A French Open-label Extension Study of Canakinumab in Patients Who Participated in International Phase III Studies CACZ885G2301E1 or CACZ885G2306 in Systemic Juvenile Idiopathic Arthritis and CACZ885N2301 in Hereditary Periodic Fevers (TRAPS, HIDS, or crFMF)
Phase: PHASE3
Conditions: Systemic Juvenile Idiopathic Arthritis, Hereditary Periodic Fevers
Sponsor: Novartis Pharmaceuticals

C li nic al  D e vel o p m e nt  
[ A C Z 8 8 5/ c a n aki n u m a b]  
Cli ni c al  Tri a l Pr ot o c o l C A C Z 8 8 5 G F R 0 1 / N C T 0 2 3 3 4 7 4 8 
A  Fr e n c h  o p e n-l a b el  e xt e n si o n  st u d y  of  c a n a k in u m a b  i n p at i e nt s 
w h o  p arti ci p at e d  i n i nt er nat io n al p h a s e  III st u di e s C AC Z 8 8 5 G 2 3 0 1 E 1  
or  C A C Z 8 8 5 G 2 3 0 6  i n S y st e mi c  J u v e n ile I di o p at hi c  Art h riti s a n d 
C A C Z 8 8 5 N 2 3 0 1  i n H er e di t ar y P er io d i c F e v er s  ( T RA P S,  HI D S , or 
cr F M F).  
A u th o r: 
 M . D. 
D o c u m e n t ty p e : 
A m e n d e d C li ni ca l T ria l Pro to c o l 
E U D R A C T  n u m b e r: 
2 0 1 4 -0 0 2 8 7 2 -9 5  
V e r sio n  n u m b e r: 
V 0 5  (P ro to c o l a m e n d m e nt 5 ) 
D e v e l op m e n t p h a s e : 
III  
R el e a s e  d a te : 
1 5  d e c e m b er 2 0 1 7  
Pr o p ert y of N o v arti s 
C o nfi d e nti al 
M a y n ot b e u s e d, di v ul g e d, p u bli s h e d, or ot h er wi s e di s cl o s e d 
wit h o ut t h e c o n s e nt of N o v arti s 

N o v artis 
C lin ica l T rial P rot o co l v 0 5  
C o n fid e nt ial  
P ag e 2  
P rot o co l N o . C A C Z 8 8 5 G F R 0 1  
 
T a ble of C o nte nts 
List of a b bre vi ati o ns ................................ ........................................................................................ 4 
Gl ossar y of  t er ms ............................................................................................................................. 5 
Pr ot oc ol s y n o psis ............................................................................................................................. 8  
1          I ntr o d u cti o n ....................................................................................................................... 1 3 
1. 1        Bac k gr o u n d ................................................................ ................................................... 1 3 
1. 2        P ur p ose......................................................................................................................... 1 6  
2          St u d y o b jecti ves  ................................................................................................................ 1 6 
3          I n vesti g atio nal p la n ........................................................................................................... 1 6 
3. 1        St u d y d esi g n ................................................................................................................. 1 6  
3. 2        Rati o nal e of st u d y desi g n ............................................................................................. 1 7  
3. 3  
Rati o nal e of d ose/r e gi me n, r o ute of a d mi nistrati o n a n d  durati o n of tr eat m e nt ............... 1 7  
3. 4        P ur p ose a n d ti mi n g of  i nteri m a nal yses / desi g n a da pt ati o ns ......................................... 1 7 
3. 5        Ris ks a n d be nefits ................................................................................................ ........ 1 7 
4          P o p ul atio n ................................ ......................................................................................... 1 7 
4. 1        I ncl usi o n cri t eri a .......................................................................................................... 1 8 
4. 2        E x cl usi o n crit eria ......................................................................................................... 1 8  
5          Treat me nt .......................................................................................................................... 1 9  
5. 1        Pr ot oc ol re q u este d treat me nt ........................................................................................ 2 0  
5 .1 . 1       I n vesti gati o nal treat me nt......................................................................................... 2 0  
5 .1 . 2       A d diti o nal st ud y tr e at me nt ...................................................................................... 2 1  
5. 2        Treat me nt ar ms  ............................................................................................................ 2 1 
5. 3        Treat me nt assi g n m e nt, ran d o miz ati o n ................................................................ ......... 2 1 
5. 4        Treat me nt bli n di n g .......................................................................................................  2 1 
5. 5        Treati n g t he p atie nt ...................................................................................................... 2 1  
5 .5 . 1       Patie nt n u m beri n g ................................................................................................... 2 1 
5 .5 . 2       Di s p e nsi n g t he i nv esti gati o nal tre at me nt ................................................................ 2 1  
5 .5 . 3       H a n dli n g of st ud y tr eat me nt ................................ ................................................... 2 1 
5 .5 . 4       I nstr ucti o ns f or prescri bi n g a n d ta k i n g st ud y treat me nt ................................ ......... 2 2 
5 .5 . 5       Per mitte d d ose a dj ust me nts a n d i nterr u pti o ns of st ud y tr eat me nt .......................... 2 2  
5 .5 . 6       Re s cu e  me dica tio n  .................................................................................................. 2 2 
5 .5 . 7       C o n c o mita nt tr eat me nt ............................................................................................ 2 2  
5 .5 . 8       Pr o hi bite d Trea t me nt .............................................................................................. 2 2 
5 .5 . 9       Di s co nti n uati o n of st ud y treat me nt a n d pre m at ure p atie nt w ith dra w al .................. 2 2  
5 .5 . 10     E m er ge nc y br ea ki n g of tr eat me nt assi g n me nt ........................................................ 2 3  
5 .5 . 11     E arl y st ud y t er mi nati o n ........................................................................................... 2 3 

N o v artis 
C lin ica l T rial P rot o co l v 0 5  
C o n fid e nt ial  
P ag e 3  
P rot o co l N o . C A C Z 8 8 5 G F R 0 1  
 
6          Visit sch e d ule a n d assess m e nts......................................................................................... 2 3 
6. 1  
Patie nt de m o gra p h i cs/ ot her b aseli ne c h aracteristics ....................................................... 2 4 
6. 2        St u d y tr eat m e nt dis pe nsati o n ....................................................................................... 2 4  
6. 3        Efficac y ........................................................................................................................ 2 4  
6. 4        Safet y ........................................................................................................................... 2 4  
7          Safet y m o nit o rin g  ............................................................................................................. 2 4 
7. 1        A d vers e e ve nts ............................................................................................................. 2 4  
7. 2        Seri o us a d verse e ve nt ( S A E) ........................................................................................ 2 5  
7. 2. 1 De fi niti o n of a S A E ...................................................................................................... 2 5 
7 .2 . 2  S eri o us a dverse e ve nt re p orti n g .................................................................................. 2 6 
7. 3        Pre g na n c y re p orti n g ................................................................................................. 2 7 
8          Data r e vie w a n d data b ase ma n a g e me nt ............................................................................ 2 7 
8. 1        Site m o nit ori n g ............................................................................................................ 2 7  
8. 2        Data c oll ecti o n ............................................................................................................. 2 7 
8. 3        Data bas e ma na g e m e nt a n d q ualit y c o ntr ol ................................................................... 2 7 
8. 4        Data M o nit ori n g C o m mittee ........................................................................................ 2 8  
8. 5        A dj u dic ati o n C o m m ittee .............................................................................................. 2 8  
9          Data a n al ysis ..................................................................................................................... 2 8 
9. 1        A n a l ysis sets ................................................................................................................. 2 8 
9. 2        Patie nt de m o gra p hi cs a nd  ot her b as eli ne c haracteristics ............................................. 2 8 
9. 3        Treat me nts ................................................................................................................... 2 8  
9. 4        A n a l ysis of varia b l es .................................................................................................... 2 8 
9 .4 . 1       V aria bles ................................................................................................................. 2 8 
9 .4 . 2       Statistical m o del, h y p o t hesis, a n d m et ho d of a nal ys is ............................................ 2 9 
9 .4 . 3       H a n dli n g of mi ssi n g val ues/cens ori n g/ disc o n ti n uati o ns......................................... 2 9 
9. 5        I nteri m a n al ys es  ........................................................................................................... 2 9 
9. 6        Sa m ple siz e calc u l ati o n ................................................................................................ 2 9 
1 0        Et h ical c o nsi derati o ns ....................................................................................................... 2 9 
1 0. 1      Re g ulat or y a n d et hi cal c om plia n ce .............................................................................. 2 9 
1 0. 2      I nf or me d c o ns e n t pr oce d ures  ....................................................................................... 2 9 
1 0. 3      Res p o nsi biliti es of t he i n vesti gat or a n d I R B/I E C ........................................................ 3 0 
1 0. 4      P u blicati o n of st u d y pr ot o c ol a n d res u lts ..................................................................... 3 0 
1 1        Pr ot o c ol a d here nce  ............................................................................................................ 3 0 
1 1. 1      Pr ot oc ol A me n d me nts .................................................................................................. 3 0  
1 2        Refere n ces  ......................................................................................................................... 3 0 
1 3  A p p e nd i x 1  : S u m ma r y of p r o d uct c har acteristics  ................................................................. 3 2 
 

N o v artis 
C lin ica l T rial P rot o co l v 0 5  
C o n fid e nt ial  
P ag e 4  
P rot o co l N o . C A C Z 8 8 5 G F R 0 1  
 
 
Li st  of  a b br e vi ati o n s 
 
A E  
A d verse E v e nt 
 
C R F  
Ca se Re p ort/ Recor d F or m ( pa pe r o r electr o nic) 
C P O  
C o u ntr y P h ar ma Or ga niz ati o n  
C R O  
C o ntr act Researc h Or ga niz ati o n 
 
D S & E  
Dr u g Saf et y & E pi de mi o l og y 
 
IC H   
I nt er nati o nal C o nfere n ce o n  Har m o nizati o n of Tech nical Re q uire m e nts f or 
Re g istr ati o n of P h ar mace uti cals f or H u ma n Us e 
 
IE C  
I nd e p e nd e nt Et hics C o m mitte e 
I R B  
I nstit uti o nal Re vie w B o ar d 
S A E   
Seri o us A d v ers e E v e nt 

N o v artis 
C lin ica l T rial P rot o co l v 0 5  
C o n fid e nt ial  
P ag e 5  
P rot o co l N o . C A C Z 8 8 5 G F R 0 1  
 
Gl o s s a r y of  t er m s 
 
A s s e s s m e n t 
A p ro c e d u r e u s e d  to  g e n e ra te  d a t a re q ui re d  b y  t he  s tu d y  
In v e s tig a tio n a l d ru g  
T h e  d ru g  w h o s e  p ro p e rtie s  a re  b ei n g  te s te d  in  th e  s tu d y ; th is  d e fin itio n  is 
c o n si s te n t w it h U S 
C F R  2 1  S e c tio n  3 1 2 . 3 a n d  is  s y n o n y m o u s  w it h 
“i nv e s tig a ti o na l n e w  d ru g ” o r “in v e s tig a tio n a l m e d ici n a l p ro d u c t.” 
In v e s tig a tio n a l tre a tm e n t 
A ll i nv e s tig a tio n a l d ru g (s ) w h o s e  p ro p e rti es  a r e b e in g  te s te d  in  th e  s tu d y a s  
w el l a s  th ei r a s s o c i ate d  tre a tm e n t c o n tro l s. 
T hi s  in cl u d e s a n y  p la c e b o s , a n y  a c tiv e  c o n tro ls , a s  w el l a s  a p p ro v e d  d ru g s 
u s e d  o u tsi d e  o f th e ir in d ic a tio n /a p p ro v e d  d o s a g e  o r te s te d  in  a  fix e d 
c o m bi n a tio n . 
In v e s tig a tio n a l tre a tm e n t g e n e rall y  d o e s  n o t in c l u de  o th e r tre a tm e n t s 
a d m in is te re d  a s  c o n c o m ita n t b a c k g ro u n d  th e ra p y  re q ui re d  o r all o w e d  b y t h e  
p ro to c o l w h e n  u s e d  w ithi n  a p p ro v e d  i nd ic a tio n /d o s a g e  
M e di c a ti on  n u m b e r 
A u ni q u e  id e n tifie r o n  t he  l ab e l o f e a c h  i nv e s ti g ati on al /s tu d y  d ru g  p a c k a g e in  
s tu d ie s  th a t d is p e n s e  m e d ic a ti on  u s i ng  a n  IR T  s y s te m  
S u bj e c t N u m b e r 
A n u m b e r a s s i gn e d  to  e a c h  p a ti e nt w h o  e n ro lls  i nt o th e  s tu d y  
Pr e m a tu r e p a tie n t w ith d ra w a l 
P oi n t/tim e  w h e n  t he  p a ti e nt e x it s fro m  th e  s tu d y  p rio r to  th e  p la n n e d 
c o m pl e ti on  o f a ll i nv e s ti g ati on a l/s tu d y  tre a tm e n t a d mi n i stra tio n  a n d  al l 
a s s e s s m e n t s (in cl u di n g  fo ll ow -u p)  
St u d y  d ru g / tre a tm e n t 
A n y  si n g le  d ru g  o r c o m b i n atio n  o f d ru g s  a d mi n i ste re d  t o th e  p a tie n t a s  p a rt o f 
th e  re q u ire d  s tu d y  p ro c e d u re s ; in c l u de s  in v e s ti g ati on a l d r ug  (s ), a c tiv e d ru g  
ru n -in s  o r b a c k g ro u n d  th e ra p y  
St u d y /i nv e s ti ga ti on a l 
tre a tm e n t di s c o n ti nu a tio n  
P oi n t/tim e  w h e n  p a ti e nt p e rm a n e n tly  s to p s  ta k in g  s tu d y /i nv e s ti g ati o na l 
tre a tm e n t fo r a n y  re a s o n ; m a y  o r m a y  n o t a l so  b e  th e  p oi n t/tim e  o f 
p re m a tu r e p a tie n t w ith d ra w a l 
V a ri ab le  
In fo rm a tio n  u s e d  in  th e  d a t a a n al y s is ; d e riv e d  di re c tly  o r i ndi re c tly  fro m d a t a 
c o ll ec te d  u s i ng  s p e ci fi ed  a s s e s s m e n t s a t s p e ci fi ed  tim e  p oi n ts  
 
A me n d me nt 5 
C ha n ges t o t he pr ot oc ol are relate d t o t he f oll o wi n g secti o ns:  
 
Secti o n 4. 1. i ncl usi o n criteria 
 
T he c urre nt versi o n of i n cl usi o n criteria sti p ulates t hat “ p a ti e nts w h o h ave c o m plete d t he 
i nter nati o n al C A C Z 8 8 5 G 2 3 0 6 st u d y a n d w h o s uccessf ully wit h dre w c a n aki n u m a b tre at me nt 
per pr ot oc ol b ut wit h a dise ase rel a pse wit hi n o ne ye ar fr o m t he E n d of st u dy visit will be 
all o we d t o p artici p ate i n C A C Z 8 8 5 G F R 0 1 st u dy ”.  
T he p ur p ose of t he c ha n ge is t o e na ble t hese patie nts w h o e x perie nce d a rela pse t o be i ncl u de d i n t he 
l ocal e xte nsi o n st u d y C A C Z 8 8 5 G F R 0 1 wit h n o ti me li mitati o n after t he e n d of st u d y visit.  
Ca na ki n u ma b is still n ot c o m merciall y a vaila ble i n Fra nce i n t he SJI A ( S yste mic J u ve nile I di o pat hic 
Art hritis) i n dicati o n at t he date of t he a me n d me nt 5. T he i ncl usi o n i n t he l ocal e xte nsi o n st u d y is t he 
o nl y o pti o n t o treat t hese patie nts a n d t o res u me ca na ki n u ma b, w he n me dicall y j ustifie d.  
 
Secti o n 5. Treat me nt 
F or patie nts pre vi o usl y i ncl u de d i n st u d y C A C Z 8 8 5 G 2 3 0 1 E 1 ( SJI A), t he o pti o n t o i nterr u pt 
ca na ki n u ma b after a pr ol o n ge d re missi o n acc or di n g t o t he i n vesti gat ors j u d g me nt has bee n a d de d. 
E ver y patie nt wit h dra w n fr o m C A C Z 8 8 5 G F R 0 1 st u d y d ue t o a re missi o n will be all o we d t o res u me 
ca na ki n u ma b i n case of rela pse a n d will be f oll o we d u p a gai n i n t he st u d y. 
 
Secti o n 5. 1. 1 . I n vesti gati o nal treat me nt  
N o vartis has bee n s u p pl yi n g t he o pe n-la bel i n vesti gati o nal dr u g (ca na ki n u ma b) u n der t he f or m of a 
l y o p hilisate i n vial. A mar keti n g a ut h orizati o n has bee n gra nte d i n Fe br uar y 2 0 1 7 b y t he E ur o pea n 

N o v artis 
C lin ica l T rial P rot o co l v 0 5  
C o n fid e nt ial  
P ag e 6  
P rot o co l N o . C A C Z 8 8 5 G F R 0 1  
 
C o m missi o n f or ca na ki n u ma b as a s ol uti o n f or i njecti o n. 
If necessar y (f or l o gistic reas o ns), N o vartis ma y s u p pl y o ne or t he ot her p har mace utical f or m f or t he 
trial. T here will n ot be a n y c ha n ge f or t he patie nt i n t he wa y t he me dicati o n is a d mi nistere d 
(s u bc uta ne o usl y).  
 
