G B P N S T will be c o m plete d b y t he st u d y s u bject a n d  t he st u d y d oct or 
t o assess c ha n ges i n n e ur o pat h y. Pr o v e n tra nslati o ns will be use d f or n o n- E n glis h s pea ki n g 
s u bjects, w he ne v er p ossi ble. A n a d mi nistrat or will facilitate c o m pleti o n of t he S F - 3 6 a n d E Q-
5 D- 5 L q uesti o n naires b y t he s u bjects, b ut will n ot c o m plete t he f or ms f or t he s u bjects. T he 
a d mi nistrat or will esta blis h a ra p p ort wit h t he s u bj ect, e m p hasize t he i m p orta nce of c o m pleti n g 
t he f or m, a n d ser ve t o a ns wer q uesti o ns a n d a d dress c o ncer ns. T h e q uesti o n naires s h o ul d be 
c o m plete d b y s u bject s bef ore seei n g th e I n vesti gat or at t he visit.  
8. 2.  
S afet y Assess me nts  
8. 2. 1.  
P h ysic al E x a mi n ati o ns, Vit al Si g ns , a n d E C Gs 
A c o m plete p h ysical e x a mi nati o n (i ncl u di n g e val uati o n of ge neral a p peara nce/ me ntal stat us, 
H E E N T [ hea d, e yes, ears, n ose, t hr oat], a n d t he f oll o wi n g b o d y s yst e ms: der mat ol o gic, 
car di o vas c ular, r es pirat or y, gastr oi ntesti nal, m usc ul os keletal a n d ne ur ol o gic) f or safet y, 
assess me nt s will be perf or me d at visits i n dicate d i n t he Ti me a n d E ve nts T a ble . 
B o d y wei g ht will be meas ure d as part of t he p h ysi cal e x a mi nati o ns . Hei g ht nee ds t o be rec or d e d 
at scree ni n g o nl y. B MI will be calc ulate d  fr o m t he b o d y w ei g ht a n d hei g ht meas ure me nts. 
Vital si g ns will be meas ure d d uri n g scree ni n g a n d o n eac h sc h e d ule d st u d y da y as i n dicate d i n 
t he Ti me a n d E ve nts T a ble. Bl o o d press ure, p ulse rate, a n d b o d y te m p erat ure will be meas ure d. 
All vital si g ns assess me nts will be perf or me d after t he s u bject has rest e d f or at least t hree 
mi n utes , w hile s u bject is seate d. 
A baseli ne 1 2 -lea d E C G, after r esti n g f or at least 3 mi n utes, will be perf or me d at scree ni n g a n d 
assesse d f or a n y cli nicall y si g nifica nt a b n or malitie s. All a b n or malities will be rec or de d i n t he 

C C X 1 4 0- B 
 
Pr ot oc ol C L 0 1 1 _ 1 4 0 
 
  
A me n d me nt 4. 0 (2 9 Oct o ber  2 0 1 8) 
C he m o Ce ntr y x, I n c . 
C O N FI D E N TI A L  
Pa ge 7 6  of 9 3  
E D C s yste m.  Ass u mi n g t he E C G a b n or malit y d oes n ot precl u de st u d y e ntr y, a n E C G m a y be 
re peat e d as cli nicall y i n dicate d. 
8. 2. 2.  
Cli nic al S af et y L a b or at or y Assess me nts 
T he f oll o wi n g t ests will be perf or me d at t he visits i de ntifie d i n t he Ti me a n d E ve nts Ta ble . 
•  He mat ol o g y: h e m o gl o bi n, he mat ocrit, R B C  c o u nt, W B C  c o u nt wit h differe ntial, platelet 
c o u nt, mea n cell he m o gl o bi n , mea n cell he m o gl o bi n c o nce ntrati o n, mea n c or p usc ular 
v ol u me, retic ul oc yte c o u nt a n d sc hist oc ytes ; 
•  Ser u m C he mistr y: li ver p a nel (t otal , direct a n d i n direct  bilir u bi n, lactate d e h y dr o ge nas e 
[ L D H], A S T, A L T), re n al pa nel ( B U N, creati ni ne), creati ne p h os p h o ki n ase ( C P K), al b u mi n, 
s o di u m, p otassi u m, ma g nesi u m, bicar b o nate, c hl ori de, calci u m, i n or ga nic p h os p h or us, 
gl uc ose, t otal pr otei n , al k ali ne p h os p hatase, uri c aci d, ser u m a m ylase, s er u m li pase, a n d 
c ystati n C ; at s pecifie d visits, c oa g ulati o n pa n el ( P T, P T T, I N R), li pi d pa n el ( H D L, L D L, 
Tri gl yceri des, T otal C h ol ester ol) will be i ncl u de d  
•  Uri nal ysis: At t he ce ntral la b orat or y, nitrite, bl o o d, a n d pr otei n, will be test e d. If p ositi ve , 
micr osc o p y will be perf or me d;  
•  Vir ol o g y ( m eas ur e d o nl y at scree ni n g): he patitis B s urface a nti ge n, he p atitis C a nti b o dies, 
HI V 1 a n d 2 a nti b o dies; vir ol o g y tests d o ne wit hi n 6 wee ks pri or t o scree ni n g are acce pt a ble 
f or eli gi bilit y assess me nt; 
•  T B scr ee n: O nl y i nterfer o n γ releas e assa y (I G R A) d o ne wit hi n 6 wee ks pri or t o scree ni n g is 
all o we d f or eli gi bilit y ass ess me nt.  
8. 2. 3.  
A d verse E ve nts  
A n a d vers e e ve nt ( A E) is defi ne d as a n y u nt o war d me dical occ urre n ce ass o ciate d wit h t he use of 
a dr u g i n h u ma ns, w het h er or n ot c o nsi dere d dr u g relate d. A n a d vers e e ve nt c o ul d t heref ore be 
a n y u nfa v ora ble a n d/ or u ni nte n de d si g n (i n cl u di n g a b n or mal la b orat or y fi n di n gs), s y m pt o m, or 
disease te m p orall y ass o ciate d wit h t he use of t he dr u g, w het her or n ot c o nsi dere d relate d t o t he 
d r u g. T his d efi niti o n i ncl u des i nterc urre nt ill nesses or i nj uries, a n d e x acer b ati o n of pre-e xisti n g 
c o n diti o ns. 
A n u ne x pecte d a d verse e ve nt is a n a d vers e e ve nt t hat is n ot i de ntifie d i n nat ure, se verit y, or 
fre q ue n c y i n t he c urre nt I n vesti gat or’s Br oc h ure, or t hat is of great er se v erit y t ha n e x pecte d 
base d o n t he i nf or mati o n i n t he Refere n ce Safet y I nf or mati o n listi n g wit hi n t he I n v esti gat or’s 
Br oc h ure.  
All a d verse e ve nts occ urri n g i n s u bject s w h o ha v e bee n ra n d o mize d t o treat me nt will be rec or d e d 
i n t he E D C s yste m a n d will be re p orte d i n acc or d a nce wit h re g ulat or y re q uire me nts. A d verse 
e ve nts re p ort e d pri or t o c o m me nce me nt of a d mi nistrati o n of st u d y me dicati o n will be c o nsi dere d 
pre -treat me nt e ve nts. If s u bject st o ps ta ki n g C C X 1 4 0- B/ place b o, a d v erse e ve nt re p orti n g s h o ul d 
be c o nti n ue d as l o n g as st u d y is acti ve. 
All a d verse e ve nts will be m o nit ore d u ntil res ol uti o n or, if t he a d verse e v e nt is deter mi ne d t o be 
c hr o nic, u ntil a ca us e is i de ntifie d. If a n a d verse e ve nt re mai ns u nres ol v e d at t he c o ncl usi o n of 
t he st u d y, a cli nical assess me nt will be ma de b y t h e I n vesti gat or a n d t h e S p o ns or’s Me dical 
M o nit or t o deter mi ne w h et her c o nti n ue d f oll o w- u p of t he a d verse e v e nt is warra nte d.  

C C X 1 4 0- B 
 
Pr ot oc ol C L 0 1 1 _ 1 4 0 
 
  
A me n d me nt 4. 0 (2 9 Oct o ber  2 0 1 8) 
C he m o Ce ntr y x, I n c . 
C O N FI D E N TI A L  
Pa ge 7 7  of 9 3  
8. 2. 3. 1.  
A d verse E ve nt Se verit y Assess me nt  
T he se verit y of eac h a d v erse e v e nt will be deter m i ne d b y t he i n v esti gat or usi n g t he f oll o wi n g 
scale: 
•  Mil d ( Gra de 1):  n o li mitati o n of us ual acti vities  
•  M o derate ( Gra d e 2):  s o me  li mitati o n of us ual acti vities 
•  Se vere ( Gra d e 3):  i na bilit y t o carr y o ut us ual acti vities  
•  Lif e -t hreate ni n g ( Gra de 4):  a n i m me diate ris k of deat h 
•  Deat h ( Gra de 5)  
8. 2. 3. 2.  
C a us alit y Assess me nt  
T h e relati o ns hi p of st u d y dr u g ( C C X 1 4 0- B/ place b o)  t o a n a d verse e v e nt will be deter mi ne d b y 
t he I n v esti gat or a n d S p o ns or base d o n t he f oll o wi n g defi niti o ns: 
•  Pr o ba bl y N ot Relat e d:  t he a d vers e e v e nt was m ore li kel y e x plai ne d b y ca uses ot her t ha n 
st u d y dr u g ( C C X 1 4 0-B/ place b o) . 
•  P ossi bl y Relate d:  t here is e vi de nce f or a reas o n a ble p ossi bilit y t hat st u d y dr u g ( C C X 1 4 0-
B/ place b o)  a d mi nistrati o n ca use d t he a d vers e e ve nt . 
8. 2. 3. 3.  
Seri o us A d verse E ve nts  
A seri o us a d ver se e v e nt ( S A E) is defi ne d as a n y u nt o war d me dical o cc urre nce t hat at a n y d os e: 
•  Res ults i n deat h ; 
•  Is life-t hreate ni n g (i.e., t h e s u bject was, i n t he o pi ni o n of t he I n vesti gat or, at i m me diate ris k 
of deat h fr o m t he e ve nt as it occ urre d ); 
•  Re q uires or pr ol o n gs h os pitalizati o n ; 
•  Res ults i n persiste nt or si g nifica nt disa bilit y or i nca pacit y ; 
•  Is a c o n ge nital a n o mal y or birt h defect; 
•  Is a n i m p orta nt a n d si g nifica nt me dical e ve nt t hat, base d o n a p pr o priate me dical j u d g me nt, 
ma y je o p ar dize t he s u bject a n d/ or 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 ot her o ut c o mes defi ni n g s eri o us. 
Electi ve s ur ger y alrea d y k n o w n d uri n g s cree ni n g t o occ ur i n t he c o urse of t he st u d y, a n d electi ve 
h os pitalizati o ns f or c o n ve nie nce of t he s u bject w hic h are clearl y u nrelate d t o a n y m e dical 
c o n diti o n, a n d a gree d u p o n bet wee n t he I n vesti gat or a n d t he s u bject, will n ot ha ve t o be re p orte d 
as S A Es. H os pital sta ys o n t he e ve ni n g of D a y 1 ( or be y o n d) will als o n ot be c o nsi dere d a n S A E, 
u nless ot her S A E criteri a are met.  
8. 2. 3. 4.  
S A R s a n d S U S A Rs 
A seri o us a d verse r eacti o n ( S A R) is defi ne d as a n S A E f or w hic h t here is at least a reas o na ble 
p ossi bilit y t hat t he st u d y dr u g ( C C X 1 4 0-B/ place b o) ca use d t h e e ve nt . 

