An Open-label Extension to the Phase 2 Randomized, Double-blind, Placebo-controlled, Crossover Multicenter Study to Evaluate the Safety and Efficacy of KZR-616 in the Treatment of Patients With Active Polymyositis or Dermatomyositis
Phase: PHASE2
Conditions: Polymyositis, Dermatomyositis
Sponsor: Kezar Life Sciences, Inc.

 
K Z R- 6 1 6- 0 0 3 E 
A N O P E N- L A B E L E X T E N SI O N T O T H E 
P H A S E 2 R A N D O MI Z E D, D O U B L E- B LI N D, 
P L A C E B O- C O N T R O L L E D, C R O S S O V E R 
M U L TI C E N T E R S T U D Y T O E V A L U A T E T H E 
S A F E T Y A N D E F FI C A C Y O F K Z R- 6 1 6 I N T H E 
T R E A T M E N T O F P A TI E N T S WI T H A C TI V E 
P O L Y M Y O SI TI S A N D D E R M A T O M Y O SI TI S 
  
 
 
 
Cli nicaltrials. g o v I de ntifier 
N C T 0 4 6 2 8 9 3 6 
Date of pr ot oc ol: 
1 3 Se pte m ber 2 0 2 1 
 
 
 

C LI NI C A L S T U D Y P R O T O C O L  
Pr ot oc ol Title:  
A n O pe n -la b el E xte nsi o n t o t he P hase 2 Ra n d o mize d, 
D o u ble- bli n d, Place b o-c o ntr olle d, Cr oss o ver M ultice nter St u d y t o 
E val uate t he Safet y a n d Efficac y of K Z R - 6 1 6 i n t he Treat me nt of 
Patie nts wit h Acti ve P ol y m y ositis or Der mat o m y ositis  
Pr ot oc ol N u m ber : 
K Z R - 6 1 6- 0 0 3 E 
I n vesti g ati o n al 
Me dici n al Pr o d uct:  
K Z R - 6 1 6 
I n dic ati o ns: 
P ol y m y ositis ( P M) a n d Der mat o m y ositis ( D M)  
De vel o p m e nt P h ase:  
2 
U S I N D N u m ber : 
 
E u dr a C T N u m ber:  
2 0 2 0- 0 0 4 3 8 2- 3 9 
S p o ns or:  
Kezar Life Scie n ces, I n c.  
4 0 0 0 S h oreli ne C o urt, S uite 3 0 0 
S o ut h Sa n Fra ncisc o, C A 9 4 0 8 0 
Tele p h o ne: 6 5 0- 8 2 2- 5 6 0 0 
Ori gi n al Pr ot oc ol D ate: 
1 7 Se pte m ber 2 0 2 0 
A m e n d m e nt 1  
1 3 Se pte m ber 2 0 2 1 
 
 
C o nfi de nti alit y St ate me nt  
T he c o nce pts a n d i nf or m ati o n c o ntai ne d herei n are c o nfi de ntial a n d pr o pri etar y a n d s h all n ot 
be discl ose d i n w h ole or part wit h o ut t he e x press writte n c o nse nt of t he S p o ns or. 
 
 
C o m pli a nce St ate me nt  
T his st u d y will be c o n d ucte d i n acc or da n ce wit h t his pr ot oc ol, t he I nt er nati o nal C o nfere n ce o n 
Har m o nisati o n (I C H), G ui deli ne f or G o o d Cli nical Practice ( G C P), a n d t h e a p plica ble c o u ntr y 
a n d re gi o nal (l o cal) re g ul at or y re q uire me nts. 
 
 
 

Pr ot oc ol  A me n d me nt 1  
K Z R -6 1 6 -0 0 3 E  
Kezar Life Scie nces, I nc.  
1 3 Se pte m ber 2 0 2 1  
 
C o nfi de ntial  
Pa ge 3  of 6 6  
 
S T U D Y P E R S O N N E L  
 
Kez ar/ Cli nic al St u d y Le a d  
Na me  
Title  
 
Cli nical Researc h Ass o ciate  
A d dress 
Tele p h o ne N o. 
4 0 0 0 S h oreli ne C o urt, S uite 3 0 0, S o ut h Sa n Fra ncisc o, C A 9 4 0 8 0 
 
Seri o us A d verse E ve nt Re p orti n g C o nt act 
S afet y Le a d  
Na me  
Title  
 
Ass ociate Pr oject Ma n a g er  
Tele p h o ne N o. 
 
S eri o us A d verse E ve nt  Re p orti n g Det ails (t o be use d f or s u b mitti n g S A E f or ms):  
 
Ce ntral Safet y Fa x:  
 
* = c o u ntr y e xit c o d e 
 
 
 
 

Pr ot oc ol  A me n d me nt 1  
K Z R -6 1 6 -0 0 3 E  
Kezar Life Scie nces, I nc.  
1 3 Se pte m ber 2 0 2 1  
 
C o nfi de ntial  
Pa ge 4  of 6 6  
 
P R O T O C O L A C C E P T A N C E P A G E  
I h a ve r ea d a n d a gr ee t o t he pr ot oc ol, as det aile d i n t his d oc u me nt. I a m a w are of m y 
res p o nsi bilities as a n I n v esti gat or u n der t he I nter n ati o nal C o nfere n ce o n H ar m o nisati o n 
G ui deli ne (I C H) f or G o o d Cli nical Practice ( G C P), t he Decl arati o n of H elsi n ki, all  l ocal, 
re gi o nal, a n d nati o nal re g ulat or y re q uire m e nts (i ncl u di n g t he C o de of Fe d eral Re g ulati o ns [ C F R] 
Title 2 1 f or U S I n vesti gat ors), re q uire m e nts of t he a p plica ble I nstit uti o nal Re vie w 
B oar d/I n de pe n d e nt Et hics C o m mittee, a n d t he cli nical trial pr ot oc ol.  I a gree t o c o n d uct t he trial 
acc or di n g t o t hes e re g ulati o ns a n d g ui deli nes, t o a p pr o priatel y direct a n d assist t he staff u n der 
m y c o ntr ol t hat will be i n v ol ve d i n t he trial, a n d e ns ure t hat all staff me m b ers are a ware of t heir 
cli nical trial  res p o nsi bilities. 
I n v esti gat or Na me: 
 
Na me of I nstit uti o n/ Site:  
 
Si g nat ure: 
 
Date:  
 
 
 
 

Pr ot oc ol  A me n d me nt 1  
K Z R -6 1 6 -0 0 3 E  
Kezar Life Scie nces, I nc.  
1 3 Se pte m ber 2 0 2 1  
 
C o nfi de ntial  
Pa ge 5  of 6 6  
 
P R O T O C O L S Y N O P SI S  
N A M E O F I N V E S TI G A TI O N A L P R O D U C T:  
K Z R -6 1 6  
N A M E O F A C TI V E I N G R E DI E N T:  
K Z R -6 1 6  
C LI NI C A L C O N DI TI O N( S)/I N DI C A TI O N( S)  
•  
P ol y m y ositis ( P M)  
•  
Der mat o m y ositis  ( D M) 
P R O T O C O L N U M B E R:  K Z R -6 1 6 -0 0 3 E  
P R O T O C O L TI T L E:  
A n O pe n -la bel E xte nsi o n t o t he P hase 2 Ra n d o mize d, D o u ble -bli n d, Place b o -c o ntr olle d, Cr oss o ver 
M ultice nter St u d y t o E val uate t he Safet y a n d Efficac y of K Z R -6 1 6 i n t he Treat me nt of Patie nts wit h Acti ve 
P ol y m y ositis or Der mat o m y ositis  
S H O R T TI T L E: A n O pe n -la bel E xte nsi o n t o St u d y K Z R -6 1 6 -0 0 3  
S T U D Y P H A S E:  P hase 2  
S T U D Y O B J E C TI V E S:  
Effic ac y : T o e val uate t he l o n g-ter m efficac y of K Z R-6 1 6 i n patie nts wit h P M or D M.  
S afet y:  T o e val uate t he l o n g -ter m safet y a n d t olera bilit y of K Z R -6 1 6 i n patie nts wit h P M or D M.  
S T U D Y D E SI G N:  
T his is a n o pe n -la bel st u d y t o e val uate t he l o n g-ter m efficac y a n d safet y of K Z R-6 1 6 i n patie nts wit h acti ve 
P M or D M  w h o  c o m plete d t he d o u ble -bli n d  treat me nt peri o d of St u d y K Z R-6 1 6 -0 0 3 , u p t o a n d i ncl u di n g t he 
Wee k 3 2 Visit , pri or t o t he first d ose of o pe n -la bel K Z R -6 1 6.  
Patie nts will be e val uate d f or eli gi bilit y  acc or di n g t o t he e ntr y criteria  at, or wit hi n 8 wee ks after, t he Wee k 3 2 
Visit (ie, t he E n d of Treat me nt [ E O T ] Visit [ Visit 3 4]) of  St u d y K Z R -6 1 6 -0 0 3 . I nf or me d c o nse nt ma y be 
si g ne d pri or t o t he Wee k 3 2 Visit of St u d y K Z R -6 1 6 -0 0 3, a n d  m ust be si g ne d pri or t o a n y st u d y -relate d 
acti vit y  i n K Z R-6 1 6 -0 0 3 E. F or patie nts w h o are eli gi ble a n d willi n g t o e nr oll i n t he o pe n -la bel e xte nsi o n 
st u d y, t he K Z R-6 1 6 -0 0 3 Wee k 3 2 Visit ma y als o ser ve as Visit 1 ( Da y  1) f or t he o pe n -la bel e xte nsi o n st u d y. 
Assess me nts at t his visit perf or me d as part of St u d y K Z R -6 1 6 -0 0 3 will be use d as baseli ne val ues f or t he 
e xte nsi o n st u d y; t heref ore, t hese assess me nts m ust  be perf or me d pri or t o t he first d ose of o pe n -la bel 
K Z R -6 1 6.  
All p atients will recei ve a s u bc uta ne o us (S C ) i njecti o n of 3 0 m g K Z R-6 1 6 at Visit 1 ( Da y 1), f oll o we d b y 
wee kl y S C i njecti o ns of 4 5  m g K Z R -6 1 6 u p t o  a ma xi m u m of 9 6 wee ks . S t u d y dr u g a d mi nistrati o n will e n d  
f or all patie nts i n St u d y K Z R -6 1 6 -0 0 3 E  w he n t he last patie nt e nr olle d  has c o m plete d 4 8  wee ks of d osi n g . 
Patie nt s will ha ve a f i nal f oll o w-u p visit 1 2 wee ks after t he ir last d ose of K Z R-6 1 6 ( E n d of St u d y [ E O S] 
Visit), f or a ma xi m u m p ote ntial le n gt h of partici pati o n of 1 0 8 wee ks.  
O n -site st u d y visits will occ ur at Wee ks 1 2, 2 4, 3 6, 4 8, 6 0, 7 2, 8 4, a n d 9 6 ( E O T Visit), a n d t he E O S Visit. At 
t hese visits, safet y a n d efficac y assess me nts will be perf or me d acc or di n g t o t he Sc he d ule of Assess me nts 
(Ta ble  1). W hile t hese visits are ma n dat or y, i n rec o g niti o n of c o nstrai nts i m p ose d b y t he S A R S -C o V -2 
pa n de mic, site s ma y elect t o use a c o m bi nati o n of tele me dici ne (as per mitte d b y t heir i nstit uti o ns) a n d/ or 
h o me healt h pr o vi der s, i ncl u di n g at-h o me a d mi nistrati o n of K Z R -6 1 6.  All ot her st u d y visits ma y occ ur eit her 
at t he site  or  at patie nts’ h o me s via h o me healt h pr o vi der s (Ta ble  2). If necessar y, sa m ples f or cli nical 
la b orat or y assess me nts will be c ollecte d b y h o me healt h pr o vi der s a n d se nt t o t he la b orat or y. F or at -h o me 
K Z R -6 1 6 a d mi nistrati o n, d oses  ma y be a d mi nistere d b y h o me healt h pr o vi der s or, f or patie nts  dee me d  
a p pr o priate  b y t he I n vesti gat or , b y t he patie nt or care gi ver f oll o wi n g a p pr o priate i nstr ucti o n (see Secti o n 5. 4 ). 

Pr ot oc ol  A me n d me nt 1  
K Z R -6 1 6 -0 0 3 E  
Kezar Life Scie nces, I nc.  
1 3 Se pte m ber 2 0 2 1  
 
C o nfi de ntial  
Pa ge 6  of 6 6  
 
E N D P OI N T S:  
Effic ac y E n d p oi nts : 
•  
Mea n c ha n ge i n TI S o ver ti me f or all patie nts, f or patie nts wit h D M o nl y, f or patie nts wit h P M o nl y, 
a n d f or patie nts wit h a m y ositis -ass ociate d a nti b o d y or m y ositis -s pecific a nti b o d y at t he Scree ni n g 
Visit of St u d y K Z R -6 1 6 -0 0 3  
•  
Pr o p orti o n of patie nts b y TI S res p o nse ( mi ni mal res p o nse = TI S ≥ 2 0 , m o derate res p o nse = TI S ≥ 4 0 , 
maj or res p o nse = TI S ≥ 6 0)  
•  
Pr o p orti o n of patie nts meeti n g I nter nati o nal M y ositis Assess me nt a n d Cli nical St u dies Gr o u p 
(I M A C S) defi niti o n of i m pr o ve me nt ( D OI) o ver ti me f or patie nts wit h baseli ne c ore set meas ures as 
ascertai ne d at t he be gi n ni n g of K Z R -6 1 6 -0 0 3  
•  
Mea n c ha n ge a n d mea n perce nta ge c ha n ge o ver ti me i n t he I M A C S i n di vi d ual  c ore set acti vit y 
meas ures  (C S A Ms ) a n d  c or e set da ma ge meas ures  ( CS D Ms ), stratifie d b y all patie nts a n d patie nts 
wit h m y ositis -ass ociate d or  m y ositis -s pecific a nti b o d y at t he Scree ni n g Visit of St u d y K Z R-6 1 6 -0 0 3  
•  
M ea n c ha n ge o ver ti me i n t he C uta ne o us Der mat o m y ositis Disease Area a n d Se verit y I n de x  
( C D A SI) f or all patie nts wit h D M, a n d f or patie nts wit h D M w h o ha ve acti ve s ki n ma nifestati o ns at 
baseli ne  of St u d y K Z R -6 1 6 -0 0 3 E  
•  
Mea n c ha n ge o ver ti me i n t he M y ositis Da ma ge I n de x ( M DI ) 
•  
Mea n c ha n ge o ver ti me i n m uscle e nz y mes  
•  
C ha n ge i n pr o p orti o n a n d d os e of c ortic oster oi d a n d n o n -c ortic oster oi d i m m u n os u p pressa nts d uri n g 
St u d y K Z R -6 1 6 -0 0 3 E f or all patie nts, a n d f or patie nts ta ki n g c ortic oster oi ds or n o n -c ortic oster oi d 
i m m u n os u p pressa nts at baseli ne of St u d y K Z R-6 1 6 -0 0 3 E  
•  
Perce nta ge of patie nts re q uiri n g a d diti o nal me dicati o n f or m y ositis treat me nt d uri n g St u d y 
K Z R -6 1 6 -0 0 3 E  
•  
Mea n c ha n ge o ver ti me i n t he E ur o Q ol 5 -di me nsi o n 5 -le vel (E Q -5 D -5 L ) 
•  
A d diti o nal e x pl orat or y e n d p oi nts ( P h ysicia n Gl o bal I m pressi o n of C ha n ge [ M D GI C ], F u ncti o nal 
I n de x- 2 [FI - 2], Patie nt Gl o bal I m pressi o n of C ha n ge [ P GI C ], a n d P ea k P r uritis N u merical Rati n g 
Scale [ N R S]) will be assesse d at m ulti ple ti me p oi nts  
S afet y E n d p oi nts : 
•  
I nci de nce, nat ure, a n d se verit y of a d verse e ve nts ( A Es ) a n d  seri o us a d verse e ve nts (S A Es ) 
•  
I nci de nce of A Es lea di n g t o K Z R -6 1 6  disc o nti n uati o n  
•  
C ha n ges i n sta n dar d la b orat or y para meters  a n d  vital si g ns  
E x pl or at or y E n d p oi nt s: 
•  
Relati o ns hi ps bet wee n cli nical efficac y, cli nical safet y,  a n d vari o us bi o mar ker  e n d p oi nts i ncl u di n g 
c ha n ges i n circ ulati n g c yt o ki ne a n d w h ole bl o o d ge ne e x pressi o n  
•  
C ortic oster oi d -free TI S res p o nse b y visit (c ortic oster oi d-free is defi ne d as c ortic oster oi d f ull y ta pere d 
off f or ≥ 1 2 wee ks [ 3 m o nt hs ] pri or t o a visit; mi ni mal res p o nse = TI S ≥ 2 0 , m o derate res p o nse =  TI S 
≥ 4 0 , maj or res p o nse = TI S ≥ 6 0)   

Pr ot oc ol  A me n d me nt 1  
K Z R -6 1 6 -0 0 3 E  
Kezar Life Scie nces, I nc.  
1 3 Se pte m ber 2 0 2 1  
 
C o nfi de ntial  
Pa ge 7  of 6 6  
 
I N V E S TI G A TI O N AL P R O D U C T( S), D O S E, A N D M O D E O F A D MI NI S T R A TI O N:  
Acti ve Pr o d uct:  
I n vesti g ati o n al Me dici n al Pr o d uct: K Z R -6 1 6 is s u p plie d as a refri gerate d l y o p hilize d dr u g pr o d uct i n 
si n gle-use b or osilicate glass vial s pac ka ge d i n m ulti -vial cart o ns. F or patie nts eli gi ble f or at -h o me 
a d mi nistrati o n b y t he patie nt or care gi ver, a pre meas ure d, pre -fille d s yri n ge ( P F S) c o ntai ni n g sterile water f or 
i njecti o n ( W FI), a nee dleless vial a da pt or s yste m, a n d a d diti o nal cli nical su p plies nee de d f or rec o nstit uti o n 
will als o be pr o vi de d.  
D ose a n d D ose Fre q ue nc y:  K Z R -6 1 6 will be a d mi nistere d b y S C i njecti o n o nce wee kl y. T he first i njecti o n 
will be a 3 0 -m g d ose, a n d s u bse q ue nt i njecti o ns will be a 4 5 -m g d ose.  
C o ntr ol/ C o m p ar at or:  
T his is a n o pe n -la bel st u d y wit h n o c o ntr ol or c o m parat or. 
P A TI E N T S E L E C TI O N:  
T ar gete d N u m ber of P atie nts:  U p t o 2 4 patie nts  
Pl a n ne d N u m ber of Sites:  U p t o 2 4  sites 
I ncl usi o n Criteri a: 
1.  M ust ha ve s uccessf ull y c o m plete d St u d y K Z R -6 1 6 -0 0 3 t hr o u g h Wee k 3 2, i ncl u di n g t he Wee k 3 2 
V isit assess me nts, be willi n g a n d a ble t o pr o vi de writte n i nf or me d c o nse nt pri or t o a n y st u d y -relate d 
pr oce d ures, a n d be willi n g a n d a ble t o c o m pl y wit h st u d y re q uire me nts.   
2.  W o me n of c hil d beari n g p ote ntial ( W O C B P) m ust ha ve a ne gati ve u ri ne or ser u m  pre g na nc y test 
pri or t o t he first d ose of K Z R-6 1 6  i n St u d y K Z R-6 1 6 -0 0 3 E,  a n d m ust a gree t o c o nti n ue t o use a 
hi g hl y effecti ve met h o d of birt h c o ntr ol u ntil c o m pleti o n of t he st u d y ( or 3 0 da ys f oll o wi n g t he last 
d ose of K Z R -6 1 6 i n case of earl y wit h dra wal). W o me n of c hil d beari n g p ote ntial  are defi ne d as 
p ost p u besce nt fe male patie nts, u nless t he patie nt is p ost me n o pa usal ( defi ne d b y a me n orr hea f or at 
least 2 years or a me n orr hea f or at least 1 year wit h c o nfir mat or y f ollicle sti m ulati n g h or m o ne [ F S H] 
le vel i n t he p ost me n o pa usal ra n ge, as d oc u me nte d hist oricall y or meas ure d b y t he ce ntral or l ocal 
la b orat or y a n d if patie nt is n ot o n s u p ple me ntar y h or m o nal t hera p y) or s ur gicall y sterile (ie, t u bal 
li gati o n, h ysterect o m y, bilateral sal pi n g o o p h orect o m y). 
3.  Male patie nts m ust c o nti n ue t o use a n effecti ve c o ntrace pti o n met h o d (e g, c o n d o m wit h s per mici de) 
f or 1 wee k f oll o wi n g t heir last d ose of K Z R-6 1 6 or be c o n ge nitall y or s ur gicall y sterile (e g, 
vasect o m y wit h d oc u me nte d c o nfir mati o n of p ost -s ur gical as per mia). 
E xcl usi o n Criteri a : 
1.  Ha ve cli nical e vi de nce of si g nifica nt u nsta ble or u nc o ntr olle d diseases ot her t ha n t he disease u n der 
st u d y (e g, car diac [i ncl u di n g c o n gesti ve heart fail ure, h y perte nsi o n, a n gi na, or m y ocar dial 
i nfarcti o n], p ul m o nar y [i ncl u di n g p ul m o nar y h y perte nsi o n or i nterstitial l u n g disease], he mat ol o gic, 
gastr oi ntesti nal, e n d ocri n ol o gic, he patic, re nal,  ne ur ol o gical, or i nfecti o us disease, a n y o n g oi n g 
S A E (s), or A E (s) ≥ Gra de 3 b y Nati o nal Ca ncer I nstit ute C o m m o n Ter mi n ol o g y Criteria f or A d verse 
E ve nts [ N CI-C T C A E]) t hat, i n t he o pi ni o n of t he I n vesti gat or or S p o ns or/ desi g nee, c o ul d c o nf o u n d 
t he res ults of t he st u d y, p ut t he patie nt at u n d ue ris k, or i nterfere wit h pr ot oc ol a d here nce. 
2.  H as partici pate d i n a n y  cli nical st u d y ot her t ha n K Z R -6 1 6 -0 0 3 bet wee n t he Wee k 3 2 Visit of St u d y 
K Z R -6 1 6 -0 0 3 a n d t he first st u d y visit of K Z R -6 1 6 -0 0 3 E , if t he y are n ot o n t he sa me cale n dar da y. 
3.  Are fe males w h o are breastfee di n g  or w h o pla n t o bec o me pre g na nt d uri n g t he st u d y, or w h o are 
acti vel y tr yi n g t o c o ncei ve at t he ti me of si g ni n g of t he  i nf or me d c o nse nt f or m (I C F). 
4.  Ha ve h y perse nsiti vit y t o K Z R -6 1 6 or a n y of its e xci pie nts.  

Pr ot oc ol  A me n d me nt 1  
K Z R -6 1 6 -0 0 3 E  
Kezar Life Scie nces, I nc.  
1 3 Se pte m ber 2 0 2 1  
 
C o nfi de ntial  
Pa ge 8  of 6 6  
 
S T A TI S TI C A L A N A L Y SI S : 
T his st u d y is descri pti ve i n nat ure, a n d n o f or mal h y p ot hesis testi n g will be perf or me d. N o f or mal statistical 
sa m ple size esti mati o n has bee n perf or me d, si nce t he n u m ber of patie nts i n t his st u d y is deter mi ne d b y t he 
n u m ber of patie nts w h o c o m plete d St u d y K Z R -6 1 6 -0 0 3 a n d e nr olle d i n t his st u d y. 
A n al ysis Sets:  
F ull A nal ysis Set ( F A S) : T he F A S f or s u m maries of efficac y e n d p oi nts will i ncl u de all patie nts w h o recei ve 
K Z R -6 1 6 i n t his st u d y a n d ha ve baseli ne a n d a n y p ost baseli ne data. All o bser ve d data will be i ncl u de d i n t he 
statistical s u m maries. N o missi n g data will be i m p ute d  e xce pt as pre -defi ne d i n t he statisti cal a nal ysis pla n 
( S A P). 
Per Pr ot oc ol ( P P) : A P P p o p ulati o n ma y be use d t o a nal yze select efficac y e n d p oi nts, a n d will be base d o n 
K Z R -6 1 6 e x p os ure (ti me o n treat me nt) a n d pr ot oc ol de viati o ns. T he decisi o n t o s u m marize a P P p o p ulati o n 
will be ma de pri or t o data base l oc k.  
Safet y P o p ulati o n : T he safet y p o p ulati o n will i ncl u de all patie nts e nr olle d  w h o recei ve d at least o ne  d ose of 
K Z R -6 1 6, a n d will be t he p o p ulati o n use d f or t he a nal ysis of safet y. A d verse e ve nt data will be c o de d t o 
s yste m or ga n class a n d preferre d ter m usi n g Me dical Dicti o nar y f or Re g ulat or y Acti vities ( Me d D R A; 
Versi o n  1 9. 1 or later).  
F urt her details of t he statistical met h o d ol o g y, i ncl u di n g met h o ds f or ha n dli n g missi n g dat a a n d earl y 
wit h dra wals, will be pr o vi de d i n a n S A P  t hat will be fi nalize d pri or t o data base l oc k. 
 
