Clinical trial NCT03536754
Conditions: FSGS Focal Segmental Glomerulosclerosis Glomerulosclerosis
Sponsor: Amgen
Start date: 2018-05-17; Completion date: 2020-02-19
Enrollment: 46 participants; Allocation: RANDOMIZED; Intervention model: SEQUENTIAL

Brief summary:
A Multicenter, Randomized, Double-Blind, Placebo-Controlled Dose-Ranging Study to Evaluate the Safety and Efficacy of CCX140-B in Subjects with FSGS to be conducted in the North America, Europe and Australia

Detailed description:
A Multicenter, Randomized, Double-Blind, Placebo-Controlled Dose-Ranging Study to Evaluate the Safety and Efficacy of CCX140-B in Subjects with Focal Segmental Glomerulosclerosis (FSGS) to be conducted in the North America, Europe and Australia. The aim of this study is to evaluate the effect of treatment with CCX140-B, a selective antagonist of C-C chemokine receptor type 2 in subjects with focal segmental glomerulosclerosis on urinary protein excretion as assessed by changes in urine protein to creatinine ratio (UPCR).

Study acquired by Amgen and all disclosures were done by previous sponsor ChemoCentryx.

Arms: arm 1: Placebo (N=10) arm 2: CCX140-B 5 mg once daily (N=10) arm 3: CCX140-B 10 mg twice daily (N=10) arm 4: CCX140-B 15 mg twice daily (N=10)
Interventions: intervention 1: Placebo intervention 2: CCX140-B intervention 3: CCX140-B intervention 4: CCX140-B
Intervention descriptions: intervention 1: Three placebo tablets, taken twice daily (BID), per os, for 84 days (12 weeks) intervention 2: One 5 mg CCX140-B tablet and 2 placebo tablets in the morning; 3 placebo tablets in the evening; per os, for 84 days. intervention 3: Two 5 mg CCX140-B tablets and 1 placebo tablet, taken BID; per os, for 84 days. intervention 4: Three 5 mg CCX140-B tablets, taken BID; per os, for 84 days.

Protocol documents:
Prot_000.pdf: 
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. 
 
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _         
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
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 
 
  
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C he m o Ce ntr y x, I n c . 
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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 
 
  
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 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 
 
  
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 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 . 
C O N FI D E N TI A L  
Pa ge 6 3  of 9 3  
•  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. 

SAP_001.pdf: 
 
 
Page 1 of 34 
 
 
STATISTICAL ANALYSIS PLAN 
 
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) 
 
 
 
Protocol Number: 
CL011_140 
Protocol Version/Date: 
V4.0 / 29 October 2018 
Investigational Product: 
Selective antagonist of human C-C chemokine receptor type 2 
(CCR2) 
 
 
Sponsor: 
ChemoCentryx, Inc.  
 
 
 
SAP Version/Date: 
V1.0 / 06APR2020 
 
 
 
 
CONFIDENTIALITY STATEMENT 
The information contained herein is the property of the Sponsor and may not be reproduced, 
published or disclosed to others without written authorization of the Sponsor.  
This study will be conducted according to the principles of Good Clinical Practice as described in 
International Conference on Harmonization guidelines, including the archiving of essential 
documents.  
 




ChemoCentryx, Inc.  
CONFIDENTIAL 
Statistical Analysis Plan 
Protocol CL011_140  
 
Version 1.0, 06APR2020 
Page 3 of 34 
 
VERSION HISTORY 
Version 
Version Date 
Description 
1.0 
06APR2020 
Original signed version 
 
 


ChemoCentryx, Inc.  
CONFIDENTIAL 
Statistical Analysis Plan 
Protocol CL011_140  
 
Version 1.0, 06APR2020 
Page 4 of 34 
 
TABLE OF CONTENTS 
1 
Introduction ........................................................................................................................................... 8 
2 
Study Overview ..................................................................................................................................... 8 
2.1 
Study Objectives .................................................................................................. 8 
2.1.1 
Primary Objective ................................................................................................ 8 
2.1.2 
Secondary Objectives .......................................................................................... 8 
2.1.3 
Exploratory Objective .......................................................................................... 8 
2.2 
Study Design........................................................................................................ 9 
2.2.1 
Overview ............................................................................................................. 9 
2.2.2 
Randomization and Blinding ............................................................................. 14 
2.2.3 
Study Drug ......................................................................................................... 14 
2.2.4 
Sample Size Determination ............................................................................... 14 
2.3 
Study Endpoints ................................................................................................. 15 
2.3.1 
Primary Efficacy Endpoint ................................................................................ 15 
2.3.2 
Secondary Efficacy Endpoints ........................................................................... 15 
2.3.3 
Exploratory Endpoints ....................................................................................... 15 
2.3.4 
Pharmacokinetic Endpoints ............................................................................... 16 
2.3.5 
Pharmacodynamic Endpoints ............................................................................ 16 
2.3.6 
Safety Endpoints ................................................................................................ 17 
3 
Statistical Methodology ...................................................................................................................... 18 
3.1 
General Considerations ...................................................................................... 18 
3.1.1 
Analysis Day...................................................................................................... 18 
3.1.2 
Analysis Visits for Efficacy ............................................................................... 18 
3.1.3 
Definition of Baseline ........................................................................................ 19 
3.1.4 
Summary Statistics ............................................................................................ 19 
3.1.5 
Hypothesis Testing ............................................................................................ 19 
3.1.6 
Evaluation of Site Effect .................................................................................... 19 
3.2 
Analysis Populations ......................................................................................... 19 
3.2.1 
Intent-to-Treat (ITT) Population ........................................................................ 19 
3.2.2 
Intent-to-Treat (ITT) Population ........................................................................ 20 
3.2.3 
Per-Protocol (PP) Population ............................................................................. 20 
3.2.4 
Safety Population ............................................................................................... 20 
3.2.5 
Pharmacokinetic Population .............................................................................. 21 
3.2.6 
Pharmacodynamic Population ........................................................................... 21 
3.3 
Subject Data and Study Conduct ....................................................................... 21 
3.3.1 
Subject Disposition ............................................................................................ 21 
3.3.2 
Protocol Deviations ........................................................................................... 21 
3.3.3 
Analysis Populations ......................................................................................... 21 


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Statistical Analysis Plan 
Protocol CL011_140  
 
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3.3.4 
Demographic and Baseline Characteristics ....................................................... 21 
3.3.5 
Medical History ................................................................................................. 22 
3.3.6 
Concomitant Medications .................................................................................. 22 
3.3.7 
Study Drug Exposure and Compliance .............................................................. 22 
3.4 
Efficacy Assessment .......................................................................................... 23 
3.4.1 
Primary Efficacy Endpoint ................................................................................ 23 
3.4.2 
Secondary Efficacy Endpoints ........................................................................... 26 
3.4.3 
Exploratory Efficacy Endpoints ........................................................................ 28 
3.5 
Pharmacokinetic and Pharmacodynamic Marker Analysis ............................... 28 
3.5.1 
Data Assembly ................................................................................................... 28 
3.5.2 
Pharmacokinetic Concentration ......................................................................... 29 
3.5.3 
Pharmacokinetic Parameter ............................................................................... 30 
3.6 
Safety Assessment ............................................................................................. 31 
3.6.1 
Adverse Events (AEs) ....................................................................................... 31 
3.6.2 
Clinical Laboratory Tests .................................................................................. 32 
3.6.3 
Vital Signs ......................................................................................................... 32 
3.6.4 
Electrocardiograms ............................................................................................ 32 
3.6.5 
Physical Examinations ....................................................................................... 33 
3.6.6 
ACTG-BPNST ................................................................................................... 33 
4 
Data Monitoring Committee ............................................................................................................... 33 
5 
Analysis Timing .................................................................................................................................. 33 
5.1 
Interim Analysis ................................................................................................ 33 
5.2 
Final Analysis .................................................................................................... 33 
6 
Changes from Protocol-Specified Statistical Analyses ....................................................................... 33 
7 
Programming Specifications ............................................................................................................... 33 
Appendix A:  References ............................................................................................................................ 34 
 
 
 


ChemoCentryx, Inc.  
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Statistical Analysis Plan 
Protocol CL011_140  
 