C C X 1 4 0- B 
 
Pr ot oc ol C L 0 1 1 _ 1 4 0 
 
  
A me n d me nt 4. 0 (2 9 Oct o ber  2 0 1 8) 
C he m o Ce ntr y x, I n c . 
C O N FI D E N TI A L  
Pa ge 7 8  of 9 3  
A s us pecte d u ne x pecte d seri o us a d vers e reacti o n ( S U S A R) is defi ne d as a n S A E f or w hic h t here 
is at least a reas o na ble p ossi bilit y t hat t he st u d y dr u g ( C C X 1 4 0- B/ place b o) ca use d t he e ve nt, a n d 
t he S A E is ‘ u ne x pecte d’, i.e., n ot descri be d i n ter ms of nat ure, se v erit y, or fre q ue n c y i n t he 
Refere n ce Safet y I nf or mati o n wit hi n t he  curre nt I n vesti gat or’s Br oc h ure. 
‘ Reas o na ble p ossi bilit y’ mea ns t hat t here is e vi d e nce t o s u g gest a ca usal relati o ns hi p bet wee n t he 
st u d y dr u g a n d t h e a d verse e ve nt. Wit hi n t he re p orti n g re q uire me nts, t he f oll o wi n g e x a m ples 
ill ustrate t he t y pes of e vi de nce t hat w o ul d s u g gest a ca usal relati o ns hi p: 
•  A si n gle o cc urre nce of a n e ve nt t hat is u nc o m m o n a n d k n o w n t o be str o n gl y ass oci ate d 
wit h dr u g e x p os ure (e. g., a n gi o e de ma, h e patic i nj ur y, Ste v e ns-J o h ns o n S y n dr o me); 
•  O ne or m ore o cc urre n ces of a n e ve nt t hat is n ot c o m m o nl y  ass ociate d wit h dr u g 
e x p os ure, b ut is ot her wise u nc o m m o n i n t he p o p ulati o n e x p ose d t o t he dr u g (e. g., te n d o n 
r u pt ure); 
•  A n a g gre gate a n al ysis of s pecific e v e nts o bser ve d i n a cli nical trial (s uc h as k n o w n 
c o nse q ue nces of t he u n d erl yi n g disease or c o n diti o n u n der i n vesti gati o n or ot her e ve nts 
t hat c o m m o nl y occ ur i n t he st u d y p o p ulati o n i n de pe n de nt of dr u g t hera p y) t hat i n dicates 
t h ose e ve nts occ ur m ore fre q ue ntl y i n t he dr u g treat me nt gr o u p t h a n i n a c o nc urre nt or 
hist orical c o ntr ol gr o u p. 
E ve nts relate d t o t he u n d erl yi n g disease, s uc h as rela pses  or w orse ni n g of disease  will n ot be 
c o nsi dere d as S U S A Rs, u nless t here is a reas o na ble p ossi bilit y t hat C C X 1 4 0- B use was 
ass ociate d wit h t hese e ve nts.  
8. 2. 3. 5.  
L a b or at or y A b n or m alities 
Safet y l a b orat or y t ests ar e perf or me d f re q ue ntl y o ver t he c o urse of t he st u d y. La b orat or y re p orts 
wit h a b n or mal fi n di n gs will be re vie we d b y t h e I n vesti gat or a n d t he Me di cal M o nit or. T he 
I n v esti gat or will be a d vis e d t o f oll o w s u bjects wit h n ota bl y hi g h li ver pa n el tests cl osel y a n d t o 
ta ke a p pro priate ste ps, s u c h as p ote ntiall y dis c o nti n ui n g st u d y me dicati o n, i n case t he 
a b n or malities persist.  
8. 2. 3. 6.  
Pre g n a ncies  
A n y pre g na n cies t hat occ ur i n fe male s u bjects or p art ners of m ale st u d y s u bjects m ust be 
re p orte d t o Me d p ace Cli nical Safet y  wit hi n 2 4 h o urs of a w are n ess t o t he c o ntacts details o utli ne d 
i n Secti o n  8. 2. 5 . A n e x p os ure i n Uter o f or m will t he n be f or war d e d f or c o m pleti o n as s o o n as 
p ossi ble. All pre g n a ncies m ust be f oll o we d u p u ntil c o ncl usi o n a n d t he o ut c o me of t he 
pre g na nc y re p ort e d wit hi n 2 4 h o urs of a w are n ess t o Me d pace Cli nical Safet y . S h o ul d t he 
o utc o me of t he pr e g na nc y meet criteria f or a n S A E, t his s h o ul d be re p orte d as i n dicate d i n 
Secti o n  8. 2. 5 . 
8. 2. 4.  
S peci al  Sit u ati o n Re p orti n g  
S pecial sit uati o n re p orts i ncl u de re p orts of o ver d os e, mis use a n d a b use of t he I M P: 
•  
O ver d ose: r efers t o t he a d mi nistrati o n of a q ua ntit y of a me dici nal pr o d u ct gi ve n p er 
a d mi nistrati o n or c u m ulati vel y (acci de nt all y or i nt e nti o nall y),  w hi c h is a b o ve t he ma xi m u m 
rec o m me n de d d os e acc ordi n g t o t he pr ot oc ol. Cli nical j u d ge me nt s h o ul d al wa ys be a p plie d. I n 

C C X 1 4 0- B 
 
Pr ot oc ol C L 0 1 1 _ 1 4 0 
 
  
A me n d me nt 4. 0 (2 9 Oct o ber  2 0 1 8) 
C he m o Ce ntr y x, I n c . 
C O N FI D E N TI A L  
Pa ge 7 9  of 9 3  
cases of a discre p a nc y i n t he dr u g acc o u nta bilit y, o ver d ose will be esta blis h e d o nl y w h e n it is 
clear t hat t he s u bj ect has ta ke n e x cess d ose(s) or t he i n vesti gat or has reas o n t o s us pect t hat t he 
s u bject has ta ke n a d diti o nal d ose (s). 
•  
Mis use: refers t o sit uati o ns w here t he m e dici nal pr o d uct is i nte nti o nall y a n d i na p pr o priatel y 
use d n ot i n a wa y t hat is n ot i n acc or da n ce wit h t h e pr ot oc ol i nstr ucti o ns or l ocal prescri bi n g 
i nf or mati o n a n d ma y be acc o m pa ni e d b y har mf ul p h ysical a n d/ or ps yc h ol o gical effects. 
•  
A b use: is defi ne d as p ersiste nt or s p ora dic, i nte nti o nal e x cessi ve use of a m e dici nal pr o d uct, 
w hic h is acc o m pa ni e d b y har mf ul p h ysical  or ps yc h ol o gical effects.  
•  
Me dicati o n Err or: M e dicati o n err or is a n y u ni nte nti o nal err or i n t he prescri bi n g, dis pe nsi n g 
or a d mi nistrati o n of a me dici nal pr o d uct b y a healt hcare pr ofessi o nal, p atie nt or c o ns u mer, 
res pecti vel y. T h e a d mi nistrati o n or c o ns u m pti o n of t he u nassi g ne d treat me nt a n d a d mi nistrati o n 
of a n e x pire d pr o d uct are al wa ys re p orta ble as m e dicati o n err ors, cases of s u bjects missi n g d oses 
of i n vesti gati o nal pr o d u ct are n ot c o nsi dere d re p orta ble as me dicati o n err or. 
All s pecial sit uati o n re p or ts m ust be re p orte d o n t he s pecial sit uati o ns re p ort f or m a n d f or war d e d 
t o Me d pace Cli nical Saf et y wit hi n 2 4 h o urs. 
All a d verse e ve nts ( A Es) ass ociate d wit h t hese s p ecial sit uati o n re p orts s h o ul d be re p orte d as 
A Es or S A Es at t he sa me ti me usi n g t he A E e C R F a n d/ or t he S A E re p ort f or m. Details of t he 
s y m pt o ms a n d si g ns, cli nical ma na ge me nt a n d o utc o me will be re p orte d, w he n a vaila ble. 
8. 2. 5.  
Seri o us A d verse E ve nt  Re p orti n g  
A n y s eri o us a d verse e v e nt occ urri n g fr o m scree ni n g t hr o u g h t he e n d of t he treat me nt peri o d, 
w het her or n ot c o nsi dere d st u d y rel ate d, will be re p orte d i m me diatel y ( wit hi n 2 4 h o urs) t o t he 
Safet y t ea m. Re p orti n g is d o ne b y c o m pleti n g t h e S A E f or m i n t he E D C  s yste m. If it is n ot 
p ossi ble t o access t he E D C s yste m, t he I n vesti gat or will se n d a n e mail t o t he a p pr o pri ate re gi o n al 
cli nical safet y mail b o x (see i nf or mati o n bel o w) or call t heir re gi o nal S A E h otli ne a n d fa x t he 
c o m plete d S A E re p ort f or m wit hi n 2 4 h o urs of a w are ness. W he n access t o t he E D C s yste m is 
res u me d, t he S A E i nf or m ati o n s h o ul d be e ntere d as s o o n as p ossi ble. C o ntact details are as 
f oll o ws: 
Me d pace Cli nical Saf et y  
 
 
 