 
 
 
 
 
 

Pr ot oc ol  A me n d me nt 1  
K Z R -6 1 6 -0 0 3 E  
Kezar Life Scie nces, I nc.  
1 3 Se pte m ber 2 0 2 1  
 
C o nfi de ntial  
Pa ge 9  of 6 6  
 
T A B L E O F C O N T E N T S  
1.  
I ntr o d ucti o n ................................................................................................................... 1 6 
1. 1.  
2 6 S Pr oteas o me Bac k gr o u n d .......................................................................................... 1 6  
1. 2.  
Pr oteas o me I n hi bit ors f or t he Treat me nt of I nfla m mat or y 
Dis or ders  ......................................................................................................................... 1 6 
1. 3.  
K Z R - 6 1 6 Bac k gr o u n d..................................................................................................... 1 7 
1. 4.  
Rati o nale f or Use of K Z R - 6 1 6 i n t he Pr o p ose d St u d y 
P o p ulati o ns, a n d Rati o nale f or t he St u d y........................................................................ 1 8  
1. 5.  
Rati o nale f or St u d y E n d p oi nts ........................................................................................ 1 9  
1. 6.  
S u m mar y of P ote ntial Ris ks a n d Be nefits ...................................................................... 1 9  
2.  
St u d y O bjecti ves a n d E n d p oi nts  ................................................................................. 2 1 
2. 1.  
St u d y O bjecti ves ............................................................................................................. 2 1  
2. 2.  
St u d y E n d p oi nts .............................................................................................................. 2 1  
2. 2. 1.  
Effic ac y E n d p oi nts .......................................................................................................... 2 1  
2. 2. 2.  
Safet y E n d p oi nts ............................................................................................................. 2 2  
2. 2. 3.  
E x pl orat or y E n d p oi nts .................................................................................................... 2 2  
3.  
St u d y Desi g n  .................................................................................................................. 2 3 
3. 1.  
T y pe a n d Desi g n of St u d y .............................................................................................. 2 3  
3. 1. 1.  
St u d y Desi g n Rati o nale................................................................................................... 2 4  
3. 2.  
Mi ni mizati o n of Bias  ...................................................................................................... 2 4 
3. 3.  
N u m ber of Sites .............................................................................................................. 2 4  
4.  
P atie nt Selecti o n a n d E nr oll me nt  ................................................................................ 2 5 
4. 1.  
N u m ber of Patie nts ......................................................................................................... 2 5  
4. 2.  
I n cl usi o n Criteria ............................................................................................................ 2 5 
4. 3.  
E xcl usi o n Criteria  ........................................................................................................... 2 5 
5.  
St u d y Tre at m e nt I nf or m ati o n  ..................................................................................... 2 7 
5. 1.  
P h ysical Descri pti o n of K Z R- 6 1 6................................................................................... 2 7  
5. 2.  
Pac ka gi n g a n d La b eli n g .................................................................................................. 2 7  
5. 3.  
S u p pl y, Dis pe nsi n g, St ora ge, a n d K Z R- 6 1 6 Acc o u nta bilit y .......................................... 2 7  
5. 4.  
At -H o me A d mi nistrati o n of K Z R - 6 1 6 b y Patie nt or Care gi ver ..................................... 2 7 
6.  
D os a ge a n d K Z R- 6 1 6 A d mi nistr ati o n......................................................................... 2 9  
6. 1.  
K Z R - 6 1 6 A d mi nistrati o n ................................................................................................ 2 9 
6. 1. 1.  
A d mi nistrati o n Site  ......................................................................................................... 2 9 
6. 1. 2.  
S u g geste d Meas ures t o I m pr o ve K Z R- 6 1 6 T olera nce .................................................... 2 9  
6. 1. 3.  
D ose M o dificati o n G ui deli nes ........................................................................................ 3 0  
6. 2.  
Pri or a n d C o nc o mita nt Treat me nts ................................................................................. 3 0  
6. 2. 1.  
Per mitte d C o nc o mita nt Me dicati o ns  ............................................................................... 3 1 
6. 2. 2.  
Ot her Restricti o ns a n d Pr o hi biti o ns ................................................................................ 3 2  
7.  
St u d y E v al u ati o ns ......................................................................................................... 3 3  
7. 1.  
Sc he d ul e of Assess me nts  ................................................................................................ 3 3 
7. 1. 1.  
U nsc he d ule d Visits ......................................................................................................... 3 3  
7. 1. 2.  
Tele healt h Visits  ............................................................................................................. 3 3 
7. 2.  
St u d y Pr oce d ures a n d Assess me nts ................................................................................ 4 0  

Pr ot oc ol  A me n d me nt 1  
K Z R -6 1 6 -0 0 3 E  
Kezar Life Scie nces, I nc.  
1 3 Se pte m ber 2 0 2 1  
 
C o nfi de ntial  
Pa ge 1 0  of 6 6  
 
7. 2. 1.  
De m o gra p hic Data  .......................................................................................................... 4 0 
7. 2. 2.  
P ol y m y ositis/ Der mat o m y ositis Classificati o n  ................................................................ 4 0 
7. 2. 3.  
Me dical Hist or y  .............................................................................................................. 4 0 
7. 2. 4.  
Efficac y Assess me nts ...................................................................................................... 4 0 
7. 2. 5.  
Patie nt Re p orte d O utc o m e Meas ures  .............................................................................. 4 2 
7. 2. 6.  
Safet y Assess me nts  ......................................................................................................... 4 3 
7. 2. 7.  
E x pl orat or y Bi o mar kers .................................................................................................. 4 4  
7. 2. 8.  
C o ntrace pti o n Re q uire m e nts a n d Pre g na n c y Testi n g ..................................................... 4 5  
8.  
St u d y Disc o nti n u ati o n  .................................................................................................. 4 7 
8. 1.  
St u d y a n d I n di vi d ual Patie nt St o p pi n g R ules ................................................................. 4 7  
8. 1. 1.  
St u d y St o p pi n g R ules  ...................................................................................................... 4 7 
8. 1. 2.  
I n di vi d ual Patie nt St o p pi n g R ules .................................................................................. 4 7 
8. 2.  
Earl y Wit h dra w al of Pati e nts fr o m t he St u d y ................................................................. 4 7  
8. 3.  
L ost t o F oll o w- U p  ........................................................................................................... 4 8 
8. 4.  
Earl y Ter mi nati o n Visit  .................................................................................................. 4 9 
8. 5.  
Ter mi nati o n or S us pe nsi o n of t he St u d y......................................................................... 4 9  
9.  
A d verse E ve nts  .............................................................................................................. 5 0 
9. 1.  
A d verse E v e nt Re p orti n g ................................................................................................ 5 0  
9. 1. 1.  
Defi niti o n of a n A d verse E ve nt ...................................................................................... 5 0  
9. 1. 2.  
Assess me nt of Se verit y  ................................................................................................... 5 0 
9. 1. 3.  
Assess me nt of Ca usalit y  ................................................................................................. 5 0 
9. 1. 4.  
Acti o n Ta ke n wit h Re gar d t o K Z R - 6 1 6.......................................................................... 5 1 
9. 1. 5.  
F oll o w- u p of A d v erse E v e nts ......................................................................................... 5 1  
9. 1. 6.  
D oc u me ntati o n a n d Re p orti n g of A d verse E ve nts.......................................................... 5 2  
9. 2.  
Seri o us A d verse E v e nts .................................................................................................. 5 2  
9. 2. 1.  
Defi niti o n of a Seri o us A d verse E ve nt ........................................................................... 5 2  
9. 2. 2.  
Seri o us A d verse E v e nt Re p orti n g a n d D oc u me nt ati o n 
Re q uire me nts  .................................................................................................................. 5 3 
9. 3.  
Pre g na nc y Re p orti n g....................................................................................................... 5 3  
9. 4.  
Ne w  or W orse ni n g Disease Ma nifestati o ns .................................................................... 5 4 
9. 5.  
I njecti o n Site Reacti o ns .................................................................................................. 5 4 
9. 5. 1.  
A d verse E v e nts of S peci al I nt erest  ................................................................................. 5 4 
9. 6.  
U ne x pect e d A d verse Reacti o ns  ...................................................................................... 5 5 
9. 6. 1.  
Defi niti o n of a n U ne x p ecte d A d verse R eacti o n ............................................................. 5 5  
9. 7.  
Data M o nit ori n g C o m mittee  ........................................................................................... 5 5 
1 0.  
St atistic al A n al yses ....................................................................................................... 5 6  
1 1.  
Et hic al a n d A d mi nistr ati ve C o nsi der ati o ns ............................................................... 5 8  
1 1. 1.  
C o m plia nce State me nt  .................................................................................................... 5 8 
1 1. 2.  
I nstit uti o nal Re vie w B oar d or I n de p e n de nt Et hics C o m mittee ...................................... 5 8 
1 1. 3.  
I nf or me d C o nse nt a n d H u ma n Patie nt Pr otecti o n .......................................................... 5 8 
1 1. 4.  
Direct Access t o S o urce Data, S o urce D oc u me nts, a n d St u d y 
Re p orts ............................................................................................................................ 5 9  
1 1. 5.  
Data C ollecti o n a n d Ha n dli n g......................................................................................... 5 9  
1 1. 6.  
C o nfi de ntialit y  ................................................................................................................ 5 9 
1 1. 7.  
Fi na nci n g a n d I ns ura n ce ................................................................................................. 5 9  

Pr ot oc ol  A me n d me nt 1  
K Z R -6 1 6 -0 0 3 E  
Kezar Life Scie nces, I nc.  
1 3 Se pte m ber 2 0 2 1  
 
C o nfi de ntial  
Pa ge 1 1  of 6 6  
 
1 1. 8.  
A u dit a n d I ns pecti o n ....................................................................................................... 6 0  
1 1. 9.  
M o nit ori n g ...................................................................................................................... 6 0  
1 1. 1 0.  
Data Ma na g e me nt a n d C o di n g  ....................................................................................... 6 0 
1 1. 1 1.  
Re p orti n g a n d P u blicati o n, I n cl u di n g Arc hi vi n g ............................................................ 6 1  
1 2.  
Refere nces  ...................................................................................................................... 6 2 
1 3.  
A p pe n dices  ..................................................................................................................... 6 6 
1 3. 1.  
A p pe n di x A: Pr ot oc ol Hist or y ........................................................................................ 6 6  
1 3. 2.  
A p pe n di x B: We bsites f or Patie nt- Re p orte d O utc o mes 
Assess me nts  .................................................................................................................... 6 7 
 
LI S T O F T A B L E S  
Ta ble  1 
Sc he d ule of Assess me nts  ............................................................................................ 3 4 
Ta ble  2 
Sc he d ule of K Z R- 6 1 6 A d mi nistrati o n a n d Assess me nts ............................................ 3 7  
Ta ble  3 
Ca usalit y Cate g ories  ................................................................................................... 5 1 
 
LI S T O F FI G U R E S  
Fi g ure 1  
St u d y K Z R- 6 1 6- 0 0 3 E St u d y Desi g n Sc he ma ............................................................. 2 4  
 

Pr ot oc ol  A me n d me nt 1  
K Z R -6 1 6 -0 0 3 E  
Kezar Life Scie nces, I nc.  
1 3 Se pte m ber 2 0 2 1  
 
C o nfi de ntial  
Pa ge 1 2  of 6 6  
 
LI S T O F A B B R E VI A TI O N S  
A b bre vi ati o n or Ter m  
Defi niti o n  
A C R  
A merica n C olle ge of R he u mat ol o g y  
A E  
A d verse e ve nt 
A E SI  
A d verse e ve nt of s pecial i nterest  
A L T  
Ala ni ne a mi n otra nsferase  
A S T  
As partate a mi n otra nsferase  
C D  
Cl uster of differe ntiati o n  
C D A SI  
C uta ne o us Der mat o m y ositis Disease Area a n d Se verit y I n de x  
C F R  
C o de of Fe deral Re g ulati o ns 
C GI  
Cli nical Gl o bal I m pressi o ns scale  
CI M  
C- pr otei n i n d uce d m y ositis  
C K  
Creati ne ki nase  
C -L  
C as pase -li ke 
C T - L 
C h y m otr y psi n- li ke 
C R P  
C- reacti ve pr otei n 
C S A M  
C ore set acti vit y meas ures  
C S D M  
C ore set da ma ge meas ures  
C Y P  
C yt oc hr o me P 4 5 0 
D DI  
Dr u g -dr u g i nteracti o n  
D M  
Der mat o m y ositis  
D M C  
Data M o nit ori n g C o m mittee  
D N A  
De o x yri b o n ucleic aci d  
D OI  
Defi niti o n of I m pr o ve me nt 
E C G  
Electr ocar di o gra m  
e C R F 
Electr o nic case re p ort f or m  
E D C  
Electr o nic data ca pt ure  
E LI S A  
E nz y me- li n ke d i m m u n os or be nt assa y 
E O S  
E n d of St u d y  
E O T  
E n d of treat me nt  
E Q - 5 D- 5 L 
E ur o Q ol 5 - di me nsi o n 5-le vel 
E Q -V A S  
E ur o Q ol vis ual a nal o g scale  
E T V  
Earl y Ter mi nati o n Visit  
E U L A R  
E ur o pea n Lea g ue A gai nst R he u matis m  
F A S  
F ull A nal ysis Set  
F D A  
F o o d a n d Dr u g A d mi nistrati o n 

Pr ot oc ol  A me n d me nt 1  
K Z R -6 1 6 -0 0 3 E  
Kezar Life Scie nces, I nc.  
1 3 Se pte m ber 2 0 2 1  
 
C o nfi de ntial  
Pa ge 1 3  of 6 6  
 
A b bre vi ati o n or Ter m  
Defi niti o n  
FI - 2 
F u ncti o nal I n de x- 2 
F S H  
F ollicle sti m ulati n g h or m o ne  
G C P  
G o o d Cli nical Practice  
G L P  
G o o d La b orat or y Practice  
G M P  
G o o d Ma n ufact uri n g Practice  
H A Q -DI  
Healt h Assess me nt Q uesti o n naire -Disa bilit y I n de x  
h C G  
Beta - h u ma n c h ori o nic g o na d otr o pi n 
I C F 
I nf or me d c o nse nt f or m 
I C H 
I nter nati o nal C o u ncil f or Har m o nisati o n 
I/ E 
I ncl usi o n/ E xcl usi o n 
I E C 
I n de pe n de nt Et hics C o m mittee  
I F U 
I nstr ucti o ns f or Use  
I g G 
I m m u n o gl o b uli n G 
I M A C S 
I nter nati o nal M y ositis Assess me nt a n d Cli nical St u dies Gr o u p 
I V 
I ntra ve n o us 
I R B 
I nstit uti o nal Re vie w B oar d 
I S R 
I njecti o n site reacti o n 
L D H  
Lactate de h y dr o ge nase  
L M P  
L o w -m olec ular mass p ol y pe pti de  
L N  
L u p us ne p hritis 
M D A A T  
M y ositis Disease Acti vit y Assess me nt T o ol  
M D G A  
P h ysicia n Gl o bal Assess me nt  
M D GI C  
P h ysicia n Gl o bal I m pressi o n of C ha n ge 
M DI  
M y ositis Da ma ge I n de x  
M E C L - 1 
M ulticatal ytic e n d o pe pti dase c o m ple x -li ke 1 
Me d D R A  
Me dical Dicti o nar y f or Re g ulat or y Acti vities 
MI T A X  
M y ositis I nte nti o n t o Treat Acti vit y I n de x 
M M F  
M yc o p he n olate m ofetil  
M M T - 8 
Ma n ual M uscle Testi n g -8 M uscle Gr o u ps  
M Y O A C T  
M y ositis Disease Acti vit y Assess me nt Vis ual A nal o g ue Scales 
N CI -C T C A E  
Nati o nal Ca ncer I nstit ute C o m m o n Ter mi n ol o g y Criteria f or A d verse E ve nts  
N R S  
N u meric al Rati n g Scale  
P B M C  
Peri p heral bl o o d m o n o n uclear cell 
P D  
P har mac o d y na mic 
P F S  
Pre -fille d s yri n ge 
P GI C  
Patie nt Gl o bal I m pressi o n of C ha n ge 

Pr ot oc ol  A me n d me nt 1  
K Z R -6 1 6 -0 0 3 E  
Kezar Life Scie nces, I nc.  
1 3 Se pte m ber 2 0 2 1  
 
C o nfi de ntial  
Pa ge 1 4  of 6 6  
 
A b bre vi ati o n or Ter m  
Defi niti o n  
P- g p 
P- gl yc o pr otei n 
P K  
P har mac o ki netic  
P M  
P ol y m y ositis  
P P  
Per pr ot oc ol  
P R O M  
Patie nt -re p orte d o utc o me meas ure 
Pt G A D A  
Patie nt Gl o bal Assess me nts of Disease Acti vit y  
Pt G A D D  
Patie nt Gl o bal Assess me nts of Disease Da ma ge  
R A  
R he u mat oi d art hritis 
R N A  
Ri b o n ucleic aci d 
S A E  
Seri o us a d verse e ve nt  
S A P  
Statistical a nal ysis pla n  
S C  
S u bc uta ne o us  
S D  
Sta n dar d de viati o n 
S L E  
S yste mic l u p us er yt he mat os us 
S T S  
Sit -t o-sta n d 
S U S A R  
S us pecte d u ne x pecte d seri o us a d verse reacti o n  
T E A E  
Treat me nt -e mer ge nt a d verse e ve nt  
T h  
T hel per cell  
T -L  
T r y psi n-li ke 
TI S  
T otal I m pr o ve me nt Sc ore  
Tre g  
Re g ulat or y T cell 
U S  
U nite d States  
V A S  
Vis ual a nal o g scale  
W FI  
Water f or i njecti o n  
W H O  
W orl d Healt h Or ga nizati o n 
W O C B P  
W o me n of c hil d beari n g p ote ntial 
 

Pr ot oc ol  A me n d me nt 1  
K Z R -6 1 6 -0 0 3 E  
Kezar Life Scie nces, I nc.  
1 3 Se pte m ber 2 0 2 1  
 
C o nfi de ntial  
Pa ge 1 5  of 6 6  
 
1.  
I N T R O D U C TI O N 
St u d y K Z R- 6 1 6- 0 0 3 E is a n o pe n-la b el e xte nsi o n of t he P hase 2 st u d y K Z R- 6 1 6- 0 0 3, w hic h is a 
ra n d o mize d, d o u ble- bli n d, place b o- c o ntr olle d cr oss o ver st u d y t o e val uate t he effi cac y a n d safet y 
of K Z R -6 1 6 i n t he treat m e nt of patie nts wit h acti v e p ol y m y ositis ( P M) or der mat o m y ositis 
( D M). 
1. 1.  
2 6 S Pr ote as o me  B ac k gr o u n d  
T he 2 6 S pr oteas o me is a u bi q uit o usl y e x presse d pr otei n c o m ple x res p o nsi ble f or t he h o me ostatic 
c o ntr ol of pr otei n t ur n o v er a n d r e g ulate d d e gra d ati o n of pr otei ns i n v ol ve d i n m ost cell ular 
f u ncti o ns (Ciec ha n o v er 2 0 1 2 ; C o u x 1 9 9 6 ; Wil k 1 9 8 3 ). Eac h pr ot eas o me c o ntai ns a 2 0 S c ore, 
c o ntai ni n g 2 c o pies of 3 disti nct pr ote ol ytic e nz y mes, a n d 2 re g ulat or y ca ps f or mi n g a 2 6 S 
c o m ple x. 
T he  pr oteas o me e xists i n 2 f or ms: t he c o nstit uti ve pr oteas o me a n d t h e i m m u n o pr oteas o me. T he 
c o nstit uti ve pr oteas o me is e x presse d u bi q uit o usl y t hr o u g h o ut t he b o d y a n d is res p o nsi ble f or 
pr otei n de gra d ati o n i n tiss ues s uc h as t he heart, ki d ne y, a n d li ver. I n t h e c o nstit uti ve pr oteas o me, 
pr ote ol ytic acti vities are e nc o de d i n t he β 5, β 1, a n d β 2 s u b u nits a n d are c h aracterize d b ase d o n 
s u bstrate s pecificit y as c h y m otr y psi n-li ke ( C T-L), cas pase -li ke ( C- L) a n d tr y psi n-li ke ( T-L), 
res pecti vel y. T h e i m m u n o pr oteas o me is e x presse d pri maril y i n  he mat o p oietic ce lls (e g, 
l y m p h oc ytes a n d m o n oc ytes), a n d is i n d uce d i n c yt o ki ne-e x p ose d n o n he m at o p oietic cells 
(Gl y n ne 1 9 9 1 ; Marti nez 1 9 9 1 ; Na n di 1 9 9 6 ). I n t he i m m u n o pr oteas o me, l o w-m olec ular m ass 
p ol y pe pti de ( L M P) 7, L M P 2, a n d m ulticatal ytic e n d o pe pti dase c o m ple x-li ke 1 ( M E C L-1) 
re place t he β 5, β 1, a n d β 2  s u b u nits of t he c o nstit uti ve pr oteas o me, res pecti vel y. L o w -m olec ular 
mass p ol y pe pti de 7 has a si milar s u bstr ate prefere nce as β 5 a n d is t h us referre d t o as t he C T -L 
s u b u nit of t he i m m u n o pr oteas o me. 
T he pr oteas o me h as bee n vali date d as a t hera pe utic dr u g tar g et t hr o u g h re g ulat or y a p pr o val of 
3 c o m p o u n ds, b ortez o mi b ( V E L C A D E ® ), carfilz o mi b ( K Y P R O LI S® ), a n d i xaz o mi b 
( NI N L A R O® ), f or use i n t he treat me nt of t he plas ma cell ne o plas m, m ulti ple m yel o ma. T hese 
c o m p o u n ds all s h o w e q ui vale nt p ote nc y f or t he β 5 s u b u nit of t he c o nstit uti ve pr oteas o me a n d t he 
L M P 7 s u b u nit of t he i m m u n o pr oteas o me ( Kir k 2 0 1 2 ; Kissele v 2 0 1 2 ). T his d ual-tar geti n g nat ure 
is necessar y f or t heir a bilit y t o i n d uce c yt ot o xicit y i n m ulti ple m yel o ma cells a n d ot her cell 
t y pes. Selecti ve i n hi bit ors of L M P 7 or β 5 al o ne ha ve n o c yt ot o xic p otential ( Parlati 2 0 0 9 ). 
1. 2.  
Pr ote as o me I n hi bit ors f or t he Tre at me nt of I nfl a m m at or y Dis or ders  
T he pr oteas o me h as bee n p osite d as a tar get f or dr u g de vel o p me nt i n c hr o nic i nfla m mat or y 
c o n diti o ns a n d a ut oi m m u ne dis or ders ( Elli ott 2 0 0 3 ). B ortez o mi b, a c o nstit uti ve or d ual-tar g eti n g 
pr oteas o me i n hi bit or, bl oc ks c yt o ki ne rel ease fr o m i m m u ne effect or cells a n d has de m o nstrate d 
a nti-i nfla m mat or y acti vit y i n se veral a ni mal m o dels of a ut oi m m u ne dis or ders i ncl u di n g 
r he u mat oi d art hritis ( R A) (Pal o m bella 1 9 9 8 ) a n d s yste mic l u p us er yt he mat os us ( S L E) 
(Ne u bert 2 0 0 8 ). M ore rece ntl y, b ortez o mi b was s h o w n t o ha ve ra pi d cli nical acti vit y i n patie nts 
wit h refract or y S L E a n d l u p us ne p hritis ( L N) w h o ha d faile d sta n d ar d i m m u n os u p pressi ve 
t hera pies (Al e xa n der 2 0 1 5 ; Z ha n g 2 0 1 7 ; de Gr o ot 2 0 1 5 ). H o we v er, s yste mic t o xicities 
ass ociate d wit h d ual -tar g eti n g pr oteas o me i n hi biti o n, s uc h as a ne mia a n d t hr o m b oc yt o pe nia, 
restrict chr o ni c a d mi nistrati o n ( Br oss 2 0 0 4 ). F urt h er, b ortez o mi b is ass ociate d wit h a 

Pr ot oc ol  A me n d me nt 1  
K Z R -6 1 6 -0 0 3 E  
Kezar Life Scie nces, I nc.  
1 3 Se pte m ber 2 0 2 1  
 
C o nfi de ntial  
Pa ge 1 6  of 6 6  
 
d ose-li miti n g si de effect of peri p her al ne ur o p at h y, li kel y ca use d b y off- tar g et i n hi biti o n of t he 
seri ne pr otease Htr A 2 i n ne ur o ns (Ar ast u - Ka p ur 2 0 1 1). Peri p heral ne ur o pat h y is n ot i n d uce d b y 
pe pti de ket oe p o xi de pr ot eas o me i n hi bit ors s uc h as carfilz o mi b ( Arast u - K a p ur 2 0 1 1; Di m o p o ul os 
2 0 1 6 ). 
T he disc o ver y of P R- 9 5 7 ( n o w calle d O N X 0 9 1 4), a selecti ve i m m u n o pr oteas o me i n hi bit or, 
de m o nstrate d t hat t he i m m u n o m o d ulat or y a n d a nti- i nfla m mat or y effects of d ual-tar geti n g 
pr oteas o me i n hi bit ors are d ue t o i n hi biti o n of i m m u n o pr oteas o me acti vit y i n i m m u ne effect or 
cells a n d i nfla me d tiss ues ( Ic hi ka w a 2 0 1 2; M uc ha m uel 2 0 0 9 ). O N X 0 9 1 4 is a tri pe pti de 
ket oe p o xi de a n al o g of carfilz o mi b t hat selecti vel y i n hi bits t he i m m u n o pr oteas o me i n vitr o a n d 
u p o n a d mi nistrati o n t o mice. O N X 0 9 1 4 e x p os ure i n hi bite d c yt o ki ne pr o d ucti o n i n i m m u ne 
effect or cells, re d uce d t he n u m ber a n d acti vit y of i nfla m mat or y T cell s u bs ets s uc h as T hel per 
( T h) cells 1 a n d T h 1 7, i n creas e d t he n u m ber of re g ulat or y T cells ( Tre g), a n d bl oc ke d 
a ut oa nti b o d y f or mati o n ( Ic hi ka wa 2 0 1 2; M uc ha m uel 2 0 0 9 ; Kali m 2 0 1 2 ). O N X 0 9 1 4 was s h o w n 
t o be t hera pe uticall y acti ve i n m o use m o dels of S L E, i n w hic h it de m o nstrate d e q ui vale nt 
acti vit y b ut better t olera bilit y t ha n b ortez o mi b ( Ic hi ka wa 2 0 1 2; Kali m 2 0 1 2 ). I n a d diti o n, 
treat me nt of mice wit h O N X 0 91 4 di d n ot re d uce t he n u m ber of s ple nic l y m p h oc ytes or i m pair 
viral cleara nce i n m ulti ple i nfecti o n m o dels ( M uc ha m uel 2 0 0 9 ; M u n dt 2 0 1 6 ). 
1. 3.  
K Z R- 6 1 6  B ac k gr o u n d  
K Z R - 6 1 6 is a tri pe pti de ket oe p o xi de t hat is a n a n al o g of b ot h O N X 0 9 1 4 a n d t he Unite d States 
( U S) F o o d a n d Dr u g A d mi nistrati o n ( F D A)-a p pr o ve d a ge nt carfilz o mi b. K Z R - 6 1 6 was 
de vel o pe d i n a me di ci nal c he mistr y eff ort t o o pti mize p ote nc y a n d s electi vit y f or m ulti ple 
i m m u n o pr oteas o me s u b u nits. K Z R- 6 1 6 de m o nstrates p ote nt a n d selecti ve i n hi biti o n of t he 
L M P 7 s u b u nit of t he i m m u n o pr oteas o me a n d tar gets m ulti ple s u b u nits of t he 
i m m u n o pr oteas o me at t hera pe uticall y rele v a nt c o nce ntrati o ns. K Z R- 6 1 6 h as n o a p pare nt 
off -tar g et acti vities, n o si g nifica nt si g nals i n safet y p har mac ol o g y st u dies, a n d n o a p pare nt 
ge n ot o xic p ote ntial. 
K Z R - 6 1 6 bl oc ks c yt o ki ne pr o d ucti o n acr oss m ulti ple i m m u ne cell t y pes, re d uces t he acti vit y of 
i nfla m mat or y T h  cell s u bsets, a n d bl oc ks plas ma cell f or mati o n a n d a ut oa nti b o d y pr o d ucti o n. I n 
m o use m o dels of S L E a n d L N , K Z R- 6 1 6 treat me nt i m pr o ve d re nal f u n cti o n i n disease d a ni mals 
a n d dra maticall y re d uce d tiss ue da ma ge a n d le u k o c yte i nfiltrati o n i n ki d ne ys. I n a d diti o n, 
c o m bi ni n g K Z R- 6 1 6 wit h m yc o p he n olate m ofetil ( M M F ) i mpr o ve d t h e t hera pe utic res p o nse 
vers us eit her tr eat me nt al o ne i n t he sa me m o use m o dels. T he p har mac o ki netics ( P K) a n d 
meta b olic pr o perties of K Z R -6 1 6 i n precli nical m o dels i n dicate little ris k f or dr u g - dr u g 
i nteracti o ns ( D DIs) a n d are si milar t o carfilz o mib, a n a ge nt w hic h h as bee n s h o w n t o ha ve little 
t o n o D DI ris k (Wa n g 2 0 1 3 ). I n b ot h ra n g e-fi n di n g a n d G o o d La b orat or y Practice 
( G L P)-c o m plia nt t o xicit y st u dies, K Z R - 6 1 6 was w ell t olerate d at d oses t hat res ulte d i n selecti ve 
a n d p ote nt i n hi biti o n of t he i m m u n o pr oteas o me. 
T he safet y, P K, a n d pr oteas o me i n hi biti o n le vel of K Z R- 6 1 6 has bee n st u die d i n healt h y 
v ol u nteers i n 2 P hase 1 trials, K Z R - 6 1 6- 0 0 1 a n d K Z R- 6 1 6- 0 0 4. S u bc uta ne o us ( S C) 
a d mi nistrati o n of K Z R - 6 1 6 was well t olerat e d at d oses t hat res ulte d i n p ote nt a n d selecti ve 
i n hi biti o n of t he i m m u n o pr oteas o me, b ut n ot t he c o nstit uti ve pr oteas o me. A d verse e ve nts ( A Es) 
were g e ner all y mil d a n d tra nsie nt a n d w ere pre d o mi na ntl y i njecti o n site reacti o ns (I S Rs) s uc h as 
er yt he ma, i n d ur ati o n, a n d te n der ness ( p ai n). Treat me nt wit h K Z R - 6 1 6 f or 4 wee ks di d n ot a p pear 