Version 1.0, 06APR2020 
Page 6 of 34 
 
LIST OF ABBREVIATIONS 
Abbreviation 
Definition 
ADaM 
Analysis Data Model 
ANCOVA 
Analysis of Covariance 
AUC0-6 
Area under the plasma concentration-time curve from time of 
dosing to 6 hours post-dose  
CCL2 
CC Chemokine Ligand 2, also known as MCP-1  
CCR2  
CC Chemokine Receptor 2 
CCX140-B  
Sodium Salt of CCX140 
CDISC 
Clinical Data Interchange Standards Consortium 
CI 
Confidence Interval 
CKD-EPI 
Chronic Kidney Disease Epidemiology Collaboration 
Cmax 
Maximum Plasma Concentration 
Cmin 
Minimum Plasma Concentration 
CPK 
Creatine Phosphokinase 
CS 
Compound Symmetry 
CSR 
Clinical Study Report 
DB 
Double Blind 
DMC 
Data Monitoring Committee 
ECG 
Electrocardiogram 
eGFR 
Estimated Glomerular Filtration Rate 
EOS 
End of Study 
FSGS 
Focal Segmental Glomerulosclerosis 
IMP 
Investigational Medicinal Products 
ITT 
Intent-to-Treat 
LOCF 
Last Observation Carried Forward 
MAR 
Missing at Random 
MCP-1 
Monocyte Chemoattractant Protein 1, also known as CCL2 
MCP-MOD 
Multiple Comparison Procedure - Modelling 
MDRD 
Modification of Diet in Renal Disease 
MedDRA 
Medical Dictionary for Regulatory Activities 
MMRM 
Mixed-effects Model for Repeated Measures 
OLE 
Open Label Extension 
PD 
Pharmacodynamic 
PK 
Pharmacokinetic 
PP 
Per-Protocol 
PT 
Preferred Term 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SD 
Standard Deviation 
SOC 
System Organ Class 
TEAE 
Treatment Emergent Adverse Event  
TESAE 
Treatment Emergent Serious Adverse Event 
TFL 
Tables, Listings, Figures 
Tmax 
Time of Maximum Plasma Concentration 


ChemoCentryx, Inc.  
CONFIDENTIAL 
Statistical Analysis Plan 
Protocol CL011_140  
 
Version 1.0, 06APR2020 
Page 7 of 34 
 
Abbreviation 
Definition 
UACR 
Urinary Albumin to Creatinine Ratio  
UPCR 
Urine Protein to Creatinine Ratio 
 
 


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Statistical Analysis Plan 
Protocol CL011_140  
 
Version 1.0, 06APR2020 
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1 INTRODUCTION 
The purpose of this Statistical Analysis Plan (SAP) is to provide a description of the statistical 
methods to be implemented for the analysis of data from the study with protocol number 
CL011_140.  The SAP will be finalized prior to database lock.  For the final Clinical Study 
Report (CSR), the analysis outlined in the SAP will supersedes those described in the protocol. 
2 STUDY OVERVIEW 
2.1 Study Objectives 
The aim of this study is to evaluate the effect of treatment with CCX140-B (sodium salt of 
CCX140), a selective antagonist of C-C chemokine receptor type 2 (CCR2), in subjects with 
focal segmental glomerulosclerosis (FSGS).  
2.1.1 Primary Objective 
The primary safety objective of this study is to evaluate the safety and tolerability of CCX140-B 
in subjects with FSGS with proteinuria.  
The primary efficacy objective of this study is to evaluate the effect of CCX140-B treatment on 
urinary protein excretion in subjects with FSGS, as assessed by change from baseline in the urine 
protein to creatinine ratio (UPCR) at Week 12.  
2.1.2 Secondary Objectives 
The secondary objectives of this study are: 
 To evaluate the effect of CCX140-B on renal function, as assessed by estimated 
glomerular filtration rate (eGFR) at Weeks 12 and 24; 
 To evaluate the effect of CCX140-B treatment on fraction of subjects achieving complete 
and partial renal remission (by 2 different partial remission definitions); 
 To evaluate the pharmacokinetic (PK) profile of CCX140-B in subjects with FSGS.  
2.1.3 Exploratory Objective 
The exploratory objectives are: 
 To evaluate the effect of CCX140-B on urinary monocyte chemoattractant protein-1 
(MCP-1, also known as CCL2) and other serum and urinary markers of renal function 
and inflammation;  
 To explore the effect of CCX140-B on levels of blood monocytes, T, B and NK cells, and 
other blood and urinary markers potentially associated with CCR2 antagonism; 
 To explore the effect of CCX140-B on Health-related Quality of Life changes based on 
answers to the Short Form 36 version 2 (SF-36 v2) and EuroQuality of Life-5 Domains-5 
Levels (EQ-5D-5L) questionnaires; 


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Statistical Analysis Plan 
Protocol CL011_140  
 
Version 1.0, 06APR2020 
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 To explore the relationship among exposure (PK) of CCX140-B, serum albumin level, 
and UPCR.  
2.2 Study Design 
2.2.1 Overview 
This study will evaluate the efficacy, safety, tolerability, and pharmacokinetics of up to 12 weeks 
of treatment with each of three dose regimens of CCX140-B or placebo, when used in 
combination with stable standard of care therapy in subjects with FSGS with significant 
proteinuria, assessed as UPCR > 1g/g at Screening.  
The target is to enroll 40 adult male or female subjects in this randomized, double-blind, 
placebo-controlled, Phase 2 study. Subjects will be randomized 1:1:1:1 to one of four treatment 
groups:  
• 
Group A: Placebo (N=10)  
• 
Group B: CCX140-B 5 mg once daily (N=10)  
• 
Group C: CCX140-B 10 mg twice daily (N=10)  
• 
Group D: CCX140-B 15 mg twice daily (N=10)  
Subjects will be screened within a period not to exceed 28 days prior to Study Day 1 (the first 
day of dosing). All subjects will take blinded study medication in the morning and evening, with 
or without food, for 84 consecutive days. Following the 84-day blinded dosing period, all 
subjects will take open label CCX140-B for an additional 84 days at the highest dose under 
evaluation, currently planned to be 15 mg twice daily. 
During the treatment period, eligible subjects will visit the study center on Study Days 1, 8, 15, 
29 (Week 4), and Weeks 8, 12 (primary endpoint), 13, 16, 20, and 24 for study procedures 
including interval history, physical examination and vital signs, ECG, study questionnaires, and 
collection of blood and urine. Subjects will discontinue study drug as of Study Day 169 (Week 
24) and will return for a follow up visit on Week 28. When feasible, upon discontinuation of 
treatment for any reason a sample of whole blood should be collected for assessment of 
elimination 2, 7 and 14 days after the final dose of CCX140-B (or placebo).  
A study schema is depicted in Figure 1. All study procedures are presented in Table 1.  


 
 
 
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Figure 1 
Study Schema 
 
1If eligible subjects wish to participate in an Open-Label Extension; all subjects including those on placebo will be switched to CCX140-B (at 
the highest safe dose) after the completion of 12 weeks of blinded study drug treatment. 
 
 
  
 
 
 


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Table 1. Time and Events Table  
Assessments 
Screening 
Double-Blind Treatment1 
Open-Label Treatment 
Follow-Up  
Variable 
 
 
Initial Study Phase 
Extension Phase 
Elimination 
Days 
≤ 28 days 
1 
8  
15 
29 
57 
857 
92  
113 
141  
170  
  
1137 &198  
2,7 & 14 
days post 
final dose  
Weeks  
≤4 weeks  
  
1  
2  
4  
8  
127  
13  
16  
20  
24  
167 & 28  
  
Informed consent  
X  
  
  
  
  
  
  
  
  
  
  
  
  
Demographics, medical 
history, prior medications  
X  
  
  
  
  
  
  
  
  
  
  
  
  
HIV, HBV, HCV testing  
X  
  
  
  
  
  
  
  
  
  
  
  
  
Screening for tuberculosis4  
X  
  
  
  
  
  
  
  
  
  
  
  
  
Renal needle biopsy for FSGS 
confirmation (if not done 
previously and if diagnosis not 
based on genetic information)  
X  
  
  
  
  
  
  
  
  
  
  
  
  
Enrollment, Stratification and  
Randomization  
  
X  
  
  
  
  
  
  
  
  
  
  
  
Physical examination2  
X  
X3  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
  
Vital signs  
X  
X3  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
  
12-lead ECG  
X  
X  
  
  
  
  
X  
X  
  
  
X  
X  
  
Serum pregnancy test for 
women of childbearing 
potential  
X  
X  
  
  
X  
  
X  
  
X  
X  
X  
X  
  
Hematology, Serum chemistry 
(coagulation panel and lipids 
included at specified visits9)  
X  
X3,9  
X9  
X  
X9  
X  
X9  
X9  
X9  
X  
X9  
X9  
  
Whole blood for DNA  
  
X  
  
  
  
  
  
  
  
  
  
  
  