A n y m e di cati o n or ot her t hera pe utic meas ures us e d t o treat t he e ve nt, i n a d diti o n t o t he o utc o me 
of t he a d verse e v e nt , will be rec or de d i n t he E D C s yste m. 
F oll o w- U p Re p orts 
T he i n vesti gat or m ust c o nti n ue t o f oll o w t he s u bject u ntil t he S A E has s u bsi de d or u ntil t he 
c o n diti o n bec o mes c hr o nic i n nat ure, sta bilizes (i n t he case of persiste nt i m pair me nt) , or t he 
s u bject dies.  
Wit hi n 2 4 h o urs of recei pt of f oll o w- u p i nf or mati o n, t he i n vesti gat or m ust u p date t he S A E f or m 
electr o nicall y i n t he E D C s yste m f or t h e st u d y a n d s u b mit a n y s u p p orti n g d oc u me ntati o n (e. g., 

C C X 1 4 0- B 
 
Pr ot oc ol C L 0 1 1 _ 1 4 0 
 
  
A me n d me nt 4. 0 (2 9 Oct o ber  2 0 1 8) 
C he m o Ce ntr y x, I n c . 
C O N FI D E N TI A L  
Pa ge 8 0  of 9 3  
s u bject disc har ge s u m mar y or a ut o ps y re p orts) t o Me d pace Cli nical Safet y via fa x or e -mail. If it 
is n ot p ossi ble t o access t he E D C s yste m, refer t o t he pr oce d ures o utli ne d a b o ve f or i nitial 
re p orti n g of S A Es. 
S A E re p orti n g s h o ul d c o nti n ue f or 2 8 da ys after st o p pi n g st u d y dr u g . T he S p o ns or s h o ul d be 
n otifie d if t he i n vesti gat or bec o mes a ware of a n y S A E t hat occ urs after t he e n d of t he A E 
re p orti n g peri o d, if t he y belie ve t hat a n ev e nt is relate d t o t he pri or st u d y dr u g treat me nt.  
T he S p o ns or or its re pr ese ntati ves will re p ort all S U S A Rs t o nati o nal healt h a ut h orities a n d 
et hics c o m mittees i n a n e x pe dite d ma n ner i n acc or da nce wit h Cli nical Trial Directi ve, Articles 
1 6 a n d 1 7, I C H G ui deli n e E 2 A a n d E N T R C T 3 o n t he re p orti n g of all S U S A Rs. 
8. 3.  
P h ar m ac o ki netic Assess me nts  
C o nce ntrati o ns of C C X 1 4 0 will be deter mi ne d i n plas ma fr o m 4. 0 ml bl o o d sa m ples c ollecte d i n 
K 2E D T A  t u bes acc or di n g t o t he sc h e d ule i n t he Ti me a n d E ve nts Ta ble . T he f oll owi n g 
para meters will be deter mi ne d, w here p ossi ble: 
  
Cma x    
Ma xi m u m plas ma c o nce ntrati o n  
  
Tma x    
Ti me of ma xi m u m plas m a c o nce ntrati o n 
A U C 0- 6 
Area u n d er t he plas ma c o nce ntrati o n -ti me c ur ve fr o m Ti me 0 t o H o ur 6 o n Da y 1 
a n d Da y 1 5 
C mi n  
Tr o u g h l e vel plas ma c o n ce ntrati o ns at P K visits ot her t ha n o n Da ys 1 & 1 5  
O n Da y s 1 a n d 1 5, sa m pl es will be ta ke n at pre- d ose, 0. 5, 1, 2, 3, 4, a n d 6 h o urs after d osi n g. T h e 
bl o o d sa m ples c ollecte d o n t he ot her rel e va nt st u d y da ys n ee d t o be c ollect e d pri or t o ta ki n g t he 
C C X 1 4 0- B / place b o d os e. 
T he relati o ns hi p bet wee n P K a n d ser u m al b u mi n a n d bet wee n P K a n d U P C R will be e x pl ore d, 
w here p ossi ble. 
T otal plas ma c o nce ntrati o ns of C C X 1 4 0 will be deter mi ne d usi n g vali date d a nal yti cal met h o ds. 
T hese plas ma sa m ples m a y als o be use d t o meas ure ot her mar kers ass ociat e d wit h F S G S.  
8. 4.  
E x pl or at or y P h ar m ac o d y n a mic Assess me nts   
Bl o o d sa m ples ( plas ma a n d ser u m) a n d uri ne s a m ples f or P D meas ure me nt will be c ollecte d 
acc or di n g t o t he s c he d ule i n t he Ti me a n d E ve nts Ta ble . 
E x pl orat or y assess me nts ma y i ncl u d e: 
•  Pr ofile of F S G S relat e d ge ne m utati o ns; 
•  C ha n ge fr o m bas eli ne i n uri nar y M C P- 1; creati ni ne rati o;  
•  C ha n ge fr o m bas eli ne i n uri nar y al b u mi n t o creati ni ne rati o ( U A C R) 
•  C ha n ge fr o m bas eli ne i n bl o o d m o n oc ytes, T, B a n d N K cells; 
•  C ha n ge fr o m bas eli ne i n  ot her uri nar y a n d bl o o d e x pl orat or y mar kers p ote ntiall y ass ociat e d 
wit h acti vit y of F S G S or i n hi biti o n of t he C C R 2/ M C P- 1 pat h wa ys. T h ese ma y i ncl u d e 
meas ure me nt of:  

C C X 1 4 0- B 
 
Pr ot oc ol C L 0 1 1 _ 1 4 0 
 
  
A me n d me nt 4. 0 (2 9 Oct o ber  2 0 1 8) 
C he m o Ce ntr y x, I n c . 
C O N FI D E N TI A L  
Pa ge 8 1  of 9 3  
o  Tra nsf or mi n g gr o wt h fact or -beta ( T G F - B), c o n necti ve tiss ue gr o wt h fact or ( C T G F), N-
acet yl gl uc osa mi ne ( N A G), β 2 micr o gl o b uli n, a di p o necti n, C-reacti ve pr otei n ( C R P), 
c ystati n C, s y na pt o p o di n, ne utr o p hil gel ati nase- ass ociate d li p ocali n ( N G A L), li ver -
fatt y aci d- bi n di n g pr otei n ( L F A B P), ki d ne y i nj ur y m olec ule-1( KI M - 1), i ntact P T H, 
le pti n, reisti n, c he meri n, reti n ol bi n di n g pr otei n 4 ( R B P- 4), M C P- 1, I L -1 β, I L - 6, 
s u P A R, mi R- 1 9 3a, C L C F- 1 a n d T N F-α.  
8. 5.  
St u d y C o m pleti o n a n d Wit h dr a w al  
T he Wee k 1 6 visit will be t he last St u d y Da y f or all s u bjects, e x ce pt f or t h ose partici pati n g i n t he 
O pe n -La b el E xte n si o n (last visit will be Wee k 2 8). Pr oce d ures f or t his da y will be c o m plete d per 
t he Ti me a n d E ve nts Ta ble . Eac h s u bject’s c o n diti o n will be e val uate d b y t he I n vesti gat or at t he 
e n d of t he cli nical trial a n d a p pr o priate sta n d ar d of care me dical treat me nt will be pr o vi de d t o all 
s u bjects as nee d e d. F or earl y wit h dra w als fr o m t he st u d y, t he pr oce d ures f or t he Earl y 
Ter mi nati o n visit  will be perf or me d , w he n p ossi bl e (see Secti o n 7. 1 4 ). 
T he cli nical trial will be t er mi nate d earl y if t here is a safet y c o n cer n t hat ca n n ot be a d dress e d b y 
a m o dificati o n of t he pr ot oc ol. 
9.  
S T A TI S TI C S 
Details of t he statistical a nal ysis will be pr o vi de d i n a se parate statistical a n al ysis pla n ( S A P), 
w hic h will be writte n, fi n alize d, a n d a p pr o ve d pri or t o data base l o c k a n d will be i ncl u de d i n t he 
Cli nical St u d y Re p ort ( C S R) f or t his pr ot oc ol. T he S A P will s u perse de t he statistical a nal ysis 
met h o ds descri be d i n t his cli nical pr ot oc ol. A n y de viati o n fr o m t he pr ot oc ol will be d oc u me nte d 
a n d descri b e d i n t he fi nal re p ort. If c ha n ges t o pri nci pal feat ures state d i n t h e pr ot oc ol are 
re q uire d, t hes e will be d o c u me nte d i n a pr ot oc ol a me n d me nt. T he fi nal S A P will ta ke i nt o 
acc o u nt a n y a me n d me nt t o t he pr ot oc ol. Data a n al ysis a n d writi n g of a C S R f or all st u d y d at a 
will be perf or me d b y t h e desi g nat e d C R O i n acc or da nce wit h its S O Ps. A nal ysis of P K  a n d P D 
data , a n d writi n g of P K  a n d P D re p orts will be perf or me d b y desi g nate d P K a n d P D tea ms i n 
acc or d a nce wit h t heir sta n dar d o per ati n g pr oce d ures. 
S u m mar y statistics  will be calc ul ate d f or eac h of t he e n d p oi nts. F or c o nti n u o us varia bles, 
n u m ber ( of s u bjects), mea n, sta n dar d d e viati o n, me dia n, a n d ra n ge will be pr o vi de d. F or 
cate g or y v aria bles, n u m b er a n d perce nt of s u bjects will be pr o vi de d f or eac h cate g or y. F or 
vari a bles r e q uiri n g l o garit h mic tra nsf or mati o n, e. g., U P C R, ge o metric mea ns will be calc ulate d.  
A nal ysis will c o m me nce w he n all s u bjects ha v e c o m plete d or disc o nti n ue d pri or t o t he Da y 8 5 
visit, a n d a gai n w h e n all s u bjects ha ve c o m plet e d or disc o nti n ue d pri or t o t he Da y 1 6 9 visit. 
9. 1.  
S u bject  P o p ul ati o n s 
9. 1. 1.  
M o difie d I nte nt -t o- Tre at P o p ul ati o n 
T he m o difie d I nte nt- t o-Treat ( mI T T) P o p ulati o n will i ncl u de all s u bjects w h o are ra n d o mize d, 
ha ve recei ve d a d ose of t he st u d y dr u g, a n d ha v e at least o ne p ost- baseli ne efficac y ass ess me nt.  