A me n d me nt 4 
T he p ur p ose of a me n d me nt 4 is t o m o dif y t he para gra p h 4. 1 (I ncl usi o n criteria ), t o ta ke i nt o acc o u nt 
partic ular sit uati o ns of s o me patie nts w h o ha ve bee n i ncl u de d i n i nter nati o nal p hase III st u d y 
C A C 8 8 5 G 2 3 0 6, t o e na ble t he m t o be i ncl u de d i n t he l ocal e xte nsi o n st u d y C A C Z 8 8 5 G F R 0 1. T his 
a me n d me nt is ai mi n g: 
 t o e xte n d t he peri o d t o all o w i ncl usi o n of patie nts f or t he patie nts w h o have  c o m plet e d t he 
i nter nati o nal C A C Z 8 8 5 G 2 3 0 6 st u d y a n d w h o s uccessf ull y wit h dre w ca na ki n u ma b treat me nt 
per pr ot oc ol b ut wit h a disease rela pse i n t he f oll o wi n g m o nt hs. After a me n d me nt 4, patie nts 
w h o will rela pse wit hi n o ne ye ar fr o m t he E n d of st u d y visit  (i nstea d of wit hi n o ne year 
fr o m e n d of treat me nt) will be all o we d t o partici pate i n C A C Z 8 8 5 G F R 0 1 st u d y. 
 
 t o a d d a ne w i ncl usi o n criteria t o ta ke i nt o acc o u nt t he s pecific sit uati o n of t he patie nts of 
C A C Z 8 8 5 G 2 3 0 6 st u d y, n ot ra n d o mize d (after ra n d o mizati o n cl os ure), a n d w h o, acc or di n g t o 
t he i nter nati o nal pr ot oc ol, are s u p p ose d t o re mai n at 4 m g/ k g e ver y 4 wee ks u ntil t he e n d of 
t he st u d y. After a sta ble a n d pr ol o n ge d re missi o n i n part II t he i n vesti gat ors ma y pr o p ose t o 
re d uce t he ca na ki n u ma b d ose i n t he i nterest of t he patie nts as pr o p ose d i n c urre nt practice ( b ut 
n ot all o we d i n t he c urre nt pr ot oc ol). T hese patie nts ( 3 t o 5 patie nts), will be wit h dra w n fr o m 
C A C Z 8 8 5 G 2 3 0 6 st u d y a n d will be all o we d t o partici pate i n C A C Z 8 8 5 G F R 0 1 st u d y t o 
c o nti n ue ca na ki n u ma b treat me nt. 
 
A me n d me nt 3 
T he p ur p ose of a me n d me nt 3 is t o o pe n t he recr uit me nt of st u d y C A C Z 8 8 5 G F R 0 1 t o patie nts w h o will 
c o m plete: 
 t h e p hase III i nter nati o nal st u d y C A C Z 8 8 5 N 2 3 0 1 desi g ne d t o assess efficac y a n d t olera bilit y 
of c a n a ki n u m a b i n patie nts s ufferi n g fr o m 3  r ar e He re dit ar y Perio d ic F e v ers [ T R AP S  ( T N F 
rece pt or ass ociate d peri o dic s y n dr o me), HI D S ( h y peri m m u n o gl o b uli ne mia D s y n dr o me) or 
crF M F ( c olc hi ci ne resista nt Fa mili al M e dit err a ne a n Fe ver)], 
 or t h e p h as e III i nt er n ati o n al st u d y C A C Z 8 8 5 G 2 3 0 6 d esi g n e d t o assess 2 differe nt 
ca na ki n u ma b ta per re gi me ns i n patie nts s ufferi n g fr o m SJI A ( S yste mic J u ve nile I di o pat hic 
Art hritis) wit h cli nical re missi o n (i nacti ve disease f or at least 2 4 c o nti n u o us wee ks) o n 
ca na ki n u ma b treat me nt. 
T h e o bj e cti v e is t o pr o vi de c o nti n u o us treat me nt t o t hese patie nts o nce C A C Z 8 8 5 N 2 3 0 1 a n d 
C A C Z 8 8 5 G 2 3 0 6 are c o m plete d a n d u ntil t his me dicati o n is c o m merciall y a vaila ble i n Fra nce f or 
t hese ne w i n dicati o ns. 
T a ki n g i nt o acc o u nt t he stat us of t hese o n g oi n g st u dies at t he date of Ma y 2 0 1 6, we ma y a ntici pate t hat 
a ma xi m u m of 8 patie nts i ncl u de d i n C A C Z 8 8 5 N 2 3 0 1 ( wit hi n 4 Fre nc h c e nters) ma y be i ncl u de d i n 
C A C Z 8 8 5 G F R 0 1 fr o m 
N o ve m ber 2 0 1 6 a n d t hat a 
ma xi m u m of 2 1 patie nts i ncl u de d i n 
C A C Z 8 8 5 G 2 3 0 6 ( wit hi n 3 Fre nc h ce nters) fr o m Oct o ber 2 0 1 6. 
T he last visit of st u d y C A C Z 8 8 5 N 2 3 0 1 wi ll be  t he first visit of st u d y C A C Z 8 8 5 G F R 0 1. P atie nts wi ll 
c o nti n ue o n t heir last d osi n g r e g i me n of t he o pe n-l a be l lo n g t er m treat me nt e p ochs  ( Ep o c hs 4) 
c o nsi dere d t o c o nstit ut e t he l o west c linica lly e ffic aci o us d oses t o 
mai nt ai n clini c a l effic ac y i n 
i n di vi d ual patie nts. Patie nts m a y r ecei ve a n u p-titratio n if t he y re-flar e ( ma xi m u m d ose of 3 0 0 m g/ 4 
mg/ k g f or patie nts wei g h in g  ≤4 0 k g) q 4 w. 

N o v artis 
C lin ica l T rial P rot o co l v 0 5  
C o n fid e nt ial  
P ag e 7  
P rot o co l N o . C A C Z 8 8 5 G F R 0 1  
 
T he f oll o w- u p of patie nts wit h Here ditar y Peri o dic Fe ver will be t he sa me as t he o ne f or patie nts wit h 
SJI A.  
T he last visit of st u d y C A C Z 8 8 5 G 2 3 0 6 will als o be t he first visit of st u d y C A C Z 8 8 5 G F R 0 1. P atie nts 
wi ll c o nti nue  o n t heir d osin g  r e gi me n c o nsi dere d  t o c o nstit ut e t he lo west clinica lly e ffic aci o us d ose t o 
ma i nt ai n clini c a l effic ac y i n i n di vi d ual pa tie nts.  
T he st u d y d urati o n of C A C Z 8 8 5 G F R 0 1 st u d y will be e xte n de d u ntil ca na ki n u ma b (Ilaris ® ) is 
c o m merciall y a vaila ble f or all i n dicati o ns.  
C ha n ges t o t he pr ot oc ol are relate d t o t he f oll o wi n g secti o ns:  
 
Secti o n 1. 1. Bac k gr o u n d 
 
Secti o n 1. 2. P ur p ose 
 
Secti o n 3. 1. St u d y desi g n 
 
Secti o n 3. 3. Rati o nale of d ose/re gi me n, r o ute of a d mi nistrati o n a n d d urati o n of treat me nt 
 
Secti o n 3. 5. Ris ks a n d be nefits 
 
Secti o n 4. P o p ulati o n 
 
Secti o n 5. Treat me nt 
 
Secti o n 6. Visit sc he d ule a n d assess me nts 
 
Secti o n 9. 4. A nal ysis of varia bles 
 
A me n d me nt 2  
T he p ur p ose of t his st u d y C A C Z 8 8 5 G F R 0 1 is t o pr o vi de c o nti n u o us Ilaris ®  (ca na ki n u ma b) treat me nt 
t o patie nts i n Fra nce w h o c o m plete d St u d y C A C Z 8 8 5 G 2 3 0 1 E 1 (l o n g ter m p hase III st u d y) u ntil t his 
me dicati o n is c o m merciall y a vaila ble a n d rei m b urse d i n Fra nce f or t he s yste mic J u ve nil e I di o pat hic 
Art hritis i n dicati o n. T he c urre nt versi o n of t he pr ot oc ol sti p ulates t hat t he treat me nt peri o d will be a 
ma xi m u m 1 2 m o nt hs or c o ul d e n d s o o ner if Ilaris
®  was c o m merciall y a vaila ble i n Fra nce. 
Beca use it is a ntici pate d t hat t he rei m b urse me nt of Ilaris ®  (ca na ki n u ma b) ma y n ot be ac hie ve d at 
act ual date of st u d y c o m pleti o n, t he st u d y d urati o n will be e xte n de d ( o ne year e xte nsi o n).  
C ha n ges t o t he pr ot oc ol are relate d t o t he f oll o wi n g secti o ns:  
 
Secti o n 1. 1. Bac k gr o u n d 
 
Secti o n 1. 2. P ur p ose 
 
Secti o n 3. 1. St u d y desi g n 
 
Secti o n 6. Visit sc he d ule a n d assess me nts 
 
A me n d me nt 1 
T he p ur p ose of a me n d me nt 1 is t o ma ke clear t hat N o vartis will s u p pl y t he o pe n-la bel i n vesti gati o nal 
dr u g (ca na ki n u ma b) fr o m c o m mercial pac ka ges or cli nical batc hes.  
F urt her m ore, a me n d me nt 1 als o a d dresses t he re q uest fr o m t he i n vesti gat ors t o a d d t he o pti o n t o 
re d uce t he ca na ki n u ma b d ose i n patie nts wit h a de q uate res p o nse b y pr ol o n gi n g t he ca na ki n u ma b d ose 
i nter val (i.e. e ver y 6 or 8 wee ks) acc or di n g t o cli nical res p o nse a n d i n vesti gat ors j u d g me nt. 
C ha n ges t o t he pr ot oc ol are relate d t o t he f oll o wi n g secti o ns:  
 
Secti o n 5. 1. 1 I n vesti gati o nal treat me nt 
 
Secti o n 5 Treat me nt 
 
Secti o n 6. Visit sc he d ule a n d assess me nts 

N o v artis 
C lin ica l T rial P rot o co l v 0 5  
C o n fid e nt ial  
P ag e 8  
P rot o co l N o . C A C Z 8 8 5 G F R 0 1  
 
Pr ot o c ol  s y n op si s  
 
 
Pr o to c ol  n u m b e r 
C A C Z 8 8 5 G F R 0 1  
T itl e 
A  F re n c h  o p e n -la b e l e x t e n si o n st u d y  o f c a n a ki n u m a b  i n p a tie nt s 
w h o 
p a rti ci pa te d  
i n  
i n te r na tio n a l 
p h a s e  
III 
st u d i e s 
C A C Z 8 8 5 G 2 3 0 1 E 1  
or 
C A C Z 8 8 5 G 2 3 0 6 i n S y st e mi c J u v e ni le  I di o pa t hic A rt hritis  a n d  C A C Z 8 8 5 N 2 3 0 1 i n 
H er e di t ar y P eri o di c F e v er ( T R A P S, HI D S or cr F M F). 
Br ief  titl e 
F re n c h 
st u d y  e x t e n si o n t o st u d y 
C A C Z 8 8 5 G 2 3 0 1 E 1 , C A C Z 8 8 5 G 2 3 0 6 
a n d 
C A C Z 8 8 5 N 2 3 0 1 . 
S p o n s or  a n d  Cli ni c al  
P h a s e  
N o v a rti s P h a r m a S A S  
III 
I nv e s ti g ati o n ty p e  
B i olo g ic a l 
S tu d y  ty p e  
In te r ve nt io n a l 
P u rp o s e  a n d  rati o n al e  
T h e  p ur p o s e  of  t his  st u d y i s  t o p ro vi d e  c o nt in u o u s  c a n a ki n u m a b ( Il aris ® ) tre a tm e nt 
t o pa tie nt s i n F ra n c e w h o  c o m p le t e d s t ud y C A C Z 8 8 5 G 2 3 0 1 E 1 , C A C Z 8 8 5 G 2 3 0 6 or  
C A C Z 8 8 5 N 2 3 0 1 .  
T h e l o c al e xt e n si o n st u d y will b e c o m pl et e d a s s o o n a s c a n a ki n u m a b i s 
c o m m e r ci ally a v a ila bl e a n d r e im b ur s e d i n  F ra n c e  for t h e s e i n di ca tio n s , or if 
a p pli c a bl e, w h e n it will b e c o nfir m e d t h at t h e l a st i n di c ati o n c o ul d n ot b e r ei m b ur s e d 
i n Fr a n c e. H o w e v er, a s t h e c o m m er ci ali z ati o n of t h e diff er e nt i n di c ati o n s will b e 
eff e cti v e at diff er e nt d at e s, p ati e nt s 
will di s c o nti n u e t h e st u d y i n di c ati o n b y 
i n di c ati o n. 
T hi s  st u d y 
will  o n ly  b e  p r o p o se d  t o F re n c h  c e nt e rs  i n v olv e d  i nto  st u d y  
C A C Z 8 8 5 G 2 3 0 1 E 1 , C A C Z 8 8 5 G 2 3 0 6 a n d C A C Z 8 8 5 N 2 3 0 1 .  
 
O bj e c tiv e( s)  
T h e  o bj e c tiv e  of  t his  e x t e n si o n p rot o c ol  i s t o c ol le c t s a fe ty d a t a (s e ri o u s a n d n o n -
s e ri o u s a d v e r s e e v e nt s ) a n d  t o p ro vi d e c o nt in u o u s  c a n a ki n u m a b  to  p a tie nt s  i n 
F ra n c e  
w h o  
c o m p le t e d  
st ud y  
C A C Z 8 8 5 G 2 3 0 1 E 1 , 
C A C Z 8 8 5 G 2 3 0 6  
or 
C A C Z 8 8 5 N 2 3 0 1  u nt il a  d e c i sio n r e g a r din g  r eim b ur s e m e n t i n F ra n c e  i s ef f ec tiv e  f or 
c a n a ki n u m a b ( Il ari s® ) i n t h e s e i n di ca tio n s . 

N o v artis 
C lin ica l T rial P rot o co l v 0 5  
C o n fid e nt ial  
P ag e 9  
P rot o co l N o . C A C Z 8 8 5 G F R 0 1  
 
S tu d y  d e si g n  
T hi s  i s a n  o p e n -l ab e l (s in g l e tre a tm e nt  a rm ) e x t e n si o n s a fe ty  st u d y  f or p ati e nt s 
w h o  c o m p le t e d t h e i nte r na tio n a l st u d i e s: 
 
C A C Z 8 8 5 G 2 3 0 1 E 1  
 
or C A C Z 8 8 5 N 2 3 0 1  
 
or C A C Z 8 8 5 G 2 3 0 6  
T h e  l a st vi s it of  st u d y C A C Z 8 8 5 G 2 3 0 1 E 1 , C A C Z 8 8 5 G 2 3 0 6 or C A C Z 8 8 5 N 2 3 0 1  will  
b e  t h e first  vi s it of t hi s  e x t e n si o n s t ud y .  
P ati e nt s f oll o w u p:  
F or p ati e nt s pr e vi o u sl y i n cl u d e d i n st u d y C A C Z 8 8 5 G 2 3 0 1 E 1  ( S JI A i n di c ati o n) 
T h e s e p a tie nt s  will  c o nt in u e t h e  s a m e  d o si n g  r eg im e n  u s e d  a t t h e e n d  o f 
C A C Z 8 8 5 G 2 3 0 1 E 1.  
Vi s it s will t a k e pl a c e  a t c a n a ki n u m a b d o s e  a d m ini s tra tio n s,  a p pr o x im a t ely e v e ry  
4  w e e k s  ( or l e s s fr e q u e ntl y a c c or di n g t o i n v e sti g at or s j u d g m e nt i. e. 6, 8 or 1 2 
w e e k s ). T h e s a fe ty o f c a n a ki n u m a b will  b e  e v a l u ate d  (a d v e rs e e v e nt s a n d 
s e ri o u s a d v e r s e e v e nt s c ol l ec tio n).  P a tie nt s will  b e f oll o w e d u p a c c o rdi n g  t o 
S m P C (s e e  a p p e n di x  1) a n d l o c a l pra c tic e.  
F or 
p ati e nt s 
pr e vi o u sl y i n cl u d e d i n st u d y 
C A C Z 8 8 5 N 2 3 0 1 ( P eri o di c 
F e v er 
s y n dr o m e s ) 
T h e s e p ati e nt s will c o nti n u e th e  m ai nt e n a n c e d o s e a s d et er mi n e d at t h e e n d 
of t h e o p e n -l a b el p eri o d/ e p o c h 4 (i. e t h e lo w e s t c lin ic a lly  e ffic a c io u s  d o s e  to  
m a i nta in  c lin ic a l e ffic a c y  i n in d iv id u a l p a tie n ts  wit h a g o o d t ol er a bilit y).  
Vi sit s  will  t a k e pl a c e  a t s c h e d ul e d  a d m ini s tra tio n  d a t e s, a p pr o x im a t ely  e v e ry  
4 , 8  or 1 2  w e e k s.  T h e s a fe ty  o f c a n a ki n u m a b will  b e  e v a l u ate d  (a d v e r s e 
e v e nt s  a n d  s e ri o u s a d v e r s e e v e nt s).  P a tie nt s  will t h e n b e  fol lo w e d u p 
a c c o rdi n g t o S m P C a p pr o v e d b y E M A (E ur o p e a n M e di ci n e s A g e n c y ). 
F or p ati e nt s pr e vi o u sl y i n cl u d e d i n st u d y C A C Z 8 8 5 G 2 3 0 6  ( S JI A) 
T h e s e p ati e nt s  w ill c o n tin u e  o n  th e ir d o s in g  re g i me n  c o n s id e re d  to  c o n s titu te  
th e  lo w e s t c lin ic a lly  e ffic a c io u s  d o s e  to  m a i nta in  c lin ic a l e ffic a c y  i n in d iv id u a l 
p a tie n ts.   
Vi s it s will t a k e pl a c e  a t c a n a ki n u m a b  d o s e  a d m ini s tra tio n , a p pr o x im a t ely e v e ry  
4 , 8 or 1 2 w e e k s . T h e s a fe ty o f c a n a ki n u m a b will  b e  e v a l u ate d  (a d v e rs e e v e nt s 
a n d s e ri o u s a d v e r s e e v e nt s c ol l ec tio n).  P a tie nt s will  b e f oll o w e d u p a c c o rdi n g  t o 
S m P C (s e e  a p p e n di x  1) a n d i n v e sti g at or s j u d g m e nt.  
 
P o p u l ati o n 
U p t o 4 0 p ati e nt s m a y b e i n cl u d e d i n t h e Fr e n c h e xt e n si o n st u d y C A C Z 8 8 5 G F R 0 1 (i n 
3 c e nt er s).  
 T w el v e p ati e nt s pr e vi o u sl y e nr oll e d i nt o st u d y C A C Z 8 8 5 G 2 3 0 1 E 1  
 U p t o 2 8  p ot e nti al a d diti o n al p ati e nt s  a c c or di n g t o a m e n d m e nt 3:  
o  
U p t o 2 1  p ati e nt s  i n cl u d e d i n C A C Z 8 8 5 G 2 3 0 6 st u d y (i n 3 Fr e n c h c e nt er s) 
o  
U p t o 7  p ati e nt s i n cl u d e d i n C A C Z 8 8 5 N 2 3 0 1 st u d y (i n 3  Fr e n c h c e nt er s).  
 

