A Randomized, Double-blind, Placebo-controlled Phase 2 Study to Evaluate the Effect of Filgotinib on Semen Parameters in Adult Males With Active Rheumatoid Arthritis, Psoriatic Arthritis, Ankylosing Spondylitis or Non-radiographic Axial Spondyloarthritis
Phase: PHASE2
Conditions: Rheumatoid Arthritis, Psoriatic Arthritis, Ankylosing Spondylitis, Non-Radiographical Axial Spondyloarthritis
Sponsor: Galapagos NV

 
 
 
 
 
C LI NI C A L S T U D Y P R O T O C O L  
 
 
St u d y Title:  
A Ra n d o mize d, D o u ble -bli n d, Place b o -c o ntr olle d P hase 2 St u d y t o 
E val uate t he Effect of Fil g oti ni b o n Se me n Para m eters i n A d ult 
Males wit h A cti ve R he u mat oi d Art hritis, Ps oriatic Art hritis, 
A n k yl osi n g S p o n d ylitis or N o n -ra di o gra p hic A xial 
S p o n d yl o art hritis.  
 
 
S p o ns or:  
Gala pa g os N V  
Ge neraal De Wittelaa n L 1 1 A 3  
2 8 0 0 Mec hele n, Bel gi u m  
 
 
 
E u dr a C T N u m ber:  
Cli nic al Tri als. g o v 
I de ntifier: 
2 0 1 8 -0 0 3 9 3 3 -1 4  
 
N C T 0 3 9 2 6 1 9 5  
 
 
I n dic ati o n: 
R he u mat oi d art hritis, ps oriatic art hritis, a n k yl osi n g s p o n d ylitis, or 
n o n -ra di o gra p hical a xial s p o n d yl oart hritis 
 
 
Pr ot oc ol I D:   
G L P G 0 6 3 4 -C L -2 2 7  
 
 
Cli nic al De vel o p me nt 
Le a der : 
 
 
 
Me dic al Le a der : 
 
 
 
Pr ot oc ol 
Versi o n/ D ate:  
Ori gi nal:  0 5 Fe b  2 0 1 9  
A me n d me nt 1: 2 6 Ma y 2 0 2 0  
 
A me n d me nt  2: 0 9 Se p  2 0 2 2  
 
C O N FI D E N TI A LI T Y S T A T E M E N T  
T he i nf or mati o n c o ntai ne d i n t his d oc u me nt is pri vile ge d a n d c o nfi de ntial. It is t he pr o pert y of Gala pa g os N V a n d 
ma y n ot b e use d, discl ose d, re pr o d uce d or ot her wise disse mi nate d wit hi n y o ur or ga nizati o n or c o m m u nicate d t o 
a n y t hir d parties wit h o ut t he e x press writte n a ut h orizati o n of Gala pa g os N V . 
 
P P D
P P D

Fil g oti ni b  
 
Pr ot oc ol  G L P G 0 6 3 4 -C L -2 2 7  
Fi nal  
Gala pa g os  
A me n d me nt 2  
C O N FI D E N TI A L  
P a ge  2  
0 9 Se p 2 0 2 2  
C LI NI C A L S T U D Y P R O T O C O L HI S T O R Y  
Cli nic al st u d y pr ot oc ol ( C S P ) / 
A me n d me nt #  
D ate  
M ai n R ati o n ale  
Ge neric / C o u ntr y / Site S pecific  
C S P  Versi o n 1. 0  
0 5 -Fe b -2 0 1 9  
I nitial C S P Versi o n 
Ge neric  
C S P  Versi o n 2. 0 / A me n d me nt # 1  
2 6 -Ma y -2 0 2 0  
 
 re q uest 
Ge neric  
C S P  Versi o n 3 . 0 / A me n d me nt #2  
0 9 -Se p -2 0 2 2  
C ha n ge i n w or di n g a b o ut bli n di n g  
Ge neric  
C CI