C C X 1 4 0- B 
 
Pr ot oc ol C L 0 1 1 _ 1 4 0 
 
  
A me n d me nt 4. 0 (2 9 Oct o ber  2 0 1 8) 
C he m o Ce ntr y x, I n c . 
C O N FI D E N TI A L  
Pa ge 8 2  of 9 3  
9. 1. 2.  
Per Pr ot oc ol P o p ul ati o n  
T he Per Pr ot oc ol ( P P) p o p ulati o n will c o nsist of all mI T T s u bjects w h o ha v e ≥8 0 % c o m plia nce 
wit h t he st u d y dr u g a d mi nistrati o n, d o n ot ha ve pr ot oc ol de viati o ns t hat c o ul d si g nifica ntl y affect 
t he i nter pretati o n of t he r es ults f or t he pri mar y e n d p oi nts. S u bject s’ i ncl usi o n/e x cl usi o n fr o m t he 
P P p o p ulati o n will be deter mi ne d a nd d oc u m e nte d pri or t o t he data bas e l oc k a n d u n bli n di n g. 
9. 1. 3.  
S af et y P o p ul ati o n 
T he safet y p o p ulati o n will i ncl u de all s u bjects w h o are ra n d o mize d a n d ha ve recei ve d at least 
o ne d ose of st u d y dr u g. 
9. 2.  
A n al ysis E n d p oi nts  
9. 2. 1.  
Pri m ar y Effic ac y E n d p oi nt s 
C ha n ge fr o m bas eli ne i n uri ne pr otei n:creati ni ne rati o  ( U P C R) at wee k 1 2  
9. 2. 2.  
Sec o n d ar y Effic ac y E n d p oi nts  
•  C ha n ge fr o m bas eli ne i n e G F R calc ulate d b y t he C K D E PI c yst ati n C e q uati o n, C K D -
E PI Cre ati ni ne e q u ati o n, C K D -E PI Cre ati ni ne - C yst ati n C e q u ati o n a n d M D R D 
Cre ati ni ne e q u ati o n  at W ee ks 1 2 a n d 2 4 
•  Pr o p orti o n of s u bjects ac hie vi n g c o m plete re n al re missi o n  at Wee ks 1 2 a n d 2 4 
C o m plete Re missi o n (i ncl u des all of t he f oll o wi n g)  
- 
re d ucti o n i n U P C R t o < 0. 3 g/ g 
- 
Ser u m al b u mi n wit hi n n or m al r a n ge  
- 
F or p ati e nts wit h a b n or m al ser u m cre ati ni ne le vels at b aseli ne, ret ur n t o 
n or m al le v els f or t h at a ge gr o u p 
- 
F or p ati e nts wit h n or m al ser u m cre ati ni ne le vels at b aseli ne, fi n al v al ue 
wit hi n 2 0 % of b aseli ne le vels  
•  Pr o p orti o n of s u bjects ac hie vi n g partial re missi o n b y t he f oll o wi n g t w o differe nt 
defi nit i o ns assesse d at Wee ks 1 2 a n d 2 4: 
- 
U P C R re d ucti o n of ≥ 5 0 % fr o m b aseli ne  a n d U P C R < 3. 5 g/ g 
- 
decre ase i n U P C R t o less t h a n 1. 5 g/ g a n d at le ast a 4 0 % re d uctio n i n 
pr otei n uri a f r o m b aseli ne  
9. 2. 3.  
E x pl or at or y Effic ac y E n d p oi nts 
•  C ha n ge fr o m bas eli ne of pr otei n uria i n s u bjects treate d wit h C C X 1 4 0- B vers us place b o 
o ver ti me  
•  C ha n ge fr o m bas eli ne i n uri nar y M C P-1:creati ni ne rati o;  
•  C ha n ge fr o m bas eli ne i n bl o o d m o n oc ytes, T, B a n d N K cells; 

C C X 1 4 0- B 
 
Pr ot oc ol C L 0 1 1 _ 1 4 0 
 
  
A me n d me nt 4. 0 (2 9 Oct o ber  2 0 1 8) 
C he m o Ce ntr y x, I n c . 
C O N FI D E N TI A L  
Pa ge 8 3  of 9 3  
•  C ha n ge fr o m bas eli ne i n Healt h -relate d Q u alit y of Life c ha n ges base d o n S h ort F or m 3 6 
versi o n 2 ( S F- 3 6 v 2 a n d E Q- 5 D-5 L. ); 
•  C ha n ge fr o m bas eli ne i n ser u m al b u mi n; 
•  Relati o ns hi p a m o n g P K, e G F R, s er u m al b u mi n a n d U P C R; 
•  C ha n ge fr o m bas eli ne i n U A C R . 
9. 2. 4.  
S af et y E n d p oi nts i ncl u de  
•  S u bject i nci de nce of treat me nt -e mer ge nt a d vers e e ve nts, a d verse e ve n ts lea di n g t o st u d y 
wit h dra wal, a n d s eri o us a d verse e v e nts; 
•  C ha n ge fr o m bas eli ne a n d s hifts fr o m baseli ne i n all safet y la b orat or y para meters;  
•  C ha n ge fr o m bas eli ne i n vital si g ns; 
•  C ha n ge f or m bas eli ne i n sc ore o n t he A C T G B P N S T  
•  Cli nicall y si g nifica nt a b n or mal E C G fi n di n gs  
•  P h ysical e x a mi nati o ns  
Treat me nt -e mer ge nt a d v erse e v e nts ( T E A E) will be s u m marize d f or eac h treat me nt gr o u p b y 
Me d D R A S yste m Or ga n Class ( S O C) a n d preferre d ter m ( P T), b y relat e d ness a n d ma xi m u m 
se verit y. Treat me nt-e mer ge nt seri o us a d verse e v e nts ( T E S A E) a n d T E A E l ea di n g t o st u d y 
wit h dra wal will be se p ar atel y liste d a n d m a y be s u m marize d if warra nte d b y t he s u bject 
i nci de nces. 
Vital si g ns a n d la b or at or y test r es ults, a n d t heir c h a n ges fr o m bas eli ne will be s u m marize d b y 
treat me nt gr o u p a n d visit. A b n or mal la b orat or y v al ues will be fla g ge d i n t h e data listi n g. S hift 
ta bles will be ge ner ate d b y st u d y visit. 
I n di vi d ual E C G fi n di n gs a n d c ha n ge fr o m bas eli ne i n E C G fi n di n gs will b e liste d b y treat me nt 
gr o u p, s u bject, a n d st u d y visit, a n d s u m marize d b y treat me nt gr o u p a n d visit. 
Fi n di n gs fr o m p h ysi cal e x a mi nati o ns will be liste d.  
9. 2. 5.  
P h ar m a c o ki netic E n d p oi nts  
C C X 1 4 0 plas ma c o nce ntrati o n res ults will be use d t o calc ulate  rele va nt P K para met ers a n d 
tr o u g h plas ma c o nce ntrati o ns ( Cmi n ) o ver t he c o urs e of t h e cli nical trial.  
9. 2. 6.  
P h ar m a c o d y n a mi c E n d p oi nts  
T he f oll o wi n g P D e n d p oi nts ma y be assesse d: 
•  C ha n ge a n d perce nt c ha n ge fr o m baseli ne i n plas ma bi o mar kers.  
•  C ha n ge a n d perce nt c ha n ge fr o m baseli ne i n uri ne bi o mar kers. 
9. 3.  
St atistic al A n al ysis Met h o d ol o g y  
T his st u d y will e val uate t he effi cac y, s afet y, t olera bilit y a n d p har mac o ki netics of u p t o 1 2 wee ks 
of treat me nt wit h eac h of t hree d ose r e gi me ns of C C X 1 4 0- B or place b o, w he n use d i n 

C C X 1 4 0- B 
 
Pr ot oc ol C L 0 1 1 _ 1 4 0 
 
  
A me n d me nt 4. 0 (2 9 Oct o ber  2 0 1 8) 
C he m o Ce ntr y x, I n c . 
C O N FI D E N TI A L  
Pa ge 8 4  of 9 3  
c o m bi nati o n wit h sta ble sta n dar d of care t hera p y i n s u bjects wit h pri mar y F S G S or F S G S 
ass ociate d wit h hi g h ris k ge n e vari a nts. F oll o wi n g t he 1 2- wee k bli n de d treat me nt peri o d, 
s u bjects will recei ve acti ve treat me nt f or a n a d diti o nal 1 2 wee ks t o ass ess safet y a n d d ura bilit y of 
effect.  
T he effi cac y a nal yses will be perf or m e d usi n g t h e m I T T a nd P P p o p ulati o ns, wit h t he m I T T 
a nal ysis b ei n g t h e pri mar y a n al ysis. Safet y a nal ysis will be perf or me d usi n g t he safet y 
p o p ulati o n. 
Baseli ne is defi ne d as t he last  n o n-missi n g  val ue pri or t o start of d osi n g wit h st u d y me dicati o n 
(t y picall y t he Da y 1 pr e- d ose val ue). 
As t his is a n e x pl orat or y st u d y i n rare diseas e, u nless s pecifie d ot her wise, all statistical tests a n d 
c o nfi de nce i nter val will be base d o n a 2-si de d al p ha of 0. 1 0. N o m ulti plicit y a dj ust me nt will be 
a p plie d t o t he m ulti ple d ose a n d m ulti ple e n d p oi nts c o m paris o ns. 
9. 3. 1.  
S u bject  Dis p ositi o n  
T he n u m ber a n d p erce nt of s u bjects w h o were scree ne d, scree n faile d ( b y reas o n), c o m plet e d 
Wee k 1 2, w h o c o m plete d t he O pe n- La bel E xte nsi o n, wit h dre w earl y fr o m t he st u d y, al o n g wit h 
t he reas o ns f or wit h dra w al, will be prese nted b y treat me nt gr o u p.  
9. 3. 2.  
De m o gr a p hics a n d B aseli ne C h ar acteristics  
All s u bject baseli ne c h ar acteristics a n d d e m o gra p hic data (a ge, se x, race, et h nicit y, wei g ht, 
hei g ht, b o d y mass i n de x) , viral test res ults, F S G S d urati o n (fr o m ti me of first dia g n osis base d o n 
re nal bi o ps y), e G F R, pr otei n uria ( U P C R), dia g n osis of ne p hr otic s y n dr o me, p h ysical 
e x a mi nati o n a b n or malities, me dical hist or y, pre vi o us ( wit hi n 6 m o nt hs of scree ni n g) a n d 
c o nc o mita nt me dicati o ns (i ncl u di n g ot her treat me nts f or F S G S) at st u d y e ntr y will be liste d b y 
st u d y ce nt er a n d s u bject n u m ber, a n d will als o be s u m marize d. 
9. 3. 3.  
Pri o r a n d C o nc o mit a nt Me dic ati o ns  
All pri or (wit hi n 1 2 wee ks  of scree ni n g,) a n d c o nc o mita nt me dicati o ns will be liste d a n d 
s u m marize d b y A nat o mi c T her a pe utic C he mistr y ( A T C) classificati o n . All B- cell de pleti n g  
a nti b o dies, gl uc o c ortic oi ds a n d i m m u n os u p presa nts ta ke n wit hi n 6 m o nt hs pri or t o scree ni n g 
ma y b e s u m marize d se paratel y.  
9. 3. 4.  
St u d y Dr u g E x p os ure a n d C o m pli a nce  
S u bject  dr u g e x p os ure will be calc ulate d b ase d o n t he st u d y dr u g dis pe nsi n g a n d ret ur n rec or ds, 
as well as C C X 1 4 0 plas ma c o nce ntr ati o ns o ver t he c o urse of t he st u d y. T he C C X 1 4 0- B/ place b o 
c o m plia nce will be calc ulate d c o m pari n g t he st u d y dr u g dis pe ns e d a n d t he st u d y dr u g ret ur ne d. 
T he st u d y dr u g e x p os ure ( d urati o n, t otal d ose, a n d a vera ge dail y d ose) a n d c o m plia nce will be 
liste d a n d s u m marize d. 
9. 3. 5.  
Effic ac y A n al yses 
S u m mar y statistics will be calc ul ate d f or eac h of t he effi cac y p ara m eters. F or cate g orical 
e n d p oi nts, n u m ber a n d p erce nt a ges will be calc ul ate d. F or c o nti n u o us vari a bles, n u m bers, 
mea ns, me dia ns, ra n ges a n d sta n dar d de viati o ns will be calc ulate d. P oi nt esti mates a n d 