Lymphocyte subset8  
X  
X  
X  
X  
X  
  
X  
  
X  
  
X  
X  
  
Urinalysis  
X  
X3  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
  


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Assessments  
Screening  
Double-Blind Treatment1  
Open-Label Treatment  
Follow-Up  
Variable  
 
  
Initial Study Phase  
Extension Phase  
Elimination  
Days  
≤ 28 days  
1  
8  
15  29  
57  857  
92  
113  
141 
170  
  
1137 &198   
2,7 & 14 days 
post final dose 
Weeks  
≤4 weeks  
  
1  
2  
4  
8  
127  
13  
16  
20  
24  
167 & 28  
  
First morning void for urine 
protein and creatinine assays  
(UPCR, UACR and Cystatin  
C assessment)  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
  
24-hour urine collection  
  
X  
  
  
  
  
X  
  
  
  
X  
  
  
ACTG Brief Peripheral  
Neuropathy Screening Tool  
X  
X3  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
  
SF-36 v2 & EQ-5D-5L  
  
X3  
  
  
X  
  
X  
  
X  
  
X  
X  
  
CCX140-B/Placebo dispensing   
  
X  
  
  
X  
X  
  
  
  
  
  
  
  
CCX140-B/Placebo double-blind 
dosing   
  
X →  →  
→  
→  
→  
  
  
  
  
  
  
  
CCX140-B Open label 
dispensing  
  
  
  
  
  
  
X  
  
X  
X  
  
  
  
CCX140-B Open label dosing6  
  
  
  
  
  
  
X →  
→  
→  
→  
→  
  
  
CCX140-B accountability  
  
  
X  
X  
X  
X  
X  
X  
X  
X  
X  
  
  
Plasma MCP-1  
  
X3  
X  
X  
X  
  
X  
X  
X  
  
X  
X  
  
PD plasma/serum sample 
collection  
  
X3  
X  
X  
X  
  
X  
X  
X  
  
X  
X  
  
Urine MCP1-1,   
MCP-1/Creatinine  
  
X3  
X  
X  
X  
  
X  
X  
X  
  
X  
X  
  
PD urine sample collection  
  
X3  
X  
X  
X  
  
X  
X  
X  
  
X  
X  
  
PK plasma sample collection 
  
X3,5  
X  
X5  
X  
X 
X  
X  
X  
X  
X  
X11  
X11   


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Assessments  
Screening  
Double-Blind Treatment1  
Open-Label Treatment  
Follow-Up  
Variable  
 
  
Initial Study Phase  
Extension Phase  
Elimination  
Days  
≤ 28 days  
1  
8  
15  
29  
57  
857  
92  
113  
141  
170  
  
1137 &198  
  
2,7 & 14 
days post 
final dose  
Weeks  
≤4 weeks  
  
1  
2  
4  
8  
127  
13  
16  
20  
24  
167 & 28  
  
Concomitant medications  
X10  
X  
X  
X   
X  
X  
X  
X  
X  
X  
X  
X  
  
Adverse event assessment  
  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
  
1Week 1 and 2 visits must occur with a ± 1 day window. Week 4 through Week 28 visits may occur within a ± 3 day window.  
2Physical examination will include body weight measurements. Height will only be measured at Screening. Full physical examination will be performed at 
Screening and Day 1. At all other visits, limited, physical examination will be performed directed by review of systems, laboratory findings and Investigator 
discretion.  
3These procedures must be performed before taking the first dose of CCX140-B on Day 1; in addition, CBC and bilirubin will be assessed at 2 and 6 hours 
following dosing in blood to be drawn at the same time as the PK sample  
4TB screening by Interferon γ release assay (IGRA) done within 6 weeks prior to Screening or done during Screening.  
5PK blood sample will be collected on Days 1 and 15 prior to the morning dose (time 0), and at 0.5, 1, 2, 3, 4, and 6 hours following dosing. PK samples at all 
other visits will be collected at time 0 only, just prior to administration of the first daily dose.   
6 Eligible subjects may enter an Open-Label Extension at the highest safe dose of CCX140-B. The minimum eligibility requirements for the Open-Label 
Extension include no withdrawal of subject consent and no new infections that in the judgment of the investigator would preclude addition of a new 
immunosuppressive or immunomodulatory treatment, no requirement for addition of new immunosuppressive treatment during the prior 12 weeks and no 
anticipated requirement during the next 12 weeks.   
7The Week 16 visit is a safety follow up visit for subjects stopping study drug at Week 12, and not going onto the Open-Label Extension. For those going on the 
Open-Label Extension, Week 16 is a regularly scheduled study visit.  
8Whole blood for analysis of absolute count of T-cells, B-cells and Natural Killer Cells  
9 Serum chemistry at each visit to include liver panel (total, direct and indirect bilirubin, LDH, AST, ALT), alkaline phosphatase, etc. (see Section 8.2.2 of the 
protocol); at specified visits, to include coagulation panel (PT, PTT & INR) and lipids (HDL, LDL, Triglycerides and Total Cholesterol) as well  
10 Concomitant medications will be recorded for all medications taken 12 weeks prior to screening. Glucocorticoids and immunosuppressives will be recorded for 
up to 6 months prior to screening. If the subject has received prior rituximab treatment or other B-cell depleting antibodies, the medication use, as well as any 
available urinary protein values, should be recorded for up to 1 year prior to screening.   
11 PK blood samples will be collected at 2 days, 7 days and 14 days following the last dose of study drug, as well at the Follow-up Visit (Week 16 or Week 28) to 
assess elimination.  


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2.2.2 Randomization and Blinding 
Randomization will be stratified by UPCR <3.5 g protein/g creatinine versus UPCR ≥3.5 g 
protein/g creatinine at baseline and by the current use of glucocorticoids and/or 
immunosuppressive medications (yes vs no).  
Blinded study medication will be taken by the subjects for 84 days, as follows:  
• 
Group A: Three placebo tablets, taken twice daily;  
• 
Group B: One 5 mg CCX140-B tablet and two placebo tablets in the morning; three 
placebo tablets in the evening;  
• 
Group C: Two 5 mg CCX140-B tablets and one placebo tablet, taken twice daily;  
• 
Group D: Three 5 mg CCX140-B tablets, taken twice daily. 
Following the 84-day blinded dosing period, all subjects will take open label CCX140-B for an 
additional 84 days at the highest dose under evaluation, currently planned to be 15 mg twice 
daily. 
2.2.3 Study Drug 
Study drug will be administered as 3 tablets twice daily (5 mg CCX140-B tablets, matched 
placebo, or combination) for up to 12 weeks in a double-blind manner.  
CCX140-B will be administered as up to 3 tablets (5 mg each) twice daily during study weeks 13 
through 24 in an open-label manner.  
Study drug will be supplied to the study center in plastic bottles, each bottle containing 30 
tablets.  
During the blinded portion of the study, study drug will be supplied to the subject in kits, each kit 
containing 3 bottles labeled with a yellow band for use in the morning and 3 bottles labeled with 
a blue band for use in the evening. Each bottle will be also labeled with a distinguishing number. 
Subjects will be instructed to take one tablet from each of the three yellow bottles in the 
morning, and one tablet from each of the three blue bottles in the evening and to maintain a 
dosing diary.  
2.2.4 Sample Size Determination 
Assuming the standard deviation (SD) for the group difference in change from baseline in the 
logarithmic transformation of UPCR is 0.70, with 10 subjects per treatment group, the 90% 
confidence interval (CI) for the between group difference in the log scale will have a ½ width of 
0.543. In other words, if the ratio of the treatment over placebo is 0.5 (50% reduction from 
placebo) in UPCR, the 90% CI will be (0.29, 0.86) (i.e., 14% to 71% reduction).  
Assuming SD =8.5 for the group difference in change from baseline in eGFR, with 10 subjects 
per group, the 90% CI for the between group difference will have a ½ width of 6.6. If the 
difference between treatment and placebo is observed to be 10 mL/min/1.73m2, the 90% CI will 
be (3.4, 16.6).  