N o v artis 
C lin ica l T rial P rot o co l v 0 5  
C o n fid e nt ial  
P ag e 1 0  
P rot o co l N o . C A C Z 8 8 5 G F R 0 1  
 
I n cl u si o n c rit eri a 
Crit eri a a p pli c a bl e f or p ati e nt s wit h S y st e mi c J u v e nil I di o p at hi c Art hriti s S JI A)  
 P ati e nt s  
w h o  
h a v e  
c o m pl et e d  
t h e  
i nt er n ati o n al  
st u di e s 
C A C Z 8 8 5 G 2 3 0 1 E 1 or C A C Z 8 8 5 G 2 3 0 6 wit h o ut a n y si g nifi c a nt s af et y 
i s s u e a c c or di n g t o I n v e sti g at or’ s o pi ni o n . 
 P a tie nt s  w h o  h a v e  c o m p l ete d  t h e i nte r na tio n a l C A C Z 8 8 5 G 2 3 0 6  st u d y  
a n d w h o s u c c e s sf ull y wit h dr e w c a n a ki n u m a b tr e at m e nt p er pr ot o c ol b ut 
wit h a di s e a s e r el a p s e aft er t h e e n d of st u d y vi sit will b e all o w e d t o 
p arti ci p at e i n C A C Z 8 8 5 G F R 0 1 st u d y ( w h at e v er t h e ti m e of r el a p s e fr o m 
t h e e n d of st u d y vi sit), if t h e i n v e sti g at or st at e s t h at t h er e i s a n i n di c ati o n 
t o r e s u m e c a n a ki n u m a b. 
 P a tie nt s  w h o  h a v e  p arti ci p at e d i n t h e i nte r na tio n a l C A C Z 8 8 5 G 2 3 0 6  
st u d y 
b ut 
c o ul d 
n ot 
b e r a n d o mi z e d 
a n d t h e n 
h a v e 
c o nti n u e d 
c a n a ki n u m a b i n p art I u ntil t h e e n d of t h e st u d y at a d o s e of 4 m g/ k g 
e v er y 4 
w e e k s 
m a y b e s wit c h e d t o 
C A C Z 8 8 5 G F R 0 1 st u d y if t h e 
i n v e sti g at or t hi n k s t h at, i n t h e i nt er e st of t h e p ati e nt, t h er e i s a n i n di c ati o n 
t o t a p er off c a n a ki n u m a b d o s e aft er a pr ol o n g e d r e mi s si o n. 
 
Crit eri a  a p pli c a bl e f or p ati e nt s wit h P eri o di c F e v er s y n dr o m e s  ( T R A P S, HI D S, 
cr F M F)  
 P ati e nt s w h o h a v e c o m pl et e d t h e i nt er n ati o n al C A C Z 8 8 5 N 2 3 0 1 st u d y 
wit h o ut a n y si g nifi c a nt s af et y i s s u e  a c c or di n g t o I n v e sti g at or’ s o pi ni o n . 
 
Crit eri a a p pli c a bl e f or all p ati e nt s  
 P ar e nt' s or l e g al g u ar di a n' s writt e n i nf or m e d c o n s e nt a n d c hil d' s a s s e nt, 
if a p pr o pri at e, or p ati e nt' s writt e n i nf or m e d c o n s e nt f or p ati e nt s ≥ 1 8 
y e ar s of a g e 
m u st b e o bt ai n e d b ef or e a n y st u d y r el at e d a cti vit y or 
a s s e s s m e nt i s p erf or m e d.  
E x c lu si o n  c rit eria  
1. Hi st o ry of r e c u rrin g i nf e c tio n s, or u n d e rly in g c o n di ti o n s w hi c h  m a y p r edi s p o s e  
th e m  t o i nfe c tio n s.  T r e atm e nt  wit h  c a n a ki n u m a b s h o ul d  n ot  b e  c o nt in u e d i n  p a tie nt s  
wit h  s e v e r e in f e ctio n s  re q uiri n g m e di c a l int e rv e nt io n.  
2. H y p e rs e n si ti vity t o  t h e a c tiv e  s u b s ta n c e  or  t o a n y of  th e e x c i pie nt s ( s e e  S m P C, 
s e c tio n 6. 1 ). 
3.  C o n c o m it a nt u s e  of  s e c o n d  lin e a g e nt s  s u c h  a s  di s e a s e -m o d ify in g a n d/ or  
im m u n o s u p pr e s s iv e d ru g s  will  n ot b e  a llo w e d  wit h  t h e e x c e pt io n o f: 
• M et h otr e x a t e, a n d  f olic /f oli ni c a c i d s u p pl e m e n ta tio n ( a c c o rdi n g  t o st a n da r d 
m e di c a l pra c tic e ) 
• N o n -st e roi d al a nt i-i nfla m m a t ory  dr u g  (N S A ID ) 
• S y st e mi c  c o rtic o s te r oid tr e a tm e nt.  
4.  C o n c o m it a nt u s e  of  a n ot h er  bi o lo g ic  a g e nt  or  a n y i n v e sti g a tio n a l dru g . 
5.  P r eg n a nt  or  n ur si n g  (la c t atin g ) fe m al e  p a tie nt s , w h e re  p r eg n a n c y i s  d e fi ne d  a s  
t h e st at e  of  a  fe m a le a fte r c o n c e pt io n  a n d  u nt il t h e t erm in a tio n  of  g e st ati o n,  
c o nfi rm e d  b y  a  p o sit iv e  h C G  l a b or at ory t e st or a n uri n a ry  p r eg n a n c y  te st.  
6.  F e m al e p a tie nt s  w h o  a r e of c hi ld -b e a rin g p ot e nt ia l d e fi ne d  a s  a ll fe m al e s  
p h y si o lo g i ca lly c a p a bl e  o f b e c o m in g p r eg n a nt,  u nl e s s  t he y a r e u sin g e ffe c tiv e  
m et h o d s  of  c o ntr a c e pt io n  d uri n g d o si n g of  st u d y tr e a tm e nt.  

N o v artis 
C lin ica l T rial P rot o co l v 0 5  
C o n fid e nt ial  
P ag e 1 1  
P rot o co l N o . C A C Z 8 8 5 G F R 0 1  
 
T re a tm e n t 
All p ati e nt s will b e t r e ate d wit h  c a n a ki n u m a b . 
F or p ati e nt s pr e vi o u sl y i n cl u d e d i n st u d y C A C Z 8 8 5 G 2 3 0 1 E 1 ( S JI A)  
T h e s e p a tie nt s  will  c o nt in u e  th e  s a m e  d o s e  a s  t h eir l a st d o s e  a d m ini s te re d i n  
t h e st u d y  C A C Z 8 8 5 G 2 3 0 1 E 1: c a n a ki n u m a b  4 m g /k g  (o r 3 0 0 m g m a x ) or 2 m g / k g 
( 1 5 0m g /m a x ) e v e ry  4 w e e k s  ( or l e s s fr e q u e ntl y a c c or di n g t o i n v e sti g at or s 
j u d g m e nt i. e. 6, 8 or 1 2 w e e k s ). 
F or p ati e nt s pr e vi o u sl y i n cl u d e d i n st u d y C A C Z 8 8 5 G 2 3 0 1 E 1 , th e c a n a ki n u m a b 
d o s e i nt er v al 
m a y b e pr ol o n g e d (i. e. e v er y 8  or 1 2  w e e k s) i n p ati e nt s wit h 
a d e q u at e r e s p o n s e  a c c or di n g t o t h e cli ni c al r e s p o n s e 
a n d i n v e sti g at or s 
j u d g m e nt. 
 
F or p ati e nt s pr e vi o u sl y i n cl u d e d i n st u d y C A C Z 8 8 5 N 2 3 0 1  (P eri o di c F e v er 
s y n dr o m e s ) 
T h e s e p ati e nt s  w ill c o n tin u e  o n  th e ir la s t d o s in g  re g i me n  of  th e  o p e n -la b e l lo n g 
te rm tre a tm e n t e p o c h s  ( Ep o c h s  4)  c o n s id e re d  to  c o n s titu te  th e  lo w e s t c lin ic a lly  
e ffic a c io u s  d o s e  to  m a i nta in  c lin ic a l e ffic a c y  i n in d iv id u a l p a tie n ts . 
P ati e nt s will t h e n c o nti n u e o n e of t h e f oll o wi n g r e gi m e n:  
- 
C a n a ki n u m a b 1 5 0 m g  ( or 2 m g/ k g fo r p a tie n ts  w e ig h in g  ≤4 0  k g ) q 4 w   
- 
C a n a ki n u m a b 1 5 0 m g ( or 2 m g/ k g fo r p a tie n ts  w e ig h in g  ≤4 0  k g ) q 8 w   
- 
C a n a ki n u m a b 3 0 0 m g ( or 4 m g/ k g fo r p a tie n ts  w e ig h in g  ≤4 0  k g ) q 4 w   
- 
C a n a ki n u m a b 3 0 0 m g ( or 4 m g/ k g fo r p a tie n ts  w e ig h in g  ≤4 0  k g ) q 8 w . 
I n c a s e of re -fla re ( a c c or di n g t o i n v e sti g at or s j u d g m e nt), p ati e nt s will b e all o w e d 
t o i n cr e a s e t h e d o s e a s f oll o ws : 
- 
If p ati e nt s  r e c ei v e c a n a ki n u m a b 1 5 0 m g q 8 w, t h e d o s e of c a n a ki n u m a b 
will b e i n cr e a s e d t o 1 5 0 m g q 4 w  
- 
If p ati e nt s r e c ei v e c a n a ki n u m a b 1 5 0 m g q4 w, t h e d o s e of c a n a ki n u m a b 
will b e i n cr e a s e d t o 3 0 0 m g q 4 w  
- 
If p ati e nt s r e c ei v e c a n a ki n u m a b 3 0 0  m g q 8 w, t h e d o s e of c a n a ki n u m a b 
will b e i n cr e a s e d t o 3 0 0 m g q 4 w . 
F or p ati e nt s pr e vi o u sl y i n cl u d e d i n st u d y C A C Z 8 8 5 N 2 3 0 1, t h e c a n a ki n u m a b 
d o s e i nt er v al 
m a y b e pr ol o n g e d (i. e. e v er y 8 or 1 2 w e e k s) i n p ati e nt s wit h 
a d e q u at e r e s p o n s e  a c c or di n g t o t h e cli ni c al  r e s p o n s e a n d i n v e sti g at or s 
j u d g m e nt. 
 
F or p ati e nt s pr e vi o u sl y i n cl u d e d i n st u d y C A C Z 8 8 5 G 2 3 0 6  ( S JI A): 
T h e s e p ati e nt s will  c o nt in u e  th e  s a m e  d o s e  a s  t h eir l a st d o s e  a d m ini s te re d at 
t h e e n d of t h e t a p eri n g p eri o d st ud y  C A C Z 8 8 5 G 2 3 0 6 . 
T h e n, p ati e nt s will c o nti n u e o n e of t h e f oll o wi n g r e gi m e n s:  
- 
C a n a ki n u m a b 4 m g/ k g  q 4 w k s  
- 
C a n a ki n u m a b 2 m g/ k g q 4 w k s  
- 
C a n a ki n u m a b 1 m g/ k g q 4 w k s  
- 
C a n a ki n u m a b 4 m g/ k g q 8 w k s  
- 
C a n a ki n u m a b 4 m g/ k g q 1 2 w k s . 
P a tie n ts  m a y  re c e iv e  a n  u p -titra tio n  if th e y  re -fla re ( m a xi m u m d o s e of 3 0 0 m g 
(or  4  m g/ k g  s .c  fo r p a tie n ts  ≤4 0  k g)  q 4 w).  
 
P ati e nt s w h o s u c c e s sf ull y wit h dr e w  c a n a ki n u m a b p er pr ot o c ol b ut wit h a di s e a s e 
r el a p s e will b e all o w e d t o p arti ci p at e i n C A C Z 8 8 5 G F R 0 1 st u d y ( w h at e v er t h e 
ti m e of r el a p s e fr o m t h e e n d of st u d y vi sit) a n d will r e c ei v e a st arti n g d o s e of 4 
m g/ k g s .c  ( 3 0 0 m g fo r p a tie n ts  ≥4 0  k g)  e v er y 4 w e e k s.  T hi s d o s e ( or d o s e 
i nt er v al) m a y b e a dj u st e d a c c or di n g t o t h e r e s p o n s e a n d i nv e sti g at or s j u d g m e nt.  
F or p ati e nt s pr e vi o u sl y i n cl u d e d i n st u d y C A C Z 8 8 5 G 2 3 0 6 , th e c a n a ki n u m a b d o s e 
i nt er v al 
m a y al s o b e pr ol o n g e d (i. e. e v er y 8  or 1 2  w e e k s) i n p ati e nt s wit h 
a d e q u at e r e s p o n s e  a c c or di n g t o t h e cli ni c al r e s p o n s e 
a n d i n v e sti g at or s 
j u d g m e nt.  
F or all i n di c ati o n s, t h e m a xi m u m c a n a ki n u m a b d o s e i s 4 m g/ k g or 3 0 0 m g f or 
p ati e nt s ≥ 4 0 k g.  

N o v artis 
C lin ica l T rial P rot o co l v 0 5  
C o n fid e nt ial  
P ag e 1 2  
P rot o co l N o . C A C Z 8 8 5 G F R 0 1  
 
I n v e sti g ati o n al tr e at m e nt 
N o v arti s h a s b e e n s u p pl yi n g t h e o p e n -l a b el i n v e sti g ati o n al dr u g ( c a n a ki n u m a b) u n d er 
t h e f or m of a l y o p hili s at e i n vi al. A m ar k eti n g a ut h ori z ati o n h a s b e e n gr a nt e d i n 
F e br u ar y 2 0 1 7 b y t h e E ur o p e a n C o m mi s si o n f or c a n a ki n u m a b a s a s ol uti o n f or 
i nj e cti o n. If n e c e s s ar y (f or l o gi sti c r e a s o n s), N o v arti s m a y s u p pl y o n e or t h e ot h er 
p h ar m a c e uti c al f or m f or t h e tri al.  T h er e  will n ot b e a n y c h a n g e f or t h e p ati e nt i n t h e w a y 
t h e m e di c ati o n i s a d mi ni st er e d ( s u b c ut a n e o u sl y). 
E ffi ca c y  a s s e s s m e n ts  
T h e r e i s n o e ffic a c y  a s s e s s m e nt in t h is s tu d y  
S af e ty  a s s e s s m e n ts  
A E s a n d S A E s will  b e  c o lle c t e d 
Ot h er  a s s e s s m e nt s  
N o n e  
D at a  a n al y s is  
T h e d at a will b e pr e s e nt e d i n a d e s cri pti v e m a n n er. A d v er s e e v e nt s will b e c o d e d 
u si n g t h e M e d D R A di cti o n ar y t h at pr o vi d e s t h e pri m ar y s y st e m or g a n cl a s s a n d 
pr ef err e d t er m i nf or m ati o n.  
A d v e r s e e v e nt s  will  b e  s u m m a riz e d  f or e a c h i n di c ati o n b y  p re s e nt in g  t h e n u m b er  a n d 
p e r ce nt a g e  of  p a ti ent s  h a vi n g  a n y a d v e rs e  e v e nt,  h a vi n g  a n y a d v e r s e e v e nt  i n e a c h  
p rim ar y  s y st e m  o rg a n  c l a s s a n d  h a v i n g e a c h  i n divi d u al a d v e r s e e v e nt  b a s e d  o n  t h e 
p r ef err ed  t erm.  All  ot h er i nf o r ma tio n c ol l e ct e d ( e. g. s e v e rit y, r el ati o n s hi p t o st u d y  
d ru g , or  m i cr o or g ani s m f or i nf e c tio u s  a d v e r s e e v e nt s)  will  b e t a b ul at e d  a n d  list e d  a s 
a p pr o p riat e.  
D e a t h s, s e ri o u s a d v e r s e e v e nt s,  a n d  a d v e r s e e v e nt s  l ea di n g t o di s c o nti n u a tio n of  
st u d y  d ru g will  b e  s u m m a riz e d  b y  p ri m ary  s y st e m o rg a n c l a s s a n d p re fe rre d  t erm a n d 
li st e d. 
T h e  e x p o s ur e  t o st u d y d r u g (n u m b er  o f i nje c tio n s)  a n d  d ur a tio n  of e x p o s ur e  (d a y s) 
will  b e  s u m m a riz e d a n d l ist e d . 