C C X 1 4 0- B 
 
Pr ot oc ol C L 0 1 1 _ 1 4 0 
 
  
A me n d me nt 4. 0 (2 9 Oct o ber  2 0 1 8) 
C he m o Ce ntr y x, I n c . 
C O N FI D E N TI A L  
Pa ge 8 5  of 9 3  
c orres p o n di n g 9 0 % c o nfi de nce i nter v als will be esti mate d f or t he differe n ce bet wee n C C X 1 4 0- B 
a n d place b o gr o u ps. 
Data t hat ar e n ot n or mall y distri b ute d, e. g., U P C R, will be l o g- tra nsf or me d bef ore a nal ysis. 
P oi nt esti mates a n d c orres p o n di n g 9 0 % c o nfi de nce i nter vals will be esti mate d f or t he differe n ce 
bet wee n C C X 1 4 0- B a n d place b o gr o u ps.  
Beca use of t h e rel ati vel y s mall size of t he st u d y, i nfere ntial s tatistical a n al ys es ma y n ot be 
a p pr o priate. W her e p ossi ble, c ha n ge fr o m baseli n e t o Da y 8 5 a n d fr o m Da y 8 5 t o Da y 1 6 9 i n 
U P C R will be a nal yz e d usi n g t he mi x e d -effects m o del f or re p eate d m eas ures ( M M R M), wit h 
treat me nt gr o u p, visit, a n d treat me nt-b y -visit a s fact ors a n d baseli ne U P C R a n d a ge as 
c o variates. T h e bet w ee n gr o u p c o m paris o n will be c o m p ute d usi n g t h e si m ple c o ntrast fr o m t he 
m o del. A nal ysis of c o varia nce ( A N C O V A) wit h last o bser vati o n carrie d f or war d ( L O C F) f or 
missi n g data will als o be use d f or se nsiti vit y a n al ysis. T he M M R M a n d A N C O V A a nal yses will 
als o be a p plie d t o t he e G F R e n d p oi nt. 
Pr o p orti o n of s u bjects ac hie vi n g partial res p o nse will be calc ulate d f or eac h treat me nt gr o u p. T he 
bet wee n gr o u p c o m paris o n will be carri e d o ut usi n g t he Fis her’s e x act test. 
T he e x pl orat or y e n d p oi nts will be a nal yze d usi n g M M R M m o del or A N C O V A as des cri be d f or 
t he pri mar y efficac y e n d p oi nt a nal ysis. 
9. 3. 6.  
S af et y A n al yses 
All cli nical safet y a n d t ol era bilit y d ata will be liste d b y treat me nt gr o u p a n d b y s u bject, a n d will 
be s u m marize d b y tr eat m e nt gr o u p a n d visit. 
Treat me nt -e mer ge nt a d v erse e v e nts ( T E A E) will be s u m marize d f or eac h  treat me nt gr o u p b y 
Me d D R A S yste m Or ga n Class ( S O C) a n d preferre d ter m ( P T), b y relat e d ness a n d ma xi m u m 
se verit y. Treat me nt -e mer ge nt seri o us a d verse e v e nts ( T E S A E) a n d T E A E l ea di n g t o st u d y 
wit h dra wal will be se p ar atel y liste d a n d m a y be s u m marize d if warra nte d b y t he s u bject 
i nci de nces. 
Vital si g ns a n d la b or at or y test r es ults, a n d t heir c h a n ges fr o m bas eli ne will be s u m marize d b y 
treat me nt gr o u p a n d visit. A b n or mal la b orat or y v al ues will be fla g ge d i n t h e data listi n g. S hift 
ta bles will be ge ner ate d b y st u d y visit. 
I n di vi d ual E C G fi n di n gs a n d c ha n ge fr o m bas eli ne i n E C G fi n di n gs will b e liste d b y treat me nt 
gr o u p, s u bject, a n d st u d y visit, a n d s u m marize d b y treat me nt gr o u p a n d visit. 
Fi n di n gs fr o m p h ysi cal e x a mi nati o ns will be liste d.  
9. 3. 7.  
P h ar m a c o ki netic a n d P h ar m a c o d y n a mic M ar k er A n al ysis 
I n di vi d ual plas ma c o nce ntrati o ns of C C X 1 4 0 will be liste d, pl otte d, a n d s u m marize d 
descri pti vel y a n d gr a p hicall y f or s u bjects recei vi n g C C X 1 4 0- B. T he f oll o wi n g para meters will 
be deter mi ne d f or C C X 1 4 0: 
C ma x  
Ma xi m u m plas ma c o nce ntrati o n  
tma x  
Ti me of ma xi m u m plas ma c o nce ntrati o n  
A U C 0- 6 
Area u n d er t he plas ma c o nce ntrati o n -ti me c ur ve fr o m Ti me 0 t o Ti me 6 

C C X 1 4 0- B 
 
Pr ot oc ol C L 0 1 1 _ 1 4 0 
 
  
A me n d me nt 4. 0 (2 9 Oct o ber  2 0 1 8) 
C he m o Ce ntr y x, I n c . 
C O N FI D E N TI A L  
Pa ge 8 6  of 9 3  
S u m mar y statisti cs f or st ea d y state tr o u g h plas ma c o nce ntrati o ns will als o be perf or me d.  
T he relati o ns hi p bet wee n P K para meters a n d re nal f u ncti o n base d o n e G F R, U P C R a n d ser u m 
al b u mi n will be e val uate d. T he data ma y als o be use d t o e val uate t he P K/ P D relati o ns hi p of 
C C X 1 4 0- B treat me nt. T o t his e n d, t he c ha n ge a n d/ or perce nt c ha n ge fr o m b aseli ne i n first 
m or ni n g U P C R, e G F R, a n d ot her bi o mar kers m a y be use d as P D mar k ers. P har mac o d y na mics 
bi o mar ker dat a ma y be a nal yze d t he sa m e wa y as t he efficac y d ata.  
9. 3. 8.  
H a n dli n g of Missi n g D at a  
F or t he M M R M a nal ysis, data will be a nal yze d as is wit h o ut missi n g data i m p utati o n. F or 
A N C O V A a n al ysis a n d a nal ysis of r es p o nses, missi n g data will be i m p ute d usi n g t he last 
o bser vati o n carrie d f or w ar d ( L O C F) met h o d. T his met h o d ma y i m p ute Wee k 1 2 mi ssi n g dat a 
wit h t he baseli ne val ue if t here are n o sc h e d ule d or u nsc he d ule d d ata pri or t o t he missi n g ti me 
p oi nt. Ot her i m p utati o n met h o d will be detaile d i n t he S A P.  
9. 3. 9.  
Str atifie d A n al ysis  
T he a nal ysis of t he efficac y e n d p oi nts ma y b e a dj uste d b y t he f oll o wi n g v aria bles i n t he f or m of 
stratifie d a nal ysis: 
•  U P C R < 3. 5 g pr otei n/ g cre ati ni ne at b aseli ne vers us U P C R ≥3. 5 g pr otei n/ g 
cre ati ni ne at b aseli ne . 
•  C urre nt  use of gl uc o c orti c oi ds/i m m u n os u p pressi ve me dicati o ns ( yes vs. n o) 
9. 4.  
S a m ple Size J ustific ati o n   
Ass u mi n g t he sta n dar d d e viati o n ( S D) f or t he c ha n ge fr o m baseli ne i n t he l o garit h mic 
tra nsf or mati o n of UP C R  is 0. 7 0, wit h 1 0 s u bjects per treat me nt gr o u p, t he 9 0 % c o nfi de n ce 
i nter val ( CI) f or t he bet w ee n gr o u p differe nce i n t he l o g scale will ha ve a ½ wi dt h of 0. 54 3. I n 
ot her w or ds, if t he rati o of t he treat me nt o v er place b o is 0. 5 ( 5 0 % re d ucti o n fr o m place b o) i n 
U P C R , t he 9 0 % CI  will be ( 0. 2 9, 0. 8 6) (i. e., 1 4 % t o 7 1 % re d ucti o n). 
Ass u mi n g S D = 8. 5 f or c ha n ge fr o m b aseli ne i n e G F R, wit h 1 0 s u bjects per gr o u p, t he 9 0 % CI 
f or t he bet w ee n gr o u p differe n ce will ha v e a ½ wi dt h of 6. 6. If t he differe n ce bet w ee n treat me nt 
a n d place b o is o bser ve d t o be 1 0 m L/ mi n/ 1. 7 3 m 2, t he 9 0 % CI will be ( 3. 4, 1 6. 6). 
N ote t he a b o ve calc ulati o n is base d o n t he S D esti mate d fr o m St u d y C L 0 0 5 _ 1 4 0 a n d a n 
u na dj uste d 2-si de d al p ha of 1 0 %. 
9. 5.  
Pr ot oc ol De vi ati o ns  
Si g nifica nt  ( eit her maj or or critical) pr ot oc ol de viati o ns will be liste d a n d s u m marize d b y 
cate g or y. T h e effect of si g nifica nt pr ot oc ol de viati o ns o n t he safet y a n d effi cac y o utc o m es ma y 
be ass esse d b y c o n d ucti n g se nsiti vit y a nal yses e x cl u di n g s u bjects a n d/ or st u d y visits wit h 
si g nifica nt pr ot o c ol de viati o ns. T his will be deter mi ne d a n d d oc u me nte d b ef ore u n bli n di n g t he 
st u d y. 
T he S p o ns or will assess eac h pr ot o c ol de viati o n a n d deci de w h et her t he y s h o ul d be re p orte d t o 
C o m pete nt A ut h orities as a seri o us breac h of G C P a n d t he pr ot oc ol. E x a m ples of maj or 
de viati o ns ma y i ncl u d e b ut are n ot li mite d t o:  

