A Phase 2, Multi-Center, Randomized, Placebo Controlled, Single-Blind Study With LJPC-401 for the Treatment of Iron Overload in Adult Patients With Hereditary Hemochromatosis
Phase: PHASE2
Conditions: Hereditary Hemochromatosis
Sponsor: La Jolla Pharmaceutical Company



Pr ot oc ol LJ 4 0 1- H H 0 1  
LJ P C - 4 0 1 
2 
La J olla P har mace utical - C o nfi de ntial  
Date :  1 4  Dece m ber  2 0 1 8  ( Versi o n 6. 0) 
P RI N CI P A L I N V E S TI G A T O R S T A T E M E N T O F A G R E E M E N T  
I, t he u n dersi g ne d Pri nci pal I n vesti gat or, ha ve rea d a n d u n derst o o d t he f oll o wi n g pr ot oc ol 
LJ 4 0 1- H H 0 1 versi o n 6. 0, 1 4 Dece m ber 2 0 1 8 a n d its a p pe n dices.  
I pr o mise t o a bi de b y t he I nter nati o nal C o u ncil o n Har m o nisati o n (I C H) G ui deli nes f or G o o d 
Cli nical Practice s ( G C P), t he Declarati o n of Helsi n ki, a n d all a p plica ble la ws a n d re g ulati o ns, a n d 
a gree t hat, i n all cases, t he m ost restricti ve re g ulati o n relate d t o a gi ve n as pect of researc h i n v ol vi n g 
pr otecti o n of h u ma n s u bjects will be f oll o we d.  I n t he e ve nt t hat I ha ve a q uesti o n re gar di n g m y 
o bli gati o ns d uri n g t he c o n d uct of t his pr ot oc ol, I ha ve rea d y access t o t hese af ore me nti o ne d 
re g ulati o ns, as eit her m y pers o nal c o p y, or a vaila ble o n file fr o m t he C hair pers o n of t he I nstit uti o nal 
Re vie w B oar d (I R B) / Et hics C o m mittee ( E C) or t he S p o ns or, via l ocal a u t h orities a n d,  
I a m a ut h orize d t o e nter i nt o t his c o m mit me nt t o c o n d uct t he st u d y o utli ne d i n t his pr ot oc ol, a n d m y 
si g nat ure bel o w si g nifies t hat I a gree t o c o n d uct t he st u d y as o utli ne d herei n. 
 
 
 
  
  
  
  
  
  
  
  
  
  
  
  
 
Pri nte d Na me of I n vesti gat or  
 
  
  
  
  
  
  
  
  
  
  
  
  
 
Si g nat ure of I n vesti gat or 
 
  
  
  
  
  
  
  
  
  
  
  
  
 
Date  

Pr ot oc ol LJ 4 0 1- H H 0 1  
LJ P C - 4 0 1 
4 
La J olla P har mace utical - C o nfi de ntial  
Date :  1 4  Dece m ber  2 0 1 8  ( Versi o n 6. 0) 
1.  
S Y N O P SI S  
N a me of S p o ns or/ C o m p a n y:  
La  J olla P har mace utical C o m pa n y ( La  J olla)  
N a me of I n vesti g ati o n al Pr o d uct:  
LJ P C -4 0 1  (s ol uti o n f or s u bc uta ne o us [ S C] i njecti o n) 
N a me of Dr u g S u bst a nce : 
S y nt hetic h u ma n he pci di n  ( he pci di n-2 5  acetate) 
Title of St u d y:  
A P hase 2, M ultice nter, Ra n d o mize d, Place b o -c o ntr olle d, Si n gle -bli n d St u d y wit h LJ P C -4 0 1  f or t he 
Treat me nt of Ir o n O verl oa d i n A d ult Patie nts wit h Here ditar y He m o c hr o mat osis  
St u d y Site(s):   A p pr o xi matel y 3 0  
P h ase of De vel o p me nt:  2  
O bjecti ves:    
Pri m ar y:  
•  
T o c o m pare  t he effect of LJ P C -4 0 1 vers us place b o o n tra nsferri n sat urati o n ( T S A T) i n 
a d ult patie nts wit h here ditar y he m oc hr o mat osis . 
Sec o n d ar y:  
•  
T o c o m pare  t he effect of LJ P C -4 0 1 vers us place b o o n p hle b ot o m y re q uire me nts . 
•  
T o esta blis h t he s afet y a n d t olera bilit y  of LJ P C -4 0 1 vers us place b o  i n a d ult patie nts wit h 
here ditar y he m o c hr o mat osis . 
•  
T o c o m pare  t he effect of LJ P C -4 0 1  vers us place b o  o n s er u m ferriti n . 
E x pl or at or y:  
•  
T o c o m pare t he effect of LJ P C -4 0 1 vers us place b o o n ser u m ir o n para meters . 
•  
T o c o m pare t he effect of LJ P C -4 0 1 vers us place b o o n t h yr oi d f u ncti o n. 
•  
T o c o m pare t he effect of LJ P C -4 0 1 vers us place b o o n li ver f u ncti o n.  
•  
T o c o m pare t he effect of LJ P C -4 0 1 vers us place b o o n gl y ce mic c o ntr ol.  
•  
T o c o m pare t he effect of LJ P C -4 0 1 vers us place b o o n re d bl o o d cell ( R B C) para meters 
i ncl u di n g he m o gl o bi n c o nce ntrati o n, R B C c o u nt, a n d re d cell distri b uti o n wi dt h ( R D W) . 
•  
T o c o m pare t he effect of LJ P C -4 0 1 vers us place b o o n q ualit y of life as meas ure d b y 
Q ualit y of Life Q uesti o n naire s, S h ort F or m ( 3 6) Healt h S ur ve y, Versi o n 2 (S F - 36 v 2 ), 
Wester n O ntari o a n d Mc Master U ni versities Oste oart hritis I n de x ( W O M A C) , a n d 
m o difie d Dreisler i n dices f or art hritis. 

Pr ot oc ol LJ 4 0 1- H H 0 1  
LJ P C - 4 0 1 
5 
La J olla P har mace utical - C o nfi de ntial  
Date :  1 4  Dece m ber  2 0 1 8  ( Versi o n 6. 0) 
E n d p oi nts:  
Pri m ar y effic ac y e n d p oi nt :  
•  
C ha n ge i n T S A T , defi ne d as f oll o ws: 
− F or patie nts wit h 1 p hle b ot o m y (t he sta n dar d of care t hera pe utic p hle b ot o m y o n 
Da y  1 [ pre d ose]), c ha n ge i n T S A T fr o m baseli ne t o Wee k 1 6 ( 2 4 [ ± 4] h o urs 
p ost d ose).  
− F or patie nts u n der g oi n g 2 or m ore  p hle b ot o m ies, c ha n ge i n T S A T fr o m baseli ne t o 
t he m ost rece nt p ost d ose fasti n g T S A T o bser ve d pri or t o t he sec o nd p hle b ot o m y.  
Sec o n d ar y effic ac y e n d p oi nts:  
•  
N u m ber of p hle b ot o mies fr o m Da y 2 t o E n d of St u d y ( E O S )/ 3 0 (+ 3) da ys after t he last 
d ose of st u d y dr u g . 
•  
C ha n ge i n ser u m ferriti n, defi ne d as f oll o ws:  
− F or patie nts wit h 1 p hle b ot o m y (t he sta n dar d of care t hera pe utic p hle b ot o m y o n 
Da y  1 [ pre d ose]), c ha n ge i n ser u m ferriti n fr o m baseli ne t o Wee k 1 6 ( 2 4 [ ± 4] h o urs 
p ost d ose).  
− F or patie nts u n der g oi n g 2 or m ore  p hle b ot o m ies, c ha n ge i n ser u m ferriti n fr o m 
baseli ne t o t he m ost rece nt p ost d ose ser u m ferriti n  o bser ve d pri or t o  t he sec o n d 
p hle b ot o m y.  
S afet y a n d t oler a bilit y e n d p oi nts:  
•  
A d verse e ve nts ( A Es)  fr o m c o nse nt to E O S . 
•  
C ha n ges i n cli nical la b orat or y e val uati o ns i ncl u di n g ser u m ir o n para meters  fr o m baseli ne  
t o E O S . 
•  
C ha n ges i n vital si g ns, electr ocar di o gra ms ( E C Gs), use of c o nc o mita nt me dicati o ns, a n d 
p h ysical e xa mi nati o ns fr o m baseli ne  t o E O S . 
•  
I m m u n o ge nicit y (a nti-dr u g a nti b o d y) / p har mac o ki netics ( P K) fr o m baseli ne  to E O S . 
E x pl or at or y e n d p oi nts:  
•  
C ha n ge i n ser u m ir o n para meters , defi ne d as f oll o ws: 
− F or patie nts wit h 1 p hle b ot o m y (t he sta n dar d of care t hera pe utic p hle b ot o m y o n 
Da y  1 [ pre d ose]) , c ha n ge i n ser u m ir o n para meters fr o m baseli ne t o Wee k 1 6 
( 2 4 [ ± 4] h o urs p ost d ose).  
− F or patie nts u n der g oi n g 2 or m ore  p hle b ot o m ies, c ha n ge i n ser u m ir o n para meters 
fr o m baseli ne t o t he m ost rece nt p ost d ose ser u m ir o n para meters o bser ve d pri or t o  t he 
sec o n d p hle b ot o m y.  
− F or patie nts wit h 1 p hle b ot o m y (t he sta n dar d of care t hera pe utic p hle b ot o m y o n 
Da y  1 [ pre d ose]) , c ha n ge i n ser u m ir o n para meters fr o m baseli ne t o Wee k 1 7  
(a p pr o xi matel y 7 da ys after t he last d ose of st u d y dr u g). 

Pr ot oc ol LJ 4 0 1- H H 0 1  
LJ P C - 4 0 1 
6 
La J olla P har mace utical - C o nfi de ntial  
Date :  1 4  Dece m ber  2 0 1 8  ( Versi o n 6. 0) 
− F or patie nts u n der g oi n g 2 or m ore  p hle b ot o m ies, c ha n ge i n ser u m ir o n para meters 
fr o m baseli ne t o t he m ost rece nt pre d ose ser u m ir o n para meters o bser ve d pri or t o  t he 
sec o n d p hle b ot o m y.  
•  
C ha n ge i n t h yr oi d f u ncti o n fr o m baseli ne t o Wee k 1 6 . 
•  
C ha n ge i n li ver f u ncti o n fr o m baseli ne t o Wee k 1 6 . 
•  
C ha n ge i n he m o gl o bi n A 1 c fr o m baseli ne t o Wee k 1 6 . 
•  
C ha n ge i n R B C para meters i ncl u di n g he m o gl o bi n c o nce ntrati o n, R B C c o u nt, a n d R D W  
as defi ne d as  f oll o ws: 
− F or patie nts wit h 1 p hle b ot o m y (t he sta n dar d of care t hera pe utic p hle b ot o m y o n 
Da y  1 [ pre d ose]), c ha n ge i n R B C para meters fr o m baseli ne t o 
Wee k  1 6  ( 2 4 [ ± 4]  h o urs p ost d ose) . 
− F or patie nts u n der g oi n g 2 or m ore p hle b ot o mies, c ha n ge i n R B C para meters fr o m 
baseli ne t o t he m ost rece nt p ost d ose R B C para meters o bser ve d pri or t o t he sec o n d 
p hle b ot o m y.  
•  
C ha n ge i n Q ualit y of Life Q uesti o n naire s, S F -3 6 v 2 , W O M A C, a n d m o difie d Dreisler 
i n dices f or art hritis, fr o m baseli ne  t o Wee k 1 6 . 
St u d y Desi g n:   T his st u d y is a m ultice nter, ra n d o mize d, place b o -c o ntr olle d, si n gle-bli n d st u d y.  T he 
pri mar y o bjecti ve of t he st u d y is t o e val uate t he effect of LJ P C -4 0 1  o n T S A T i n  a d ults wit h 
here ditar y he m o c hr o mat osis.  
Eli gi b le patie nts will be ra n d o mize d 1: 1 t o LJ P C -4 0 1  or place b o .  Ra n d o mizati o n will be stratifie d b y 
baseli ne T S A T ( > 4 5 % t o 7 0 % vers us  > 7 0 %) a n d p hle b ot o m y fre q ue nc y o ver t he last 1 2  m o nt hs 
( 0 t o 3 vers us >  3). 
All ra n d o mize d patie nts will recei ve a sta n dar d of care t hera pe utic p hle b ot o m y ( 5 00 cc  or a p pr o priate 
f or wei g ht) o n Da y 1  ( pre d ose).  T hereafter, p hle b ot o m y decisi o ns b y t he I n vesti gat or will be base d 
o n t he patie nt’s fasti n g T S A T res ults c ollecte d 2 4  ( ± 4) h o urs p ost d ose at Wee k 4  (Da y 2 3 ); Wee k  8 
(Da y 5 1 ); Wee k 1 2  (Da y  7 9 ); a n d Wee k  1 6  (Da y 1 0 7 ); a n d base d o n t he 2 0 1 1 Ir o n Dis or ders I nstit ute 
(I DI) p hle b ot o m y g ui deli nes f or patie nts wit h here ditar y he m oc hr o mat osis .  If a p hle b ot o m y is 
i n dicate d base d o n t he T S A T criteria of t he I DI p hle b ot o m y g ui deli ne s, t he patie nt s h o ul d recei ve 
p hl e b ot o m y treat me nt pre d ose , o n or bef ore t he f oll o wi n g visit . 
T he pri mar y efficac y a nal ysis will ta ke place after all patie nts ha ve c o m plete d t he We ek 1 6 
assess me nts  ( or ha ve wit h dra w n fr o m t he st u d y earl y).    
N u m ber of p atie nts ( pl a n ne d):   A p pr o xi matel y 6 8 t o 7 6 patie nts   

Pr ot oc ol LJ 4 0 1- H H 0 1  
LJ P C - 4 0 1 
7 
La J olla P har mace utical - C o nfi de ntial  
Date :  1 4  Dece m ber  2 0 1 8  ( Versi o n 6. 0) 
I ncl usi o n Criteri a: 
1.  Patie nts wit h a c li nical dia g n osis of here ditar y he m o c hr o mat osis. 
2.  Patie nts w h o are prescri be d  t hera pe utic p hle b ot o m y f or t he treat me nt of here ditar y 
he m oc hr o mat osis.  
3.  Patie nts ≥ 1 8 y ears of a ge.   
4.  Patie nts wit h a ser u m  ferriti n le vel ≥ 1 0 0 n g/ m L.  
5.  Patie nts wit h a T S A T le vel > 4 5 %.  
6.  Fe male patie nts m ust be of n o nc hil d beari n g p ote ntial or usi n g a hi g hl y effecti ve met h o d of 
c o ntrace pti o n d uri n g partici pati o n i n t he st u d y  a n d f or 3 0 da ys after t he last d ose of st u d y 
dr u g .  Hi g hl y effecti ve met h o ds of c o ntrace pti o n are defi ne d as t h ose, al o ne or i n 
c o m bi nati o n, t hat res ult i n a l o w fail ure rate w he n use d c o nsiste ntl y a n d c orrectl y.   Refer t o 
Secti o n  1 0. 1. 6. 5. 1  f or t he list of hi g hl y effecti ve met h o ds of c o ntrace pti o n t hat ca n be use d i n 
t his st u d y. 
7.  Fe male patie nts of c hil d beari n g p ote ntial m ust ha ve a ne gati ve ser u m pre g na nc y test at 
Scree ni n g  ( wit hi n 3 0 da ys pri or t o t he first d ose of st u d y dr u g), a n d a ne gati ve uri ne 
pre g na nc y test o n Da y 1  (ie, pri or t o  i nitial d osi n g  of st u d y dr u g). 
8.  Male patie nts m ust be s ur gicall y sterile  ( vasect o m y) or usi n g a hi g hl y effecti ve met h o d of 
c o ntrace pti o n d uri n g partici pati o n i n t he st u d y  a n d f or 3 0 da ys after t he last d ose of st u d y 
dr u g .  Hi g hl y effecti ve met h o ds of c o ntrace pti o n are defi ne d as t h ose, al o ne or i n 
c o m bi nati o n, t hat res ult i n a l o w fail ure rate w he n use d c o nsiste ntl y a n d c orrectl y .  Refer t o 
Secti o n  1 0. 1. 6. 5. 1  f or t he list of hi g hl y effecti ve met h o ds of c o ntrace pti o n t hat ca n be use d i n 
t his st u d y. 
9.  Patie nt m ust  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.  
 

Pr ot oc ol LJ 4 0 1- H H 0 1  
LJ P C - 4 0 1 
8 
La J olla P har mace utical - C o nfi de ntial  
Date :  1 4  Dece m ber  2 0 1 8  ( Versi o n 6. 0) 
E xcl usi o n Criteri a:  
1.  Patie nts  recei vi n g ir o n c helati o n t hera p y wit hi n 7 da ys pri or t o t he first d ose of st u d y dr u g .  
2.  Patie nts rece ntl y dia g n ose d, w h o ha ve i nitiate d p hle b ot o m y treat me nts less t ha n 3 m o nt hs 
pri or t o t he first d ose of st u d y dr u g . 
3.  Patie nts wit h a c o nc o mita nt disease, disa bilit y or c o n diti o n, i ncl u di n g la b orat or y a b n or malit y  
a n d E C G fi n di n gs, w hic h ma y i nterfere wit h t he c o n d uct of t he st u d y, or w hic h w o ul d, i n t he 
o pi ni o n of t he In vesti gat or, p ose a n u nacce pta ble ris k t o t he patie nt i n t his st u d y, i ncl u di n g, 
b ut n ot li mite d t o, cli nicall y si g nifica nt arr h yt h mias, alc o h ol de pe n de nc y or a b use, dr u g 
de pe n de nc y or a b use, or ps y c hiatric disease.   Patie nts wit h de pressi o n are eli gi ble if recei vi n g 
a sta ble d ose of me dicati o n f or at least 9 0 da ys pri or t o t he first d ose of st u d y dr u g.  
4.  Pre g na nt or lactati n g w o me n.  
5.  Patie nts ta ki n g a n i m m u n os u p pressi ve a ge nt t hat has n ot bee n a p pr o ve d b y La J olla f or use 
(e xcl u di n g t o pical o ver-t he-c o u nter ster oi ds, i n hale d ster oi d me dicati o ns,  a n d n o nster oi dal 
a nti-i nfla m mat or y dr u gs).  Refer t o Secti o n  7. 1  f or t he list of pr o hi bite d  me dicati o ns a n d 
pr oce d ures.  
6.  Patie nts partici pati n g i n a n u na p pr o ve d i n vesti gati o nal dr u g or i n vesti gati o nal t hera pe utic 
de vice st u d y wit hi n 3 0 da ys pri or t o st u d y dr u g d osi n g, ie, t here m ust be at least 3 0 da ys i n 
bet wee n t he last d ose o n a pri or st u d y a n d t he first d ose a d mi nistrati o n o n t his trial.  
7.  Patie nts w h o are u n willi n g or u na ble t o c o m pl y wit h t he st u d y pr ot oc ol re q uire me nts.  
8.  Patie nts wit h t y pe 1 dia betes  or t y pe 2 dia betes wit h he m o gl o b i n Alc greater t ha n 8 % wit hi n 
2 m o nt hs pri or t o ra n d o mizati o n . 
9.  Patie nts wit h u nc o ntr olle d a cti ve he patitis B, he patitis C, or h u ma n i m m u n o deficie nc y vir us 
( HI V) i nfecti o n. 
1 0.  Patie nts wit h C hil d P u g h class C  cirr h osis or li ver fail ure . 
1 1.  Patie nts wit h se vere c o n gesti ve heart fail ure ( Ne w Y or k Heart Ass ociati o n [ N Y H A]  = 
Class  4). 
1 2.  Patie nts w h o ha ve a d va nce d re nal fail ure wit h a n esti mate d gl o mer ular filtrati o n rate (e G F R) 
< 1 5 m L/ mi n/ 1. 7 3 m 2. 
1 3.  Patie nts wit h a h ist or y of aller gic reacti o n t o he pci di n or e xci pie nts. 
1 4.  Patie nts w h o ha ve pla n ne d s ur ger y  (e xcl u di n g de ntal s ur ger y or si m ple der mat ol o gic 
pr oce d ures)  d uri n g partici pati o n i n t his  st u d y. 
I n vesti g ati o n al Pr o d uct/ D os a ge F or m ul ati o n: 
LJ P C -4 0 1  (s y nt hetic h u ma n he pci di n) sol uti o n f or S C injecti o n  

Pr ot oc ol LJ 4 0 1- H H 0 1  
LJ P C - 4 0 1 
9 
La J olla P har mace utical - C o nfi de ntial  
Date :  1 4  Dece m ber  2 0 1 8  ( Versi o n 6. 0) 
D ose Re gi me n a n d R o ute of A d mi nistr ati o n:  
Patie nts  will be d ose d  o nce -wee kl y wit h LJ P C -4 0 1  or place b o ( 0. 9 % s o di u m c hl ori de) a d mi nistere d 
S C f or 1 6  wee ks.   LJ P C -4 0 1 d ose will start at 5 m g at Wee k 1 , a n d t he d ose will i ncrease t o 1 0 m g at 
Wee k s 2 a n d 3.  T he patie nt’s fasti n g T S A T at Wee k 3 (Da y 1 6 ), c ollecte d 2 4  ( ± 4) h o urs p ost d ose,  
will deter mi n e t he Wee k  4 d ose .  At Wee k  4, i f t he patie nt’s fasti n g T S A T is  > 4 5 % , t he n t he 
LJ P C -4 0 1 d ose will i ncrease t o 2 0 m g.  If t he fasti n g T S A T re mai ns ≤ 4 5 % t he n t he d ose will re mai n 
at 1 0 m g .  T he patie nt’s fasti n g T S A T res ult s at Wee k  8 ( Da y 5 1) a n d Wee k 1 2 ( Da y 7 9) , c ollecte d 
2 4  ( ± 4) h o urs p ost d ose,  will be use d t o deter mi ne if a d ose a dj ust me nt is nee de d at Wee ks  9 a n d 1 3.  
Refer t o Secti o n 5. 4  f or d ose a dj ust me nts i nf or mati o n.  
F or t h ose patie nts ra n d o mize d t o place b o, a s yri n ge of 0. 9 % s o di u m c hl ori de i njecti o n will be 
pre pare d b y t he st u d y p har macist or desi g nee.  T o mai ntai n t he st u d y si n gle-bli n d, s yri n ge s wit h st u d y 
dr u g ( place b o a n d acti ve dr u g) will be i de ntical.      
D ur ati o n of tre at me nt: 1 6 Wee ks    
St atistic al Met h o ds:  
A sa m ple size of 4 8  patie nts has 8 0 % p o wer t o detect a 1 5 % differe nce i n t he c ha n ge i n T S A T  
bet wee n t he place b o ar m a n d t he LJ P C -4 0 1  ar m, ass u mi n g a c o m m o n sta n dar d de viati o n of 1 8 % a n d 
a 2- si de d t y pe I err or of 0. 0 5.   
Patie nts w h o d o n ot e nr oll u n der gl o bal pr ot oc ol versi o n 4. 0/ U nite d Ki n g d o m ( U K ) pr ot oc ol versi o n 
4. 1 or later or disc o nti n ue t h e st u d y earl y pri or t o d osi n g will be re place d.  Patie nts w h o recei ve st u d y 
dr u g a n d disc o nti n ue pri or t o Wee k 1 6 ma y be re place d.  A p pr o xi matel y 2 0 t o 2 8 patie nts are 
e x pecte d t o be re place d.  T he pla n is t o e nr oll a n d ra n d o mize a p pr o xi matel y 6 8 t o 7 6 pat ie nts ( 1: 1 t o 
LJ P C -4 0 1 or place b o) t o e ns ure t hat at least 4 8 patie nts are i ncl u de d i n t he pri mar y efficac y a nal ysis.  
T he pri mar y efficac y a nal ysis a n d sec o n dar y efficac y a nal yses will i ncl u de t he Efficac y Patie nt 
P o p ulati o n  w hic h is defi ne d as all patie nts e nr olle d u n der gl o bal p r ot oc ol versi o n 4. 0/ U K pr ot oc ol 
versi o n 4. 1  or later w h o recei ve d st u d y dr u g, a n d w h o  c o m pleted t he Wee k 1 6 assess me nts or ha d a n 
o n -st u d y p hle b ot o m y after t he sta n dar d of care t hera p e utic p hle b ot o m y o n Da y  1 ( pre d ose) a n d b ef ore 
Wee k  1 6 . 
All e nr olle d p atie nts, re gar dless of pr ot oc ol versi o n, w h o recei ve at least 1 d ose  of st u d y dr u g will be 
incl u de d i n t he safet y a nal yses.  
Ce ntral ra n d o mizati o n will be use d wit h stratificati o n b y baseli ne T S A T ( > 4 5 % t o 7 0 % vers us  
> 7 0 %) a n d p hle b ot o m y fre q ue nc y o ver t he last 1 2 m o nt hs (0 t o 3 vers us >  3). 
D ata will be s u m marize d b y treat me nt gr o u p, st u d y visit, a n d, if a p pr o priate, st u d y i nter val usi n g 
s u m mar y statistics f or c o nti n u o us varia bles a n d n u m b er a n d perce nta ge f or cate g orical val ues.  
Statistical c o m p aris o ns of differe nces b et wee n treat me nt ar ms will be ma de usi n g Wilc o x o n ra n k -s u m 
tests, mi xe d effects re peate d meas ures, a n d/or a nal ysis of varia nce ( A N O V A ) f or c o nti n u o us or 
or di nal varia bles, C hi -S q uare or C oc hra n -Ma ntel -Hae nszel tests f or cate g orical varia bles, Fis h er’s 
e xact tests f or bi nar y varia bles, a n d P oiss o n re gressi o n m o del f or c o u nt data (e g, n u m ber of 
p hle b ot o mies) .  

Pr ot oc ol LJ 4 0 1- H H 0 1  
LJ P C - 4 0 1 
1 0 
La J olla P har mace utical - C o nfi de ntial  
Date :  1 4  Dece m ber  2 0 1 8  ( Versi o n 6. 0) 
S u b gr o u ps t hat are c o nsi dere d of i nterest i ncl u de a ge, se x, race, et h nicit y, co u ntr y, ge o gra p hic re gi o n, 
b o d y mass i n de x, baseli ne T S A T, p hle b ot o m y fre q ue nc y o ver t he last 1 2 m o nt hs , baseli ne he pci di n 
le vel, baseli ne ser u m ir o n le vel, a n d baseli ne ser u m ferriti n le vel. 
T he c ha n ge i n T S A T , ser u m ir o n pa nel, t h yr oi d f u ncti o n, li ver f uncti o n, gl y ce mic c o ntr ol, R B C 
para meters , a n d q ualit y of life q uesti o n naire sc ore s fr o m baseli ne t o Wee k 1 6 (a n d Wee k 1 6 
2 4  ( ± 4) h o urs  p ost d ose  f or ser u m ir o n para meters), a n d t he c ha n ge i n ser u m ir o n para meters  fr o m 
baseli ne t o Wee k 1 7,  will be e val uate d, w here a p pr o priate, usi n g t he a p pr o priate statistical met h o ds 
liste d a b o ve wit h a dj ust me nt f or baseli ne T S A T a n d p hle b ot o m y fre q ue nc y  o ver t he last 1 2  m o nt hs . 
N u m ber of  p hle b ot o mies a n d t he n u m ber of ti mes a patie nt met criteria f or a p hle b ot o m y will be 
a nal y ze d.  W het her a patie nt meets t he criteria f or a p hle b ot o m y ( yes or n o) will be assesse d after t he 
res ults of eac h fasti n g T S A T rec or de d at p ost d ose 2 4 ( ± 4) h o urs o n  Wee k 4  (Da y 2 3 ); Wee k 8 
(Da y  5 1 ); Wee k 1 2 (Da y 7 9 ); a n d Wee k 1 6 (Da y 1 0 7 ) are k n o w n .  T he patie nt s h o ul d recei ve 
p hle b ot o m y treat me nt pre d ose, o n or bef ore t he f oll o wi n g visit .  T he prese nce of a n y p hle b ot o m y  will 
be a nal y ze d b y  a C oc hra n - Ma ntel- Hae nszel test wit h a dj ust me nt f or baseli ne T S A T a n d p hle b ot o m y 
fre q ue nc y o ver t he last 1 2 m o nt hs .  T he fre q ue nc y of a p hle b ot o m y will be a nal yze d b y P oiss o n 
re gressi o n m o del wit h baseli ne T S A T a n d p hle b ot o m y fre q ue nc y  o ver t he last 1 2 m o nt hs  i ncl u de d i n 
t he m o del. 
Se nsiti vit y a nal yses of T S A T , ser u m ferriti n, a n d n u m b er of p hle b ot o m ies will be c o n d ucte d.  Details 
will be pr o vi de d i n t he statistical a nal ysis pla n.  
Safet y data i ncl u di n g a nal yses of A Es , cli nical la b orat or y data, E C G, vital si g ns, a n d i m m u n o ge nicit y  
fi n di n gs will be s u m marize d b y descri pti ve statistics wit hi n a n d acr oss treat me nt ar ms.  Se verit y, 
relate d ness, a n d seri o us ness of A Es will be s u m marize d.  P h ysical e xa mi nati o n  data  will be pr o vi de d 
i n t he listi n gs. 