N o v artis 
C lin ica l T rial P rot o co l v 0 5  
C o n fid e nt ial  
P ag e 1 3  
P rot o co l N o . C A C Z 8 8 5 G F R 0 1  
 
1          I ntro d u ct i o n 
 
1. 1        B a c k gr o u n d 
 
S yste mic J u ve nile I di o pa t hic Art hritis ( SJI A) is a s u bset of J u ve nile I di o pat hic Art hritis (JI A), a 
seri o us a n d p ote ntiall y disa bli n g f or m of art hritis t hat occu rs i n chi l dren  1 6 years of age  a n d 
y o u n ge r, a n d acco u nts f or a p pr o xi ma tel y 4 - 1 7 % of JI A (Q u artier 2 0 0 7, Ra velli a n d 
Marti ni 
2 0 0 7 ). I n c o ntrast t o ot her JI A s u bt y p es SJI A is ass ociate d wit h s yste mic s ym p t o ms s uc h as fe ver, 
ras h, a ne mia, leu k o c yt osis, ele vate d er yt hr oc yte se di me ntati o n rate a n d acut e- p h ase. T he peak  
a ge of disea se o nset lies bet ween  1 8 m o nt hs a n d 2 years, b ut SJI A ma y occ ur i n c hil dren of a n y 
a ge a n d, rarel y, i n y o u n g a d ults t o o ( W o o 2 0 0 6 ). 
Se veral li nes of e vi de nce s h o w t hat i n terle u ki n- 1 (I L- 1) pl a ys a pi v otal r ole i n t he pat h o ge nesis of 
SJI A ( Di narell o 2 0 0 5 , Pasc u al et al 2 0 0 5). 
Il aris®  ( Ca na ki n u ma b) is a h u ma n m o n ocl o nal a nti- h u ma n i nterle u ki n- 1 be ta (I L- 1 beta) a ntib o d y of 
t he I g G 1/ κ is ot y pe. Ca na ki n u ma b bi n ds wit h hi g h aff i nit y s pecificall y t o h u ma n I L- 1 bet a an d  
n eut ralizes t he bi ol o gi cal activi t y of h u ma n I L- 1 bet a b y bl oc ki n g its i nteracti o n wit h I L- 1 rece pt ors, 
t here b y prev e nti n g I L- 1 beta-i n d uce d gene  acti vati o n a n d t he pr o d ucti o n of i nfla m mat or y me diat ors. 
Ca na ki n u ma b has a half-li fe of a p pr o xi ma tel y 2 1- 2 8 da ys. 
T o  
date, f ou r cli nical st u dies ( C A C Z 8 8 5 A 2 2 0 3, C A C Z 8 8 5 G 2 3 0 5, 
C A C Z 8 8 5 G 2 3 0 1, a n d 
C A C Z 8 8 5 G 2 3 0 1 E 1 ) h a ve b een  perf or me d b y N o vartis t o e val uate cana ki n u ma b as a tr eat me nt f or 
p atie nts wit h SJI A.  
Il aris®  recei ve d Ma r keti n g A ut h orizati o n b y t he E M A f or patie nts wit h S yste mic J u ve nil e I di o pat hic 
Art hritis ( SJIA)  o n A u g ust 2 0 1 3 f or t he tre at me nt of  active Syste mic J u veni le I di o p at hic Art hritis 
( SJI A) i n p atie nts a ge d 2 years a n d ol der w h o h ave res p o n de d i n a de q u at e ly t o previ o us t her a py wi t h 
n o n-ster oi d al a nti- i nfl a m m at ory dr u gs (N S AI Ds) a n d syste m ic c ortic oster oi ds. Il aris®  c a n b e giv e n 
as m o n ot her a py or i n c o m bi n ati o n wi t h met h otrexate.  
S t ud y C A C Z 8 8 5 G 2 3 0 1 E 1 is a P h ase III st u d y desi g ne d t o assess l o n g-t er m safet y a n d effic ac y da ta 
f or patie nts wit h SJI A w h o eit her partici pate d i n t he C A C Z 8 8 5 G 2 3 0 5 a n d C A C Z 8 8 5 G 2 3 0 1 
reg istrati o n st u di es or were treat me nt- nai ve t o ca na ki n uma b . I n Fra nce, 4 8 patie nts were e nrol le d i n 
t he C A C Z 8 8 5 G 2 3 0 1 E 1  st u dy at f ou r ce nters ( Nec ker, Kremli n- B icêtr e, L y o n, a n d Stras b o ur g ). 
S t ud y C A C Z 8 8 5 G 2 3 0 1 E 1 is e n di n g o n N o v e m ber 2 0 1 4 a n d 3 sites ( Nec ker, Kre mli n- Bicê tre, 
a n d L y o n) still ha ve patie nts u n der treat me nt. 
N o vartis P har ma Fra nc e wis he d  t o set u p a l ocal prot oc ol t o all o w patie nts w h o be nefite d fr om 
cana ki n u ma b tr eat me nt recei ve d i n t he C A C Z 8 8 5 G 2 3 0 1 E 1 st u d y t o c o nti n ue 
t o recei ve 
cana ki n u ma b tr eat me nt u ntil c a n a ki n u m a b (Il aris ® ) is a vaila ble a n d r ei m b urse d o n t he Fre n ch 
ma r ket f or t h e SJI A i n dicati o n. 
 
 

N o v artis 
C lin ica l T rial P rot o co l v 0 5  
C o n fid e nt ial  
P ag e 1 4  
P rot o co l N o . C A C Z 8 8 5 G F R 0 1  
 
A me n d me nt 3 has bee n pr o p ose d t o o pe n t he recr uit me nt of st u d y C A C Z 8 8 5 G F R 0 1 t o patie nts w h o 
will c o m pl et e: 
 t he p hase III i nter nati o nal st u d y ( C A C Z 8 8 5 N 2 3 0 1) desi g ne d t o assess efficac y a n d 
t olera bilit y of c a n a ki n u m a b i n patie nts s ufferi n g fr o m 3 r are He re ditar y Perio d i c F e v ers 
( T R AP S,  HI D S or crF M F), 
 a n d t h e p h as e III i nt er n ati o n al st u d y C A C Z 8 8 5 G 2 3 0 6 d esi g n e d t o assess 2 differe nt 
ca na ki n u ma b ta per re gi me ns i n patie nts wit h cli nical re missi o n (i nacti ve disease f or at least 
2 4 c o nti n u o us wee ks) o n ca na ki n u ma b treat me nt i n SJI A. 
T h e o bj e cti v e of a me n d m e nt 3 is t o pr o vi de c o nti n u o us treat me nt t o t hese patie nts o nce t he y ha ve 
c o m plete d C A C Z 8 8 5 N 2 3 0 1 or C A C Z 8 8 5 G 2 3 0 6 u ntil t he me dicati o n is c o m merciall y a vaila ble i n 
Fra nce f or t hese ne w i n dicati o ns. 
 
 St u d y C A C Z 8 8 5 N 2 3 0 1 i n He re ditar y Perio d i c F e v ers ( T R AP S,  HI D S or crF M F)  
C A C Z 8 8 5 N 2 3 0 1 is a ra n d o mi z e d, d o u b l e-bl in d , pl ace bo c o n trol l e d stu d y 
wit h s u b se qu e nt 
ra n d o mize d with d ra wal/ d o si n g fre q ue nc y re d ucti o n a n d o pe n-l a bel lo n g t erm treat me nt e p oc hs. I n 
t his st u d y, a n i nitial d ose re gi me n of 1 5 0 m g s. c ( or 2 mg/ k g f or patie nts ≤ 4 0 k g) e ver y 4 we e ks 
( q 4 w) has bee n use d w hile all o wi n g f or u p -titr ati o n t o a ma xi mal d ose of c a na ki n u ma b 3 0 0 mg ( or 
4  m g/ k g f or patie nts wei g hi n g ≤4 0 k g)  q 4 w t o o pti mize t he re gi me n a n d t h us ac hie ve effic ac y i n 
d iffic ult cases.  
I n or der t o e valuat e if cli nical effic acy ca n be  mai nt ai ne d at a l o wer d osi n g freq u e nc y, ca na ki n u ma b 
1 5 0 mg ( or 2 mg/ k g f or patie nts ≤ 4 0 k g)  at a r e d uce d fr e q ue nc y ( q 8 w) h as b e e n e valua t e d d uri n g a 
r a n d omi z e d wit h dr aw a l e po c h ( Ep o c h 3). 
T he d ose re g i me n use d i n t he o pe n-l a bel lo n g t erm treat me nt e p ochs  ( mai nte n a nc e d os e; E p o c hs 4)  
is c o nsi dere d t o c o nstit ut e t he l o west clinica lly e ffic aci o us d ose t o mai nt ai n clini c a l effic ac y i n 
i n di vi d ual patie nts. A t ot al of 1 8 1  patie nts ( 4 6 T R A P S, 6 3 HI D S, 7 2 cr F M F) was ra n d o mize d i n 1 5 
c o u ntries w orl d wi de. T he pr ot o c ol i ncl u de d pa tie nts as yo u n g as 2 years ol d. 
I n or der t o s u p p ort reg ulat or y fili n g, t he a nal yses of t he pri mar y efficac y va ria ble a n d all seco n dar y 
efficac y a n d safet y varia bles u p t o W eek 1 6 we re perf or me d after all patie nts c o m plete d t he fi nal 
visit of t he ra n d o m ize d treat me nt e p oc h ( E p oc h 2)  of t he st u d y. 
E p oc h 2 res ults fr o m st u d y C A C Z 8 8 5 N 2 3 0 1 pr o vi de str o n g e vi d e nce of t he s up eri ority o f 
cana ki n u ma b o ver place b o. Ca na ki n u ma b has s h o w n a fa st o nset of  res p o nse an d  efficaci o us c o ntr ol 
of cli nical si g ns, s y m p t o ms a n d ser ol o gical ma nifestati o ns i n all 3 c o h orts of cr F M F, HID S  a n d 
T R A P S patie nts.  
As s h o w n i n ta ble 1 bel o w, t he pri mar y o bj ecti ve  was achie ve d f or a ll i n dicati o ns ( T R A P S, HI D S 
a n d cr F M F): cana ki n u ma b was s u peri or t o place b o i n t he pr o p orti o n of p atie nts w h o res ol ve d t heir 
i nd e x disea se flare at Da y 1 5 a n d ha d n o ne w flare o ver t he 1 6 w eeks of  treat me nt. 
Ca na ki n u ma b als o de m o nstrate d s u peri or efficac y c o m pare d t o place b o o n t he sec o n dar y e n d p oi nts 
of gl o bal assess me nt disease acti vit y ( P G A) < 2 a n d C R P ≤ 1 0 m g/ L f or all c o h orts. 
 
 

N o v artis 
C lin ica l T rial P rot o co l v 0 5  
C o n fid e nt ial  
P ag e 1 5  
P rot o co l N o . C A C Z 8 8 5 G F R 0 1  
 
T a ble 1. C o m p aris o n bet w ee n tre at me nt gr o u ps  f or p atie nts wh o  resp o n de d at wee k 1 6 b y 
c o h ort (I T T) 
 
A C Z 8 8 5 1 5 0 m g q 4 w 
Pl ace b o  
Tr e atme nt  
c o m p aris o n 
 
 
C o h o rt 
 
n /M  
(% ) 
 
9 5 %  CI  
 
n /M  
(% ) 
 
9 5 %  CI  
Ri sk  
d ifferen ce 
(9 5 %  
CI)  
O d d s 
R a ti o 
(9 5 %  
CI)  
O n e-
side d p -
v a lu e 
cr FM F  
1 9 /3 1  
(4 2 .1 9 , 7 8 .1 5 ) 
2 /3 2  
(0 .7 7 , 
2 0 .8 1 ) 
0 .5 5  
2 3 .7 5  
< 0 .0 0 0 1 *  
 
(6 1 .2 9 )  
(6 .2 5 )  
(0 .3 1 , 0 .7 3 ) 
(4 .3 8 , 2 2 7 .5 3 )  
HI D S  
1 3 /3 7  
(2 0 .2 1 , 5 2 .5 4 ) 
2 /3 5  
(0 .7 0 , 
1 9 .1 6 ) 
0 .2 9  
8 .9 4  
0 .0 0 2 0 *  
 
(3 5 .1 4 )  
(5 .7 1 )  
(0 .0 6 , 0 .5 0 ) 
(1 .7 2 , 8 6 .4 1 )  
T R A P S  
1 0 /2 2  
(2 4 .3 9 , 6 7 .7 9 ) 
2 /2 4  
(1 .0 3 , 
2 7 .0 0 ) 
0 .3 7  
9 .1 7  
0 .0 0 5 0 *  
 
(4 5 .4 5 )  
(8 .3 3 ) 
 
(0 .0 8 , 0 .6 1 ) 
(1 .5 1 , 9 4 .6 1 ) 
 
n = n u m ber of pati e n ts w h o resp o n d e d; M = n u m b er of p a tie n ts e v al u ate d f or res p o n s e; CI =c o n fi de n ce I nter val. 
* i n dic ates statisti cal si gnifi c an ce ( o n e-s i de d ) at t h e 0. 0 2 5 level b a s ed o n Fis h e r e xa ct test. 
T h ere were n o ne w or u ne x pecte d safet y fi n di n gs i n t he can a ki n u ma b-treate d patie nts t hr o u g h e p oc h 
2. Si milar t o w hat was o bs er ve d i n SJI A patie nts treat e d wit h can a ki n u ma b, t he m o st freq ue nt l y 
affecte d S O C i n cr F M F, HID S  a n d T R A P S patie nts was i nfecti o ns a n d i nfestati o ns, wit h t he m ost 
c o m m o n i nf ecti o ns bei n g t h ose of t h e u p per res pirat or y tract. 
As a res ult of t his p ositi ve i nteri m a nal ys is at t he e n d of E p oc h 2, a re gistrati o n d ossier was 
s u b mitte d t o t he E M A o n A pril 2 0 1 6. A mar keti n g a ut h orizati o n has bee n gra nte d i n E U i n Marc h 
2 0 1 7. 
 
T he first Fre nc h patie nts i ncl u de d C A C Z 8 8 5 N 2 3 0 1 will c o m plete t he st u d y fr o m N o ve m ber 2 0 1 6 . 
Acc or di n g t o a me n d me nt 3, patie nts w h o ha ve be neficiate d fr o m ca na ki n u ma b treat me nt will t he n 
bee n e nr olle d i n t he Fre nc h C A C Z 8 8 5 G F R 0 1 st u d y. 
 
 St u d y C A C Z 8 8 5 G 2 3 0 6 i n SJI A  
St u d y C A C Z 8 8 5 G 2 3 0 6 has bee n re q ueste d b y E M A a n d desi g ne d t o assess 2 differe nt ca na ki n u ma b 
ta per re gi me ns i n patie nts wit h SJI A wit h cli nical re missi o n o n ca na ki n u ma b treat me nt (i nacti ve disease 
f or at least 2 4 c o nti n u o us wee ks) wit h o ut c o nc o mita nt C S or M T X. Data fr o m t his st u d y will be use d t o 
hel p g ui de p h ysicia ns re gar di n g ca na ki n u ma b d ose re d ucti o n i n a p pr o priate SJI A patie nts. 
Eli gi ble patie nts were e ntere d St u d y Part I d uri n g w hic h all patie nts were treate d wit h ca na ki n u ma b 4 
m g/ k g e ver y 4 wee ks u ntil t he y q ualif y a n d e nter Part II of t he st u d y.  
Patie nts w h o bec o me eli gi ble f or ra n d o mizati o n e nter t he St u d y Part II a n d u n der g o ca na ki n u ma b 
ta peri n g (t o recei ve ca na ki n u ma b at eit her a re d uce d d ose or a pr ol o n ge d d ose i nter val). Part II is a 7 2-
wee k ra n d o mize d treat me nt / f oll o w- u p peri o d ( 4 8 wee ks of ca na ki n u ma b ta peri n g f oll o we d b y 2 4 
wee ks of f oll o w- u p w hile c o m pletel y off-treat me nt). 
Patie nts w h o d o n ot bec o me eli gi ble f or ra n d o mizati o n ma y re mai n i n St u d y Part I f or t he d urati o n of 
t he st u d y, a n d si nce patie nts w h o fail a n y of t he 3 ca na ki n u ma b ta peri n g ste ps d uri n g Part II ma y 
re mai n i n St u d y Part II f or t he d urati o n of t he st u d y, b ot h st u d y parts ha ve bee n assi g ne d a n esti mate d 
ma xi m u m d urati o n (f or a gi ve n patie nt) of 2 1 6 wee ks ).   
 
T he st u d y p o p ulati o n c o nsists of male a n d fe male patie nts a ge d ≥ 2 t o < 2 0 years i n t w o c o h orts: 
C o h ort 1 : Patie nts pre vi o usl y partici pati n g i n St u d y C A C Z 8 8 5 G 2 3 0 1 E 1 w h o at t he ti me of 
e val uati o n f or partici pati o n i n C A C Z 8 8 5 G 2 3 0 6 were treate d wit h ca na ki n u ma b 4 m g/ k g 
a n d ha d i nacti ve disease  
C o h ort 2: Patie nts, w h o at scree ni n g ha d acti ve SJI A a n d were ca na ki n u ma b treat me nt- naï ve.  
 

N o v artis 
C lin ica l T rial P rot o co l v 0 5  
C o n fid e nt ial  
P ag e 1 6  
P rot o co l N o . C A C Z 8 8 5 G F R 0 1  
 
A t ot al of 1 7 2 patie nts ha ve bee n e nr olle d ( 2 5 patie nts were e nr olle d i n 3 Fre nc h ce nters).  
 
T he o bjecti ve of C A C Z 8 8 5 G F R 0 1 st u d y is t o c ollect a d diti o nal safet y data (seri o us a n d n o n- seri o us 
a d verse e ve nts) a n d pr o vi de c o nti n u o us ca na ki n u ma b treat me nt f or patie nts c o m pleti n g st u dies 
C A C Z 8 8 5 G 2 3 0 1 E 1, C A C Z 8 8 5 N 2 3 0 1 or C A C Z 8 8 5 G 2 3 0 6 i n Fra nce pe n di n g rei m b urse me nt of 
ca na ki n u ma b (Ilaris ® ) i n t hese i n dicati o ns.  
 
1. 2        P ur p o s e 
 
T he p ur p ose of t his st u d y is t o pr o vi d e c o nti n u o us ca na ki n u ma b treat me nt t o patie nts i n Fra nce w h o 
c o m plete d t he f oll o wi n g st u dies: C A C Z 8 8 5 G 2 3 0 1 E 1, C A C Z 8 8 5 N 2 3 0 1 or C A C Z 8 8 5 G 2 3 0 6 u ntil 
ca na ki n u ma b (Il aris ® ) is c o m mer ciall y a vaila ble a n d r ei m b urse d i n Fra nce f or t h ese i n dicati o ns.  
 
T his l ocal e xte nsi o n st u d y 
will o nl y be pr o p os e d t o t he 4 Fre nc h ce nters i n v ol ve d i nt o 
C A C Z 8 8 5 G 2 3 0 1 E 1, C A C Z 8 8 5 N 2 3 0 1 or C A C Z 8 8 5 G 2 3 0 6 st u d y. 
 
2          St u d y o b j e cti ve s  
 
T he o bjecti ve  of t his pr ot oc ol is t o col lect a d diti o nal safety d ata (serio us  a n d n o n-seri o us a d verse 
e ve nts) a n d t o pr o vi de c o nti n u o us Il aris®  (ca n a ki n u ma b) treat me nt t o patie nts i n Fra n ce w h o 
c o m plete d C A C Z 8 8 5 G 2 3 0 1 E 1, C A C Z 8 8 5 N 2 3 0 1 or C A C Z 8 8 5 G 2 3 0 6 st u d y. 
 