C C X 1 4 0- B 
 
Pr ot oc ol C L 0 1 1 _ 1 4 0 
 
  
A me n d me nt 4. 0 (2 9 Oct o ber  2 0 1 8) 
C he m o Ce ntr y x, I n c . 
C O N FI D E N TI A L  
Pa ge 8 7  of 9 3  
1.  Fail ure t o pr o p erl y o btai n i nf or me d c o nse nt 
2.  E nr oll me nt of i neli gi ble s u bjects  
3.  Perf or ma nce of pr oce d ur es n ot i n t he pr ot oc ol or o missi o n of pr ot oc ol- re q uire d 
pr oce d ur es 
4.  St u d y m e dicati o n d osi n g a n d dis pe nsi n g err ors 
5.  Fail ure t o pr o p erl y r e p ort Seri o us A d verse E v e nts  
6.  A n y d e viati o ns fr o m t he pr ot oc ol t hat je o par dize eit her s u bject safet y or t he i nte grit y of 
t he st u d y 
1 0.  
S T U D Y C O M P L E TI O N A N D  T E R MI N A TI O N  
1 0. 1.  
St u d y C o m pleti o n  
A s u bject has c o m plete d t he st u d y w h e n s/ he has c o m plete d t he st u d y pr o ce d ures per pr ot oc ol. 
1 0. 2.  
St u d y Ter mi n ati o n  
T he e n d of st u d y is defi n e d as t he last st u d y visit of t he last cli nical trial s u bject. N ote t hat all 
st u d y s u bjects are e x pect e d t o ret ur n t o t he cli nic f or bl o o d dra ws 2, 7 a n d 1 4 da ys after 
disc o nti n uati o n fr o m treat me nt f or a n y reas o n. 
1 1.  
R E G U L A T O R Y A N D A D MI N I S T R A TI V E R E Q UI R E M E NT S 
1 1. 1.  
I n vesti g at or Res p o nsi bilities 
Pri or t o trial i nitiati o n, t he I n vesti gat or will pr o vi d e t he S p o ns or wit h a f ull y e x ec ute d a n d si g n e d 
F D A F or m 1 5 7 2, a Fi na n cial Discl os ure F or m , a Me dical Lice ns e (fr o m  rele va nt c o u ntries) a n d 
c urric ul u m vitae . Fi na nci al Discl os ure F or ms als o will be c o m plete d f or all S u b-I n v esti gat ors 
liste d o n t he F or m 1 5 7 2 w h o will be i n v ol ve d directl y i n t he treat me nt or e val uati o n of researc h 
s u bjects i n t his trial. 
T he st u d y will be c o n d ucte d i n acc or d a nce wit h t he Decl arati o n of H elsi n ki (a me n de d b y t he 5 9 t h 
W orl d Me dical Ass ocia ti o n Ge ner al Asse m bl y, O ct o ber 2 0 0 8) a n d G o o d Cli nical Practice ( G C P) 
acc or di n g t o I nt er nati o nal C o nfere nce o n Har m o nisati o n (I C H) g ui deli nes. S pecificall y, t he 
st u d y is base d o n a de q uat el y p erf or m e d la b orat or y a n d a ni mal e x peri me ntati o n; t he st u d y will be 
c o n d ucte d u n der a pr ot o c ol re vie we d b y a pr o perl y c o nstit ute d I R B/ E C; t he st u d y will be 
c o n d ucte d b y scie ntifi call y a n d me di call y q ualifie d pers o ns; t he be nefits of t he st u d y are i n 
pr o p orti o n t o t he ris ks; t he ri g hts a n d welfare of t he s u bjects will be res p ect e d; a n d eac h s u bject  
or his/ her le gal g uar dia n will gi ve his/ her writte n I nf or me d C o nse nt bef ore a n y pr ot oc ol-s pecific 
tests or e val uati o ns ar e p erf or me d. 
1 1. 2.  
I nstit uti o n al Re vie w B o ar d or Et hics C o m mittee 
Pri or t o i nitiati n g t he st u d y, t he I n vesti gat or will o btai n writte n c o nfir mati o n fr o m t he I R B/ E C 
t hat t he I R B/ E C was pr o perl y c o nstit ute d a n d met t he defi niti o n of all U nite d States C o de of 

C C X 1 4 0- B 
 
Pr ot oc ol C L 0 1 1 _ 1 4 0 
 
  
A me n d me nt 4. 0 (2 9 Oct o ber  2 0 1 8) 
C he m o Ce ntr y x, I n c . 
C O N FI D E N TI A L  
Pa ge 8 8  of 9 3  
Fe deral Re g ulati o ns Title 2 1, Secti o n 3 1 2. 3( b) a n d Part 5 6, a n d/ or t he a p pli ca ble l ocal, re gi o nal 
or nati o nal Re g ulat or y r e q u ire me nts. A c o p y of t h e c o nfir mati o n will be pr o vi de d t o t he S p o ns or. 
T he Pri nci pal I n vesti gat or will pr o vi de t he I R B/ E C wit h all a p pr o priate materials, i ncl u di n g t he 
pr ot oc ol a n d I nf or me d C o nse nt d oc u me nts. T he trial will n ot be i nitiate d u ntil  I R B/ E C a p pr o v al 
of t he pr ot oc ol, t he I nf or me d C o nse nt d oc u me nt, a n d all recr uiti n g materials are o btai ne d i n 
writi n g b y t he I n v esti gat or a n d c o pies are recei ve d b y t he S p o ns or. A p pr o priate re p orts o n t he 
pr o gress of t he st u d y will be ma de t o t he I R B/ E C a n d t he S p o ns or b y t h e Pri nci pal I n vesti gat or 
i n acc or d a nce wit h a p plica ble g o ver n me ntal re g ulati o ns a n d i n a gree me nt wit h t he p olic y 
esta blis he d b y t h e S p o ns or. 
1 1. 3.  
I nf or me d C o nse nt 
A pr o perl y e x ec ute d, writte n, a n d a p pr o pri atel y e x plai ne d I nf or me d C o nse nt F or m, i n 
c o m plia nce wit h t he D eclarati o n of Helsi n ki, I C H G C P, a n d U S C o de of Fe deral Re g ul ati o ns f or 
Pr otecti o n of H u ma n S u bject s ( 2 1 C F R 5 0. 2 5[a, b], C F R 5 0. 2 7, a n d C F R Part 4 6, S u b part A), 
will be si g ne d b y eac h s u bject  or his/ her le gal g u ar dia n pri or t o e nteri n g t he trial. Eit her t he 
I n v esti gat or or t he I n v esti gat or’s desi g nee will o btai n t he c o nse nt of t he st u d y s u bject. T h e 
s u bject will be pr o vi de d as m uc h ti me as necessar y t o re vi e w t he d oc u m e nt, t o i n q uire a b o ut 
details of t he trial, a n d t o deci de w h et he r or n ot t o partici pate i n t he st u d y. T he I nf or m e d C o nse nt 
will be si g ne d a n d d ate d b y t he st u d y s u bject a n d b y t he p ers o n w h o c o n d u cte d t he Inf or me d 
C o nse nt disc ussi o n. T he I n v esti gat or will pr o vi de a c o p y of t he si g ne d I nf or me d C o nse nt F or m 
t o eac h s u bject a n d will mai ntai n a c o p y i n t he s u bject’s rec or d file. 
1 1. 4.  
Pr ot oc ol M o dific ati o ns  
O nl y t he S p o ns or ma y m o dif y t he pr ot oc ol. T he o nl y e x ce pti o n is w he n t he I n v esti gat or 
c o nsi ders t hat a s u bject’s safet y w o ul d be c o m pr o mise d wit h o ut i m me diate acti o n. I n t his 
circ u msta nce, i m me diate a p pr o val of t he c hair p ers o n of t he I R B/ E C m ust be s o u g ht, a n d t he 
I n v esti gat or s h o ul d i nf or m t he S p o ns or’s Me dical M o nit or a n d t he f ull I R B/ E C wit hi n fi ve 
w or ki n g d a ys aft er t he e mer ge nc y o cc urre d. All ot her a me n d me nts t hat ha ve a n i m pact o n 
s u bject ris k or t he st u d y o bjecti ves, a n d/ or t hat re q uire re visi o n of t he I nf or me d C o nse nt F or m, 
m ust recei ve a p pr o val fr o m t he I R B/ E C pri or t o t heir i m ple me ntati o n, e x ce pt w he n t he c h a n ges 
i n v ol ve o nl y l o gistical or a d mi nistrati ve as pects of t he trial. T he I R B/ E C m ust be n otifie d of 
c ha n ges t hat are ma d e t o st u d y c o ntact pers o n nel, b ut I R B/ E C re vie w or a p pr o val of t hese 
c ha n ges is n ot re q uir e d. If pr ot oc ol a me n d me nts are s u bsta ntial a n d are li kel y t o ha ve a n i m pact 
o n t he safet y of t he trial s u bjects or t o c ha n ge t he i nter pretati o n of t he s cie ntific d oc u me nts i n 
s u p p ort of t he c o n d uct of t he trial, or if t he y are ot her wise si g nifica nt, t he s p o ns or s hall n otif y t he 
F D A a n d ot h er c o m p ete nt a ut h orities c o ncer n e d of t he reas o ns f or, a n d c o nte nt of, t h ese 
a me n d me nts acc or di n g t o t he E ur o pea n Directi ve “ Detaile d g ui da n ce o n t h e re q uest t o t he 
c o m pete nt a ut h orities f or a ut h orizati o n of a cli nical trial o n a me dical pr o d u cts f or h u ma n use, 
t he n otificati o n of s u bsta ntial a me n d me nts a n d t he declarati o n of the e n d of trial ( C T - 1)( 2 0 1 0/ C 
8 2/ 0 1)” a n d ot her re g ulat or y g ui da nce . 
1 1. 5.  
Re g ul at or y D oc u me nt ati o n  
All re g ul at or y d oc u me nt ati o n i ncl u di n g re g ul at or y s u b missi o ns, 1 5 7 2 f or ms, a n d c orres p o n d e nce 
re gar di n g t his st u d y will be ke pt b y t he S p o ns or. T he C R O t hat will c o n d uct t he st u d y o n be h alf 