Pr ot oc ol  A me n d me nt 1  
K Z R -6 1 6 -0 0 3 E  
Kezar Life Scie nces, I nc.  
1 3 Se pte m ber 2 0 2 1  
 
C o nfi de ntial  
Pa ge 1 7  of 6 6  
 
t o res ult i n persiste nt la b orat or y a b n or m alities as c o m m o nl y see n wit h t he d ual-tar geti n g 
pr oteas o me i n hi bit ors (e g, t hr o m b oc yt o pe nia, a ne mia, a n d ne utr o pe nia). 
S u bc uta ne o us a d mi nistrati o n of K Z R - 6 1 6 res ulte d i n c o nsiste nt, d ose- pr o p orti o nal P K. At all 
d ose le vels teste d, K Z R - 6 1 6 was ra pi dl y a bs or b e d a n d cleare d wit h n o acc u m ulati o n f oll o wi n g 
wee kl y re p eat d oses. Dr u g le vels wer e bel o w t he li mit of q ua ntitati o n b y 2 4 h o urs p ost d ose. T he 
p har mac ol o g y w as c o nsiste nt acr oss s u bjects, wit h l o w i nter -s u bject varia bilit y i n b ot h e x p os ure 
a n d tar get i n hi biti o n, re g ar dless of c o n c o mita nt treat me nt wit h or wit h o ut c ortic oster oi ds a n d 
a nti hista mi nes. T h o u g h K Z R- 6 1 6 is a wea k ti me- de pe n de nt i n hi bit or of C yt oc hr o me P 4 5 0 
(C Y P ) 3 A 4 a n d a s u bstrate of P- gl yc o pr otei n ( P- g p), t he ra pi d cl eara nce a n d e xtra he p atic 
meta b olis m of K Z R - 6 1 6 b y e p o xi de h y dr olases str o n gl y s u g gest t hat t here is mi ni mal ris k f or a 
D DI.  
Acr oss a d ose ra n g e fr o m 7. 5 t o 7 5 m g, S C a d mi nistrati o n of K Z R- 6 1 6 res ulte d i n selecti ve a n d 
d ose- de pe n d e nt i n hi biti o n of peri p her al bl o o d m o n o n uclear cell ( P B M C) C T- L acti vit y 
( pre d o mi na ntl y i m m u n o pr oteas o me), wit h d oses of ≥3 0 m g res ulti n g i n mea n i n hi biti o n of 
P B M C C T -L acti vit y > 8 0 % a n d mea n i n hi biti o n of w h ole bl o o d C T- L acti vit y ( pre d o mi na ntl y 
c o nstit uti ve pr oteas o me) ≤3 6 %. Data f urt her s h o w e d t hat des pite i nc o m plet e rec o v er y of 
i m m u n o pr oteas o me acti vit y o n Da y 7 ( 6 da ys after d osi n g), t here w as n ot a n acc u m ulati o n of 
pr oteas o me i n hi biti o n. Fr o m a P K a n d p har mac o d y na mic ( P D) pers pecti ve, wee kl y S C 
a d mi nistrati o n of K Z R - 6 1 6 a p pear e d e q ui val e nt t o serial e pis o dic d osi n g. 
1. 4.  
R ati o n ale f or Use of K Z R -6 1 6 i n t he Pr o p ose d St u d y P o p ul ati o ns , 
a n d R ati o n ale f or t he St u d y  
I di o pat hic i nfla m mat or y m y o pat hies s uc h as P M a n d D M are c haracterize d b y i nfla m mat or y 
i nfiltrates i n t he s keletal m uscle. I n nate a n d a da pti ve i m m u ne mec ha nis ms (e g, macr o p ha ges, 
a ut oreacti ve l y m p h oc ytes, a ut oa nti b o dies, pr o-i nfla m mat or y c yt o ki ne pr o d ucti o n) a n d i ntri nsic 
defects i n s kelet al m uscle c o ntri b ute t o m uscle w ea k ness a n d d a ma ge i n  m y ositis. F or e xa m ple, 
Tre g ar e c o nsi dere d i nstr u me ntal f or heali n g via i nteracti o ns wit h m uscle ste m cells, w hereas 
acc u m ulati o n of cl uster of differ e ntiati o n  (C D )4 + a n d C D 8 + T l y m p h oc ytes are ass o ciate d wit h 
f urt her i m m u ne- me di ate d i nj ur y, as occ urs i n i nfl a m mat or y m y ositis a n d s o me m usc ular 
d ystr o p hies ( Sci orati 2 0 1 6 ). T he  i m m u n o pr oteas o me has als o bee n s h o w n t o be u pre g ulate d i n 
t he m uscle of patie nts wit h P M a n d D M a n d t he s ki n of patie nts wit h  D M  (B hattarai 2 0 1 6 ; 
G ha n na n 2 0 1 4 ). F urt her , i ncreas e d le vels of circ ul ati n g pr oteas o mes, li kel y reflecti n g 
i m m u n o pr oteas o mes, ha ve bee n o bser ve d i n patie nts wit h i nfla m mat or y m y ositis a n d a p pear t o 
be ass ociate d wit h diseas e mar kers s uc h as creati ne ki nase ( C K ) a n d m y o gl o bi n le vels 
(E gerer  2 0 0 2). 
I n vitr o, K Z R- 6 1 6 a n d ot her i m m u n o pr oteas o me i n hi bit ors bl oc k c yt o ki ne pr o d ucti o n acr oss 
m ulti ple i m m u ne cell t y pes, re d uce t he acti vit y of i nfla m mat or y T h cell s u bsets, i ncreas e t he 
n u m ber of Tr e g cells, a n d bl oc k plas ma cell  f or m ati o n a n d a ut oa nti b o d y pr o d ucti o n 
(Ic hi ka w a 2 0 1 2; Kali m 2 0 1 2 ; M uc ha m uel 2 0 0 9 ). K Z R - 6 1 6 d oes n ot i n d uce c yt ot o xicit y i n vitr o, 
has de m o nstrate d pr o misi n g t her a pe utic acti vit y i n a ni mal m o dels of R A  a n d S L E/ L N. I n 
partic ular,  i n a C- pr otei n i n d uce d m y ositis ( CI M) m o del, K Z R- 6 1 6 treat me nt i m pr o ve d gri p 
stre n gt h i n disease d mice, w hic h c orr elate d wit h re d uce d ser u m le vels of C K a n d re d u ce d tiss ue 
da ma ge a n d l y m p h oc ytic i nfiltrati o n of t he trice ps a n d gastr oc n e mi us m uscles. Of n ote, gri p 

Pr ot oc ol  A me n d me nt 1  
K Z R -6 1 6 -0 0 3 E  
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1 3 Se pte m ber 2 0 2 1  
 
C o nfi de ntial  
Pa ge 1 8  of 6 6  
 
stre n gt h i n t he disease d mice treate d wit h K Z R- 6 1 6 was e q ui vale nt t o a g e- matc he d c o ntr ol 
a ni mals i n w hic h m y ositis ha d n ot bee n i n d uce d ( data o n file). 
Beca use of t h e pr o misi n g n o ncli nical c haracteristics of K Z R - 6 1 6, al o n g wit h its fa v ora ble safet y 
pr ofile i n healt h y v ol u nteers, K Z R - 6 1 6 re pres e nts a ne w a g e nt wit h a n o vel mec ha nis m of acti o n 
t hat ma y ha ve br o a d t her a pe utic p ote ntial acr oss a ut oi m m u ne c o n diti o ns, i ncl u di n g P M a n d D M. 
As patie nts e xist w h o ha ve a n i na de q u ate res p o nse t o c urre ntl y a vaila ble treat me nts, a n u n met 
me dical nee d re mai ns f or ne w t hera pi es f or t he treat me nt of P M a n d D M. 
T his o pe n-la bel st u d y was desi g ne d t o all o w u p t o 9 6 wee ks of a d diti o nal treat me nt  wit h K Z R -
6 1 6, w hic h will all o w f or assess me nt of t he d ura bilit y of t hera pe utic res p o nse a n d e val u ati o n of 
l o n ger-ter m i m pr o ve m e nt i n t he s y m pt o ms of P M a n d D M. 
1. 5.  
R ati o n ale f or St u d y E n d p oi nts 
T he M y ositis Res p o nse Criteria ar e rec o m me n de d f or use as pri mar y e n d p oi nts i n m y ositis 
t hera pe utic trials. T h e criteria use c ore set acti vit y meas ures ( C S A Ms) fr o m t he I nt er nati o nal 
M y ositis Assess me nt a n d Cli nical St u dies Gr o u p (I M A C S). B y c o m bi ni n g t he a bs ol ute 
perce nt a ge c h a n ge i n t hese 6 c ore s et meas ures (eac h wit h var yi n g w ei g hts), a T otal 
I m pr o v e me nt Sc ore ( TI S), ra n gi n g fr o m 0 t o 1 0 0, is o btai ne d. T he I M A C S C S A Ms c o nsist of: 
•  Ma n ual M uscle Testi n g - 8 M uscle Gr o u ps ( M M T- 8) 
•  P h ysicia n Gl o bal Assess me nt ( M D G A) 
•  Patie nt Gl o bal Assess me nts of Disease A cti vit y  ( Pt G A D A) 
•  Healt h Assess me nt Q uesti o n naire -Disa bilit y I n de x  ( H A Q-DI)  
•  M uscle e nz y mes (cli nical la b orat or y ass ess me nts):  C K , al d olase, lactat e de h y dr o ge nase 
( L D H), ala ni ne a mi n otra nsferas e ( A L T), a n d as p artate a mi n otra nsferas e ( A S T) 
•  M y ositis Disease Acti vit y Assess me nt T o ol ( M D A A T, 2 0 0 5 versi o n) 
 
I n a d diti o n, I M A C S has defi ne d t he f oll o wi n g c ore set da ma ge m eas ures ( CS D Ms):  
•  M y ositis Da ma ge I n de x ( M DI) 
•  Patie nt Gl o bal Assess me nt of Disease D a ma ge  ( Pt G A D D) 
 
Mea n c ha n g e fr o m start t o e n d of K Z R- 6 1 6 treat me nt was t he pri mar y effi cac y e n d p oi nt f or 
St u d y K Z R- 6 1 6- 0 0 3, a n d sec o n dar y a n d e x pl orat or y e n d p oi nts utilize d t he C S A Ms a n d C S D Ms , 
al o n g wit h ot her meas ur es of f u ncti o n a n d o utc o m es. T o deter mi ne l o n g- t er m efficac y i n t he 
sa me patie nt p o p ulati o n, ma n y  of t he e n d p oi nts use d i n St u d y K Z R- 6 1 6- 0 0 3 will als o be use d i n 
t his st u d y wit h c o nsi derati o n f or treat me nt peri o ds (see Secti o n 1 0 ). 
1. 6.  
S u m m ar y of P ote nti al Ris k s a n d Be nefits  
K Z R - 6 1 6 is a selecti ve a n d irre versi ble i n hi bit or of t he i m m u n o pr oteas o me, a ke y i ntracell ular 
f u ncti o n i n i m m u ne effect or cells. Selecti ve i n hi biti on of t he i m m u n o pr otea s o me is 

Pr ot oc ol  A me n d me nt 1  
K Z R -6 1 6 -0 0 3 E  
Kezar Life Scie nces, I nc.  
1 3 Se pte m ber 2 0 2 1  
 
C o nfi de ntial  
Pa ge 1 9  of 6 6  
 
i m m u n o m o d ulat or y rat her t ha n i m m u n os u p pressi ve i n precli nical m o dels. K Z R- 6 1 6 is 
de m o nstrate d t o ha ve m ar ke d a bilit y t o bl oc k t he i nfla m mat or y res p o nse i n m ulti ple m o use 
m o dels of a ut oi m m u ne disease, i ncl u di n g b ut n ot li mite d t o, m o dels of R A, t he pr o gressi o n of 
ne p hritis i n 2 m o use m o dels of S L E, a n d i n t he CI M  m o use m o del of m y ositis.  
K Z R - 6 1 6 is a n i n vesti gati o nal a ge nt. T o date, 2 st u dies i n healt h y v ol u nteers usi n g d oses ra n gi n g 
fr o m 7. 5 t o 7 5 m g K Z R- 6 1 6 wee kl y ha v e bee n c o m plete d. I n a d diti o n, a P hase 2 st u d y i n 
patie nts wit h S L E wit h or wit h o ut L N ( K Z R - 6 1 6- 0 0 2) a n d a st u d y of p atie nts wit h P M or D M 
( K Z R- 6 1 6- 0 0 3) are o n g oi n g. A d verse e v e nts m ost ofte n ass ociate d wit h K Z R- 6 1 6 t o date ha ve 
bee n I S Rs t hat are tr a nsie nt, ge nerall y mil d, a n d d o n o t a p pear t o i ncreas e i n se verit y or 
fre q ue n c y wit h re p eat d osi n g. T olera bilit y of K Z R- 6 1 6 is i m pr o ve d wit h a n i nitial 3 0 m g S C 
d ose of K Z R- 6 1 6, f oll o w e d b y s u bse q ue nt hi g her t ar get d oses of 4 5 or 6 0 m g. It is a ntici pat e d 
t hat partici pa nts i n K Z R- 6 1 6- 0 0 3 E will ha ve alrea d y de m o nstrate d t olera bilit y t o K Z R- 6 1 6 
f oll o wi n g partici pati o n i n K Z R- 6 1 6- 0 0 3. N o net hel ess, i nitial hi g h d oses of K Z R- 6 1 6 ha ve b ee n 
ass ociate d wit h at least o ne of t he f oll o wi n g si g ns/s y m pt o ms: h y p ote nsi o n, tac h ycar dia, na us ea, 
v o miti n g, dizzi ness, hea d ac he, p yr e xia, ri g ors a n d/ or c hills. 
Base d o n n o ncli nical st u dies wit h K Z R- 6 1 6, i ncl u di n g a m o use m o del of m y ositis, t he safet y of 
K Z R - 6 1 6 at 4 5 m g i n healt h y v ol u nteers, t he safet y of K Z R- 6 1 6 t o date i n 4 6 patie nts wit h S L E, 
a n d t he p ote ntial be nefit fr o m a nti-i nfla m mat or y acti vit y i n d uce d b y i m m u n o pr oteas o me 
i n hi biti o n, t he o verall p ositi ve be nefit-ris k bala n ce of K Z R- 6 1 6 s u p p orts its c o nti n ue d 
de vel o p me nt i n patie nts wit h P M a n d D M. 
F or a d diti o nal i nf or mati o n, please r efer t o t he c urre nt versi o n of t he K Z R - 6 1 6 I n v esti gat or’s 
Br oc h ure. 

Pr ot oc ol  A me n d me nt 1  
K Z R -6 1 6 -0 0 3 E  
Kezar Life Scie nces, I nc.  
1 3 Se pte m ber 2 0 2 1  
 
C o nfi de ntial  
Pa ge 2 0  of 6 6  
 
2.  
S T U D Y O B J E C TI V E S A N D E N D P OI N T S  
2. 1.  
St u d y O bjecti ves  
T he effi cac y o bj ecti ve is t o e val uate t he l o n g -ter m efficac y of K Z R- 6 1 6 i n patie nts wit h P M or 
D M.  
T he safet y o bjecti ve is t o e val uate t he l o n g-t er m s afet y a n d t olera bilit y of K Z R - 6 1 6 i n patie nts 
wit h P M or D M.  
2. 2.  
St u d y E n d p oi nts  
2. 2. 1.  
Effic ac y E n d p oi nts  
•  Mea n c ha n g e i n TI S o ver ti me f or all patie nts, f or patie nts wit h D M o nl y, f or patie nts 
wit h P M o nl y, a n d f or pat ie nts wit h a m y ositis-ass ociate d a nti b o d y or m y ositis-s pecific 
a nti b o d y at t he Scree ni n g Visit of St u d y K Z R- 6 1 6- 0 0 3 
•  Pr o p orti o n of patie nts b y TI S r es p o nse ( mi ni mal res p o nse = TI S ≥ 2 0, m o derate res p o nse 
= TI S ≥ 4 0, maj or res p o nse = TI S ≥ 6 0) 
•  Pr o p orti o n of patie nts meeti n g I M A C S defi niti o n of i m pr o ve me nt ( D OI) o ver ti me  f or 
patie nts wit h baseli ne c or e set me as ures as as certai ne d at t he be gi n ni n g of K Z R- 6 1 6- 0 0 3 
•  Mea n  c ha n g e a n d mea n p erce nt a ge c h a n ge o v er ti me  i n t he I M A C S i n di vi d ual C S A Ms 
a n d C S D Ms , stratified b y all patie nts a n d patie nts wit h m y ositis -ass ociate d or 
m y ositis -s pecific a nti b o d y at t he Scree ni n g Visit of St u d y K Z R- 6 1 6- 0 0 3 
•  M ea n c ha n g e o ver ti me  i n t he C uta ne o us Der mat o m y ositis Disease Area a n d Se verit y 
I n d e x ( C D A SI) f or all patie nts wit h D M, a n d f or p atie nts wit h D M w h o ha v e acti ve s ki n 
ma nifestati o ns at baseli n e  of St u d y K Z R- 6 1 6- 0 0 3 E 
•  Mea n c ha n g e o ver ti me i n t he M DI 
•  Mea n c ha n g e o ver ti me i n m uscle e nz y mes  
•  C ha n ge i n pr o p orti o n a n d d ose of c ortic oster oi d a n d n o n-c ortic oster oi d 
i m m u n os u p pressa nts d uri n g St u d y K Z R- 6 1 6- 0 0 3 E f or all patie nts, a n d f or patie nts ta ki n g 
c ortic oster oi ds or n o n- c ortic oster oi d i m m u n os u p pressa nts at bas eli ne of St u d y 
K Z R - 6 1 6- 0 0 3 E 
•  Perce nta g e of patie nts r e q uiri n g a d diti o nal me dicati o n f or m y ositis treat me nt d uri n g 
St u d y K Z R- 6 1 6- 0 0 3 E 
•  Mea n c ha n g e o ver ti me i n t he E ur o Q ol 5- di me nsi o n 5- le vel (E Q - 5 D- 5 L) 
•  A d diti o nal e x pl orat or y e n d p oi nts ( P h ysicia n Gl o bal I m pressi o n of C ha n ge [ M D GI C ], 
F u ncti o nal I n de x - 2 [FI - 2], Patie nt Gl o bal I m pressi o n of C ha n ge [P GI C ], a n d Pea k 
P r uritis N u merical Rati n g Scale [ N R S]) will be assesse d at m ulti ple ti me p oi nts 
 

Pr ot oc ol  A me n d me nt 1  
K Z R -6 1 6 -0 0 3 E  
Kezar Life Scie nces, I nc.  
1 3 Se pte m ber 2 0 2 1  
 
C o nfi de ntial  
Pa ge 2 1  of 6 6  
 
As K Z R - 6 1 6- 0 0 3 E is a n o pe n-la bel e xt e nsi o n st u d y, a d diti o nal e x pl orat or y e n d p oi nts ma y  be 
c o n d ucte d, a n d will be descri be d i n t he fi n al statistical a nal ysis pla n ( S A P). E fficac y en d p oi nts 
ma y i ncl u de treat me nt p eri o ds t hat i ncl u de data fr o m St u d y K Z R - 6 1 6- 0 0 3 base d o n treat me nt 
se q ue nce i n t hat st u d y. S ee Secti o n 1 0  f or a d diti o nal details of statistical a nal yses. 
All e n d p oi nts, e xce pt w h ere n ote d, will i ncl u de a n al yses of all patie nts, t h ose wit h D M o nl y, a n d 
t h ose wit h P M o nl y. 
2. 2. 2.  
S afet y E n d p oi nts  
•  I n ci de nce, nat ur e, a n d se verit y of A Es  a n d s eri o us a d verse e ve nts ( S A Es) 
•  I n ci de nce of A Es lea di n g t o K Z R- 6 1 6 disc o nti n uati o n 
•  C ha n ges i n sta n dar d la b orat or y para meters a n d vital si g ns 
 
2. 2. 3.  
E x pl or at or y E n d p oi nts  
•  Relati o ns hi ps bet wee n cli nical efficac y, cli nical safet y,  a n d v ari o us bi o mar k er  e n d p oi nts 
i ncl u di n g c ha n ges i n cir c ulati n g c yt o ki ne a n d w h ole bl o o d ge ne e x pressi o n 
•  C ortic oster oi d -free TI S r es p o nse b y visit (c ortic oster oi d-free is defi n e d as c ortic oster oi d 
f ull y ta pere d off f or ≥ 1 2 wee ks [ 3 m o nt hs] pri or t o a visit; mi ni mal res p o nse = TI S ≥ 2 0, 
m o derate r es p o nse = TI S ≥ 4 0, maj or res p o nse = TI S ≥ 6 0)  
 

Pr ot oc ol  A me n d me nt 1  
K Z R -6 1 6 -0 0 3 E  
Kezar Life Scie nces, I nc.  
1 3 Se pte m ber 2 0 2 1  
 
C o nfi de ntial  
Pa ge 2 2  of 6 6  
 
3.  
S T U D Y D E SI G N  
3. 1.  
T y pe a n d Desi g n of St u d y  
T his is a n o pe n-la bel st u d y t o e val uate t he l o n g- ter m efficac y a n d s afet y of K Z R- 6 1 6 i n patie nts 
wit h acti ve P M or D M w h o c o m plete d t he d o u ble- bli n d treat me nt peri o d of St u d y K Z R- 6 1 6- 0 0 3, 
u p t o a n d i ncl u di n g t he Wee k 3 2 Visit, pri or t o t he first d ose of o p e n- la bel K Z R- 6 1 6. 
T he st u d y desi g n sc he ma is prese nte d i n Fi g ure 1 . 
Patie nts will be e val uate d f or eli gi bilit y acc or di n g t o  t he e ntr y criteri a (see Secti o n 4 ) at, or 
wit hi n 8 wee ks after, t he Wee k 3 2 Visit (ie, t he E n d of Treat me nt [ E O T] Visit [ Visit 3 4]) of 
St u d y K Z R- 6 1 6- 0 0 3. I nf or me d c o nse nt ma y b e si g ne d pri or t o t he Wee k 3 2 Visit of St u d y 
K Z R - 6 1 6- 0 0 3, a n d m ust be si g ne d pri or t o a n y st u d y-relate d acti vit y i n K Z R- 6 1 6- 0 0 3 E. F or 
patie nts w h o are eli gi ble a n d willi n g t o e nr oll i n t he o pe n-la b el e xte nsi o n st u d y, t he 
K Z R - 6 1 6- 0 0 3 Wee k 3 2 Visit ma y als o ser ve as Visit 1 ( Da y  1) f or t he o p e n-la bel e xte nsi o n 
st u d y. Assess me nts at t his visit perf or me d as part of St u d y K Z R- 6 1 6- 0 0 3 will be use d as baseli ne 
val ues f or t he e xte nsi o n st u d y; t heref ore, t h ese ass ess me nts m ust be perf o r me d pri or t o t he first 
d ose of o pe n- l a bel K Z R- 6 1 6 (see Fi g ure 1 ). 
All patie nts will recei ve a S C i njecti o n of 3 0 m g K Z R - 6 1 6 at Visit 1 ( Da y 1), f oll o we d b y 
wee kl y S C i njecti o ns of 4 5 m g K Z R - 6 1 6 u p t o a ma xi m u m of 9 6 wee ks. St u d y dr u g 
a d mi nistrati o n will e n d f or all patie nts i n St u d y K Z R - 6 1 6- 0 0 3 E w he n t he l ast patie nt e nr olle d 
has c o m plete d 4 8 wee ks of d osi n g. Patie nts will ha ve a fi n al f oll o w - u p visit 1 2 wee ks aft er t heir 
last d ose of K Z R- 6 1 6 ( E n d of St u d y [ E O S] Visit), f or a ma xi m u m p ote ntial le n gt h of 
partici pati o n of 1 0 8 wee ks.  
O n -site st u d y visits will occ ur at Wee ks 1 2, 2 4, 3 6, 4 8, 6 0, 7 2, 8 4, a n d 9 6 ( E O T Visit), a n d t he 
E O S  Visit . At t hese visits, safet y a n d efficac y ass ess me nts will be perf or m e d acc or di n g t o t he 
Sc he d ule of Assess me nts ( Ta ble  1). W hile t hese visits are ma n dat or y, i n rec o g niti o n of 
c o nstrai nts i m p ose d b y t he S A R S- C o V- 2 pa n de mic, sites ma y elect t o use a c o m bi nati o n of 
tele me dici ne ( as per mitte d b y t heir i nstit uti o ns) a n d/ or h o me healt h pr o vi ders, i ncl u di n g at- h o me 
a d mi nistrati o n of K Z R - 6 1 6. All ot her st u d y visits ma y occ ur eit her at t he site or at patie nts ’ 
h o mes via h o me healt h pr o vi ders ( Ta bl e  2). If necessar y, sa m ples f or cli nical la b orat or y 
assess me nts will be c ollecte d b y h o me healt h pr o vi ders a n d se nt t o t he la b orat or y. F or at- h o me 
K Z R - 6 1 6 a d mi nistrati o n, d oses ma y be a d mi nistere d b y h o me healt h pr o vi d ers or, f or patie nts 
dee me d a p pr o priate b y t h e I n vesti gat or, b y t he p atie nt or care gi ver foll o wi n g a p pr o priate 
i nstr ucti o n (see Secti o n 5. 4 ). 
Efficac y assess me nts will be perf or m e d f or all patie nts, u nless i n dicate d ot her wise ; t hese 
assess me nts are dis c usse d i n Secti o n 7. 2. 4 . 
Safet y will be assesse d t hr o u g h o ut t he st u d y b y m o nit ori n g of vital si g ns, cli nical la b orat or y 
tests, a n d p h ysical e xa mi nati o ns, a n d b y rec or di n g a n d a nal yzi n g all A Es a n d S A Es . 