3          I n ve st i gat io n al pl a n  
3. 1        St u d y d e si g n 
 
T his is a n o pe n-lab el (si n g le treat me nt ar m) e xte nsi o n peri o d f or patie nts i n Fra nce w h o h a ve 
c o m plete d t he i nter nati o nal st u dies: 
 
C A C Z 8 8 5 G 2 3 0 1 E 1  
 
or C A C Z 8 8 5 N 2 3 0 1  
 
or C A C Z 8 8 5 G 2 3 0 6. 
T he last visit of C A C Z 8 8 5 G 2 3 0 1 E 1, C A C Z 8 8 5 N 2 3 0 1 or C A C Z 8 8 5 G 2 3 0 6 st u dies wi ll be  t he first 
visit of t h is e xte nsi o n st u d y.  
Patie nts f oll o w u p: 
Patie nts pre vi o usl y i ncl u de d i n st u d y C A C Z 8 8 5 G 2 3 0 1 E 1 ( SJI A): 
T hese patie nts will c o nti n ue t he sa me  d osi n g regi me n use d at t he e n d of C A C Z 8 8 5 G 2 3 0 1 E 1 .  
Visits will ta ke place at ca na ki n u ma b d ose a d mi nistrati o n  dates, a p pr o xi matel y e ver y 4 weeks  
( or less fre q ue ntl y acc or di n g t o i n vesti gat ors j u d g me nt i.e. 6, 8 or 1 2 wee ks). T h e safet y of 
cana ki n u ma b will be e val uate d (a d verse e ve nts a n d seri o us a d verse e ve nts). Pa tie nts will be 
f oll o we d u p accor di n g t o S m P C (see a p p e n di x 1) wit h p ossi ble a da ptati o n base d o n i n vesti gat ors 
j u d g me nt relate d t o s pecific patie nt me dical c o nsi derati o n.  
Patie nts pre vi o usl y i ncl u d e d i n st u d y C A C Z 8 8 5 N 2 3 0 1 ( Peri o dic Fe ver s y n dr o mes i n dicati o ns: 
T R A P S, HI D S or cr F M F): 
T hese patie nts will c o nti n ue t he m ai nt e n a n c e d os e as deter mi ne d at t he e n d of t he o pe n-la bel 
peri o d/ e p oc h 4 (i. e t h e l o west c linica lly e ffic acio us d ose t o mai nt ai n clini c a l effic ac y i n 
i n di vi d ual pa tie nts wit h a g o o d t olera bilit y). Visits will ta ke place at sc he d ule d a d mi nistrati o n 

N o v artis 
C lin ica l T rial P rot o co l v 0 5  
C o n fid e nt ial  
P ag e 1 7  
P rot o co l N o . C A C Z 8 8 5 G F R 0 1  
 
d ates, a p pr o xi ma tel y e ver y 4, 8 or 1 2 weeks . T h e safet y of ca na ki n u ma b will be e val uate d 
(a d verse e ve nts a n d seri o us a d verse e ve nts c ollecti o n). Patie nts will t he n be f oll o we d u p 
acco r di n g t o S m PC wit h p ossi ble a da ptati o n base d o n i n vesti gat ors j u d g me nt relate d t o s pecific 
patie nt me dical c o nsi derati o n.  
Patie nts pre vi o usl y i ncl u de d i n st u d y C A C Z 8 8 5 G 2 3 0 6 ( SJI A i n dicati o n): 
T hese p atie nts wi ll c o nti nue  o n t heir d osi n g re gi me n c o nsi der e d  t o c o nstit ut e t he lo west clinica lly 
e ffic aci o us d ose t o mai nt ai n clini c a l effic ac y i n i n di vi d ual patie nts.  
Visi ts will ta ke place at ca na ki n u ma b d ose a d mi nistrati o ns, a p pr o xi mately e ver y 4, 8 or 1 2 wee ks 
acc or di n g t o t he i n di vi d ual dr u g re gi me n of t he e n d C A C Z 8 8 5 G 2 3 0 6 a n d i n vesti gat ors j u d g me nt . 
T he safet y of ca na ki n u ma b will be e val uate d (a d v ers e e ve nts a n d seri o us a d verse e ve nts 
c ollecti o n). Patie nts will be f oll o we d u p acc or di n g t o S m PC (see a p pe n di x 1) wit h p ossi ble 
a da ptati o n base d o n i n vesti gat ors j u d g me nt relate d t o s pecific patie nt me dical c o nsi derati o n.  
 
T he st u d y d urati o n will de pe n d o n t he da te of rei m b urse me nt of ca na ki n u ma b (Ilaris® ) i n Fra n ce f or 
t he ne w i n dicati o ns a n d will be e xte n de d u ntil t he me dicati o n is c o m merciall y a vaila ble f or eac h 
i n dicati o n. H o we ver, as t he c o m mercializati o n of  t he differe nt i n dicati o ns ma y be effecti ve at 
differe nt dates, t he patie nts will disc o nti n ue i n dicati o n b y i n dicati o n (see secti o n 5 ; e n d of treat me nt). 
 
3. 2        R ati o n al e of  st u d y d e si g n 
 
Gi ve n t he p ur p ose of t his e xte nsi o n st u d y, a n o pe n-la bel desi g n is a p pr o p riate. 
 
3 . 3 
R ati o n al e of  d o s e/r e gi m e n, r o ut e of  a d mi ni str ati o n an d  d ur ati o n of 
tr e at m e nt 
 
Patie nts wit h SJI A will be treate d wit h ca na ki n u ma b i n a n o pe n-la bel ma n ner a n d f oll o we d u p 
accor di n g t o t he a p pr o ve d E ur o pea n S m Pc (a p p e n di x 1). 
F or patie nts wit h Peri o dic Fe ver s y n dr o mes ( T R A P S, HI D S or cr F M F), t he d ose of use d i n t he 
e xte nsi o n st u d y will n ot e xcee d t he ma xi m u m d ose use d i n C A C Z 8 8 5 N 2 3 0 1 ( 3 0 0 m g/ 4 mg/ k g f or 
patie nts wei g h i n g ≤4 0 k g). T he patie nts will t he n be f oll o we d u p acc or di n g t he E ur o pea n S m Pc o nce 
a vaila ble after E M A a ut h orizati o n.  
 
3. 4        P ur p o s e a n d ti mi n g of  i nt eri m a n al y s e s / d e si g n a d a pt ati o n s 
 
N ot a p pli cable. 
 
3. 5        Ri s k s a n d  b e n efit s 
Ca na ki n u ma b offers a ne w t hera pe utic o pti o n f or patie nts wit h SJI A or Peri o dic Fe ver s y n dr o mes 
w h o d o n ot res p o n d t o sta n dar d t hera p y. Ca na ki n u ma b e na bles patie nts t o c o ntr ol t heir disease a n d 
re d uce t heir use of ster oi ds, a mai n ca use of i m paire d gr o wt h a n d si de effects i n SJI A or Peri o di c 
Fe ver s y n dr o mes c hil dre n. All t he patie nts i ncl u de d i n t his e xte nsi o n st u d y ha ve d e m o nstrate d 
cli nical res p o nse t o c a na ki n u ma b treat me nt f or at least 2 years i n st u d y C A C Z 8 8 5 G 2 3 0 1 E 1, 
C A C Z 8 8 5 G 2 3 0 6 or C A C 8 8 5 N 2 3 0 1. T he ris k t o patie nts i n t his trial will be 
mi ni mi ze d b y 
c o m plia n ce wit h t he eli gi bilit y criteria, cl ose cli nic al m o nit ori n g a n d a d here nce t o t he pr ot oc ol 
g ui deli nes f or d os e a d mi nistrati o n / re d ucti o n / i nter val pr ol o n gati o n / disc o nti n uati o n. 
4          P o p u lat i o n 
 
U p t o 4 1 patie nts ma y be i ncl u de d i n t he Fre nc h e xte nsi o n st u d y C A C Z 8 8 5 G F R 0 1 (i n 3 centers). 

N o v artis 
C lin ica l T rial P rot o co l v 0 5  
C o n fid e nt ial  
P ag e 1 8  
P rot o co l N o . C A C Z 8 8 5 G F R 0 1  
 
 T wel ve patie nts pre vi o usl y e nr olle d i nt o st u d y C A C Z 8 8 5 G 2 3 0 1 E 1  
 
 T we nt y ni ne p ote ntial a d diti o nal patie nts acc or di n g t o a me n d me nt 3: 
- 
u p t o 2 1  p atie nts pre vi o usl y e nr olle d i nt o C A C Z 8 8 5 G 2 3 0 6 st u d y (i n 3 ce nters) 
- 
u p t o 8 patie nts pre vi o usl y e nr olle d i nt o C A C Z 8 8 5 N 2 3 0 1 st u d y (i n 4 Fre nc h ce nters). 
4. 1        I n cl u si o n crit eri a 
 
Patie nts eli g i ble f or i ncl usi o n i n t his pr ot oc ol ha ve t o f ulfill all of t he fol l o wi n g criteria: 
Cr iteria ap p licable f or p atie nts wit h S yste mic J u ve nil I di o pat hic Art hritis ( SJI A) 
1.  Pa tients w h o ha ve  c o m plete d t he i nter nati o nal CA C Z 8 8 5 G 2 3 0 1 E 1 or C A C Z 8 8 5 G 2 3 0 6 st u dies 
wit h o ut a ny si g nifi cant  safety iss ue acc or di n g t o I n vesti gat or’s o pi ni o n.  
2.  Patie nts w h o ha ve c o m plete d t he i nter nati o nal C A C Z 8 8 5 G 2 3 0 6 st u d y a n d w h o s uccessf ull y 
wit h dre w ca na ki n u ma b treat me nt per pr ot oc ol b ut wit h a disease rela pse after t he e n d of st u d y 
visit will be all o we d t o partici pate i n C A C Z 8 8 5 G F R 0 1 st u d y ( w hate ver t he ti me of rela pse 
fr o m t he e n d of st u d y visit), if t he i n vesti gat or states t hat t here is a n i n dicati o n t o res u me 
ca na ki n u ma b. 
3.  Patie nts w h o ha ve partici pate d i n t he i nter nati o nal C A C Z 8 8 5 G 2 3 0 6 st u d y b ut c o ul d n ot be 
ra n d o mize d a n d t he n ha ve c o nti n ue d ca na ki n u ma b i n part I u ntil t he e n d of t he st u d y at a d ose 
of 4 m g/ k g e ver y 4 wee ks ma y be s witc he d t o C A C Z 8 8 5 G F R 0 1 st u d y if t he i n vesti gat or 
t hi n ks t hat, i n t he i nterest of t he patie nt, t here is a n i n dicati o n t o ta per off ca na ki n u ma b d ose 
after a pr ol o n ge d re missi o n 
Cr iteria ap p licable f or p atie nts wit h P eri o di c F e v er s y n dr o m es ( T R A P S, HI D S, cr F M F) 
1.  Patie nts w h o ha ve c o m plete d t he i nter nati o nal C A C Z 8 8 5 N 2 3 0 1 st u d y wit h o ut a n y si g nifica nt 
safet y iss ue acc or di n g t o I n vesti gat or’s o pi ni o n. 
Cr iteria a p plicable f or all patie nts 
1.  Pare nt's or le gal g uar dia n's writte n i nf or me d c o nse nt a n d c hil d's asse nt, if a p pr o priate, or 
patie nt's writte n i nf or me d c o nse nt f or patie nts ≥ 1 8 years of a ge m ust be o btai ne d bef ore a n y 
st u d y relate d acti vit y or assess me nt is perf or me d. 
 
4. 2        E x cl u si o n  crit eri a  
 
1.  Hist or y of r ecu rri n g i nf ecti o ns, or  u n derl yi n g c o n diti o ns w hic h ma y pre dis p ose t he m t o 
i nfecti o ns. Treat me nt wit h c a n a ki n u ma b s h o ul d n ot be c o nti n ue d i n patie nts wit h se vere 
i nfecti o ns re q uiri n g me dical i nter ve nti o n. 
2.  H y perse nsiti vit y t o t he acti ve s u bsta nce or t o a n y of t he e xci pie nts (see S m P C, secti o n 6. 1). 
3.  C o nc o mita nt use of sec o n d li ne a ge nts s uc h as disease- m o dif yi n g a n d/ or i m m u n os u p pressi ve 
dr u gs will n ot be all o we d wit h t he e xce pti o n of: 
 
Met h otr e x ate, a n d f olic/f oli nic 
aci d s u p pl e me ntati o n (acc or di ng t o sta n dar d 
me dical 
p ractice) 
 
N o n -ster oi dal ant i-i nfl a m mat or y dr u g (N S AI D)  
 
S yste mic c ortic oste r oi d treat me nt. 
4.  C o nc o mita nt use of a n ot her bi ol o gic a ge nt or a n y i n vesti gati o nal dr u g. 
5.  Pre g na nt or n ursi n g (lactati n g) fe male patie nts, w here pre g na nc y is defi ne d as t he state of a 
fe male after c o nce pti o n a n d u ntil t he ter mi nati o n of gestati o n, c o nfir me d b y a p ositi ve h C G 
la b orat or y test or a n uri nar y pre g na nc y test. 
6.  Fe male patie nts w h o are of c hil d- beari n g p ote ntial, defi ne d as all fe males p h ysi ol o gicall y 
ca pa ble of bec o mi n g pre g n a nt, u nless t he y are usi n g effecti ve met h o ds of c o ntrace pti o n d uri n g 
d osi n g of st u d y treat me nt. Effecti ve c o ntrace pti o n met h o ds i ncl u de: 
 
T otal a bsti ne nce ( w he n t his is i n li ne wit h t he preferred  a n d us ual lifest yle of t he 
s u bject). Peri o dic a bsti ne nce (e. g., cale n dar, o v ulati o n, s ym p t ot her mal, p ost- o v ulati o n 
met h o ds) a n d wit h dra wa l are n ot acce pta ble met h o ds of c o ntracept i o n 

N o v artis 
C lin ica l T rial P rot o co l v 0 5  
C o n fid e nt ial  
P ag e 1 9  
P rot o co l N o . C A C Z 8 8 5 G F R 0 1  
 
 
Fe male sterilizati o n ( ha ve  ha d s ur gic al bilateral o o p h orec t om y 
wit h or 
wit h o ut 
h yster ect om y) or t ub al li gati o n at least si x weeks be f ore t a ki n g st u d y treat me nt. I n case 
of o o p h orec t om y al o ne, o nl y w h e n t he re pr o d ucti ve  stat us of t he w o ma n has bee n 
c o nfir me d b y f oll o w u p h or m o ne le vel asse ssme nt 
 
Male sterilizati o n (a t least 6 m o nt hs pri or t o i ncl usi o n). F or fe male s u bj ects o n t he st u d y, 
t he vasect omize d male part ner s h o ul d be t he s ole pa rtn er f or t hat s u bject 
 
Bar rier met h o ds 
of c o ntrace pti o n: 
C o n d o m 
or 
Occl usi ve  cap ( di a p hra g m 
o r 
cer vical/ va ult caps) wit h s per mici dal f oa m/ gel/ fil m/crea m/ va gi nal s u p p osit or y 
 
Use of oral, i nj ecte d or i m p la nte d h or m o nal met h o ds of c o ntracept i o n or ot her f or ms of 
h or m o nal c o ntr acepti o n t hat ha ve c o m para ble efficac y (fail ure rate 
 
< 1 % ), f or e x a m ple h or m o ne va gi nal ri n g or tra ns d er mal h or m o ne c o ntrace pti o n 
 
P laceme nt of a n i n tra uteri ne de vice (I U D) or i ntra uteri ne s yste m (I U S) 
I n case of use of  oral c o ntracept i o n w o me n s h o ul d have  bee n sta ble o n t he same  pill f or a mi ni m u m 
of 3 m o nt hs be f ore t aki n g st u d y tr eat me nt. 
Relia ble c o ntra cepti o n s h o ul d be 
mai ntai ne d t hr o u g h o ut t he st u d y a n d u ntil 3 
m o nt hs after 
ca na ki n u ma b disc o nti n uati o n. 
5          Tr e at m e nt 
 
I nitial ca na ki n u ma b d ose: 
F or patie nts pre vi o usl y i ncl u de d i n st u d y C A C Z 8 8 5 G 2 3 0 1 E 1 ( SJI A) 
Patie nts 
will c o nti n ue t he sa me d ose as t heir last d ose a d mi nistere d i n t he st u d y 
C A C Z 8 8 5 G 2 3 0 1 E 1: ca na ki n u ma b 4 m g/ k g ( or 3 0 0 m g ma x) or 2 m g/ k g ( 1 5 0 m g ma x) e ver y 4 
wee ks. 
Ca na ki n u ma b d ose re d ucti o n fr o m 4 m g/ k g t o 2 m g/ k g e ver y 4 wee ks i n ster oi d-free patie nts wit h 
pr ol o n ge d str o n g res p o nse was per mitte d i n t he o n g oi n g e xte nsi o n st u d y C A C Z 8 8 5 G 2 3 0 1 E 1 at 
t he re q uest of t he treati n g p h ysicia n a n d wit h t he a gree me nt of N o vartis. 
Si milarl y, i n t his st u d y, t he ca na ki n u ma b d ose ma y be re d uce d fr o m 4 m g/ k g ( 3 0 0 m g ma x) t o 
2 m g/ k g ( 1 5 0 m g ma x) e ver y 4 wee ks a n d t he n i nterr u pte d after a pr ol o n ge d re missi o n acc or di n g 
t o t he i n vesti gat ors j u d g me nt.  
 
F or patie nts pre vi o usl y i ncl u de d i n st u d y C A C Z 8 8 5 N 2 3 0 1 ( Peri o dic Fe ver s y n dr o mes i n dicati o ns: 
T R A P S, HI D S or cr F M F)  
Patie nts will c o nti n ue o ne of t he f oll o wi n g re gi me ns as recei ve d at t he e n d of t he st u d y: 
- 
ca na ki n u ma b 1 5 0 m g ( or 2 m g/ k g  f or patie nts wei g h i n g ≤ 4 0 k g) q 4 w  
- 
ca na ki n u ma b 1 5 0 m g ( or 2 m g/ k g  f or patie nts wei g h i n g ≤ 4 0 k g) q 8 w  
- 
ca na ki n u ma b 3 0 0  m g ( or 4 m g/ k g  f or patie nts wei g h i n g ≤ 4 0 k g) q 4 w  
- 
ca na ki n u ma b 3 0 0  m g ( or 4 m g/ k g  f or patie nts wei g h i n g ≤ 4 0 k g) q 8 w  
I n c ase of r e-flar e (acc or di n g t o i n vesti gat ors j u d g me nt), patie nts will be all o we d t o i ncrease t he 
d ose as f oll o w: 
- 
If patie nts recei ve ca na ki n u ma b 1 5 0 m g q 8 w, t he d ose of ca na ki n u ma b will be i ncrease d t o 
1 5 0 m g q 4 w 
- 
If patie nts recei ve ca na ki n u ma b 1 5 0 m g q 4 w, t he d ose of ca na ki n u ma b will be i ncrease d t o 
3 0 0 m g q 4 w 
- 
If patie nts recei ve ca na ki n u ma b 3 0 0  m g q 8 w, t he d ose of ca na ki n u ma b will be i ncrease d t o 
3 0 0 m g q 4 w 
 
F or patie nts pre vi o usl y i ncl u de d i n st u d y C A C Z 8 8 5 G 2 3 0 6 ( SJI A): 

N o v artis 
C lin ica l T rial P rot o co l v 0 5  
C o n fid e nt ial  
P ag e 2 0  
P rot o co l N o . C A C Z 8 8 5 G F R 0 1  
 
T he patie nts will c o nti n ue t he sa me  d ose as t heir last d ose a d mi nistere d at t he e n d of t he ta peri n g 
peri o d st u d y C A C Z 8 8 5 G 2 3 0 6.  
T he n, patie nts will c o nti n ue o ne of t he f oll o wi n g re gi me ns: 
- 
Ca na ki n u ma b 4 m g/ k g q 4 w ks 
- 
Ca na ki n u ma b 2 m g/ k g q 4 w ks 
- 
Ca na ki n u ma b 1 m g/ k g q 4 w ks 
- 
Ca na ki n u ma b 4 m g/ k g q 8 w ks 
- 
Ca na ki n u ma b 4 m g/ k g q 1 2 w ks 
T he patie nts w h o ha ve wit h dra w n ca na ki n u ma b per pr ot oc ol ma y res u me ca na ki n u ma b after a rela pse 
at a starti n g d ose of 4 m g/ k g ( ma xi m u m 3 0 0 m g) e ver y 4 wee ks. 
 