Pr ot oc ol LJ 4 0 1- H H 0 1  
LJ P C - 4 0 1 
1 1 
La J olla P har mace utical - C o nfi de ntial  
Date :  1 4  Dece m ber  2 0 1 8  ( Versi o n 6. 0) 
2.  
T A B L E O F C O N T E N T S, L I S T O F T A B L E S, A N D LI S T O F 
FI G U R E S  
P RI N CI P A L I N V E S TI G A T O R S T A T E M E N T O F A G R E E M E N T  .............................................. 2 
1.  
S Y N O P SI S  ................................................................................................................... 4 
2.  
T A B L E O F C O N T E N T S, L I S T O F T A B L E S, A N D LI S T O F FI G U R E S ............... 1 1 
LI S T O F A B B R E VI A TI O N S A N D D E FI NI TI O N S O F  T E R M S  ................................................ 1 6 
3.  
I N T R O D U C TI O N ...................................................................................................... 1 9 
3. 1.  
S u m mar y of LJ P C - 4 0 1 N o ncli nical P har mac ol o g y I nf or mati o n ............................... 2 0 
3. 2.  
S u m mar y of LJ P C -4 0 1 T o xic ol o g y I nf or mati o n  ........................................................ 2 2 
3. 3.  
S u m mar y of LJ P C -4 0 1 Cli nical St u dies  ..................................................................... 2 4 
3. 3. 1.  
LJ 4 0 1- T P P 0 1  .............................................................................................................. 2 4 
3. 3. 2.  
LJ 4 0 1- N H V 0 1  ............................................................................................................ 2 5 
3. 3. 3.  
LJ 4 0 1- N H V 0 2  ............................................................................................................ 2 6 
3. 4.  
Cli nical Rati o nale f or t he LJ 4 0 1- H H 0 1 St u d y ........................................................... 2 6  
3. 4. 1.  
Rati o nale f or t he St u d y Desi g n f or St u d y LJ 4 0 1- H H 0 1  ............................................. 2 6 
3. 4. 2.  
Rati o nale f or Usi n g Ir o n Dis or ders I nstit ute P hle b ot o m y G ui deli nes ........................ 2 7  
4.  
T RI A L O BJ E C TI V E S A N D  P U R P O S E  .................................................................... 2 9 
4. 1.  
Pri mar y O bjecti ve  ....................................................................................................... 2 9 
4. 2.  
Sec o n dar y O bjecti ves  ................................................................................................. 2 9 
4. 3.  
E x pl orat or y O bjecti ves  ............................................................................................... 2 9 
5.  
I N V E S TI G A TI O N A L P L A N ..................................................................................... 3 0 
5. 1.  
O verall St u d y Desi g n  .................................................................................................. 3 0 
5. 2.  
N u m ber of Patie nts  ..................................................................................................... 3 0 
5. 3.  
Treat me nt Assi g n me nt  ................................................................................................ 3 0 
5. 4.  
D ose A dj ust me nt Criteria  ........................................................................................... 3 1 
5. 4. 1.  
Safet y Criteria f or A dj ust me nt or St o p pi n g D oses  ..................................................... 3 1 
5. 5.  
Criteria f or St u d y Ter mi nati o n  ................................................................................... 3 2 
5. 6.  
Sc he d ule of Assess me nts  ............................................................................................ 3 2 
6.  
S E L E C TI O N A N D WI T H D R A W A L O F P A TI E N T S  .............................................. 3 7 
6. 1.  
Patie nt I ncl usi o n Criteria  ............................................................................................ 3 7 
6. 2.  
Patie nt E xcl usi o n Criteria  ........................................................................................... 3 7 
6. 3.  
Patie nt Wit h dra wal Criteria  ........................................................................................ 3 8 

Pr ot oc ol LJ 4 0 1- H H 0 1  
LJ P C - 4 0 1 
1 2 
La J olla P har mace utical - C o nfi de ntial  
Date :  1 4  Dece m ber  2 0 1 8  ( Versi o n 6. 0) 
7.  
T R E A T M E N T O F P A TI E N T S .................................................................................. 4 0  
7. 1.  
C o nc o mita nt Me dicati o ns a n d Pr oce d ures  ................................................................. 4 0 
7. 2.  
Treat me nt C o m plia nce  ................................................................................................ 4 0 
7. 3.  
Ra n d o mizati o n a n d Si n gle- Bli n d  ................................................................................ 4 1 
7. 4.  
St u d y Pr oce d ures ........................................................................................................ 4 1  
7. 4. 1.  
Scree ni n g ( Wit hi n 9 0 da ys of Wee k 1/ Da y 1) ............................................................ 4 2  
7. 4. 2.  
Wee k 1 ( Da y 1) ........................................................................................................... 4 3  
7. 4. 3.  
Wee k 2 ( Da y 8) ........................................................................................................... 4 3  
7. 4. 4.  
Wee k 3 ( Da y 1 5 a n d Da y 1 6) ..................................................................................... 4 4  
7. 4. 5.  
Wee k 4 ( Da y 2 2) ......................................................................................................... 4 4  
7. 4. 6.  
Wee ks 5, 6, a n d 7 ( Da ys 2 9, 3 6, a n d 4 3) .................................................................... 4 5  
7. 4. 7.  
Wee k 8 ( Da y 5 0 a n d Da y 5 1) ..................................................................................... 4 5  
7. 4. 8.  
Wee ks 9, 1 0, a n d 1 1 ( Da ys 5 7, 6 4, a n d 7 1) ................................................................ 4 6  
7. 4. 9.  
Wee k 1 2 ( Da y 7 8 a n d Da y 7 9) ................................................................................... 4 6  
7. 4. 1 0.  
Wee ks 1 3, 1 4, a n d 1 5 ( Da ys 8 5, 9 2, a n d 9 9) .............................................................. 4 7  
7. 4. 1 1.  
Wee k 1 6 ( Da y 1 0 6 a n d Da y 1 0 7) ............................................................................... 4 7  
7. 4. 1 2.  
Wee k 1 7 ( Da y 1 1 3) ..................................................................................................... 4 8  
7. 4. 1 3.  
F oll o w- u p ( 3 0 da ys [ + 3 da ys] fr o m last d ose of st u d y dr u g) .................................... 4 8  
7. 4. 1 4.  
Earl y Wit h dra wal  ........................................................................................................ 4 9 
8.  
S T U D Y D R U G M A T E RI A L S  A N D M A N A G E M E N T  ........................................... 5 0 
8. 1.  
St u d y Dr u g .................................................................................................................. 5 0  
8. 2.  
St u d y Dr u g Pac ka gi n g a n d La beli n g .......................................................................... 5 0  
8. 3.  
St u d y Dr u g St ora ge ..................................................................................................... 5 0  
8. 4.  
St u d y Dr u g Pre parati o n .............................................................................................. 5 0  
8. 5.  
St u d y Dr u g A d mi nistrati o n ......................................................................................... 5 0  
8. 6.  
St u d y Dr u g Acc o u nta bilit y ......................................................................................... 5 1  
8. 7.  
St u d y Dr u g Ha n dli n g a n d Dis p osal ............................................................................ 5 1  
9.  
A S S E S S M E N T O F E F FI C A C Y  ................................................................................ 5 2 
9. 1.  
C o m plete Ir o n St u dies ................................................................................................ 5 2  
9. 2.  
P hle b ot o m y ................................................................................................................. 5 2  
1 0.  
A S S E S S M E N T O F S A F E T Y  ..................................................................................... 5 3 
1 0. 1.  
Safet y Para meters  ....................................................................................................... 5 3 

Pr ot oc ol LJ 4 0 1- H H 0 1  
LJ P C - 4 0 1 
1 3 
La J olla P har mace utical - C o nfi de ntial  
Date :  1 4  Dece m ber  2 0 1 8  ( Versi o n 6. 0) 
1 0. 1. 1.  
De m o gra p hics ............................................................................................................. 5 3  
1 0. 1. 2.  
Me dical Hist or y  .......................................................................................................... 5 3 
1 0. 1. 3.  
Vital Si g ns  .................................................................................................................. 5 3 
1 0. 1. 4.  
P h ysical E xa mi nati o n  ................................................................................................. 5 3 
1 0. 1. 5.  
Electr ocar di o gra m  ....................................................................................................... 5 3 
1 0. 1. 6.  
La b orat or y Assess me nts  ............................................................................................. 5 4 
1 0. 1. 6. 1.  
He mat ol o g y ................................................................................................................. 5 4  
1 0. 1. 6. 2.  
Cli nical C he mistries  .................................................................................................... 5 4 
1 0. 1. 6. 3.  
T h yr oi d F u ncti o n ........................................................................................................ 5 5  
1 0. 1. 6. 4.  
Gl yce mic C o ntr ol ........................................................................................................ 5 5  
1 0. 1. 6. 5.  
Pre g na nc y Scree n  ........................................................................................................ 5 5 
1 0. 1. 6. 6.  
Uri nal ysis  .................................................................................................................... 5 6 
1 0. 1. 6. 7.  
I m m u n o ge nicit y .......................................................................................................... 5 6 
1 0. 2.  
Q ualit y of Life Q uesti o n naires  ................................................................................... 5 6 
1 1.  
A D V E R S E A N D S E RI O U S A D V E R S E E V E N T S  ................................................... 5 7 
1 1. 1.  
Defi niti o n of A d verse E ve nts ..................................................................................... 5 7  
1 1. 1. 1.  
A d verse E ve nt ............................................................................................................. 5 7  
1 1. 1. 2.  
Seri o us A d verse E ve nt  ................................................................................................ 5 7 
1 1. 2.  
Relati o ns hi p t o I n vesti gati o nal Pr o d uct a n d Se verit y  ................................................. 5 8 
1 1. 3.  
Re p orti n g of A d verse E ve nts a n d Seri o us A d verse E ve nts ........................................ 5 9  
1 1. 3. 1.  
Re p orti n g of A d verse E ve nts ...................................................................................... 5 9  
1 1. 3. 2.  
Re p orti n g of Seri o us A d verse E ve nts ......................................................................... 5 9  
1 1. 4.  
F oll o w- u p of A Es a n d S A Es ....................................................................................... 6 0  
1 1. 5.  
Pre g na nc y a n d F oll o w- u p  ........................................................................................... 6 0 
1 2.  
S T A TI S TI C S  .............................................................................................................. 6 2 
1 2. 1.  
Statistical H y p ot hesis  .................................................................................................. 6 2 
1 2. 2.  
Sa m ple Size a n d P o wer C o nsi derati o ns ..................................................................... 6 2  
1 2. 3.  
Stratificati o n a n d Ra n d o mizati o n  ............................................................................... 6 2 
1 2. 4.  
Re place me nt of Patie nts  ............................................................................................. 6 2 
1 2. 5.  
Pla n ne d A nal yses ........................................................................................................ 6 3  
1 2. 6.  
A nal ysis Para meters  .................................................................................................... 6 3 
1 2. 6. 1.  
E n d p oi nts .................................................................................................................... 6 3  

Pr ot oc ol LJ 4 0 1- H H 0 1  
LJ P C - 4 0 1 
1 4 
La J olla P har mace utical - C o nfi de ntial  
Date :  1 4  Dece m ber  2 0 1 8  ( Versi o n 6. 0) 
1 2. 6. 1. 1.  
Pri mar y Efficac y E n d p oi nt ......................................................................................... 6 3  
1 2. 6. 1. 2.  
Sec o n dar y Efficac y E n d p oi nts .................................................................................... 6 3  
1 2. 6. 1. 3.  
Safet y a n d T olera bilit y E n d p oi nts .............................................................................. 6 4  
1 2. 6. 1. 4.  
E x pl orat or y E n d p oi nts  ................................................................................................ 6 4 
1 2. 6. 2.  
Defi niti o n of S u b gr o u ps ............................................................................................. 6 5  
1 2. 7.  
A nal ysis P o p ulati o n .................................................................................................... 6 5  
1 2. 8.  
Statistical Met h o ds  ...................................................................................................... 6 6 
1 2. 8. 1.  
Patie nt Dis p ositi o n, De m o gra p hic, a n d Bac k gr o u n d C haracteristics ......................... 6 6  
1 2. 8. 2.  
Me dical Hist or y  .......................................................................................................... 6 7 
1 2. 8. 3.  
Pri or a n d C o nc o mita nt Me dicati o ns a n d Pr oce d ures .................................................. 6 7  
1 2. 8. 4.  
Efficac y A nal yses  ....................................................................................................... 6 8 
1 2. 8. 4. 1.  
Pri mar y E n d p oi nt A nal yses ( P ost d ose T S A T) ........................................................... 6 8  
1 2. 8. 4. 2.  
Sec o n dar y Efficac y E n d p oi nt A nal yses ...................................................................... 6 8  
1 2. 8. 4. 3.  
E x pl orat or y E n d p oi nt A nal yses  .................................................................................. 6 9 
1 2. 8. 5.  
Safet y A nal ysis  ........................................................................................................... 7 0 
1 2. 8. 5. 1.  
A d verse E ve nts ........................................................................................................... 7 0  
1 2. 8. 5. 2.  
St u d y Dr u g E x p os ure .................................................................................................. 7 1  
1 2. 8. 5. 3.  
Cli nical La b orat or y Data  ............................................................................................ 7 1 
1 2. 8. 5. 4.  
I m m u n o ge nicit y/ P har mac o ki netics ............................................................................ 7 1 
1 2. 8. 5. 5.  
P h ysical E xa m  ............................................................................................................ 7 1 
1 2. 8. 5. 6.  
Vital Si g ns  .................................................................................................................. 7 1 
1 2. 8. 5. 7.  
Electr ocar di o gra m  ....................................................................................................... 7 1 
1 2. 8. 6.  
Missi n g Val ues a n d Criteria f or Data E xcl usi o ns  ....................................................... 7 2 
1 2. 8. 7.  
Q ualit y of Life A nal ysis  ............................................................................................. 7 2 
1 3.  
DI R E C T A C C E S S T O S O U R C E D A T A/ D O C U M E N T S  ......................................... 7 3 
1 3. 1.  
St u d y M o nit ori n g, A u dits, a n d I ns pecti o ns ................................................................ 7 3  
1 4.  
Q U A LI T Y C O N T R O L A N D Q U A LI T Y A S S U R A N C E  ......................................... 7 4 
1 5.  
I R B (I N S TI T U TI O N A L RE VI E W B O A R D) / E T HI C S  ........................................... 7 5 
1 5. 1.  
I R B / Et hics Re vie w ................................................................................................... 7 5 
1 5. 2.  
Pr ot oc ol C o m plia nce .................................................................................................. 7 5  
1 5. 3.  
Et hical C o n d uct of t he St u d y ...................................................................................... 7 5  
1 5. 4.  
Writte n I nf or me d C o nse nt .......................................................................................... 7 6  

Pr ot oc ol LJ 4 0 1- H H 0 1  
LJ P C - 4 0 1 
1 5 
La J olla P har mace utical - C o nfi de ntial  
Date :  1 4  Dece m ber  2 0 1 8  ( Versi o n 6. 0) 
1 5. 5.  
Patie nt C o nfi de ntialit y  ................................................................................................ 7 6 
1 5. 5. 1.  
Ge neral Data Pr otecti o n Re g ulati o n f or Cli nical St u die s C o n d ucte d i n t he 
E ur o pea n Ec o n o mic Ar ea ........................................................................................... 7 6  
1 6.  
R E C O R D K E E PI N G  ................................................................................................... 7 8 
1 6. 1.  
I ns pecti o n of Rec or ds ................................................................................................. 7 8 
1 6. 2.  
Rete nti o n of Rec or ds .................................................................................................. 7 8  
1 7.  
P U B LI C A TI O N P O LI C Y  .......................................................................................... 7 9 
1 8.  
R E F E R E N C E S  ........................................................................................................... 8 0 
1 8. 1.  
P u blicati o ns ................................................................................................................. 8 0  
1 8. 2.  
St u d y Re p orts .............................................................................................................. 8 1  
1 8. 2. 1.  
Cli nical  ........................................................................................................................ 8 1 
1 8. 2. 2.  
N o ncli nical .................................................................................................................. 8 1  
A P P E N DI X  1. S U M M A R Y O F L A B O R A T O R Y P A R A M E T E R S  ......................................... 8 3 
 
LI S T O F T A B L E S  
Ta ble  1: 
A b bre viati o ns a n d S pecialist Ter ms  ........................................................................... 1 6 
Ta ble  2: 
S u m mar y of LJ P C -4 0 1 N o ncli nical T o xic ol o g y St u dies  ........................................... 2 3 
Ta ble  3: 
Sc he d ule of Assess me nts  ............................................................................................ 3 3 
Ta ble  4: 
Relati o ns hi p of A d verse E ve nts t o I n vesti gati o nal Pr o d uct ....................................... 5 8  
Ta ble  5: 
Se verit y of A d verse E ve nts ........................................................................................ 5 9  
 
LI S T O F FI G U R E S  
Fi g ure 1:  
Perce nt C ha n ge i n Ser u m Ir o n i n Rats a n d D o gs at Si milar H u ma n E q ui vale nt 
D oses  ........................................................................................................................... 2 1 
 

Pr ot oc ol LJ 4 0 1- H H 0 1  
LJ P C - 4 0 1 
1 6 
La J olla P har mace utical - C o nfi de ntial  
Date :  1 4  Dece m ber  2 0 1 8  ( Versi o n 6. 0) 
LI S T O F A B B R E VI A TI O N S A N D D E FI NI TI O N S O F  T E R M S  
T he f oll o wi n g a b bre viati o ns a n d s pecialist ter ms are use d i n t his st u d y pr ot oc ol. 
T a ble  1: 
A b bre vi ati o ns a n d S peci alist T er ms 
A b bre vi ati o n or S peci alist Ter m  
E x pl a n ati o n  
A D A  
a nti-dr u g a nti b o d y 
A E  
a d verse e ve nt 
A L T 
ala ni ne a mi n o tra nsferase 
A N O V A  
a nal ysis of varia nce  
A S T  
as partate a mi n otra nsferase  
A T C 
A nat o mical T hera pe utic C he mical  
B MI  
b o d y mass i n de x  
C R A  
Cli nical Researc h Ass ociate  
C V  
c oefficie nt of variati o n  
E C G  
electr ocar di o gra m  
e C R F 
electr o nic case re p ort f or m  
e G F R 
esti mate d gl o mer ular filtrati o n rate  
E O S 
E n d of St u d y  
F D A  
F o o d a n d Dr u g A d mi nistrati o n  
G C P  
G o o d Cli nical Practice  
G D P R  
Ge neral Data Pr otecti o n Re g ulati o n  
H A M P  
he pci di n a nti micr o bial pe pti de  
H E D 
h u ma n e q ui vale nt d ose  
H E E N T  
hea d , e yes, ears, n ose , t hr oat 
H F E  
h u ma n fact ors e n gi neeri n g  
H F E 2  
h u ma n fact ors e n gi neeri n g t y pe 2  
HI V  
h u ma n i m m u n o deficie nc y vir us  
I C H 
I nter nati o nal C o u ncil o n Har m o nisati o n  
I C MJ E 
I nter nati o nal C o m mittee of Me dical J o ur nal E dit ors 
I DI 
Ir o n Dis or ders I nstit ute 
I E C / E C 
I nter nati o nal Et hics C o m mittee / Et hics C o m mittee 
I R B 
I nstit uti o nal Re vie w B oar d  
I T T 
I nte nt t o Treat 
I X R S 
I nteracti ve V oice/ W e b Res p o nse S yste m 

Pr ot oc ol LJ 4 0 1- H H 0 1  
LJ P C - 4 0 1 
1 7 
La J olla P har mace utical - C o nfi de ntial  
Date :  1 4  Dece m ber  2 0 1 8  ( Versi o n 6. 0) 
T a ble  1: 
A b bre vi ati o ns a n d S peci alist Ter ms ( C o nti n ue d)  
A b bre vi ati o n or S peci alist Ter m  
E x pl a n ati o n  
I U D 
i ntra uteri ne de vice 
I U S 
i ntra uteri ne s yste m 
La J olla 
La J olla P har mace utical C o m pa n y 
L D H 
lactate de h y dr o ge nase 
L O C F  
last o bser vati o n carrie d f or war d 
Me d D R A  
Me dical Dicti o nar y f or Re g ulat or y Acti vities  
mI T T  
M o difie d I nte nt t o Treat  
M O E  
Mar gi ns of e x p os ure  
NI H  
Nati o nal I nstit utes of Healt h  
N T BI  
n o ntra nsferri n b o u n d ir o n  
N Y H A  
Ne w Y or k Heart Ass ociati o n  
P D  
p har mac o d y na mic  
P K  
p har mac o ki netic  
P P  
Per Pr ot oc ol P o p ulati o n  
P T  
preferre d ter m  
R B C  
re d bl o o d cell 
R D W  
re d cell distri b uti o n wi dt h 
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(l y) 
S D  
sta n dar d de viati o n 
S F -3 6 v 2  
S h ort F or m ( 3 6) Healt h S ur ve y, Versi o n 2  
SI  
S ysté me I nter nati o nal  
S L C 4 0 A 1  
s ol ute carrier fa mil y 4 0 me m ber 1 
S O C  
s yste m or ga n class 
T 3 
T rii o d ot h yr o ni ne 
T 4 
t h yr o xi ne 
T E A E 
treat me nt-e mer ge nt a d verse e ve nt 
T F R 
tra nsferri n rece pt or 2 ( T F R 2) 
TI B C  
t otal ir o n bi n di n g ca pacit y 
T S A T 
tra nsferri n sat urati o n 
T S H 
t h yr oi d-sti m ulati n g h or m o ne 

Pr ot oc ol LJ 4 0 1- H H 0 1  
LJ P C - 4 0 1 
1 8 
La J olla P har mace utical - C o nfi de ntial  
Date :  1 4  Dece m ber  2 0 1 8  ( Versi o n 6. 0) 
T a ble  1: 
A b bre vi ati o ns a n d S peci alist Ter ms ( C o nti n ue d)  
A b bre vi ati o n or S peci alist Ter m  
E x pl a n ati o n  
UI B C  
u nsat urate d ir o n bi n di n g ca pacit y  
U K  
U nite d Ki n g d o m  
U S P  
U nite d States P har mac o peia  
U S PI  
U nite d States Prescri bi n g I nf or mati o n  
W H O -D D  
W orl d Healt h Or ga nizati o n Dr u g Dicti o nar y  
W O M A C  
Wester n O ntari o a n d Mc Master U ni versities Oste oart hritis I n de x  

Pr ot oc ol LJ 4 0 1- H H 0 1  
LJ P C - 4 0 1 
1 9 
La J olla P har mace utical - C o nfi de ntial  
Date :  1 4  Dece m ber  2 0 1 8  ( Versi o n 6. 0) 
3.  
I N T R O D U C TI O N 
Here ditar y he m oc hr o mat osis is a n a ut os o mal recessi ve dis or der t hat ca uses e xcessi ve a m o u nts of 
ir o n t o be a bs or be d a n d st ore d i n t he b o d y.  It is t he m ost c o m m o n here ditar y dis or der o bser ve d i n 
Ca ucasia ns ( Bac o n  2 0 1 1) a n d occ urs m ost ofte n i n pe o ple of n ort her n E ur o pea n desce nt, partic ularl y 
t h ose wit h N or dic or Celtic a ncestr y.  
M utati o ns i n se veral ge nes, i ncl u di n g hi g h ir o n (als o k n o w n as h u ma n fact ors e n gi neeri n g [ H F E ] 
pr otei n ), H F E 2, he pci di n a nti micr o bial pe pti de ( H A M P), s ol ute carrier fa mil y 4 0 me m ber 
1 ( S L C 4 0 A 1), a n d tra nsferri n rece pt or 2 ( T F R 2), ca n ca use here ditar y  he m oc hr o mat osis  
(Nati o nal I nstit utes  of Healt h [NI H ] 2 0 1 7).  A p pr o xi matel y 8 0 % of here ditar y  he m oc hr o mat osis  
cases are ca use d b y H F E m utati o ns, a n d t he re mai ni n g 2 0 % of cases are desi g nate d as n o n -H F E 
he m oc hr o mat osis ( de Li ma Sa nt os 2 0 1 0 ).   Classical here ditar y  he m oc hr o mat osis  prese nts wit h 
fasti n g tra nsferri n sat urati o n ( T S A T) > 4 5 % a n d ele vate d ser u m ferriti n > 3 0 0 n g/ m L i n males or 
> 2 0 0 n g/ m L i n fe males, wit h p ositi ve H F E ge netic testi n g of t he C 2 8 2 Y h o m oz y g ote or 
C 2 8 2 Y/ H 6 3 D c o m p o u n d heter oz y g ote ( Ir o n Dis or ders I nstit ute 2 0 1 1).  Alt h o u g h h o m oz y g osit y f or 
t he C 2 8 2 Y m utati o n is prese nt i n a p pr o xi matel y 1 per 2 2 0 t o 2 5 0 pe o ple wit h n ort her n E ur o pea n 
a ncestr y, less t ha n 1 0 % of t hese i n di vi d uals will de vel o p se vere ir o n o verl oa d acc o m pa nie d b y 
or ga n da ma ge a n d cli nical ma nifestati o ns of he m oc hr o mat osis.  
He pci di n c o ntr ols ir o n h o me ostasis b y dictati n g h o w ir o n is a bs or be d, use d, a n d st ore d i n t he b o d y.  
He pci di n re g ulates e ntr y of ir o n i nt o circ ulati o n t hr o u g h i n hi biti o n of ferr o p orti n, w hic h c o ntr ols 
ir o n e x p ort o ut of cells i n t he g ut a n d li ver as well as circ ulati n g er yt hr o p ha g oc ytic macr o p ha ges.  
I n patie nts wit h here ditar y  he m oc hr o mat osis , l o w plas ma he pci di n le vels ca use ferr o p orti n t o direct 
ir o n i nt o circ ulati o n (ie, a re d ucti o n i n he pci di n c orrelates wit h a n i ncrease i n circ ulati n g ir o n).  
Si nce h u ma ns lac k t he a bilit y t o e xcrete e xcess ir o n, it pr o gressi vel y acc u m ulates i n t he plas ma a n d 
or ga ns.  I n healt h y h u ma ns, t otal b o d y ir o n c o nte nt is a p pr o xi matel y 4 0 t o 5 0 m g/ k g b o d y wei g ht, 
wit h m ost of t he ir o n ( 3 0 m g/ k g) c o ntai ne d i n circ ulati n g re d bl o o d cells ( R B Cs) s uc h as 
he m o gl o bi n; 5 t o 6 m g/ k g is prese nt i n tiss ues i n a variet y of he me c o m p o u n ds, e nz y mes wit h 
ir o n-s ulf ur c o m ple xes, a n d ot her ir o n -de pe n de nt e nz y mes; 5  t o 1 2 m g/ k g is st ore d as ferriti n a n d 
he m osi deri n i n t he li ver, b o ne marr o w, s plee n, a n d m uscle; a n d a s mall fracti o n ( 3 m g/ k g) circ ulates 
i n t he plas ma.  I ncreases i n tiss ue le vels of ir o n ≥ 2 0 m g/ k g are ass ociate d wit h s y mpt o matic ir o n 
o verl oa d ( G or de u k  1 9 8 7, M u n oz  2 0 0 9), wit h p ote ntial da ma ge t o t he li ver, heart, a n d e n d ocri ne 
gla n ds, a n d e ve n deat h ( H off bra n d  2 0 1 2). 
T he pri mar y treat me nt f or here ditar y  he m oc hr o mat osis  is p hle b ot o m y (Bac o n 2 0 1 1 ).  
A p pr o xi matel y 9 0 % t o 1 0 0 % of patie nts will ac hie ve ir o n de pleti o n wit h t his treat me nt 
(Hic ke n  2 0 0 3), alt h o u g h 2 t o 3 years of wee kl y or bi wee kl y p hle b ot o m y ma y be re q uire d t o 
a de q uatel y re d uce ir o n st ores i n patie nts wit h t otal b o d y ir o n > 3 0 g ( Bac o n 2 0 1 1).   T hereafter, 
p hle b ot o m y ca n be st o p pe d a n d t he patie nt assesse d f or mai nte na nce t hera p y.  T he fre q ue nc y of 
mai nte na nce t he ra p y varies b y i n di vi d ual patie nts, wit h s o me re q uiri n g m o nt hl y p hle b ot o m y a n d 
ot hers re q uiri n g p hle b ot o m y o nl y o nce or t wice a year.  S o me patie nts de vel o p i nt olera nce t o 
p hle b ot o m y, a n d patie nt c o m plia nce wit h mai nte na nce p hle b ot o m y has bee n s h o w n t o dec li ne o ver 
ti me. 
Ot her  treat me nts t hat ma y  be use d i n cases of se vere ir o n o verl oa d or i n patie nts  i nt olera nt of 
p hle b ot o m y  i ncl u de er yt hr oc yta p heresis,  defer o xa mi ne  c helati o n, or deferasir o x  c helati o n 
(A da ms  2 0 1 0).  T hese treat me nts are ass ociate d wit h t he ris k of si g nifica nt si de effects, s uc h as 

Pr ot oc ol LJ 4 0 1- H H 0 1  
LJ P C - 4 0 1 
2 5 
La J olla P har mace utical - C o nfi de ntial  
Date :  1 4  Dece m ber  2 0 1 8  ( Versi o n 6. 0) 
Acr oss all d ose gr o u ps, t he m ost fre q ue ntl y occ urri n g A Es b y preferre d ter m ( P T) were i njecti o n site 
reacti o ns ( 1 2 patie nts [ 6 6. 7 %]), na usea ( 2 patie nts [ 1 1. 1 %]), A L T  i ncrease d ( 2 patie nts [ 1 1. 1 %]), 
decrease d a p petite ( 2 patie nts [ 1 1. 1 %]) a n d h y p oest hesia ( 2 patie nts [ 1 1. 1 %]).  T he fre q ue nc y of 
i njecti o n site reacti o ns i n eac h d ose gr o u p was 0 i n 3 ( 0 %) i n  t he 1- m g gr o u p, 3 o ut of 3 ( 1 0 0 %) i n 
t he 5- m g gr o u p, 0 i n 3 ( 0%) i n  t he 1 0- m g gr o u p, 6 o ut of 6 ( 1 0 0 %) i n t he 2 0- m g gr o u p, a n d 3 o ut of 
3 ( 1 0 0 %) i n t he 3 0 - m g gr o u p.  All i njecti o n site reacti o ns were mil d i n se verit y a n d res ol ve d b y t he 
e n d of t he st u d y ( Da y 2 2).  T he mea n a n d me dia n d urati o n of i njecti o n site reacti o ns were as 
f oll o ws:  5 m g ( 1. 0 a n d 1. 0 da ys), 2 0 m g ( 2. 0 a n d 1. 0 da ys), a n d 3 0 m g ( 1 4. 8 a n d 4. 0 da ys). 
All sa m ples were c o nfir me d ne gati ve f or a nti - dr u g a nti b o dies t o LJ P C- 4 0 1. 
3. 3. 2.  
L J 4 0 1- N H V 0 1  
T he P hase 1 cli nical trial LJ 4 0 1- N H V 0 1  was a ra n d o mize d, d o u ble- bli n d, place b o-c o ntr olle d, 
si n gle-ce nter st u d y t o deter mi ne t he safet y, t olera bilit y, P K, ser u m ir o n ki netics, a n d 
i m m u n o ge nicit y of escalati n g si n gle d oses of LJ P C - 4 0 1 i n 3 2 healt h y a d ult s u bjects.  T he st u d y 
e nr olle d s u bjects i n 4 d ose gr o u ps of 8 s u bjects per c o h ort, wit h 6 s u bjects assi g ne d t o LJ P C - 4 0 1 
a n d 2 s u bjects assi g ne d t o place b o i n eac h c o h ort.  T he starti n g d ose was 5 m g of LJ P C - 4 0 1 or 
place b o; s u bse q ue nt d ose gr o u ps recei ve d 1 0 m g, 2 0 m g, a n d 3 0 m g, res pecti vel y.  S u bjects 
recei ve d bet wee n o ne a n d t hree 1- m L S C i njecti o ns t o deli ver t he desire d d ose le vel.  LJ P C - 4 0 1 
c o nce ntrati o n was eit her 5 m g/ m L or 1 0 m g/ m L.  F or data a nal ysis p ur p oses, place b o s u bjects f or all 
c o h ort gr o u ps were p o ole d. 
A decrease i n ser u m ir o n le vels c o m pare d t o baseli ne was o bser ve d i n all 4 d ose gr o u ps, wit h mea n 
ma xi m u m re d ucti o n of 3 3 % t o 6 5 % at 8- h o urs p ost d ose.  Ser u m ir o n le vels ret ur ne d t o baseli ne 
bef ore 4 8 h o urs.  A si g nifica nt d ose res p o nse was o bser ve d, wit h lar ger re d ucti o ns i n ser u m ir o n 
ge nerall y ass ociate d wit h i ncreases i n d ose u p t o 2 0 m g.  T here was n o a p pare nt differe nce i n t he 
ma xi m u m re d ucti o n bet wee n t he 2 0 a n d 3 0 m g d ose le vels.  Ferriti n, TI B C, tra nsferri n, a n d T S A T 
were i ncrease d fr o m baseli ne at Da y 8 f or all treat me nt  gr o u ps.  T here was n o tre n d ass ociate d wit h 
a n i ncrease i n LJ P C - 4 0 1 d ose a n d t he a m o u nt of i ncrease i n a n y of t hese ir o n para meters.  
U nsat urate d ir o n bi n di n g ca pacit y ( U I B C) le vels s h o we d n o tre n ds i n c ha n ges fr o m baseli ne at 
Da y  8. 
T E A Es wer e re p orte d b y all 2 4 s u bjects ( 1 0 0 %) i n t he LJ P C - 4 0 1 d ose gr o u ps a n d 2 of 8 s u bjects 
( 2 5 %) i n t he place b o gr o u p.  All T E A Es were c o nsi dere d mil d ( Gra de 1) i n se verit y, a n d n o ne were 
dee me d seri o us or le d t o earl y disc o nti n uati o n or deat h.  T he n u m ber of T E A Es was si mi lar a m o n g 
all d ose gr o u ps.  Acr oss all d ose gr o u ps, t he m ost fre q ue ntl y re p orte d A Es were i njecti o n site 
reacti o ns ( 2 4 s u bjects [ 1 0 0 %] LJ P C - 4 0 1 a n d 1 s u bject [ 1 2. 5 %] place b o), cat heter site p hle bitis 
( 3 s u bjects [ 1 2. 5 %] LJ P C - 4 0 1), hea dac he ( 2 s u bjects [ 8. 3%] LJ P C - 4 0 1), pres y nc o pe ( 1 s u bject 
[ 1 2. 5 %] place b o), a n d a n xiet y, na usea, a n d ha n d der matitis ( 1 s u bject [ 4. 2 %] LJ P C - 4 0 1 eac h).  All 
i njecti o n site reacti o ns were mil d i n se verit y, a n d all b ut 1 res ol ve d bef ore t he e n d of t he st u d y.  T he 
mea n a n d me dia n d urati o n of i njecti o n site reacti o ns i n t he 5 d ose gr o u ps were as f oll o ws:  place b o 
( 1. 0, 1. 0 da ys), 5 m g ( 1. 0, 1. 0 da ys), 1 0 m g ( 5. 6, 8. 0 da ys), 2 0 m g ( 1 3. 3, 1 5. 5 da ys), a n d 3 0 m g 
( 1 1. 7, 8. 0 da ys). 
All sa m ples were c o nfir me d ne gati ve f or a nti - dr u g a nti b o dies t o LJ P C- 4 0 1. 