Pr ot oc ol  A me n d me nt 1  
K Z R -6 1 6 -0 0 3 E  
Kezar Life Scie nces, I nc.  
1 3 Se pte m ber 2 0 2 1  
 
C o nfi de ntial  
Pa ge 2 3  of 6 6  
 
Fi g ure  1 
St u d y K Z R - 6 1 6- 0 0 3 E St u d y Desi g n Sc he m a 
 
a 
I nf or me d c o nse nt ma y b e si g n e d at a n y ti me relati v e t o ste p 2; h o we v er, it m ust b e si g n e d pri or t o ste ps 3 a n d 4. 
b 
Val ues use d as b aseli n e v al u es f or K Z R -6 1 6 -0 0 3 E  
c 
T he first d ose ( Da y 1) will b e 3 0 m g K Z R -6 1 6 S C; s u bse q u e nt d oses will b e 4 5 m g K Z R -6 1 6 S C.  
A b bre viati o ns: I/ E =i n cl usi o n/e x cl usi o n; S C =s u b c uta n e o us  
 
3. 1. 1.  
St u d y Desi g n R ati o n ale 
T his is a n o pe n- la bel, u p t o 1 0 8- wee k st u d y t o e val uate t he l o n g- ter m efficac y a n d safet y of 
K Z R - 6 1 6 i n patie nts wit h P M or D M w h o c o m plete d t he d o u ble- bli n d treat me nt peri o d of 
St u d y K Z R - 6 1 6- 0 0 3 (ie, u p t o a n d i ncl u di n g t he Wee k 3 2 Visit pri or t o t h e first d ose of 
o pe n- la bel K Z R- 6 1 6). 
3. 2.  
Mi ni miz ati o n of Bi as  
K Z R - 6 1 6- 0 0 3 E is a n o pe n-la bel st u d y.  
3. 3.  
N u m ber of Sites  
U p t o 2 4 sites are pla n ne d t o partici pate i n t his st u d y. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
  
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 

Pr ot oc ol  A me n d me nt 1  
K Z R -6 1 6 -0 0 3 E  
Kezar Life Scie nces, I nc.  
1 3 Se pte m ber 2 0 2 1  
 
C o nfi de ntial  
Pa ge 2 4  of 6 6  
 
4.  
P A TI E N T S E L E C TI O N A N D E N R O L L M E N T  
4. 1.  
N u m ber of P atie nts  
U p t o 2 4 patie nts are pla n ne d f or e nr oll me nt. 
Patie nts will be e val uate d f or eli gi bilit y i n t he o pe n -la bel e xt e nsi o n st u d y acc or di n g t o t he 
eli gi bilit y criteria (see Secti o n 4 ) at, or wit hi n 8 w ee ks aft er, t he Wee k 3 2 Visit of St u d y 
K Z R - 6 1 6- 0 0 3. T he I n v esti gat or will e ns ure t hat t he patie nt has pr o vi de d writte n i nf or me d 
c o nse nt bef or e a d mi nistr ati o n of o pe n- la b el K Z R- 6 1 6 as part of t he o p e n-la bel e xte nsi o n st u d y 
K Z R - 6 1 6- 0 0 3 E. 
O nce i nf or m e d c o nse nt is o btai ne d, t he e val uati o ns ma y be gi n t o assess st u d y eli gi bilit y 
(i ncl usi o n/e xcl usi o n criteria). T he p atie nt i de ntificati o n n u m ber use d i n St u d y K Z R- 6 1 6- 0 0 3 will 
c o nti n ue t o be use d t o i de ntif y t he patie nt t hr o u g h o ut st u d y partici pati o n. 
4. 2.  
I ncl usi o n Criteri a  
O nl y i n di vi d uals w h o meet all of t he f oll o wi n g criteria ma y  be e nr olle d i n t he st u d y. 
1.  M ust ha ve s uccessf ull y c o m plete d St u d y K Z R - 6 1 6- 0 0 3 t hr o u g h Wee k 3 2, i ncl u di n g t he 
Wee k 3 2 V isit assess me nts, be willi n g a n d a ble t o pr o vi de writte n i nf or me d c o nse nt pri or 
t o a n y st u d y-relate d pr oce d ures, a n d b e willi n g a n d a ble t o c o m pl y wit h st u d y 
re q uire me nts.  
2.  W o me n of c hil d beari n g p ote ntial ( W O C B P) m ust ha ve a n e gati ve uri ne or ser u m  
pre g na nc y t est pri or t o t he first d ose of K Z R - 6 1 6 i n K Z R- 6 1 6- 0 0 3E, a n d m ust a gree t o 
c o nti n ue t o use a hi g hl y effecti ve met h o d of birt h c o ntr ol u ntil c o m pleti o n of t he st u d y 
( or 3 0 da ys f oll o wi n g t he last d ose of K Z R - 6 1 6 i n case of earl y wit h dra wal). W o me n of 
c hil d beari n g p ote ntial ar e defi ne d as p ost p u bes ce nt fe male patie nts, u nless t he pa tie nt is 
p ost me n o pa usal ( defi n e d b y a me n orr h ea f or at least 2 years or a m e n orr h ea f or at least 
1 year wit h c o nfir mat or y f ollicle sti m ulati n g h or m o ne [ F S H] l e vel i n t he p ost me n o pa usal 
ra n ge, as d o c u me nte d hist oricall y or meas ure d b y t he ce ntral or l ocal la borat or y a n d if 
patie nt is n ot o n s u p ple me ntar y h or m o nal t hera p y) or s ur gicall y sterile (i e, t u bal li gati o n, 
h ysterect o m y, bilater al sal pi n g o o p h orect o m y). See Secti o n 7. 2. 8  f or det aile d 
re q uire me nts f or W O C B P. 
3.  Male patie nts m ust  c o nti n ue t o use a n effecti ve c o ntrace pti o n met h o d (e g, c o n d o m wit h 
s per mici de) f or 1 wee k  f oll o wi n g t heir last d ose of K Z R - 6 1 6 or be c o n ge nitall y or 
s ur gicall y sterile (e g, v as ect o m y wit h d oc u me nte d c o nfir mati o n of p ost-s ur gical 
as per mia).  
 
4. 3.  
E xcl usi o n Criteri a   
O nl y i n di vi d uals w h o d o n ot meet a n y of t he f oll o wi n g criteria ma y  b e e nr olle d i n t he st u d y. 
1.  Ha ve c li nical e vi de nce of si g nifica nt u nsta ble or u nc o ntr olle d diseases ot her t ha n t he 
disease u n der st u d y (e g, car diac [i ncl u di n g c o n g esti ve heart fail ure, h y pert e nsi o n, a n gi na, 

Pr ot oc ol  A me n d me nt 1  
K Z R -6 1 6 -0 0 3 E  
Kezar Life Scie nces, I nc.  
1 3 Se pte m ber 2 0 2 1  
 
C o nfi de ntial  
Pa ge 2 5  of 6 6  
 
or m y ocar dial i nf arcti o n], p ul m o nar y [i ncl u di n g p ul m o nar y h y perte nsi o n or i nterstitial 
l u n g disease], he mat ol o gic, gastr oi ntesti nal, e n d ocri n ol o gic, he patic, re nal, ne ur ol o gical, 
or i nfecti o us disease , a n y o n g oi n g S A E(s), or A E (s) ≥Gra de 3 b y Nati o nal Ca ncer 
I nstit ute C o m m o n Ter mi n ol o g y Criteria f or A d verse E ve nts [ N CI-C T C A E] ) t hat, i n t he 
o pi ni o n of t he I n v esti gat or or S p o ns or/ desi g nee, c o ul d c o nf o u n d t he res ults of t he st u d y, 
p ut t he patie nt at u n d ue ris k, or i nterfere wit h pr ot oc ol a d here nce. 
2.  Has partici pat e d i n a n y cli nical st u d y ot her t ha n K Z R- 6 1 6- 0 0 3 bet wee n t he Wee k 3 2 
Visit of St u d y K Z R- 6 1 6- 0 0 3 a n d t he first st u d y visit of K Z R- 6 1 6- 0 0 3 E, if t he y are n ot o n 
t he sa me cal e n dar d a y. 
3.  Are fe males w h o are  breastfee di n g  or w h o pla n t o bec o me pre g na nt d uri n g t he st u d y, or 
w h o are acti vel y tr yi n g t o c o ncei ve at t he ti me of si g ni n g of t he i nf or me d c o nse nt f or m 
(I C F). 
4.  Ha ve h y perse nsiti vit y t o K Z R- 6 1 6 or a n y of its e x ci pie nts. 
 

Pr ot oc ol  A me n d me nt 1  
K Z R -6 1 6 -0 0 3 E  
Kezar Life Scie nces, I nc.  
1 3 Se pte m ber 2 0 2 1  
 
C o nfi de ntial  
Pa ge 2 6  of 6 6  
 
5.  
S T U D Y T R E A T M E N T  I N F O R M A TI O N 
I nstr u cti o ns f or t he r ecei pt, i ns pecti o n, st ora ge, pre parati o n, a d mi nistrati o n, a n d dis p osal of 
K Z R - 6 1 6 will  be pr o vi de d i n a se par ate P har mac y Ma n ual at eac h cli nical site.  
5. 1.  
P h ysic al Descri pti o n of K Z R -6 1 6  
K Z R - 6 1 6 is s u p plie d as a refri gerate d l y o p hilize d dr u g pr o d uct i n si n gle use b or osilicate glass 
vial s. Eac h vial is rec o nstit ute d wit h sterile water f or i njecti o n pri or t o a d mi nistrati o n. 
5. 2.  
P ac k a gi n g a n d L a beli n g  
T he l y o p hilize d dr u g pr o d uct will be s u p plie d i n si n gle- use vials pac k a ge d i n m ulti- vial cart o ns. 
F or patie nts eli gi ble f or at - h o me a d mi nistrati o n b y t he patie nt or care gi ver, a pre meas ure d, 
pre -fille d s yri n ge ( P F S) c o ntai ni n g sterile water f or i njecti o n ( W FI), a nee dl eless vial a da pt or 
s yste m, a n d a d diti o nal cli nical s u p plies nee de d f or rec o nstit uti o n will als o be pr o vi de d. All 
K Z R - 6 1 6 vials a n d pre-fille d s yri n ges will be la bele d acc or di n g t o a p pr o pri ate re g ulat or y 
g ui deli nes. All pac ka gi n g a n d la beli n g o perati o ns will be perf or me d acc or di n g t o G o o d 
Ma n ufact uri n g Pr actice ( G M P) f or Me dic i nal Pr o d ucts a n d t he rel e va nt re g ulat or y re q uire m e nts. 
5. 3.  
S u p pl y, Dis pe nsi n g, St or a ge, a n d K Z R -6 1 6  Acc o u nt a bilit y  
Refer t o t he I n v esti gat or’s Br oc h ure a n d P har mac y Ma n ual f or st ora ge c o n diti o ns f or K Z R- 6 1 6. 
T he I n vesti gat or or d esi g nee m ust c o nfir m a p pr o priate te m perat ure c o n diti o ns ha ve bee n 
mai ntai ne d d uri n g tra nsit f or all K Z R - 6 1 6 recei v e d a n d a n y discre pa nci es are re p orte d a n d 
res ol ve d bef ore us e of t h e K Z R- 6 1 6. 
O nl y partici pa nts e nr olle d i n t he st u d y ma y recei v e K Z R- 6 1 6. All i n vesti gati o nal pr o d ucts 
s h o ul d be st ore d i n a n e n vir o n me ntall y c o ntr olle d a n d m o nit ore d ( ma n ual or a ut o mate d) area i n 
acc or d a nce wit h t he la bel e d st ora ge c o n diti o ns. Access t o i n vesti gati o nal pr o d uct m ust be li mite d 
t o t he In v esti gat or a n d a ut h orize d site staff.  
T he I n vesti gat or, i ns tit uti o n, or t he hea d of t he me dical i nstit uti o n ( w here a p plica ble) is 
res p o nsi ble f or st u d y treat me nt acc o u nta bilit y, rec o nciliati o n, a n d rec or d mai nte na nce (s uc h as 
recei pt, r ec o n ciliati o n a n d fi nal dis p ositi o n rec or ds). 
U p o n recei pt of t he K Z R- 6 1 6, t he I n vesti gat or ( or desi g nee) will c o n d u ct a n i n ve nt or y of t he 
s u p plies a n d verif y t hat K Z R- 6 1 6 s u p plies are recei ve d i ntact a n d i n t he c orrect a m o u nts. T he 
St u d y M o nit or ma y c hec k t he st u d y s u p plies at eac h st u d y ce nter at a n y ti me d uri n g t he st u d y. 
It is t he r es p o nsi bilit y of t he St u d y M o nit or t o e ns ure t hat t he I n v esti gat or ( or desi g nee ) h as 
c orrectl y d oc u me nte d t he a m o u nt of t he K Z R - 6 1 6 recei v e d, dis pe nse d, a n d ret ur ne d o n t he 
dis pe nsi n g l o g t hat will be pr o vi de d. A f ull dr u g acc o u nta bilit y l o g will be mai ntai ne d at t he 
st u d y ce nter at all ti mes. T he St u d y M o nit or will perf or m a n i n v e nt or y of K Z R - 6 1 6 at t he 
cl ose o ut visit t o t he st u d y ce nter. All discre pa n cies m ust be acc o u nte d f or a n d d oc u me nte d. 
5. 4.  
At -H o me A d mi nistr ati o n of K Z R -6 1 6  b y P atie nt or C are gi ver  
K Z R - 6 1 6 f or at-h o m e a d mi nistrati o n b y t he patie nt or care gi ver ma y b e dis pe nse d as des cri be d 
i n t he P har mac y Ma n u al. 

Pr ot oc ol  A me n d me nt 1  
K Z R -6 1 6 -0 0 3 E  
Kezar Life Scie nces, I nc.  
1 3 Se pte m ber 2 0 2 1  
 
C o nfi de ntial  
Pa ge 2 7  of 6 6  
 
T he site will asses s patie nts’  willi n g ness a n d a bilit y t o u n der g o at-h o me a d mi nistrati o n of 
K Z R - 6 1 6. Patie nts c o nsi dere d f or at-h o me a d mi nistrati o n m ust:  
•  be willi n g t o self -a d mi nister (i ncl u di n g a d mi nistrati o n b y care gi v er) K Z R- 6 1 6, a n d 
•  ha ve bee n assesse d as a p pr o priate f or at - h o me a d mi nistrati o n b y t he I n vesti gat or 
(e g, de m o nstrate d t olera bilit y t o K Z R - 6 1 6, p h ysicall y a n d me ntall y a ble). 
 
Patie nts or care gi v ers ma y a d mi nister K Z R - 6 1 6 S C after a p pr o priate i nstr u cti o n. 
Patie nts a n d car e gi vers will be pr o vi de d s pecific I nstr ucti o ns f or Use (I F U) t o e ns ure pr o p er 
ha n dli n g, st ori n g, rec o nstit uti o n, a d mi nistrati o n, a n d dis p osal of K Z R- 6 1 6. T he I F U will be 
acc o m pa ni e d b y a n i nstr ucti o nal vi de o de m o nstrati n g eac h ste p i n v ol ve d. 
Patie nts will d oc u me nt details of dates, ti mes, a n d v ol u mes of eac h a d mi nistere d d ose i n a 
patie nt diar y. Patie nts will be i nstr ucte d t o ret ur n all use d vials of dr u g pr o d uct t o t he 
i n vesti gati o nal site. 
Patie nts w h o d o n ot wis h t o a d mi nister K Z R- 6 1 6 at h o me will ha ve t he o pti o n of ha vi n g 
K Z R - 6 1 6 a d mi nistere d at t he site or b y a h o me healt h pr o vi der. 

Pr ot oc ol  A me n d me nt 1  
K Z R -6 1 6 -0 0 3 E  
Kezar Life Scie nces, I nc.  
1 3 Se pte m ber 2 0 2 1  
 
C o nfi de ntial  
Pa ge 2 8  of 6 6  
 
6.  
D O S A G E A N D K Z R -6 1 6  A D MI NI S T R A TI O N  
6. 1.  
K Z R- 6 1 6  A d mi nistr ati o n  
K Z R - 6 1 6 will be a d mi nistere d b y S C i njecti o n o nce wee kl y. T he first i njecti o n will be a 3 0 - m g 
d ose, a d mi nistere d at t he st u d y site, a n d s u bse q ue nt i njecti o ns will be a 4 5- m g d ose. I d eall y, t he 
first d ose will be gi ve n o n t he sa me cal e n dar d a y as t he Wee k 3 2 Visit of St u d y K Z R- 6 1 6- 0 0 3, 
b ut m ust be gi ve n n o later t ha n 8 wee ks after t he Wee k 3 2 Visit of St u d y K Z R- 6 1 6- 0 0 3. 
After t he first d ose, K Z R - 6 1 6 will be a d mi nistere d b y st u d y pers o n nel at t he site or b y a h o me 
healt h  pr o vi der at t he patie nt’s h o me. At -h o me a d mi nistrati o n of K Z R - 6 1 6 b y t he patie nt or 
care gi v er ma y als o be a v aila ble as a n o pti o n , as a p pr o priate (s ee  Secti o n  5. 4 ). D oses will be 
a d mi nist ere d acc or di n g t o t he Sc he d ules of Assess me nts (Ta ble  1 a n d T a ble  2). 
F urt her d etails re g ar di n g dr u g pr o d uct f or m ulati o n, pre parati o n, a n d a d mi nistrati o n of K Z R- 6 1 6 
will be pr o vi de d i n a se p arate P har mac y Ma n u al.  
6. 1. 1.  
A d mi nistr ati o n Site  
S u bc uta ne o us i njecti o n sites s h o ul d be r otate d (e g, 4 a b d o mi nal q ua dra nts, p osteri or u p per ar ms, 
a nteri or t hi g hs), a n d a mi ni m u m of 4 wee ks s h o ul d se parat e i njecti o ns t o t he sa me a n at o mic site , 
if p ossi ble. 
6. 1. 2.  
S u g gest e d Me as ures t o I m pr o ve K Z R - 6 1 6 T oler a nce  
I nitial S C d oses of 6 0 m g K Z R- 6 1 6 are ass ociate d wit h at least o ne of t he f oll o wi n g 
si g ns/s y m pt o ms: h y p ote nsi o n, tac h ycar di a, na usea, v o miti n g, dizzi ness, hea dac he, p yre xia, 
ri g ors a n d/ or c hills. T hes e si g ns/s y m pt o ms t y picall y be gi n wit hi n 8 t o 2 4 h o urs after d osi n g, a n d 
us uall y res ol ve wit hi n 4 8 h o urs after d osi n g. 
Alt h o u g h t he n u m bers ar e s mall, t he perce nta ge of patie nt re p orti n g treat me nt- e mer g e nt A Es 
( T E A Es) of t h e a b o ve si g ns/s y m pt o ms a p pears t o be l o wer i n patie nts w h o recei v e d K Z R - 6 1 6 as 
ste p- u p d oses a n d/ or wit h pre-/ p ost- d ose pr o p h yl a xis, s u g gesti n g t hat t hese met h o ds are effecti ve 
at t olerizi n g patie nts t o hi g her d oses of K Z R- 6 1 6. 
Ste p - u p D osi n g 
It is u n k n o w n w h et her p atie nts w h o start, st o p, a n d t he n res u me treat me nt wit h K Z R- 6 1 6 will 
e x perie n ce t oler a bilit y iss ues (e g, patie nts ra n d o mize d t o Ar m A of St u d y K Z R- 6 1 6- 0 0 3). T h us, 
t o mai ntai n t he bli n d f or St u d y K Z R- 6 1 6- 0 0 3, all patie nts e nr olli n g i n St u d y K Z R - 6 1 6- 0 0 3 E will 
recei v e a n i nitial d ose of 3 0 m g K Z R- 6 1 6, t o be f oll o we d wee kl y b y t he tar get d ose of 4 5 m g. 
Pre/ P ost D ose Pr o p h yla xis 
Pr o p h ylactic meas ur es ma y be c o nsi dere d if a n y of t he si g ns a n d/ or s y m pt o ms liste d a b o ve 
de vel o p, a n d ma y b e use d as treat me nt, eit her w hile t he patie nt is at t he st u d y site o r after l ea vi n g 
t he st u d y site. Meas ures t hat ha ve bee n de m o nstrat e d t o re d uce t he i nci de n ce a n d se verit y of 
i nf usi o n-relate d r eacti o ns wit h ot her pr oteas o me i n hi bit ors i ncl u de t he f oll o wi n g: 
•  Fl ui d h y drati o n, e g, 2 5 0- 5 0 0 m L oral ( or i ntra v e n o us [ I V] if n ecess ar y) of a n 
electr ol yte s ol uti o n u p t o 4 8 h o urs pri or t o d osi n g, or u p t o 2 4 h o urs after d osi n g if 
s y m pt o ms are prese nt 

Pr ot oc ol  A me n d me nt 1  
K Z R -6 1 6 -0 0 3 E  
Kezar Life Scie nces, I nc.  
1 3 Se pte m ber 2 0 2 1  
 
C o nfi de ntial  
Pa ge 2 9  of 6 6  
 
•  A ntie metics, n o n -se dati n g a nti hista mi nes, a n d/ or aceta mi n o p he n (if fe v er is prese nt)  
 
If a d diti o nal g ui da nce f or i m pr o vi n g i nitial t olera bilit y s y m pt o ms is re q uire d, t he Me dical 
M o nit or s h o ul d be c o ns ulte d. H o me healt h pr o vi d ers d o n ot pr o vi de or a d mi nister a n y of t he 
fl ui ds or me dicati o ns liste d a b o ve. 
6. 1. 3.  
D ose M o dific ati o n G ui deli nes  
6. 1. 3. 1.  
D ose Re d ucti o n  
Patie nts w h o e x perie n ce a K Z R - 6 1 6-r elate d A E at t he 4 5 m g d ose are p er mitte d t o u n der g o d ose 
re d ucti o n t o 3 0 m g K Z R - 6 1 6 f or s u bse q ue nt d oses at t he discreti o n of t he I n vesti gat or, i n 
c o ns ultati o n wit h t he Me dical M o nit or. Writte n a p pr o val fr o m t he Me di cal M o nit or s h o ul d be 
o btai ne d i n a d va nce of i m ple me nti n g d ose re d ucti o n, w he n p ossi ble. After d ose re d ucti o n is 
i m ple me nte d, patie nts s h o ul d re mai n o n 3 0 m g K Z R- 6 1 6 f or at least 2 d os es, after w hic h t he 
d ose ma y be r e-es calate d t o 4 5 m g. If t he 4 5- m g d ose is n ot t olerate d aft e r re-escalati o n, t he 
3 0- m g d ose ma y be c o nti n ue d f or t he re mai n der of t he st u d y , or re-escalati o n t o 4 5 m g ma y be 
re-atte m pte d after writte n a p pr o val fr o m t he M e dical M o nit or . A n y d ose m o dificati o ns  s h o ul d be 
d oc u me nte d i n t he electr o nic case re p ort f or m (e C R F ) as per Secti o n 9. 1. 4 . 
6. 1. 3. 2.  
Misse d D oses  
D oses s h o ul d be a d mi nistere d wit hi n t he visit wi n d o ws as per t he Sc h e d ule of Assess me nts 
(Secti o n 7. 1 ). A n y d oses a d mi nistere d o utsi de of t he visit wi n d o w will be c o nsi dere d a pr ot oc ol 
de viati o n; h o we ver, if n ecessar y t o a v oi d missi n g a d ose, d oses ma y  b e a d mi nistere d u p t o 3 da ys 
fr o m t he date of s c he d ule d a d mi nistrati o n wit h a mi ni m u m of 4 da ys re q uire d bet wee n d oses. 
Patie nts w h o meet i n di vi d ual patie nt st o p pi n g rules ( Secti o n 8. 1. 2 ) ma y res u me d osi n g after 
disc ussi o n bet wee n t he I n vesti gat or a n d Me dical M o nit or. U p o n res u m pti o n of d osi n g, 
s u bse q ue nt d oses s h o ul d be ti me d acc or di n g t o t he ori gi nal d osi n g sc he d ule base d o n Da y 1. 
Misse d d oses s h o ul d be d oc u me nte d i n t he e C R F as per Secti o n 9. 1. 4 . Patie nts w h o are 
disc o nti n ue d f or misse d d oses s h o ul d ha ve t heir disc o nti n uati o n rec or de d i n t he e C R F base d o n 
t he reas o n t he d os es were misse d, e g, A E, pr ot oc ol n o nc o m plia nce (s ee Secti o n 8. 2 ). 
If K Z R - 6 1 6 is per m a ne ntl y disc o nti n ue d d ue t o a n A E, t he pla n ne d ass ess me nts (see Sc he d ule of 
Assess me nts  i n Ta ble  1) s h o ul d c o nti n ue f or t he pr ot oc ol-s pecifi e d time peri o d. If t he patie nt 
ca n n ot c o nti n ue wit h t he pla n ne d assess me nts, t he Earl y Ter mi nati o n Visit ( E T V) s h o ul d be 
acc o m plis he d at a mi ni m u m  (see Secti o n 8. 2 ). 
6. 2.  
Pri or a n d C o nc o mit a nt Tre at me nts  
A n y c o nc o mita nt t hera pi es m ust be rec or de d o n t he e C R F. A c o n c o mita nt t hera p y is a n y t hera p y 
t hat ma y be use d, e g, p h ysical t hera p y, s ur g er y, or me dicati o n. A c o nc o mita nt me dicati o n is a n y 
prescri pti o n or o ver-t he- c o u nter pre p arati o n, i ncl u di n g vita mi ns a n d s u p ple me nts. C o nc o mita nt 
me dicati o n use will be rec or de d u ntil t he last f oll o w - u p visit. Details t o be rec or de d i n cl u de, b ut 
are n ot li mite d t o, t he c o nc o mita nt me dicati o n ge neric na me, d os e, r o ute, fre q ue nc y of 
a d mi nistrati o n, a n d i n dicati o n.  

Pr ot oc ol  A me n d me nt 1  
K Z R -6 1 6 -0 0 3 E  
Kezar Life Scie nces, I nc.  
1 3 Se pte m ber 2 0 2 1  
 
C o nfi de ntial  
Pa ge 3 0  of 6 6  
 
6. 2. 1.  
Per mitte d  C o nc o mit a nt Me dic ati o ns 
6. 2. 1. 1.  
M y ositis Dise ase -rel ate d C o nc o mit a nt Me dic ati o ns  
I m m u n os u p pr essa nt a n d c ortic oster oi d d ose a n d fre q ue nc y ma y b e re d u ce d at t he I n vesti gat or’s 
discreti o n  (see Secti o n 6. 2. 1. 1. 1  re gar di n g o pti o nal ta peri n g of oral c ortic oster oi d s). If a 
c o nc o mita nt treat me nt f or m y ositis is decrease d or disc o nti n ue d, t he reas o n m ust be d oc u me nte d 
i n t he e C R F. 
If a n I n v esti gat or deter mi nes t hat a patie nt nee ds a d diti o nal me dicati o n f or treat me nt of m y ositis, 
t he Me dical M o nit or s h o ul d be i nf or me d; if p ossi ble, a disc ussi o n s h o ul d occ ur bet w ee n t he 
I n v esti gat or a n d Me di cal M o nit or pri or t o i m ple me ntati o n of t he a d diti o nal me dicati o n. If a 
c o nc o mita n t treat me nt f or m y ositis is a d de d, t he reas o n m ust be d oc u me nt e d i n t he e C R F. 
6. 2. 1. 1. 1.  O pti o n al T a peri n g of Or al C ortic oster oi ds 
T a pers of c o nc o mita nt or al c ortic oster oi ds are o pti o nal a n d ma y be i nitiate d at t he I n vesti gat or’s 
discreti o n. Patie nts wit h  well -c o ntr olle d diseas e, i n t he I n v esti gat or's o pi ni o n, ma y be c o nsi dere d 
f or ta pers (e g, t h ose wit h n o, mi ni mal , or sta ble acti ve disease bas e d o n o verall e val uati o n of 
acti vit y s uc h as wea k ness, m yal gia, ras h, C K a n d ot her assess me nts). T h ere is n o pr ot oc ol-
defi ne d, ma n dat or y ta peri n g sc he d ule. P ossi ble sc he d ules f or gra d ual ta p eri n g of pre d nis o ne or 
pre d nis o ne e q ui val e nts i n t he setti n g of m y ositis  i ncl u de: 
•  Ta per  c urr e nt d ose b y 5 m g/ da y e ver y 1 2 w ee ks u ntil 1 0 m g/ da y, t he n b y 2. 5 m g/ da y 
e ver y 1 2 w ee ks u ntil disc o nti n ue d or w orse ni n g of disease re q uires a n i ncrease, i n t he 
I n v esti gat or's o pi ni o n. 
•  F or a sl o wer t a per fr o m 5 m g/ d ay u ntil disc o nti n u ati o n or w orse ni n g of dise ase : 
Fr o m 5 m g/ da y d ose , ta p er b y 1- 2. 5 m g/ da y e v er y 1 2 wee ks u ntil disc o nti n ue d or 
w orse ni n g of diseas e re q uires a n i ncrease, i n t he I n vesti gat or's o pi ni o n. 
 