D ose a dj ust me nts (f or all patie nts): 
Patie nts ma y r ecei ve a n u p-titr ati o n o r m a y r e s u m e c a n a ki n u m a b if t he y r e-flar e 
( ma xi m u m d ose of 3 0 0 m g ( or 4 mg/ k g s. c f or patie nts ≤4 0 k g  q 4 w). 
T he ca na ki n u ma b d ose i nter val (i.e. e ver y 6, 8 or 1 2 wee ks) ma y als o be pr ol o n ge d i n patie nts 
wit h a de q uate res p o nse acc or di n g t o i n vesti gat ors j u d g me nt.  
E ver y patie nt wit h dra w n fr o m C A C Z 8 8 5 G F R 0 1 st u d y d ue t o a re missi o n will be all o we d t o res u me 
ca na ki n u ma b i n case of rela pse a n d will be f oll o we d u p a gai n i n t he st u d y. 
 
Ca na ki n u ma b will be a d mi nistere d at t he st u d y ce nter.  
 
E n d of treat me nt 
F or patie nts treate d f or SJI A:  
I n vesti gat ors will be i nf or me d as s o o n as t his i n dicati o n is c o m merciall y a vaila ble i n or der t o 
or ga nize at t he ne xt pla n ne d visit t he dr o p o ut of t he patie nts. If n o visit is pla n ne d wit hi n 2 m o nt hs of 
n otificati o n rece pti o n, t he i n vesti gat ors will ha ve t o c o ntact t he patie nt i n or der t o or ga nize patie nt's 
st u d y ter mi nati o n. I n vesti gat ors 
will ha ve t he p ossi bilit y t o perf or m a last can a ki n u ma b 
a d mi nistrati o n d uri n g t he last visit of t he pr ot oc ol .  
 
F or patie nts treate d f or T R A P S, HI D S a n d cr F M F:  
I n vesti gat ors will be i nf or me d as s o o n as t his i n dicati o n is c o m merciall y a vaila ble i n or der t o 
or ga nize at t he ne xt pla n ne d visit t he dr o p o ut of t he patie nts. If n o visit is pla n ne d wit hi n 2 m o nt hs of 
n otificati o n rece pti o n, t he i n vesti gat ors will ha ve t o c o ntact t he patie nt i n or der t o or ga nize patie nt's 
st u d y ter mi nati o n. I n vesti gat ors 
will ha ve t he p ossi bilit y t o perf or m a last can a ki n u ma b 
a d mi nistrati o n d uri n g t he last visit of t he pr ot oc ol. 
 
5. 1        Pr ot o c ol r e q u e st e d tr e at m e nt  
 
5. 1. 1       I n v e sti g ati o n al tr e at m e nt 
 
N o vartis will s u p pl y o n e of t he f oll o wi n g o pe n-la bel i n ve sti gati o nal dr u gs as c o m mercial pack a ges 
or cli nical bat c hes w hic h are la belle d acc or di n g t o legislati o n i n Fra n ce relate d t o cli nical trial pr o d uct: 
 A C Z 8 8 5 1 5 0 m g: Acti ve  cana ki n u ma b i n i n di vi d ual 6 m L glass vials, eac h c o ntai ni n g 1 5 0 m g 
ca na ki n u ma b l y o p hilisate i n via l. 
Or  

N o v artis 
C lin ica l T rial P rot o co l v 0 5  
C o n fid e nt ial  
P ag e 2 1  
P rot o co l N o . C A C Z 8 8 5 G F R 0 1  
 
 A C Z 8 8 5 1 5 0 m g/ 1 m L : 1 m L of s ol uti o n f or i njecti o n i n a 2 m L vial (t y pe I glass) wit h a st o p per 
(la mi nate d c hl or o b ut yl r u b ber) a n d fli p- off ca p (al u mi ni u m). 
T he ma xi mal t otal si n gle d ose of  can a ki n u ma b all o we d is 3 0 0 m g, w hic h is a d mi nistere d as t w o 
s u bc uta ne o us 1 5 0 m g i njecti o ns o nce e ver y 4 weeks. 
5. 1. 2       A d diti o n al st u d y tr e at m e nt 
 
N o a d diti o nal tr eat me nt be y o n d i n vestigati o na l treat me nt is req u este d f or t his t rial. 
 
5. 2        Tr e at m e nt  arm s  
 
All patie nts will recei ve can a ki n u ma b as i n vesti gati o nal dr u g me di cati o n. 
 
5. 3        Tr e at m e nt  a s si g n m e nt, r an d o mi z ati o n 
 
All patie nts will be treate d wit h acti ve o pe n-l a bel cana ki n u ma b. 
 
5. 4        Tr e at m e nt  bli n di n g 
 
N ot a p plica bl e. 
 
5. 5        Tr e ati n g t h e p ati e nt  
 
5. 5. 1       P ati e nt n u m b eri n g 
 
E ach  patie nt is u ni q uel y i de ntifie d b y a S u bject N u m ber, assi g ne d at i ncl usi o n c o m p ose d b y t he site 
n u m ber a ssi g ne d b y N o vartis a n d a se q u ent ial n u m ber. I n t his st u d y, t h e patient  will keep t he sa me 
i de ntifier as i n st u d y C A C Z 8 8 5 G 2 3 0 1 E 1/ C A C Z 8 8 5 N 2 3 0 1/ C A C Z 8 8 5 G 2 3 0 6. 
5 . 5. 2       Di s p e n si n g t h e i nv e sti g ati o n al tr e at m e nt 
 
Eac h st u d y site will be s u p plie d b y N o vartis wit h i n vesti gati o nal treat me nt la belle d acc or di n g t o 
le gislati o n i n Fra nce relate d t o cli nical trial pr o d uct. 
5. 5. 3       H a n dli n g of st u d y tr e at m e nt 
5. 5. 3. 1    H a n dli n g of i n v e s ti g ati o n al tr e at m e nt 
 
I n vesti gati o nal treatme nt m u st be recei ve d b y a desig n ate d pers o n at t he st u d y site, ha n dle d a n d 
st ore d safel y a n d pr o perl y, a n d kept  i n a secu red l ocati o n t o w hic h o nl y t h e i n vesti gat or a n d 
d esig n ees have  access. U p o n recei pt, all i n vesti gati o nal treat me nt s h o ul d be st ore d acco r di n g t o t he 
i nstr ucti o ns s pecifie d o n t he la bels. Cl i nical s u p plies are t o be  dis pe nse d o nl y i n accor da nce wit h t he 
p r ot oc ol. 
Me di cati o n la bels will be i n t he l ocal la n g uage  a n d c o m pl y wit h t he le gal re q uire me nts. T he y will 
i ncl u de st ora ge c o ndi ti o ns f or t he i n vesti gati o nal treat me nt b ut n o i nf or mati o n a b o ut t he patie nt. 
T he i n vesti gat or m ust mai ntai n a n acc u rate recor d of t h e s hi p me nt a n d dis pe nsi n g of i n vesti gati o nal 
treat me nt i n a dr u g acc o u nta bilit y l og. M o nit ori n g of dr u g acc o u nta bilit y will be p erf or me d b y t he 
fiel d m o nit or d uri n g site visits a n d at the  c o m pleti o n of t he trial. 
At  t he c o ncl usio n  of t he st u d y, a n d as a p pr o priate d uri n g t he c o urs e of t he st u d y, t he i n vesti gat or 
will ret ur n a ll u n use d i n vesti gati o n al treat me nt, pack a gi n g, dr u g lab els, a n d a c o p y of t he 
c o m plete d dr u g acc o u nta bilit y l o g t o t he N o vartis m o nit or or  t o t he N o vartis ad dr ess pr o vi de d i n t he 
i n vesti gat or f ol der at eac h site. 

N o v artis 
C lin ica l T rial P rot o co l v 0 5  
C o n fid e nt ial  
P ag e 2 2  
P rot o co l N o . C A C Z 8 8 5 G F R 0 1  
 
5. 5. 3. 2          H a n dli n g of ot h er st u d y tr e at m e nt 
 
N ot a p pli cable. 
 
5. 5. 4       I n str u cti o n s f or pr e s cri bi n g a n d t a ki n g st u d y tr e at m e nt 
 
All d osa ge s prescri be d an d  dis pe nse d t o t he patie nt a n d all d ose c ha n ges d uri n g t h e st u d y m ust 
be rec or d e d o n t he D osa ge A d mi nistrati o n Rec or d C R F . 
 
5. 5. 5       P er mitt e d d o s e a dj u st m e nt s a n d i nt err u pti o n s of st u d y tr e at m e nt 
 
S t ud y dr u g d ose a dj ust me nts a n d/ or i nterr u pti o ns are per mitte d, accor di n g t o t he i n vesti gat or 
j u d g me nt. T hes e c ha n ges m ust be rec or de d o n t he D osa ge A d mi nistrati o n Rec ord C R F. 
 
5. 5. 6       R e s c u e m e di c ati o n 
 
N ot a p pli cable 
5. 5. 7       C o n c o mit a nt tr e at m e nt  
 
T he i n vesti gat or s h o ul d i nstr uct t he p atie nt  t o n otif y t he st u d y site a b o ut a ny n e w me di cati o ns he/s he 
ta kes after t he start of t he st u d y dr u g.  
5 . 5. 8       Pr o hi bit e d Tr e at me nt  
 
T he e x p ressi o n of he patic C Y P 4 5 0 e nz y mes may b e s u p presse d b y t he c yt o ki nes t hat sti m u late 
c hr o nic i nfla m mati o n, s uc h as I L- 1 b eta. T h us, C Y P 4 5 0 e x pressio n  ma y be re verse d w he n p ote nt 
c yt o ki ne i n hi bi t or y t hera p y, s uc h as cana ki n u ma b, is i ntr o d u ced.  T his is cli nicall y relev ant  f or 
C Y P 4 5 0 s u bstrates wit h a narr o w t hera pe ut ic i n de x w h ere t he d ose is i n di vi d ually a dj uste d. I n 
p atie nts bei n g tr eate d wit h t his t y pe of  me dici nal pr o d uct w hile o n cana ki n u ma b, t hera pe uti c 
m o nit ori n g of t h e effect or of t he active  s u bsta nce c o nce ntrati o n s h o ul d be perf or me d an d  t he 
i n di vi d ual d ose of t he me dici nal pr o d uct a dj uste d as necessar y. 
Use of ca na ki n u ma b wit h T N F i n hi bi t ors is n ot reco m me n de d be cause t his may i ncrease t he ris k of 
seri o us i nfecti o ns (a n i ncrease d i nci de nce of seri o us i nfecti o ns has bee n ass ociate d 
wit h 
a d mi nistrati o n of a n ot her I L- 1 bl oc ker i n c o m bi nati o n wit h T N F i n hi bi t ors) 
N o  data are a vaila ble o n eit her t he effects of  live  vacci nati o n or  t he sec o n dar y tra ns missi o n of 
i nfectio n  b y live  vacci nes i n patie nts recei vi n g ca na ki n u ma b. T h eref ore, live  vacci nes s h o ul d n ot be 
gi ve n c o nc urre nt l y wit h ca na ki n u ma b, b ut pri or t o i nitiati n g Ilaris®  t herap y. 
5. 5. 9       Di s c o nti n u ati o n of st u d y tr e at m e nt a n d pr e m at ur e p ati e nt  with dr a w al  
 
Patie nts ma y v ol u nta ril y wit h draw fr o m t he st u d y f or a n y reas o n at a n y ti me. St ud y treat me nt m ust 
be disc o nti n ue d u n der t he f oll o wi n g cir c u msta n ces: 
 T he a vaila bi lit y of re pai d pr o d uct i n Fra nce f or t he patie nt’s disease, 
 If, o n b ala nce t he i n vesti gat or belie ves t hat c o ntin u ati o n w o ul d be detri me nt al t o t he 
p atie nt’s well- b e i ng, 
 U nsati sfact or y t hera pe utic effect base d o n i n vesti gat or j u d g me nt, 
 Use of pr o hi bite d treat me nt / Pr ot oc ol vi olati o n, 
 O nset of mali g n a nc y, 
 O ccurre nce of  a n u nc o ntr olle d li fe-t hreate ni n g i nfectio n , 
 Pr e gn a nc y, 
 Ot he r A d verse E v e nt nee di n g st u d y disc o nti n uati o n, 
 L ost t o f oll o w- u p, 
 A d mi nistrati ve reas o ns, 

N o v artis 
C lin ica l T rial P rot o co l v 0 5  
C o n fid e nt ial  
P ag e 2 3  
P rot o co l N o . C A C Z 8 8 5 G F R 0 1  
 
 D eat h. 
If pre mat ure wit h dra wal occurs f or a n y reas o n, t he i n vesti gat or m ust ma ke  e very eff ort t o c o m ple te 
E n d of st u d y visi t i n t he C R F  a n d t o deter mi ne t he prima r y reas o n f or a patie nt’s premat ure 
wit h dra wal fr o m t he st u d y a n d recor d t his i nf or mati o n. 
5. 5. 1 0     E m er g e n c y br e a ki n g of tr e at m e nt  a s si g n m e nt 
 
N ot a p pli cable 
5. 5. 1 1     E arl y st u d y t er mi n ati o n 
T he st u d y ca n be  ter mi nate d at a n y time  f or a ny reas o n b y N o vartis. S h o ul d t his be necessar y, t he 
p atient  s h o ul d be see n as s o o n as p ossi ble a n d treate d f or a premat urel y wit h dr a w n  patie nt. T he 
i n vesti gat or may be i nf or me d of a d diti o nal p r oced u res t o be f oll o we d i n or der t o e ns ure t hat 
a de q ua te c o nsi derati o n is gi ve n t o t he pr otecti o n of t he patie nt’s i nterests. 
 
6          Vi sit s c h e d u l e a n d a s s e s s me n t s 
 
Visits will ta ke place at t he patie nt’s sc he d ule d dr u g  a d mi nistrati o n date (a p pr o xi matel y e ver y 4 
w eeks  or less fre q ue ntl y acc or di n g t o i n vesti gat ors j u d g me nt i.e. 6, 8 or 1 2 wee ks ). 
If n o a d mi nistrati o n is perf or me d wit hi n t he 1 2 wee ks of pre vi o us i njecti o n, a c o ntr ol visit will be 
perf or me d at Wee k 1 3 +/- 7 da y s after t he last a d mi nistrati o n i n or der t o e val uate safet y a n d nee d f or 
t he patie nt t o c o nti n ue t he treat me nt a n d t he st u d y. 
T a ble : sc he d ule d visits a n d e val u ati o ns  
 
 
Visits  
I ncl usi o n(1 ) Visits f or c a n a ki n u m a b 
a d mi nistr ati o n (4 )  
E n d  o f t he 
st ud y vis it (2 ) 
 
 
 
 
Visit w in d o w  ( d a ys) 
+/ - 7  
+/ - 7  
+/ - 7  
In cl usio n/ e x cl usio n criteria 
X  
 
 
W ritte n i nf orme d co nse n t 
X  
 
 
D em o gr ap hic d ata 
X  
 
 
T reatm ent a d mi n istratio n  
X  
X  
X  
C o n co m ita nt treatm ent  
X (3 ) 
X  
X  
A d v erse ev ents  
 
X  
X  
E n d of  t he st ud y  
 
 
X  
 
 
1)   T he date of last visit of C A C Z 8 8 5 G 2 3 0 1 E 1/ C A C Z 8 8 5 N 2 3 0 1/ C A C Z 8 8 5 G 2 3 0 6 st u d y will be t he f irst visit 
of t h is e xtensi o n st u d y. 
2)   T he e n d of st u d y is defi ne d  as pr e mat ure ter mi nati o n or e n d of t he st u d y acc or di n g t o pr ot oc ol: i n t he 
m o nt h f o llo wi n g t he a vaila bilit y of re pai d pr o d u ct i n Fr anc e. 
3)   C or ticos ter oi ds a n d met h otre xate o nl y. 
4)    Visits will ta ke place at sc he d ule d a d mi nistrati o n date e ver y 4, 6, 8 or 1 2 wee ks (secti o n 5). D ose i nter val 
ma y be pr ol o n ge d d uri n g t he st u d y (i.e. visits e ver y 6 , 8 or 1 2 wee ks or l o n ger i n case of a de q uate res p o nse at 
t he discreti o n of t he i n vesti gat or (secti o n 5). If n o a d mi nistrati o n is perf or me d wit hi n t he 1 2 wee ks of 
pre vi o us i nj ecti o n, a c o ntr ol visit will be perf or me d at W ee k 1 3 +/- 7 da ys after t he l ast a d mi nistrati o n i n 
or der t o e val uate safet y a n d ne e d f or t he patie nt t o c o nti n ue t he treat me nt a n d t he st u d y. 
 

N o v artis 
C lin ica l T rial P rot o co l v 0 5  
C o n fid e nt ial  
P ag e 2 4  
P rot o co l N o . C A C Z 8 8 5 G F R 0 1  
 
6. 1 
P ati e nt d e m o gr a p hi c s/ ot h er b a s eli n e c h ar a ct eri sti c s 
 
De m o gra p h y 
i nf or mati o n 
a n d 
ot her 
baseli ne 
c har acteristics 
are 
t h ose 
col lecte d 
i n 
C A C Z 8 8 5 G 2 3 0 1 E 1 / C A C Z 8 8 5 N 2 3 0 1 / C A C Z 8 8 5 G 2 3 0 6 st u d y. 
6. 2        St u d y tr e at m e nt  di s p e n s ati o n 
 
Basic st u d y treat me nt dis pe nsati o n  data will be col lecte d ( date of i nj ecti o n a n d t otal v ol u me 
i njecte d). 
6. 3        Effi c a c y 
 
N o efficac y d ata a re col lecte d i n t his st u d y. 
6. 4        S af et y 
 
Safet y assess me nts 
will c o nsist of  rec or di n g a n d 
m o nit ori n g of 
A d vers e E v e nts ( AE)  a n d 
Seri o us A d verse E ve nts ( SA E). 
 