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Note the above calculation is based on the SD estimated from Study CL005_140 and an 
unadjusted 2-sided alpha of 10%.  
2.3 Study Endpoints 
2.3.1 Primary Efficacy Endpoint 
The primary efficacy endpoint is the change from baseline in urine protein:creatinine ratio 
(UPCR) at Week 12.  
2.3.2 Secondary Efficacy Endpoints 
Secondary efficacy endpoints include: 
 Change from baseline in eGFR calculated by the Chronic Kidney Disease Epidemiology 
Collaboration (CKD-EPI) cystatin C equation, CKD-EPI Creatinine equation, CKD-EPI 
Creatinine-Cystatin C equation and modification of diet in renal disease (MDRD) 
Creatinine equation at Weeks 12 and 24 
 Proportion of subjects achieving complete renal remission by the following definition at 
Weeks 12 and 24: 
o reduction in UPCR to <0.3 g/g 
and 
o serum albumin within normal range 
and 
 for patients with abnormal serum creatinine levels at baseline, return to 
normal levels for that age group 
or 
 for patients with normal serum creatinine levels at baseline, final value 
within 20% of baseline levels  
 Proportion of subjects achieving partial remission by the following two definitions 
assessed at Weeks 12 and 24: 
o UPCR reduction of ≥50% from baseline and UPCR < 3.5 g/g 
o decrease in UPCR to less than 1.5 g/g and at least a 40% reduction in proteinuria 
from baseline 
 
2.3.3 Exploratory Endpoints 
Exploratory endpoints include: 
 Change from baseline of proteinuria in subjects treated with CCX140-B versus placebo 
over time 
 Change from baseline (absolute and percent change) in urinary albumin:creatinine ratio 
(UACR). The response rate across dose groups for patients achieving 30% reduction in 


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UACR from baseline at Week 12 will be calculated, with the number of subjects in the 
respective treatment group in the ITT (or PP) population being the denominator. The 
analysis will be repeated for reductions of 20%, 40% and 50%. 
 Change from baseline in urinary MCP-1:creatinine ratio 
 Change from baseline in blood monocytes (absolute and %), T, B and NK cells  
 Change from baseline in Health-related Quality of Life changes based on Short Form 36 
version 2 (SF-36 v2) and EuroQuality of Life-5 Domains-5 Levels (EQ-5D-5L) 
questionnaires 
 Change from baseline in serum albumin 
 Relationship among PK, eGFR, serum albumin and UPCR 
2.3.4 Pharmacokinetic Endpoints   
Concentrations of CCX140 will be determined in plasma from 4.0-mL blood samples collected 
in K2EDTA tubes according to Table 1. The following parameters will be determined, where 
possible: 
  Cmax  
Maximum plasma concentration  
  Tmax  
Time of maximum plasma concentration   
 AUC0-6  Area under the plasma concentration-time curve from Time 0 to Hour 6 on Day 
1 and Day 15  
 Cmin        Trough level plasma concentrations at post-Day 1 visits  
On Days 1 and 15, samples will be taken at pre-dose, 0.5, 1, 2, 3, 4, and 6 hours after dosing. The 
blood samples collected on the other relevant study days need to be collected prior to taking the 
CCX140-B/ placebo dose.  
The relationship between PK and serum albumin and between PK and UPCR may be explored, 
where possible.  
Total plasma concentrations of CCX140 will be determined using validated analytical methods. 
These plasma samples may also be used to measure other markers associated with FSGS.  
2.3.5 Pharmacodynamic Endpoints 
Blood samples (plasma and serum) and urine samples for PD measurement will be collected 
according to the schedule in Table 1.  
In addition to those included in the exploratory efficacy endpoints, the following PD endpoints 
may be assessed if measured:  
• 
Profile of FSGS related gene mutations;  
• 
Change from baseline in other urinary and blood exploratory markers potentially associated 
with activity of FSGS or inhibition of the CCR2/MCP-1 pathways. These may include 
measurement of:  


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o Transforming growth factor-beta (TGF-B), connective tissue growth factor (CTGF), 
Nacetylglucosamine (NAG), β2 microglobulin, adiponectin, C-reactive protein (CRP), 
cystatin C, synaptopodin, neutrophil gelatinase-associated lipocalin (NGAL), liverfatty 
acid-binding protein (LFABP), kidney injury molecule-1(KIM-1), intact PTH, leptin, 
reistin, chemerin, retinol binding protein 4 (RBP-4), MCP-1, IL-1β, IL-6, suPAR, miR-
193a, CLCF-1 and TNF-α.  
2.3.6 Safety Endpoints 
2.3.6.1 Adverse Events  
Safety endpoints related to adverse events include subject incidence of treatment-emergent adverse 
events (TEAE), adverse events leading to study withdrawal, and serious adverse events. An 
adverse event will be considered treatment-emergent if the start date of the event is on or after the 
date of administration of the first dose of study medication.  
2.3.6.2 Clinical Laboratory Assessments  
Safety endpoints related to clinical laboratory assessments include change from baseline and 
shifts from baseline in all safety laboratory parameters.  
The following tests will be performed at the visits identified in the Time and Events Table (Table 
1).  
• 
Hematology: hemoglobin, hematocrit, RBC count, WBC count with differential, platelet 
count, mean cell hemoglobin, mean cell hemoglobin concentration, mean corpuscular 
volume, reticulocyte count and schistocytes;  
• 
Serum Chemistry: liver panel (total, direct and indirect bilirubin, lactate dehydrogenase 
[LDH], AST, ALT), renal panel (BUN, creatinine), creatine phosphokinase (CPK), albumin, 
sodium, potassium, magnesium, bicarbonate, chloride, calcium, inorganic phosphorus, 
glucose, total protein, alkaline phosphatase, uric acid, serum amylase, serum lipase, and 
cystatin C; at specified visits, coagulation panel (PT, PTT, INR), lipid panel (HDL, LDL, 
Triglycerides, Total Cholesterol) will be included  
• 
Urinalysis: At the central laboratory, nitrite, blood, and protein, will be tested. If positive, 
microscopy will be performed;  
• 
Virology (measured only at screening): hepatitis B surface antigen, hepatitis C antibodies, 
HIV 1 and 2 antibodies; virology tests done within 6 weeks prior to screening are acceptable 
for eligibility assessment;  
• 
TB screen: Only interferon γ release assay (IGRA) done within 6 weeks prior to screening is 
allowed for eligibility assessment.  
2.3.6.3 Vital Signs 
Safety endpoints include change from baseline in vital signs. Vital signs will be measured during 
screening and on each as specified in Table 1. Vital signs assessments will be performed after the 
subject has rested for at least three minutes while seated, and will include the following: 


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 Blood pressure 
 Pulse rate  
 Body temperature 
2.3.6.4 Electrocardiogram 
Safety endpoints include clinically significant abnormal electrocardiogram (ECG) findings. A 12-
lead ECG, after resting for at least 3 minutes, will be performed at screening and assessed for any 
clinically significant abnormalities. All abnormalities will be recorded in the EDC system. 
Assuming the ECG abnormality does not preclude study entry, an ECG may be repeated as 
clinically indicated.  
2.3.6.5 Physical Examination 
Safety endpoints include physical examination findings. A complete physical examination 
(including evaluation of general appearance/mental status, HEENT [head, eyes, ears, nose, throat], 
and the following body systems: dermatologic, cardiovascular, respiratory, gastrointestinal, 
musculoskeletal and neurologic) for safety, assessments will be performed at visits indicated in 
Table 1.   
Body weight will be measured as part of the physical examinations. Height needs to be recorded 
at screening only. BMI will be calculated from the body weight and height measurements.  
2.3.6.6 ACTG-BPNST  
Safety endpoints include change from baseline in score on the AIDS Clinical Trial Group Brief 
Peripheral Neuropathy Screening Test (ACTG-BPNST). ACTG-BPNST will be completed by the 
study subject and the study doctor to assess changes in neuropathy. Proven translations will be 
used for non-English speaking subjects, whenever possible. 
3 STATISTICAL METHODOLOGY 
3.1 General Considerations 
3.1.1 Analysis Day 
Analysis day will be calculated from the date of first dose of study drug.  The day of the first dose 
of study drug will be Day 1, and the day immediately before Day 1 will be Day -1.  There will be 
no Day 0. 
3.1.2 Analysis Visits for Efficacy 
Scheduled visits will be assigned to analysis visits as recorded in the electronic data capture 
(EDC) system. If a scheduled visit is not available, unscheduled and early termination visits will 
be assigned to analysis visits using analysis visit windows based on the actual date the 
assessment took place. The start day of the analysis window will be calculated as the midpoint 
between the scheduled assessment and previously scheduled assessment for that parameter. The 
end day of the analysis window will be calculated as the midpoint between the scheduled 
assessment and the next scheduled assessment for that parameter. Where multiple measurements 