6. 2. 1. 2.  
Ot her C o nc o mit a nt T her a pies  
Ot her c o nc o mita nt t hera pies f or c o m or bi d c o n diti o ns (e g, a nti h y perte nsi v es or li pi d l o weri n g 
a ge nts) ar e per mitte d; t hese t hera pies s h o ul d be rec or de d i n t he e C R F. Details re gar di n g p h ysical 
t hera p y, occ u pati o nal t hera p y, or e x ercis e s h o ul d als o be rec or de d i n t he e C R F. 
6. 2. 1. 3.  
P ote nti al Dr u g -Dr u g I nter acti o ns  
K Z R - 6 1 6 s h o ul d be a d mi nistere d at least 6 h o urs b ef ore, or 4 h o urs after, dr u gs t hat are k n o w n 
i n hi bit ors of P- g p (e g, c y cl os p ori ne [ n ot per mitte d d uri n g t he st u d y], at or vastati n, azit hr o m yci n, 
c olc hici ne, o me pr az ole).   
6. 2. 1. 4.  
V acci n ati o ns 
It is str o n gl y rec o m me n d e d t hat patie nts be u p t o date o n i m m u nizati o ns per c urre nt 2 0 1 5 
A merica n C olle ge of R he u mat ol o g y ( A C R) g ui deli nes ( Si n g h 2 0 1 6 ). Vacci nati o ns recei v e d at 
a n y ti me d uri n g t he st u d y s h o ul d be rec or de d i n t he e C R F. Li ve vacci nati o ns are n ot per mitte d 
d uri n g t he st u d y. If vacci nati o n a gai nst her pes z oster is re q uire d d uri n g t he st u d y, S hi n gri x or 

Pr ot oc ol  A me n d me nt 1  
K Z R -6 1 6 -0 0 3 E  
Kezar Life Scie nces, I nc.  
1 3 Se pte m ber 2 0 2 1  
 
C o nfi de ntial  
Pa ge 3 1  of 6 6  
 
ot her n o n- li ve vacci ne (if a vaila ble) is preferre d o ver li ve vacci nes. Si milarl y,  vacci nati o n 
a gai nst  i nfl ue nza vir us wit h i nacti vate d vacci n e  is preferre d. 
6. 2. 2.  
Ot her Rest ri cti o ns a n d Pr o hi biti o ns  
F or patie nts r e q uiri n g s ur ger y, or f or a n y pla n n e d s ur ger y d uri n g t he st u d y, t he Me dical M o nit or 
s h o ul d be c o ns ulte d t o disc uss K Z R - 6 1 6 d osi n g. 

Pr ot oc ol  A me n d me nt 1  
K Z R -6 1 6 -0 0 3 E  
Kezar Life Scie nces, I nc.  
1 3 Se pte m ber 2 0 2 1  
 
C o nfi de ntial  
Pa ge 3 2  of 6 6  
 
7.  
S T U D Y E V A L U A TI O N S  
7. 1.  
Sc he d ule of Assess me nts  
T he Sc he d ule of Assess me nts  is prese nte d i n Ta ble  1, a n d t he Sc he d ule of  K Z R - 6 1 6 
A d mi nistrati o n  (wit h  vital si g ns a n d pre g na nc y testi n g) is prese nte d i n Ta bl e  2. 
O n -site st u d y visits will occ ur at Wee ks 1 2, 2 4, 3 6, 4 8, 6 0, 7 2, 8 4, a n d 9 6, a n d t he E O S Visit . At 
t hese visits, safet y a n d efficac y assess me nts will be perf or me d  a n d K Z R - 6 1 6 will be 
a d mi nistere d acc or di n g t o t he Sc he d ule of Ass ess me nts ( Ta ble  1). All ot her st u d y visits ma y 
occ ur eit her at t he site or at patie nts ’ h o mes via h o me healt h pr o vi ders ( Ta ble  2). 
7. 1. 1.  
U nsc he d ule d Visits  
All atte m pts s h o ul d be ma de t o kee p p atie nts o n t he st u d y sc he d ule. U ns c he d ule d visits ma y be 
necessar y t o re p eat testi n g f oll o wi n g a b n or mal la b orat or y res ults, f or f oll o w- u p of A Es, or f or 
ot her reas o ns, as warra nt e d. D uri n g a n u nsc h e d ule d visit, i nf or mati o n re gar di n g c o nc o mita nt 
me dicati o ns a n d A Es ( at a mi ni m u m) will be c ollecte d. A n y of t he ot her pr oce d ures liste d f or t he 
Wee k 2 4 visit ma y als o b e perf or me d at t he I n ves ti gat or’s discreti o n.  
7. 1. 2.  
Tele he alt h Visits  
W hile t he st u d y visits i n Ta ble  1 ar e ma n dat or y, i n rec o g niti o n of c o nstrai nts i m p ose d b y t he 
S A R S - C o V- 2 pa n de mic, sites ma y elect t o use a c o m bi nati o n of tele me dici ne (as per mitte d b y 
t heir i nstit uti o ns) a n d/ or h o me healt h pr o vi ders t o c o n d uct t hese visits. All ot her visits, i ncl u di n g 
wee kl y K Z R - 6 1 6 i njecti o ns, ma y occ ur at t he site or at patie nts’ h o mes via h o me healt h 
pr o vi ders. 
F or tele h ealt h visits, a li mite d p h ysical e xa mi nati o n will be perf or me d a n d t he M M T -8 will n ot 
be assesse d. All ot her ass ess me nts s h o ul d be perf or me d, if feasi ble. Sa m ples f or cli nical 
la b orat or y ass ess me nts will be c ollecte d b y h o me healt h pr o vi ders a n d s e nt t o t he ce ntral 
la b orat or y. 
Please ref er t o Secti o ns 7. 2. 4 , 7. 2. 6. 1 , 7. 2. 6. 2 , a n d 7. 2. 6. 3  f or a d diti o nal i nf or mati o n re gar di n g 
assess me nts  perf or me d at  tele healt h visits.  

Pr ot oc ol  A me n d me nt 1  
K Z R -6 1 6 -0 0 3 E  
Kezar Life Scie nces, I nc.  
 
 
1 3 Se pte m ber 2 0 2 1  
 
C o nfi de ntial  
Pa ge 3 5  of 6 6  
 
j 
S h o ul d be perf or me d o nl y i n patie nts wit h  D M.  
k 
It is rec o m me n de d t hat P R O Ms are c o m plete d first at eac h visit w here perf or me d (ie, pri or t o a n y ot her pr oce d ures or assess ments ot her t ha n si g ni n g of 
i nf or me d c o nse nt). 
l 
See Secti o n 7. 2. 6. 4  f or assess me nts. 
m 
O nl y f or t he E T V.  
n 
Bl o o d  sa m pli n g f or c yt o ki nes a n d pr ote o mics will  be  perf or me d  pri or t o  d osi n g.  
o 
Sa m ples will be c ollec te d pri or t o d osi n g i n patie nts w h o ha ve pr o vi de d t he pr o per i nf or me d c o nse nt f or ge netic a nal yses.  
p 
Patie nts  will  recei ve st u d y dr u g wee kl y  acc or di n g t o Ta ble  1 a n d Ta ble  2. At -h o me a d mi nistrati o n b y t he patie nt  or care gi ver ma y be a n o pti o n f or patie nts 
dee me d a p pr o priate b y t he I n vesti gat or (see Secti o n 5. 4 ). H o me  healt h  pr o vi der s will  be arra n ge d f or patie nts w h o c h o ose n ot t o ret ur n t o t he site or a d mi nister 
st u d y dr u g at h o me.  
q 
T he Wee k 3 2 assess me nts fr o m St u d y K Z R -6 1 6 -0 0 3 m ust be perf or me d, a n d i nf or me d c o nse nt f or t his o pe n -la bel e xte nsi o n st u d y si g ne d pri or t o t he first 
d ose of o pe n -la bel K Z R-6 1 6.  
r 
D oes n ot a p pl y t o t he E T V.  
 

Pr ot oc ol  A me n d me nt 1  
K Z R -6 1 6 -0 0 3 E  
Kezar Life Scie nces, I nc.  
1 3 Se pte m ber 2 0 2 1  
 
C o nfi de ntial  
Pa ge 3 8  of 6 6  
 
7. 2.  
St u d y Pr oce d ures a n d Assess me nts  
All patie nts m ust be pr o vi de d a c o nse nt f or m descri bi n g t he st u d y wit h s ufficie nt i nf or mati o n f or 
t he m t o ma ke a n i nf or me d decisi o n re gar di n g t heir partici pati o n as per Secti o n 1 1. 3 . I nf or me d 
c o nse nt m ust be si g ne d pri or t o a n y pr oce d ures f or t he o pe n- la bel e xte nsi o n. All st u d y 
pr oce d ur es a n d ass ess me nts s h o ul d be perf or me d acc or di n g t o t he s c he d ules prese nte d i n Ta bl e  1 
a n d Ta ble  2. 
If a patie nt is n ot a ble t o c o me t o t he st u d y site f or a n o n-site visit as per t he Sc he d ule of 
Assess me nts ( Ta ble  1), a tele healt h visit s h o ul d occ ur. Please refer t o Secti o ns 7. 2. 4 , 7. 2. 6. 1 , 
7. 2. 6. 2 , a n d 7. 2. 6. 3  f or a d diti o nal i nf or mati o n re gar di n g assess me nts perf or me d at tele healt h 
visits.  
7. 2. 1.  
De m o gr a p hic D at a 
De m o gra p hic d ata c ollecte d i n K Z R - 6 1 6- 0 0 3 will be use d f or t his st u d y. 
7. 2. 2.  
P ol y m y ositis/ Der m at o m y ositis Cl assific ati o n 
Patie nt classificati o n of P M or D M base d o n t he 2 0 1 7 A C R/ E ur o pea n Lea g ue A gai nst 
R he u matis m ( E U L A R)  classificati o n criteria (L u n d ber g 2 0 1 6 ) fr o m K Z R - 6 1 6- 0 0 3 will be use d 
f or t his st u d y. 
7. 2. 3.  
Me dic al Hist or y  
Me dical hist or y data c oll ecte d i n K Z R - 6 1 6- 0 0 3 will be use d f or t his st u d y, wit h t he p ote ntial t o 
u p date. 
7. 2. 4.  
Effic ac y Assess m e nts   
Efficac y assess me nts will be perf or m e d f or all patie nts, u nless i n dicate d ot her wise, at t he visits  
s h o w n i n t he Sc he d ule of Assess me nts (Ta ble  1). As i nterrater relia bilit y ma y res ult i n i ncrease d 
varia bilit y of wit hi n -patie nt assess me nts, it is rec o m me n de d t hat t he sa me i n di vi d ual perf or ms 
t he assess me nts at all visits f or a n i n di vi d ual patie nt. All pers o n nel perf or mi n g t he assess me nts 
m ust be q ualifie d t o perf or m t he m. 
We bsites f or t he i n di vi d u al assess me nts ( w here a v aila ble) are pr o vi de d i n S ecti o n 1 3. 2  
( A p pe n di x B). 
7. 2. 4. 1.  
T ot al I m pr o ve m e nt Sc ore  ( TI S) 
T he TI S uses t he 6 I M A C S c ore set meas ures, c o m bi ni n g t he a bs ol ute perce nta ge c ha n g e i n eac h 
wit h var yi n g wei g hts t o o btai n a TI S o n a scal e of 0- 1 0 0. T hres h ol ds of i m pr o ve me nt ha ve b ee n 
set f or mi ni mal, m o derat e, a n d maj or r es p o nse. T he TI S is t he pri mar y o ut c o me meas ure f or t his 
st u d y, a n d will n ot be calc ulate d b y sites. 
7. 2. 4. 2.  
M a n u al M uscle Testi n g -8 M uscle Gr o u ps ( M M T - 8) 
T his t o ol assesses m uscle stre n gt h usi n g ma n ual m uscle testi n g. A 0 t o 1 0- p oi nt scale is pr o p ose d 
f or use. A n a b bre viat e d gr o u p of 8 pr o xi mal, distal, a n d a xial m uscles ( n ec k fle x ors, delt oi ds, 

Pr ot oc ol  A me n d me nt 1  
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bice ps brac hii, gl ute us ma xi m us, gl ute us me di us, q ua drice ps, wrist e xte ns ors, a n kle d orsifle x ors) 
perf or ms si milarl y t o a t otal of 2 4 m u scle gr o u ps, a n d t his a b bre viate d gr o u p is als o pr o p ose d f or 
use f or r esearc h st u dies  (Ri der 2 0 1 0 ; Ri der 2 0 1 1 ).  
7. 2. 4. 3.  
M y ositis Dise ase Acti vit y Assess me nt T o ol  ( M D A A T) 
T his t o ol meas ures t he de gree of disease acti vit y of e xtra m usc ular or ga n s yste ms a n d m uscle. 
T his is a c o m bi ne d t o ol t hat i ncl u des t he M y ositis Disease A cti vit y Assess me nt Vis ual A nal o g ue 
Scales ( M Y O A C T), w hic h is a series of p h ysicia n's assess me nts of diseas e acti vit y of vari o us 
or ga n s yst e ms m o difie d fr o m t he Vasc ulitis Acti vit y I n de x , (W hiti n g - O’ Keefe 1 9 9 9) a n d t h e 
M y ositis I nte nti o n t o Treat Acti vit y I n d e x ( MI T A X), w hic h is m o difie d fr o m t he Britis h Isles 
L u p us Assess me nt Gr o u p a p pr oac h t o assess dise ase acti vit y i n S L E  (Ha y 1 9 9 3 ). T he MI T A X is 
c o m p ose d of a s eries of or ga n- s pecific q uesti o ns relati n g t o t he prese n ce or a bse nce of t he 
cli nical feat ur e a n d t he d e gree of treat me nt nee d e d f or it (i nte nti o n t o treat)  (Ri der 2 0 1 1 ; 
S ulta n  2 0 0 8). 
7. 2. 4. 4.  
P h ysici a n Gl o b al Assess m e nt of Dise ase Acti vit y  ( M D G A) 
T his t o ol meas ures t he gl o bal e val uati o n b y t he treati n g p h ysicia n of t he o verall disease acti vit y 
of t he patie nt at t he ti me of assess me nt usi n g a 1 0 c m vis ual a nal o g scal e ( V A S) a n d a 5- p oi nt 
Li kert scale  (Ri der 2 0 1 1 ). 
7. 2. 4. 5.  
P h ysici a n Gl o b al I m pressi o n of C h a n ge ( M D GI C) 
T he M D GI C c o nsists of 1 ite m ta ke n fr o m t he Cli nical Gl o bal I m pressi o ns scale ( C GI), w hic h 
was p u blis he d i n 1 9 7 6 b y t he U S Nati o nal I nstit ute of Me ntal Healt h. A ns w ers are base d o n a 
7- p oi nt Li kert scale r a n gi n g fr o m ver y m uc h i m pr o ve d t o ver y m uc h w orse, as ki n g re gar di n g t he 
patie nt’s o verall stat us  (G u y 1 9 7 6 ). 
7. 2. 4. 6.  
F u ncti o n al I n de x - 2 ( FI- 2) 
T he FI - 2 is a f u n cti o nal o utc o me de vel o pe d f or patie nts wit h a d ult P M or D M, assessi n g m uscle 
e n d ura nce i n 7 m uscle gr o u ps. Eac h m uscle gr o u p is sc ore d as t he n u m ber of c orrectl y 
perf or me d re p etiti o ns wit h  6 0 or 1 2 0 ma xi mal n u m ber of re p etiti o ns ( de pe n di n g o n m uscle 
gr o u p). T he FI- 2 is a f urt her de vel o p me nt of t he ori gi nal FI, w h ere re d u n da nt tas ks were 
eli mi nate d a n d t he n u m ber of r e petiti o ns f or eac h tas k were i n crease d t o a v oi d ceili n g effects. It 
has bee n vali dat e d as t o c o nte nt a n d c o nstr uct vali dit y a n d i ntra- a n d i nterrater relia bilit y. T he 
FI - 2 ca n be p erf or me d o n j ust t he d o mi na nt si de, w hic h ta kes a p pr o xi matel y 2 1 mi n utes. 
(Ale xa n ders o n 2 0 0 6 ; Ri der 2 0 1 1 ) 
7. 2. 4. 7.  
F u ncti o n al Assess m e nt:  Sit -t o-St a n d Test  ( S T S) 
T he  S T S t est sc ore is t he n u m ber of ti mes t hat t he patie nt rises t o a f ull sta n d fr o m t he seate d 
p ositi o n wit h ar ms f ol de d acr oss t he c hest wit hi n 3 0 sec o n ds ( A g ar wal 2 0 0 6 ). T he S T S test will 
be use d as a f u ncti o nal assess me nt f or t his st u d y. 

Pr ot oc ol  A me n d me nt 1  
K Z R -6 1 6 -0 0 3 E  
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1 3 Se pte m ber 2 0 2 1  
 
C o nfi de ntial  
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7. 2. 4. 8.  
M y ositis D a m a ge I n de x ( M DI) 
T he M DI is a t o ol t hat assesses t he de gree of dis ease da ma ge of all or ga n s yste ms. It is 
c o m p ose d of a s eries of or ga n -s pecific q uesti o ns relati n g t o t he prese n ce or a bse nce of a gi ve n 
si g n or s y m pt o m or pr o ble m t o meas ure t he e xte nt of da ma ge, a n d a n o verall rati n g of t he 
disease da ma g e of eac h s yste m usi n g a 1 0 c m V A S t o meas ure t he se verit y of da ma ge  
(Ri der  2 0 1 1; S ulta n 2 0 1 1 ). 
7. 2. 4. 9.  
C ut a ne o us Der m at o m y ositis Dise ase Are a a n d Se verit y I n de x  ( C D A SI) 
T he C D A SI will be perf or me d o nl y f or t h ose patie nts wit h D M. 
T he C D A SI is a cli nicia n -sc ore d si n gle-pa ge i nstr u me nt t hat se parat el y meas ures acti vit y a n d 
da ma ge i n t he s ki n of D M patie nts f or use i n cli nical practice or cli nical/t hera pe utic st u dies. T h e 
m o difie d C D A SI ( Versi o n 2) is t he o ne i n c urre nt use. T he m o difie d C D A SI h as 3 acti vit y 
meas ures ( er yt he ma,  s cal e, a n d er osi o n/ ulcerati o n) a n d 2 da ma ge m eas ures ( p oi kil o der ma a n d 
calci n osis) w hic h are assesse d o ver 1 5 b o d y areas. I n a d diti o n, G ottr o n’s pa p ules o n t he ha n ds 
are e v al uate d b ot h f or acti vit y a n d da ma ge. Lastl y, t he acti vit y of peri u n g ual c ha n ges a n d 
al o pecia is assess e d  (Ri der 2 0 1 1 ; Yassaee 2 0 1 0 ). 
7. 2. 5.  
P atie nt Re p ort e d O utc o m e Me as ures  
T he patie nt -r e p orte d o utc o me meas ures ( P R O Ms) o utli ne d i n t he secti o ns t hat f oll o w will be 
assesse d  i n t his st u d y. F or  visits at w hic h P R O Ms are perf or m e d, it is rec o m me n de d t hat t he y be 
c o m plete d pri or t o a n y ot her assess me nts or pr oce d ures. All P R O Ms will be c o m plete d b y t he 
patie nt or a desi g nee o n a ta blet, m o bile p h o ne, or ot her electr o nic de vice, wit h t he e xce pti o n of 
t he E Q- 5 D- 5 L, w hic h is a pa per-base d assess me nt.  
We bsites f or t he i n di vi d u al assess me nts  ( w here a v aila ble) are pr o vi de d i n S ecti o n 1 3. 2  
( A p pe n di x B). 
7. 2. 5. 1.  
P atie nt Gl o b al Assess me nt of Dise ase A cti vit y  ( Pt G A D A) 
T he Pt G A D A is a  t o ol t hat meas ures t he gl o b al e v al uati o n of t he patie nt's o verall disease acti vit y 
at t he ti me of assess me nt usi n g a 1 0 c m V A S ( Ri der 2 0 1 1 ).  
7. 2. 5. 2.  
He alt h Assess m e nt Q uesti o n n aire -Dis a bilit y I n de x  ( H A Q-DI)  
T he H A Q - DI is a t o ol t o assess p h ysical f u ncti o n i n m y ositis (Ri der 2 0 1 1 ). 
7. 2. 5. 3.  
P atie nt Gl o b al I m pressi o n of C h a n ge ( P GI C) 
T he P GI C is t he P R O M c o u nter part t o t he C GI, w hic h was p u blis he d i n 1 9 7 6 b y t he U S Nati o nal 
I nstit ute of Me nt al Healt h. It c o nsists of o n e ite m ta ke n fr o m t he C GI a n d a da pte d t o t he patie nt. 
A ns wers are bas e d o n a 7 - p oi nt Li kert scale ra n gi n g fr o m ver y m uc h i mpr o v e d t o ver y m uc h 
w orse, as ki n g r e gar di n g t he patie nt’s o verall stat us (G u y 1 9 7 6 ). 

Pr ot oc ol  A me n d me nt 1  
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1 3 Se pte m ber 2 0 2 1  
 
C o nfi de ntial  
Pa ge 4 1  of 6 6  
 
7. 2. 5. 4.  
E ur o Q o L 5- di m e nsi o n 5 -le vel ( E Q- 5 D- 5 L) 
E Q - 5 D- 5 L is a sta n d ar di ze d i nstr u me nt de vel o p e d b y t he E ur o Q o L Gr o u p as a meas ure of 
healt h -rel ate d q ualit y of life t hat ca n b e use d i n a wi de ra n ge of healt h c o n diti o ns a n d treat me nts. 
T he E Q - 5 D- 5 L c o nsists of a descri pti ve s yste m a n d t he E ur o Q ol vis ual a n al o g scale (E Q -V A S ). 
T he descri pti ve s yste m c o m prises 5 le vels of se verit y f or eac h of 5 di me nsi o ns (ie, m o bilit y, 
self-care, us ual acti vities, pai n/ disc o mf ort, a n d a n xiet y/ de pressi o n). T he E Q-V A S rec or ds t he 
patie nt’s self -r ate d healt h o n a vertical V A S. T his ca n be use d as a q u a ntitati ve meas ure of healt h 
o utc o me t hat reflects t he patie nt’s o w n j u d g me nt. T he sc ores o n t h ese 5 di me nsi o ns ca n be 
prese nte d as a healt h pr ofile or c o n vert e d t o a si n gle s u m mar y i n de x n u m ber ( utilit y) reflecti n g 
prefera bilit y c o m pare d t o ot her healt h pr ofiles. 
7. 2. 5. 5.  
P atie nt Gl o b al Assess me nt of Dise ase D a m a ge ( Pt G A D D) 
T he P t G A D D is a t o ol t hat meas ures t he gl o b al e v al uati o n of t he patie nt's o verall disease d a ma ge 
at t he ti me of assess me nt usi n g a 1 0 c m V A S.  
7. 2. 5. 6.  
Pe a k Pr urit us N u m eric al R ati n g Sc ale ( N R S) 
I n a st u d y of patie nts wit h D M, 5 0 % re p ort e d m o derate-t o-se vere itc h, w hi c h was c orrelat e d wit h 
i ncreas e d c uta n e o us se verit y (Ki m 2 0 1 8 ). T he Pea k Pr urit us N R S, use d t o e val uate itc h i n at o pic 
der matitis, will be utilize d t o e val uate t he se v erit y of itc h i n patie nts wit h D M. T he Pea k Pr urit us 
N R S  ra n ges fr o m 0 t o 1 0, wit h 0 re pres e nti n g n o itc h a n d 1 0 re prese nti n g t he w orst itc h 
i ma gi na ble d uri n g t he w orst m o me nt wit hi n a 2 4- h o ur recall peri o d. 
7. 2. 6.  
S afet y Assess m e nts  
Safet y will be assesse d t hr o u g h o ut t he st u d y b y m o nit ori n g of vital si g ns, p h ysical e xa mi nati o ns, 
a n d la b orat or y t ests; a n d b y rec or di n g a n d a nal y zi n g all A Es a n d S A Es. 
7. 2. 6. 1.  
Vit al Si g n Me as ure m e nts  
Bl o o d press ure, p ulse r ate, a n d te m per at ure will be meas ure d at t he visits s h o w n i n t he Sc he d ules 
of Assess me nts ( Ta ble  1 a n d Ta ble  2). Bl o o d press ure a n d p ulse rate s h o ul d be c ollecte d after t h e 
patie nt has ha d at least 5 mi n utes of rest i n t he seate d p ositi o n. If t he bl o o d press ure is ele vate d 
o n t he first meas ure m e nt at scree ni n g a n d baseli ne, it s h o ul d be re peate d aft er at least a n 
a d diti o nal 5 mi n utes of rest. It is r ec o m me n de d t h at bl o o d press ure is meas ure d usi n g t he sa me 
ar m at eac h assess me nt. W he n t he ti me of vital si g ns meas ure me nt c oi n ci des wit h a bl o o d 
sa m ple c ollecti o n, t he vital si g ns will be meas ure d bef ore bl o o d s a m ple c ollecti o n. 
7. 2. 6. 2.  
Wei g ht  
W he n p ossi ble, b o d y wei g ht will be rec or d e d at t h e o n -site visits s h o w n i n t he Sc he d ule of 
Assess me nts ( Ta ble  1 ). B o d y wei g ht, wit h t he patie nt weari n g li g ht cl ot hi n g a n d t he s h oes a n d 
jac ket or c o at re m o ve d, will be meas ure d a n d rec or de d i n kil o gra ms. 
F or tele h ealt h visits, wei g ht will n ot be meas ure d; a wei g ht fr o m a n y s o urce ot her t ha n t he st u d y 
site s h o ul d n ot be rec or d e d. 

Pr ot oc ol  A me n d me nt 1  
K Z R -6 1 6 -0 0 3 E  
Kezar Life Scie nces, I nc.  
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C o nfi de ntial  
Pa ge 4 2  of 6 6  
 
7. 2. 6. 3.  
P h ysic al E x a mi n ati o n 
C o m plete p h ysical e xa mi nati o ns will be perf or me d at t he o n-site visits s pecifie d o n t he Sc he d ule 
of Assess me nts ( Ta ble  1). A c o m plete p h ysical e x a mi nati o n s h o ul d i ncl u de assess me nts of at 
least t he foll o wi n g s yste ms: ge neral a p p eara nce, hea d, ears, e y es, n ose a n d t hr oat, nec k, 
der mat ol o gical, res pirat or y, car di o v asc ular, a b d o me n, e xtre mities, ne ur ol o gical, m usc ul os keletal. 
At ot her visits (i ncl u di n g ot her o n- site visits a n d u nsc he d ule d visits), a li mite d p h ysical 
e xa mi nati o n ma y be perf or me d as directe d b y t he patie nt c o m plai nts a n d t he cli nical j u d g me nt of 
t he I n v esti gat or. Me dicall y si g nifica nt c ha n ges fr o m p h ysical e xa mi nati o n will be rec or d e d as 
A Es. M uscle e val u ati o n fi n di n gs ca pt ure d i n t he m uscl e assess me nt i nstr u me nts will n ot be 
rec or d e d u nless t he y are classifia ble as S A Es, as p er Secti o n 9. 2. 1 . 
Li mite d p h ysical e xa mi nati o ns will be perf or me d at tele healt h visits.  
7. 2. 6. 4.  
Cli nic al L a b or at or y Assess me nts 
Cli nical la b orat or y tests f or safet y, i ncl u di n g he mat ol o g y, cli nical c he mistr y, i m m u n o gl o b uli ns, 
a n d cli nical la b or at or y assess me nts f or efficac y meas ures will be perf or me d at a ce ntral 
la b orat or y at t he visits s h o w n o n t he Sc he d ules of Assess me nt (Ta ble  1).  
He mat ol o g y: c o m plete bl o o d c o u nt wit h differe nti al. 
Cli nical c he mistr y : c he mist r y pa nel i ncl u di n g electr ol ytes, A S T, A L T,  a n d t otal bilir u bi n; 
al d olase, L D H , C K , a n d C- reacti ve pr otei n (C R P ).  
A d diti o nal bl o o d will be se nt f or bi o mar ker st u dies as per Secti o n 7. 2. 7 .  
U nsc he d ule d or a d diti o nal la b orat or y sa m ples m a y be c ollecte d a n d a nal y ze d b y l ocal 
la b orat ories if i m me diate res ults are n ecess ar y f or ma na ge me nt of T E A Es or d osi n g 
deter mi nati o n. Uri ne pr e g na nc y tests will be perf or me d l ocall y. 
U nless ot her wise n ote d, w he n sc he d ul e d si m ulta ne o usl y wit h a d osi n g visit, sa m ples f or 
la b orat or y e v al uati o ns s h o ul d be c ollecte d pri or t o a d mi nistrati o n of K Z R- 6 1 6. 
Cli nical la b orat or y res ults t he I n v esti gat or dee ms cli nicall y si g nifica ntl y a b n or mal s h o ul d be 
re peat e d wit hi n 4 8 t o 7 2 h o urs fr o m w he n t he res ult beca me a v aila ble, w he n p ossi ble. 
7. 2. 6. 5.  
M uscle E nz y m es  
M uscle e nz y mes (al d olas e, A L T, A S T, C K, a n d L D H) will be meas ure d as  per Secti o n 7. 2. 6. 4 .  
7. 2. 7.  
E x pl or at or y Bi o m ar kers 
A d diti o nal bl o o d a n d ser u m will be se nt f or bi o mar ker st u dies. D etaile d i nstr ucti o ns f or sa m ple 
c ollecti o n, pr ocessi n g, st ora ge a n d s hi p me nt will be pr o vi de d i n t he La b orat or y Ma n ual. 
7. 2. 7. 1.  
C yt o ki nes a n d Pr ote o mics  
Bl o o d sa m ples will be c ollecte d at t he ti mes s h o w n i n t he Sc he d ule of Assess me nts ( Ta ble  1) f or 
t he meas ure m e nt of c yt o ki nes b y e nz y me-li n ke d i m m u n os or be nt assa y (E LI S A ). A d diti o nal 
i nf or mati o n re gar di n g sa m ple c ollecti o n a n d ha n dli n g are o utli ne d i n t he La b orat or y Ma n ual. 