Pr ot oc ol LJ 4 0 1- H H 0 1  
LJ P C - 4 0 1 
2 6 
La J olla P har mace utical - C o nfi de ntial  
Date :  1 4  Dece m ber  2 0 1 8  ( Versi o n 6. 0) 
3. 3. 3.  
L J 4 0 1- N H V 0 2  
T he P hase 1 cli nical trial LJ 4 0 1- N H V 0 2  is a ra n d o mize d, d o u ble- bli n d, place b o-c o ntr olle d, si n gle 
a n d m ulti ple d ose escalati o n st u d y t o assess t he safet y a n d t olera bilit y of LJ P C - 4 0 1 i n healt h y a d ult 
s u bjects. 
T he st u d y e nr olle d 2 1 s u bjects t otal.  I n t he si n gle d ose ar m of t he st u d y, 1 0 s u bjects recei ve d 
LJ P C - 4 0 1 a n d 3 s u bjects recei ve d place b o.  I n t he m ulti ple d ose ar m of t he st u d y, 6 s u bjects 
recei ve d LJ P C - 4 0 1 a n d 2 s u bjects recei ve d place b o 4 ti mes o ver a 2- wee k peri o d.  Res ults 
de m o nstrate d t hat LJ P C - 4 0 1 was well t olerate d at all a d mi nistere d d oses ( 4 m g, 1 0 m g a n d 2 0 m g).  
T here were n o d ose- li miti n g t o xicities at a n y d ose.  C o nsiste nt wit h b ot h c o m plete d P hase 1 st u dies, 
t he m ost c o m m o n a d verse e ve nt ( A E) was i njecti o n site reacti o n.  B ot h se verit y a n d d urati o n of 
t hese s ki n reacti o ns were si milar i n t his st u d y i n b ot h t he si n gle a n d m ulti ple d osi n g c o h orts 
c o m pare d t o t he pre vi o us f or m ulati o n use d i n st u dies LJ 4 0 1- T P P 0 1  a n d LJ 4 0 1- N H V 0 1 . 
3. 4.  
Cli nic al R ati o n ale f or t he L J 4 0 1 -H H 0 1 St u d y  
Patie nts wit h here ditar y  he m oc hr o mat osis  a bs or b t o o m uc h ir o n fr o m t heir diet (NI H  2 0 1 7).  H u ma n 
ir o n eli mi nati o n is li mite d a n d u na ble t o c o m pe nsate f or a n a b n or mal state of ir o n a bs or pti o n.  T his 
e xcess ir o n ca n e ve nt uall y da ma ge tiss ues a n d or ga ns, partic ularl y t he s ki n, heart, li ver, pa ncreas, 
a n d j oi nts.  T he pri mar y treat me nt f or here ditar y  he m oc hr o mat osis  is p hle b ot o m y.  T y picall y, 
p hle b ot o m y is i nitiall y perf or me d at wee kl y or t wice-wee kl y i nter vals u ntil desire d ir o n le vels are 
attai ne d, a n d t he n perf or me d less ofte n ( 2 t o 4 ti mes per year) o n a n i n defi nite basis ( C o u ns yl  2 0 1 7).  
P hle b ot o m y is i nc o n ve nie nt a n d te di o us, a n d patie nt c o m plia nce decreases o ver ti me ( Hic ke n  2 0 0 3).  
Hic ke n et al ( 2 0 0 3) re p orte d t hat 5 3 % ( 7 5/ 1 4 2 patie nts) of patie nts beca me n o nc o m plia nt at s o me 
ti me d uri n g mai nte na nce t hera p y, less t ha n 5 0 % of patie nts c o m plie d wit h mai nte na nce t hera p y b y 
t he e n d of t heir si xt h year after ac hie vi n g ir o n de pleti o n, a n d t hat a vera ge c o m plia nce wit h 
mai nte na nce t hera p y decrease d 6. 8 % a n n uall y.  Ot her treat me nts f or ir o n o verl oa d, i ncl u di n g 
er yt hr oc yta p heresis a n d c helati o n t hera p y ha ve si g nifica n t a n d un desira ble si de effects.  
T he ir o n-re g ulati n g effects of he pci di n, w hic h is re d uce d i n patie nts wit h here ditar y  
he m oc hr o mat osis , ma ke it a p ote ntiall y be neficial t hera pe utic f or t he treat me nt of here ditar y  
he m oc hr o mat osis .  LJ P C - 4 0 1, a s y nt hetic e q ui vale nt of t he e n d o ge n o us circ ulati n g pe pti de 
he pci di n- 2 5, is e x pecte d t o re d uce ir o n o verl oa d i n t his patie nt p o p ulati o n.  T he safet y pr ofile t o date 
i n dicates t hat t he pr o d uct is well t olerate d, wit h i njecti o n site reacti o n bei n g t he m ost fre q ue ntl y 
re p orte d A E .  I n a d diti o n, t he o nce- wee kl y si n gle- d ose a d mi nistrati o n, is e x pecte d t o be less 
b ur de ns o me t ha n sta n dar d p hle b ot o m y wit h a lar ge b ore nee dle. 
3. 4. 1.  
R ati o n ale f or t he St u d y Desi g n f or St u d y L J 4 0 1- H H 0 1  
T his st u d y was desi g ne d t o e val uate t he efficac y of LJ P C - 4 0 1 f or t he treat me nt of here ditar y  
he m oc hr o mat osis  b y s h o wi n g a si g nifica nt a n d cli nicall y mea ni n gf ul c ha n ge i n T S A T le vels.  T S A T 
was c h ose n as a n a p pr o priate e n d p oi nt f or assessi n g t he cli nical efficac y of LJ P C - 4 0 1 si nce it 
c o nsi ders b ot h t he ir o n le vel a n d t he TI B C  (A A C C  2 0 1 5).  N o ntra nsferri n b o u n d ir o n ( N T BI), t he 
t o xic f or m of ir o n, has bee n c orrelate d wit h car diac disease (Pi ga  2 0 1 3), a n d T S A T c orrelates wit h 
b ot h car di ac disease a n d le vels of N T BI.  
T he st u d y will e m pl o y a ra n d o mize d, place b o-c o ntr olle d, si n gle- bli n d desi g n.  Ra n d o mizati o n will 
be use d t o mi ni mize bias i n t he assi g n me nt of patie nts t o treat me nt gr o u ps b y i ncreasi n g t he 

Pr ot oc ol LJ 4 0 1- H H 0 1  
LJ P C - 4 0 1 
2 7 
La J olla P har mace utical - C o nfi de ntial  
Date :  1 4  Dece m ber  2 0 1 8  ( Versi o n 6. 0) 
li keli h o o d t hat k n o w n a n d u n k n o w n patie nt attri b utes (e g, de m o gra p hic a n d baseli ne c haracteristics) 
are e ve nl y bala nce d, t here b y e n ha nci n g t he vali dit y of statistical c o m paris o ns a cr oss treat me nt 
gr o u ps ( LJ P C - 4 0 1 vers us place b o).  I n vesti gat ors will n ot be bli n de d t o treat me nt ar m or T S A T 
res ults s o t he y ca n a dj ust st u d y dr u g per t he d ose a dj ust me nt criteria if nee de d. 
Ra n d o mizati o n will occ ur i n a 1: 1 rati o a n d will be stratifie d b y baseli ne T S A T ( > 4 5 % t o 7 0 % 
vers us > 7 0 %) a n d p hle b ot o m y fre q ue nc y o ver t he last 1 2 m o nt hs ( 0 t o 3 vers us >  3), si nce 
a de q uatel y treate d patie nts ha ve a better pr o g n osis t ha n t h ose treate d i na de q uatel y ( D uc hi ni  2 0 1 7). 
A treat me nt peri o d of 1 6 wee ks was c o nsi dere d a de q uate t o e val uate t he efficac y of LJ P C - 4 0 1 a n d 
ser ve as t he basis f or t he desi g n of a P hase 3 st u d y.  T he decisi o n t o i ncl u de 1 p hle b ot om y at Da y  1 
( pre d ose) was ma de i n c o nsi derati o n of t he li kel y ele vati o ns i n T S A T a n d ferriti n i n t he st u d y 
p o p ulati o n at baseli ne. 
T he d ose ra n ge t hat will be use d i n t his st u d y ( Secti o n 5. 3 ) has bee n e val uate d i n 3 P hase 1 cli nical 
trials.  T he 5- m g starti n g d ose was selecte d f or t his st u d y base d o n data fr o m pre vi o us st u dies i n 
patie nts a n d healt h y v ol u nteers ( Secti o n  3. 3 ) a n d has bee n pre vi o usl y teste d i n patie nts wit h ir o n 
o verl oa d ( Secti o n  3. 3. 1 ).  T he re d ucti o n i n T S A T i n t hese patie nts at 5 m g was a p pr o xi matel y 2 7 %, 
w hic h occ urre d at 8 t o 1 2 h o urs a n d ret ur ne d t o baseli ne b y 7 2 t o 9 6 h o urs.  LJ P C- 4 0 1 5 m g was 
well t olerate d a n d pr o vi de d a mi ni mal efficac y of re d ucti o n i n T S A T.  As s uc h, t he first d ose is 
li kel y t o be b ot h safe a n d s u b-t hera pe utic wit h a n all o wa nce f or a dj ust me nt.  T he ma xi m u m d ose of 
2 0 m g was c h ose n f or t his st u d y base d o n t he res ults of patie nt St u d y LJ 4 0 1- T T P 0 1 t hat s h o we d a 
lar ger d ose-resp o nse/re d ucti o n i n ser u m ir o n was ge nerall y ass ociate d wit h i ncreasi n g d ose u p t o 
2 0 m g.  LJ P C- 4 0 1 has bee n e val uate d at d oses as hi g h as 3 0 m g ( healt h y v ol u nteer LJ 4 0 1- N H V 0 1); 
h o we ver, i n St u d y LJ 4 0 1- T T P 0 1, it was o bser ve d t hat patie nts wit h he m oc hr o mat osis ha d a l o wer 
mea n ser u m ir o n le vel at baseli ne c o m pare d wit h patie nts wit h he m o gl o bi n o pat hies.  T his is 
c o nsiste nt wit h t he hi g her mea n e n d o ge n o us he pci di n c o nce ntrati o n o bser ve d i n patie nts wit h 
he m oc hr o mat osis.  As s uc h, LJ P C- 4 0 1 2 0 m g is c o nsi dere d t he a p pr o priate ma xi m u m d ose f or t he 
patie nt p o p ulati o n i n t his st u d y.  B ot h t he ma xi m u m d ose ( 2 0 m g) a n d d ose- escalati o n pla n w ere 
well -t olerate d a n d efficaci o us i n b ot h P hase 1 st u dies.  
A 3 0- da y f oll o w- u p visit was c h ose n base d o n re g ulat or y g ui da nce f or a ssessi n g a n d m o nit ori n g 
safet y, i ncl u di n g p ote ntial i m m u n o ge nic effect, i n patie nts w h o ha ve disc o nti n ue d or c o m plete d 
cli nical st u dies of i n vesti gati o nal a ge nts wit h pr o m pt acti o n a n d relati vel y s h ort eli mi nati o n 
half- li ves (F o o d a n d Dr u g A d mi nistrati o n [ F D A ], 2 0 1 0). 
3. 4. 2.  
R ati o n ale f or Usi n g Ir o n Dis or ders I nstit ute P hle b ot o m y G ui deli nes  
T his st u d y will use t he 2 0 1 1 Ir o n Dis or ders I nstit ute (I DI) p hle b ot o m y g ui deli nes as t he basis f or 
defi n i n g t he criteria f or p hle b ot o m y.  T he I DI is part nere d wit h t he U nite d States Ce nters f or 
Disease C o ntr ol a n d Pre ve nti o n, t he Nati o nal I nstit utes of Healt h, a n d m ulti ple patie nt a d v ocac y 
gr o u ps f or pe o ple wit h ir o n dis or ders.  Ir o n Dis or ders I nstit ute pr o vi des cli nical s u p p ort, ser vices, 
a n d e d uca ti o nal i nf or mati o n.  T he I DI Me dical a n d Scie ntific A d vis or y B oar d is c o m prise d of 
e x perts i n ir o n meta b olis m a n d ir o n bala nce.  T he materials p u blis he d b y I DI c o ntai n refere nce 
ra n ges, dia g n osis al g orit h ms, dia g n ostic ai ds, t hera pe utic a p pr oac hes, a n d ge n etic a n d diet 
i nf or mati o n.  T his c o nte nt has bee n peer-re vie we d a n d a p pr o ve d b y me m bers of t he I DI Me dical a n d 
Scie ntific A d vis or y B oar d. 

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I n a d diti o n, use of t he T S A T criteria of t he I DI p hle b ot o m y g ui deli nes will e ns ure t hat patie nts are 
prescri be d p hle b ot o m y i n a c o nsiste nt ma n ner acr oss b ot h gr o u ps a n d i m pr o ves patie nt safet y as t he 
rec o m me n dati o ns are e n d orse d b y me dical a n d scie ntific e x perts. 

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4.  
T RI A L O B J E C TI V E S A N D  P U R P O S E  
T o e val uate t he effect of o nce- wee kl y d osi n g of LJ P C - 4 0 1 f or 1 6 wee ks  o n t he f oll o wi n g para meters 
i n a d ult patie nts wit h here ditar y he m oc hr o mat osis.  
4. 1.  
Pri m ar y O bjecti ve  
T o c o m pare t he effect of LJ P C - 4 0 1 vers us place b o  o n tra nsferri n sat urati o n ( T S A T) i n a d ult patie nts 
wit h here dit ary he m oc hr o mat osis. 
4. 2.  
Sec o n d ar y O bjecti ves  
•  T o c o m pare t he effect of LJ P C - 4 0 1 vers us place b o  o n p hle b ot o m y re q uire me nts. 
•  T o esta blis h t he s afet y a n d t olera bilit y of LJ P C - 4 0 1 vers us place b o  i n a d ult patie nts wit h 
here dit ary he m oc hr o mat osis. 
•  T o c o m pare t he effect of LJ P C - 4 0 1 vers us place b o o n s er u m ferriti n . 
4. 3.  
E x pl or at or y O bjecti ves  
•  T o c o m pare t he effect of LJ P C - 4 0 1 vers us place b o o n ser u m ir o n para meters . 
•  T o c o m pare t he effect of LJ P C - 4 0 1 vers us place b o o n t h yr oi d f u ncti o n. 
•  T o c o m pare t he effect of LJ P C - 4 0 1 vers us place b o o n li ver f u ncti o n. 
•  T o c o m pare t he effect of LJ P C - 4 0 1 vers us place b o o n gl yce mic c o ntr ol. 
•  T o c o m pare t he effect of LJ P C - 4 0 1 vers us place b o o n re d bl o o d cell ( R B C) para meters 
i ncl u di n g he m o gl o bi n c o nce ntrati o n, R B C  c o u nt, a n d re d cell distri b uti o n wi dt h ( R D W). 
•  T o c o m pare t he effect of LJ P C - 4 0 1 vers us place b o o n q ualit y of life as meas ure d b y  
Q ualit y of Life Q uesti o n naire s:  3 6-Ite m S h ort F or m (S F - 3 6 v 2), t he Wester n O ntari o a n d 
Mc Master U ni versities Oste oart hritis I n de x  (W O M A C) , a n d t he m o difie d Dreisler 
i n dices f or art hritis. 

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LJ P C - 4 0 1 
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Date :  1 4  Dece m ber  2 0 1 8  ( Versi o n 6. 0) 
5.  
I N V E S TI G ATI O N A L P L A N  
5. 1.  
O ver all St u d y Desi g n  
T his st u d y is a m ultice nter, ra n d o mize d, place b o-c o ntr olle d, si n gle- bli n d st u d y.  T he pri mar y 
o bjecti ve of t he st u d y is t o e val uate t he effect of LJ P C - 4 0 1 o n T S A T i n a d ults wit h here ditar y 
he m oc hr o mat osis. 
Eli gi ble patie nts will be ra n d o mize d o n a 1 : 1 sc he d ule a n d bli n de d t o st u d y treatme nt , LJ P C - 4 0 1 or 
place b o .  Ra n d o mizati o n will be stratifie d b y baseli ne T S A T ( > 4 5 % t o 7 0 % vers us > 7 0 %) a n d 
p hle b ot o m y fre q ue nc y o ver t he last 1 2 m o nt hs ( 0 t o 3 vers us > 3). 
All ra n d o mize d patie nts will recei ve sta n dar d of care t hera pe utic p hle b ot o m y  ( 5 0 0 cc or a p pr o priate 
f or wei g ht) o n Da y 1  ( pre d ose).  T hereafter, p hle b ot o m y decisi o ns b y t he I n vesti gat or  will be base d 
o n t he patie nt’s fasti n g T S A T res ults c ollecte d at Wee k  4 ( Da y 2 3); Wee k 8 ( Da y 5 1); Wee k 1 2 
( Da y 7 9); a n d Wee k 1 6 ( Da y 1 0 7); a n d base d o n t he T S A T criteria of t he I DI p hle b ot o m y g ui deli nes 
f or patie nts wit h here ditar y he m oc hr o mat osis.  If a p hle b ot o m y is i n dicate d, base d o n t he T S A T 
criteria of t he I DI g ui deli nes, t he patie nt s h o ul d recei ve p hle b ot o m y treat me nt pre d ose, o n or bef ore 
t he f oll o wi n g visit. 
I n vesti gat ors are n ot bli n de d t o treat me nt ar m or T S A T res ults  s o t he y ca n a dj ust st u d y dr u g per t he 
d ose a dj ust me nt criteria if nee de d . 
T he pri mar y efficac y a nal ysis will ta ke place after all o n-st u d y patie nts ha ve c o m plete d t he Wee k  1 6 
assess me nts  ( or ha ve wit h dra w n fr o m t he st u d y earl y). 
5. 2.  
N u m ber of P atie nts  
A p pr o xi matel y 6 8 t o 7 6 patie nts  are pla n ne d t o be e nr olle d  a n d ra n d o mize d acr oss a p pr o xi matel y 
3 0 sites t o e ns ure t hat at least 4 8 patie nts c o m plete t he Wee k 1 6 assess me nts a n d are i ncl u de d i n t he 
pri mar y effi cac y a nal ysis ( Secti o n  1 2. 2 ).  All pa tie nts m ust meet t he eli gi bilit y criteria o utli ne d i n 
Secti o n  6 .  O ne rescree ni n g f or eli gi bilit y will be all o we d f or eac h patie nt.  As i ncl usi o n criteria are 
la b orat or y para meters t hat are d y na mic i n t his p o p ulati o n, ad diti o nal rescree ns ma y be all o we d u p o n 
a p pr o val fr o m t he Me dical M o nit or.  If rescree ne d, t he patie nt will kee p t he pre vi o usl y assi g ne d 
scree ni n g n u m ber. 
5. 3.  
Tre at me nt Assi g n me nt  
Patie nts will be  d ose d o nce - wee kl y wit h  LJ P C -4 0 1  or place b o a d mi nistere d S C f or 1 6 wee k s.  
LJ P C - 4 0 1 d ose will start at 5 m g at Wee k 1 a n d i ncrease t o 1 0 m g at Wee k 2.  Refer t o Secti o n  5. 4  
f or d ose a dj ust me nts o utsi de of t hese fi xe d d oses.  F or  t h ose patie nts ra n d o mize d t o place b o, a 
s yri n ge of 0. 9 % s o di u m c hl ori de i njecti o n, U nite d States P har mac o p oeia ( U S P; or e q ui vale nt) will 
be pre pare d b y t he st u d y p har macist or desi g nee.  T o mai ntai n t he st u d y si n gle- bli n d, s yri n ges wit h 
st u d y dr u g ( place bo a n d acti ve dr u g) will be i de ntical .  Refer t o t he st u d y s pecific P har mac y Ma n ual 
f or detaile d g ui da nce.  

Pr ot oc ol LJ 4 0 1- H H 0 1  
LJ P C - 4 0 1 
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La J olla P har mace utical - C o nfi de ntial  
Date :  1 4  Dece m ber  2 0 1 8  ( Versi o n 6. 0) 
5. 4.  
D ose A dj ust me nt Criteri a  
D osi n g A dj ust me nts:  
•  Wee k 1:  5 m g LJ P C - 4 0 1 or place b o 
•  Wee k 2:  1 0 m g LJ P C - 4 0 1 or place b o 
•  Wee k 3 :  1 0 m g LJ P C- 4 0 1 or place b o 
Wee k 3:  Fasti n g T S A T ( p ost d ose 2 4 [ ± 4] h o urs), ie, 2 0 t o 2 8 h o urs, deter mi nes t he Wee k 4 d ose:  
− If t he T S A T  is > 4 5 %, d ose i ncreased t o 2 0 m g LJ P C - 4 0 1 or place b o 
− If t he T S A T is ≤ 4 5 %, d ose re mai ns at 1 0 m g LJ P C- 4 0 1 or place b o 
•  Wee k 4 :  LJ P C - 4 0 1 ( or place b o ) d ose as i n dicate d b y Wee k 3 fasti n g T S A T ( 1 0 t o 2 0 m g 
LJ P C - 4 0 1 or place b o) 
•  At Wee ks 9 a n d 1 3 (after Wee ks 8 a n d 1 2 fasti n g T S A T res ults are a vaila ble ): 
− Mai ntai n or i ncrease d ose t o 2 0 m g if T S A T is > 4 5 % 
− Mai ntai n d ose ( 1 0 or 2 0 m g ) if T S A T re mai ns ≤ 4 5 %, a n d n o d ose re d ucti o n is 
re q uire d f or t o xicit y (refer t o Secti o n 5. 4. 1 ) 
•  F or d o w n titrati o n, f oll o w t he safet y criteria o utli ne d i n Secti o n  5. 4. 1 . 
I m p ort a nt G ui deli nes: 
1.  T he last ce ntral la b orat or y fasti n g T S A T res ult at Wee k  3 ( Da y 1 6), Wee k 8 ( Da y 5 1) , a n d 
Wee k 1 2 ( Da y 7 9) will be use d t o deter mi ne if a d ose a dj ust me nt is nee de d at Wee ks  4, 9, 
a n d 1 3.  T S A T  f or d ose a dj ust me nts m ust  be c ollecte d 2 4 ( ± 4) h o urs p ost d ose. 
2.  If fasti n g T S A T le vel is greater t ha n 4 5 %  c ollecte d at p ost d ose 2 4 ( ± 4) h o urs o n Wee k 4 
( Da y 2 3); Wee k 8 ( Da y 5 1); Wee k 1 2 ( Da y 7 9); a n d Wee k 1 6 ( Da y 1 0 7), a p hle b ot o m y 
( 5 0 0 cc or a p pr o priate f or wei g ht) is i n dicate d pre d ose, o n or bef ore t he f oll o wi n g visit.     
3.  R o u n d T S A T wit h deci mal val ues usi n g t he sta n dar d r o u n di n g r ule. 
T he p har macist, or desi g nee, will pre pare t he st u d y dr u g ( LJ P C - 4 0 1 or place b o) t o e ns ure t he patie nt  
will re mai n bli n de d.  Refer t o t he st u d y s pecific P har mac y Ma n ual  f or detaile d g ui da nce. 
5. 4. 1.  
S afet y Criteri a f or A dj ust me nt or St o p pi n g D oses  
F or eac h i n di vi d ual patie nt, t he safet y criteria use d t o a dj ust (re d uce) d osi n g i ncl u de 1 or m ore of t he 
f oll o wi n g: 
1.  i njecti o n site reacti o n(s) se verit y gra de of se vere 
2.  patie nt ca n n ot or will n ot t olerate assi g ne d i njecti o ns (refer t o Secti o n  5. 4  f or d ose 
a dj ust me nt directi o ns)  
F or eac h i n di vi d ual patie nt, t he safet y criteria use d t o st o p d oses i ncl u de 1 or m ore of t he f oll o wi n g: 
1.  T E A Es, i ncl u di n g i njecti o n site reacti o n(s) se verit y gr a de of se vere or hi g her  
2.  patie nt ca n n ot or will n ot t olerate S C i njecti o n(s)  

Pr ot oc ol LJ 4 0 1- H H 0 1  
LJ P C - 4 0 1 
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Date :  1 4  Dece m ber  2 0 1 8  ( Versi o n 6. 0) 
3.  cli nicall y si g nifica nt la b orat or y para meters, i ncl u di n g if T S A T is less t ha n 1 0 %  (if t his 
occ urs, c o ns ult t he Me dical M o nit or)  
5. 5.  
Criteri a f or St u d y Ter mi n ati o n  
T his st u d y ma y be pre mat urel y ter mi nate d if i n t he o pi ni o n of La  J olla, t here is s ufficie nt reas o na ble 
ca use.  Writte n n otificati o n d oc u me nti n g t he reas o n f or st u d y ter mi nati o n w o ul d be pr o vi de d t o t he 
I n vesti gat ors b y La  J olla.  Circ u msta nces t hat ma y warra nt ter mi nati o n i ncl ude, b ut are n ot li mite d 
t o: 
•  Deter mi nati o n of u ne x pecte d, si g nifica nt, or u nacce pta ble ris k t o patie nts 
•  Fail ure t o e nr oll st u d y  patie nts at a n acce pta ble rate  
•  I ns ufficie nt a d here nce t o pr ot oc ol re q uire me nts 
•  I ns ufficie nt a n d/ or u ne val ua ble data 
•  Pla ns t o m o dif y, s us pe n d, or disc o nti n ue de vel o p me nt of t he st u d y dr u g 
5. 6.  
Sc he d ule of Assess me nts  
T he pr oce d ures a n d ti mi n g of t he assess me nts sc he d ule d f or t his st u d y are dis pla ye d i n Ta ble  3.  
Efficac y a n d safet y assess me nts are descri be d i n Secti o n  9  a n d Secti o n  1 0 , res pecti vel y.  Refer t o 
Secti o n  1 0. 1. 6  lists of pr ot oc ol- s pecifie d la b orat or y a nal ytes. 
 

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Ge ner al I nstr ucti o ns:  
All assess me nts m ust be perf or me d pri or t o d osi n g u nless ot her wise s pecifie d.  
Patie nts are n ot t o eat a n y f o o d or dri n k a n y be vera ges, e xce pt water, f or at least 6 h o urs pri or t o 
c ollecti n g bl o o d f or la b orat or y tests i ncl u di n g ir o n st u dies (I m m u n o ge nicit y/ P K a n d pre g na nc y test  
sa m ples are n ot re q uire d t o be fasti n g). 
Fr o m Wee ks 2 t hr o u g h 1 7 t here is a ± 2- da y wi n d o w f or visits; o nce t he visit occ urs, t he patie nt 
s h o ul d ret ur n t o t he re g ular i nter val sc he d ule. 
Assess me nts:  
1.  F or patie nts w h o wit h dra w earl y, all Wee k 1 6 pr oce d ures pl us a 1 2-lea d E C G a n d uri ne 
pre g na nc y test (fe males of c hil d - beari n g p ote ntial o nl y) will be perf or me d, t o t he e xte nt 
p ossi ble, f or t he Earl y Wit h dra wal Visit. 
2.  T he E O S f oll o w-u p visit will occ ur 3 0 da ys ( + 3 da ys; a p pr o xi matel y Wee k 2 0 ) after t he last 
d ose of st u d y dr u g. 
3.  C o nfir m i ncl usi o n/e xcl usi o n criteria at Scree ni n g a n d o n Wee k 1/ Da y  1 ( pre d ose).  
Scree ni n g l a b orat or y res ults m ust be recei ve d a n d re vie we d f or eli gi bilit y pri or t o d osi n g.  
4.  Ra n d o mizati o n m ust occ ur after i ncl usi o n/e xcl usi o n criteria are c o nfir me d. 
5.  Hei g ht will be perf or me d at S cree ni n g o nl y; wei g ht will be perf or me d at Scree n i n g a n d 
Wee k  1 6. 
6.  Vitals will i ncl u de bl o o d press ure, heart rate, res pirati o n rate , a n d b o d y te m perat ure.  Bl o o d 
press ure will be assesse d after t he patie nt has bee n resti n g i n t he sitti n g p ositi o n f or at least 
5 mi n utes. 
7.  Rec or d all me dicati o ns ta ke n a n d a n y pr oce d ures perf or me d, be gi n ni n g 1 4  da ys pri or t o 
Scree ni n g .  Starti n g Wee k 2, rec or d all ne w or c ha n ges t o c o nc o mita nt me dicati o ns t hr o u g h 
t he f oll o w-u p visit t hat will  occ ur 3 0 da ys ( + 3 da ys) after t he last d ose of st u d y dr u g. 
8.  Rec or d a n y A Es  a n d S A Es  starti n g at c o nse nt.  Re p ort a n y S A Es per Secti o n  1 1. 3. 2 . 
9.  Patie nts will be d ose d o nce - wee kl y.  Refer t o  Secti o n  5. 4  f or d ose a dj ust me nt criteria. 
1 0.  1 2- lea d E C Gs will be c ollecte d i n tri plicate ( ≥ 1 mi n ute a part).  T he  Scree ni n g E C G m ust be 
perf or me d wit hi n 3 0 da ys pri or t o t he first d ose of st u d y dr u g.  A b n or malities n ote d at 
Scree ni n g s h o ul d be i ncl u de d i n t he me dical hist or y.  A d diti o nal E C Gs will be c ollecte d if 
cli nicall y i n dicate d ( ie, pal pitati o ns, li g ht hea de d ness).  If a patie nt wit h dra ws  fr o m t he st u d y 
earl y, a 1 2 -lea d E C G will be perf or me d as part of t he Earl y Wit h dra wal pr oce d ures (if 
p ossi ble). 
1 1.  All ra n d o mize d patie nts will recei ve a sta n dar d of care t hera pe utic p hle b ot o m y ( 5 0 0 cc or 
a p pr o priate f or wei g ht ) o n Da y  1 ( pre d ose).  T hereafter, p hle b ot o m y decisi o ns b y t he 
I n vesti gat or will be base d o n t he patie nt’s fasti n g T S A T res ults c ollecte d p ost d ose at 
Wee ks  4 ( Da y 2 3); Wee k 8 ( Da y 5 1); Wee k 1 2 ( Da y 7 9); a n d Wee k 1 6 ( Da y 1 0 7);  a n d base d 
o n t he T S A T criteria of t he I DI g ui deli nes f or patie nts wit h here ditar y he m oc hr o mat osis.  If a 
p hle b ot o m y is i n dicate d, base d o n t he T S A T criteria of t he I DI g ui deli nes , t he patie nt s h o ul d 
recei ve p hle b ot o m y treat me nt pre d ose, o n or bef ore t he f oll o wi n g visit.  If t hera pe utic 

Pr ot oc ol LJ 4 0 1- H H 0 1  
 
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p hle b ot o m y is perf or me d t he sa me da y as d osi n g, t he or der s h o ul d be:  la b orat or y sa m ples; 
p hle b o t o m y; LJ P C- 4 0 1 or place b o d ose. 
1 2.  If t he fasti n g Scree ni n g ferriti n a n d T S A T le vels d o n ot meet e ntr y criteria, t he patie nt’s 
re g ularl y sc he d ule d p hle b ot o m y ma y be deferre d, a n d fasti n g  a n d c o m plete ir o n st u dies 
re peate d e ver y 3 0 da ys f or u p t o 9 0 da ys u ntil e ntr y criteria are met. 
1 3.  Bl o o d f or fasti n g c o m plete ir o n st u dies m ust be c ollecte d pre d ose a n d a gai n 2 4 ( ± 4) h o urs 
after d osi n g at t he sa me ti me of da y eac h visit w he ne ver p ossi ble.  T S A T at Wee ks 3, 8, a n d 
1 2 ( 2 4 [ ± 4] h o urs p ost d ose) will deter mi ne t he LJ P C- 4 0 1 d ose f or s u bse q ue nt st u d y visits 
( Wee ks 4, 9, a n d 1 3).  Refer t o Secti o n  5. 4  f or d ose i nf or mati o n a n d d ose a dj ust me nts.  
A d diti o nal bl o o d sa m ples will be c ollecte d f or scie ntific researc h, i ncl u di n g P K a nal yses a n d 
a nal yses o f a p oferriti n a n d h ol oferriti n. 
1 4.  C ollect bl o o d f or c o m plete ir o n st u dies. 
1 5.  Ser u m pre g na nc y test (fe male patie nts of c hil d beari n g p ote ntial o nl y – Scree ni n g) m ust be 
perf or me d wit hi n 3 0 da ys pri or t o t he first d ose of st u d y dr u g (fasti n g is n ot re q uire d). 
1 6.  Uri ne pre g na nc y test (ie, di pstic k) will  be perf or me d f or fe males of c hil d beari n g p ote ntial o n 
Wee k 1 / Da y 1 pre d ose a n d Wee k 2 0 or Earl y Wit h dra wal (if p ossi ble). 
1 7.  Bl o o d f or i m m u n o ge nicit y / P K testi n g t o be c ollecte d (fasti n g is n ot re q uire d) at Scree ni n g 
a n d pre d ose at :  Wee k  1 ( wit h a wi n d o w of −3 0 mi n utes  bef ore d osi n g), Wee k 2, Wee k 4, 
Wee k 8, Wee k  1 2, Wee k 1 6; a n d E O S/ 3 0  da ys ( + 3 da ys) after t he last d ose of st u d y dr u g 
(a p pr o xi matel y Wee k 2 0).  A d diti o nal i m m u n o ge nicit y testi n g ma y be perf or me d as 
descri be d i n  Secti o n  1 0. 1. 6. 7 . 
1 8.  T w o bl o o d sa m ples ( 2 t u bes) nee d t o be c ollecte d  f or t he i m m u n o ge nicit y/P K  a nal ysis at 
Scree ni n g; t hese sa m ples ma y be c ollecte d at t he sa me visit . 
1 9.  C ollect a d diti o nal bl o o d sa m ples  (fasti n g is n ot re q uire d) f or i m m u n o ge nicit y/P K a nal ysis  
p ost d ose 1 h o ur or later  at Wee ks 1 a n d 1 6. 
2 0.  Q ualit y of Life Q uesti o n naires, ( S F - 3 6 v 2), Wester n O ntari o a n d Mc Master U ni versities 
Oste oart hritis I n de x ( W O M A C), a n d m o difie d Dreisler i n dices f or art hritis, s h o ul d be 
c o m plete d pri or t o p hle b ot o m y. 