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for a particular parameter appear within an analysis window, the scheduled visit will be used. If 
no scheduled visit appears in the analysis window, the result closest to the target day will be 
used. If equidistant and both are unscheduled and/or early termination visits, the later result will 
be used for the summary measure. 
Though all measures may not be used in data summaries (e.g., two lab measures within the same 
analysis visit window), all measurements appear in the datasets and listings. For subjects where 
the event date is missing, the study day and analysis window will also be missing. See the 
following table for an example of analysis windows. 
Analysis Visit 
Analysis Day Target 
Analysis Day Window 
Week 1 
8 
2 - 11 
Week 2 
15 
12 - 22 
Week 4 
29 
23 - 43 
Week 8  
57 
44 - 71 
Week 12 
85 
72 - 88 
Week 13 
92 
89 - 102 
Week 16 
113 
103 - 127 
Week 20 
141 
128 - 155 
Week 24 
170 
156 - 181 
Week 28 
198 
≥ 182  
3.1.3 Definition of Baseline  
Baseline is defined as the last non-missing value prior to start of dosing with study medication 
(typically the Day 1 pre-dose value).  
3.1.4 Summary Statistics 
Categorical data will be summarized with counts and percentages of subjects.  Continuous data 
will generally be summarized with descriptive statistics including n (number of non-missing 
values), mean, median, standard deviation, minimum, and maximum. 
3.1.5 Hypothesis Testing 
As this is an exploratory study in a rare disease, unless specified otherwise, all statistical tests 
and confidence intervals will be based on a 2-sided alpha of 0.10. No multiplicity adjustment 
will be applied to the multiple dose and multiple endpoints comparisons.  
3.1.6 Evaluation of Site Effect 
This is a multi-center study enrolling subjects from approximately 40 study sites across North 
America, Europe, and Australia and New Zealand. Site effect will not be evaluated since the 
number of subjects at each site is expected to be too small. 
3.2 Analysis Populations 
3.2.1 Intent-to-Treat (ITT) Population 
The ITT Population is defined as all randomized subjects.   


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3.2.2 Intent-to-Treat (ITT) Population 
The ITT Population is defined as all randomized subjects who received at least one dose of study 
drug and have a baseline assessment and at least one post baseline efficacy assessment.  This will 
be the primary analysis population for the evaluation of efficacy. 
3.2.3 Per-Protocol (PP) Population 
The PP Population is defined as all subjects in the ITT Population who have ≥80% compliance 
with the study drug administration and do not have protocol deviations that could significantly 
affect the interpretation of the results for the primary endpoints. The PP Population will be a 
secondary population for analysis of the primary efficacy endpoint.  
The following aspects will be considered for subjects to be excluded from the PP analysis: 
 Subjects with significant protocol deviations regarding inclusion and exclusion criteria that 
may impact evaluation of the primary endpoints. 
 Subjects with significant lack of compliance of study medication administration (CCX140-
B /placebo) defined as:  All subjects who were <80% compliant with taking CCX140-B 
/placebo based on study medication accountability records. 
 Subjects administered non-protocol allowed medications such as, calcineurin inhibitors, 
ACE-inhibitors or ARBs, sprironolactone, eplerenone, antihypertensive, diuretics, 
immunosuppressants or calcineurin inhibitors or subjects with dose increases of such drugs 
during the course of the study. 
 
Subjects to be excluded from the PP population will be identified and documented prior to the 
database lock and unblinding for analysis. A subject’s data could be partially excluded from 
analysis depending on when the deviation occurred.  For example, if a deviation occurred during 
the open-label extension (OLE) that did not impact the data from the double-blind period, only the 
data during the OLE will be excluded.  
3.2.4 Safety Population 
The Safety Population is defined as all randomized subjects who received at least one dose of study 
drug.  All safety data will be analyzed using the Safety Populations by the treatment groups that 
subjects are randomized to.  In the event that a subject takes the wrong study drug (i.e., did not 
take the randomized study drug), the actual treatment received will be used for analysis. 
Notations for Treatment Groups 
Period A: initial 12-week blinded treatment period, Day 1 –Week12 
Period B: open-label treatment period plus 4 Weeks of Follow-up, Week 12 to End of Study 
(EOS) 
 
We have defined 3 Safety Populations for this study: 


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1. The Safety Population in Period A (Safety_A) is defined as all subjects who received at 
least one dose of study drug in Period A. 
2. The Safety Population in Period B (Safety_B) is defined as all subjects who received at 
least one dose of study drug in Period B. 
3. The All CCX140-B Treated Population is defined as all subjects received at least one 
dose of CCX140-B in the study. 
 
3.2.5 Pharmacokinetic Population 
The PK Population is defined as all randomized subjects who received at least one dose of study 
drug and have at least one evaluable PK sample. Subjects with major protocol deviation such as 
PK deviation or compliance issues may be excluded from the PK analyses (i.e. descriptive 
statistics) upon agreement with the Sponsor on case by case basis but all data will be listed. Values 
that are excluded from the analysis will be footnoted appropriately. 
3.2.6 Pharmacodynamic Population 
The PD Population is defined as all randomized subjects who received at least one dose of study 
drug and have at least one evaluable PD sample.  
3.3 Subject Data and Study Conduct 
3.3.1 Subject Disposition 
The number and percent of subjects who were screened, screen failed (by reason), completed 
Week 12, who completed the Open-Label Extension, withdrew early from the study, along with 
the reasons for withdrawal, will be presented by treatment group.  
3.3.2 Protocol Deviations 
Major protocol deviations, i.e., those pertaining to GCP violations and those that may majorly 
affect the efficacy or safety evaluation, will be captured in the Study Management System as CSR 
Reportable deviations. These major deviations will be listed and summarized by category. These 
deviations will be reviewed prior to database lock to determine the potential impact on the 
interpretation of the efficacy and safety outcomes. The effect of any major protocol deviations and 
compliance will be assessed by conducting per-protocol analyses for the primary efficacy endpoint 
excluding subjects and/or study visits with major protocol deviations. This will be determined and 
documented prior to unblinding the study.  
3.3.3 Analysis Populations 
Counts and percentages of subjects in each analysis population will be summarized by treatment 
group and in total based on all randomized subjects.  Reasons for exclusion from each analysis 
population will also be summarized. 
3.3.4 Demographic and Baseline Characteristics 
All subject baseline characteristics and demographic data (age, sex, race, ethnicity, weight, height, 
body mass index), viral test results, FSGS duration (from time of first diagnosis based on renal 


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biopsy), eGFR, proteinuria (UPCR), level of proteinuria (UPCR <3.5 vs UPCR ≥3.5 g/g), 
proteinuria (UACR), prior Glucocorticoids or Immunosuppressant treatment, Calcineurin Inhibitor 
treatment (Cyclosporine, Tacrolimus), and diagnosis of nephrotic syndrome (defined as UPCR 
≥3.5 g/g) will be listed and summarized by treatment group and in total based on all randomized 
subjects. 
3.3.5 Medical History 
Medical history will be coded to system organ class and preferred term using the Medical 
Dictionary for Regulatory Activities (MedDRA) Version 20.1. Counts and percentages of 
subjects with medical history by system organ class and preferred term will be summarized by 
treatment and in total based on all randomized subjects. 
3.3.6 Concomitant Medications 
Concomitant medications will be coded using the World Health Organization (WHO) Drug 
Dictionary (September 2016E B2).  Prior medications are defined as any medication taken prior 
to the first dose of study medication (within 12 weeks of screening).  Concomitant medications are 
defined as any medication taken on or after the first dose of study medication. A medication can 
be classified as both prior and concomitant if it started before or during the screening period and 
continued into the treatment period. All prior and concomitant medications will be listed and 
summarized by Anatomic Therapeutic Chemistry (ATC) classification. All B-cell depleting 
antibodies, glucocorticoids and immunosuppressants taken within 6 months prior to screening may 
be summarized separately.  
3.3.7 Study Drug Exposure and Compliance 
Duration of exposure to study drug will be calculated as (date of last dose – date of first dose + 1).  
If date of last dose is not available, the date of discontinuation from study will be used. Duration 
of exposure to study medication will be summarized with descriptive statistics for double-blind 
period, open-label period and both periods. Exposure data will be provided for the following 
intervals, defined to align with the efficacy endpoints: 
 <=4 weeks (days 1-29) 
 >4 and <=12 weeks (days 30-85) 
 >12 and <=24 weeks (day 86-169) 
 >24 weeks (days >169) 
Percent compliance to study drug will be summarized for double-blind period, open-label period 
and both periods, calculated as follows: 
Percent Compliance = 100 × number of capsules taken / (6 × number of days in the 
specified period). 
Percent compliance to the study drug regimen will be summarized by treatment group based on 
the Safety Population using counts and percentages of subjects with compliance in the following 
categories: 