Pr ot oc ol  A me n d me nt 1  
K Z R -6 1 6 -0 0 3 E  
Kezar Life Scie nces, I nc.  
1 3 Se pte m ber 2 0 2 1  
 
C o nfi de ntial  
Pa ge 4 3  of 6 6  
 
7. 2. 7. 2.  
Ge ne  E x pressi o n  
Ge ne e x pressi o n (ri b o n u cleic aci d [ R N A]) pr ofili n g ma y be assesse d i n bl o o d sa m ples. A w h ole 
bl o o d sa m ple will be c ollecte d f or ge ne e x pressi o n  a nal ysis f or st ora g e a n d a nal ysis at a later 
date as s pecifie d i n t he Sc he d ule of Ass ess me nts ( Ta ble  1) a n d t o t he e xte nt per mitte d b y t he 
nati o nal a n d/ or l ocal la ws a n d re g ulati o ns. 
Sa m ples will be use d t o c o n d uct retr os pecti ve disease or p o p ulati o n ge n etic researc h as a 
se parat e a nal ysis n ot i ncl u de d i n t his st u d y. Sa m ples ma y be use d t o i n vesti gate varia bl e res p o ns e 
t o K Z R- 6 1 6 a n d t o i n vesti gate ge netic or e pi ge neti c varia nts t h o u g ht t o pla y a r ole i n t he diseas es 
u n der i n vesti gati o n i n t his st u d y. Assess me nt of varia ble res p o ns e ma y i ncl u de e val uati o n of A Es 
or differ e nces i n efficac y. T he res ults ma y be re p orte d i n t he se parate re p ort.  
A d diti o nal i nf or mati o n re gar di n g sa m ple c ollecti o n a n d ha n dli n g are o utli ne d i n t he La b orat or y 
Ma n ual.  
7. 2. 8.  
C o ntr ace pti o n Re q uire m e nts  a n d Pre g n a nc y Testi n g  
W o me n of c hil d beari n g p ote ntial m ust ha ve a ne g ati ve uri ne pre g na nc y t est bef ore d oses of 
K Z R - 6 1 6 o utli ne d i n Ta b le 1 a n d Ta ble  2, a n d m ust a gree t o use hi g hl y effecti ve a n d me dicall y 
acce pta ble met h o ds of c o ntrace pti o n t o pre v e nt pre g na nc y d uri n g t he st u d y a n d f or 4 w ee ks after 
a d mi nistrati o n of t he last d ose of K Z R- 6 1 6. F or t h e p ur p oses of t his st u d y, W O C B P are defi n e d 
as p ost p u besce nt f e male patie nts, u nless t he patie nt is p ost me n o pa usal ( defi ne d b y a me n orr hea 
f or at least 2 years or a m e n orr hea f or at least 1 year wit h c o nfir mat or y F S H le vel i n t he 
p ost me n o pa usal ra n ge, as d oc u me nte d hist oricall y or meas ure d b y t he ce ntral or l ocal la b orat or y 
a n d if patie nt is n ot o n s u p ple me ntar y h or m o nal t h era p y) or s ur gicall y steril e (ie, t u bal li gati o n, 
h ysterect o m y, bilater al sal pi n g o o p h orect o m y). 
Hi g hl y effecti ve c o ntrace pti o n is defi ne d as t he us e of a n i ntra ut eri ne de vi ce or h or m o nal 
c o ntrac e pti ves (e g, i m pla nt or oral) or h a vi n g a vasect o mize d part ner. I n re gi o ns w here it is 
c o nsi dere d hi g hl y effecti ve c o ntrace pti o n, 2 barrier met h o ds (e g, fe male dia p hra g m a n d male 
c o n d o m O R 1 barrier met h o d wit h s per mici de) ma y be use d. 
If usi n g a h or m o nal f or m of c o ntrace pti o n, use m ust ha ve bee n sta bl e f or at least 4 wee ks pri or t o 
t he Wee k 1 Da y 1 Visit, a n d if usi n g c o nc o mita nt m yc o p he n olate, t he p atie nt m ust use a n ot her 
hi g hl y effecti ve n o n h or m o nal f or m of c o ntrace pti o n. A bsti ne nce will be acce pta ble o n l y if it is i n 
li ne wit h t he preferre d a n d us ual lifest yle of t he patie nt. Peri o dic a bsti ne nce (e g, cal e n dar, 
o v ulati o n) a n d wit h dra w al are n ot acce pta ble met h o ds of c o ntrace pti o n. 
F or W O C B P, uri ne pre g na nc y testi n g will be perf or me d at t he ti me p oi nts s h ow n i n Ta ble  1 a n d 
Ta ble  2. K Z R- 6 1 6 s h o ul d n ot be a d mi nistere d pri or t o c o nfir mati o n of a n e gati ve test at visits at 
w hic h pre g na nc y tests ar e perf or me d. P ositi ve uri ne pre g na n c y tests s h o ul d be c o nfir me d b y a 
ser u m pre g na nc y test. 
Sa m ples f or F S H testi n g ma y be c ollecte d at a n y ti me d uri n g t he st u d y t o c o nfir m 
p ost me n o pa usal stat us i n fe male patie nts w h os e c hil d beari n g p ote ntial stat us has c ha n ge d si n ce 
t he Scree ni n g Visit of St u d y K Z R- 6 1 6- 0 0 3. O nl y after c o nfir mati o n of p ost me n o pa usal stat us is 
pre g na nc y t esti n g n ot re q uire d. 

Pr ot oc ol  A me n d me nt 1  
K Z R -6 1 6 -0 0 3 E  
Kezar Life Scie nces, I nc.  
1 3 Se pte m ber 2 0 2 1  
 
C o nfi de ntial  
Pa ge 4 4  of 6 6  
 
Male patie nts m ust c o nti n ue  t o use a n effecti ve c o ntrace pti o n met h o d (e g, c o n d o m wit h 
s per mici de) f or 1 wee k f oll o wi n g t he last d ose of K Z R- 6 1 6 or be c o n g e nitall y or s ur gicall y 
sterile (e g, vas ect o m y wit h d oc u me nte d c o nfir m ati o n of p ost-s ur gical as per mia). T he decrease i n 
male c o ntr ace pti o n use fr o m 1 2 wee ks i n pri or K Z R- 6 1 6 pr ot oc ols t o 1 wee k i n St u d y 
K Z R - 6 1 6- 0 0 3 E is s u p p orte d b y t he s h ort half-life of K Z R- 6 1 6 ( < 2 h o urs), f ull rec o ver y of 
i m m u n o pr oteas o me i n hi biti o n wit hi n 3 da ys of d osi n g, lac k of m uta ge nic p ote ntial as deter mi ne d 
i n vitr o a n d i n vi v o n o ncli nical st u dies, a n d lac k of re pr o d ucti ve or ga n fi n di n gs i n t he 6- a n d 
9- m o nt h r o de nt a n d m o n ke y re peat- d ose t o xicit y st u dies. A d diti o nall y, n o terat o ge nic effects 
were f o u n d i n t he defi niti ve e m br y of etal t o xicit y st u dies i n rats a n d ra b bits. As per I nter nati o nal 
C o u ncil f or Har m o nisati o n ( I C H) M 3 g ui da nce, l ac k of re pr o d ucti ve a n d t erat o ge nic fi n di n gs i n 
ge neral t o xicit y a n d e m br y ofetal t o xicit y st u dies is s ufficie nt t o s u p p ort t he treat me nt of male 
patie nts i n P hase 1 a n d 2 trials pri or t o c o n d ucti n g fertilit y st u dies.  

Pr ot oc ol  A me n d me nt 1  
K Z R -6 1 6 -0 0 3 E  
Kezar Life Scie nces, I nc.  
1 3 Se pte m ber 2 0 2 1  
 
C o nfi de ntial  
Pa ge 4 5  of 6 6  
 
8.  
S T U D Y DI S C O N TI N U A TI O N  
T he I n vesti gat or m ust ma ke e v er y r eas o na ble eff ort t o kee p eac h patie nt o n st u d y f or t he 
d urati o n of t he st u d y, i ncl u di n g t hr o u g h t he safet y f oll o w- u p, l ost t o f oll o w- u p, c o nse nt 
wi t h dra wal, or e n d of st u d y, w hic he ver occ urs first (see Secti o n 8. 2  f or a d diti o nal details). 
8. 1.  
St u d y a n d I n di vi d u al P atie nt St o p pi n g R ules  
8. 1. 1.  
St u d y St o p pi n g R ules  
If a n y of t he f oll o wi n g e ve nts occ ur, a d mi nistrati o n of K Z R - 6 1 6 will be te m p oraril y 
disc o nti n ue d u ntil a t h or o u g h re vie w of t h e acc u m ulate d safet y dat a is u n derta ke n b y t he Data 
M o nit ori n g C o m mittee  (D M C ) ( or a p pr o priate alter nati ve): 
•  Deat h i n a n y patie nt , u nl ess t he ca use of deat h is d ue t o o b vi o us alter nati v e eti ol o g y 
•  U ne x pect e d life -t hr eate ni n g e ve nt i n a n y patie nt , u nless d ue t o o b vi o us alter nati ve 
eti ol o g y 
•  T hree or m ore of t he s a m e Gra d e 3 or hi g her A E (j u d ge d b y t he I n vesti gat or, Me dical 
M o nit or, or S p o ns or’s re prese ntati ve), o cc urri n g i n 2 0 % or m ore i n di vi d uals, u nless d ue 
t o o b vi o us alter nati ve eti ol o g y 
•  A n y e ve nt of t hr o m b otic micr oa n gi o pat h y, t hr o m b oc yt o pe nic p ur p ura, or h e m ol ytic 
ure mic s y n dr o me  
•  A n y e ve nt t hat, i n t he o pi ni o n of t he Me dical M o nit or, D M C ( or a p pr o pri ate alter nati ve), 
or S p o ns or, c o ntrai n dicat es f urt her d osi n g of a d diti o nal patie nts 
 
8. 1. 2.  
I n di vi d u al P atie nt St o p pi n g R ules 
If a n y of t he f oll o wi n g e ve nts occ ur, a d mi nistrati o n of K Z R - 6 1 6 t o a n i n di vi d ual patie nt s h o ul d 
be disc o nti n ue d u ntil a re vie w of t he acc u m ulate d safet y data is u n derta ke n b y t he D M C ( or 
a p pr o priate alter nati ve ): 
•  A n y e ve nt t hat f ulfills criteria f or a st u d y st o p pi n g r ule, u nless d ue t o a n o b vi o us 
alter nati ve eti ol o g y  (see Secti o n 8. 1. 1 ) 
•  A n y e ve nt t hat, i n t he o pi ni o n of t he I n vesti gat or, Me dical M o nit or, D M C ( or a p pr o priat e 
alter nati ve), or S p o ns or, c o ntrai n dicates f urt her  d osi n g 
 
After s uc h a re vi e w, res u m pti o n of d osi n g ma y be c o nsi dere d at t he sa me or l o wer d ose 
i ncl u di n g c o nsi derati o n f or a n y pr o p h ylactic i nter ve nti o ns (e g, as per Secti o n 6. 1. 2 ) 
8. 2.  
E arl y Wit h dr a w al of P atie nts fr o m t he St u d y  
Patie nts m ust be wit h dra w n fr o m t he st u d y f or a n y of t he f oll o wi n g reas o ns: 

Pr ot oc ol  A me n d me nt 1  
K Z R -6 1 6 -0 0 3 E  
Kezar Life Scie nces, I nc.  
1 3 Se pte m ber 2 0 2 1  
 
C o nfi de ntial  
Pa ge 4 6  of 6 6  
 
•  Patie nt re q uest/ i nf or me d c o nse nt wit h dra w n d u e t o a n A E 
•  Patie nt re q uest/i nf or me d c o nse nt wit h dra w n f or a n y reas o n ot her t ha n a n A E 
•  Patie nt bec o mes pre g n a nt  
•  A E ( w het her or n ot r elate d t o K Z R- 6 1 6) t hat precl u des f urt her p artici pati o n i n t he st u d y, 
i n t he j u d g me nt of t he I n vesti gat or a n d/ or S p o ns or 
•  A n y e ve nt of t hr o m b otic micr oa n gi o pat h y, t hr o m b oc yt o pe nic p ur p ura, or h e m ol ytic 
ure mic s y n dr o me 
 
Patie nts ma y  be wit h dra w n fr o m t he st u d y f or a n y of t he f oll o wi n g reas o ns: 
•  Pr ot oc ol n o n- c o m plia nce , i n t he j u d g me nt of t he I n vesti gat or a n d/ or S p o ns or 
•  L ost t o f oll o w- u p 
•  T he I n vesti gat or or S p o ns or c o nsi ders t hat it is i n t he patie nt ’s best i nterest n ot t o 
c o nti n ue partici pati o n i n t he st u d y 
•  A d mi nistrati ve decisi o n b y t he I n vesti gat or or S p o ns or 
 
Patie nts are fr ee t o wit h dra w fr o m t he st u d y at a n y ti me wit h o ut pr o vi di n g reas o n(s) f or 
wit h dra wal a n d wit h o ut prej u dice t o f urt h er treat me nt. T he reas o n(s) f or wit h dra wal will be 
d oc u me nte d i n t he e C R F. If a patie nt wit h dra ws c o nse nt, all sa m ples o btai ne d will be retai ne d 
f or a nal ysis u nless t he patie nt c o nfir ms t hat he or s he wis hes t he sa m ples t o be discar d e d.  
Patie nts wit h dra wi n g fr o m st u d y treat me nt will be e nc o ura g e d t o c o m plete t he E T V wit hi n 
1 4 da ys a n d ret ur n f or a n E O S  Visit a p pr o xi matel y 1 2 wee ks after recei pt of t heir last d ose  of 
K Z R - 6 1 6 t o c o m plete t he fi nal e val u ati o ns acc or di n g t o t his pr ot oc ol, partic ularl y safet y 
e val uati o ns. T he ai m is t o rec or d d ata i n t he sa me wa y as f or patie nts w h o c o m plete t he st u d y. 
8. 3.  
L ost t o F oll o w -U p  
T he I n vesti gat or m ust ma ke reas o na ble eff orts t o c o ntact patie nts w h o fail t o ret ur n f or s c he d ule d 
visits s o t hat t he y will n ot be declar e d “l ost t o f oll o w - u p.” Patie nts will be c o nsi dere d “l ost t o 
f oll o w- u p” o nl y after reas o na ble, d oc u me nte d atte m pts t o reac h t he patie nt pr o ve u ns uccessf ul. 
T hese atte m pts i ncl u de,  b ut are n ot li mite d t o, t he f oll o wi n g:  
1.  Atte m pt c o ntact  at all tel e p h o ne n u m bers f or t he p atie nt a n d his/ her liste d c o ntacts (t o be 
c ollecte d i n t he s o ur ce  d o c u me nts at t he patie nt’s e ntr y i nt o t he st u d y), as a p plica ble. 
2.  C o ntact t he patie nt’s pri mar y care p h ysicia n, referri n g s pecialist, or ot her healt hcare 
pr ofessi o nal, as a p plica bl e. 
3.  Se n d e mails a n d  te xts, a n d certifie d letters t hr o u g h t he  p ostal ser vice t o all t he patie nt’s 
a d dresses a n d c o ntacts, as a p plica ble.  

Pr ot oc ol  A me n d me nt 1  
K Z R -6 1 6 -0 0 3 E  
Kezar Life Scie nces, I nc.  
1 3 Se pte m ber 2 0 2 1  
 
C o nfi de ntial  
Pa ge 4 7  of 6 6  
 
4.  Re vie w a vaila ble m e dical rec or ds/ n otes f or  details of h os pitalizati o ns, cli nic visits, or 
ot her pr oce d ures t hat ma y i n dicate t he stat us of t h e patie nt, as a p plica ble. 
5.  Perf or m a n i nter n et searc h f or a d diti o nal c o ntact i nf or mati o n, as a p plica bl e. 
6.  C hec k l ocal, r e gi o nal, a n d nati o nal p u blic rec or ds t o l ocate t he patie nt or searc h f or 
m ortalit y stat us as all o we d b y la w, as a p plica bl e.  
 
T he i nf or mati o n a n d dat es of atte m pte d c o ntact m ust be rec or d e d i n t he patie nt’s rec or ds a n d t he 
patie nt’s fi nal stat us rec or de d i n t he a p pr o priate e C R F. O nce all atte m pts t o c o ntact t he patie nt 
ha ve bee n e x ha uste d a n d d oc u me nte d, t he S p o ns or or S p o ns or’s desi g nee s h o ul d be c o ntacte d 
f or a d diti o nal g ui da nce. 
8. 4.  
E arl y Ter mi n ati o n  Visit  
If p ossi ble, the E T V  s h o ul d ta ke place wit hi n 1 4 da ys after wit h dra w al. Pr oce d ures liste d o n t he 
Sc he d ule of Assess me nts ( Ta ble  1) s h o ul d be p erf or me d at t he E T V . 
8. 5.  
Ter mi n ati o n or S us pe nsi o n of t he St u d y  
T he S p o ns or has t he ri g ht t o ter mi nate t he st u d y at a n y ti me i n case of S A Es or circ u msta nces 
c o ncer ni n g K Z R - 6 1 6 or t he c o m pa n y, t hat ma k es f urt her treat me nt of patie nts i m p ossi ble. I n t his 
e ve nt, I n vesti gat ors will be i nf or me d of t he reas o n f or st u d y ter mi nati o n. 

Pr ot oc ol  A me n d me nt 1  
K Z R -6 1 6 -0 0 3 E  
Kezar Life Scie nces, I nc.  
1 3 Se pte m ber 2 0 2 1  
 
C o nfi de ntial  
Pa ge 4 8  of 6 6  
 
9.  
A D V E R S E E V E N T S  
9. 1.  
A d verse E ve nt Re p orti n g  
9. 1. 1.  
Defi niti o n of a n A d verse E ve nt  
A n A E is defi ne d as a n y u nt o war d me dical o cc urre nce i n a cli nical st u d y patie nt a d mi nistere d a 
me dici nal pr o d uct, w hic h d oes n ot necess aril y ha v e a ca usal rel ati o ns hi p wit h t hi s treat me nt. A n 
A E ca n t heref ore be a n y u nfa v ora bl e a n d u ni nte n d e d si g n (i ncl u di n g a n a b n or mal la b orat or y 
fi n di n g), s y m pt o m, or disease te m p or all y ass ociate d wit h t he use of a me dici nal (i n vesti gati o nal) 
pr o d uct, w het her or n ot it is relate d t o t he me dici n al (i n vesti gati o nal) pr o d u ct. T his i ncl u des a n 
e xacer bati o n of pr e- e xisti n g c o n diti o ns or e ve nts, i nterc urre nt ill nesses, dr u g i nteracti o n or t he 
si g nifica nt w orse ni n g of t he i n dicati o n u n der i n vesti gati o n t hat is n ot rec or de d else w here i n t he 
e C R F u n der s pecific effi cac y assess me nts. A ntici pate d fl uct uati o ns of pre -e xisti n g c o n diti o ns, 
i ncl u di n g t he disease u n d er st u d y, t hat d o n ot re prese nt a cli nicall y si g nifica nt e xacer bati o n or 
w orse ni n g nee d n ot b e c o nsi dere d. 
It is t he r es p o nsi bilit y of t he I n v esti gat or t o d oc u me nt all A Es t hat occ ur d uri n g t he st u d y. A Es 
will be elicite d b y as ki n g t he patie nt a n o nlea di n g q uesti o n s uc h as, “ H a ve y o u e x perie n ce d a n y 
ne w or c h a n ge d s y m pt o ms si nce we last as ke d/si nce y o ur last visit?” A d v erse e v e nts s h o ul d be 
re p orte d o n t he a p pr o pri ate pa ge of t he e C R F. 
9. 1. 2.  
Assess m e nt of Se verit y  
Se verit y  of A Es  will  be gra de d  acc or di n g  t o t he N CI -C T C A E  ( Versi o n 4. 0 3). If t here is a c h a n ge 
i n se verit y of a n A E, it m ust be rec or d e d as a se parate  e ve nt.  
9. 1. 3.  
Assess m e nt of C a us alit y  
A d vers e e ve nts will be d ee me d r elate d t o K Z R - 6 1 6 u nless clearl y u nrelate d t o K Z R - 6 1 6. 
T he I n vesti gat or will ass ess t he ca usal relati o ns hi p bet wee n K Z R - 6 1 6 a n d t he A E. O ne of t h e 
cate g ories  i n T a ble  3 s h o ul d be selecte d b ase d o n me dical j u d g me nt, c o nsi deri n g t he defi niti o ns 
a n d all c o ntri b uti n g fact ors. 

Pr ot oc ol  A me n d me nt 1  
K Z R -6 1 6 -0 0 3 E  
Kezar Life Scie nces, I nc.  
1 3 Se pte m ber 2 0 2 1  
 
C o nfi de ntial  
Pa ge 4 9  of 6 6  
 
T a ble 3  
C a us alit y C ate g ories 
Relate d  
A cli nical e ve nt, i ncl u di n g la b orat or y test a b n or malit y, t hat occ urs i n a 
pla usi ble ti me relati o ns hi p t o treat me nt a d mi nistrati o n, a n d t hat c o nc urre nt 
disease or ot her dr u gs or c he micals ca n n ot e x plai n. T he res p o nse t o 
wit h dra wal of t h e tr eat m e nt ( dec h alle n ge a) s h o ul d be cli nicall y pla usi ble. T he 
e ve nt m ust be defi niti ve p har mac ol o gicall y or p he n o me n ol o gicall y, usi n g a 
satisfact or y r ec halle n g e b pr oce d ure, if necessar y. 
U nrelate d  
A cli nical e ve nt, i ncl u di n g la b orat or y test a b n or malit y, wit h little or n o 
te m p oral relati o ns hi p t o treat me nt a d mi nistrati o n. Ma y ha ve ne g ati ve 
dec halle n g e a a n d rec halle n geb i nf or mati o n. T y picall y e x plai ne d b y e xtra n e o us 
fact ors ( e g, c o n c o mita nt disease, e n vir o n me nt al fact ors, or ot her dr u gs or 
c he micals).  
A b bre viati o ns: A E =a d verse e ve nt  
a 
Dec halle n ge:  U p o n disc o nti n uati o n of a dr u g s us pecte d of ca usi n g a n A E, t he s y m pt o ms of t he A E disa p pear 
partiall y or c o m pletel y, wit hi n a reas o na ble ti me fr o m dr u g disc o nti n uati o n, ( p ositi ve dec halle n ge), or t he 
s y m pt o ms c o nti n ue des pite wit h dra wal of t he dr u g ( ne gati ve dec halle n ge). N ote t hat t here are e xce pti o ns 
w he n a n A E d oes n ot disa p pear u p o n disc o nti n uati o n of t he dr u g, yet dr u g -relate d ness clearl y e xists (e g, b o ne 
marr o w s u p pressi o n, fi xe d dr u g er u pti o ns, or tar di ve d ys ki nesia).  
b 
Rec halle n ge:  U p o n re -a d mi nistrati o n of a dr u g s us pecte d of ca usi n g a n A E i n a s pecific patie nt i n t he past, t he 
A E rec urs u p o n e x p os ure ( p ositi ve rec halle n ge), or t he A E d oes n ot rec ur ( ne gati ve rec halle n ge).  
 
9. 1. 4.  
A cti o n T a ke n  wit h R e g ar d t o K Z R - 6 1 6 
T he I n vesti gat or will des cri be t he acti o n ta ke n wit h K Z R - 6 1 6 i n t he a p pr o priate secti o n of t he 
e C R F, as f oll o ws: 
•  N o ne 
•  K Z R - 6 1 6 st o p pe d 
•  K Z R - 6 1 6 te m p oraril y i nterr u pte d 
•  K Z R - 6 1 6 d ose re d u ce d ( wit h writte n c o nfir mati o n fr o m Me dical M o nit or) 
•  Ot her (s pecif y)  
 
9. 1. 5.  
F oll o w- u p of A d verse E ve nts  
A d verse e ve nts ar e i nte n de d t o be c ollecte d acc or di n g t o t he pr oce d ures o utli ne d a b o ve fr o m t he 
ti me of i nf or me d c o nse nt a n d c o nti n ui n g f or 3 0 da ys f oll o wi n g t he last d ose, or t he E O S  Visit, 
w hic he ver o cc urs later.  
All I n vesti gat ors s h o ul d f oll o w u p patie nt A Es u ntil t he e ve nt is res ol ve d or u ntil, i n t he o pi ni o n 
of t he I n vesti gat or, t he e ve nt is sta bilize d or deter mi ne d t o be c hr o nic. D etails of A E res ol uti o n 
m ust be d oc u me nte d i n t he e C R F.  

Pr ot oc ol  A me n d me nt 1  
K Z R -6 1 6 -0 0 3 E  
Kezar Life Scie nces, I nc.  
1 3 Se pte m ber 2 0 2 1  
 
C o nfi de ntial  
Pa ge 5 0  of 6 6  
 
9. 1. 6.  
D oc u m e nt ati o n a n d Re p orti n g of A d verse  E ve nts  
A d verse e ve nts  (i ncl u di n g S A Es) s h o ul d be re p ort e d a n d d oc u me nt e d i n acc or da nce wit h t he 
pr oce d ur es o utli ne d bel o w. All A Es occ urri n g d uri n g t he st u d y m ust be d oc u me nte d o n t he 
rele va nt e C R F p a ges. T h e f oll o wi n g data s h o ul d b e d oc u me nte d f or eac h A E. 
•  Dia g n osis, or descri pti o n of t he s y m pt o ms if a dia g n osis is n ot esta blis he d 
•  Classificati o n of ‘seri o us’ or ‘ n ot seri o us’ 
•  Se verit y  
•  Date of first o cc urre nce a n d date of res ol uti o n (if a p plica ble) 
•  Acti o n ta ke n wit h re g ar d t o K Z R - 6 1 6 
•  O utc o me of t he e v e nt ( u n k n o w n, rec o v ere d, n ot y et rec o vere d, rec o vere d wit h se q uelae, 
deat h [ wit h date a n d ca us e  re p orte d]) 
 
9. 2.  
Seri o us A d verse E ve nts  
9. 2. 1.  
Defi niti o n of a Seri o us A d verse E ve nt  
A n S A E is a n y u nt o war d me dical occ urre n ce or affect t hat, at a n y d os e:  
•  Res ults i n deat h  
•  Is life-t hreate ni n g ( An A E is life -t hreate ni n g if t h e patie nt was at i m me diat e ris k of deat h 
fr o m t he e ve nt as it occ urre d, ie, it d oes n ot i ncl u d e a reacti o n t hat mi g ht ha ve ca use d 
deat h if it ha d occ u rre d i n a m ore seri o us f or m.) 
•  Re q uires or pr ol o n gs i n p atie nt h os pitalizati o n. ( C o m plicati o ns occ urri n g d uri n g 
h os pitalizati o n are A Es a n d are c o nsi d ere d S A Es if t he y ca us e pr ol o n gati o n of t he c urre nt 
h os pitalizati o n. H os pitalizati o n f or el ecti ve treat me nt of a pre -e xisti n g n o n- w orse ni n g 
c o n diti o n is n ot, h o we ver, c o nsi dere d a n A E. T he details of s uc h h os pitalizati o ns m ust be 
rec or d e d o n t he me dical hist or y or p h ysical e xa mi nati o n pa ge of t he e C R F.) 
•  Res ults i n persiste nt or si g nifica nt disa bilit y/i nca pacit y. ( A n A E is i nca p acitati n g or 
disa bli n g if it res ults i n a s u bsta ntial a n d/ or per ma ne nt disr u pti o n of t he patie nt’s a bilit y 
t o carr y o ut n or mal lif e f u ncti o ns.) 
•  Res ults i n a c o n ge nital a n o mal y/ birt h defect. 
 