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La J olla P har mace utical - C o nfi de ntial  
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6.  
S E L E C TI O N A N D WI T H D R A W A L O F P A TI E N T S  
Eac h patie nt m ust meet all t he f oll o wi n g i ncl usi o n criteria a n d n o ne of t he e xcl usi o n criteria i n 
or der t o be e nr olle d i n t he st u d y. 
6. 1.  
P atie nt  I ncl usi o n Criteri a 
1.  Patie nts wit h a cli nical dia g n osis  of here ditar y he m oc hr o mat osis.  
2.  Patie nts w h o are prescri be d t hera pe utic p hle b ot o m y f or t he treat me nt of here ditar y 
he m oc hr o mat osis.  
3.  Patie nts  ≥ 1 8 years of a ge.  
4.  Patie nts wit h a ser u m ferriti n le vel ≥ 1 0 0 n g/ m L. 
5.  Patie nts wit h a T S A T le vel > 4 5 %.  
6.  Fe male patie nts m ust be of n o nc hil d beari n g p ote ntial or usi n g a hi g hl y effecti ve met h o d 
of c o ntrace pti o n d uri n g partici pati o n i n t he st u d y a n d f or 3 0 da ys after t he last d ose of 
st u d y dr u g.  Hi g hl y effecti ve met h o ds of c o ntrace pti o n are defi ne d as t h ose, al o ne or i n 
c o m bi nati o n, t hat res ult i n a l o w fail ure rate w he n use d c o nsiste ntl y a n d c orrectl y.  Refer 
t o Secti o n 1 0. 1. 6. 5. 1  f or t he list of hi g hl y effecti ve met h o ds of c o ntrace pti o n t hat ca n be 
use d i n t his st u d y. 
7.  Fe male patie nts  of c hil d beari n g p ote ntial m ust ha ve a ne gati ve ser u m pre g na nc y test 
d uri n g S cree ni n g  ( wit hi n 3 0 da ys pri or t o t he first d ose of st u d y dr u g), a n d a ne gati ve 
uri ne pre g na nc y test at Da y 1  (ie, pri or t o i nitial d osi n g of st u d y dr u g). 
8.  Male patie nts m ust be s ur gicall y sterile  ( vasect o m y) or usi n g a hi g hl y effecti ve met h o d of 
c o ntrace pti o n d uri n g partici pati o n i n t he st u d y a n d f or 3 0 da ys after t he last d ose of st u d y 
dr u g.  Hi g hl y effecti ve met h o ds of c o ntrace pti o n are defi ne d as t h ose, al o ne or i n 
c o m bi nati o n, t hat res ult i n a l o w fail ure rate w he n use d c o nsiste ntl y a n d c orrectl y.  Refer 
t o Secti o n 1 0. 1. 6. 5. 1  f or t he list of hi g hl y effecti ve met h o ds of c o ntrace pti o n t hat ca n be 
use d i n t his st u d y. 
9.  Patie nt m ust 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. 
6. 2.  
P atie nt  E xcl usi o n Criteri a  
1.  Patie nts recei vi n g ir o n c helati o n t hera p y  wit hi n 7 da ys pri or t o t he first d ose of st u d y 
dr u g. 
2.  Patie nts i nitiati n g p hle b ot o m y treat me nts less t ha n 3 m o nt hs pri or t o t he first d ose of 
st u d y dr u g. 
3.  Patie nts wit h a c o nc o mita nt disease, disa bilit y or c o n diti o n, i ncl u di n g la b orat or y 
a b n or malit y  a n d E C G fi n di n gs, w hic h ma y i nterfere wit h t he c o n d uct of t he st u d y, or 
w hic h w o ul d, i n t he o pi ni o n of t he I n vesti gat or, p ose a n u nacce pta ble ris k t o t he patie nt 
i n t his st u d y, i ncl u di n g, b ut n ot li mite d t o, cli nicall y si g nifica nt arr h yt h mias, alc o h ol 
de pe n de nc y or a b use, dr u g de pe n de nc y or a b use, or ps yc hiatric disease.  Patie nts wit h 

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de pressi o n are eli gi ble if recei vi n g a sta ble d ose of me dicati o n f or at least 9 0 da ys pri or t o 
t he first d ose of st u d y dr u g. 
4.  Pre g na nt or lactati n g w o me n. 
5.  Patie nts ta ki n g a n i m m u n os u p pressi ve a ge nt t hat has n ot bee n a p pr o ve d f or use b y 
La  J olla (e xcl u di n g t o pical o ver-t he-c o u nter ster oi ds, i n hale d ster oi d me dicati o ns, a n d 
n o nster oi dal a nti-i nfla m mat or y dr u gs ).  Refer t o Secti o n  7. 1  f or t he list of pr o hi bite d 
me dicati o ns a n d pr oce d ures.  
6.  Patie nts partici pati n g i n a n u na p pr o ve d i n vest i gati o nal dr u g or i n vesti gati o nal t hera pe utic 
de vice st u d y wit hi n 3 0 da ys pri or t o st u d y dr u g d osi n g, ie, t here m ust be at least 3 0 da ys 
i n bet wee n t he last d ose o n a pri or st u d y a n d t he first d ose a d mi nistrati o n o n t his trial. 
7.  Patie nts w h o are u n willi n g or u na ble t o c o m pl y wit h t he st u d y pr ot oc ol re q uire me nts. 
8.  Patie nts wit h t y pe 1 dia betes  or t y pe 2 dia betes wit h he m o gl o bi n Alc greater t ha n 8 % 
wit hi n 2 m o nt hs pri or t o ra n d o mizati o n . 
9.  Patie nts wit h u nc o ntr olle d acti ve he patitis B, he patitis C, or h u ma n i m m u n o deficie nc y 
vir us ( HI V) i nfecti o n.  
1 0.  Patie nts wit h C hil d P u g h class C cirr h osis or li ver fail ure.  
1 1.  Patie nts wit h se vere c o n gesti ve heart fail ure ( N Y H A = Class 4).  
1 2.  Patie nts w h o ha ve a d va nce d re nal fail ure wit h a n esti mate d gl o mer ular filtrati o n rate 
(e G F R) < 1 5 m L/ mi n/ 1. 7 3 m 2. 
1 3.  Patie nts wit h a h ist or y of aller gic reacti o n t o he pci di n or e xci pie nts. 
1 4.  Patie nts  w h o ha ve pla n ne d s ur ger y (e xcl u di n g de ntal s ur ger y or si m ple der mat ol o gic 
pr oce d ures) d uri n g partici pati o n i n t his st u d y. 
6. 3.  
P atie nt  Wit h dr a w al Criteri a  
Pat ie nts will be i nf or me d t hat t he y ha ve t he ri g ht t o wit h dra w fr o m t he st u d y at a n y ti me a n d f or 
a n y reas o n, wit h o ut prej u dice t o t heir me dical care.  T he I n vesti gat or als o has t he ri g ht t o 
wit h dra w patie nts 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: 
1.  C li nicall y si g nifica nt i nterc urre nt ill ness 
2.  Occ urre nce of a n u nacce pta ble A E.  A Es of c o ncer n m ust  be disc usse d wit h La  J olla’s 
Me dical M o nit or f or p ossi ble a dj ust me nts i n d osi n g sc he d ule ( dela y, s ki p, or 
rec halle n ge). 
3.  At patie nt’s re q uest  
4.  I m p orta nt pr ot oc ol de viati o n / vi olati o n 
5.  N o n -c o m plia nce 
6.  A d mi nistrati ve reas o n  
7.  Fail ure t o ret ur n f or f oll o w- u p 

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8.  Ge neral or s pecific c ha n ges i n t he patie nt’s c o n diti o n u nacce pta ble f or f urt her 
partici pati o n base d u p o n t he j u d g me nt of t he I n vesti gat or 
Patie nts t hat ma y wit h dra w pri or t o Wee k 1 6 s h o ul d be disc usse d wit h t he Me dical M o nit or.  At 
t he ti me of wit h dra wal, all eff orts s h o ul d be ma de t o perf or m pr oce d ures e q ui vale nt t o Wee k 1 6 
pl us a 1 2- lea d E C G  a n d uri ne pre g na nc y test (Ta ble  3), t o t he e xte nt p ossi ble.  Patie nts s h o ul d be 
e nc o ura ge d t o c o m plete E O S  f oll o w- u p pr oce d ures 3 0 da ys ( + 3 da ys) after t he last d ose of 
LJ P C - 4 0 1.  T he reas o n(s) f or a patie n t’s wit h dra wal fr o m t he st u d y m ust  be rec or de d o n t he 
a p pr o priate electr o nic  Case Re p ort F or m ( eC R F ). 

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7.  
T R E A T M E N T O F P A TI E N T S  
F or d escri pti o n of st u d y dr u g, see Secti o n  8 . 
 
I n vesti g ati o n al Pr o d uct 
Pr o d uct N a me:  
LJ P C - 4 0 1 (s y nt hetic h u ma n he pci di n) 
D os a ge F or m: 
S ol uti o n f or I njecti o n  
U nit D ose : 
5 or 1 0 m g/ m L  
R o ute of A d mi nistr ati o n : 
S u bc uta ne o us 
P h ysic al Descri pti o n : 
LJ P C - 4 0 1 f or S C a d mi nistrati o n is a clear c ol orless s ol uti o n , 
wit h  esse ntiall y n o visi ble partic les, s u p plie d i n clear glass 
vials, wit h a r u b ber st o p per, al u mi n u m o ver- seal, a n d plastic 
fli p-off ca p . 
7. 1.  
C o nc o mit a nt Me dic ati o ns  a n d Pr oce d ures  
All me dicati o ns a n d ot her t hera pies t hat are a d mi nistere d  starti n g fr o m 1 4 da ys pri or t o 
Scree ni n g a n d d uri n g t he st u d y, i ncl u di n g t he start a n d st o p date(s), d ose a n d a m o u nt 
a d mi nistere d, a n d i n dicati o n, m ust be rec or de d i n t he e C R Fs a n d i n t he s o urce d oc u me nts.  N o 
ot her e x peri me ntal t hera p y is per mitte d.  C o nc o mita nt me dicati o ns f or ot her me dical c o n diti o ns 
are per mitte d as cli nicall y i n dicate d, s u bject t o s pecific re q uire me nts o utli ne d i n t his pr ot oc ol.  
Pr o hi bite d me dicati o ns a n d t hera pies:  
•  A n y i n vesti gati o nal a ge nt ot her t ha n LJ P C - 4 0 1 
•  A n y i m m u n os u p pressi ve a ge nt t hat has n ot bee n a p pr o ve d f or use b y La J olla 
(e xcl u di n g t o pical o ver-t he-c o u nter ster oi ds, i n hale d ster oi d me dicati o ns, a n d 
n o nster oi dal a nti-i nfla m mat or y dr u gs) 
•  V ita mi n C s u p ple me nts 
•  S ur ger y f or a n y reas o n (e xcl u di n g de ntal s ur ger y or si m ple der mat ol o gic pr oce d ures) 
W he n a n i m me diate de viati o n fr o m t he pr ot oc ol is re q uire d t o eli mi nate a n i m me diate hazar d(s) 
t o a patie nt, t he I n vesti gat or will c o ntact t he st u d y Me dical M o nit or, if circ u msta nces per mit, t o 
disc uss t he pla n ne d c o urse of acti o n.  A n y i m p orta nt de viati o ns fr o m t he pr ot oc ol m ust be f ull y 
d oc u me nte d o n t he a p pr o priate e C R F a n d i n t he s o urce d oc u me ntati o n. 
7. 2.  
Tre at me nt C o m pli a nce  
St u d y dr u g will be a d mi nistere d t o eli gi ble pa tie nts u n der t he s u per visi o n of t he I n vesti gat or or 
i de ntifie d S u b-I n vesti gat or(s).  U p o n c o m pleti o n of a p pr o priate trai ni n g, t he I n vesti gat or ma y 
dele gate st u d y dr u g a d mi nistrati o n t o a trai ne d h o me care n urse/researc h staff .  T he p har macist 
or desi g nee will mai ntai n rec or ds of st u d y dr u g recei pt, pre parati o n, a n d dis pe nsi n g, i ncl u di n g 
t he t otal dr u g a d mi nistere d.  T he place b o l ot n u m ber (fr o m vial of s o di u m c hl ori de f or i njecti o n) 

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a n d t he q ua ntit y of place b o s ol uti o n a d mi nistere d t o t he place b o patie nt w ill be mai ntai ne d i n t he 
p har mac y rec or ds.  A n y discre pa nc y bet wee n t he assi g ne d d ose a n d d ose a d mi nistere d, as well 
as t he reas o n f or t he discre pa nc y, m ust  be rec or de d i n t he s o urce d oc u me nts. 
7. 3.  
R a n d o miz ati o n a n d Si n gle -Bli n d  
T his is a ra n d o mize d, place b o -c o ntr olle d, si n gle- bli n d st u d y.  I n vesti gat ors are n ot bli n de d t o 
treat me nt ar m or T S A T res ults  s o t he y ca n a dj ust st u d y dr u g per t he d ose a dj ust me nt criteria if 
nee de d .  T he st u d y patie nts will n ot be i nf or me d of t he treat me nt bei n g a d mi nistere d  (t o mai ntai n 
t he si n gle- bli n d).  A st u d y p har macist or desi g nee at t he cli nical site will o btai n t he a p pr o priate 
ra n d o mizati o n c o de fr o m t he I nteracti ve V oice/ We b Res p o nse S yste m (I X R S) s yste m  i n or der t o 
dis pe nse st u d y dr u g t o eac h patie nt.  T he l ot n u m ber will be rec or de d wit hi n t he I X R S s yste m.  
Refer t o t he st u d y s pecific P har mac y Ma n ual f or detaile d g ui da nce.  
LJ P C - 4 0 1 will be s u p plie d i n vials as o pe n-la bel st oc k.  La beli n g will f ulfill all re q uire me nts 
s pecifie d b y g o ver ni n g re g ulati o ns. 
7. 4.  
St u d y Pr oce d ures  
T he ti mi n g a n d fre q ue nc y of assess me nts a n d t he details pr o vi de d i n  Ta ble  3 s h o ul d be t he 
pri mar y s o urce.  Fr o m Wee ks 2 t hr o u g h 1 7 t here is a ± 2- da y wi n d o w f or visits; o nce t he visit 
occ urs, t he patie nt s h o ul d ret ur n t o t he re g ular i nter val sc he d ule.  All assess me nts m ust be 
perf or me d pri or t o d osi n g, u nless ot her wise s pecifie d.  If t hera pe utic p hle b ot o m y is perf or me d 
t he sa me da y as d osi n g, t he pr oce d ure or der s h o ul d be:  la b orat or y sa m ples, t he n p hle b ot o m y, 
t he n st u d y dr u g ( LJ P C- 4 0 1 or place b o) d ose. 
Patie nts are n ot t o eat a n y f o o d or dri n k a n y be vera ges, e xce pt water, f or at least 6 h o urs pri or t o 
c ollecti n g bl o o d f or la b orat or y tests i ncl u di n g ir o n st u dies (I m m u n o ge nicit y/ P K a n d pre g na nc y 
test sa m ples are n ot re q uire d t o be fasti n g). 
Bl o o d f or c o m plete ir o n st u dies m ust be c ollecte d pre d ose a n d a gai n 2 4 ( ± 4) h o urs after d osi n g.  
Refer t o Secti o n  5. 4  f or s pecifics o n d osi n g a n d d ose a dj ust me nts.  Bl o o d f or i m m u n o ge nicit y 
m ust f oll o w t he s pecifie d c ollecti o n ti mes o utli ne d i n  Ta ble  3 is per t he f oll o wi n g secti o ns. 

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7. 4. 1.  
Scree ni n g  (Wit hi n 9 0 d a ys of Wee k 1/ D a y 1) 
T he f oll o wi n g assess me nts will be perf or me d as reflecte d i n  Ta ble  3:  Scree ni n g ( wit hi n 9 0 da ys 
of Wee k  1/Da y  1) 
•  O btai n i nf or me d c o nse nt 
•  O btai n t he patie nt’s c o m plete me dical hist or y, i ncl u di n g t he de m o gra p hic 
i nf or mati o n, here ditar y he m oc hr o mat osis dia g n osis a n d ge n ot y pe (if a vaila ble), 
s ur gical hist or y a n d t hera pe utic p hle b ot o m y hist or y 
•  Rec or d me dicati o ns  a n d pr oce d ures, be gi n ni n g 1 4  da ys pri or t o Scree ni n g  
•  Perf or m a p h ysical e xa mi nati o n a n d meas ure me nt of hei g ht a n d wei g ht 
•  O btai n vital si g ns after t he patie nt has bee n resti n g i n t he sitti n g p ositi o n f or at least 
5 mi n utes 
•  Perf or m 1 2- lea d E C G (i n tri plicate a n d ≥ 1 mi n a part) wit hi n 3 0 da ys pri or t o t he first 
d ose of st u d y dr u g 
•  C ollect bl o o d pre d ose f or: 
− c o m plete ir o n st u dies (i ncl u di n g a n a d diti o nal sa m ple f or a p oferriti n a n d 
h ol oferriti n) ; if ferriti n a n d T S A T le vels d o n ot meet e ntr y criteria, t he patie nt’s 
re g ularl y sc he d ule d p hle b ot o m y ma y  be deferre d , a n d fasti n g a n d c o m plete ir o n 
st u dies re peate d e ver y 3 0 da ys f or u p t o 9 0 da ys u ntil e ntr y criteria are met 
− he mat ol o g y  
− ser u m c he mistr y  
− ser u m pre g na nc y test wit hi n 3 0 da ys pri or t o t he first d ose of st u d y dr u g f or 
fe males of c hil d beari n g p ote ntial o nl y (fasti n g is n ot re q uire d) 
− i m m u n o ge nicit y/ P K testi n g (c ollect 2 bl o o d sa m ples [ 2 t u bes], fasti n g is n ot 
re q uire d) 
•  C ollect uri ne f or uri nal ysis  
•  Assess  i ncl usi o n/e xcl usi o n criteria a n d patie nt eli gi bilit y 
•  Assess a n d rec or d A Es a n d S A Es , starti n g at c o nse nt 

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LJ P C - 4 0 1 
4 3 
La J olla P har mace utical - C o nfi de ntial  
Date :  1 4  Dece m ber  2 0 1 8  ( Versi o n 6. 0) 
7. 4. 2.  
Wee k 1  ( D a y 1) 
T he f oll o wi n g assess me nts will be perf or me d as reflecte d i n  Ta ble  3:  Wee k 1/ Da y 1 
•  C o nfir m i ncl usi o n/e xcl usi o n criteria a n d patie nt eli gi bilit y pri or t o ra n d o mizati o n  
•  Assess a n d rec or d A Es a n d S A Es  
•  Rec or d ne w or c ha n ges t o c o nc o mita nt me dicati o ns/ pr oce d ures 
•  O btai n vital si g ns after t he patie nt has bee n resti n g i n t he sitti n g p ositi o n f or at least 
5 mi n utes 
•  C ollect bl o o d  pre d ose f or: 
− c o m plete ir o n st u dies, i ncl u di n g a n a d diti o nal sa m ple f or a p oferriti n a n d 
h ol ofer riti n 
− he mat ol o g y 
− ser u m c he mistr y 
− t h yr oi d f u ncti o n testi n g 
− he m o gl o bi n A 1 c testi n g 
− i m m u n o ge nicit y/ P K testi n g ( wit h a wi n d o w of - 3 0 mi n utes bef ore d osi n g, fasti n g 
is n ot re q uire d) 
•  C ollect uri ne fr o m fe males of c hil d beari n g p ote ntial  o nl y (ie, di pstic k) pri or t o st u d y 
dr u g a d mi nistrati o n  
•  A d mi nister Q ualit y of Life Q uesti o n naire s (S F -3 6 v 2) , W O M A C, a n d m o difie d 
Dreisler i n dices f or art hritis ) pri or t o p hle b ot o m y  
•  Sta n dar d of care t hera pe utic p hle b ot o m y ( 5 0 0 cc or a p pr o priate f or wei g ht).  
P hle b ot o m y s h o ul d be perf or me d after la b orat or y sa m ples are c ollecte d a n d bef ore 
st u d y dr u g d ose (ie, or der is la b orat or y sa m ples, p hle b ot o m y, LJ P C- 4 0 1 or place b o 
d ose). 
•  C o m plete ra n d o mizati o n pr oce d ures 
•  A d mi nister si n gle- bli n de d st u d y dr u g  (LJ P C - 4 0 1 or place b o) 
− Patie nts will n ot be i nf or me d of t he treat me nt bei n g a d mi nistere d ( t o mai ntai n t he 
si n gle- bli n d). 
•  C ollect p ost d ose bl o o d f or i m m u n o ge nicit y/ P K  ( 1 h o ur or later, fasti n g is n ot 
re q uire d) 
7. 4. 3.  
Wee k 2 ( D a y 8)  
T he f oll o wi n g assess me nts will be perf or me d as reflecte d i n  Ta ble  3:  Wee k 2/ Da y 8 
•  Assess a n d rec or d A Es a n d S A Es  
•  Rec or d ne w or c ha n ges t o c o nc o mita nt me dicati o ns/ pr oce d ures 

Pr ot oc ol LJ 4 0 1- H H 0 1  
 
LJ P C - 4 0 1 
4 4 
La J olla P har mace utical - C o nfi de ntial  
Date :  1 4  Dece m ber  2 0 1 8  ( Versi o n 6. 0) 
•  O btai n vital si g ns after t he patie nt has bee n resti n g i n t he sitti n g p ositi o n f or at least 
5 mi n utes 
•  C ollect bl o o d f or i m m u n o ge nicit y / P K testi n g (fasti n g is n ot re q uire d)  
•  A d mi nister si n gle- bli n de d st u d y dr u g (LJ P C - 4 0 1 or place b o) 
− Patie nts will n ot be i nf or me d of t he treat me nt bei n g a d mi nistere d (t o mai ntai n t he 
si n gle- bli n d).   
7. 4. 4.  
Wee k 3  ( D a y 1 5 a n d D a y 1 6) 
T he f oll o wi n g assess me nts will be perf or me d as reflecte d i n  Ta ble  3:  Wee k 3/ Day 1 5  a n d 
Da y  1 6 
•  Assess a n d rec or d A Es a n d S A Es  
•  Rec or d ne w or c ha n ges t o c o nc o mita nt me dicati o ns/ pr oce d ures 
•  O btai n vital si g ns after t he patie nt has bee n resti n g i n t he sitti n g p ositi o n f or at least 
5 mi n utes  
•  C ollect bl o o d f or c o m plete ir o n st u dies , i ncl u di n g a n a d diti o nal sa m ple f or a p oferriti n 
a n d h ol oferriti n 
•  A d mi nister si n gle- bli n de d st u d y dr u g (LJ P C - 4 0 1 or place b o) 
− Patie nts will n ot be i nf or me d of t he treat me nt bei n g a d mi nistere d (t o mai ntai n t he 
si n gle- bli n d).   
•  Wee k 3 ( D a y 1 6) :  C ollect bl o o d 2 4 ( ±  4) h o urs p ost d ose f or c o m plete ir o n st u dies 
f or T S A T t o deter mi ne t he LJ P C - 4 0 1 d ose f or Wee k 4.  R efer t o d ose a dj ust me nt 
criteria a n d g ui deli nes i n Secti o n  5. 4 .) 
7. 4. 5.  
Wee k 4  ( D a y 2 2) 
T he f oll o wi n g assess me nts will be perf or me d as reflecte d i n  Ta ble  3:  Wee k 4/ Da y 2 2 
•  Assess a n d rec or d A Es a n d S A Es  
•  Rec or d ne w or c ha n ges t o c o nc o mita nt me dicati o ns/ pr oce d ures 
•  O btai n vital si g ns after t he patie nt has bee n resti n g i n t he sitti n g p ositi o n f or at least 
5 mi n utes  
•  C ollect bl o o d pre d ose f or: 
− c o m plete ir o n st u dies, i ncl u di n g a n a d diti o nal sa m ple f or a p oferriti n a n d 
h ol oferriti n  
− he mat ol o g y 
− ser u m c he mistr y 
− i m m u n o ge nicit y/ P K testi n g (fasti n g is n ot re q uire d) 
•  A d mi nister si n gle- bli n de d st u d y dr u g ( LJ P C- 4 0 1 or place b o) 

Pr ot oc ol LJ 4 0 1- H H 0 1  
 
LJ P C - 4 0 1 
4 5 
La J olla P har mace utical - C o nfi de ntial  
Date :  1 4  Dece m ber  2 0 1 8  ( Versi o n 6. 0) 
− Patie nts will n ot be i nf or me d of t he treat me nt bei n g a d mi nistere d (t o mai ntai n t he 
si n gle- bli n d). 
•  Wee k 4 ( D a y  2 3):  C ollect bl o o d 2 4 ( ± 4) h o urs p ost d ose f or c o m plete ir o n st u dies 
f or T S A T t o deter mi ne t he if t he patie nt re q uires a p hle b ot o m y.  If t he T S A T res ult 
fr o m Wee k 4, Da y 2 3 is > 4 5 %, t he patie nt m ust be c o ntacte d s o he/s he ca n recei ve a 
p hle b ot o m y ( base d o n t he T S A T criteria of t he I DI g ui deli nes). 
− If i n dicate d, phle b ot o m y m ust be c o m plete d o n or bef ore Wee k 5.  If t hera pe utic 
p hle b ot o m y is perf or me d t he sa me da y as d osi n g, t he or der s h o ul d be:  la b orat or y 
sa m ples; p hle b ot o m y; LJ P C- 4 0 1 or place b o d ose. 
7. 4. 6.  
Wee ks 5, 6, a n d 7  ( D a ys 2 9, 3 6, a n d 4 3) 
T he f oll o wi n g assess me nts will be perf or me d as reflecte d i n  Ta ble  3:  Wee ks 5, 6, a n d 
7/ Da ys 2 9, 3 6, a n d 4 3  
•  Assess a n d rec or d A Es a n d S A Es  
•  Rec or d ne w or c ha n ges t o c o nc o mita nt me dicati o ns/ pr oce d ures 
•  O btai n vital si g ns after t he patie nt has bee n resti n g i n t he sitti n g p ositi o n f or at least 
5 mi n utes  
•  A d mi nister si n gle- bli n de d st u d y dr u g (LJ P C - 4 0 1 or place b o)  
− Patie nts will n ot be i nf or me d of t he treat me nt bei n g a d mi nistere d (t o mai ntai n t he 
si n gle- bli n d).   
7. 4. 7.  
Wee k 8  ( D a y 5 0 a n d D a y 5 1) 
T he f oll o wi n g assess me nts will be perf or me d as reflecte d i n  Ta ble  3:  Wee k 8/ Da y 5 0 a n d 
Da y  5 1 
•  Assess a n d rec or d A Es a n d S A Es  
•  Rec or d ne w or c ha n ges t o c o nc o mita nt me dicati o ns/ pr oce d ures  
•  O btai n vital si g ns after t he patie nt has bee n resti n g i n t he sitti n g p ositi o n f or at least 
5 mi n utes 
•  C ollect bl o o d  pre d ose f or: 
− c o m plete ir o n st u dies, i ncl u di n g a n a d diti o nal sa m ple f or a p oferriti n a n d 
h ol oferriti n  
− he mat ol o g y 
− ser u m c he mistr y 
− i m m u n o ge nicit y/ P K testi n g (fasti n g is n ot re q uire d) 
•  A d mi nister si n gle- bli n de d st u d y dr u g (LJ P C - 4 0 1 or place b o) 
− Patie nts will n ot be i nf or me d of t he treat me nt bei n g a d mi nistere d (t o mai ntai n t h e 
si n gle- bli n d). 