C C X 1 4 0- B 
 
Pr ot oc ol C L 0 1 1 _ 1 4 0 
 
  
A me n d me nt 4. 0 (2 9 Oct o ber  2 0 1 8) 
C he m o Ce ntr y x, I n c . 
C O N FI D E N TI A L  
Pa ge 8 9  of 9 3  
of t he S p o ns or will mai ntai n all st u d y d oc u me nt ati o n acc or di n g t o t heir S O Ps. Cli nical trial 
relate d d oc u m e nts will be arc hi v e d f or t he l o n gest of:  
1.  1 0 years acc or di n g t o nati o nal S we dis h a n d E U re g ulati o ns ( L V F S 2 0 0 3: 3), or 
2 
F o r 2 years f oll o wi n g t he date a f ull mar k eti n g a p plicati o n is a p pr o ve d, or 
3  F or 2 years after t he F D A is n otifie d t hat t he I N D is disc o nti n ue d if t here is n o mar keti n g 
a p plicati o n . 
1 1. 6.  
S u bject  I de ntific ati o n Re gister 
T he I n vesti gat or a grees t o c o m plete a s u bject i de ntificati o n re gister, w hic h will be use d f or t he 
p ur p ose of l o n g ter m f oll o w- u p, if nee d e d. T his f or m will be treate d as c o nfi de ntial, a n d will be 
file d b y t he I n vesti gat or i n a sec ur e l oc ke d pl ace. Ot her wise, all re p orts a n d c o m m u nicati o ns 
relati n g t o t he st u d y will i de ntif y partici pa nts b y i nitials a n d/ or assi g ne d n u m ber o nl y. 
1 1. 7.  
Rec or d Rete nti o n  
T he I n vesti gat or m ust ret ai n all st u d y r ec or ds re q uire d b y t h e S p o ns or a n d b y t he a p plica ble 
re g ulati o ns i n a sec ure a n d safe f acilit y. T h e I n vesti gat or m ust c o ns ult t he S p o ns or bef ore 
dis p osal of a n y st u d y rec or ds, a n d m ust n otif y t he S p o ns or of a n y c ha n ge i n t he l ocati o n, 
dis p ositi o n, or c ust o d y of t he st u d y files. Cli nical trial relate d d o c u me nts will be arc hi ve d f or t he 
l o n gest of:  
1.  1 0 years acc or di n g t o nati o nal S we dis h a n d E U re g ulati o ns ( L V F S 2 0 0 3: 3), or 
2.  F or 2 years f oll o wi n g t he date a f ull mar k et i n g a p plicati o n is a p pr o ve d, or 
3.  F or 2 years after t he F D A is n otifie d t hat t he I N D is disc o nti n ue d if t here is n o mar keti n g 
a p plicati o n . 
1 1. 8.  
C ase Re p ort F or m C o m plet i o n 
Electr o nic Case Re p ort F or ms ( C R Fs) will be ge n erate d f or eac h s u bject. The electr o ni c data 
ca pt ure ( E D C) s yste m will c o m pl y wit h C F R 2 1 Part 1 1. 
It is t he p olic y of t he S p o ns or t hat st u d y data m ust be verifia bl e t o t he s o urce data, w hic h 
necessitates access t o all ori gi nal r ec or di n gs, la b orat or y re p orts, a n d s u bjects’ rec ords. T he 
I n v esti gat or m ust t heref ore a gr ee t o all o w access t o s u bjects’ rec or ds, a n d s o urce dat a m ust be 
ma de  a vaila ble f or all st u d y dat a. T he s u bjects ( or t heir le gal re prese ntati ves) m ust als o all o w 
access t o t he s u bject s’ m e dical rec or ds, a n d t h e y will be i nf or me d of t his re q uire me nt a n d will 
i n dicate t heir a gr ee me nt w he n gi vi n g I nf or me d C o nse nt. U p o n c o m pleti o n of t he st u d y, 
electr o nic c o pies of t he C R Fs will be pr o vi de d t o t he i n vesti gat ors a n d s h o ul d be i ncl u de d as part 
of his/ her st u d y files a n d retai ne d as p er F D A or l o cal re g ulati o ns. 
1 1. 9.  
M o nit ori n g  
At i nter vals d uri n g t h e st u d y, as well as after t he c o m pleti o n of s u bject e nr oll me nt at t he st u d y 
ce nter, t he st u d y ce nter will be m onit ore d b y a C R A f or c o m plia nce, w hic h will i ncl u de e ns uri n g 
t hat acc ur ate a n d c o m plete data ar e pr o m ptl y rec or de d i n E D C, re vie wi n g s o urce d oc u m e ntati o n, 
all re g ulat or y d oc u m e ntati o n a nd dr u g acc o u nt a bilit y rec or ds. T he st u d y will be c o n d ucte d 

C C X 1 4 0- B 
 
Pr ot oc ol C L 0 1 1 _ 1 4 0 
 
  
A me n d me nt 4. 0 (2 9 Oct o ber  2 0 1 8) 
C he m o Ce ntr y x, I n c . 
C O N FI D E N TI A L  
Pa ge 9 0  of 9 3  
acc or di n g t o t he pri nci ples of G C P as acce pte d i n t he U nite d States a n d acc or di n g t o 
C P M P/I C H/ 1 3 5/ 9 5. 
1 1. 1 0.  
O n- site Visits a n d A u dits  
T he S p o ns or’s re prese ntati ves will visit t he st u d y ce nter pri or t o i nitiati o n of t he st u d y t o re vie w 
wit h t he ce nter p ers o n nel i nf or mati o n re gar di n g t h e i n vesti gati o nal a ge nt, pr ot oc ol re q uire m e nts, 
m o nit ori n g re q uir e me nts, d oc u me ntati o n re q uire me nts a n d re p orti n g of s eri o us a d verse e ve nts. 
I n cert ai n circ u msta nces, a sec o n dar y a u dit ma y be c o n d ucte d b y me m bers of a Q ualit y 
Ass ura nce gr o u p desi g nate d b y t he S p o ns or. T h e I n vesti gat or will be i nf or me d if t his is t o ta ke 
place a n d a d vise d as t o t he nat ure of t he a u dit. Re prese ntati ves of t h e F o o d a n d Dr u g 
A d mi nistrati o n ( F D A) a n d/ or re pres e ntati ves of ot her re g ul at or y a ut h orities ma y als o c o n d uct a n 
a u dit of t he st u d y. If i nf or me d of s uc h a n a u dit, t he I n vesti gat or s h o ul d n otif y t he S p o ns or 
i m me diatel y. 
1 1. 1 1.  
Use of I nf or m ati o n a n d P u blic ati o n  
It is u n derst o o d b y t he I n vesti gat or t h at t he i nf or m ati o n ge n erat e d i n t his st u d y will be use d b y 
t he S p o ns or i n c o n necti o n wit h t he de vel o p me nt of t he pr o d uct a n d t h eref ore ma y be discl ose d t o 
g o ver n me nt a ge n cies i n vari o us c o u ntries. T o all o w f or t he use of i nf or mati o n deri ve d fr o m t he 
st u d y, it is u n derst o o d t hat t he I n vesti gat or is o bli ge d t o pr o vi de t he S p o ns or wit h c o m plete test 
res ults, all st u d y data, a n d access t o all st u d y rec or ds. 
T he S p o ns or rec o g nizes t he i m p orta nce of c o m m u nicati n g st u d y data a n d will discl ose or p u blis h 
t he res ults i n a s uita ble f or m re gar dl ess of o utc o me. T he S p o ns or will p ost t he cli nical trial 
i nf or mati o n o n a p pr o priate re gistries, e. g., cli nicaltrials. g o v pri or t o e nr oll me nt of t he first 
s u bjects, a n d p u blis h t he res ults of t his st u d y i n sci e ntific j o ur nals, at se mi n ars or c o nfere nces, 
a n d/ or i n ot her ma n ner(s) it s o c h o oses. Res ul ts fr o m t his st u d y s hall n ot be ma de a vaila ble t o 
a n y t hir d p art y b y t he i n v esti gati n g tea m wit h o ut t he e x press per missi o n of t he S p o ns or. 