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 <80% 
 80-120% 
 >120% 
 
Covariates and Subgroups 
The analysis of the efficacy endpoints may be adjusted by the following variables in the form of 
covariate analysis and/or subgroup analysis: 
 UPCR <3.5 g protein/g creatinine versus UPCR ≥3.5 g protein/g creatinine at baseline  
 UPCR <1.5 g protein/g creatinine versus UPCR ≥1.5 g protein/g creatinine at baseline  
 Concomitant use of glucocorticoids and/or immunosuppressive medications (yes vs no) 
 Concomitant use of  Calcineurin Inhibitor (Cyclosporine, Tacrolimus) therapy (yes vs no) 
a. Cyclosporin (yes vs.no) 
b. All Calcineurin Inhibitors combined, i.e. Cyclosporin,or tacrolimus, etc.  (yes vs.no) 
 
Concomitant use of ACE inhibitor or ARB or Aldosterone antagonist use vs not 
 
Concomitant use of use of diuretic/additional antihypertensive agent  
a. Diuretics 
b. Additional antihypertensive treatments 
 Serum Albumin <3.5 g/dl vs  ≥3.5 g/dl   at baseline 
 Urinary albumin-to-creatinine ratio/Urinary protein-to-creatinine ratio ≥1.5 vs < 1.5 
 Patients with podocyte effacement of ≥30% versus <30% based on electron microscopy 
 
Patients with glomeruli showing segmental lesions >1 vs ≤1 based on electron microscopy 
 
3.4 Efficacy Assessment 
The overall efficacy hypothesis for this study is that CCX140-B will be effective in reduction in 
urine protein:creatinine ratio (UPCR) in treatment of subjects with FSGS. All available efficacy 
data will be listed for the ITT Population. Analyses of the efficacy endpoints will be performed 
using the ITT and PP populations, with the ITT population being the primary analysis population. 
3.4.1 Primary Efficacy Endpoint 
UPCR Change from Baseline 
The primary efficacy endpoint (UPCR) will be summarized by treatment group over time using 
descriptive statistics. Spaghetti plots of UPCR as well as percent change of UPCR (derived from 
morning void spot urine. If missing 24 hour urine evaluations will be used, if available) from 
baseline to weeks 4, 8, 12, 13, 16, 20, 24, and week 28 (if available) will be produced by treatment 
group and for all individual patients for visual inspection. Additionally, percent change of UPCR 
from week 12 to week 13, 16, 20, 24, and week 28 will be summarized by prior treatment group 
during the open-label period. The same analyses of for UPCR will be performed at baseline, week 
12 and week 24 solely using UPCR values derived from 24-hour urine evaluations (missing 
assessments will not be replaced with morning void spot urine values).   


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The primary analysis will use the morning void spot urine results.  If baseline or post-baseline 
morning void spot urine results are not available, 24 hour urine results will be used where available. 
Please note 24-hour urine assessments at Day 1, Week 12 and Week 24 were added after Protocol 
Amendment 4.0. 
For inferential analysis of the ratio to baseline, UPCR will be loge-transformed to alleviate 
skewness of the data since data are not normally distributed.  A mixed effect model for repeated 
measures (MMRM) will be performed in the ITT population with treatment, group, visit, and 
treatment-by-visit interaction as factors and baseline value and age as covariates.  Least squares 
mean differences and the corresponding 90% confidence intervals (CI) between each of the 
CCX140-B (5, 10, or 15 mg) groups and the placebo group will be back transformed to the original 
scale.  Corresponding P-values will also be presented. 
In the MMRM model, missing data will not be imputed.  This analysis is unbiased under the 
missing at random (MAR) assumption.  Toeplitz covariance matrix will be used to model within-
subject variance-covariance structure for the model errors. If the model does not converge using 
the Toeplitz covariance matrix, AR(1) covariance matrix will be used. If convergence is still not 
met, then compound symmetry (CS) will be used. 
 
The code used to generate the MMRM analysis will be similar to the following: 
********************************************************************************** 
Note:  
TRT01AN = randomized treatment group (numeric):  
          1=Placebo, 2=CCX140-B 5 mg, 3=CCX140-B 10 mg, 3=CCX140-B 15 mg 
VISITN = Visit Number  
LR2BASE = Ratio of Visit Value to Baseline Value (log-transformed)  
LBASE = Baseline value of response (log transformed) 
proc mixed data=lab_log; 
class SUBJID TRT01AN(ref='1') VISITN; 
model LR2BASE = TRT01AN LBASE AGE AVISITN TRT01AN*VISITN/ residual 
outp=residual ddfm=kr; 
Repeated VISITN / TYPE=TOEP sub=SUBJID; 
 
 
 
 
 
**use AR(1) if no convergence, then CS; 
lsmeans VISITN*TRT01AN / alpha=.10 cl pdiff slice=VISITN; 
ods output LSMeans=LSM 
           Diffs=DiffLSM; 
 
run; 
 
********************************************************************************** 
 
The same analysis described above will be performed for change from baseline in the open-label 
period and change from Week 12 in the open-label period. 
 
 


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Sensitivity analyses  
1. Given the high variability in morning void spot urine UPCR values, the baseline will be 
defined as the average of the screening and Day 1 morning void spot urine UPCR values 
if both are available. The UPCR analyses will be repeated using this baseline definition. If 
only one of 2 morning void spot urine values is available, that value will be used as the 
baseline. Post-baseline assessments will use the same approach as for the primary analysis 
prioritizing morning void spot urine and replacing missing assessments with 24 hour urine 
results where available.  
2. As 24-hour urine evaluations were not available for all subjects. The following analysis 
will be conducted: 
-Baseline will be calculated by averaging the screening and Day 1 values using 24 hour 
urine results where available.   
-Post baseline assessments will prioritize the 24 hour results where available.  Spot urine 
values will be used when 24 hour assessments are not available. 
3. A sensitivity analysis will be conducted using the same approach as the primary analysis, 
however, for subjects who have been identified as taking non-allowed medications, all data 
after the initiation of the non-allowed medication will be imputed using the last observation 
prior to the initiation of the non-allowed medication. 
 
Per-Protocol Analysis of UPCR 
The primary analysis of UPCR during the double-blind period will be run using the Per-Protocol 
population.  
 
Responder Analyses 
The response rate across dose groups for patients achieving 30% reduction in UPCR (whenever 
available 24-hour urine evaluations will be used) from baseline at Week 12 will be calculated, 
with the number of subjects in the respective treatment group in the ITT (or PP) population being 
the denominator. The 90% Clopper-Pearson exact CIs will be estimated for the response rates in 
each treatment group. The estimated difference and its associated 90% CIs of response rates 
between each of the CCX140-B (5, 10, or 15 mg) groups and the placebo group will be provided 
using stratified analysis using the Newcombe hybrid-score method. The Stratification factors are 
the same as used in the randomization: UPCR <3.5 g protein/g creatinine versus UPCR ≥3.5 g 
protein/g creatinine at baseline and by the current use of glucocorticoids and/or 
immunosuppressive medications (yes vs no) if there are enough responders. If there are not 
enough patients in any strata, the stratification variable will be removed from the model. 
 


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Non-responder imputation for non-allowed medications: 
All subjects who started new therapy or increased the doses of an existing therapy that is clinically 
significant and was not allowed per protocol will be imputed as non-responders for the responder 
analysis.  For example, the new use or clinically significant increase doses of an angiotensin 
converting enzyme (ACE) inhibitor, angiotensin receptor blocker (ARB) or other blocker of the 
renin angiotensin aldosterone system (RAAS) or new use of glucocorticoids, a calcineurin 
inhibitor or other immunomodulatory or immunosuppressive therapy will be reviewed before 
database lock.  
 
Dose-Response Analysis 
To demonstrate the dose-response relationship between CCX140-B treatment (including placebo) 
and the primary endpoint, a Multiple Comparison Procedure – Modelling (MCP-MOD) approach 
(Bretz et al., 2005) will be carried out. This analysis allows for uncertainty in the dose-response 
relationship through inclusion of contrasts from multiple pre-specified candidate models to assess 
dose-response. If a dose-response relationship exists, then the primary efficacy endpoint will be 
estimated in each of the treatment groups using the selected dose-response models. Four candidate 
models will be considered for the primary analysis. The models include a linear model, a logistic 
model, a quadratic model and an Emax model. Within each model, dose-response will be tested 
using dese levels of 0 (placebo), 1 (CCX140-B 5mg), 2 (CCX140-B 10mg) and 3 (CCX140-B 
15mg). 
The MCP-Mod procedure requires pre-specified parameter estimates for the candidate models 
based on available information in order to derive optimum contrast coefficients for testing the null 
hypothesis that a dose-response does not exist in any of the candidate models. The procedure will 
be carried out by the R package MCPMod (Bornkamp et al., 2017).  
Point estimates and the corresponding 90% CIs from the selected dose-response models will be 
displayed. 
 