7          S af et y mo n it orin g 
 
7. 1        A d v er s e e v e nt s 
 
A n  a d vers e e ve nt ( A E) is a n y u nt o war d me dic al occ urre nce (i.e., a n y u nfa v o ra ble a n d u ni nte n de d 
sig n [i ncl u di n g a b n or mal la b o rat ory fi n di n gs], s ym p to m  or disease) i n a s u bject or cli nical 
i n vesti gati o n s u bject af ter pr ovi di n g writte n i nf or me d c o nse nt f or partici pati o n i n t he st u d y. 
T heref o re, a n A E ma y or ma y n ot be t e m p orall y or causall y ass oci ate d wit h t he use of  a me dici nal 
(i n vesti gati o nal) pr o d uct. 
T he occ urre nce of  a d vers e e ve nts s h o ul d b e s ou g ht b y n o n- dir ective  q uesti o ni n g of t he patie nt at 
eac h visit d uri n g t he st u d y. A d verse e ve nts als o ma y b e detecte d w h e n t he y are v ol u nteere d b y t he 
p atient  d uri n g or bet ween visi ts or t hr o u g h p h y sical e xa mi nati o n, la b orat or y t est, or ot her 
assess me nts. 
A b n or mal la b o rat or y val ues or test res ults c o nstitute a d verse e ve nts o nl y if t he y f ulfill at least o ne 
of t he f ol l o wi n g criteria: 
 t he y i n d uce cli nical si g ns or s y m pt o ms, 
 t he y are c o nsi dere d cli nicall y si g nifica nt, 
 t he y re q uire t hera p y. 
 
A d verse e ve nts s h o ul d be rec o r de d i n t he A d vers e E v e nts C R F  u n der t he sig ns, s y m p t o ms or 
dia g n osis ass ociate d wit h t he m, a cco m pa nie d b y t he f oll o wi n g i nf o r mati o n: 
 t he se verit y gra de 
- mil d: us uall y tra nsie nt i n nat ure a n d ge nerall y n ot i nterferi n g wit h n or mal acti vities 
- m o derate: s ufficie ntl y disc o mf orti n g t o i nterfere wit h n or mal acti vities 
- se vere: pre ve nts n or mal acti vities 
 its relati o ns hi p t o t he st u d y me dicati o n 
 st u d y treat me nt ( n o/ yes), or 
 i n vesti gati o nal treat me nt ( n o/ yes), or 
 t he ot her st u d y treat me nt ( n o n-i n vesti gati o nal) ( n o/ yes), or 
 b ot h or i n disti n g uis ha ble, 
 its d urati o n (start a n d e n d dates) or if t he e ve nt is o n g oi n g a n o utc o me of n ot rec o ver e d/ n ot 
res ol ve d s h o ul d be re p orte d 

N o v artis 
C lin ica l T rial P rot o co l v 0 5  
C o n fid e nt ial  
P ag e 2 5  
P rot o co l N o . C A C Z 8 8 5 G F R 0 1  
 
 w het her it c o nstit utes a seri o us a d verse e ve nt ( S A E - See secti o n 7. 2 f or defi niti o n) acti o n 
ta ke n re gar di n g ca na ki n u ma b treat me nt. 
All a d verse e v e nts s h o ul d be treate d a p pr o priatel y. Treat me nt ma y i n cl u de o ne or m ore of t he 
f oll o wi n g: 
 n o acti o n ta ke n (i.e. f urt her o bser vati o n o nl y) 
 st u d y treat me nt d osa ge a dj uste d/te m p oraril y i nterr u pte d 
 st u d y treat me nt per ma ne ntl y disc o nti n ue d d ue t o t his a d verse e ve nt 
 c o nc o mita nt me dicati o n gi ve n 
 n o n- dr u g t hera p y gi ve n 
 patie nt h os pitalize d/ patie nt’s h os pitalizati o n pr ol o n ge d 
 its 
o utc o me ( n ot reco v ere d/ n ot 
res ol ve d; reco v ere d /res ol ve d; r ec o ve rin g/res ol vi n g, 
rec o vered/ r es ol ve d wit h se q uelae; fatal; or u n k n o w n) 
O n ce a n a d verse e ve nt  is detecte d, it s h o ul d be f oll o we d u ntil its res ol uti o n or  u ntil it is 
j u d ge d t o be per ma n e nt, a n d assess me nt s h o ul d b e ma de at eac h visit ( or m ore fre q u e ntl y, if 
n ecessar y) of  a ny c ha n ges i n se verit y, t he s us pecte d relati o ns hi p t o t he st u d y treat me nt, t he 
i nter ve nti o ns re q uire d t o treat it, a n d t he o utc o me. 
I nf or mati o n a b o ut c o m mo n  si de effects alrea d y k n o w n a b o ut t he i n vesti gati o nal dr u g can  be f o u n d 
i n t he S m P C or will be c o m m u nicate d bet ween S m P C u p dates i n t he f or m of I n ve sti gat or 
N otifi cati o ns. T his i nf or mati o n will be i ncl u de d i n t he patient  i nf or me d c o nse nt a n d s h o ul d be 
disc usse d wit h t he patie nt d uri n g t h e st u d y as nee de d. 
T he i n vesti gat or s h o ul d als o i nst r uct each  patie nt t o re p ort a n y n e w a d verse e ve nt ( be y o n d t he 
p r ot oc ol o bser vati o n peri o d) t hat t he patie nt, or t he patie nt’s pers o nal p h ysicia n, belie ves mi ght  
reas on a bl y be relate d t o st u d y treat me nt. 
T his i nf or mati o n s ho ul d be rec o r de d i n t he 
i n vesti gat or’s s o urce d oc u me nts. H o we ver, if t he A E meets t he criteria of a n S A E, it m u st be 
re p orte d t o N o vartis. 
 
7. 2        S eri o u s a d v er s e e v e nt ( S A E) 
7. 2. 1 D efi niti o n of a S A E 
 
A S A E  is defi ne d as an y  a d verse e vent  (ap p eara nce of  ( or w orse ni n g of a n y p re-e xisti ng ) 
u n desira ble si g n (s), s ym p t o m(s) or me dical c o n diti o ns(s) w hic h mee ts a n y o ne of t he f oll o wi n g 
criteria: 
 is fatal or life-t hreate ni n g 
 res ults i n persiste nt or si g nifica nt disa bilit y/i nca pacit y 
 c o nstit utes a c o n ge nital a n o mal y/ birt h defect 
 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, u nless 
h os pitalizati o n is f or: 
 r o uti ne treat me nt or 
m o nit ori n g of t he st u die d i n dicati o n, n ot ass ociate d 
wit h a n y 
deteri orati o n i n c o n diti o n (s pecif y w hat t his i ncl u des) 
 electi ve or pre- pla n ne d treat me nt f or a pre-e xisti n g c o n diti o n t hat is u nrelate d t o t he 
i n dicati o n u n der st u d y a n d has n ot w orse ne d si nce si g ni n g t he i nf or me d c o nse nt 
 treat me nt o n a n e mer ge nc y o ut patie nt basis f or a n e ve nt n ot f ulfilli n g a n y of t he defi niti o ns 
of a S A E gi ve n a b o ve a n d n ot res ulti n g i n h os pital a d missi o n 
 s ocial reas o ns a n d res pite care i n t he a bse nce of a n y deteri orati o n i n t he patie nt’s 
 ge neral c o n diti o n 
 is me dicall y si g nifica nt, i.e. defi ne d as a n e ve nt t hat je o par dizes t he patie nt or ma y re q uire 
me dical or s ur gical i nter ve nti o n. 
 

N o v artis 
C lin ica l T rial P rot o co l v 0 5  
C o n fid e nt ial  
P ag e 2 6  
P rot o co l N o . C A C Z 8 8 5 G F R 0 1  
 
Life-t hreate ni n g i n t he c o nte xt of a S A E refers t o a reacti o n i n w hic h t he patie nt was at ris k of d eat h 
at t he ti me of t he reacti o n; it d oes n ot refer t o a reacti o n t hat h y p ot heticall y mi g ht ha ve cause d d eat h 
if m ore se vere (s ee I C H- E 2 D G ui deli ne a vaila ble at: 
htt p:// w w w.ic h. or g/file a d mi n/ P u blic _ We b _ Site/I C H _ Pr o d uc ts/ G ui deli nes/ Efficac y/ E 2 D/ St e p4/ E 2 D _
G ui deli ne. p df ). 
All 
mali g na nt ne o plas ms 
will 
be  assesse d as seri o us u n der “ me di call y sig nifi cant ” if ot her 
seri o us ness criteria are n ot met. 
A n y s us pect e d tra ns mi ssio n  via a me dici nal pr o d uct of a n i nfecti o us a gent  is als o c o nsi dere d a 
seri o us a d vers e reacti o n. 
Me di cal a n d scie ntific j u d g me nt s h o ul d be e xercise d i n deci di n g w h et her ot her sit uati o ns s h o ul d be 
c o nsi dere d seri o us re acti o ns, s uc h as i m p ort ant  me dical e ve nts t hat mi g ht n ot be i m me diatel y life 
t hreat e ni n g or res ult i n deat h or h os pitalizati o n b ut mi g ht j e o par dize t he patie nt or  mi g ht re q uire 
i nter ve nti o n t o preve nt o ne of t he ot her o utc o mes liste d a b o ve. E xa m p les of s uc h e ve nts are i nte nsi ve 
treat me nt i n a n eme r ge nc y r o o m or at h o me f or aller gic br o nc h os pas m, bl o o d d ys crasias or 
c o n v ulsi o ns t hat d o n ot res ult i n h os pitalizati o n or de vel o p me nt of de pe n de nc y or a b use (see I C H-
E 2 D G ui deli ne  a vaila bl e at: 
htt p:// w w w.ic h. or g/file a d mi n/ P u blic _ We b _ Site/I C H _ Pr o d uc ts/ G ui deli nes/ Efficac y/ E 2 D/ Ste p 4/ E 2 D _
G ui deli ne. p df ). 
 
7. 2. 2 S eri o u s a d v er s e e v e nt  r e p orti n g 
 
T o  e ns ure patient  safet y, e ver y S A E, regar dle ss of causalit y, o ccu rri n g after t he patie nt  has 
p r o vi de d i nf or me d c o nse nt a n d u ntil 3 0 da ys [ after t he last st u d y visit/ f oll o wi n g t he last 
a d mi nistrati o n of  st u dy treat me nt if t here are p ost-treat me nt f oll o w- u p visits wit h n o  re q uired 
p r oced ure s] m ust be re p orte d t o N o vartis wit hi n 2 4 h o urs of lear ni n g of its occurre nce. A n y S A Es 
e x perie nce d a fter t he 3 0 da ys peri o d s h o ul d o nl y b e re p orte d t o N o vartis if t he i nv esti gat or s us pects 
a cau sal relati o ns hi p t o st u d y treat me nt. 
R ecurre nt  e pis o des, c om p licati o ns, or pr o gressi o n of t he i nitial S A E m ust be re p orte d as f oll o w- u p 
t o t he ori gi nal e pis o de, regar dle ss of w h e n t he e ve nt occur s. T his re p ort m ust be s u b mitte d 
wit hi n 2 4 h o u rs of t he i n vesti gat or recei vi n g t h e f oll o w- u p i nf or mati o n. A n  S A E t hat is c o nsi dere d 
c o m pletel y u nrelate d t o a previ o usl y re p orte d o n e s h o ul d be re p orte d se parat el y as a ne w e ve nt. 
I nf or mati o n a b o ut all S A Es (eit her i niti al or f oll o w u p i nf or m ati o n) is c ollecte d a n d rec or de d o n t he 
p a per Seri o us A d verse E ve nt Re p ort F or m.  T h e i n vesti gat or m ust assess t h e relati o ns hi p t o t he 
st u dy tre at me nt c o m plete t he S A E Re p ort F or m i n E n glis h, a n d se n d t he c o m plete d, sig ne d f o r m 
b y fa x wit hi n 2 4 h o urs a fter a ware ness of  t he SA E  t o t he l ocal N o vartis Dr u g Safet y a n d 
E pi de mi ol o g y De p art me nt. T he tele p h o ne a n d fa x n u m ber of t he c o ntact pers o ns i n t he l ocal 
d e part me nt of Dr u g Safet y a n d E pi de mi ol o g y, s pecific t o t he site, are liste d i n t he i n vesti gat or f ol der 
p r o vi de d t o eac h site. T he ori gi nal c o p y of t he SA E  Re p ort F or m a n d t he fa x c o nfir mati o n s heet 
m ust be ke pt wit h t he case re p ort f or m d oc u me ntati o n at t he st u d y site. Fol l o w- u p i nf or mati o n 
s h o uld be pr o vi de d usi n g a ne w pa per S A E  Re p ort F or m stati n g t h a t t his is a f oll o w- u p t o a 
p revi o usl y re p orte d S A E  
F oll o w- u p i nf o r matio n  pr o vi de d s h o ul d descri be w h et her t h e e ve nt has res ol ve d or c o nti n ues, if a n d 
h o w  it was treate d w h et her t he patie nt c o nti n ue d or  wit h dre w fr o m st u d y partici pati o n. Each re-
o ccur ren ce, c o m plicati o n, or pr o gressio n  of t he ori gi nal e vent  s h o ul d be re p orte d as a f oll o w- u p t o 
t hat e ve nt r e gar dless of w he n it occur s. 
If t he SA E  is n ot previ o usl y d oc u me nte d i n t he S m P C (see a p pe n di x 1) ( ne w occur ren ce) a n d is 
t h o u g ht t o be relate d t o t he st u d y treat me nt a Dr u g S afet y a n d E pi de mi ol o gy D e part me nt ass ocia te 
ma y ur ge ntl y re q uire f urt her i nf or mati o n fr o m t he i n vesti gat or f or  Healt h A ut h orit y re p orti n g. 
N o va rtis ma y nee d t o issue  a n I n vesti gat or N otificatio n  (IN)  t o i nf or m all i n vesti gat ors i n v ol ve d i n 

N o v artis 
C lin ica l T rial P rot o co l v 0 5  
C o n fid e nt ial  
P ag e 2 7  
P rot o co l N o . C A C Z 8 8 5 G F R 0 1  
 
a n y st u d y wit h t he sa me  i n vesti gati o nal treat me nt t hat t his SA E  has been re p o rte d. S us pecte d 
U n e x pecte d Seri o us A d verse Reacti o ns ( S U S A Rs) will be col lecte d a n d re p orte d t o t he c o m pet ent  
a ut h orities a n d  rele va nt et hics c o m mittees i n acc or da nce wit h Dir ective  2 0 0 1/ 2 0/ E C or as per 
n ati o nal reg ulat or y req uire me nts. 
 
7. 3        Pr e g n a n c y r e p orti n g 
 
T o  e ns ure patient  safet y, eac h pre g n a nc y occ urri n g w hile t he patient  is o n st u d y treat me nt m ust 
be re p orte d t o N o vartis wit hi n 2 4  h o urs of lear ni n g of its occurre n ce. T he p reg na n c y s h o ul d be  
f oll o we d u p t o deter mi ne o utc o me, i ncl u di n g s p o nta ne o us or v o lu ntar y ter mi nati o n, details of t he 
birt h, a n d t he p rese n ce or  a bse nce of a n y birt h defects, c o n ge nital a b n or malities, or mater nal a n d/ or 
ne w b or n c o m pl icati o ns. 
Pr e gn a nc y s h o ul d be rec or de d o n a Cl i nical Trial Pre gn a nc y F o r m a n d re p orte d b y t he i n vesti gat or 
t o t he l ocal N o vartis Dr u g Safet y a n d E pi de mi ol o g y De p art me n t. Preg na nc y f oll o w- u p s h o ul d be 
rec or de d o n t he sa me f o r m a n d s h o ul d i n cl u de a n assess me nt of t he p ossi ble relati o ns hi p t o t he st u d y 
treat me nt. 
A n y S A E  e x perie nced d uri n g p reg na n c y m ust be re p orte d o n t he S A E Re p ort F or m.  
 
8          D at a r e vi e w a nd d at a b a s e m a n a g e m e nt 
 
8. 1        Sit e m o nit ori n g 
 
Bef o re st u d y i niti ati o n, at a site i nitiati o n visit or  at a n i nv esti gat or’s me eti n g, a N o vartis 
re prese ntati ve will revi e w t he pr ot oc ol a n d C R Fs wit h t he i n vesti gat ors a n d t heir staf f. 
T he i n vesti gat or m ust gi ve  t he m o nit or access t o all rele va nt s o urce d o c u me nts t o c o nfir m t heir 
c o nsiste nc y wit h t he C R F  e ntries. N o vartis m o nit ori n g sta n dar ds re q uire f ull verificati o n f or t he 
p rese nce of  i nf or me d c o nse nt, ad h ere nce t o t he i ncl usi o n/ex cl usi o n criteria, d oc u me ntati o n of 
S A Es, a n d of  data t hat 
will be use d f or all pri mar y varia bles. 
A d diti o n al c hecks  of t h e 
c o nsiste n c y of t he s o urce d a ta wit h t he C R Fs are perf or me d a ccor di n g t o t he st u d y-s pecific 
m o nit ori n g pla n. N o  i nf or mati o n i n s o urce d oc u me nts a b out  t he i de ntit y of t he patie nts will be  
discl ose d. 
8. 2        D at a c o ll e cti o n 
 
De sig n ate d i n vesti gat or staff m ust e nter t he i nf or mati o n re q uire d b y t h e pr ot oc ol o nt o t h e N o va rtis 
C R Fs t hat a re pri nte d o n 3  - p art, n o n-car b o n-re q uire d p a per. Fiel d m o nit ors will re vie w t he C R Fs f or 
c o m p lete ness an d  acc urac y a n d i nstr uct site pers o n nel t o 
ma ke a n y re q uire d c orrecti o ns or  
a d diti o ns. T he C R Fs pa ges will be c ol lecte d b y fiel d m o nit ors after m o nit ori n g vali dati o n, wit h 
o ne c o p y b ei n g retai ne d at t he i n vesti gati o nal site. O n ce t h e C R Fs pa ges c oll ecte d, t he ori gi nal c o p y 
w ill be  placed i n t he st u d y Trial Mast er file, a n d t he n o n- car b o n-re q uire d c o py will be  f or war de d t o 
t h e C R O  i n c h ar ge of  Dat a Ma na ge me nt f or pr o cessi n g. 
8. 3        D at a b a s e m a n a g e m e nt a n d q u alit y c o ntr ol 
 
Da ta fr o m t he C R Fs will be  e ntered i nt o t he st u d y datab ase b y C R O staff, usi n g d o u ble data e ntr y 
a n d f oll o wi n g t he ir o w n i nter nal sta n d ar d o perati n g pr o ced ures (t hat ha ve  bee n re vie we d an d 
a p pr o ve d b y N o va rtis). 
S u bse q ue nt l y, t he e ntered da ta will be s yste maticall y c hec ke d b y Data Ma na ge me nt staff, usi n g 
err or messa ges pri nte d fr o m  vali datio n  pr o grams  an d  data bas e listi n gs. Ot her err ors or o missi o ns 
will be e nte red  o n Data Q u er y F or ms, w hi c h will be ret ur ne d  t o t he i n vesti gati o nal site f or 
res ol uti o n. T he sig ne d ori gi nal a n d res ol ve d Da ta Q u er y F or ms  will be kept  wit h t he C R Fs at t he 
i n vesti gat or site, a n d a c o p y will be  sent  t o t he CR O  s o t he res ol uti o ns can  be e ntered  i nt o t he 

N o v artis 
C lin ica l T rial P rot o co l v 0 5  
C o n fid e nt ial  
P ag e 2 8  
P rot o co l N o . C A C Z 8 8 5 G F R 0 1  
 
d atab ase. Q u alit y c o ntr ol a u dits of  all key d a ta i n t he data base will be ma d e pri or t o l oc ki n g t he 
d a tab ase. 
A d verse e ve nts will be c o d e d usi n g t he 
Me di cal dicti o nar y f or re g ul at ory activi ties ( Me d D R A) 
ter mi n ol o g y. 
After t he se acti o ns ha ve been  c o m plete d a n d t he data bas e has been d ecl are d t o b e c o m plete a n d 
acc urate, it will be  l oc ked.  A n y c ha n ges t o t he data base after t hat ti me  can o n ly b e ma d e after 
writte n a gr eeme nt b y N o v artis. 
8. 4        D at a M o nit ori n g C o m mitt e e 
 
N ot req uire d. 
8. 5        A dj u di c ati o n C o m mitt e e 
 
N ot req uire d. 
 