C C X 1 4 0- B 
 
Pr ot oc ol C L 0 1 1 _ 1 4 0 
 
  
A me n d me nt 4. 0 (2 9 Oct o ber  2 0 1 8) 
C he m o Ce ntr y x, I n c . 
C O N FI D E N TI A L  
Pa ge 9 1  of 9 3  
1 2.  
R E F E R E N C E S  
1.  
Ba nfi, G. et al.( 1 9 9 1) T h e i m pact of pr ol o n ge d i m m u n os u p pressi o n o n t he o utc o me of 
i di o pat hic f ocal-se g m e ntal gl o mer ul os cler osis wit h ne p hr otic s y n dr o me i n a d ults. A 
c olla b orati ve r etr os pecti v e. Cli n Ne p hr ol 3 6( 2) 5 3- 9. 
2.  
Bes bas N et al. ( 2 0 1 5) M C P 1 2 5 1 8 A/ G p ol y m or p his m affects pr o gressi o n of c hil d h o o d 
f ocal se g me nt al gl o mer ul oscler osis. Re n Fail 3 7 ( 9): 1 4 3 5- 1 4 3 9. 
3.  
B urt o n CJ et al. ( 1 9 9 9) Secreti o n of c he m o ki nes a n d c yt o ki nes b y h u ma n t u b ular 
e pit helial cells i n res p o ns e t o pr otei ns. Ne p hr ol Di al Tra ns pla nt 1 4 ( 1 1): 2 6 2 8- 2 6 3 3. 
4.  
Cattra n a n d A p pel, i n Tr eat me nt of Pri mar y F ocal Scler osis Gl o mer ul oscler osis, U p T o 
Dat e, 2 0 1 6 
5.  
Cattra n D C, Reic h H N, Bea nl a n ds HJ, Miller J A, Sc h ole y J W, Tr o ya n o v S, Ge nes G, 
Gl o mer ul o ne p hritis G ( 2 0 0 8) T he i m pact of s e x i n pri mar y gl o mer ul o ne p hritis. Ne p hr ol 
Di al Tr a ns pl a nt  2 3( 7): 2 2 4 7- 2 2 5 3. 
6.  
Cattra n, D C a n d Ra o, P ( 1 9 9 8) L o n g- ter m o utc o m e i n c hil dre n a n d a d ults wit h classic 
f ocal se g me nt al gl o mer ul oscler osis. A m J Ki d ne y Dis. J ul; 3 2( 1) 7 2- 9. 
7.  
C he n, Y- C et al. ( 2 0 1 5) 1 3- year n ati o n wi de c o h ort st u d y of c hr o nic ki d ne y disease ris k 
a m o n g tr eat me nt -n aï ve p atie nts wit h c hr o nic he p atitis B i n Tai wa n.  B M C Ne p hr ol o g y 
1 6: 1 1 0. 
8.  
C h o w F Y et al. ( 2 0 0 6) M o n oc yt e c he m o attracta nt pr otei n- 1 pr o m otes t he d e vel o p me nt 
of dia betic r e nal i nj ur y i n stre pt oz ot oci n-treate d mice. Ki d ne y I nt 6 9 ( 1): 7 3- 8 0. 
9.  
C h o w F Y et al. ( 2 0 0 7) M o n oc yt e c he m o attracta nt pr otei n- 1-i n d uce d tis s ue i nfla m mati o n 
is critical f or t he d e vel o p me nt of re nal i nj ur y b ut n ot t y pe 2 dia b etes i n o bese d b/ d b 
mice. Dia bet ol o gia 5 0 ( 2): 4 7 1- 4 8 0. 
1 0.  D' A gati V D, Kas k el FJ, Fal k RJ ( 2 0 1 1) F ocal s e g me ntal gl o mer ul os cler osis. N E n gl J 
Me d 3 6 5( 2 5): 2 3 9 8- 2 4 1 1. 
1 1.  D' A gati , V. D., F o g o, A. B., Br uij n, J. A., & J e n nette, J. C. ( 2 0 0 4). Pat h ol o gic 
classificati o n of f o cal se g me ntal gl o mer ul os cler osis: a w or ki n g pr o p osal. A m J Ki d ney 
Dis, 4 3 ( 2), 3 6 8- 3 8 2. 
1 2.  de Zee u w  D et al. ( 2 0 1 5) T he effect of C C R 2 i n hi bit or C C X 1 4 0- B o n resi d ual 
al b umi n uria i n s u bjects wit h t y pe 2 dia b etes a n d ne p hr o pat h y: a ra n d o mise d trial. La ncet 
Dia betes E n d ocri n ol 3 ( 9): 6 8 7- 6 9 6. 
1 3.  D har ni d har k a V R, K w o n C, Ste ve ns G. ( 2 0 0 2) Ser u m c yst ati n C is s u peri or t o ser u m 
creati ni ne as a mar k er of ki d ne y f u ncti o n: a meta -a nal ysis. A m J Ki d ne y Dis . 4 0: 2 2 1 –
2 2 6. 
1 4.  Ear dle y K S et al. ( 2 0 0 6) T he relati o ns hi p bet wee n al b u mi n uria, M C P- 1/ C C L 2, a n d 
i nterstitial macr o p ha ges i n c hr o nic ki d ne y disease. Ki d ne y I nt 6 9 ( 7): 1 1 8 9- 1 1 9 7. 
1 5.  Gi ps o n D S, Tr o ost J P, Lafa yette R A, et al. ( 2 0 1 6) C o m plete Re missi o n i n t he Ne p hr otic 
S y n dr o me St u d y Net w or k. Cli n J A m S oc Ne p hr ol 1 1( 1 ): 8 1- 8 9. 

C C X 1 4 0- B 
 
Pr ot oc ol C L 0 1 1 _ 1 4 0 
 
  
A me n d me nt 4. 0 (2 9 Oct o ber  2 0 1 8) 
C he m o Ce ntr y x, I n c . 
C O N FI D E N TI A L  
Pa ge 9 2  of 9 3  
1 6.  I n k er L A et al, ( 2 0 1 2) Esti mati n g gl o mer ular filtrati o n rate fr o m ser u m creati ni ne a n d 
c ystati n C. N E n gl J Me d.; 3 6 7( 1): 2 0- 2 9. 
1 7.  I n v esti gat ors Br oc h ur e, E diti o n 9. 0. 
1 8.  J effers on J A ( 2 0 0 8) Pr otei n uria i n dia betic ki d ne y disease: a mec ha nistic vie w p oi nt. 
Ki d ne y I nt 7 4 ( 1): 2 2- 3 6. 
1 9.  Ka n g Y S et al. ( 2 0 1 0) C C R 2 a nta g o nis m i m pr o ves i ns uli n resista nce, li pi d meta b olis m, 
a n d dia betic ne p hr o pat h y i n t y pe 2 dia b etic mice. Ki d ne y I nt 7 8 ( 9): 8 8 3- 8 9 4. 
2 0.  Ki d ne y Disease: I m pr o vi n g Gl o bal O ut c o mes ( K DI G O) Gl o mer ul o ne p hritis W or k 
Gr o u p K DI G O Cli nical Practice G ui deli ne f or Gl o mer ul o ne p hritis. Ki d ne y I nt S u p pl. 
2 0 1 2; 2( S u p pl 2): 1 3 9 – 2 7 4. 
2 1.  K or bet S M ( 2 0 1 2) Tr eat me nt of pri mar y F S G S i n a d ults. J A m S oc Ne p hr ol 2 3 
( 1 1): 1 7 6 9- 1 7 7 6. 
2 2.  Le v e y A S, B os c h J P, Le wis J B, Gree ne T, R o gers N, R ot h D. ( 1 9 9 9) A m ore acc urate 
met h o d t o esti mate gl o m er ular filtrati o n rate fr o m ser u m creati ni ne: A ne w pre dicti o n 
e q uati o n. M o dificati o n of Diet i n Re nal Diseas e St u d y Gr o u p. A n n I nter n 
Me d; 1 3 0( 6): 4 6 1 – 4 7 0. 
2 3.  Le v e y A S, C ores h J, Gree ne T, Ste ve ns L A, Z h a n g Y L, He n dri kse n S, et al. ( 2 0 0 6) 
Usi n g sta n dar dize d ser u m creati ni ne val u es i n t he m o dificati o n of diet i n re nal diseas e 
st u d y e q u ati o n f or esti mati n g gl o mer ular filtrati o n rate. A n n I nt er n Me d; 1 4 5( 4): 2 4 7 – 5 4. 
2 4.  P C 0 6 8 4 _ 1 4 0 Effects of C C R 2 a nta g o nist i n a dria m yci n-i n d uce d a n d 5/ 6 n e p hrect o m y 
m o use m o dels of f ocal se g me ntal gl o mer ul os cler osis . 
2 5.  R y del,JJ et al. ( 1 9 9 5) F ocal se g me ntal gl o mer ular scler osis i n a d ults: prese ntati o n, 
c o urse, a n d res p o nse t o tr eat me nt. A m J Ki d ne y Dis A pr; 2 5( 4): 5 3 4- 4 2. 
2 6.  Sc h wartz GJ, et al.  ( 2 0 0 9) Ne w e q uati o ns t o esti mate G F R i n c hil dre n wit h C K D. J A m 
S oc Ne p hr ol; 2 0: 6 2 9 – 6 3 7. 
2 7.  Selistre L, et al. ( 2 0 1 6) C o m paris o n of t he Sc h wartz a n d C K D- E PI E q u ati o ns f or 
Esti mati n g Gl o mer ular Filtrati o n Rate i n C hil dre n, A d olesce nts, a n d A d ults: A 
Retr os pecti ve Cr oss - Secti o nal St u d y. P L o S Me d; 1 3: e 1 0 0 1 9 7 9. 
d oi: 1 0. 1 3 7 1/j o ur nal. p me d. 1 0 0 1 9 7 9 
2 8.  Si m , JJ et al. ( 2 0 1 6) Distri b uti o n of Bi o ps y- Pr o ve n Pres u me d Pri mar y 
Gl o mer ul o ne p hr o pat hies i n 2 0 0 0- 2 0 1 1 A m o n g a Raciall y a n d Et h nicall y Di verse U S  
P o p ulati o n. A m J Ki d ne y Dis. Oct; 6 8( 4): 5 3 3- 5 4 4. 
2 9.  Ste ve ns, L A, et al. ( 2 0 0 8) Esti mati n g G F R Usi n g Ser u m C ystati n C Al o ne a n d i n 
C o m bi nati o n wit h Ser u m Creati ni ne: A P o ole d A n al ysis of 3, 4 1 8 I n di vi d uals wit h C K D. 
A m J K D, 5 1 ( 3): 3 9 5- 4 0 6. 
3 0.  S ulli va n TJ et al. ( 2 0 1 3) E x peri me ntal e vi de nce f or t he use of C C R 2 a nta g o nists i n t he 
treat me nt of t y pe 2 dia b etes. Meta b olis m 6 2 ( 1 1): 1 6 2 3- 1 6 3 2. 

C C X 1 4 0- B 
 
Pr ot oc ol C L 0 1 1 _ 1 4 0 
 
  
A me n d me nt 4. 0 (2 9 Oct o ber  2 0 1 8) 
C he m o Ce ntr y x, I n c . 
C O N FI D E N TI A L  
Pa ge 9 3  of 9 3  
3 1.  Tr o ya n o v S, Wall C A, Miller J A, Sc h ole y J W, Cattra n D C, T or o nt o Gl o mer ul o ne p hr itis 
Re gistr y G ( 2 0 0 5) F o cal a n d se g me ntal gl o mer ul oscler osis: defi niti o n a n d rele va nce of a 
partial re missi o n. J A m S oc Ne p hr ol 1 6( 4): 1 0 6 1- 1 0 6 8. 
3 2.  Wasile ws ka A et al. ( 2 0 1 1) Uri nar y m o n o c yt e c he m oattracta nt pr otei n - 1 e x creti o n i n 
c hil dre n wit h gl o mer ular pr otei n uria. Sca n d J Ur ol Ne p hr ol 4 5 ( 1): 5 2- 5 9. 
3 3.  Ya da v A et al. ( 2 0 1 0) M C P- 1: c he m oattracta nt wit h a r ole be y o n d i m m u nit y: a re vie w. 
Cli n C hi m Acta 4 1 1 ( 2 1- 2 2): 1 5 7 0- 1 5 7 9.