I n a d diti o n, me dical a n d scie ntific j u d ge me nt is re q uire d t o deci de if pr o m pt n otificati o n is 
re q uire d i n sit uati o ns ot her t ha n t h ose defi ne d f or S A Es a b o ve. T his ma y i ncl u de a n y e v e nt t hat 
t he I n v esti gat or r e gar ds as seri o us t hat di d n ot strictl y meet t he criteri a a b o ve b ut ma y ha ve 
je o par dize d t h e patie nt or re q uire d i nter v e nti o n t o pre ve nt o ne of t he o utc o mes liste d a b o ve, or 

Pr ot oc ol  A me n d me nt 1  
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t hat w o ul d s u g gest a n y si g nifica nt hazar d, c o ntrai n dicati o n, si de effect, or preca uti o n t hat ma y b e 
ass ociate d wit h t he use of K Z R - 6 1 6. 
9. 2. 2.  
Seri o us A d ver se E ve nt Re p orti n g a n d D oc u me nt ati o n Re q uire me nts  
A n S A E m ust be re p orte d (see Secti o n 9. 1. 6 ) b y t he I n vesti gat or if it occ urs fr o m t he ti me of 
si g ne d c o nse nt t hr o u g h 3 0 da ys after t h e last d ose of K Z R - 6 1 6, w het her or n ot t he S A E is 
c o nsi dere d t o be relate d t o K Z R - 6 1 6. After t h e re p orti n g peri o d, S A Es s h o ul d be re p orte d if t h e 
I n v esti gat or assess es t he e ve nt t o be rel ate d t o K Z R - 6 1 6. A n S A E re p ort c o nsists of t he S A E 
f or m, pr o vi de d se p aratel y, al o n g wit h re q ueste d a d diti o nal s o urce d oc u me ntati o n as c o nsi dere d 
necessar y.  
Seri o us a d verse e ve nts  t h at occ ur d uri n g t he re p orti n g peri o d m ust be re p ort e d b y t he 
I n v esti gat or via e ntr y of data i nt o t he e C R F wit hi n 2 4 h o urs fr o m t he ti me t he I n v esti gat or 
bec o mes a w ar e of t he S A E. T his e ntr y will tri g ger a n e mail n otificati o n t o t he Seri o us A d vers e 
E ve nt Re p orti n g e- mail a d dress (see St u d y Pers o n nel  pa ge) t hat a n S A E has occ urre d. If t he 
electr o nic d ata ca pt ure  (E D C ) s yste m is d o w n or u na vaila ble, a c o p y of t h e S A E f or m s h o ul d be 
c o m plete d a n d e m aile d or fa xe d b y t h e I n vesti gat or t o t he Seri o us A d vers e E ve nt Re p orti n g 
e-mail a d dr ess or de dicate d fa x (s ee St u d y Pers o n nel  pa ge) wit hi n 2 4 h o urs fr o m t he ti me t he 
I n v esti gat or bec o m es a w are of t h e S A E. O nce t he E D C s yste m is a vaila ble, t he S A E s h o ul d be 
e ntere d i n t he e C R F. T he I n v esti gat or s h o ul d n ot wait f or a d diti o nal i nf or ma ti o n t o f ull y 
d oc u me nt t he S A E bef or e re p orti n g it, t h o u g h a d diti o nal i nf or mati o n ma y be re q uest e d. 
Re q ueste d s o urce d oc u m e ntati o n (ie, rele v a nt la b orat or y res ults, h os pital case rec or ds, or a ut o ps y 
re p orts) t hat is c o nsi der e d necessar y s h o ul d be pr o vi de d se paratel y t o t he Seri o us A d verse E v e nt 
Re p orti n g e- mail a d dr ess (see St u d y Pers o n nel  pa ge) usi n g a c o v er s heet. 
I nsta n ces of d eat h, c o n g e nital a b n or malit y, or a n e ve nt of s uc h cli nical c o ncer n as t o i nfl ue nce 
t he o verall assess me nt of safet y, if br o u g ht t o t he atte nti o n of t he I n vesti gat or at a n y ti me after 
cessati o n of K Z R - 6 1 6 a d mi nistrati o n a n d li n ke d b y t he I n v esti gat or t o t his st u d y, s h o ul d be 
re p orte d t o t he St u d y M o nit or. 
T he S p o ns or a n d/ or desi g nee will pr o m ptl y n otif y all rele va nt I n v esti gat ors a n d t he re g ulat or y 
a ut h orities of fi n di n gs t hat c o ul d a d vers el y affect t he safet y of p atie nts, i m pact t he c o n d u ct of t he 
st u d y, or alter t he D M C (or a p pr o priat e alter n ati ve )/I nstit uti o nal Re vie w B o ar d 
(I R B)/I n d e pe n d e nt Et hics C o m mittee (I E C) a p pr o val/fa v ora bl e o pi ni o n of t he st u d y. I n a d diti o n, 
t he S p o ns or or desi g nee will e x pe dite t he re p orti n g of all a d vers e reacti o ns t hat are b ot h seri o us 
a n d u ne x pecte d t o all c o n cer ne d I n vesti gat ors, t o t he D M C ( or a p pr o priate 
alter nati ve)/I R Bs/I E Cs w here r e q uire d, a n d t o rele va nt re g ulat or y a ut h orities. 
F or S A Es t hat ha v e bee n re p orte d i n t he K Z R- 6 1 6 de vel o p me nt pr o gra m, please refer t o t he m ost 
c urre nt K Z R - 6 1 6 I n vesti gat or’s Br oc h ure. 
9. 3.  
Pre g n a nc y Re p orti n g  
Pre g na nc y occ urri n g i n f e male patie nts or fe male part ners of m ale patie nts partici pati n g i n t he 
st u d y or d uri n g a cli nical i n vesti gati o n m ust be re p orte d t o t he 
(s ee 
St u d y Pers o n nel  pa ge) wit hi n 2 4 h o urs a n d e ntere d i nt o t he E D C. T he o utc o me of a pre g na nc y 
s h o ul d be f oll o we d u p caref ull y, a n d a n y a b n or mal o utc o me f or t he m ot her or t he c hil d s h o ul d be 

Pr ot oc ol  A me n d me nt 1  
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re p orte d. I nfa nts s h o ul d be f oll o we d f or a mi ni m u m of 8 wee ks, a n d all fi n di n gs s h o ul d be 
re p orte d t o t he S p o ns or. KZ R - 6 1 6 is t o be disc o nti n ue d i m me diatel y u p o n I n v esti gat or 
k n o wle d ge of t he pre g na nc y a n d re p orte d as p er S ecti o n 8. 2 . 
If t he o utc o me of t h e pre g na nc y meets a criteri o n f or i m me diate classificati o n as a n S A E (ie, 
s p o nta ne o us a b orti o n [f or w hic h a n y c o n ge nital a n o mal y detecte d i n a n a b orte d fet us is t o be 
d oc u me nte d], still birt h, ne o natal deat h, or c o n ge nital a n o mal y), t he I n v esti gat or s h o ul d f oll o w 
t he pr oce d ures f or e x pe dite d re p orti n g of S A Es as o utli ne d i n Secti o n 9. 2. 2 . 
F ull details will be rec or de d o n t he wit h dra w al pa ge of t he e C R F, or a n S A E re p ort will be 
c o m plete d if t he patie nt h as c o m plete d t he st u d y. 
9. 4.  
Ne w or W or se ni n g Dise ase M a nifest ati o ns  
Ne w or w orse ni n g ma nif estati o n(s) of P M or D M s h o ul d n ot be rec or d e d as A Es u nless t he y are 
assesse d as seri o us.  
9. 5.  
I njecti o n Site Re acti o ns 
I n st u d y partici pa nts  w h o ha ve recei ve d K Z R - 6 1 6 S C, I S Rs, i ncl u di n g br uisi n g, disc ol orati o n, 
disc o mf ort, er yt he ma, i n d urati o n, pai n, pr urit us a n d/ or s welli n g, ha ve bee n descri be d i n t he 
maj orit y of partici pa nts  i n K Z R- 6 1 6 st u dies t o date; t hese e ve nts h a ve bee n pred o mi na ntl y mil d . 
N o i nter ve nti o ns ha ve b ee n f or mall y st u die d t o pre ve nt or treat t hese reacti o ns; h o we ver, l ocal 
t hera p y s uc h as t o pical a nti hista mi nes or c ortic oster oi ds ma y be hel pf ul, a n d/ or s yste mic 
a nti hista mi nes, a nti -i nfla m mat or y dr u gs, a n d/ or c ortic oster oi ds ma y be a p pr o priate i n m ore 
se vere cases. 
9. 5. 1.  
A d verse E ve nts of S peci al I nterest  
A n A E of s pecial i nterest ( A E SI ) is o ne t hat is of s cie ntific a n d me dical c o n cer n s pecific t o t he 
S p o ns or's pr o d uct or pr o gra m, f or w hi c h o n g oi n g m o nit ori n g a n d ra pi d c o m m u nicati o n b y t he 
I n v esti gat or t o t he S p o ns or ca n be a p pr o pri ate, re gar dless of t he s eri o us ness, e x pecte d n ess, or 
relate d ness of t he A E t o t he a d mi nistrati o n of a pr o d uct or c o m p o u n d. A c o m ple x of t olera bilit y 
s y m pt o ms (f or merl y ref erre d t o as s yste mic i njecti o n reacti o n; see Secti o n 9. 5. 1. 1 ) a n d 
t hr o m b otic micr oa n gi o pat h y ha ve bee n i d e ntifie d as A E SI s, a n d s h o ul d be re p orte d wit hi n 
2 4 h o urs usi n g t he A E e C R F.  
9. 5. 1. 1.  
T oler a bilit y S y m pt o m C o m ple x  
I nitial S C d oses of 6 0 m g K Z R-6 1 6 are ass ociate d wit h a c o m ple x of t olera bilit y s y m pt o ms , wit h 
at least o ne of t he f oll o wi n g si g ns or s y m pt o ms: h y p ote nsi o n, tac h ycar dia, na usea, v o miti n g, 
dizzi ness, hea d ac h e, p yre xia, ri g ors, a n d/ or c hills. T hese s y m pt o ms t y picall y be gi n wit hi n 8 t o 
2 4 h o urs after d osi n g, a n d us uall y res ol ve wit hi n 4 8 h o urs of d osi n g. T he s e si g ns a n d s y m pt o ms 
ca n occ ur wit h a n y d ose, t h o u g h t he y are m ore li kel y t o occ ur wit h i nitial d oses of 6 0 m g or 
hi g her. W he n s ee n, t he y t e n d t o be m ore c o m m o n wit h t he first d ose t ha n wit h s u bse q ue nt d oses.  
T he c o m ple x of t oler a bilit y s y m pt o ms  see n wit h i nitial hi g h d oses of K Z R- 6 1 6 are si milar t o 
t h ose see n wit h i nf usi o n reacti o ns r e p orte d f or carfilz o mi b (K Y P R O LI S 2 0 1 8 ), as well as wit h 
s yste mic i nfla m mat or y res p o nse s y n dr o me, a cli ni cal s y n dr o me t hat is a s u bset of c yt o ki ne 

Pr ot oc ol  A me n d me nt 1  
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releas e s y n dr o me ma nif este d b y at least 2 of t he f oll o wi n g fi n di n gs: tac h ycar dia ( > 9 0 beats per 
mi n ute), le u k oc yt osis ( > 1 2 × 1 0 9/ L or < 4 × 1 09/ L, or > 1 0 % i m mat ure [ ba n d] f or ms), tac h y p nea 
(res pirat or y rate of m ore t ha n 2 0 breat hs per mi n ute or art erial car b o n di o xi de te nsi o n [ Pa C O 2] 
of less t ha n 3 2 m m H g), a n d fe ver (te m perat ure of m ore t ha n 3 8° C [ 1 0 0. 4° F] or less t ha n 3 6° C 
[ 9 6. 8° F]) (B o ne 1 9 9 2 ). T he relati ve r oles of t he i m m u n o pr oteas o me vers us c o nstit uti ve 
pr oteas o mes t o t hese s pecific e ve nts are n ot k n o w n.  
I n re p orti n g T E A Es relat e d t o K Z R-6 1 6 t olera bilit y , ter ms s uc h as t he N CI-C T C A E ter ms of 
‘i nf usi o n-relate d reacti o n,’ ‘c yt o ki ne r eleas e s y n dro me,’ ‘ac ute i nf usi o n reacti o n,’ or ‘aller gic or 
h y perse nsiti vit y reacti o n’ s h o ul d n ot be use d. I nstea d, eac h si g n or s y m pt o m s h o ul d be rec or d e d 
as a n i n di vi d ual T E A E. If m ulti ple si g ns or s y m pt o ms occ ur wit h a gi ve n s yste mic 
i njecti o n-relate d e ve nt, eac h si g n or s y m pt o m s h o ul d be rec or de d se p arat el y wit h its o w n le vel of 
se verit y. 
Ma na ge me nt of t h ese s y m pt o ms is descri be d i n Secti o n 6. 1. 2 . 
9. 5. 1. 2.  
T hr o m b otic Micr o a n gi o p at h y 
Cases of t hr o m b otic micr oa n gi o pat h y, i ncl u di n g t hr o m b oc yt o pe nic p ur p ura a n d he m ol ytic 
ure mic s y n dr o me, ha v e b ee n descri be d wit h t he n o ns pecific pr oteas o me i n hi bit ors, b ortez o mi b, 
carfilz o mi b, a n d i x az o mi b. T he cli nical pres e ntati o n of t hr o m b otic micr oa n gi o pat h y t y picall y 
i ncl u des fe ver, micr oa n gi o pat hic he m ol ytic a ne mi a ( wit h sc hist oc ytes o n bl o o d s mear), 
t hr o m b oc yt o pe nia, re n al fail ure, p ur p ura, a n d n e ur ol o gical ma nifestati o ns. Patie nts s h o ul d be 
m o nit ore d f or si g ns a n d s y m pt o ms of t hr o m b oc yt o pe nic p ur p ura/ he m ol ytic ure mic s y n dr o me . If 
t he dia g n osis is s us pecte d, i nterr u pt treat me nt wit h K Z R - 6 1 6 a n d e v al uate (refer t o 
Secti o n  8. 1. 2 ). Misse d d oses s h o ul d be a d dress e d as per Secti o n 6. 1. 3. 2 . If t he dia g n osis of 
t hr o m b oc yt o pe nic p ur p ur a/ he m ol ytic ure mic s y n dr o me is e xcl u de d, K Z R - 6 1 6 ma y be res u me d. 
If t he dia g n osis is c o nfir me d, K Z R - 6 1 6 m ust be per ma ne ntl y disc o nti n ue d (refer t o Secti o n 8. 2 ). 
9. 6.  
U ne x pecte d A d verse Re acti o ns  
9. 6. 1.  
Defi niti o n of a n U ne x pecte d A d vers e Re a cti o n  
A n u ne x pect e d a d verse r eacti o n is a n y u nt o war d a n d u ni nte n de d res p o nse t hat is relate d t o t he 
a d mi nistrati o n of K Z R - 6 1 6 at a n y d ose t hat is n ot c o nsiste nt wit h t he a p plica ble pr o d uct 
i nf or mati o n (e g, t he Ref ere nce Safet y i nf or m ati o n of t he K Z R- 6 1 6 I n v esti gat or’s Br oc h ure ). 
All s us pecte d u ne x pecte d seri o us a d vers e reacti o ns ( S U S A Rs) will be s u bject t o e x pe dite d 
re p orti n g. T he S p o ns or or desi g nee s hall e ns ure t h at all rele va nt i nf or mati o n a b o ut a S U S A R t hat 
is fatal or life-t hr eate ni n g is re p orte d t o t he rele va nt c o m pete nt a ut h orities a n d I R B/I E C wit hi n 
7 da ys after k n o wle d ge b y t he S p o ns or of s uc h a case, a n d t hat rele va nt f oll o w- u p i nf or mati o n is 
c o m m u nicate d wit hi n a n a d diti o nal 8 da ys. All ot her S U S A Rs will be re p ort e d t o t he rele v a nt 
c o m pete nt a ut h orities  a n d I R B/I E C wit hi n 1 5 da ys after k n o wle d ge b y t he S p o ns or of s uc h a 
case. All I n v esti gat ors s h o ul d f oll o w u p S U S A Rs u ntil t he e ve nt is res ol ve d or u ntil, i n t he 
o pi ni o n of t he I n v esti gat or, t he e ve nt is sta bilize d or deter mi ne d t o be c hr o nic. P ost st u d y 
S U S A Rs t hat occ ur after t he patie nt has c o m plete d t he cli nical st u d y m ust be re p ort e d b y t he 
I n v esti gat or t o t he S p o ns or. 

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9. 7.  
D at a M o nit ori n g C o m mittee  
A st u d y- s pecific D M C or ot her a p pr o pri ate re vie w c o m mittee ma y be use d t o e n ha nce t h e safet y 
a n d i nte grit y of t he st u d y data f or i nteri m safet y m o nit ori n g. If s u c h a c o m mittee is use d, t he 
s pecific r es p o nsi bilities a n d c o m p ositi o n will be  o utli ne d i n a se parat e D M C C harter.  

Pr ot oc ol  A me n d me nt 1  
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1 0.  
S T A TI S TI C A L A N A L Y S E S   
T his st u d y is descri pti ve i n nat ure, a n d n o f or mal h y p ot hesis testi n g will be perf or me d. N o 
f or mal statistical sa m ple size esti mati o n has bee n perf or me d, si n ce t he n u m ber of patie nts i n t his 
st u d y is deter mi ne d b y t he n u m ber of p atie nts w h o c o m plete d St u d y K Z R - 6 1 6- 0 0 3 a n d e nr olle d 
i n t his st u d y. Descri pti ve statistics, i ncl u di n g t he n u m bers a n d perce nta g es f or cate g orical 
varia bles; a n d t he n u m b ers, mea ns, sta n dar d de viati o ns ( S D), me dia ns, mi ni m u ms a n d 
ma xi m u ms f or c o nti n u o us varia bles will be pr o vi d e d b y treat me nt gr o u p, b y i n dicati o n ( D M, 
P M),  a n d o verall. 
T he n u m ber a n d p erce nta ge of patie nts w h o e x p eri e nce T E A Es, S A Es/ deat h, A Es lea di n g t o 
treat me nt/st u d y disc o nti n uati o n, a n d treat me nt m o dificati o n/ dela y d ue t o A E(s) will be 
s u m marize d b y treat me nt gr o u p a n d o verall. T he n u m ber a n d perce nt a ge of patie nts e x perie n ci n g 
a n y T E A E(s), o v er all, a n d b y s yste m or ga n class ( S O C) a n d preferre d ter m a n d b y gra de will be 
ta b ulate d. 
C o nti n u o us meas ures i n la b orat or y, vital si g n, E C G, a n d efficac y data will be s u m mari ze d 
descri pti vel y ( mea n, m e dia n, S D, a n d mi ni m u m a n d ma xi m u m val ues) b y treat me nt gr o u p a n d 
o verall a n d will be s u m m arize d b y pr ot oc ol- s pecifie d ti me p oi nt al o n g wit h a s u m mar y of 
c ha n ge fr o m baseli ne at eac h ti me p oi nt. C ha n ges i n p h ysical e xa mi nati o ns wi ll be liste d f or eac h 
patie nt a n d descri be d. I n a d diti o n, 9 5 % c o nfi de nce i nter vals ma y be pr o vi de d t o descri be s o me 
c o nti n u o us efficac y data. 
Patie nt listi n gs will be pr o vi de d t o s u p p ort t hese s u m maries. 
P K a nal yses will i ncl u de deter mi nati o n of plas ma le v els of K Z R - 6 1 6 i ncl u di n g Cma x , Tma x , a n d 
A U C.  
F ull A nal ysis Set ( F A S) : T he F A S f or s u m maries of efficac y e n d p oi nts will i ncl u de all patie nts 
w h o recei ve K Z R - 6 1 6 i n t his st u d y a n d ha ve baseli ne a n d a n y p ost- bas eli ne data. All o bser ve d 
data will be i ncl u de d i n t he statistical s u m maries. No missi n g data will be i m p ute d  e xce pt as 
pre - defi ne d i n t he S A P.  
Per Pr ot oc ol ( P P) : A P P p o p ulati o n ma y be use d t o a nal yze s elect efficac y e n d p oi nts, a n d will be 
base d o n K Z R- 6 1 6 e x p os ure (ti me o n treat me nt) a n d pr ot oc ol de viati o ns. T he decisi o n t o 
s u m marize a P P p o p ulati o n will be ma de pri or t o data base l oc k.  
Safet y P o p ulati o n: T he safe t y p o p ulati o n will i ncl u de all patie nts e nr olle d w h o recei ve d at least 
o ne d ose of K Z R- 6 1 6, a n d will be t he p o p ulati o n use d f or t he a nal ysis of s afet y. A d verse e v e nt 
data will be c o de d t o s yst e m or ga n class a n d preferre d ter m usi n g Me dical Dicti o nar y f or 
R e g ulat or y Acti vities ( Me d D R A; Versi o n  1 9. 1 or later).  
Data will be s u m marize d f or t he f oll o wi n g gr o u ps of patie nts base d o n t he se q ue nce of 
treat me nts recei ve d i n St u d y K Z R- 6 1 6- 0 0 3: 
Gr o u p 1: 
Ar m A  ( K Z R- 6 1 6: Place b o) fr o m St u d y K Z R- 6 1 6- 0 0 3 be gi n ni n g o n Da y 1 (first d ose 
of K Z R - 6 1 6) t hr o u g h t he e n d of St u d y K Z R- 6 1 6- 0 0 3 E 
Gr o u p 2: 
Ar m B ( Place b o: K Z R - 6 1 6) fr o m St u d y K Z R- 6 1 6- 0 0 3 be gi n ni n g o n Wee k 1 6 (first 
d ose of K Z R- 6 1 6) t hr o u g h t he e n d of St u d y K Z R- 6 1 6- 0 0 3 E 

Pr ot oc ol  A me n d me nt 1  
K Z R -6 1 6 -0 0 3 E  
Kezar Life Scie nces, I nc.  
1 3 Se pte m ber 2 0 2 1  
 
C o nfi de ntial  
Pa ge 5 6  of 6 6  
 
Gr o u ps 1 a n d 2 c o m bi ne d: 
fr o m t he first d ose of K Z R- 6 1 6 i n K Z R- 6 1 6- 0 0 3 t hr o u g h t he e n d 
of K Z R - 6 1 6- 0 0 3 E 
Gr o u p 3: 
Ar m B 2: Patie nts recei vi n g K Z R - 6 1 6 fr o m Wee ks 1 6- 3 2 i n K Z R- 6 1 6-0 0 3 f oll o we d 
b y K Z R- 6 1 6 i n O L E t hr o u g h o ut K Z R- 6 1 6- 0 0 3 E, t o e val uate p atie nts w h o 
c o nti n u o usl y recei ve d K Z R- 6 1 6 fr o m K Z R- 6 1 6- 0 0 3 t hr o u g h K Z R- 6 1 6- 0 0 3 E 
Gr o u ps 1 a n d 2 are bei n g assesse d f or a n y differe n ces d ue t o t he i nter v e ni n g place b o treat me nt 
peri o d i n Gr o u p 1. T he rati o nale f or c o m bi ni n g Gr o u p 1 a n d Gr o u p 2 is t o e nc o m pass all 
K Z R - 6 1 6 treat me nt, a n d t he rati o nale f or assessi n g Gr o u p 3 is t o e nc o m pass all c o nti n u o us 
K Z R - 6 1 6 treat me nt. 
F urt her d etails of t he statistical met h o d ol o g y, i ncl u di n g met h o ds f or ha n dli n g missi n g data a n d 
earl y wit h dra wals , will be pr o vi de d i n a n S A P  t hat will be fi nalize d pri or t o data base l oc k. As 
K Z R - 6 1 6- 0 0 3 E is a n o pe n-la bel e xte nsi o n st u d y, e n d p oi nts i n a d diti o n t o t h ose descri be d i n 
Secti o n 2. 2  ma y be c o n d ucte d as des cri be d i n t he fi nal S A P. 

Pr ot oc ol  A me n d me nt 1  
K Z R -6 1 6 -0 0 3 E  
Kezar Life Scie nces, I nc.  
1 3 Se pte m ber 2 0 2 1  
 
C o nfi de ntial  
Pa ge 5 7  of 6 6  
 
1 1.  
E T HI C A L A N D A D MI NI S T R A TI V E C O N SI D E R A TI O N S  
1 1. 1.  
C o m pli a nce St ate me nt  
T he I n vesti gat or(s) a n d all parties i n v ol ve d i n t his st u d y s h o ul d c o n d uct t he st u d y i n a d here nce t o 
t he et hical pri nci ples bas e d o n t he Declarati o n of Helsi n ki, I C H g ui deli nes f or c urre nt G o o d 
Cli nical Practice ( G C P ), a n d t he a p plica ble nati o nal a n d l ocal la ws a n d re g ulat or y re q uire m e nts. 
Rele va nt st u d y d oc u me nt ati o n will be s u b mitte d t o t he re g ulat or y a ut h orities of t he partici pati n g 
c o u ntries, acc or di n g t o l ocal/re gi o nal/ nati o nal re q uire me nts, f or re vie w a n d a p pr o val bef ore t he 
be gi n ni n g of t he st u d y. O n c o m pleti o n of t he st u d y, t he re g ulat or y a ut h orities will be n otifie d 
t hat t he st ud y has e n de d. 
1 1. 2.  
I nstit uti o n al Re vie w B o ar d or I n de pe n de nt Et hics C o m mittee 
Pri or t o i nitiati o n of t he st u d y at eac h st u d y ce nter, t he pr ot oc ol, I C F, ot her writte n material 
gi ve n t o t he patie nts, a n d a n y ot her r ele va nt st u d y d oc u me ntati o n will be s u b mitte d t o t he 
a p pr o priate I R B/I E C. Writte n a p pr o val of t he st u d y a n d all rele v a nt st u d y i nf or mati o n m ust be 
o btai ne d bef or e t he st u d y ce nter ca n be i nitiate d, a n d bef ore K Z R - 6 1 6 ca n be release d t o t he 
I n v esti gat or. A n y necess ar y e xte nsi o ns or re ne wals of I R B/I E C a p pr o v al m ust be o btai ne d f or 
c ha n ges t o t he st u d y (ie, a me n d me nts t o t he pr ot o c ol, t he I C F, or ot her st u d y d oc u me ntati o n). 
T he writte n a p pr o v al of t he I R B/I E C, t o get her wit h t he a p pr o ve d I C F m ust be d oc u me nte d i n t he 
st u d y files. 
T he I n vesti gat or will pr o m ptl y re p ort a n y ne w i nf or mati o n t hat ma y a d vers el y affect t he safet y 
of t he patie nts or t he c o n d uct of t he st u d y t o t he I R B/I E C. T he I n vesti gat or will s u b mit writte n 
s u m maries of t he st u d y stat us t o t he I R B/I E C as re q uire d, a n d will i nf or m t he m w he n t he st u d y 
has e n de d. 
1 1. 3.  
I nf or me d C o nse nt a n d H u m a n P atie nt Pr otecti o n  
T he pr ocess of o btai ni n g i nf or me d c o nse nt m ust b e i n acc or da nce wit h a p plica ble re g ul at or y 
re q uire me nt(s) a n d m ust a d here t o c urre nt G C P. Patie nts will pr o vi de writte n i nf or me d c o ns e nt 
bef ore a n y st u d y-r elate d pr oce d ur es ar e perf or me d. T he I n vesti gat or is res p o nsi ble f or e ns uri n g 
t hat n o patie nt u n der g oes a n y st u d y-relate d e xa mi nati o n or acti vit y bef ore t hat patie nt has gi ve n 
writte n i nf or me d c o ns e nt t o partici pate i n t he st u d y. 
T he I n vesti gat or or d esi g nate d pers o n n el will i nf or m t he patie nt of t he o bjecti ves, met h o ds, 
a ntici pate d be nefits, a n d p ote ntial ris ks a n d i nc o n ve nie nces of t he st u d y. T he patie nt s h o ul d be 
gi ve n e ver y o p p ort u nit y t o as k f or clarificati o n of a n y p oi nts s/ he d oes n ot u n dersta n d a n d, if 
necessar y, as k f or m ore i nf or mati o n. At t he e n d of t he i nter vie w, t he patie nt will be gi ve n a m ple 
ti me t o c o nsi der t he st u d y. Patie nts will be re q uire d t o si g n a n d date t he I C F. After si g nat ures are 
o btai ne d, t he I C F will be ke pt a n d ar c hi ve d b y t he I n v esti gat or i n t he I n vesti gat or’s st u d y file. A 
si g ne d a n d date d c o p y of t he patie nt I C F will be pr o vi de d t o t he patie nt.  
It s h o ul d be e m p hasize d t hat t he patie nt ma y ref us e t o e nter t he st u d y or t o wit h dra w fr o m t he 
st u d y at a n y ti me, wit h o ut c o nse q ue nces f or t heir f urt her care or pe nalt y or l oss of be nefits t o 
w hic h t he patie nt is ot her wise e ntitle d. Patie nts w h o ref use t o gi ve or w h o wit h dra w writte n 
i nf or me d c o nse nt s h o ul d n ot be i ncl u de d or c o nti n ue i n t he st u d y. 