9          D at a a n al y si s 
 
9. 1        A n a l y si s s et s 
 
Safet y Set: C o nsists of  all patie nts w h o recei ve d at least o n e d ose of st u d y dr u g a n d ha d at least 
o ne p ost- treat me nt safet y assess me nt i n t he st u d y. T he state me nt t hat a patient  ha d n o a d verse e ve nt 
( A E) als o c o nstit utes a safet y assess me nt. 
9. 2        P ati e nt d e m o gr a p hi c s  a n d ot h er ba s el in e  c h ar a ct eri sti c s 
 
De m o gra p hic s, back gr o u n d  data an d  ke y bas eli ne c h aracteristics are t h ose col lect e d i n t h e 
C A C Z 8 8 5 G 2 3 0 1 E 1 st u d y. Se x a n d date of birt h will be  re-c ollecte d i n t he C R F. 
9. 3        Tr e at m e nt s 
 
T he e x p os ure t o st u d y dr u g ( n u m ber of i njecti o ns) a n d d urati o n of e x p os ure ( da ys) will be 
s u m marize d a n d liste d b y d ose. 
9. 4        A n a l y si s of v ari a bl es 
9. 4. 1       V ari a bl e s 
 
a.   Effic ac y v ar i ables  
 
T h ere is n o efficac y ass essme nt i n t his st u d y 
 
b.   S af et y v ari ables  
 
A d verse e ve nts will be c o de d usi n g t he Me d D R A  dicti o nar y t h at pr o vi d es t he pri mar y s yste m or gan 
class a n d preferre d term i nf or mati o n. A d verse e ve nts will be  p resent e d i n t w o parts: 
o  A d verse e ve nts (i ncl u di n g i nfecti o ns) 
o  I nf ecti o us a d verse e ve nts 
A d verse e ve nts will be s u m ma rize d f or e a c h dis e as e b y prese nti n g t he n u m b er a n d  percent a ge of  
p atie nts ha vi n g a n y a d verse e ve n t, ha vi n g a n y a d verse e ve nt i n eac h prima ry s yst e m or ga n class a n d 
h a vi n g each i n di vi d ual a d v erse e ve nt  base d o n t he preferre d term.  All ot her i nf or mati o n c ollecte d 
(e. g. se verit y, relati o ns hi p t o st u d y dr u g, or micr o or ga nis m f or i nfecti o us a d verse e ve nts) will be 
ta b ulate d a n d liste d as a p pr o priate. 
D eat hs, seri o us a d verse e ve nts, an d  a d verse e ve nts lea di n g t o disc o nti n uati o n of st u d y dr u g will 
be s u m marize d b y pri mar y s yste m or ga n class a n d p referre d ter m a n d liste d. 

N o v artis 
C lin ica l T rial P rot o co l v 0 5  
C o n fid e nt ial  
P ag e 2 9  
P rot o co l N o . C A C Z 8 8 5 G F R 0 1  
 
9. 4. 2       St ati sti c al m o d el, h y p o t h e si s, a n d m et h o d of a n al y si s 
 
T his is a n o pe n-l a bel sin gle-a r m s afet y trial f or patie nts a n d t he d ata will be prese nte d i n a 
d escri pti ve ma n ne r. 
9. 4. 3       H a n dli n g of mi s si n g v al u e s/ c e n s ori n g/ di s c o n ti n u ati o n s 
 
Missi n g val ues will n ot be ha n dle d b ut pre mat ure disc o nti n uati o n will be f ull y desc ri be d. 
 
9. 5        I nt eri m a n al y s e s  
 
N ot req uire d 
 
9. 6        S a m pl e si z e c al c u l ati o n 
 
N o  sam p le size calc ulati o n was perf or me d f or t his e xte nsi o n st ud y w hic h will i ncl u de all eli g i ble 
s u bj ects w h o c om p lete C A C Z 8 8 5 G 2 3 0 1E 1  or C A C Z 8 8 5 N 2 3 0 1 st u d y a n d me et t he eli gi bilit y 
criteria. 
1 0        Et hi c al c o n si d er ati o n s 
 
1 0. 1      R e g ul at or y a n d et hi c al c o m pli a n c e  
 
T his cli nical st u d y was de sig n e d a n d s hall be i m ple me nte d a n d re p ort e d i n accor da nce wit h t he 
IC H  
Har m o nize d 
Tri partite 
G ui deli nes f or 
G o o d Cl i nical Practice, 
wit h a p plicable l o cal 
reg ulati o ns (i ncl u di n g E ur o pea n Directi ve  2 0 0 1/ 2 0/ E C, U S  C o de of Fe deral Re g ulati o ns Title 2 1, 
a n d J a pa nese Mi nistr y of Healt h, La b or, a n d Welfare), a n d wit h t he et hical pri nci ples lai d d o w n i n 
t he Declarati o n of Helsi n ki. 
1 0. 2      I nf or m e d c o n s e nt pr o c e d u re s  
 
Eli g i ble patie nts ma y o nl y be i ncl u de d i n t he st u d y after pr o vi di n g writte n ( wit nesse d, w h ere 
re q uire d by l a w or reg ul ati o n), I R B/I E C-a p pr o ve d  i nf or me d c o nse nt, or, if i nca pa ble of  d oi n g s o, 
after s uc h c o nse nt has been  pr o vi de d b y a le gally ac ce pta ble re prese ntati ve of t he patie nt. I n cases 
w h ere t he p atie nt’s re prese nt ati ve gi ves c o nse nt, t he patient  s h o ul d be i nf or me d a b o ut t he st u d y t o 
t he e xte nt p ossi ble gi ve n his/ her u n dersta n di n g. If t he patient  is capa ble of  d oi n g s o,  he/s he  s h o ul d  
i n dicate  asse nt  b y pers o nall y  si g ni n g  a n d  dati n g  t h e  writte n  i nf or me d c o nse nt d o c u me nt or  a 
se parate asse nt f orm.  I nf or me d c o nse nt m ust be o btai ne d bef ore c o n d ucti n g a n y st u d y-s pecific 
p r oced ures (i.e. all of  t he pr oced ures descri be d i n t he pr ot oc ol). T he pr ocess of o btai ni n g i nf or me d 
c o ns ent  s h o ul d be d oc u me nte d i n t he patient  s o urce d oc u me nts. 
N o vartis will pr o vi de t o i n vesti gat ors i n a se parate d oc u me nt a pr o p ose d i nf or me d c o nse nt f or m t hat 
c o m plies wit h t he IC H  G C P g ui deli ne a n d re gu l at or y re q uire me nts a n d is c o nsi dere d a p pr o priate 
f or t his st u d y. A n y c ha n ges t o t he pr o p ose d c o ns ent  f or m s u g geste d b y t he i n vesti gat or m ust be  
a gree d t o b y N o v artis bef ore s u b missi o n t o t he I R B/I E C, a n d a c o p y of t he a p pr o ve d versi o n m ust 
be pr o vi de d t o t he N o vartis m o nit or after I R B/I E C a p pr o va l. 
W o me n of c hil d b eari n g p ote ntial s h o ul d be  i nf or me d t hat ta ki n g t he st u d y treat me nt ma y i n v ol ve 
u n k n o w n ris ks t o t he fet us if pre g na ncy we re t o occ ur d uri n g t he st u dy a n d a gree t hat i n or der t o 
p artici p ate i n t he st u d y t he y m ust a d h ere t o t he c o ntrace ptio n  re q uir e me nt f or t h e d uratio n  of t he 
st u d y. If t here is a n y q uesti o n t hat t he patient  will n ot reliab ly c o m pl y, t he y s h o ul d n ot be e ntered i n 
t he st u d y. 
 

N o v artis 
C lin ica l T rial P rot o co l v 0 5  
C o n fid e nt ial  
P ag e 3 0  
P rot o co l N o . C A C Z 8 8 5 G F R 0 1  
 
1 0. 3      R e s p o n si biliti e s  of t h e i n v e sti g ator  a n d I R B/I E C 
 
T he pr ot oc ol a n d t he p r o p ose d i nf or me d c o nse nt f or m m ust be re vie we d a n d a p pr o ve d b y a pr o perly 
c o nstit ute d I nstit uti o nal 
Re vie w 
B o ar d/In d e pen d ent  Et hics 
C o m mittee/ Researc h Et hics 
B oar d 
(I R B/I E C) bef ore st u d y start. A sig ne d a n d  date d state me nt t hat t he pr ot oc ol a n d i nf or me d c o nse nt 
h a ve  been  a p pr o ve d b y t h e IR B /IE C  m ust be gi ve n t o N o vartis bef ore st u d y i nitiati o n. Pri or t o 
st u d y start, t he i n vesti gat or is re q uire d t o sig n a pr ot oc ol  sig n at ure p a ge c o nfir mi n g his/ her 
a gree me nt t o c o n d uct t he st u d y i n acc or da n ce wit h t hese d oc u me nts a n d all of t he i nstr ucti o ns a n d 
p r oced ures f o u n d i n t his pr ot oc ol a n d t o gi ve access t o all rele vant  data a n d rec or ds t o N o vartis 
m o nit ors, a u dit or s, 
N o vartis Cl i nical Q u alit y Ass ura nce re pres e ntati ves, desi g nat e d a ge nts of  
N o vartis, I R Bs/I E Cs, a n d reg ula t ory a ut h orities as re q uire d. If a n  i ns pectio n  of t he cli nical site is 
re q ueste d b y a reg ula t ory a ut h orit y, t he i n vesti gat or m ust i nf or m N o vartis i m me diat el y t h a t t his 
req u est has been ma de. 
 
1 0. 4      P u bli c ati o n  of st u d y pr ot o col  a n d r e s ult s 
 
N o vartis ass ures t hat t he ke y d e sig n ele me nts of t his pr ot oc ol will be  p oste d i n a p u blicly accessi ble 
d ata base s uc h as cli nicalt rials. g o v. I n a d diti o n, u p o n st u d y c o m pleti o n a n d fi nal izati o n of t he st u d y 
re p ort t he res ults of t his trial will be eit her s u b mitte d f or p u blicati o n a n d/ or p oste d i n a p u blicl y 
accessi ble data base of  cli nical trial res ults. 
1 1        Pr ot o c ol ad h er e n c e  
 
I n vesti gat ors ascertai n t h e y will a p pl y d u e di li ge nce t o a v oi d pr ot oc ol d e viati o ns. U n der n o 
circ u msta nces s h o ul d t he i n vesti gat or c o nta ct N o vartis or  its a ge nts, if a n y, m o nit ori n g t he trial 
t o re q uest a p pr o val of a pr ot oc ol d e viati o n, as re q uests t o a p pr o ve d e viati o ns will n ot be gra nte d. 
T his pr ot oc ol defi nes t he st u d y o bjecti ve s, t he st u d y pr oced u res a n d t he data t o be c ollecte d o n 
st u d y partici pa nts. U n der n o circ u msta nces s h o ul d a n i n vesti gat or c ollect a d diti o nal data or 
c o n d uct a n y a d diti o nal pr o ced ures f or a n y researc h relate d p ur p ose i n v ol vi n g a n y i n vesti gati o na l 
dr u g s. 
If t h e i n vesti gat or feels a pr ot oc ol de viati o n w o ul d i m pr o ve t he c o n d uct of  t he st u d y t his m ust be 
c o nsi dere d a pr ot o c ol a me n d me nt, a n d u nless s uc h a n a me n d me nt is a g ree d u p o n b y N o va rtis a n d 
a p pr ove d  b y t he I R B/IE C  it can n ot  be i m ple me nte d. All sig nifi cant  pr ot oc ol de viati o ns will be  
rec or de d a n d re p orte d i n the  C S R.  
 
1 1. 1      Pr ot o c ol A m e n d m e nt s 
 
A n y c ha n ge or a d diti o n t o t he pr ot oc ol ca n o nl y b e ma de i n a writte n prot o c ol a me n d me nt t hat m ust 
be a p pr o ve d  by N o vartis, H ealt h A ut h orities w h ere re q uire d, a n d t he I R B/I E C. O n ly ame n d me nts 
t hat are req uire d f or patie nt safet y ma y b e i m ple me nte d pri or t o I R B/I E C a p pr ova l. N ot wit hsta n di n g 
t he need  f or a p pr o val of  f or mal prot o c ol a me n d me nts, t he i n vesti gat or is e x pecte d t o ta ke a n y 
i m me diate acti o n r e q uire d f or t he safet y of a n y patie nt i ncl u de d i n t his st u d y, e ve n if t his acti o n 
re prese nts a de vi ati o n fr o m t h e prot o c ol. I n s uc h cases, N o v artis s h o ul d be n otifie d of t his acti o n a n d 
t he I R B/IE C  at t he st ud y site s h o ul d be i nf or me d wit hi n 1 0 w or ki n g da ys or less, i f req uire d b y l o cal 
r e g ulati o ns. 
 
1 2        R ef er e n c e s 
 
Di narell o C A ( 1 9 9 6) Bi ol o gic basis f or i nterle u ki n- 1 i n disease. Bl o o d; 8 7( 6): 2 0 9 5- 1 4 7. Re vie w. 
Di narell o C A ( 2 0 0 5) Bl oc ki n g I L- 1 i n s yste mic i nfla m mati o n. J E x p Me d; 2 0 1( 9): 1 3 5 5- 9. 

N o v artis 
C lin ica l T rial P rot o co l v 0 5  
C o n fid e nt ial  
P ag e 3 1  
P rot o co l N o . C A C Z 8 8 5 G F R 0 1  
 
Pasc ual V, Alla ntaz F, Arce E, et al ( 2 0 0 5) R ole of i nterle u ki n- 1 (I L- 1) i n t he pat h o ge nesis of 
s yste mic o nset j u ve nile i di o pat hic art hritis a n d cli nical res p o nse t o I L- 1 bl oc ka de. J E x p 
Me d; 
2 0 1( 9): 1 4 7 9 -8 6.  
Q uartier P, Prie ur A M. Art hrite j u ve nile i di o pat hi q ues. Les différe ntes f or mes cli ni q ues. 
Re v  
Praticie n 2 0 0 7 ; 5 7( 1 1).  
Ra velli A, Marti ni A ( 2 0 0 7) J u ve nile i di o pat hic art hritis. La ncet; 3 6 9: 7 6 7 – 7 8. 
R u pert o N, Q uartier P, W ulffraat N, et al ( 2 0 0 8 b) A p hase II trial wit h ca na ki n u ma b, a ne w I L- 1 ß 
bl oc ki n g m o n ocl o nal a nti b o d y ( A C Z 8 8 5), t o e val uate preli mi nar y d osi n g, safet y a n d effic ac y pr ofile 
i n c hil dre n wit h s yste mic J u ve nile I di o pat hic art hritis (sJI A) [ oral prese ntati o n]. 1 5t h Pae diatric 
R he u mat ol o g y E ur o pea n S ociet y ( Pre S) C o n gress, 1 4- 1 7 Se pte m ber 2 0 0 8, L o n d o n ( U K). 
W o o P ( 2 0 0 6) S yste mic j u ve nile i di o pat hic art hritis: dia g n osis, ma na ge me nt, a n d o utc o me. Nat Cli n 
Pract R he u mat ol; 2( 1): 2 8- 3 4. 
Di narell o C A, Si m o n A, va n der Meer J W. Treati n g i nfla m mati o n b y bl oc ki n g i nterle u ki n- 1 i n a 
br oa d s pectr u m of diseases. Nat Re v Dr u g Disc o v. 2 0 1 2 ( 8): 6 3 3- 5 2. 
Dre nt h J P, va n der Meer J W. Here ditar y peri o dic f e ver. N E n gl J Me d. 2 0 0 1; 3 4 5: 1 7 4 8- 5 7. 
G ul A, Oz d o ga n H, Erer B, et al. Efficac y a n d Safet y of Ca na ki n u ma b i n A d olesce nt a n d a d ults wit h 
C olc hici ne Resista nt Fa milial Me diterra nea n Fe ver. Art hritis Res T her. 2 0 1 5; 1 7 ( 1): 2 4 3 . 
T er Haar N, Lac h ma n n H, Oze n S, et al ( 2 0 1 2). Treat me nt of a ut oi nfla m mat or y diseases:  res ultsfr o m 
t he E ur ofe ver Re gistr y a n d a literat ure re vie w. A n n R he u m Dis. 2 0 1 3; 7 2: 6 7 8-8 5. . 
 
 
 

N o v artis 
C lin ica l T rial P rot o co l v 0 5  
C o n fid e nt ial  
P ag e 3 2  
P rot o co l N o . C A C Z 8 8 5 G F R 0 1  
 
1 3  
A p p en d i x 1:  S u mm a r y of pro d u ct  c h ara ct e risti c s