Pr ot oc ol LJ 4 0 1- H H 0 1  
 
LJ P C - 4 0 1 
4 6 
La J olla P har mace utical - C o nfi de ntial  
Date :  1 4  Dece m ber  2 0 1 8  ( Versi o n 6. 0) 
•  Wee k 8 ( D a y 5 1) :  C ollect bl o o d 2 4 ( ± 4) h o urs p ost d ose f or c o m plete ir o n st u dies 
f or T S A T t o deter mi ne if t he patie nt re q uires a p hle b ot o m y.  If t he T S A T res ult fr o m 
Wee k 8, Da y 5 1 is > 4 5 %, t he patie nt m ust be c o ntacte d s o he/s he ca n recei ve a 
p hle b ot o m y ( base d o n t he T S A T criteria of t he I DI g ui deli nes).  
•  If i n dicate d, phle b ot o m y m ust be c o m plete d o n or bef ore Wee k 9.  If t hera pe utic 
p hle b ot o m y is perf or me d t he sa me da y as d osi n g, t he or der s h o ul d be:  la b orat or y 
sa m ples; p hle b ot o m y; LJ P C- 4 0 1 or place b o d ose. 
7. 4. 8.  
Wee ks 9, 1 0, a n d  1 1 ( D a ys 5 7, 6 4, a n d 7 1) 
T he f oll o wi n g assess me nts will be perf or me d as reflecte d i n  Ta ble  3:  Wee ks 9, 1 0, a n d 
1 1/ Da ys 5 7, 6 4, a n d 7 1 
•  Assess a n d rec or d A Es a n d S A Es  
•  Rec or d ne w or c ha n ges t o c o nc o mita nt me dicati o ns/ pr oce d ures 
•  O btai n vital si g ns after t he patie nt has bee n resti n g i n t he sitti n g p ositi o n f or at least 
5 mi n utes 
•  A d mi nister si n gle- bli n de d st u d y dr u g (LJ P C - 4 0 1 or place b o refer t o d ose a dj ust me nt 
Secti o n  5. 4 .) 
− Patie nts will n ot be i nf or me d of t he treat me nt bei n g a d mi nistere d ( t o mai ntai n t he 
si n gle- bli n d). 
7. 4. 9.  
Wee k 1 2 ( D a y 7 8 a n d D a y 7 9) 
T he f oll o wi n g ass ess me nts will be perf or me d as reflecte d i n  Ta ble  3:  Wee k 1 2/ Da y 7 8  a n d 
Da y  7 9 
•  Assess a n d rec or d A Es a n d S A Es  
•  Rec or d ne w or c ha n ges t o c o nc o mita nt me dicati o ns / pr oce d ures 
•  O btai n vital si g ns after t he patie nt has bee n resti n g i n t he sitti n g p ositi o n f or at least 
5 mi n utes 
•  C ollect bl o o d pre d ose f or: 
− c o m plete ir o n st u dies, i ncl u di n g a n a d diti o nal sa m ple f or a p oferriti n a n d 
h ol oferriti n  
− he mat ol o g y 
− ser u m c he mistr y 
− i m m u n o ge nicit y/ P K testi n g (fasti n g is n ot re q uire d) 
•  A d mi nister si n gle- bli n de d st u d y dr u g ( LJ P C- 4 0 1 or place b o) 
− Patie nts will n ot be i nf or me d of t he treat me nt bei n g a d mi nistere d ( t o mai ntai n t he 
si n gle- bli n d). 

Pr ot oc ol LJ 4 0 1- H H 0 1  
 
LJ P C - 4 0 1 
4 7 
La J olla P har mace utical - C o nfi de ntial  
Date :  1 4  Dece m ber  2 0 1 8  ( Versi o n 6. 0) 
•  Wee k 1 2 ( D a y 7 9) :  C ollect bl o o d 2 4 ( ± 4) h o urs p ost d ose f or c o m plete ir o n st u dies 
f or T S A T t o deter mi ne if t he patie nt re q uires a p hle b ot o m y.  If t he T S A T res ult fr o m 
Wee k 1 2, Da y 7 9 is > 4 5 %, t he patie nt m ust be c o ntacte d s o he/s he ca n recei ve a 
p hle b ot o m y ( base d o n t he T S A T criteria of t he  I DI g ui deli nes). 
•   If i n dicate d, phle b ot o m y m ust be c o m plete d o n or bef ore Wee k 1 3.  If t hera pe utic 
p hle b ot o m y is perf or me d t he sa me da y as d osi n g, t he or der s h o ul d be:  la b orat or y 
sa m ples; p hle b ot o m y; LJ P C- 4 0 1 or place b o d ose. 
7. 4. 1 0.  
Wee ks 1 3, 1 4, a n d 1 5 ( D a ys 8 5, 9 2, a n d 9 9) 
T he f oll o wi n g assess me nts will be perf or me d as reflecte d i n  Ta ble  3:  Wee ks 1 3, 1 4, a n d 
1 5/ Da ys 8 5, 9 2, a n d 9 9 
•  Assess a n d rec or d A Es a n d S A Es  
•  Rec or d ne w or c ha n ges t o c o nc o mita nt me dicati o ns/ pr oce d ures 
•  O btai n vital si g ns after t he patie nt has bee n resti n g i n t he sitti n g p ositi o n f or at least 
5 mi n utes  
•  A d mi nister si n gle- bli n de d st u d y dr u g ( LJ P C- 4 0 1 or place b o; refer t o d ose a dj ust me nt 
Sec ti o n 5. 4 .) 
− Patie nts will n ot be i nf or me d of t he treat me nt bei n g a d mi nistere d ( t o mai ntai n t he 
si n gle- bli n d). 
7. 4. 1 1.  
Wee k 1 6 ( D a y 1 0 6 a n d D a y 1 0 7) 
T he f oll o wi n g assess me nts will be perf or me d as reflecte d i n Ta ble  3:  Wee k 1 6/ Da y 1 0 6 a n d 
Da y  1 0 7 
•  Assess a n d rec or d A Es a n d S A Es  
•  Rec or d ne w or c ha n ges t o c o nc o mita nt me dicati o ns/ pr oce d ures 
•  O btai n vital si g ns after t he patie nt has bee n resti n g i n t he sitti n g p ositi o n f or at least 
5 mi n utes 
•  Perf or m a p h ysical e xa mi nati o n (i ncl u di n g wei g ht) 
•  C ollect bl o o d pre d ose f or: 
− c o m plete ir o n st u dies, i ncl u di n g a n a d diti o n al sa m ple f or a p oferriti n a n d 
h ol oferriti n  
− he mat ol o g y 
− ser u m c he mistr y 
− t h yr oi d f u ncti o n testi n g 
− he m o gl o bi n A 1 c testi n g 
− i m m u n o ge nicit y/ P K testi n g (fasti n g is n ot re q uire d) 

Pr ot oc ol LJ 4 0 1- H H 0 1  
 
LJ P C - 4 0 1 
4 8 
La J olla P har mace utical - C o nfi de ntial  
Date :  1 4  Dece m ber  2 0 1 8  ( Versi o n 6. 0) 
•  C ollect uri ne f or  uri nal ysis  
•  A d mi nister Q ualit y of Life Q uesti o n naire s ( S F- 3 6 v 2), W O M A C, a n d m o difie d 
Dreisler i n dices f or art hritis ) pri or t o p hle b ot o m y  
•  A d mi nister si n gle- bli n de d st u d y dr u g ( LJ P C- 4 0 1 or place b o) 
− Patie nts will n ot be i nf or me d of t he treat me nt bei n g a d mi nistere d ( t o mai ntai n t he 
si n gle- bli n d). 
− C ollect p ost d ose bl o o d f or i m m u n o ge nicit y/ P K ( 1 h o ur or later, fasti n g is n ot 
re q uire d) 
•  Wee k 1 6 ( D a y 1 0 7) :  C ollect bl o o d 2 4 ( ± 4) h o urs p ost d ose f or he mat ol o g y a n d 
c o m plete ir o n st u dies f or T S A T t o deter mi ne if t he patie nt re q uires a p hle b ot o m y.  If 
t he T S A T res ult fr o m Wee k 1 6, Da y 1 0 7 is > 4 5 %, t he patie nt m ust be c o ntacte d s o 
he/s he ca n recei ve a p hle b ot o m y ( base d o n t he T S A T criteria of t he  I DI g ui deli nes). 
•  If i n dicate d, phle b ot o m y m ust be c o m plete d o n or bef ore Wee k 1 7 ( Da y 1 1 3).  If 
t hera pe utic p hle b ot o m y is perf or me d t he sa me da y as t he Wee k 1 7, fasti n g ir o n 
st u dies s h o ul d be c ollecte d bef ore p hle b ot o m y. 
7. 4. 1 2.  
Wee k 1 7 ( D a y 1 1 3) 
•  C ollect bl o o d f or fasti n g ir o n st u dies  (tr o u g h sa m ple, a p pr o xi matel y 7 da ys after last 
d ose). 
7. 4. 1 3.  
F oll o w- u p ( 3 0 d a ys [ + 3 d a ys] fr o m l ast d ose of st u d y dr u g) 
T he  f oll o wi n g assess me nts will be perf or me d as reflecte d i n Ta ble  3:  A p pr o xi matel y Wee k  2 0 
( 3 0 da ys [ + 3 da ys] after t he last d ose of st u d y dr u g) 
•  Assess a n d rec or d A Es a n d S A Es 
•  Rec or d ne w or c ha n ges t o c o nc o mita nt me dicati o ns/ pr oce d ures 
•  O btai n vital si g ns after t he patie nt has bee n resti n g i n t he sitti n g p ositi o n f or at least 
5 mi n utes 
•  Perf or m a p h ysical e xa mi nati o n  
•  Perf or m 1 2-lea d E C G (i n tri plicate a n d ≥ 1 mi n a part) 
•  C ollect bl o o d f or:   
− c o m plete ir o n st u dies, i ncl u di n g a n a d diti o nal sa m ple f or a p oferriti n a n d 
h ol oferriti n  
− he mat ol o g y 
− ser u m c he mistr y 
− i m m u n o ge nicit y/ P K testi n g (fasti n g is n ot re q uire d) 

Pr ot oc ol LJ 4 0 1- H H 0 1  
 
LJ P C - 4 0 1 
4 9 
La J olla P har mace utical - C o nfi de ntial  
Date :  1 4  Dece m ber  2 0 1 8  ( Versi o n 6. 0) 
•  C ollect uri ne f or : 
− uri nal ysis  
− pre g na nc y test, f or  fe males of c hil d beari n g p ote ntial o nl y (ie, di pstic k test) 
7. 4. 1 4.  
E arl y Wit h dr a w al 
T he f oll o wi n g pr oce d ures are t o be c ollecte d, t o t he e xte nt p ossi ble, f or patie nts w h o wit h dra w 
earl y.  Pr oce d ures i ncl u de all Wee k 1 6 pr oce d ures pl us a 1 2-lea d E C G a n d uri ne pre g na nc y 
testi n g (fe males of c hil d- beari n g p ote ntial o nl y). 

Pr ot oc ol LJ 4 0 1- H H 0 1  
 
LJ P C - 4 0 1 
5 0 
La J olla P har mace utical - C o nfi de ntial  
Date :  1 4  Dece m ber  2 0 1 8  ( Versi o n 6. 0) 
8.  
S T U D Y D R U G M A T E RI A L S A N D M A N A G E M E N T  
8. 1.  
St u d y Dr u g  
LJ P C - 4 0 1 f or S C a d mi nistrati o n is a clear c ol orless s ol uti o n , wit h esse ntiall y n o visi ble particles,  
s u p plie d i n clear glass vials, wit h a r u b ber st o p per a n d al u mi n u m o ver-seal wit h a plastic fli p -off 
ca p.  Pr o d uct c o nce ntrati o n is 5 or 1 0 m g/ m L.  T he e xtracta ble fill v ol u me  is 1. 0 m L.  Refer t o 
t he pr o d uct la bel a n d/ or t he P har mac y Ma n ual f or d ose pre parati o n i nstr ucti o ns. 
8. 2.  
St u d y Dr u g P ac k a gi n g a n d L a beli n g  
LJ P C - 4 0 1 will be s u p plie d i n vials as o pe n-la bel st oc k.  La beli n g will f ulfill all re q uire me nts 
s pecifie d b y partici pati n g g o ver ni n g re g ulati o ns. 
A v ol u me- matc he d place b o  ( 0. 9 % s o di u m c hl ori de i njecti o n, U S P [or e q ui vale nt]) will be 
pr o vi de d b y t h e st u d y sites fr o m t heir o w n st oc k. 
Refer t o t he st u d y s pecific P har mac y Ma n ual f or detaile d g ui da nce.  
8. 3.  
St u d y Dr u g St or a ge  
Vials c o ntai ni n g LJ P C - 4 0 1 s h o ul d be st ore d refri gerate d at 5° C ± 3° ( 2° C t o 8° C) i n a sec ure 
area wit h li mite d access.  La  J olla has t este d pr o d uct sta bilit y a n d s h o w n t he pr o d uct t o be sta ble 
wit hi n t hat te m perat ure ra n ge f or t he a ntici pate d d urati o n of use. 
Refer t o t he st u d y s pecific P har mac y Ma n ual f or detaile d g ui da nce.  
8. 4.  
St u d y Dr u g Pre p ar ati o n  
Pri or t o a d mi nistrati o n, vials of LJ P C - 4 0 1 s h o ul d be st ore d at r o o m te m perat ure f or a mi ni m u m 
of 3 0 mi n utes f oll o wi n g re m o val fr o m t he refri gerat or.  St u d y dr u g ca n be st ore d at r o o m 
te m perat ure f or u p t o 2 4 h o urs pri or t o d osi n g. 
A p har macist or desi g nee will pre pare t he st u d y dr u g usi n g safe practices f or me dical i njecti o ns.  
F or t h ose patie nts ra n d o mize d t o place b o, a v ol u me- matc he d s yri n ge of 0. 9 % s o di u m c hl ori de 
i njecti o n, U S P ( or e q ui vale nt) will be pre pare d b y t he p har macist or desi g nee a n d la bele d as s uc h 
t hat t h ose s yri n ges c o ntai ni n g dr u g pr o d uct a n d t h ose c o ntai ni n g place b o a p pear i de ntical (t o 
mai ntai n t he st u d y si n gle- bli n d).  
Refer t o t he st u d y s pecific P har mac y Ma n ual f or detaile d g ui da nce.  
8. 5.  
St u d y Dr u g A d mi nistr ati o n  
Vials are f or si n gle -use a d mi nistrati o n a n d will be gi ve n via S C i njecti o n.  St u d y dr u g will o nl y 
be a d mi nistere d t o eli gi ble patie nts u n der t he s u per visi o n of t he I n vesti gat or or i de ntifie d 
S u b -I n vesti gat or(s).  U p o n c o m pleti o n of a p pr o priate trai ni n g, t he I n vesti gat or ma y dele gate 
st u d y dr u g a d mi nistrati o n t o a trai ne d h o me care n urse/researc h staff .  
Refer t o t he st u d y s pecific P har mac y Ma n ual f or detaile d g ui da nce.  

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8. 6.  
St u d y Dr u g  Acc o u nt a bilit y  
All use d (e m pt y or partiall y e m pt y) a n d u n use d st u d y dr u g vials m ust be sa ve d f or t he St u d y 
M o nit or f or rec o nciliati o n pri or t o destr ucti o n or i nitiati n g a ret ur n of st u d y dr u g.  Destr ucti o n of 
st u d y dr u g ma y o nl y be perf or me d if La  J olla has a gree d t o o n-site destr ucti o n of use d vials. 
Refer t o t he st u d y s pecific P har mac y Ma n ual f or detaile d g ui da nce.  
8. 7.  
St u d y Dr u g  H a n dli n g a n d Dis p o s al 
All u n use d st u d y dr u g a n d ot her st u d y materials m ust  be ret ur ne d t o La  J olla or its desi g nee 
a n d/ or destr o ye d at t he st u d y site (if a p pr o ve d b y La  J olla) after rec o nciliati o n has bee n 
c o m plete d b y t he St u d y M o nit or, or u nless ot her wise directe d b y La  Jolla .  All u n use d material 
c o ntai ni n g LJ P C - 4 0 1 will be treate d a n d dis p ose d of as hazar d o us waste i n acc or da nce wit h 
g o ver ni n g re g ulati o ns. 
Refer t o t he st u d y s pecific P har mac y Ma n ual f or detaile d g ui da nce.  

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Date :  1 4  Dece m ber  2 0 1 8  ( Versi o n 6. 0) 
9.  
A S S E S S M E N T  O F E F FI C A C Y  
9. 1.  
C o m plete Ir o n S t u dies  
Bl o o d sa m pl es f or a nal ysis of ir o n st u d y para meters i ncl u de: 
•  T otal Ser u m Ir o n  
•  Ferriti n  
•  Tra nsferri n  
•  TI B C  
•  UI B C  
•  T S A T   
C o m plete ir o n st u dies will be assesse d at ti mes s pecifie d i n  Ta ble  3.  Patie nts are n ot t o eat  a n y 
f o o d or dri n k a n y be vera ges, e xce pt water, f or at least 6 h o urs pri or t o c ollecti n g bl o o d f or 
c o m plete ir o n st u dies.  A d diti o nal bl o o d sa m ples will be c ollecte d f or scie ntific researc h, 
i ncl u di n g P K a nal yses a n d a nal yses of a p oferriti n a n d h ol oferriti n.  
9. 2.  
P hle b ot o m y  
All ra n d o mize d patie nts will recei ve a sta n dar d of care t hera pe utic p hle b ot o m y ( 5 0 0 cc or 
a p pr o priate f or wei g ht ) o n Da y 1  ( pre d ose).  T hereafter, p hle b ot o m y decisi o ns b y t he 
I n vesti gat or will be base d o n t he patie nt’s fasti n g T S A T res ults c ollecte d p ost d ose 2 4 ( ± 4) h o urs 
at Wee k 4 ( Da y 2 3); Wee k 8 ( Da y 5 1); Wee k 1 2 ( Da y 7 9); a n d Wee k 1 6 ( Da y 1 0 7).  If t he 
res ulti n g T S A T is > 4 5 % a p hle b ot o m y is i n dicate d.  If a p hle b ot o m y is i n dicate d, t he patie nt 
s h o ul d recei ve p hle b ot o m y treat me nt pre d ose, o n or bef ore t he f oll o wi n g visit. 
If t hera pe utic p hle b ot o m y is perf or me d t he sa me da y as d osi n g, t he or der s h o ul d be:  la b orat or y 
sa m ples; phle b ot o m y; LJ P C - 4 0 1 or place b o d ose. 
N u m ber of p hle b ot o mies a n d t he n u m ber of ti mes a patie nt met criteria f or a p hle b ot o m y will be 
e val uate d ( Secti o n  1 2. 8. 4. 2 ). 

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1 0.  
A S S E S S M E N T O F S A F E T Y  
Assess me nts will be perf or me d at ti mes s pecifie d i n  Ta ble  3. 
1 0. 1.  
S afet y P ar a meters  
Safet y assess me nts will i ncl u de m o nit ori n g of all A Es, re g ular m o nit ori n g of la b orat or y 
para meters i ncl u di n g he mat ol o g y, ser u m c he mistr y a n d ir o n pa nel, E C Gs, c o nc o mita nt 
m e dicati o ns, p h ysical e xa mi nati o ns, vital si g ns, a n d testi n g f or i m m u n o ge nicit y.   
1 0. 1. 1.  
De m o gr a p hics 
De m o gra p hic i nf or mati o n will be c ollecte d at Scree ni n g, t o i ncl u de a ge, se x, c hil d beari n g 
p ote ntial, race, et h nicit y,  a n d ge o gra p hic re gi o n ( w here all o we d, per l ocal re g ulati o ns).  Refer t o 
Secti o n  1 2. 8. 1  f or t he f ull list of c haracteristics t hat will be c ollecte d. 
1 0. 1. 2.  
Me dic al Hist or y  
A c o m plete re vie w of t he patie nt’s me dical hist or y s h o ul d i ncl u de t he patie nt’ s here ditar y 
he m oc hr o mat osis dia g n osis a n d ge n ot y pe (if a vaila ble), c o nc urre nt me dical c o n diti o ns, s ur gical 
a n d me dical pr oce d ures, a n d t hera pe utic p hle b ot o m y hist or y.   
Pri or a n d c o nc o mita nt me dicati o ns will be rec or de d t hr o u g h t he f oll o w- u p visit.  T his rec or di n g 
s h o ul d i ncl u de a n y me dicati o n ta ke n, i ncl u di n g oral c o ntrace pti ves, a n d me dical pr oce d ure(s) 
perf or me d fr o m 1 4 da ys pri or t o Scree ni n g t o t he f oll o w- u p visit ( 3 0 da ys [ + 3 da ys] after t he last 
d ose of st u d y dr u g). 
1 0. 1. 3.  
Vit al Si g ns  
Vital si g ns, i ncl u di n g heart rate, res pirat or y rate, b o d y te m perat ure, a n d bl o o d press ure , as 
o utli ne d i n  Ta ble  3, will  be meas ure d after t he patie nt has bee n resti n g i n a sitti n g p ositi o n f or at 
least 5 mi n utes . 
Vital si g ns ma y be perf or me d b y a n I n vesti gat or, S u b- I n vesti gat or, or I n vesti gat or- desi g nate d 
n urse, p h ysicia n’s assista nt, or a n y staff me m ber a p pr o priatel y trai ne d a n d i ncl u de d o n t he 
dele gati o n of a ut h orit y l o g as a ble t o c o n d uct t hese assess me nts.  
1 0. 1. 4.  
P h ysic al E x a mi n ati o n  
A c o m plete p h ysical e xa mi nati o n (i ncl u di n g e val uati o n of ge neral a p peara nce/ me ntal stat us, 
H E E N T [ hea d, e yes, ears, n ose, t hr oat] a n d t he f oll o wi n g b o d y s yste ms:  der mat ol o gic, 
car di o vasc ular, res pirat or y, gastr oi ntesti nal , a n d ne ur ol o gic) will be perf or me d  at s pecifie d ti mes, 
o utli ne d i n  Ta ble  3. 
T hese p h ysical e xa ms will i ncl u de disease relate d s y m pt o ms assess me nt a n d meas ure me nt of 
wei g ht at Scree ni n g a n d Wee k 1 6.  Hei g ht will be meas ure d at Scree ni n g o nl y. 
1 0. 1. 5.  
Electr oc ar di o gr a m  
1 2- lead E C Gs will be meas ure d i n tri plicate (≥ 1 mi n ute a part) after t he patie nt has bee n resti n g 
f or at least 5 mi n utes i n a s u pi ne p ositi o n.  A d diti o nal E C Gs will be c ollecte d if cli nicall y 
i n dicate d (e g, patie nts wit h pal pitati o ns, li g ht hea de d ness).  

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A b n or malities n ote d at Scree ni n g s h o ul d be i ncl u de d i n t he me dical hist or y.  If o bser ve d as 
a b n or mal a n d cli nicall y si g nifica nt t hereafter it s h o ul d be n ote d  as a n A E. 
1 0. 1. 6.  
L a b or at or y Assess me nts  
Sa m ples will be c ollecte d  at ti mes s pecifie d i n  Ta ble  3.  A p pe n di x 1  pr o vi des a s u m mar y list of 
t he la b orat or y para meters  i n t his st u d y.  All sa m ples will be se nt t o t he ce ntral la b orat or y u nless 
i n t he case of a safet y or e mer ge nt e ve nt, or ot her wise i nstr ucte d b y t he S p o ns or.  U nsc he d ule d 
la borat or y  kits s h o ul d be use d f or all re peat la b orat or y test s w he ne ver p ossi ble. 
Patie nts are n ot t o eat a n y f o o d or dri n k a n y be vera ges, e xce pt water, f or at least 6 h o urs pri or t o 
c ollecti n g bl o o d f or la b orat or y tests (i m m u n o ge nicit y / P K a n d pre g na nc y test  sa m ples are n ot 
re q uire d t o be fasti n g). 
If t hera pe utic p hle b ot o m y is perf or me d t he sa me da y as d osi n g, t he or der s h o ul d be:  la b orat or y 
sa m ples; p hle b ot om y; LJ P C - 4 0 1 or place b o d ose. 
1 0. 1. 6. 1.  He m at ol o g y  
Bl o o d sa m pl es f or a nal ysis of t he he mat ol o gic para meters i ncl u de:  
•  He mat ocrit  
 
•  He m o gl o bi n 
•  Platelet c o u nt  
•  R B C c o u nt, i ncl u di n g retic ul oc yte 
c o u nt, R D W, mea n c or p usc ular 
he m o gl o bi n, mea n c or p usc ular 
he m o gl o bi n c o nce ntrati o n, a n d 
mea n c or p usc ular v ol u me 
•  W hite bl o o d cell c o u nt a n d 
differe ntial i ncl u di n g perce nt a n d 
a bs ol ute:  ne utr o p hils, 
l y m p h oc ytes, m o n oc ytes, 
e osi n o p hils, a n d bas o p hils  
1 0. 1. 6. 2.  Cli nic al  C he mistr ies 
Bl o o d sa m pl es f or a nal ysis of cli nical c he mistr y para meters i ncl u de: 
•  Ser u m creati ni ne 
•  Uric aci d 
•  Calci u m  
•  Ma g nesi u m  
•  Al kali ne 
p h os p hatase 
•  Lactate 
de h y dr o ge nase 
( L D H) 
 
•  Bl o o d u rea n itr o ge n 
•  P h os p hate 
•  C hl ori de 
•  Bicar b o nate 
•  A L T  
(ser u m gl uta mic-
p yr u vic 
tra nsa mi nase) 
•  Al b u mi n  
•  S o di u m 
•  P otassi u m  
•  Gl uc ose 
•  As partate a mi n otra nsferase 
(A S T ) 
(ser u m gl uta mic- 
o xal oacetic tra nsa mi nase)  
•  Bilir u bi n (t otal, direct , 
a n d i n direct) 
•  T otal pr otei n  

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1 0. 1. 6. 3.  T h yr oi d F u ncti o n  
Bl o o d sa m pl es f or a nal ysis of t h yr oi d f u ncti o n para meters i ncl u de: 
•  T h yr oi d- sti m ulati n g 
h or m o ne ( T S H ) 
•  T h yr o xi ne ( T 4) 
•  Trii o d ot h yr o ni ne ( T 3 ) 
•  Free T 4  
1 0. 1. 6. 4.  Gl yce mic C o ntr ol  
Bl o o d sa m pl es f or a nal ysis of he m o gl o bi n A 1 c will be c ollecte d t o assess gl yce mic c o ntr ol.  
1 0. 1. 6. 5.  Pre g n a nc y Scree n  
A ser u m pre g na nc y test will be perf or me d f or w o me n of c hil d beari n g p ote ntial d uri n g Scree ni n g 
wit hi n 3 0 da ys pri or t o t he first d ose of st u d y dr u g.  Fasti n g is n ot re q uire d.  
A uri ne pre g na nc y test (ie, di pstic k) will  be perf or me d f or w o me n of c hil d beari n g p ote ntial at 
Wee k  1/ Da y 1 pre d ose a n d Wee k 2 0 or Earl y Wit h dra wal (if p ossi ble). 
Refer t o Secti o n  1 1. 5  f or pre g na nc y re p orti n g a n d f oll o w- u p pr oce d ures. 
1 0. 1. 6. 5. 1.  C o ntr ace pti o n 
T he effects of t he st u d y dr u g, LJ P C- 4 0 1, or pr oce d ures perf or me d d uri n g t his st u d y ma y p ose 
s o me u n k n o w n ris ks t o t he re pr o d ucti ve s yste m, de vel o pi n g fet us or d uri n g breastfee di n g.  Si nce 
t he effects of t he i n vesti gati o nal dr u g o n t he fe male a n d male re pr o d ucti ve s yste ms are still 
u n k n o w n, it is ver y i m p orta nt t hat patie nts i n t his st u d y use a hi g hl y effecti ve met h o d of 
c o ntrace pti o n d uri n g partici pati o n i n t his st u d y a n d f or 3 0 da ys after t he last d ose of st u d y dr u g, 
a n d n ot bec o me pre g na nt or fat her a c hil d d uri n g t his st u d y a n d f or 3 0 da ys after t he last d ose of 
st u d y dr u g.   
W o me n w h o are pre g na nt or breastfee di n g ma y n ot partici pate i n t his st u d y.  Hi g hl y effecti ve 
met h o ds of c o ntrace pti o n are re q uire d d uri n g partici pati o n i n t his st u d y, a n d f or 3 0 da ys after t he 
last d ose of st u d y dr u g, f or b ot h male a n d fe male patie nts a n d/ or f or t heir part ners, u nless he or 
s he is s ur gicall y sterile or of n o nc hil d beari n g p ote ntial (ie, p ost me n o pa usal, defi ne d as 
1 2 c o nsec uti ve m o nt hs wit h n o me nses wit h o ut a n alter nate me dical ca use).  Hi g hl y effecti ve 
met h o ds of c o ntrace pti o n are defi ne d as t h ose t hat res ult i n a l o w fail ure rate w he n use d 
c o nsiste ntl y a n d c orrectl y, al o ne or i n c o m bi nati o n.  N ote, t he effects of LJ P C - 4 0 1 o n t he 
effecti ve ness of h or m o nal c o ntrace pti o n are c urre ntl y u n k n o w n. 
T he f oll o wi n g are c o nsi dere d hi g hl y effecti ve met h o ds of c o ntrace pti o n: 
•  S ur gical sterilit y ( vasect o m y, bilateral t u bal li gati o n, or h ysterect o m y)  
•  I ntra uteri ne de vice (I U D) 
•  H or m o na l i ntra uteri ne s yste m (I U S), i m pla nts, or i njecti o ns  
•  C o nsiste nt use of a n a p pr o ve d oral c o ntrace pti ve pill (c o m bi ne d pr o gesti n/estr o ge n 
pill or pr o gesti n - o nl y pill) 

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•  C o m bi ne d i ntra va gi nal or tra ns der mal met h o d  
A bsti ne nce ca n be use d as a met h o d of c o ntrace pti o n.  Peri o dic a bsti ne nce (cale n dar, 
s y m pt ot her mal, p ost o v ulati o n met h o ds), wit h dra wal (c oit us i nterr u pt us), s per mici des or 
c o n d o ms o nl y, a n d lactati o nal a me n orr hea met h o d are n ot acce pta ble met h o ds of c o ntrace pti o n. 
Oral, i m pla nta ble, or i njecta ble c o nt race pti ves are o nl y c o nsi dere d effecti ve if use d pr o perl y a n d 
be g u n at least 3 0 da ys pri or t o t he Scree ni n g visit. 
1 0. 1. 6. 6.  Uri n al ysis  
Uri ne sa m ples f or r o uti ne uri nal ysis para meters i ncl u de: 
•  S pecific gra vit y  
•  p H 
•  Bl o o d 
•  Bilir u bi n  
•  Pr otei n  
•  Ket o nes 
•  Gl uc ose 
•  Nitrite  
 
A n y para meter wit h a b n or mal uri nal ysis res ults will be f urt her c haracterize d t hr o u g h uri ne 
micr osc o p y. 
1 0. 1. 6. 7.  I m m u n o ge nicit y 
Bl o o d s a m pl es will be c ollecte d t o assess i m m u n o ge nic effect .  P har mac o ki netics will be 
assesse d c o nc o mita ntl y t o deter mi ne if t here is a relati o ns hi p bet wee n dr u g c o nce ntrati o n a n d 
i m m u n o ge nicit y (if a nti- dr u g a nti b o dies or ne utralizi n g a nti b o dies de vel o p).  I n a d diti o n, t he 
s parse c o nce ntrati o n data of LJ P C- 4 0 1 t hat will be c ollecte d ma y be use d i n c o m bi nati o n wit h 
data c ollecte d fr o m ot he r st u dies t o s u p p ort f ut ure c o m p osite P K/ P D m o deli n g a n d a nal ysis t hat 
will be n ot be re p orte d i n t his st u d y . 
If a patie nt de vel o ps a nti b o dies t o LJ P C - 4 0 1, treat me nt will be disc o nti n ue d, a n d t he patie nt will 
be m o nit ore d u ntil a nti b o d y le vels ret ur n t o ba seli ne.  I n patie nts t hat ser oc o n vert, a nti b o d y 
le vels will be m o nit ore d u ntil t he y ret ur n t o baseli ne a n d c haracterize d f or titer, bi n di n g t o 
e n d o ge n o us c o u nter parts, a n d ne utralizi n g ca pacit y.  F or safet y, p atie nts ma y be as ke d t o ret ur n 
t o t he cli nic f or c ollecti o n of a d diti o nal i m m u n o ge nicit y sa m ples t o c o nfir m w het her a nti b o d y 
le vels ha ve ret ur ne d t o baseli ne .  
1 0. 2.  
Q u alit y of Life Q uesti o n n aire s 
Q ualit y - of-Life Q uesti o n na ires ( S F-3 6 v 2) , W O M A C, a n d t he m o difie d  Dreisler i n dices f or  
art hritis will be a d mi nistere d  t o patie nt s (i n l ocal la n g ua ge) t o c o m plete d uri n g st u d y visits.  
E val uati o ns will be perf or me d at ti mes s pecifie d i n Ta ble  3. 