3.4.2 Secondary Efficacy Endpoints 
Secondary efficacy endpoints include eGFR calculated by CKD-EPI cystatin C equation, CKD-
EPI Creatinine equation, CKD-EPI Creatinine-Cystatin C equation and MDRD Creatinine 
equation. They will be summarized by treatment group over time using descriptive statistics. The 
analysis of these endpoints may be performed using a mixed-effects model for repeated measures 
(MMRM) with treatment group, visit, and treatment-by-visit interaction as factors, and baseline 
value and age as covariates. Point estimates, standard errors, the corresponding 90% confidence 
intervals and p-values for the differences between treatment groups will be displayed. The 
treatment comparisons of most interest will be the Least squares (LS) means contrasts of treatment 
difference at Week 12 and Week 24. In the MMRM model, missing data will not be imputed. For 
sensitivity analysis, the change in eGFR from baseline may also be analyzed using an analysis of 
covariance (ANCOVA) model, including treatment group as a factor and baseline value and age 


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as covariates. Missing data will be imputed by the last observation carried forward (LOCF) 
method. LS means, standard errors, 90% confidence intervals and p-values for the differences 
between treatment groups will be displayed. Secondary efficacy endpoints also include the 
proportion of subjects achieving complete/partial renal remission at Weeks 12 and 24 as defined 
in section 2.3.2. The proportion will be calculated using the number of subjects in the respective 
treatment group in the ITT (or PP) population as the denominator. The 90% Clopper-Pearson exact 
CIs will be estimated for the proportion in each treatment group. The between group comparison 
will also be carried out using the Newcombe hybrid-score method with a two-sided significance 
level of 0.10.  
Stratified analyses will be conducted for testing difference in proportions between groups. The 
stratification variables are defined below as used in the randomization stratification.  The 
stratification factor values as collected in the electronic case report forms (eCRFs) will be used 
for all stratified efficacy analyses, subgroup analyses and summaries of baseline characteristics. 
 UPCR <3.5 g protein/g creatinine at baseline versus UPCR ≥3.5 g protein/g creatinine at 
baseline; 
 Current use of glucocorticoids/immunosuppressive medications (yes vs. no). 
If there is not enough patients in any strata, the stratification variable will be removed from the 
model. 
 
Analysis of Duration of Response 
Duration of response analysis will be done only for the responders. The time of duration of 
response is defined as the time from the initial response of PR or CR to disease progression (not 
PR or CR). For the subjects without disease progression, the time will be censored at the last 
clinical assessment. K-M estimate of median time and 90% CI will be provided. If there is not 
enough responders, this analysis will not be conducted. This analysis may be applied to the 
responder analyses, such as responders of 30% and 40% reduction of proteinuria. 
 
Combining CCX140-B dose groups: 
CCX140-B doses groups maybe combined to conduct pooled analysis if the efficacy responses 
are similar, i.e. all CCX 140 dose groups, and 10 mg and 15 mg BID combined. 
 
Proteinuria changes based on 24 our urine collection (see also section 3.4.1): 
Proteinuria analyses of UPCR and UACR described above that were derived from spot urine will 
be repeated for 24-hour urine analyses if available. 
 


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3.4.3 Exploratory Efficacy Endpoints  
The exploratory endpoints in section 2.3.3 will be summarized by treatment group over time using 
descriptive statistics, including MCP-1 levels by treatment group.    
An exploratory analysis of UPCR using the same MMRM analysis method as described in Section 
3.4.1 will be carried out with the addition of baseline urinary MCP-1 to creatinine ratio and 
baseline plasma MCP-1 as covariates. 
3.5 Pharmacokinetic and Pharmacodynamic Marker Analysis 
3.5.1 Data Assembly 
The concentration data of CCX140 as reported by the respective bioanalytical group will be used 
without rounding for all analysis. 
Subjects with major protocol deviation such as PK deviation or compliance issues may be 
excluded from the PK analyses (i.e. descriptive statistics) upon agreement with the Sponsor on 
case by case basis but all data will be listed. Values that are excluded from the analysis will be 
footnoted appropriately. 
The following general rules should apply for handling missing data or concentration below the 
lower limit of quantification (BLQ) on Day 1: 
 All BLQs will be set to “0” for Day 1 visit.  
 If the BLQ occurs between 2 quantifiable drug concentrations within a full PK profile for 
Day 1 visit, the BLQ is excluded from all PK assessments. 
 Missing pre-dose concentrations on Day 1 will be set as “0” and included in PK evaluation 
 Missing post-dose values on Day 1 will not be imputed and will be excluded from PK 
evaluation  
 Values that are excluded from the analysis will be documented appropriately. 
 Pre-dose values on Day 1 that are greater than 5% of Cmax will be documented. A sensitivity 
analysis (with inclusion and exclusion of the subjects with the pre-dose concentration >5% 
of Cmax) will be presented and documented in the study report. 
The following general rules should apply for handling missing or BLQ data on Day 15: 
 If the BLQ occurs between 2 quantifiable drug concentrations within a full PK profile for 
Day 15 visit, the BLQ is excluded from all PK assessments. 
 Missing pre-dose concentrations on Day 15 will be not imputed and excluded from PK 
evaluation. In case of missing pre-dose concentration on Day 15, AUCs on Day 15 will not 
be calculated for this subject. 
 Missing post-dose values on Day 15 will not be imputed and will be excluded from PK 
evaluation  
 Values that are excluded from the analysis will be documented appropriately. 
The sample time of the pre-dose samples on Day 1 and Day 15 will be uniformly considered as 


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time “0”.  
For the trough concentration for post-Day 1 visits and at 2 days, 7 days and 14 days after the last 
dose of study drug, all missing or BLQ concentration will not be imputed and will be excluded 
from the descriptive summary.  
For Day 1 and Day 15 visits, individual PK plots or individual PK parameters, since there is no 
collection window specified for post-dose PK sampling, will be based on actual times recorded.  
For concentration versus time descriptive statistical summaries and mean plot preparation, 
nominal time points will be used. If the difference of post-dose sampling time is > 5 minutes 
from the nominal sampling times for time points <2 hours or >5% for time points ≥2 hours, the 
corresponding concentration data will be excluded from the concentration summary and mean 
plot preparation, but will still be used in the individual plots and the calculation of PK parameter. 
For Day 1 and Day 15 visits, if the pre-dose PK sample is collected after dosing, the corresponding 
concentration will be treated as a post-dose value and will be used for individual plotting and PK 
parameter calculation.  
CCX140 plasma concentration results will be used to calculate trough plasma concentrations (Cmin) 
over the course of the clinical trial.  
For post-Day 1 visits, the allowable time window for PK trough sampling is ± 3 hours (i.e. 25% 
of dosing interval of 12 hours) for 10 or 15 mg BID dosing groups (C and D), and ± 6 hours (i.e. 
25% of dosing interval of 24 hours) for 5 mg QD dosing group (B) in the blinded treatment study 
phase (up to Week 12). However, in the open label extension phase (Week 13 to Week 24), all 
subjects will be given 15 mg BID, therefore, the allowable time window for PK trough sampling 
is ± 3 hours for all subjects. If the exact time (measured from dosing) is outside of the collection 
window, the corresponding concentration will be excluded from trough concentration versus time 
descriptive statistical summaries and median plot preparation, but will still be used in the 
individual plots.   
For the PK blood samples collected at 2 days, 7 days and 14 days following the last dose of study 
drug, as well at the Follow-up Visit, the actual sampling time should not exceed 5% of the nominal 
sampling time. If the exact time (measured from dosing) is outside of the collection window, the 
corresponding concentration will be excluded from concentration versus time descriptive 
statistical summaries and median plot preparation, but will still be used in the individual plots. 
Non-numerical readouts except BLQ [e.g. NA (not available) or NRE (not reliable)] will be set as 
missing and will not be included in the PK evaluation. 
3.5.2 Pharmacokinetic Concentration 
The individual plasma concentration of CCX140 will be listed.  
For subjects with serial samples collected (pre-dose and at 0.5, 1, 2, 3, 4, and 6 hour post-dose 
after the CCX140-B dose on Day 1 and on Day 15): 
 Individual plasma concentrations of CCX140 will be plotted on a linear and semi-
logarithmic scale against actual sampling time points;  
 Concentration data will be summarized by treatment at each nominal time point 
descriptively;  