Pr ot oc ol  A me n d me nt 1  
K Z R -6 1 6 -0 0 3 E  
Kezar Life Scie nces, I nc.  
1 3 Se pte m ber 2 0 2 1  
 
C o nfi de ntial  
Pa ge 5 8  of 6 6  
 
If ne w i nfor mati o n bec o mes a vaila ble t hat ma y b e rele v a nt t o t he patie nt’s willi n g ness t o 
c o nti n ue partici pati o n i n t he st u d y, a ne w I C F will be a p pr o ve d b y t he I R B(s)/I E C(s) (a n d 
re g ulat or y a ut h orities, if re q uire d). T he st u d y pati e nts will be i nf or me d a b o ut t his ne w 
i nf or mati o n a n d c o nse nt will be re- o btai ne d. 
1 1. 4.  
D irect Access t o S o urce D at a, S o urce D oc u me nts, a n d St u d y Re p orts 
T he S p o ns or or its re pr ese ntati ves ma y peri o dicall y c hec k a sa m ple of p atie nt data rec or de d 
a gai nst s o urce d o c u me nts at t he st u d y site. T he st u d y ma y be a u dite d b y t h e S p o ns or, desi g nee, 
a n d/ or re g ulat or y a ge n cies at a n y ti me. I n vesti gat ors will be gi ve n n otice bef ore a n a u dit occ urs. 
T he I n vesti gat or will kee p rec or ds of all ori gi nal s o urce dat a. T his ma y i ncl u de la b orat or y t ests, 
me dical rec or ds, a n d cli nical n otes. If re q ueste d, t he I n vesti gat or will pr o vi de t he S p o ns or, 
a p plica ble r e g ulat or y a g e ncies, a n d a p plica ble re vie w b oar ds wit h direct access t o t he ori gi nal 
s o urce d oc u m e nts. 
1 1. 5.  
D at a  C ollecti o n a n d H a n dli n g  
A n E D C  s yste m will be use d i n t his st u d y. T he sit e m ust defi ne a n d retai n all s o urce rec or ds a n d 
m ust mai ntai n a rec or d of a n y data w h ere s o urce data are directl y e ntere d i nt o t he E D C s yste m. 
Data s yste ms use d f or t h e st u d y will ha ve c o ntr ols a n d re q uire m e nts i n acc or da nce wit h  l ocal 
data pr otecti o n  la w. T he p ur p ose a n d use of patie nt pers o nal i nf or mati o n c ollecte d will be 
pr o vi de d i n a writte n d oc u me nt t o t he patie nt b y t he S p o ns or or desi g nee.  
Re mai ni n g bi ol o gical sa m ple material will be st ore d off -site at Bi ost ora ge, a n d will be accessi ble 
t o o nl y t he S p o ns or f or u p t o 2 years aft er t he c o m pleti o n of t he st u d y, or u ntil t he sa m ple 
material is e ntirel y use d u p.  
1 1. 6.  
C o nfi de nti alit y  
M o nit ors, a u dit ors, ot her a ut h orize d a g e nts of t he S p o ns or a n d/ or its desi g nee, t he I R B(s)/I E C(s) 
a p pr o vi n g t his st u d y, t he U S F D A, a n d a n y ot her a p plica ble a ge n c y(ies) will be gra nte d direct 
access t o t he patie nts’ ori gi nal me dical rec or ds f or verificati o n of cli nical st u d y pr oce d ures 
a n d/ or data, wit h o ut vi olati n g t he c o nfi de ntialit y of t he patie nts, t o t he e xt e nt per mitte d b y t he 
la w a n d re g ul ati o ns. 
All pers o nal data c ollecte d a n d pr ocess e d f or t h e p ur p oses of t his st u d y s h o ul d be ma na ge d b y 
t he I n v esti gat or a n d his/ h er staff wit h a de q uat e preca uti o ns t o e ns ure c o nfi d e ntialit y of t h ose 
data, a n d i n acc or d a nce wit h t he Healt h I ns ura n ce P orta bilit y a n d Acc o u nta bilit y Act a n d 
nati o nal, re gi o nal a n d/ or l ocal la ws a n d re g ulati o ns o n pers o nal data pr otecti o n. 
1 1. 7.  
Fi n a nci n g a n d I ns ur a nce  
Fi na nci n g a n d i ns ur a nce of t his st u d y will be o utli ne d i n a se parate a gree me nt bet wee n t h e 
S p o ns or a n d desi g nee. 

Pr ot oc ol  A me n d me nt 1  
K Z R -6 1 6 -0 0 3 E  
Kezar Life Scie nces, I nc.  
1 3 Se pte m ber 2 0 2 1  
 
C o nfi de ntial  
Pa ge 5 9  of 6 6  
 
1 1. 8.  
A u dit a n d I ns pecti o n  
St u d y ce nters a n d st u d y d oc u me ntati o n ma y be s u bject t o Q ualit y Ass ura nce a u dit d uri n g t he 
st u d y b y t he S p o ns or or its n o mi nate d re pres e ntati ve. I n a d diti o n, i ns pecti o ns ma y be c o n d ucte d 
b y re g ulat or y a ut h orities at t heir discreti o n. 
1 1. 9.  
M o nit ori n g  
Data f or eac h patie nt will be rec or de d o n a n e C R F. Data c ollecti o n m ust be c o m plete d f or eac h 
patie nt w h o si g ns a n I C F. T he St u d y M o nit or will carr y o ut s o urce d o c u me nt verificati o n i n 
acc or d a nce wit h c urr e nt G C P a n d I C H g ui deli nes at re g ular i nter vals t o e ns ure t hat t he data 
c ollecte d i n t he e C R F are acc ur ate a n d relia ble.  
T he I n vesti gat or m ust per mit t he M o nit or, t he I R B/I E C, t he S p o ns or’s i nter nal a u dit ors, a n d 
re pres entati ves fr o m r e g ulat or y a ut h orities direct access t o all st u d y -rel ate d d oc u me nts a n d 
perti ne nt h os pital or me dical rec or ds f or c o nfir mati o n of data c o ntai ne d wit hi n t he e C R Fs. 
1 1. 1 0.  
D at a M a n a ge me nt a n d C o di n g  
T he S p o ns or or desi g nee will be res p o nsi ble f or acti vities ass ociate d wit h t he data ma n a ge me nt 
of t his st u d y. T his will i ncl u de setti n g u p a rel e va nt data base a n d d ata tra nsfer mec h a nis ms, 
al o n g wit h a p pr o priate v ali dati o n of data a n d res ol uti o n of q ueries. Data g e nerate d wit hi n t his 
cli nical st u d y will be ha n dle d acc or di n g t o t he rele va nt sta n dar d o perati n g pr oce d ures of t he d ata 
ma na ge me nt a n d bi ostatistics de part me nts of S p o ns or or desi g nee. 
St u d y ce nters will e nter d ata i nt o t he E D C s yste m b y c o m pleti n g t he e C R F via a sec ure i nter n et 
c o n necti o n. Dat a transcri be d i nt o t he e C R F m ust be verifia bl e a gai nst s o urce d oc u me nts at t he 
st u d y ce nter. D ata t o be r ec or de d directl y o n t he e C R F will be i de ntifie d, a n d t he e C R F will be 
c o nsi dere d t he s o urce d o c u me nt (e S o urce c o n ce pt). A n y c ha n g es t o t he dat a e ntere d i nt o t he 
E D C s yste m will be rec or de d i n t he a u dit trail a n d will be c o m plia nt wit h F D A C o de of Fe deral 
Re g ulati o ns ( C F R ) 2 1 Part 1 1. 
A n esse ntial ele me nt of t he e S o urce c o nce pt is t hat t he cli nical assess me nt data a n d ot her s o urce 
data is e nter e d d uri n g t he cli nical visit i n a n e S o urce E D C s yste m. W he n d esi g ni n g t he s yste m 
t here are s o me f u n d a me ntal as pects t o be res pect e d: 
•  T he a bilit y of t he p h ysicia n t o rec or d cli nical i nf or mati o n i n t he patie nt me dical rec or d 
s h o ul d n ot be li mite d or c o nstrai ne d 
•  I nf or mati o n s h o ul d be rec or de d i n li ne wit h t he c urre nt practice at t he st u d y site 
•  T he i nte grit y of t he me di cal rec or ds s h o ul d n ot be c o m pr o mise d 
•  T he S p o ns or s h o ul d ha ve access o nl y t o pse u d o n y mize d i nf or mati o n ma n d ate d b y t he 
pr ot oc ol 
 
T his g ui da nce d oes n ot i ncl u de direct d ata i n p ut fr o m ta blets, m o bile p h o nes, or ot her el ectr o nic 
de vices.  

Pr ot oc ol  A me n d me nt 1  
K Z R -6 1 6 -0 0 3 E  
Kezar Life Scie nces, I nc.  
1 3 Se pte m ber 2 0 2 1  
 
C o nfi de ntial  
Pa ge 6 0  of 6 6  
 
Me dical c o di n g will use Me d D R A f or c o n c o mita nt diseases a n d A Es, a n d will use t he W orl d 
Healt h Or ga ni zati o n ( W H O) dr u g cl assificati o ns f or me dicati o ns. 
Missi n g or i nc o nsist e nt data will be q uerie d i n writi n g t o t he I n vesti gat or f or clarificati o n. 
S u bse q ue nt m o dificati o ns t o t he data base will be d oc u me nte d. 
1 1. 1 1.  
Re p orti n g a n d P u blic ati o n, I ncl u di n g Arc hi vi n g  
Esse ntial d oc u me nts are t h ose d oc u me nts t hat i n di vi d uall y a n d c ollecti vel y per mit e val uati o n of 
t he st u d y a n d q ualit y of t he data pr o d u ce d. After c o m pleti o n of t he st u d y ( E n d of St u d y defi ne d 
as t he date of t h e last visit of t he last patie nt), all d oc u me nts a n d data relati n g t o t he st u d y will be 
ke pt i n a n or derl y ma n n er b y t he I n vesti gat or i n a sec ure st u d y file. T his fil e will be a vaila ble f or 
i ns pecti o n b y t he S p o ns or or its re pres e ntati ves. Esse ntial d oc u me nts s h o ul d be retai ne d f or 
2 years after t he fi nal mar keti n g a p pr o val i n a n I C H re gi o n or f or at least 2 year s after t he 
disc o nti n uati o n of cli nical de vel o p me nt of K Z R - 6 1 6. It is t he S p o ns or’s res p o nsi bilit y t o i nf or m 
t he st u d y ce nter w h e n t hese d oc u me nts n o l o n ger n ee d t o be retai ne d. T he I n vesti gat or m ust 
c o ntact t he S p o ns or bef ore destr o yi n g a n y st u d y- relate d d oc u me ntati o n. I n a d diti o n, all patie nt 
me dical rec or ds a n d ot her s o urce d o c u me ntati o n will be ke pt f or t he ma xi m u m ti me per mitte d b y 
t he h os pital, i nstit uti o n, or me dical pr actice. 

Pr ot oc ol  A me n d me nt 1  
K Z R -6 1 6 -0 0 3 E  
Kezar Life Scie nces, I nc.  
1 3 Se pte m ber 2 0 2 1  
 
C o nfi de ntial  
Pa ge 6 1  of 6 6  
 
1 2.  
R E F E R E N C E S  
A gar w al S, Kiel y P D. T w o si m ple, relia ble a n d v ali d tests of pr o xi mal m uscle f u ncti o n, a n d t heir 
a p plicati o n t o t he ma na g e me nt of i di o pat hic i nfla m mat or y m y ositis. R he u mat ol o g y ( O xf or d). 
2 0 0 6; 4 5( 7): 8 7 4- 9. 
Ale xa n der T, Sarf ert R, Kl otsc he J, K ü hl A A, R u b bert- R ot h A, L ore n z H M, et al. T he 
pr oteas o me i n hi bit or b ort ez o mi b de pletes plas ma cells a n d a meli orat es cli nical ma nifestati o ns of 
refr act or y s yste mic l u p us er yt he mat os us. A n n R he u m Dis. 2 0 1 5; 7 4( 7): 1 4 7 4- 8. 
Ale xa n ders o n H, Br o ma n L, T oll bäc k A, J osefs o n A, L u n d ber g I E, Ste nstr ö m C H. F u ncti o nal 
I n d e x- 2: vali dit y a n d reli a bilit y of a disease-s p ecific meas ure of i m pair me nt i n patie nts wit h 
p ol y m y ositis a n d der mat o m y ositis. Art hritis R he u m. 2 0 0 6; 5 5( 1): 1 1 4- 2 2. 
Arast u - K a p ur S, A n derl J L, Kra us M, Parlati F, S he n k K D, Lee SJ, et al. N o n pr oteas o mal tar g ets 
of t he pr oteas o me i n hi bit ors b ortez o mi b a n d carfil z o mi b: a li n k t o cli nical a d verse e v e nts. Cli n 
Ca ncer Res . 2 0 1 1; 1 7( 9): 2 7 3 4- 4 3. 
B hattarai S, G ha n na m K, Kra use S, Be n ve niste O, Mar g A, de Br ui n G, et al. T he 
i m m u n o pr oteas o mes are ke y t o re g ulate m y o ki nes a n d M H C class I e x pressi o n i n i di o pat hic 
i nfla m mat or y m y o pat hies. J A ut oi m m u n. 2 0 1 6; 7 5: 1 1 8- 2 9. 
B o ne R C, Bal k R A, Cerra F B, Delli n ger R P, Fei n A M, K na us W A, et al. D efi niti o ns f or s e psis 
a n d or ga n f ail ure a n d g ui deli nes f or t he u se of i n n o vati ve thera pies i n se psis. C hest 
1 9 9 2; 1 0 1( 6 ):1 6 4 4- 5 5. 
Br oss P F, Ka ne R, Farr ell A T, A bra ha m S, Be ns o n K, Br o wer M E, et al. A p pr o val s u m mar y f or 
b ortez o mi b f or i njecti o n i n t he treat me nt of m ulti ple m yel o ma. Cli n Ca ncer Res . 
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de xa met has o ne v ers u s b ortez o mi b a n d de x a met has o ne f or patie nts wit h rela pse d or refract or y 
m ulti ple m yel o ma ( E N D E A V O R): a r a n d o mise d, p hase 3, o pe n-l a bel, m ultice ntre st u d y. La n cet 
O nc ol. 2 0 1 6; 1 7( 1): 2 7- 3 8. 
E gerer K, K uc k el k or n U, R u d ol p h P E, R üc kert J C, D ör ner T, B ur m ester G R, et al. Circ ulati n g 
pr oteas o mes are mar k ers of cell da ma g e a n d i m m u n ol o gic acti vit y i n a ut oi m m u ne diseases. J 
R he u mat ol. 2 0 0 2; 2 9( 1 0): 2 0 4 5- 5 2. 
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Pr ot oc ol  A me n d me nt 1  
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G ha n na n K, M arti nez- Ga m b oa L, S pe n gler L, Kra use S, S milja n o vic B, B o ni n M, et al. 
U pre g ulati o n of i m m u n o pr oteas o me s u b u nits i n m y ositis i n dicates acti ve i nfla m mati o n  wit h 
i n v ol ve me nt of a nti ge n prese nti n g cells, C D 8 T-cells a n d I F Nγ. P L o S O ne . 2 0 1 4; 9( 8):e 1 0 4 0 4 8. 
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Healt h, E d ucati o n, a n d Welfare, P u blic Healt h Ser vice, Al c o h ol, Dr u g A b use, a n d Me ntal H ealt h 
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a relia ble a n d vali d i nstr u me nt f or meas uri n g cli nical disease acti vit y i n s yste mic l u p us 
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Ic hi ka wa H T, C o nle y T, M uc ha m uel T, Jia n g J, L ee S, O we n T, et al. Be neficial effect of n o v el 
pr oteas o me i n hi bit ors i n m uri ne l u p us via d ual i n hi biti o n of t y pe I i nterfer o n a n d a ut oa nti b o d y-
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He mat ol. 2 0 1 2; 4 9( 3): 2 0 7- 1 4.  
Kissele v A F , v a n der Li n de n W A, O v er kleeft H S. Pr oteas o me i n hi bit ors: a n e x pa n di n g ar m y 
attac ki n g a u ni q ue tar get. C he m Bi ol. 2 0 1 2; 1 9( 1): 9 9- 1 1 5. 
K Y P R O LI S ( carfilz o mi b) [ pres cri bi n g i nf or mati o n]. T h o usa n d Oa ks, C A: A M G E N; 2 0 1 8. 
L u n d ber g I E, Miller F W, Tjar nl u n d A, B ot tai M. Dia g n osis a n d classificati o n of i di o pat hic 
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Marti nez  C K, M o nac o JJ. H o m ol o g y of pr oteas o me s u b u nits t o a maj or hist oc o m pati bilit y 
c o m ple x-li n ke d L M P ge ne. Nat ure . 1 9 9 1; 3 5 3( 6 3 4 5): 6 6 4- 7. 
M uc ha m uel T, Basler M, A uja y M A, S uz u ki E, K ali m K W, La uer C, et al. A selecti ve i n hi bit or 
of t he i m m u n o pr oteas o me s u b u nit L M P 7 bl oc ks c yt o ki ne pr o d ucti o n a n d atte n uates pr o gressi o n 
of e x peri me nt al art hritis. Nat Me d . 2 0 0 9; 1 5( 7): 7 8 1- 7. 
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i m m u n o pr oteas o me s u b u nit L M P 7 atte n uates L C M V-i n d uce d me ni n gitis. E ur J I m m u n ol. 
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Na n di D, Jia n g H, M o nac o JJ. I de ntificati o n of M E C L-1 ( L M P - 1 0) as t he t hir d I F N-
ga m ma -i n d uci ble pr oteas o me s u b u nit. J I m m u n ol. 1 9 9 6; 1 5 6( 7): 2 3 6 1- 4. 

Pr ot oc ol  A me n d me nt 1  
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Ne u bert K, M eister S, M oser K, Weisel F, Mas e d a  D, A ma n n K, et al. T he pr oteas o me i n hi bit or 
b ortez o mi b de pletes plas ma cells a n d pr otects mice wit h l u p us -li ke disease fr o m ne p hritis. Nat 
Me d . 2 0 0 8; 1 4( 7): 7 4 8- 5 5. 
Pal o m bella VJ, C o n ner E M, F useler J W, Destree A, Da vis J M, Lar o u x F S, et al. R ole of t he 
pr o teas o me a n d N F-ka p p a B i n stre pt oc occal cell wall -i n d uce d p ol yart hritis. Pr oc Natl Aca d Sci 
U S A.  1 9 9 8; 9 5( 2 6): 1 5 6 7 1- 6. 
Parlati F, Lee SJ, A uja y M, S uz u ki E, Le vits k y K, L ore ns J B, et al. Carfilz o mi b ca n i n d uce 
t u m or cell deat h t hr o u g h selecti ve i n hi biti o n of t he c h y m otr y psi n-li ke acti vit y of t he pr oteas o me. 
Bl o o d.  2 0 0 9; 1 1 4( 1 6): 3 4 3 9- 4 7. 
Ri der L G, K ozi ol D, Gia n ni ni E H, Jai n M S, S mit h M R, W hit ne y‐ Ma h o ne y K, et al. Vali dati o n 
of ma n ual m uscle testi n g a n d a s u bset of ei g ht m uscles f or a d ult a n d j u v e nile i di o pat hi c 
i nfla m mat or y m y o pat hies. Art hritis Care Res.  2 0 1 0; 6 2( 4): 4 6 5- 7 2. 
Ri der L G, Wert h V P, H u ber A M, Ale x a n ders o n H, Ra o A P, R u pert o N, et al. Meas ures of a d ult 
a n d j u ve nile der mat o m y ositis, p ol y m y ositis, a n d i ncl usi o n b o d y m y ositis: P h ysicia n a n d 
Patie nt/ pare n t Gl o bal Acti vit y, Ma n ual M uscle Testi n g ( M M T), Healt h Ass ess me nt 
Q uesti o n naire ( H A Q)/ C hil d h o o d Healt h Assess me nt Q uesti o n naire ( C- H A Q), C hil d h o o d 
M y ositis Assess me nt Scale ( C M A S), M y ositis Disease A cti vit y Assess me nt T o ol ( M D A A T), 
Disease A cti vit y Sc ore ( D A S), S h ort F or m 3 6 ( S F- 3 6), C hil d Healt h Q uesti o n naire ( C H Q), 
p h ysicia n gl o bal da ma ge, M y ositis Da ma ge I n de x ( M DI), Q u a ntitati ve M uscle Testi n g ( Q M T), 
M y ositis F u ncti o nal I n d e x- 2 ( FI - 2), M y ositis Acti vities Pr ofile ( M A P), I ncl usi o n B o d y M y ositis 
F u ncti o n al Rati n g Scale (I B M F R S), C uta ne o us Der mat o m y ositis Disease Area a n d Se v erit y 
I n d e x ( C D A SI), C uta n e o us Assess me nt T o ol ( C A T), Der mat o m y ositis S ki n Se verit y I n de x 
( D S SI), S ki n de x, a n d Der mat ol o g y Life Q ualit y I n de x ( D L QI). Art hritis Care Res. 
2 0 1 1; 6 3( S u p pl 1 1): S 1 1 8- 5 7. 
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t he s keletal m uscle. Cell Deat h Diff er. 2 0 1 6; 2 3( 6): 9 2 7- 3 7. 
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C o lle ge of R he u mat ol o g y G ui deli ne f or t he Treat me nt of R he u mat oi d Art hritis. Art hritis R he u m.  
2 0 1 6; 6 8( 1): 0 1- 2 6. 
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as pects of vali dit y  of t he m y ositis da ma ge i n de x. A n n R he u m Dis. 2 0 1 1; 7 0( 7): 1 2 7 2- 6. 
S ulta n S M, Alle n E, O d dis C V, Kiel y P, C o o per R G, L u n d ber g I E, et al. Relia bilit y a n d vali dit y 
of t he m y ositis disease acti vit y assess me nt t o ol. Art hritis R he u m. 2 0 0 8; 5 8( 1 1): 3 5 9 3- 9. 
Wa n g Z, Ya n g J, Kir k C, Fa n g Y, Alsi na M, Ba dr os A, et al. Cli nical p har mac o ki netics, 
meta b olis m, a n d dr u g- dr u g i nteracti o n of carfilz o mi b. Dr u g Meta b Dis p os. 2 0 1 3; 4 1( 1): 2 3 0- 7. 
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s yste mic necr otizi n g vasc ulitis. Art hritis R he u m . 1 9 9 9; 4 2( 1 1): 2 3 6 5- 7 1. 
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Pr ot oc ol  A me n d me nt 1  
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Yassaee M, Fi or e nti n o D, O ka wa L, T a yl or L, C ole y C, Tr o x el A B, et al. M o dificati o n of t he 
c uta ne o us der mat o m y ositis disease area a n d se v erit y i n de x, a n o utc o me i nstr u me nt. Br J 
Der mat ol.  2 0 1 0; 1 6 2: 6 6 9- 7 3. 
Z ha n g H, Li u Z, H ua n g L, H o u J, Z h o u M, H ua n g X, et al. T he s h ort- t er m efficac y of 
b ortez o mi b c o m bi ne d wit h gl uc oc ortic oi ds f or t he treat me nt of refract or y l u p us ne p hritis. L u p us.  
2 0 1 7; 2 6( 9): 9 5 2- 8. 

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1 3.  
A P P E N DI C E S  
1 3. 1.  
A p pe n di x A:  Pr ot oc ol Hist or y  
Pr ot oc ol Versi o n  
D ate Iss ue d  
R ati o n ale f or U p d ate  
Ori gi nal Pr ot oc ol  
1 7 Se pte m ber  2 0 2 0 
N/ A  
A me n d me nt 1  
1 3 Se pte m ber  2 0 2 1 
Pr ot oc ol a me n de d t o e xte n d wee kl y 
K Z R - 6 1 6 a d mi nistrati o n u ntil t he 
last patie nt e nr olle d has c o m plete d 
4 8 wee ks of d osi n g, a n d t o s u p p ort 
o pti o nal at-h o me K Z R - 6 1 6 
a d mi nistrati o n b y patie nts a n d 
care gi vers. 

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1 3. 2.  
A p pe n di x B:  We bsites f or P atie nt -Re p orte d O utc o me s Assess me nts 
Assess me nt  
We bsite  
TI S  
Sc ore calc ulat or:   
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M D A A T  
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Gl ossar y:   
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M D GI C  
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FI - 2 
Trai ni n g  g ui de: 
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Sc ori n g s heet a n d i nstr ucti o ns: 
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M DI  
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H A Q -DI  
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E Q -5 D -5 L  
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Pt G A D D  
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A b bre viati o ns: E Q -5 D -5 L = E ur o Q o L 5 -di me nsi o n 5 -le v el; FI -2 = F u n cti o n al I n d e x -2; H A Q -DI = Healt h Assess me nt 
Q uesti o n naire -Disa b ilit y I n d e x; M D A A T = M y ositis Disease Acti vit y Assess me nt T o ol; M DI = M y ositis Da ma g e I n d e x; 
M D GI C = P h ysicia n Gl o b al I m pressi o n of C h a n g e; M M T -8 = Ma n u al M uscle Testi n g -8 M uscle Gr o u ps; Pt G A D A = Patie nt Gl o bal 
Assess me nt of Disease Acti vit y; Pt G A D D = Patie nt Gl o b al A ssess me nt of Disease Da ma g e; TI S = T otal I m pr o v e me nt Sc ore