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1 1.  
A D V E R S E A N D S E RI O U S A D V E R S E E V E N T S  
1 1. 1.  
Defi niti o n of A d verse E ve nts  
1 1. 1. 1.  
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 occ urre nce i n a patie nt or cli nical i n vesti gati o n 
s u bject a d mi nistere d a p har mace utical pr o d uct a n d w hic h d oes n ot necessaril y ha ve a ca usal 
relati o ns hi p wit h t his treat me nt.  
A n A E ca n t heref ore be a n y u nfa v ora ble a n d u ni nte n de 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, f or e xa m ple), s y m pt o m, or disease te m p orall y ass ociate d wit h t he use of a me dici nal 
pr o d uct, w het her or n ot c o nsi dere d re late d t o t he me dici nal pr o d uct. 
A Es i ncl u de, b ut are n ot li mite d t o: ( 1) a w orse ni n g or c ha n ge i n nat ure, se verit y, or fre q ue nc y of 
c o n diti o n(s) prese nt at t he start of t he st u d y; ( 2) s u bject deteri orati o n d ue t o pri mar y  ill ness; 
( 3) i nterc urre nt ill ness; a n d ( 4) dr u g i nteracti o n.  F or rec or di n g p ur p oses, pre g na nc y is a me dical 
c o n diti o n a n d is n ot c o nsi dere d a n A E (see t he Pre g na nc y a n d F oll o w- u p Secti o n  1 1. 5  bel o w). 
Patie nts  s h o ul d be q uesti o ne d i n a ge neral wa y, wit h o ut lea di n g t he s u bject or as ki n g a b o ut t he 
occ ur re nce of a n y s pecific s y m pt o m. 
T he I n vesti gat or s h o ul d atte m pt t o esta blis h a dia g n osis of t he e ve nt base d o n si g ns, s y m pt o ms, 
a n d/ or ot her cli nical i nf or mati o n.  T he dia g n osis a n d n ot t he i n di vi d ual si g ns/s y m pt o ms s h o ul d 
be d oc u me nte d as t he A E.  F or e xa m ple, if t he u n derl yi n g disease pr ocess is a gastric ulcer, it 
w o ul d n ot be a p pr o priate t o rec or d t he A E b y descri bi n g t he s y m pt o ms “st o mac h pai n, or 
i n di gesti o n, or a p petite l oss, etc.”  T he A E me dical ter m of “ gastric ulcer” s h o ul d be rec or de d as 
t he A E. 
1 1. 1. 2.  
Seri o us A d verse E ve nt  
A n S A E  (e x perie nce or reacti o n) is a n A E  t hat res ults i n 1 or m ore of t he f oll o wi n g: 
•  Res ults i n deat h - A n A E  t hat ca use d or c o ntri b ute d t o a fatal o utc o me. 
•  Is life-t hreate ni n g - Refers t o a n e ve nt/reacti o n i n w hic h t he patie nt was at ris k of 
deat h at t he ti me of t he e ve nt/reacti o n.  It d oes n ot refer t o a n e ve nt/reacti o n w hic h 
h y p ot heticall y mi g ht ha ve ca use d deat h if it were m ore se vere. 
•  Re q uires i n patie nt h os pitalizati o n or pr ol o n gati o n of e xisti n g h os pitalizati o n. 
•  Res ults i n persiste nt or si g nifica nt disa bilit y/i nca pacit y.  
•  Res ults i n a c o n ge nital a n o mal y/ birt h defect.  
•  I m p ortant me dical e ve nts w he n base d u p o n a p pr o priate me dical j u d g me nt, ma y 
je o par dize t he patie nt or s u bject a n d ma y re q uire me dical or s ur gical i nter ve nti o n t o 
pre ve nt 1 of t he o utc o mes liste d i n t his defi niti o n. 

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La J olla P har mace utical - C o nfi de ntial  
Date :  1 4  Dece m ber  2 0 1 8  ( Versi o n 6. 0) 
1 1. 2.  
Rel ati o ns hi p t o I n vesti g ati o n al Pr o d uct  a n d Se veri t y 
T he I n vesti gat or will d oc u me nt her/ his o pi ni o n of t he relati o ns hi p of t he A E t o treat me nt wit h 
t he i n vesti gati o nal pr o d uct usi n g t he criteria o utli ne d i n Ta ble 4 .  A n A E f or w hic h t here is a 
“reas o na ble p ossi bilit y” t hat t he i n vesti gati o nal pr o d uct ca us e d t he A E mea ns t here is e vi de nce 
t o s u g gest a ca usal relati o ns hi p bet wee n t he i n vesti gati o nal pr o d uct a n d t he A E. 
If t he relati o ns hi p bet wee n t he A E/ S A E a n d t he i n vesti gati o nal pr o d uct is deter mi ne d t o be 
“ p ossi ble” or “ pr o ba ble,” t he e ve nt will be c o nsi d ere d t o be relate d t o t he i n vesti gati o nal pr o d uct. 
T a ble  4: 
Rel ati o ns hi p of A d verse E ve nts t o I n vesti g ati o n al Pr o d uct  
Rel ati o ns hi p  
Descri pti o n  
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, wit h a reas o na ble ti me 
se q ue nce t o a d mi nistrati o n of t he i n vesti gati o nal pr o d uct, u nli kel y t o be attri b ute d 
t o c o nc urre nt disease or ot her dr u gs or c he micals, a n d w hic h f oll o ws a cli nicall y 
reas o na ble res p o nse o n wit h dra wal ( de -c halle n ge); or  
a n e ve nt t hat c o ul d als o be e x plai ne d b y c o nc urre nt disease or ot her dr u gs or 
c he micals w h ere i nf or mati o n o n i n vesti gati o nal pr o d uct wit h dra wal ma y be lac ki n g 
or u nclear.  
Re- c halle n ge or de -c halle n ge i nf or mati o n  is n ot re q uire d t o f ulfill t his defi niti o n. 
N ot 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, wit h s ufficie nt e vi de nce t o 
acce pt t hat t here is n o ca usal relati o ns hi p t o i n vesti gati o nal pr o d uct a d mi nistrati o n 
(e g, n o te m p oral relati o ns hi p t o i n vesti gati o nal pr o d uct a d mi nistrati o n, beca use t he 
i n vesti gati o nal pr o d uct was a d mi nistere d after o nset of e ve nt; i n vesti gati o n s h o ws 
t hat t he dr u g was n ot a d mi nistere d; pr o of of ot her ca use; etc.); or 
a n e ve nt wit h a te m p oral relati o ns hi p t o i n vest i gati o nal pr o d uct a d mi nistrati o n, 
w hic h ma kes a ca usal relati o ns hi p i m pr o ba ble, a n d ot her dr u gs, c he micals or 
u n derl yi n g disease pr o vi de pla usi ble e x pla nati o ns.  
 
A Es m ust be gra de d f or se verit y ( mil d, m o derate, se vere , life-t hreate ni n g, a n d fatal) as define d i n 
Ta ble  5, a n d m ust be e ntere d o n t he A E pa ge of t he e C R F.  It s h o ul d be n ote d t hat t he ter m 
“se vere” use d t o gra de i nte nsit y is n ot s y n o n y m o us wit h t he ter m “seri o us.”  T he assess me nt of 
se verit y is ma de re gar dless of i n vesti gati o nal pr o d uct relati o ns hi p or of t he seri o us ness of t he 
A E .   

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LJ P C - 4 0 1 
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La J olla P har mace utical - C o nfi de ntial  
Date :  1 4  Dece m ber  2 0 1 8  ( Versi o n 6. 0) 
T a ble  5: 
Se verit y of A d verse E ve nts  
Gr a de  
Cli nic al Descri pti o n of Se verit y  
Mil d  
A n e x perie nce t hat is tra nsie nt  or mil d  a n d re q uires n o me dical  treat me nt 
or i nter ve nti o n.  T he e x perie nce d oes n ot ge nerall y i nterfere wit h us ual 
dail y acti vities.  T his i ncl u des tra nsie nt la b orat or y test alterati o ns.  
M o derate  
N o or mi ni mal me dical i nter ve nti o n/t hera p y re q uire d.  Mil d t o m o de rate 
li mitati o n i n acti vit y – s o me assista nce ma y be nee de d.  I ncl u des 
la b orat or y test alterati o ns i n dicati n g i nj ur y, b ut wit h o ut l o n g-ter m ris k. 
Se vere  
A n e x perie nce t hat re q uires me dical i nter ve nti o n/t hera p y, h os pitalizati o n 
p ossi ble.  Mar ke d li mitati o n  i n acti vit y, s o me assista n ce us uall y re q uire d.  
Life -t hreate ni n g 
Life -t hreate ni n g c o nse q ue nces; ur ge nt i nter ve nti o n i n dicate d. 
Fatal  
Deat h relate d t o A E  
1 1. 3.  
Re p orti n g of A d verse E ve nts a n d Seri o us A d verse E ve nts  
1 1. 3. 1.  
Re p orti n g of A d verse E ve nts  
A E data will be c ollecte d at c o nse nt  u ntil t he patie nt f ull y c o m pletes her/ his st u d y partici pati o n. 
All A Es, w het her belie ve d b y t he I n vesti gat or t o be relate d or u nrelate d t o t he i n vesti gati o nal 
pr o d uct, m ust be d oc u me nte d i n t he patie nt’s me dical rec or ds, i n acc or da nce wit h t he 
I n vesti gat or’s n or mal cli nical practice a n d o n t he A E e C R F.  Eac h A E is t o be e val uate d f or 
d urati o n, i nte nsit y, fre q ue nc y, seri o us ness, o utc o me, ot her acti o ns ta ke n, a n d relati o ns hi p t o t he 
i n vesti gati o nal pr o d uct.     
1 1. 3. 2.  
Re p orti n g of Seri o us A d verse E ve nts  
I n a greei n g t o t he pr o visi o ns of t his pr ot oc ol, t he I n vesti gat or acce pts all le gal res p o nsi bilities f or 
i m me diate re p orti n g of S A Es t o La  J olla.  I m me diate re p orti n g i m plies wit hi n 2 4 h o urs of 
bec o mi n g a ware of t h e occ urre nce of a n S A E.  
S A E data will be c ollecte d starti n g at c o nse nt u ntil t he patie nt f ull y c o m pletes her/ his st u d y 
partici pati o n.  
All S A Es t hat occ ur wit hi n 3 0 da ys f oll o wi n g t he cessati o n of i n vesti gati o nal pr o d uct, re gar dless 
of t he ca usal relati o ns hi p t o t he i n vesti gati o nal pr o d uct, m ust be re p orte d t o La  J olla b y 
f oll o wi n g t he i nstr ucti o ns pr o vi de d i n t his secti o n.  Re dacte d me dical rec or d s o urce 
d oc u me ntati o n will be re q ueste d f or all S A Es a n d e mer ge nc y r o o m visits. 
T he met h o d f or re p orti n g a S A E is b y c o m pleti n g t he A E/ S A E e C R F a n d se n di n g a Seri o us 
A d verse E ve nt Re p ort F or m.  T he Seri o us A d verse E ve nt Re p ort F or m, a n d if a p plica ble, a c o p y 
of re dacte d s o urc e d oc u me nts (s uc h as h os pital disc har ge s u m mar y, me dical rec or ds, etc.) relate d 
t o t he S A E will  be se nt t o:  
•  E- mail t o:   safet y @lj pc.c o m 
•  Or fa x t o:  + 1- 8 5 8- 2 6 3- 1 5 9 3 

Pr ot oc ol LJ 4 0 1- H H 0 1  
 
LJ P C - 4 0 1 
6 0 
La J olla P har mace utical - C o nfi de ntial  
Date :  1 4  Dece m ber  2 0 1 8  ( Versi o n 6. 0) 
T he I n vesti gat or will assess w het her t he e ve nt is ca usall y relate d t o t he i n vesti gati o nal pr o d uct.  
La  J olla will als o assess w het her t he e ve nt is ca usall y relate d t o t he i n vesti gati o nal pr o d uct, i n 
a d diti o n t o assessi n g t he o verall safet y pr ofile of t he i n vesti gati o nal pr o d uct. 
La  J olla will n otif y t he a p pr o priate re g ulat or y a ut h orities i n acc or da nce wit h c o u ntr y re g ulati o ns. 
F oll o wi n g t he i nitial re p ort, a n y a d diti o nal i nf or mati o n o btai ne d b y t he I n vesti gat or a b o ut t he 
S A E m ust be re p orte d pr o m ptl y t o La  J olla i n t he sa me ma n ner as descri be d a bo ve f or t he i nitial 
S A E re p ort.  
If a n I n vesti gat or bec o mes a ware of a n S A E t hat ma y be attri b uta ble t o t he i n vesti gati o nal 
pr o d uct after t he st u d y is c o m plete d, La  J olla s h o ul d be n otifie d as s o o n as p ossi ble via e mail, 
p h o ne, or fa x at: 
•  E- mail t o:  safet y @lj pc.c o m 
•  P h o ne (see title pa ge f or p h o ne n u m bers)   
•  Or fa x t o:  + 1 - 8 5 8- 2 6 3- 1 5 9 3 
1 1. 4.  
F oll o w -u p of A Es a n d S A Es  
All A Es m ust be f oll o we d d uri n g t he c o urse of t he st u d y u ntil t he A E res ol ves, is n o l o n ger of 
cli nical c o ncer n, has sta bilize d or is ot her wise e x plai ne d, or t he patie nt is l ost t o f oll o w- u p. 
A Es o n g oi n g at t he fi nal f oll o w- u p visit t hat are dee me d t o be “relate d” t o t he i n vesti gati o nal 
pr o d uct or of ot her cli nical si g nifica nce, m ust be f oll o we d f or as l o n g as necessar y t o a de q uatel y 
e val uate t he safet y of t he patie nt or u ntil t he e ve nt sta bilizes, res ol ves, or is n o l o n ger of cli nical 
c o ncer n.  If res ol ve d, a res ol uti o n date f or t he A E s h o ul d be d oc u me nte d i n t he e C R F.  T he 
I n vesti gat or m ust e ns ure t hat f oll o w-u p i ncl u des a n y  s u p ple me ntal i n vesti gati o ns i n dicate d t o 
el uci date t he nat ure a n d/ or ca usalit y of t he A E.  T his ma y i ncl u de a d diti o nal la b orat or y tests or 
i n vesti gati o ns, or c o ns ultati o n wit h ot her healt hcare pr ofessi o nals, as c o nsi dere d cli nicall y 
a p pr o priate b y t he I n v esti gat or. 
1 1. 5.  
Pre g n a nc y a n d F oll o w -u p  
Pre g na ncies are n ot c o nsi dere d A Es i n a n d of t he msel ves; h o we ver, if a fe male st u d y partici pa nt 
bec o mes pre g na nt w hile s he is e nr olle d i n t he cli nical st u d y, or if a male patie nt ma kes his 
part ner pre g na nt w hile he is e nr olle d i n t he cli nical st u d y, t he n t he I n vesti gat or m ust be i nf or me d 
i m me diatel y.  La  J olla m ust be n otifie d wit hi n 2 4 h o urs of t he I n vesti gat or’s lear ni n g of t he 
pre g na nc y b y c o m pleti n g a n d se n di n g t he Pre g na nc y Re p ort F or m t o safet y @lj pc.c o m ( or 
alter nati vel y, fa x t o + 1 ( 8 5 8) 2 6 3- 1 5 9 3). 
C o m pleti n g t he Pre g na nc y Re p ort F or m is n ot a s u bstit ute f or re p orti n g a n A E/ S A E w he n a n 
A E/ S A E has occ urre d.  I n t he sit uati o n w he n a n A E/ S A E has occ urre d, t he A E/ S A E re p orti n g 
pr oce d ures descri be d i n Secti o ns  1 1. 3. 1  a n d 1 1. 3. 2   m ust als o be f oll o we d. 
Fe male patie nts :  T he fe male patie nt m ust disc o nti n ue treat me nt wit h i n vesti gati o nal pr o d uct if 
s he bec o mes pre g na nt.  T he pr o gress of t he pre g na nc y will be f oll o we d b y t he I n vesti gat or u ntil 
t he o utc o me of t he pre g na nc y is k n o w n.  If t he pre g na nc y res ults i n t he birt h of a c hil d, t he 
patie nt a n d ne o nate m ust be f oll o we d f or o utc o me i nf or mati o n a n d/ or as c o nsi dere d a p pr o priate 
b y t he I n vesti gat or a n d La J olla. 

Pr ot oc ol LJ 4 0 1- H H 0 1  
 
LJ P C - 4 0 1 
6 1 
La J olla P har mace utical - C o nfi de ntial  
Date :  1 4  Dece m ber  2 0 1 8  ( Versi o n 6. 0) 
Male patie nts :  T he pr o gress of t he pre g na nc y i n a male patie nt’s part ner s h o ul d be f oll o we d 
u ntil t he o utc o me of t he pre g na nc y is k n o w n.  If t he pre g na nc y res ults i n t he birt h of a c hil d, 
a d diti o nal f oll o w- u p o utc o me i nf or mati o n ma y be re q ueste d f or t he m ot her a n d ne o nate.  
F oll o w- u p will o nl y be perf or me d t o t he e xte nt per mitte d b y a p plica ble re g ulati o ns a n d pri vac y 
c o nsi derati o ns.  
Refer t o Secti o n  1 0. 1. 6. 5. 1  f or c o ntrace pti o n g ui da nce a n d i nf or mati o n. 
 

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LJ P C - 4 0 1 
6 2 
La J olla P har mace utical - C o nfi de ntial  
Date :  1 4  Dece m ber  2 0 1 8  ( Versi o n 6. 0) 
1 2.  
S T A TI S TI C S  
1 2. 1.  
St atistic al H y p ot hesi s 
It is h y p ot hesize d t hat t h ose treate d wit h LJ P C - 4 0 1 will ha ve a differe nt c ha n ge i n T S A T fr o m 
baseli ne t o Wee k 1 6 p ost d ose 2 4 ( ± 4) h o urs t ha n t h ose treate d wit h place b o. 
N ull H y p ot hesis:    
  
  
µ acti ve = µ place b o 
Alter nati ve H y p ot hesis:     
µacti ve ≠ µplace b o 
w here µ is t he mea n c ha n ge i n T S A T fr o m baseli ne t o Wee k 1 6 p ost d ose 2 4 ( ± 4) h o urs. 
1 2. 2.  
S a m ple Size a n d P o wer C o nsi der ati o ns  
A sa m ple size of 4 8 patie nts has 8 0 % p o wer t o detect a 1 5 % differe nce i n t he c ha n ge i n T S A T 
bet wee n t he place b o ar m a n d t he LJ P C - 4 0 1 ar m, ass u mi n g a c o m m o n sta n dar d de viati o n ( S D) of 
1 8 % a n d a 2-si de d t y pe I err or of 0. 0 5.  T he pri mar y efficac y a nal ysis a n d sec o n dar y efficac y 
a nal yses will i ncl u de t he Efficac y Patie nt P o p ulati o n defi ne d i n Secti o n  1 2. 7  (ie, all patie nts 
e nr olle d u n der gl o bal p r ot oc ol versi o n 4. 0/ U nite d Ki n g d o m ( U K ) pr ot oc ol versi o n 4. 1 or later 
w h o recei ve d st u d y dr u g, a n d w h o  c o m plete d t he Wee k  1 6 assess me nt s or ha d a n o n-st u d y 
p hle b ot o m y after t he sta n dar d of care t hera pe utic p hle b ot o m y o n Da y 1 [ pre d ose ] a n d bef ore 
Wee k 1 6).  Patie nts w h o d o n ot e nr oll u n der gl o bal p r ot oc ol versi o n 4. 0/ U K pr ot oc ol versi o n 4. 1 
or later or disc o nti n ue t he st u d y earl y pri or t o d osi n g will be re place d ( patie nts ma y be re place d 
f or a d diti o nal reas o ns as descri be d i n Secti o n 1 2. 4 ).  T he pla n is t o e nr oll a n d ra n d o mize 
a p pr o xi matel y 6 8 t o 7 6 patie nts ( 1: 1 t o LJ P C- 4 0 1 or place b o) t o e ns ure t hat at least 4 8  patie nts 
are i ncl u de d i n t he pri mar y efficac y a nal ysis . 
Refer t o Secti o n  1 2. 5  f or pla n ne d a nal yses. 
1 2. 3.  
Str atific ati o n a n d R a n d o miz ati o n  
Ce ntral ra n d o mizati o n will be perf or me d  usi n g I X R S.  Eli gi ble patie nts will be ra n d o mize d o n a 
1: 1 sc he d ule t o LJ P C - 4 0 1 or place b o.  Ra n d o mizati o n will be stratifie d b y baseli ne T S A T 
( > 4 5% t o 7 0 % vers us > 7 0 %) a n d p hle b ot o m y fre q ue nc y o ver t he last 1 2 m o nt hs ( 0 t o 3 vers us 
> 3). 
1 2. 4.  
Re pl ace me nt of P atie nts  
Patie nts w h o are ra n d o mize d b ut ter mi nate pri or t o d osi n g will be re place d a n d e xcl u de d fr o m 
t he safet y a n d efficac y a nal yses.  Patie nts w h o ha ve recei ve d st u d y dr u g a n d ter mi nate t he st u d y 
earl y ma y be re place d b y decisi o n of t he I n vesti gat or a n d La J olla.  Patie nts w h o d o n o t e nr oll 
u n der pr ot oc ol versi o n 4. 0/ U K pr ot oc ol versi o n 4. 1 or later will be re place d a n d e xcl u de d fr o m 
efficac y a nal yses.  A p pr o xi matel y 2 0 t o 2 8 patie nts are e x pecte d t o be re place d.  Patie nts w h o 
c o nse nt a n d e nr oll u n der pr ot oc ol versi o n 4. 0/ U K pr ot oc ol versi o n 4. 1 or later will be i ncl u de d i n 
efficac y a nal yses.  All e nr olle d patie nts, re gar dless of pr ot oc ol versi o n, w h o recei ve at least 
1 d ose of st u d y dr u g will be i ncl u de d i n safet y a nal yses.   
Patie nt e nr oll me nt n u m bers are u ni q ue  a n d will n ot be re-assi g ne d.  Patie nts will n ot be 
per mitte d re -ra n d o mizati o n after t he i nitial ra n d o mizati o n f or a n y reas o n.  Patie nts will n ot be 
per mitte d t o re -e nr oll after wit h dra wi n g fr o m t he st u d y f or a n y reas o n. 

Pr ot oc ol LJ 4 0 1- H H 0 1  
 
LJ P C - 4 0 1 
6 3 
La J olla P har mace utical - C o nfi de ntial  
Date :  1 4  Dece m ber  2 0 1 8  ( Versi o n 6. 0) 
1 2. 5.  
Pl a n ne d A n al yses  
A n i nteri m a nal ysis of efficac y data will be c o n d ucte d after t he first 1 6 patie nts  fr o m t he Efficac y 
Patie nt P o p ulati o n  ( defi ne d i n Secti o n 1 2. 7 ) c o m plete t he Wee k  1 6 assess me nts  or ha ve a n 
o n-st u d y p hle b ot o m y aft er t he sta n dar d of care t hera pe utic p hle b ot o m y o n Da y 1 ( pre d ose) a n d 
bef ore Wee k 1 6.  T he La n  De mets a p pr oac h t o t he O’ Brie n- Fle mi n g met h o d f or se q ue ntial 
desi g ns w ill be a p plie d t o preser ve t he o verall t y pe I err or rate res ulti n g i n t y pe I rates of val ues 
of 0. 0 0 0 2 1 at t he i nteri m a nal ysis ( n = 1 6) a n d 0. 0 4 9 9 at t he fi nal a nal ysis ( n = 4 8).  A n y 
s u bse q ue nt i nteri m a nal yses will si milarl y i ncl u de a dj ust me nt usi n g t he La n Dem ets a p pr oac h t o 
t he O’ Brie n- Fle mi n g met h o d f or se q ue ntial desi g ns.   
T he fi nal a nal yses will be perf or me d after t he statistical a nal ysis pla n (S A P ) is fi nalize d a n d t he 
data base is l oc ke d.  T he details of data q ualit y ass ura nce a n d data base l oc k are pr o vi de d i n S A P . 
I n a d diti o n t o t he i nteri m a nal ysis of efficac y data, a n i nter nal Safet y M o nit ori n g C o m mittee will 
c o n d uct a n i nitial safet y re vie w si m u lta ne o usl y wit h t he i nteri m efficac y a nal ysis; a d diti o nal 
safet y re vie ws will be c o n d ucte d t hereafter.  Details, s uc h as me m bers hi p of t he c o m mittee, will 
be disc usse d i n t he Safet y M o nit ori n g C o m mittee  C harter.  
M o dificati o ns t o t he pla n ne d statistical a na l yses s h o ul d be mi ni mize d.  H o we ver, t he data 
o btai ne d fr o m t he st u d y ma y i n dicate t hat t he pla n ne d a nal yses are i na p pr o priate or t hat 
a d diti o nal a nal yses nee d t o be perf or me d d ue t o fact ors s uc h as t he distri b uti o n of t he data or t he 
prese nce of i m p orta nt c o variates.  A n y de viati o ns fr o m t he pla n ne d statistical a nal yses will be 
re p orte d i n t he cli nical st u d y re p ort. 
1 2. 6.  
A n al ysis P ar a meters  
1 2. 6. 1.  
E n d p oi nts  
1 2. 6. 1. 1.  Pri m ar y Effic ac y E n d p oi nt  
T he pri mar y efficac y e n d p oi nt is c ha n ge i n T S A T, defi ne d as f oll o ws: 
•  F or patie nts wit h  1 p hle b ot o m y (t he sta n dar d of care t hera pe utic p hle b ot o m y o n 
Da y  1 [ pre d ose]), c ha n ge i n T S A T fr o m baseli ne t o Wee k 1 6 ( 2 4 [ ± 4] h o urs 
p ost d ose). 
•  F or patie nts u n der g oi n g 2 or m ore p hle b ot o mies, c ha n ge i n T S A T fr o m baseli ne t o 
t he m ost rece nt p ost d ose fasti n g T S A T o bser ve d pri or t o t he sec o n d p hle b ot o m y. 
1 2. 6. 1. 2.  Sec o n d ar y Effic ac y E n d p oi nts  
T he sec o n dar y e n d p oi nts t o be e val uate d i ncl u de: 
•  N u m ber of p hle b ot o m ies fr o m Da y 2 t o E O S . 
•  C ha n ge i n ser u m ferriti n, defi ne d as f oll o ws: 
− F or patie nts wit h 1 p hle b ot o m y (t he sta n dar d of care t hera pe utic p hle b ot o m y o n 
Da y 1 [ pre d ose]) , c ha n ge i n ser u m ferriti n fr o m baseli ne t o Wee k 1 6 
( 2 4 ± 4] h o urs p ost d ose). 

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− F or patie nts u n der g oi n g 2 or m ore p hle b ot o m ies, c ha n ge i n ser u m ferriti n fr o m 
basel i ne t o t he m ost rece nt p ost d ose ser u m ferriti n o bser ve d pri or t o t he sec o n d 
p hle b ot o m y. 
1 2. 6. 1. 3.  S afet y a n d T oler a bilit y E n d p oi nts  
T he safet y a n d t olera bilit y e n d p oi nts t o be e val uate d i ncl u de: 
•  A d verse E ve nts fr o m c o nse nt t o E O S. 
•  C ha n ges i n cli nical la b orat or y e val uati o ns i ncl u di n g ser u m ir o n para meters fr o m 
baseli ne t o E O S . 
•  C ha n ges i n vital si g ns, electr ocar di o gra ms ( E C Gs), use of c o nc o mita nt me dicati o ns, 
a n d p h ysical e xa mi nati o ns fr o m baseli ne t o E O S. 
•  I m m u n o ge nicit y (a nti- dr u g a nti b o d y)/ P K baseli ne t o E O S. 
1 2. 6. 1. 4.  E x pl or a t or y E n d p oi nts 
T he e x pl orat or y e n d p oi nts t o be e val uate d i ncl u de: 
•  C ha n ge i n ser u m ir o n para meters , defi ne d as f oll o ws: 
− F or patie nts wit h 1 p hle b ot o m y (t he sta n dar d of care t hera pe utic p hle b ot o m y o n 
Da y 1 [ pre d ose]), c ha n ge i n ser u m ir o n para meters fr o m baseli ne t o Wee k 1 6 
( 2 4 [ ± 4] h o urs p ost d ose). 
− F or patie nts u n der g oi n g 2 or m ore p hle b ot o m ies, c ha n ge i n ser u m ir o n para meters 
fr o m baseli ne t o t he m ost rece nt p ost d ose ser u m ir o n para meters o bser ve d pri or t o 
t he sec o n d p hle b ot o m y. 
− F or patie nts wit h 1 p hle b ot o m y (t he sta n dar d of care t hera pe utic p hle b ot o m y o n 
Da y  1 [ pre d ose]), c ha n ge i n ser u m ir o n para meters fr o m baseli ne t o Wee k 1 7 
(a p pr o xi matel y 7 da ys after t he last d ose of st u d y dr u g). 
− F or patie nts u n der g oi n g 2 or m ore p hle b ot o m ies, c ha n ge i n ser u m ir o n para meters 
fr o m baseli ne t o t he m ost rece nt pre d ose ser u m ir o n para meters o bser ve d pri or t o 
t he sec o n d p hle b ot o m y. 
•  C ha n g e i n t h yr oi d f u ncti o n fr o m baseli ne t o Wee k 1 6. 
•  C ha n ge i n li ver f u ncti o n fr om baseli ne t o Wee k 1 6 . 
•  C ha n ge i n he m o gl o bi n A 1 c fr o m baseli ne t o Wee k 1 6 . 
•  C ha n ge i n R B C para met ers i ncl u di n g he m o gl o bi n c o nce ntrati o n , R B C c o u nt, a n d 
R D W  defi ne d as f oll o ws: 
− F or patie nts wit h 1 p hle b ot o m y (t he sta n dar d of care t hera pe utic p hle b ot o m y o n 
Da y  1 [ pre d ose]), c ha n ge i n R B C para meters fr o m baseli ne t o 
Wee k  1 6 ( 2 4 [ ± 4] h o urs p ost d ose). 