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 Mean (±SD) plasma concentrations of CCX140 will be plotted on a linear and semi-
logarithmic scale against nominal time points by treatment. 
For subjects with pre-dose sample collected (Post-Day 1 visits): 
 Individual plasma concentrations of CCX140 will be plotted by treatment on a linear and 
semi-logarithmic scale against visits;  
 Trough concentration data, within allowable time windows, will be summarized by 
treatment at each visit descriptively.  
 In addition, median trough concentrations (Cmin) of CCX140 will be plotted overlaid with 
the scatter plot of individual trough concentrations by treatment on a linear and semi-
logarithmic scale against visits. 
 The average steady state trough concentration of CCX140 for each individual subject will 
be calculated for a to-be-defined  steady-state time period (each subject needs to have at 
least 3 time points in this steady state period for the calculation). The global average 
steady state trough concentration of CCX140 will be listed and summarized descriptively 
by treatment.  Box and whisker plots will be prepared by treatment for comparison. 
For subjects with samples collected at 2 days, 7 days and 14 days following the last dose of study 
drug, as well at the Follow-up Visit: 
 Individual plasma concentrations of CCX140 will be plotted on a linear and semi-
logarithmic scale against actual sampling time points by the treatment in blinded phase;  
 Concentration data will be summarized by the treatment in blinded phase at each nominal 
time point descriptively;  
 Mean (±SD) plasma concentrations of CCX140 will be plotted on a linear and semi-
logarithmic scale against nominal time points by the treatment in blinded phase. 
3.5.3 Pharmacokinetic Parameter 
For subjects with serial samples collected (pre-dose and at 0.5, 1, 2, 3, 4, and 6 hour post-dose 
after the first CCX140-B dose on Day 1 and on Day 15), Cmax, Tmax, and AUC0-6 will be determined 
based on individual CCX140 plasma concentration data. AUC0-12 or AUC0-24 will be determined 
for Day 15 assuming pre-dose level being the same as the concentration at the end of the dosing 
interval.  


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Parameters 
Description 
Cmax 
Maximum drug concentration after the first dose; observed directly from the 
data. If not unique, then the first maximum concentration is used 
Tmax 
Time to Cmax 
AUC0-6 
Area under the concentration-time curve (AUC) from time 0 to 6 hours post-
dose. For 6 hours post-dose sample, the corresponding observed 
concentrations will be used for AUC calculation if the difference of the actual 
time point is <5% from the nominal time point; otherwise, the concentration 
at the nominal 6-hour time point will be predicted and then used for the AUC 
calculation.  
AUC0-12 
AUC from time 0 to 12 hours post-dose on Day 15 only following 10 or 15 
mg BID dosing (Groups C and D). The concentration at 12-hour time point 
will be assumed to be the same as the pre-dose level. 
AUC0-24 
AUC from time 0 to 24 hours post-dose on Day 15 only following 5 mg QD 
dosing (Group B). The concentration at 24-hour time point will be assumed 
to be the same as the pre-dose level.  
PK parameter calculations will be based on all seven continuous time points from Day 1 and Day 
15 (including Time 0). The PK parameters of those subjects with less than seven continuous time 
points are listed as NA. 
Plasma PK parameters will be calculated by standard non-compartmental analysis. The actual 
collection times will be used for PK parameter calculation. The linear trapezoidal rule method 
(equivalent to the Linear Trapezoidal Linear Interpolation in WinNonlin® Professional) will be 
used in the computation of AUCs. 
PK parameters will be listed and summarized by treatment descriptively.  
The relationship between PK parameters and renal function based on eGFR, UPCR and UACR 
change of UPCR or UACR from baseline, and serum albumin will be evaluated through an 
exploratory analysis and summarized in a separate report. 
3.6 Safety Assessment 
Safety analyses will be performed for the Safety Population.  All safety assessments will be based 
on actual treatments received by participants.   
3.6.1 Adverse Events (AEs) 
An overview of AEs will be provided including counts and percentages of subjects (and event 
counts) with the following: 
 
Any TEAEs (overall and by maximum severity) 
 
Any study drug related TEAEs (overall and by maximum severity) 
 
Any treatment-emergent serious AEs (TESEAEs) 
 
Any TEAEs leading to discontinuation of study drug 
 
Any AEs leading to death 


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Counts and percentages of subjects (and event counts) will also be presented by system organ class 
(SOC) and preferred term (PT) using the Medical Dictionary for Regulatory Activities (MedDRA) 
Version 20.1 any TEAEs and TESEAEs for 3 Safety Populations separately. Counts and 
percentages of subjects (and event counts) will also be presented by PT in decreasing frequency 
for any TEAEs and TESEAEs for 3 Safety Populations (see 3.2.4 for definitions) separately. 
TEAEs for the Safety Population in each period are defined as an event with a start date on or after 
the first study drug treatment in each period and up to the final observation in each period. 
Treatment periods for analysis of adverse event are defined in Section 3.2.4. TEAEs for the All 
CCX140-B Treated Population are defined as an event with a start date on or after the first dose 
of CCX140-B up to the final observation. 
 
Listings will be presented specifically for SAEs and TEAEs leading to discontinuation of study 
drug. 
The severity of AEs was assessed by the investigator using the following protocol definitions: 
 Mild (Grade 1):  no limitation of usual activities 
 Moderate (Grade 2):  some limitation of usual activities 
 Severe (Grade 3):  inability to carry out usual activities 
 Life-threatening (Grade 4):  an immediate risk of death 
 Death (Grade 5) 
 
3.6.2 Clinical Laboratory Tests 
Laboratory results and change from baseline will be summarized for each treatment group by visit 
using descriptive statistics. Summaries will be limited to values assessed by the Central 
Laboratory. Shift tables from baseline to subsequent study visits will also be generated. Counts 
and percentages of laboratory values outside the normal reference range will be summarized in the 
double-blind period and open-label period respectively.  
Listings of laboratory values collected at local laboratories will be provided. Laboratory values 
outside the reference ranges will be flagged in the listings.  
3.6.3 Vital Signs 
Vital signs parameters will be summarized using descriptive statistics for each treatment group by 
visit. The change from baseline will also be summarized.  
3.6.4 Electrocardiograms 
Abnormal ECG findings will be listed by treatment group and study visit, and clinical 
significance of abnormalities indicated.  


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3.6.5 Physical Examinations 
Physical examination findings will be listed by treatment group and study visit, and clinical 
significance of abnormalities indicated. 
3.6.6 ACTG-BPNST 
ACTG-BPNST results and change from baseline will be summarized for each treatment group 
by visit. Listings of individual ACTG-BPNST will also be provided.  
4 DATA MONITORING COMMITTEE 
A Data Monitoring Committee (DMC) monitored the safety of subjects over the course of the 
study.  The DMC met once or more during the subject enrollment period to examine the unblinded 
accumulated safety data.  Subjects, investigators, site staff and in general all personnel directly 
involved in the conduct of the study will remain blinded to the subjects’ treatment assignment until 
the completion of the study. 
Details related to the DMC responsibilities, authorities, and procedures were documented in a 
DMC charter which was finalized prior the first subject being enrolled in the study. 
5 ANALYSIS TIMING 
5.1 Interim Analysis 
No interim analyses were planned. 
5.2 Final Analysis 
After all data is cleaned and the study database is declared final, the final analysis will be 
generated. In addition to TFLs, SDTM data and ADaM data along with associated files will be 
provided.  Associated files may include:  annotated case report forms (CRFs), SDTM 
specifications, SDTM programs, ADaM specifications, ADaM programs, TFL programs, and 
CDISC Define packages for both SDTM and ADaM data and reviewer’s guides.   
6 CHANGES FROM PROTOCOL-SPECIFIED STATISTICAL 
ANALYSES 
Per ChemoCentryx’s request, responder analysis and MCP-MOD have been added for the 
analysisof the primary efficacy endpoint. 
7 PROGRAMMING SPECIFICATIONS 
Analyses will be performed using SAS® version 9.3 or higher.  All available data will be 
presented in subject data listings which will be sorted by subject and visit date as applicable.  
Detailed Programming Specifications will be provided in a separate document. 
 
 


ChemoCentryx, Inc.  
  CONFIDENTIAL 
                  Statistical Analysis Plan 
Protocol CL011_140    
 
  Version 1.0, 06APR2020 
Page 34 of 34 
 
APPENDIX A:  REFERENCES 
[1] Bretz F, Pinheiro JC, Branson M (2005). Combining Multiple Comparisons and Modeling 
Techniques in Dose-Response Studies. Biometrics, 61, 738-748. 
[2] Bornkamp B, Pinheiro J and Bretz F (2017). MCPMod: An R Package for the Design and 
Analysis of Dose-Finding Studies. R package version 1.0-10, https://CRAN.R-
project.org/package=MCPMod.