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− F or patie nts u n der g oi n g 2 or m ore p hle b ot o mies, c ha n ge i n R B C para meters fr o m 
baseli ne t o t he m ost rece nt p ost d ose R B C para meters o bser ve d pri or t o t he sec o n d 
p hle b ot o m y. 
•  C ha n ge i n Q ualit y of Life Q uesti o n naire s, (S F -3 6 v 2) , W O M A C, a n d m o difie d 
Dreisler i n dices f or art hritis,  fr o m baseli ne  t o Wee k 1 6. 
1 2. 6. 2.  
Defi niti o n of S u b gr o u ps  
T he f oll o wi n g s u b gr o u ps are c o nsi dere d of i nterest t o c o m parati vel y e x pl ore t he treat me nt effect: 
•  A ge  cate g or y :  < 6 5 years vers us ≥ 6 5 years 
•  Se x :  male vers us fe male 
•  Et h nic it y:  His pa nic or Lati n o, N ot His pa nic or Lati n o  
•  C o u ntr y:  U nite d States of A merica, A ustralia, U nite d Ki n g d o m, a n d Fra nce ( ma y be 
c olla pse d pri or t o data freeze)  
•  Ge o gra p hic re gi o ns : (t o be deter mi ne d base d o n e nr olli n g c o u ntries) 
•  Race:  W hite  vers us n o n-W hite  
•  B o d y mass i n de x ( B MI):  < 3 0 k g/ m 2; ≥ 3 0 k g/ m2 (B MI = wei g ht( k g)/ hei g ht( m) 2) 
•  P hle b ot o m y fre q ue nc y o ver t he last 1 2 m o nt hs:  0 t o 3 vers us > 3 
•  Baseli ne T S A T:   > 4 5 % t o 7 0 % vers us > 7 0 % 
•  Basel i ne he pci di n le vels:  < me dia n vers us ≥ me dia n 
•  Baseli ne ser u m ir o n le vels:  < me dia n vers us ≥ me dia n 
•  Baseli ne ser u m ferriti n le vels:  < me dia n vers us ≥ me dia n  
Baseli ne is c o nsi dere d t he last bl o o d sa m ple c ollecti o n pri or t o t he re q uire d p hle b ot o m y of 
Da y  1. 
1 2. 7.  
A n al ysis P o p ul ati o n  
A nal ysis p o p ulati o ns are as f oll o ws:  
•  I nte nt t o Treat (I T T) P o p ulati o n:  all ra n d o mize d patie nts, as ra n d o mize d. 
•  M o difie d I nte nt t o Treat ( mI T T) P o p ulati o n:  e nr olle d patie nts , as ra n d o mize d, w h o 
recei ve d at least 1 d ose of st u d y dr u g. 
•  Efficac y P o p ulati o n :  e nr olle d patie nts  u n der gl o bal p r ot oc ol versi o n 4. 0/U K pr ot oc ol 
versi o n 4. 1 or later , as ra n d o mize d, w h o recei ve d st u d y dr u g, a n d w h o c o m plete d 
4 m o nt hs ( Wee k 1 6) o n st u d y or w h o ha d at least 1 p hle b ot o m y after t he sta n dar d of 
care t hera pe utic p hle b ot o m y o n Da y 1 ( pre d ose) a n d bef ore Wee k 1 6. 
•  Per Pr ot oc ol P o p ulati o n ( P P):  Efficac y patie nts, wit h o ut a n y i m p orta nt pr ot oc ol 
de viati o ns. 

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•  Safet y P o p ulati o n:  e nr olle d patie nts, as treate d, w h o recei ve d at least 1 d ose of st u d y 
dr u g. 
•  P K P o p ulati o n:  e nr olle d patie nts , as treate d, w h o recei ve at least 1 d ose of st u d y dr u g 
a n d f or w h o m at least 1 P K para meter ca n be esti mate d . 
1 2. 8.  
St atistic al Met h o ds  
C o nti n u o us varia bles will be s u m marize d usi n g descri pti ve statistics, i ncl u di n g t he n u m ber of 
o bser vati o ns, mea n, S D , mi ni m u m, me dia n, a n d ma xi m u m val ues.  Ot her descri pti ve statistics 
s uc h as l o wer q uartile, u p per q uartile, ge o metric mea n, a n d ge o metric S D ma y be calc ulate d if 
a p pr o priate .  Cate g orical ( q ualitati ve) varia bles will be s u m marize d b y t he  n u m ber of 
o bser vati o ns a n d perce nta ges.   U nless ot her wise state d, t he calc ulati o n of pr o p orti o ns will be 
base d o n t he sa m ple size of t he p o p ulati o n of i ntere st. 
Data will be s u m marize d b y treat me nt gr o u p, st u d y visit, a n d if a p pr o priate, st u d y i nter val.  
Statistical c o m paris o ns of differe nces bet wee n treat me nt ar ms will be ma de usi n g Wilc o x o n 
ra n k-s u m tests, mi xe d effects re peate d meas ures, a n d/or a nal ysis of varia nce ( A N O V A ) f or 
c o nti n u o us or or di nal varia bles, C hi- S q uare or C oc hra n- Ma ntel -Hae nszel tests f or cate g orical  
varia bles, Fis her’s e xact tests f or bi nar y varia bles , a n d P oiss o n re gressi o n m o del f or c o u nt data 
(e g, n u m ber of p hle b ot o mies). 
All statistical tests will be d o ne at t he 2- si de d, 5 % si g nifica nce le vel, u nless ot her wise s pecifie d.  
T he ass u m pti o ns u n derl yi n g t he statistical tests a p plie d will be e val uate d f or a p pr o priate ness (ie, 
sa m ple distri b uti o n, paire d or c orrelate d data, e q ualit y of varia nces).  C o nfi de nce i nter vals will 
be d o ne at 9 5 %, u nless ot her wise s pecifie d.  
All a nal yses will be perf or me d usi n g S A S, Versi o n 9. 4 or later ( S A S I nstit ute, Car y, N C).  
Gra p hic dis pla ys ma y be pr o d uce d usi n g S A S, S- Pl us or R, Versi o n 3. 1. 1  or later ( R F o u n dati o n 
f or Statistical C o m p uti n g, Vie n na, A ustria). 
A c o m plete descri pti o n of statistical c o nsi derati o ns will be pr o vi de d i n a se parate S A P . 
1 2. 8. 1.  
P atie nt  Dis p ositi o n, De m o gr a p hic, a n d B ac k gr o u n d C h ar acteristics  
Patie nt  dis p ositi o n will be s u m mari ze d b y treat me nt gr o u p as f oll o ws: 
•  N u m ber of patie nt s e nr olle d i n t he st u d y 
•  N u m ber of patie nt s i n eac h a nal ysis p o p ulati o n  
•  Treat me nt i nitiate d? ( yes or n o)  
•  Last visit c o m plete d  
•  Last st u d y da y c o m plete d  
•  Di d t he patie nt c o m plete treat me nt? ( yes or n o) 
− If n o, pri mar y reas o n f or disc o nti n uati o n of treat me nt 
•  Patie nt ali ve at E n d of Treat me nt? ( yes or n o) 
•  Was Da y 3 0 f oll o w- u p c o n d ucte d? ( yes or n o) 

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•  Di d t he patie nt c o m plete t he st u d y? ( yes or n o) 
− If n o, pri mar y reas o n f or st u d y disc o nti n uati o n 
•  Patie nt ali ve at E O S visit? ( yes or n o)  
De m o gra p hics a n d baseli ne c haracteristics will be s u m marize d descri pti ve l y b y treat me nt gr o u p 
as f oll o ws: 
•  A ge cate g or y ( < 6 5 years, ≥ 6 5 years) a n d a ge ( years) 
•  Se x  ( male, fe male) 
•  C hil d beari n g p ote ntial ( yes , n o) 
•  Et h nicit y ( His pa nic or Lati n o, N ot His pa nic or Lati n o) 
•  Race ( A merica n I n dia n or Alas ka Nati ve, Asia n, Blac k or Africa n A merica n, Nati ve 
Ha waiia n or Ot her Pacific Isla n der, W hite, Ot her ; a n d W hite or N o n-W hite ) 
•  Ge o gra p hic re gi o n of ori gi n (t o be deter mi ne d base d o n e nr olli n g c o u ntries) 
•  Ge n ot y pe (if a vaila ble) 
•  Baseli ne hei g ht (c m)  
•  Baseli ne wei g ht ( k g)  
•  Baseli ne B MI  cate g or y ( < 3 0 k g/ m2, ≥ 3 0 k g/ m2) a n d B MI  ( k g/ m2) 
•  Baseli ne T S A T  
•  Baseli ne p hle b ot o m y fre q ue nc y o ver t he last 1 2 m o nt hs 
Refer t o t he S A P f or de m o gra p hic s u m mar y statistical met h o ds.  
1 2. 8. 2.  
Me dic al Hist or y  
Me dical hist or y will be c o de d usi n g t he Me dical Dicti o nar y f or Re g ulat or y Affairs ( Me d D R A) 
m ost rece nt versi o n a n d gr o u pe d b y s yste m or ga n class ( S O C) a n d P T.  T he c o de d ter ms will be 
s u m marize d b y treat me nt gr o u p, S O C, a n d P T i n al p ha betical or der as t he n u m ber of 
c o n diti o ns/e ve nts a n d t he n u m ber a n d perce nta ge of patie nt s wit h a c o n diti o n or e x perie nci n g a n 
e ve nt 1 or m ore ti mes.  
I n a d diti o n, s u m maries of me dical hist or y ma y be re peate d f or m ost freq ue nt me dical hist or y 
w here “ m ost fre q ue nt” is defi ne d as a me dical e ve nt occ urri n g i n > X % of t he sa m ple i n eit her 
treat me nt ar m, w here X % will be deter mi ne d fr o m t he data. 
1 2. 8. 3.  
Pri or a n d C o nc o mit a nt Me dic ati o ns a n d Pr oce d ures  
Pri or a n d c o nc o mita nt me dicati o ns will be s u m marize d se paratel y.  Pri or me dicati o ns are t h ose 
wit h a start date be gi n ni n g 1 4 da ys pri or t o Scree ni n g .  C o nc o mita nt me dicati o ns are me dicati o ns 
t hat are ta ke n a n y ti me w hile o n st u d y ( o n or after first st u d y dr u g a d mi nistrati o n). 
Pri or a n d c o nc o mita nt me dicati o ns will be c o de d usi n g t he W orl d Healt h Or ga nizati o n Dr u g 
Dicti o nar y ( W H O -D D) m ost rece nt versi o n a n d gr o u pe d b y A nat o mical T hera pe utic C he mical 
( A T C) a n d P T.  T he c o de d me dicati o ns will be s u m marize d b y treat me nt gr o u p, A T C, a n d P T i n 

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al p ha betical or der as t he n u m ber of me dicati o ns a n d t he n u m ber a n d perce nta ge of patie nt s 
recei vi n g me dicati o n 1 or m ore ti mes.  
Pri or p hle b ot o m y pr oce d ures ( n u m ber recei ve d d uri n g t he 1 2 m o nt hs pri or t o ra n d o mizati o n) a n d 
c o nc o mita nt p hle b ot o m y pr oce d ures ( n u m ber recei ve d o n st u d y) will be s u m marize d b y 
treat me nt gr o u p usi n g descri pti ve statistics . 
1 2. 8. 4.  
Effic ac y A n al yses 
1 2. 8. 4. 1.  Pri m ar y E n d p oi nt A n al yses ( P ost d ose T S A T)  
T he pri mar y e n d p oi nt will be a nal yze d usi n g a ge neral li near m o del wit h a dj ust me nt f or baseli ne 
T S A T ( > 4 5 % t o 7 0 % vers us > 7 0 %) a n d p hle b ot o m y fre q ue nc y o ver t he last 1 2 m o nt hs ( 0 t o 3 
vers us >  3) .  A 2-taile d al p ha of 0. 0 5 ( 1-si de d al p ha of 0. 0 2 5) will be use d i n testi n g t he 
h y p ot hesis of treat me nt differe nce  wit h a dj ust me nts, as a p pr o priate, f or i nteri m a nal yses . 
I n a d diti o n, T S A T will be s u m marize d b y treat me nt gr o u p a n d visit, a n d b y l o west p ost baseli ne 
val ue, hi g hest p ost baseli ne val ue, a n d last p ost baseli ne visit.  T he c ha n ge fr o m baseli ne a n d 
perce nt c ha n ge fr o m baseli ne will be s u m marize d i n a si milar ma n ner.  
T S A T a n d c ha n ge fr o m baseli ne i n T S A T will be pl otte d b y treat me nt a n d visit o n a li near scale. 
1 2. 8. 4. 1. 1.  Se nsiti vit y A n al ysis of Pri m ar y Effic ac y A n al ysis  
T he prese nce of a site effect a n d site b y treat me nt i nteracti o n will be e xa mi ne d usi n g a ge neral 
li near m o del wit h a dj ust me nt f or site a n d site b y treat me nt i nteracti o n.  Al p ha of 0. 1 5 will be 
use d f or testi n g of site effects.  Selecti o n of sites f or t he m o delli n g will be c o n d ucte d after 
e nr oll me nt has bee n  c o m plete d.  
S u b gr o u p a nal yses will be c o n d ucte d usi n g a ge neral li near m o del wit h a dj ust me nts f or 
treat me nt, s u b gr o u p, a n d s u b gr o u ps b y treat me nt i nteracti o n.   
M ulti variate a nal ysis ma y be perf or me d utilizi n g t he s u b gr o u ps of i nterest defi ne d i n 
Secti o n  1 2. 6. 2 .  Detail will be pr o vi de d i n t he statistical a nal ysis pla n.  
A se nsiti vit y a nal ysis of T S A T will be c o n d ucte d o n t he mI T T P o p ulati o n.  Detail will be 
pr o vi de d i n t he statistical a nal ysis pla n . 
E x pl orat or y  a nal yses of pre d ose T S A T will be perf or me d usi n g t he para meters descri be d a b o ve. 
1 2. 8. 4. 2.  Sec o n d ar y Effic ac y E n d p oi nt A n al yses 
C ha n ge i n ser u m ferriti n fr o m baseli ne t o eac h wee kl y p ost d ose visit a n d eac h wee kl y pre d ose 
visit  will be a nal yze d usi n g a ge neral li near m o del wit h a dj ust me nt f or baseli ne T S A T ( > 4 5 % t o 
7 0 % vers us > 7 0 %) a n d fre q ue nc y of p hle b ot o m y pr oce d ure o ver t he last 1 2 m o nt hs ( 0 t o 3 
vers us > 3) .  A se nsiti vit y a nal ysis of c ha n ge ser u m ferriti n fro m baseli ne t o eac h wee kl y 
p ost d ose visit a n d eac h wee kl y pre d ose visit  will be c o n d ucte d o n t he mI T T P o p ulati o n.  Patie nts 
n ot c o m pleti n g Wee k 1 6 or Wee k 1 7 f or t he p ost d ose a n d pre d ose a nal yses will be i ncl u de d i n 
t he a nal ysis mi xe d effects re peate d meas ures a nal ysis wit h a dj ust me nt s f or baseli ne T S A T 
( > 4 5 % t o 7 0 % vers us > 7 0 %) a n d fre q ue nc y of p hle b ot o m y pr oce d ure (0 t o 3 vers us > 3). 

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P hle b ot o m y criteria will be base d o n T S A T criteria of t he I DI g ui deli nes.  Criteria f or recei vi n g a 
p hle b ot o m y will be assesse d after t he res ults of eac h fasti n g T S A T assess me nt at p ost d ose 
( 2 4 [ ± 4] h o urs) o n Wee ks 4 ( Da y 2 3), 8 ( Da y 5 1), 1 2 ( Da y 7 9), a n d 1 6 ( Da y 1 0 7) are k n o w n. 
N u m ber of p hle b ot o mies  is defi ne d as: 
a. n u m ber of p hle b ot o mies fr o m Da y 2 t o E O S, or 
b.  n u m ber of p hle b ot o mies fr o m Da y 2 t o E O S + 1  (if, t hr o u g h t he Wee k 1 6 assess me nt, 
n o p hle b ot o m y has bee n a d mi nistere d si nce t he last o bser ve d fasti n g T S A T a n d t he 
last o bser ve d fasti n g T S A T is > 4 5 %). 
N u m ber of ti mes a p atie nt met criteri a f or a p hle b ot o m y  is defi ne d as n u m ber of ti mes fr o m 
Da y  2 t o E O S t hat 1 of t he f oll o wi n g c o n diti o ns is met: 
a. Patie nt recei ve d a p hle b ot o m y. 
b.  Patie nt ha d a fasti n g T S A T >  4 5 %, b ut t he patie nt ref use d/ misse d a p hle b ot o m y, or 
t he treati n g p h ysicia n deci de d a gai nst a p hle b ot o m y.  W het her a patie nt meets t he 
criteria f or a p hle b ot o m y ( yes or n o) will be assesse d after t he res ults of eac h fasti n g 
T S A T rec or de d at p ost d ose 2 4 ( ± 4) h o urs o n Wee ks ( Da y 2 3), 8 ( Da y 5 1), 1 2 ( 7 9), 
a n d 1 6 ( Da y 1 0 7) are k n o w n. 
T he prese nce of a n y  p hle b ot o m y will be a nal yze d b y a C oc hra n- Ma ntel- Hae nszel test wit h 
a dj ust me nt f or baseli ne T S A T a n d p hle b ot o m y fre q ue nc y o ver t he last 1 2 m o nt hs.  T he 
fre q ue nc y of p hle b ot o mies will be a nal yze d b y P oiss o n re gressi o n m o del wit h baseli ne T S A T 
a n d p hle b ot o m y fre q ue nc y o ver t he last 1 2 m o nt hs a n d will offset t o acc o u nt f or ti me at ris k . 
Se nsiti vit y a nal yses of t he n u m ber of p hle b ot o m ies will be c o n d ucte d as f oll o ws: 
•  Usi n g t he mI T T P o p ulati o n, a n a nal ysis i ncl u di n g patie nts n ot c o m pleti n g Wee k 1 6 
will be c o n d uct e d o n t he fre q ue nc y of ti mes a patie nt met criteria f or a p hle b ot o m y .  
F or t hese data , t he P oiss o n re gressi o n m o del a n d C oc hra n-Ma ntel -Hae nszel test as 
defi ne d a b o ve will be re peate d.  T o acc o u nt f or ti me at ris k, t he offset para meter will 
be use d i n t he P oiss o n re gressi o n m o del.  F or t he C oc hra n- Ma ntel -Hae nszel test, 
patie nt s w h o d o n ot c o m plete Wee k 1 6 will be cate g orize d as e x perie nci n g a 
p hle b ot o m y ( yes or n o) base d o n t heir a vaila ble data.  
•  I m pact of s u b gr o u ps of i nterest (i ncl u di n g site) will be a nal yze d b y P oiss o n 
re gressi o n wit h ter ms f or treat me nt s u b gr o u p a n d treat me nt b y s u b gr o u p i nteracti o n. 
•  A m ulti variate l o gistic re gressi o n will be perf or me d o n patie nts recei vi n g at least 
1 p hle b ot o m y ( yes or n o) utilizi n g t he s u b gr o u ps of i nterest defi ne d i n Secti o n  1 2. 6. 2 .  
Detail will be pr o vi de d i n t he S A P.  
T he n u m ber of ti mes a patie nt met c riteria f or p hle b ot o m y will be a nal yze d is a si milar ma n ner 
as descri be d a b o ve.  
1 2. 8. 4. 3.  E x pl or at or y E n d p oi nt A n al yses 
S er u m ir o n  para meters (ser u m ir o n, tra nsferri n, ferritin, a p oferriti n, h ol oferriti n,  UI B C, TI B C)  
will be a nal yze d b y eac h p ost d ose visit a n d eac h pre d ose visit  usi n g a ge neral li near  m o del wit h 
a dj ust me nt f or baseli ne T S A T  ( > 4 5 % t o 7 0 % vers us > 7 0 %) a n d fre q ue nc y of p hle b ot o m y 

Pr ot oc ol LJ 4 0 1- H H 0 1  
 
LJ P C - 4 0 1 
7 0 
La J olla P har mace utical - C o nfi de ntial  
Date :  1 4  Dece m ber  2 0 1 8  ( Versi o n 6. 0) 
pr oce d ure o ver t he last 1 2 m o nt hs  ( 0 t o 3 vers us > 3).  Se nsiti vit y a nal ysis will be c o n d ucte d o n 
t he mI T T p o p ulati o n. 
T h yr oi d f u ncti o n ( T 3, T 4, T S H, a n d free T 4), li ver f u ncti o n (al b u mi n, al kali ne p h os p hatase, 
A L T, A S T, bilir u bi n [t otal, direct , a n d i n direct], L D H, a n d t otal pr otei n) , gl yce mic c o ntr ol, a n d 
R B C para meters ( he m o gl o bi n c o nce ntrati o n, R B C c o u nt, a n d R D W) will be  a nal yze d usi n g a 
ge neral li near m o del wit h a dj ust me nt f or baseli ne T S A T ( %) ( > 4 5 % t o 7 0 % vers us > 7 0 %) a n d 
fre q ue nc y of p hle b ot o m y pr oce d ure o ver t he last 1 2 m o nt hs  ( 0 t o 3 vers us > 3).  If warra nte d , a 
l og tra nsf or mati o n ma y be a p plie d t o data. 
T otal S F - 3 6 v 2, W O M A C, a n d m o difie d Dreisler i n dices f or art hritis  sc ores will be calc ulate d 
acc or di n g t o t he a ut h ors’ i nstr ucti o ns.  T he t otal sc ore as well as t he 8 s u bscales will be a nal yze d 
as e x pl orat or y varia bl es.  F or t he t otal sc ore of eac h s u bscale, c ha n ge fr o m baseli ne t o Wee k 1 6 
will be calc ulate d a n d t he n a nal yze d usi n g a ge neral li near m o del wit h a dj ust me nt f or baseli ne 
T S A T ( %) ( >  4 5 % t o 7 0 % vers us > 7 0 %) a n d fre q ue nc y of p hle b ot o m y pr oce d ure (0 t o 3 vers us 
> 3). 
1 2. 8. 5.  
S afet y A n al ysis 
1 2. 8. 5. 1.  A d verse E ve nts  
T E A Es are t h ose A Es t hat occ ur or w orse n o n or after t he first st u d y dr u g a d mi nistrati o n t hr o u g h 
E O S, 3 0 ( + 3 da ys) da ys after last d ose of st u d y dr u g. 
T E A Es will be c o de d usi n g t he m ost rece nt versi o n of Me d D R A a n d gr o u pe d b y s yste m or ga n 
class ( S O C ) a n d preferre d ter m ( P T ).  T he c o de d ter ms will be s u m marize d b y treat me nt gr o u p, 
S O C, a n d P T i n al p ha betical or der as t he n u m ber of e ve nts a n d t he n u m ber a n d perce nta ge of 
patie nts e x perie nci n g a n e ve nt 1 or m ore ti m es. 
T E A Es will be gra de d f or se verit y usi n g mil d, m o derate , se vere, life-t hreate ni n g, a n d fatal 
(Ta ble  5).  Se verit y, relate d ness, a n d seri o us ness of A Es will be s u m marize d.  A Es lea di n g t o 
disc o nti n uati o n of st u d y dr u g a n d A Es lea di n g t o deat h will be s u m marize d if a p plica ble.  If t he 
relati o ns hi p t o st u d y dr u g is missi n g, t he T E A E will be classifie d as relate d.  I n t he case of m ore 
t ha n 1 occ urre nce o f a T E A E f or a gi ve n patie nt, b y-patie nt a nal yses will i ncl u de t he ma xi m u m 
relati o ns hi p t o st u d y dr u g a n d t he ma xi m u m se verit y of t h ose T E A Es.  
A d verse e ve nts of s pecial i nterest ma y be defi ne d b y La J olla t o s u p p ort t he c haracterizati o n of 
t he safet y pr ofile of LJ P C- 4 0 1 acr oss S O Cs a n d/ or P Ts.  T hese e ve nts ma y be defi ne d d uri n g t he 
o n g oi n g cli nical de vel o p me nt of LJ P C- 4 0 1. 
1 2. 8. 5. 1. 1.  De at hs  
Deat hs will be s u m mari ze d b y treat me nt ar m a n d ca use of deat h.  A listi n g of fatal A Es will be 
pr o vi de d a n d s u m marize d b y S O C a n d P T.  Deat hs d ue t o A E c o nsi dere d relate d t o st u d y dr u g 
will be disc usse d.  
1 2. 8. 5. 1. 2.  I njecti o n Site Re acti o n 
I njecti o n site reacti o n will be s u m marize d b y treat me nt gr o u p a n d visit.  S u m maries will c o ntai n 
t he n u m ber a n d perce nta ge of patie nts e x perie nci n g a reacti o n 1 or m ore ti mes. 

Pr ot oc ol LJ 4 0 1- H H 0 1  
 
LJ P C - 4 0 1 
7 1 
La J olla P har mace utical - C o nfi de ntial  
Date :  1 4  Dece m ber  2 0 1 8  ( Versi o n 6. 0) 
1 2. 8. 5. 2.  St u d y Dr u g E x p os ure  
T he t otal d ose a d mi nistere d , t he t otal n u m ber of i njecti o ns per wee k, a n d t he a vera ge n u m ber of 
i njectio ns per wee k  will be s u m mari ze d b y treat me nt gr o u p. 
1 2. 8. 5. 3.  Cli nic al L a b or at or y D at a 
Cli nical la b orat or y data ( he mat ol o g y, ser u m c he mistr y, ot her cli nical tests, a n d uri nal ysis) 
o btai ne d fr o m l ocal la b orat ories will be c o n verte d t o S ysté me I nter nati o nal ( SI) u nits  a n d/ or 
U nite d States c o n ve nti o nal u nits.  La b orat or y res ults will be classifie d as l o w, n or mal, a n d hi g h 
de pe n de nt o n t he refere nce ra n ges of t he l ocal la b orat or y.  Cli nicall y si g nifica nt la b orat or y 
a b n or malities t hat res ult i n treat me nt m o dificati o n a n d/ or re q uire i nter ve nti o n will be rec or de d as 
A Es per Secti o n  1 1. 1 . 
La b orat or y res ults will be s u m marize d b y treat me nt gr o u p a n d visit, l o west p ost baseli ne gra de, 
hi g hest p ost baseli ne gra de, a n d last p ost baseli ne visit.  T he c ha n ge fr o m baseli ne a n d perce nt 
c ha n ge fr o m baseli ne will als o be s u m marize d.  S hifts fr o m t he baseli ne val ue t o eac h visit, 
l o west p ost baseli ne gra de, hi g hest p ost baseli ne gra de, a n d last p ost baseli ne visit ma y be 
dis pla ye d. 
1 2. 8. 5. 4.  I m m u n o ge nicit y/ P h ar m ac o ki netics 
I m m u n o ge nicit y/ P K will be s u m mari ze d b y visit a n d ti me p oi nt (e g, Wee k 1 a n d Wee k 1 6 
re q uire pre d ose bl o o d sa m ple c ollecti o n a n d a n a d diti o nal bl o o d sa m ple c ollecti o n p ost dose 
1 h o ur or later).  Fasti n g is n ot re q uire d f or i m m u n o ge nicit y/ P K bl o o d c ollecti o ns. 
I m m u n o ge nicit y (a nti b o d y titer, base d o n scree ni n g c ut p oi nt) will be s u m marize d b y treat me nt 
gr o u p a n d visit.  At eac h assess me nt, p ote ntiall y p ositi ve res ults ( base d o n t he scree ni n g assa y ) 
will be f oll o we d b y s u bse q ue nt c o nfir mat or y assa ys, w h ere t he titer will be assi g ne d.  
T he relati o ns hi p bet wee n dr u g c o nce ntrati o n a n d i m m u n o ge nicit y (if a nti- dr u g a nti b o dies or 
ne utralizi n g a nti b o d ies de vel o p) will be assesse d. 
A va l ue of zer o will be s u bstit ute d f or all dr u g c o nce ntrati o ns bel o w t he l o wer li mit of 
q ua ntificati o n.  
1 2. 8. 5. 5.  P h ysic al E x a m 
P h ysical e xa m fi n di n gs will be re p orte d i n patie nt listi n gs. 
1 2. 8. 5. 6.  Vit al Si g ns  
Vital si g ns (s yst olic bl o o d press ure, diast olic bl o o d press ure, heart rate, res pirati o n rate, a n d 
b o d y te m perat ure) will be s u m marize d b y treat me nt gr o u p a n d visit.  T he c ha n ge fr o m baseli ne 
will als o be s u m marize d.  
1 2. 8. 5. 7.  Electr oc ar di o gr a m  
C orrecte d Q T i nter vals  will be calc ulate d usi n g t he Q T i nter val a n d heart rate.  Q Tc B will be 
deri ve d b y Bazett’s f or m ula a n d Q Tc F will be deri ve d b y Fri dericia’s f or m ula as f oll o ws: 
Q Tc B = Q T / ( 6 0/ H R) 1/ 2 

Pr ot oc ol LJ 4 0 1- H H 0 1  
 
LJ P C - 4 0 1 
7 2 
La J olla P har mace utical - C o nfi de ntial  
Date :  1 4  Dece m ber  2 0 1 8  ( Versi o n 6. 0) 
Q Tc F = Q T / ( 6 0/ H R) 1/ 3 
Q Tc B a n d Q Tc F val ues will be classifie d as f oll o ws:  
•  ≤ 4 5 0 msec 
•  > 4 5 0 msec t o ≤ 4 8 0 msec 
•  > 4 8 0 msec t o ≤ 5 0 0 msec 
•  > 5 0 0 msec 
Q Tc B a n d Q Tc F c ha n ge fr o m baseli ne will be classifie d as f oll o ws:  
•  ≤ 3 0 msec 
•  > 3 0 msec t o ≤ 6 0 msec 
•  > 6 0 msec  
Electr ocar di o gra m ( heart rate, P R i nter val, Q R S i nter val, Q T i nter val, Q Tc B i nter val, a n d Q Tc F 
i nter val) will be s u m marize d b y treat me nt gr o u p a n d visit.  T he c ha n ge fr o m baseli ne will als o 
be s u m mari ze d.  
1 2. 8. 6.  
Missi n g V al ues a n d Criteri a f or D at a E xcl usi o ns  
Missi n g val ues will n ot be esti mate d u nless s pecifie d i n t he S A P .  All data will be i ncl u de d i n 
safet y a nal ysis. 
I nc o m plete dates fr o m me dical hist or y, A E , a n d c o nc o mita nt me dicati o n l o gs will be i m p ute d t o 
calc ulate t he st u d y da y a n d d urati o ns as f oll o ws: 
•  Start/ O nset Date:  If missi n g da y a n d/ or m o nt h, t he da y will be re place d wit h  t he 1st 
of t he m o nt h a n d t he m o nt h will be re place d wit h  Ja n uar y.  F or A Es, if t he i m p ute d 
date res ults i n a date bef ore t he date of first st u d y dr u g a d mi nistrati o n, t he n t he date 
of first st u d y dr u g a d mi nistrati o n will be use d , u nless m o nt h is k n o w n a n d is pri or t o 
t he d osi n g m o nt h, i n w hic h case t he i m p ute d date will be use d. 
•  E n d/ Res ol uti o n Date:  If missi n g da y a n d/ or m o nt h, t he da y will be re place d b y t he 
last da y of t he m o nt h a n d t he m o nt h will be re place d wit h  Dece m ber .  If t he i m p ute d 
date res ul ts i n a date later t ha n t he date of deat h, t he n t he date of deat h will be use d. 
I n patie nt data listi n gs, i nc o m plete dates will be dis pla ye d as e ntere d o n t he e C R F wit h o ut a n y 
i m p utati o ns.  St u d y da ys will be deri ve d wit h i m p utati o n a n d dis pla ye d i n t he data listi n gs. 
1 2. 8. 7.  
Q u alit y of Life A n al ysis  
Sta n dar dize d S F- 3 6 v 2 sc ores will be calc ulate d acc or di n g t o t he a ut h ors’ i nstr ucti o ns. 
Eac h of t he 8 scales is directl y tra nsf or me d i nt o a 0  t o 1 0 0 scale o n t he ass u m pti o n t hat eac h 
q uesti o n carries e q ual wei g ht.  T he l o wer t he sc ore t he m ore disa bilit y.  T he hi g her t he sc ore t he 
less disa bilit y.  A nal yses will be descri be d i n a se parate S A P . 

Pr ot oc ol LJ 4 0 1- H H 0 1  
 
LJ P C - 4 0 1 
7 3 
La J olla P har mace utical - C o nfi de ntial  
Date :  1 4  Dece m ber  2 0 1 8  ( Versi o n 6. 0) 
1 3.  
DI R E C T A C C E S S T O S O U R C E D A T A / DO C U M E N T S  
1 3. 1.  
St u d y M o nit ori n g , A u dits, a n d I ns pecti o ns  
Site visits will be c o n d ucte d b y a n a ut h orize d La  J olla re prese ntati ve, w h o will i ns pect st u d y 
data, patie nt’s me dical rec or ds, a n d e C R Fs acc or di n g t o G o o d Cli nical Practice ( G C P) a n d F D A 
a n d I nter nati o nal C o u ncil o n Har m o nisati o n ( I C H) g ui deli nes.  I n a d diti o n t o m o nit ori n g b y 
La  J olla or its desi g nee s, t he st u d y ma y be a u dite d b y re prese ntati ves of t he F D A or ot her 
re g ulat or y a ut h orities, w h o will als o be all o we d access t o st u d y d oc u me nts.  T he I n vesti gat or 
s h o ul d i m me diatel y n otif y La  J olla’s Cli nical O perati o ns de part me nt of a n y pr o p ose d or 
sc he d ule d a u dits b y re g ulat or y a ut h orities. 
T he I n vesti gat or will per mit a ut h orize d re prese ntati ves of La  J olla a n d nati o nal or l ocal healt h 
a ut h orities t o i ns pect facilities a n d rec or ds rele va nt t o t his st u d y.  
T he I n vesti gat or m ust o btai n I nstit uti o nal Re vie w B oar d (I R B) / I nter nati o nal Et hics C o m mittee 
(I E C) a p pr o val f or t he i n vesti gati o n.  I nitial I R B or I E C a p pr o val, a n d all materials a p pr o ve d b y 
t he I R B or I E C f or t his st u d y i ncl u di n g t he patie nt c o nse nt f or m a n d recr uit me nt materials m ust 
be mai ntai ne d b y t he I n vesti gat or a n d ma de a vaila ble f or i ns pecti o n. 

Pr ot oc ol LJ 4 0 1- H H 0 1  
 
LJ P C - 4 0 1 
7 4 
La J olla P har mace utical - C o nfi de ntial  
Date :  1 4  Dece m ber  2 0 1 8  ( Versi o n 6. 0) 
1 4.  
Q U A LI T Y C O N T R O L A N D Q U A LI T Y A S S U R A N C E  
La  J olla or its desi g nee will i nstr uct t he st u d y site re gar di n g t he c o n d uct of t he st u d y a n d data 
ca pt ure pr oce d ures o n e C R Fs.  L o gi c a n d c o nsiste nc y c hec ks will be perf or me d o n all data 
e ntere d i nt o t he eC R F or ulti matel y tra nsferre d i nt o a data base t o e ns ure acc urac y a n d 
c o m plete ness.  
Trai ni n g sessi o ns, re g ular m o nit ori n g of t he st u d y at t he st u d y site b y t he La  J olla or desi g nate d 
pers o n nel (e g,  Cli nical Researc h Ass ociate  [C R A ]), i nstr ucti o n ma n uals, data verificati o n, cr oss 
c hec ki n g, a n d data a u dits will be perf or me d t o e ns ure q ualit y of all st u d y data.  I n vesti gat ors’ 
meeti n gs a n d/ or o nsite st u d y i nitiati o ns will be perf or me d t o pre pare I n vesti gat ors a n d ot her 
st u d y site pers o n nel f or a p pr o priate c o n d uct of t he st u d y a n d c ollecti o n of st u d y data. 
It is t he I n vesti gat or’s res p o nsi bilit y t o e ns ure t he acc urac y, c o m plete ness, a n d ti meli ness of t he 
data re p orte d f or eac h patie nt.  S o urce d oc u me ntati o n s u p p orti n g t he data s h o ul d i n dicate t he 
patie nt’s partici pati o n i n t he st u d y a n d s h o ul d d oc u me nt t he dates a n d details of st u d y 
pr oce d ures, A Es, a n d patie nt stat us. 
T he I n vesti gat or, or desi g nate d re prese ntati ve, s h o ul d c o m pl ete data e ntr y as s o o n as p ossi ble 
after i nf or mati o n is c ollecte d, prefera bl y o n t he sa me da y t hat a st u d y patie nt is see n f or a n 
e xa mi nati o n, treat me nt, or a n y ot her st u d y pr oce d ure.  A n y o utsta n di n g e ntries s h o ul d be 
c o m plete d i m me diatel y after t he fi nal  e xa mi nati o n.  A n e x pla nati o n s h o ul d be gi ve n f or all 
missi n g data.  T he I n vesti gat or m ust si g n a n d date t he I n vesti gat or’s State me nt t hat will be 
s u p plie d t o e n d orse t he rec or de d data. 
All re q uests t o u nl oc k t he data base after data base l oc k will be assesse d b y La J olla a n d will 
f oll o w La J olla  data base u nl oc ki n g sta n dar d o perati n g pr oce d ures. 
T o e ns ure c o m plia nce wit h G C P a n d all a p plica ble re g ulat or y re q uire me nts, La  J olla ma y 
c o n d uct a q ualit y ass ura nce a u dit.  

Pr ot oc ol LJ 4 0 1- H H 0 1  
 
LJ P C - 4 0 1 
7 5 
La J olla P har mace utical - C o nfi de ntial  
Date :  1 4  Dece m ber  2 0 1 8  ( Versi o n 6. 0) 
1 5.  
I R B (I N S TI T U TI O N A L R E VI E W B O A R D ) / E T HI C S  
1 5. 1.  
I RB / Et hics Re vie w  
T he fi nal st u d y pr ot oc ol, i ncl u di n g t he fi nal versi o n of t he i nf or me d c o nse nt f or m, m ust be 
a p pr o ve d or gi ve n a fa v ora ble o pi ni o n i n writi n g b y a n I R B or I E C as a p pr o priate.  T he 
I n vesti gat or m ust s u b mit writte n a p pr o val t o La  J olla bef ore he or s he ca n prese nt i nf or me d 
c o nse nt a n d be gi n scree ni n g acti vities f or a n y patie nt o n t he st u d y. 
T he I n vesti gat or is res p o nsi ble f or i nf or mi n g t he I R B or I E C of a n y a me n d me nt t o t he pr ot oc ol 
i n acc or da nce wit h l ocal re q uire me nts.  I n a d diti o n, t he I R B or I E C  m ust a p pr o ve all a d vertisi n g 
use d t o recr uit patie nts f or t he st u d y, if a p plica ble.  T he pr ot oc ol m ust be re- a p pr o ve d b y t he I R B 
or I E C  u p o n recei pt of a me n d me nts a n d a n n uall y, as l ocal re g ulati o ns re q uire. 
T he I n vesti gat or is als o res p o nsi ble f or pr o vi di n g t he I R B or I E C wit h re p orts of a n y re p orta ble 
seri o us a d verse dr u g reacti o ns fr o m a n y ot her st u d y c o n d ucte d wit h t he i n vesti gati o nal pr o d uct.  
La  J olla will pr o vi de t his i nf or mati o n t o t he I n vesti gat or.  
Pr o gress re p orts a n d n otificati o ns of seri o us a d verse dr u g reacti o ns will be pr o vi de d t o t he I R B 
or I E C  acc or di n g t o l ocal re g ulati o ns a n d g ui deli nes. 
1 5. 2.  
Pr ot oc ol C o m pli a nce  
T he I n vesti gat or will c o n d uct t he trial i n c o m plia nce wit h t he pr ot oc ol pr o vi de d b y La  J olla.  
M o dificati o ns t o t he pr ot oc ol ma y  n ot be ma de wit h o ut a gree me nt of b ot h t he I n vesti gat or a n d 
La  J olla.  C ha n ges t o t he pr ot oc ol will re q uire a writte n I R B or I E C a p pr o val/fa v ora ble o pi ni o n 
pri or t o i m ple me ntati o n, e xce pt w he n t he m o dificati o n is nee de d t o eli mi nate a n i m me diate 
hazar d(s) t o patie nts.  T he I R B or I E C ma y pr o vi de, if a p plica ble re g ulat or y a ut h orit y(ies) 
per mit, e x pe dite d re vie w a n d a p pr o val/fa v ora ble o pi ni o n f or mi n or c ha n ge(s) i n o n g oi n g trials 
t hat ha ve t he a p pr o val/fa v ora ble o pi ni o n of t he I R B or I E C. 
W he n i m me diate de via ti o n fr o m t he pr ot oc ol is re q uire d t o eli mi nate a n i m me diate hazar d(s) t o 
patie nts, t he I n vesti gat or will c o ntact La  J olla a n d/ or t he Me dical M o nit or, if circ u msta nces 
per mit, t o disc uss t he pla n ne d c o urse of acti o n.  A n y i m p orta nt de part ures fr o m t he pr ot oc ol 
m ust be f ull y d oc u me nt e d o n t he a p pr o priate e C R F a n d i n t he s o urce d oc u me ntati o n a n d 
re p orte d t o t he I R B or I E C per i nstit uti o nal a n d/ or l ocal re q uire me nts. 
T he pr ot oc ol de viati o ns l o g will be c o m plete d b y t he st u d y m o nit ors a n d peri o dicall y re vie we d 
b y t he S p o ns or, a n d cate g ories will be assi g ne d t o t he pr ot oc ol de viati o ns.  T he l o g a n d 
assi g n me nts will be fi nalize d pri or t o t he data base freeze/l oc k.  All i m p orta nt de viati o ns will be 
i ncl u de d i n t he fi nal data base. 
1 5. 3.  
Et hic al C o n d uct of t he St u d y  
T he st u d y will be perf or me d i n acc or da nce wit h et hical pri nci ples t hat ha ve t heir ori gi n i n t he 
Declarati o n of Helsi n ki a n d are c o nsiste nt wit h I C H/ G C P, a p plica ble re g ulat or y re q uire me nts, 
a n d La  J olla ( or its desi g nees) a p plica ble p olicies a n d sta n dar d o perati n g pr oce d ures. 

Pr ot oc ol LJ 4 0 1- H H 0 1  
 
LJ P C - 4 0 1 
7 6 
La J olla P har mace utical - C o nfi de ntial  
Date :  1 4  Dece m ber  2 0 1 8  ( Versi o n 6. 0) 
1 5. 4.  
Writte n I nf or me d C o nse nt  
T he I n vesti gat or(s) at eac h ce nter will e ns ure t hat t he patie nt is gi ve n f ull a n d a de q uate oral a n d 
writte n i nf or mati o n a b o ut t he nat ure, p ur p ose, p ossi ble ris k, a n d be nefit of t he st u d y.  Patie nts 
m ust als o be n otifie d t hat t he y are free t o disc o nti n ue fr o m t he st u d y at a n y ti me.  T he patie nt 
s h o ul d be gi ve n t he o p p ort u nit y t o as k q uesti o ns a n d all o we d ti me t o c o nsi der t he i nf or mati o n 
pr o vi de d. 
T he patie nt’s si g ne d a n d date d i nf or me d c o nse nt f or m m ust be o btai ne d bef or e c on d ucti n g a n y 
st u d y pr oce d ures. 
T he I n vesti gat or(s) m ust mai ntai n t he ori gi nal, si g ne d i nf or me d c o nse nt f or m.  A c o p y of t he 
si g ne d i nf or me d c o nse nt f or m m ust be gi ve n t o t he patie nt. 
1 5. 5.  
P atie nt  C o nfi de nti alit y  
I n or der t o mai ntai n patie nt pri vac y, data ca pt ure t o ols, i n vesti gati o nal pr o d uct acc o u nta bilit y 
rec or ds, st u d y re p orts, a n d c o m m u nicati o ns will i de ntif y t he patie nt o nl y b y i nitials a n d t he 
assi g ne d patie nt n u m ber.  T he I n vesti gat or will gra nt m o nit or(s) a n d a u dit or(s) fr o m La  J olla or 
its desi g nee a n d re g ulat or y a ut h orit y(ies) access t o t he patie nt’s ori gi nal me dical rec or ds, 
i ncl u di n g me dical hist or y, la b orat or y st u dies, a n d me dicati o n a d mi nistrati o ns, f or verificati o n of 
data gat here d a n d t o a u dit t he data c ollecti o n pr ocess.  T hi s i nf or mati o n will be accesse d f or t he 
d urati o n of t he researc h st u d y, i ncl u di n g t he f oll o w- u p peri o d, f or t he p ur p ose of data 
rec o nciliati o n.  T he patie nt’s c o nfi de ntialit y will be mai ntai ne d a n d will n ot be ma de p u blicl y 
a vaila ble t o t he e xte nt per mitte d  b y t he a p plica ble la ws a n d re g ulati o ns. 
1 5. 5. 1.  
Ge ner al D at a Pr otecti o n Re g ul ati o n f or Cli nic al St u dies C o n d ucte d i n t he 
E ur o pe a n Ec o n o mic Are a  
T he pr ocessi n g of pers o nal data i n t his st u d y is s u bject t o t he Ge neral Data Pr otecti o n Re g ulati o n 
( G D P R) a n d o nl y a p plies t o st u dies c o n d ucte d i n t he E ur o pea n Ec o n o mic Area.  T he G D P R 
re q uires t hat certai n i nf or mati o n be pr o vi de d t o t he st u d y s u bject/ patie nt i n t he I C F. 
F or p ur p oses of t his st u d y, S p o ns or will be t he “ data c o ntr oller” u n der t he G D P R.  T he c o ntract 
research or ga nizati o n t hat is assisti n g wit h t he st u d y is S p o ns or’s “ data pr ocess or”.  Ot her 
or ga nizati o ns i n v ol ve d i n pr ocessi n g pers o nal data o n S p o ns or’s be half f or p ur p oses of t he st u d y, 
s uc h as c o ntract la b orat ories t hat a nal yse bl o o d sa m ples, are als o S p o ns or’s data pr ocess ors.  
Eac h st u d y s u bject’s/ patie nt’s pers o nal data will be ha n dle d f or p ur p oses of t he st u d y a n d 
s u bse q ue nt researc h uses b y S p o ns or a n d t hir d parties as descri be d i n t he I C F. 
S p o ns or is res p o nsi ble f or c o m plia nce wit h data c o ntr oller o bli gati o ns u n der t he G D P R a n d ot her 
a p plica ble la ws i n c o n necti o n wit h t he data c ollecte d b y or o n be half of S p o ns or f or p ur p oses of 
t he st u d y.  S p o ns or ca n be c o ntacte d re gar di n g data pr otecti o n matters at La J olla P har mace utical 
C o m pa n y, Att n: Hea d of Pri vac y, 4 5 5 0 T o w ne Ce ntre C o urt, Sa n Die g o, Calif or nia, 9 2 1 2 1, or b y 
e-mail at pri vac y @lj pc.c o m.  
S u bject t o certai n li mitati o ns of t he G D P R a n d ot her a p plica ble data pr otecti o n la ws, st u d y 
s u bjects/ patie nts will ha ve t he ri g ht t o access a n d c orrect t heir pers o nal data, a n d t o re q uest its 
deleti o n or restricti o n or o bject t o its pr ocessi n g, b ut t hese ri g hts ma y be li mite d u n der t he 

Pr ot oc ol LJ 4 0 1- H H 0 1  
 
LJ P C - 4 0 1 
7 7 
La J olla P har mace utical - C o nfi de ntial  
Date :  1 4  Dece m ber  2 0 1 8  ( Versi o n 6. 0) 
G D P R’s pr o visi o ns relati n g t o scie ntific researc h a n d data pr ocessi n g  t hat is c o n d ucte d i n t he 
p u bl ic i nterest, or ot her gr o u n ds. 
T he la ws g o ver ni n g cli nical st u dies re q uire c o nse nt fr o m st u d y partici pa nts (a n d f or mi n ors, t o 
o btai n a pare nt or g uar dia n’s c o nse nt t o t he c hil d’s partici pati o n i n t he st u d y).  H o we ver, t he 
la ws g o ver ni n g data pr otecti o n, i ncl u di n g t he G D P R, pr o vi de le gal bases besi des c o nse nt f or t he 
pr ocessi n g of certai n pers o nal data.  F or p ur p oses of a p plica ble data pr otecti o n la ws, S p o ns or’s 
la wf ul basis f or pr ocessi n g t he pers o nal data of its st u d y s u bjects/ patie nts is t hat t he pr ocessi n g is 
necessar y f or scie ntific researc h p ur p oses, s u bject t o Article 8 9 of t he G D P R.  Pr ocessi n g t hat is 
directl y re q uire d f or carr yi n g o ut t he st u d y is d o ne o n t he basis of necessit y of e ns uri n g hi g h 
sta n dar ds of q ualit y a n d safet y of healt h care a n d of me dici nal pr o d ucts. 
A m o n g its ot her o bli gati o ns, S p o ns or i nte n ds t o tra nsfer pers o nal data o utsi de of t he E ur o pea n 
Ec o n o mic Area a n d will e ns ure t here is a la wf ul basis f or tra nsfer of data o utsi de of t he 
E ur o pea n Ec o n o mic Ar e a. 

Pr ot oc ol LJ 4 0 1- H H 0 1  
 
LJ P C - 4 0 1 
7 8 
La J olla P har mace utical - C o nfi de ntial  
Date :  1 4  Dece m ber  2 0 1 8  ( Versi o n 6. 0) 
1 6.  
R E C O R D K E E PI N G  
1 6. 1.  
I ns pecti o n of Rec or ds 
La  J olla a n d desi g nees of La  J olla will be all o we d t o c o n d uct site visits t o t he i n vesti gati o nal 
facilities f or t he p ur p ose of m o nit ori n g a n y as pect of t he st u d y.  T he I n vesti gat or a grees t o all o w 
La  J olla re prese ntati ves t o i ns pect t he dr u g st ora ge area, LJ P C - 4 0 1 i n ve nt or y, dr u g 
acc o u nta bilit y rec or ds, patie nt c harts a n d st u d y s o urce d oc u me nts, a n d ot her rec or ds relati ve t o 
t he st u d y c o n d uct. 
1 6. 2.  
Rete nti o n of Rec or ds  
T he I n vesti gat or will c o or di nate wit h t he s t u d y site t o e ns ure rete nti o n of all d oc u me ntati o ns 
relati n g t o t he st u d y f or a peri o d of 2 years after mar keti n g a p plicati o n a p pr o val, or if n ot 
a p pr o ve d, 2 years f oll o wi n g t he n otificati o n t o F D A of t he disc o nti n ua nce of t he test article f or 
i n vesti gati on.  If it bec o mes necessar y f or La  J olla or t he Re g ulat or y A ut h orit y t o re vie w a n y 
d oc u me ntati o n relati n g t o t he st u d y, t he I n vesti gat or m ust per mit access t o s uc h rec or ds. 

Pr ot oc ol LJ 4 0 1- H H 0 1  
 
LJ P C - 4 0 1 
7 9 
La J olla P har mace utical - C o nfi de ntial  
Date :  1 4  Dece m ber  2 0 1 8  ( Versi o n 6. 0) 
1 7.  
P U B LI C A TI O N P O LI C Y  
All i nf or mati o n re gar di n g LJ P C - 4 0 1 s u p plie d b y La  J olla t o t he I n vesti gat or is pri vile ge d a n d 
c o nfi de ntial i nf or mati o n.  T he I n vesti gat or a grees t o use t his i nf or mati o n t o acc o m plis h t he st u d y 
a n d will n ot use it f or a n y ot her p ur p oses wit h o ut writte n c o nse nt fr o m La  J olla.  It is u n derst o o d 
t hat t here is a n o bli gati o n t o pr o vi de La  J olla wit h c o m plete data o btai ne d d uri n g t he st u d y.  T he 
i nf or mati o n o btai ne d fr o m t he cli nical st u d y will be use d t o war d t he de vel o p me nt of La  J olla’s 
LJ P C - 4 0 1 pr o gra m a n d ma y be discl ose d t o re g ulat or y a ut h orit y(ies), ot her I n vesti gat ors, 
c or p orate part ners, s hare h ol ders, or c o ns ulta nts as re q uire d. 
It is a ntici pate d t hat t he res ults of t his st u d y will be prese nte d at scie ntific meeti n gs a n d/ or 
p u blis he d i n a peer- re vie we d scie ntific or me dical j o ur nal. 
La J olla is c o m mitte d t o t he hi g hest scie ntific a n d et hical sta n dar ds f or p u blicati o ns.  T he data 
f or all p u blicati o ns will be re p orte d i n a n o bjecti ve, acc urate, scie ntificall y-bala nce d, a n d 
c o m plete ma n ner (e g, ma n uscri pts, re vie w articles, a bstracts, p osters, a n d/ or oral prese ntati o ns 
t hat c o ntai n data fr o m La J olla s p o ns ore d st u dies, ha ve La J olla a ut h ors, or f or w hic h La J olla 
pr o vi des writi n g a n d/ or e dit orial ass ista nce). 
La J olla’s pri nci ples f or a ut h ors hi p of p u blicati o ns are c o nsiste nt wit h criteria de vel o pe d b y t he 
I nter nati o nal C o m mittee of Me dical J o ur nal E dit ors (I C MJ E; w w w.ic mje. or g). 
T he I C MJ E rec o m me n ds t hat a ut h ors hi p be base d o n t he f oll o wi n g 4 criteria: 
1.  S u bsta ntial c o ntri b uti o ns t o t he c o nce pti o n or desi g n of t he w or k; or t he ac q uisiti o n, 
a nal ysis, or i nter pretati o n of data f or t he w or k; A N D 
2.  Drafti n g t he w or k or re visi n g it criticall y f or i m p orta nt i ntellect ual c o nte nt; A N D  
3.  Fi nal a p pr o val of t he versi o n t o be s u b mitte d/ prese nte d; A N D  
4.  A gree me nt t o be acc o u nta ble f or all as pects of t he w or k i n e ns uri n g t hat q uesti o ns relate d 
t o t he acc urac y or i nte grit y of a n y part of t he w or k are a p pr o priatel y i n vesti gate d a n d 
res ol ve d. 
La J olla pr o hi bits t he practices of g uest a ut h ors hi p, g h ost writi n g, or pla giaris m o n p u blicati o ns.  
G uest a ut h ori n g is t he practice i n w hic h t he na mes of i n di vi d uals w h o c o ntri b ute d little t o n o 
c o nte nt o n t he p u blicati o n a p pear o n t he b yli ne.  G h ost writi n g is t he practice i n w hic h 
i n di vi d uals w h o wr ote t he p u blicati o n are neit her ac k n o wled ge d n or liste d o n t he b yli ne. 

Pr ot oc ol LJ 4 0 1- H H 0 1  
 
LJ P C - 4 0 1 
8 0 
La J olla P har mace utical - C o nfi de ntial  
Date :  1 4  Dece m ber  2 0 1 8  ( Versi o n 6. 0) 
1 8.  
R E F E R E N C E S  
1 8. 1.  
P u blic ati o ns  
A da ms P C , Bart o n J C. H o w I treat he m oc hr o mat osis.   Bl o o d. 2 0 1 0; 1 1 6( 3): 3 1 7- 3 2 5. 
A merica n Ass ociati o n f or Cli nical C he mistr y ( A A C C; 2 0 1 5 ). La b Tests O nli ne. TI B C, UI B C, 
a n d Tra nsferri n. htt ps://la btests o nli ne. or g/ u n dersta n di n g/a nal ytes/ti bc/ta b/test/. Accesse d 2 3 A u g 
2 0 1 7. 
Bac o n B R, A da ms P C, K o w dle y K V, P o well L W, Ta vill A S. Dia g n osis a n d Ma na ge me nt of 
He m oc hr o mat osis: 2 0 1 1 Practice G ui deli ne b y t he A merica n Ass ociati o n f or t he St u d y of Li ver 
Diseases. He pat ol o g y. 2 0 1 1; 5 4( 1) : 3 2 8- 3 4 3. 
C o u ns yl 2 0 1 7 , H F E-ass ociate d Here d itar y He m oc hr o mat osis, 
htt ps:// w w w.c o u ns yl.c o m/ser vices/f oresi g ht/ diseases/ hfe -ass ociate d -here ditar y -
he m oc hr o mat osis/, Accesse d  2 3 A u g 2 0 1 7 
Deferasir o x U S Prescri bi n g I nf or mati o n ( 2 0 1 5). 
htt ps:// w w w. p har ma. us. n o vartis.c o m/sites/ w w w. p har ma. us. n o vartis.c o m/f iles/jade n u. p df. 
Accesse d 2 3 A u g 2 0 1 7. 
Deferi pr o ne U S Prescri bi n g I nf or mati o n ( 2 0 1 1). 
htt ps:// w w w.access data.f da. g o v/ dr u gsatf da _ d ocs/la bel/ 2 0 1 1/ 0 2 1 8 2 5l bl. p df. Accesse d 2 3 A u g 
2 0 1 7. 
Defer o xa mi ne mes ylate U S Prescri bi n g I nf or mati o n ( 2 0 1 1). 
htt ps:// w w w.access data.f da. g o v/ dr u gsatf da _ d ocs/la bel/ 2 0 1 0/ 0 1 6 2 6 7s 0 4 7l bl. p df. Accesse d 2 3 
A u g 2 0 1 7. 
de Li ma Sa nt os P, Pereira A C, Ca nça d o R D, Sc hettert I T, Hirata R D, Hirata M H. He m oj u veli n 
a n d he pci di n ge nes se q ue nci n g i n Brazilia n patie nts wit h pri mar y ir o n  o verl oa d. Ge net Test M ol 
Bi o mar kers . 2 0 1 0; 1 4( 6):8 0 3- 8 0 6. 
D uc hi ni A. He m oc hr o mat osis. I n: Me dsca pe Dr u gs a n d Diseases.  U p date d 2 0 1 7 
htt p://e me dici ne. me dsca pe.c o m/article/ 1 7 7 2 1 6- o ver vie w #a 7. Accesse d 2 3 A u g 2 0 1 7. 
F D A. Ma n ual of P olicies a n d Pr oce d ures. G o o d Re vie w Practice: Cli nical Re vie w Te m plate. 
U. S. De part me nt of Healt h a n d H u ma n Ser vices F o o d a n d Dr u g A d mi nistrati o n   Ce nter f or 
Dr u g E val uati o n a n d Researc h ( C D E R). Dec 1 0, 2 0 1 0. 
G or de u k V R, Britte n ha m G M, H u g hes M, Keati n g LJ, O p plt JJ. Hi g h - d ose car b o n yl ir o n for ir o n 
deficie nc y a ne mia: A ra n d o mize d d o u ble- bli n d trial. A m J Cli n N utr . 1 9 8 7; 4 6( 6):1 0 2 9- 1 0 3 4. 
Hic ke n, B, T uc ker, D, Bart o n, J. Patie nt c o m plia nce wit h p hle b ot o m y t hera p y f or ir o n o verl oa d 
ass ociate d wit h he m oc hr o mat osis. A m Gastr oe nter ol . 2 0 0 3;9 8 : 2 0 7 2- 2 0 7 7. 
H off bra n d A V, Ta her A, D o me nica Ca p pelli ni M. H o w I treat tra nsf usi o nal ir o n o verl oa d. 
Bl o o d. 2 0 1 2; 1 2 0( 1 8 ):3 6 5 7- 3 6 6 9. 
Ir o n Dis or ders I nstit ute, Classic He m oc hr o mat osis, 2 0 1 1. htt p:// w w w.ir o n dis or ders. or g/classic -
he m oc hr o mat osis, Accesse d 2 3 A u g 2 0 1 7. 

Pr ot oc ol LJ 4 0 1- H H 0 1  
 
LJ P C - 4 0 1  
 
8 3 
La J olla P har mace utical - C o nfi de ntial  
Date :  1 4  Dece m ber  2 0 1 8  ( Versi o n 6. 0) 
A P P E N DI X  1.  S U M M A R Y O F L A B O R A T O R Y P A R A M E T E R S  
S u m m ar y of L a b or at or y P ar a meters 
Dise ase -s pecific 
He m at ol o g y 
C he mistr y  
Uri n al ysis  
S u bset/ S peci al  
•  
T otal ser u m 
ir o nb 
•  
Ser u m 
tra nsferri n 
•  
Ser u m ferriti n b 
•  
UI B C b 
•  
TI B C b 
•  
Tra nsferri n 
sat urati o nb 
•  
A p oferriti n 
•  
H ol oferriti n 
 
•  
He mat ocrit b 
•  
He m o gl o bi n b 
•  
Platelet c o u nt b 
•  
W hite bl o o d cell 
c o u nt b, c 
•  
Re d bl o o d cell 
c o u nt b, d 
•  
Ser u m creati ni ne b 
•  
Uric aci d b  
•  
Al kali ne p h os p hatase b 
•  
Bl o o d urea nitr o ge n b 
•  
Al b u mi n 
•  
Bilir u bi n (t otal , direct, 
a n d i n direct )b 
•  
P h os p hate b 
•  
Bicar b o nate b 
•  
Lactate de h y dr o ge nase  
•  
Gl uc ose b 
•  
Calci u m b 
•  
Ma g nesi u m
b 
•  
C hl ori de b 
•  
S o di u m b 
•  
P otassi u m b 
•  
Ala ni ne 
a mi n otra nsferase 
( S G P T)b 
•  
As partate  
a mi n otra nsferase 
( S G O T)b 
•  
T otal pr otei n  
•  
S pecific 
gra vit y 
•  
Bilir u bi n 
•  
Gl uc ose  
•  
p H 
•  
Pr otei n 
•  
Nitrite  
•  
Bl o o d 
•  
Ket o nes 
•  
Pre g na nc y a 
•  
P har mac o ki netics 
•  
T h yr oi d -sti m ulati n g 
h or m o ne 
•  
He m o gl o bi n Alc  
•  
T h yr o xi ne ( T 4 a n d free 
T 4) 
•  
Trii o d ot h yr o ni ne 
(free T 3) 
•  
I m m u no ge nicit y b, e 
S G O T =ser u m gl uta mic - o xal oacetic tra nsa mi nase; S G P T =ser u m gl uta mic -p yr u vic tra nsa mi nase; TI B C =t otal ir o n 
bi n di n g ca pacit y; UI B C = u nsat urate d ir o n bi n di n g ca pacit y.  
a Ser u m a n d uri ne.  
b La b orat or y para meters t hat m ust be c ollecte d t o m o nit or patie nt safet y.  
c W hite bl o o d cell c o u nt a n d differe ntial i ncl u di n g perce nt a n d a bs ol ute:  ne utr o p hils, l y m p h oc ytes, m o n oc ytes, 
e osi n o p hils, a n d bas o p hils    
d Re d bl o o d cell c o u nt, i ncl u di n g retic ul oc yte c o u nt, re d cell distri b uti o n wi dt h, mea n c or p usc ular he m o gl o bi n, mea n 
c or p usc ular v ol u me, mea n c or p usc ular he m o gl o bi n c o nce ntrati o n.  
e LJ P C-4 0 1 a nti-dr u g  a nti b o d y.