Fil g oti ni b  
 
Pr ot oc ol  G L P G 0 6 3 4 -C L -2 2 7  
Fi nal  
Gala pa g os  
A me n d me nt 2  
C O N FI D E N TI A L  
P a ge  3  
0 9 Se p 2 0 2 2  
S U M M A R Y O F C H A N G E S  
A me n d me nt 2  
T he o ver all re as o n f or t his a me n d me nt:  
T his st u d y has pr o gresse d be y o n d t h e a nal ysis ti me p oi nts of t he pri mar y, s ec o n dar y , a n d all 
e x pl orat or y e n d p oi nts , w hic h were t h e sc o pe of t he sec o n d u n bli n de d i nteri m a nal ysis (I A 2). 
T he S p o ns or pla ns t o discl ose t hese dat a of scie ntific i nterest i nt o a peer re vie we d j o ur nal 
w hile t he st u d y is still o n g oi n g , wit h o ut c o m pr o misi n g t he data i nte grit y a n d scie n tific 
vali dit y. T o t his p ur p ose, t he w or di n g a b o ut bli n di n g was re vise d t o all o w discl os ure of t he 
treat me nt assi g n me nts of s u bjects w h o c o m plete d t he st u d y bef ore  I A 2. 
Ge neral mi n or a d mi nistrati ve u p dates were ma de t hr o u g h o ut t he pr ot o c ol, i ncl u di n g 
ter min ol o g y, p u nct uati o n, a b bre viati o ns, dates, n u m bers, a n d  f or m at f or cl arit y a n d 
c o nsiste nc y.   
T he c ha n ges ma de t o t he cli nical st u d y pr ot o c ol  G L P G 0 6 3 4- C L- 2 2 7 Versi o n 2 . 0, 
2 6 -Ma y -2 0 2 0  are liste d b el o w, refl ecti n g a brief rati o nale f or eac h c h a n ge a n d t he a p plica ble 
secti o ns.  
R ati o n ale : Te xt was re vise d t o s pecif y t he dec o m missi o ni n g of t he Data M o nit ori n g 
C o m mittee ( D M C) a n d tra nsfer t he r ole of t he D M C t o t he S p o ns or Safet y Ma na ge me nt T ea m 
( S S M T). All pla n ne d D M C re vie ws ha ve b ee n c o m plete d a n d n o a d diti o nal re vie ws are 
e x pecte d. At t his a d va nce d sta ge of t he st u d y, tr eat me nt assi g n me nts ha ve bee n u n bli n de d f or 
t he maj orit y of s u bjects, n o l o n ger re q uiri n g a n e xter nal u n bli n de d re vi e w c o m mittee i n 
a d diti o n  t o t he bli n de d S p o ns or st u d y tea m. O versi g ht b y t he S S M T will i ncl u de re g ular 
re vie ws of s afet y s u m mar y u p d ates a n d will pr o vi de si milar o pti o ns f or escalate d iss ue re vi e w 
as descri be d i n t he D M C c harter b y f oll o wi n g t h e S S M T sta n dar d pr oce d ures . 
A p plic a b le Secti o ns: S y n o psis 
1. 4  Ris k/ Be nefit Assess me nt f or t he St u d y  
8. 8  Data M o nit ori n g C o m mittee/ S p o ns or Safet y Ma na ge me nt T ea m  
R ati o n ale:  Te xt a b o ut bli n di n g was r e vise d t o all o w p u blicati o n of t he treat me nt assi g n me nts 
of s u bjects w h o c o m plete d t he st u d y bef ore  I A 2. 
A p plic a ble Secti o ns : S y n o psis 
5. 1. 1  Bli n di n g  
8. 1 1  U n bli n de d I nteri m A nal ysis  
R ati o n ale:  A  st u d y dr u g i nterr u pti o n criteri o n f or s u bjects e x perie nci n g m o derate re nal f ail ure 
(esti mate d creati ni ne cle ara nce ≥3 5 m L/ mi n a n d < 6 0 m L/ mi n per C oc kcr oft -Ga ult f or m ula) 
was a d de d  t o ali g n wit h In vesti gat or’s B r oc h ure E diti o n 1 7, 1 5 -J ul-2 0 2 2 . 
A p plic a ble Secti o n : 3. 7. 1  St u d y  Dr u g I nterr u pti o n C o nsi derati o ns  

Fil g oti ni b  
 
Pr ot oc ol  G L P G 0 6 3 4 -C L -2 2 7  
Fi nal  
Gala pa g os  
A me n d me nt 2  
C O N FI D E N TI A L  
P a ge  4  
0 9 Se p 2 0 2 2  
R ati o n ale:  Te xt was a d d e d t o s pecif y t he dec o m missi o ni n g of  t he I nter n al I n de p e n de nt Safet y 
Re vie w Tea m as of t his a me n d me nt. T he i nter nal i n de pe n de nt S S M T will c o ver t he o bjecti ves 
of t he D M C a n d t he I nter nal I n d e pe n d e nt Safet y R e vie w Tea m . 
A p plic a ble Secti o ns : S y n o psis 
8. 1 0  I nter nal I n d e pe n de nt Safet y Re vi e w 
 
A me n d me nt 1  
T he o ver all re as o n f or t his a me n d me nt:  
T his a me n d me nt was i nitiate d t o a d dress c o m me nts fr o m t he 
 
) relate d t o n e w safet y i nf or mati o n s u g gesti n g a n increas e d ris k of 
t hr o m b oe m b olic e ve nts i n patie nts treate d wit h J A K i n hi bit ors. 
In a d diti o n, se veral s ecti o ns were revise d i n li ne wit h t he te m plate u p date .  
Ge neral mi n or a d mi nistrati ve u p dates were ma de t hr o u g h o ut t he pr ot o c ol, i ncl u di n g 
ter mi n ol o g y, p u nct uati o n, a b bre viati o ns, dates, n u m bers, a n d  f or m at f or cl arit y a n d 
c o nsiste nc y.   
T he c ha n ges ma de t o t he cli nical st u d y pr ot o c ol G L P G 0 6 3 4- C L- 2 2 7 Versi o n 1. 0, 0 5 -Fe b -2 0 1 9  
are liste d bel o w, reflecti n g a brief rati o nale f or eac h c ha n ge a n d t he a p plica ble  secti o ns.  
R ati o n ale:  Te xt was re vise d t o a v oi d c o nf usi o n.  
A p plic a ble Secti o n : S y n o psis  
4. 2  I n cl usi o n Criteria 
5. 3. 1  All o we d C o nc o mita nt Me dicati o ns  
R ati o n ale:  Te xt was a d de d  per a u dit fi n di n g t o clearl y d escri be t he e n d of t he D o u ble -bli n d 
Treat me nt P hase , w h e n s e me n a nal ysis res ults are a vaila ble. 
A p plic a ble Secti o ns: S y n o psis  
3. 1  D o u ble -b li n d Treat m e nt P hase 
6. 4  D o u ble -b li n d Treat m e nt P hase 
A p pe n di x 2 , St u d y Pr oce d ure Ta ble –  D o u ble -bli n d Treat me nt P hase  
R ati o n ale: T he re vise d te xt a d ds clarit y t o w he n s u bjects m ust perf or m yearl y t u b erc ul osis ( T B) 
testi n g i n t he E xte nsi o n P hase.  
A p plic a ble Secti o ns: Secti o n 3. 2  E xte nsi o n P hase  
A p pe n di x 2, St u d y Pr oce d ure Ta ble - E xte nsi o n p hase  
C CI

Fil g oti ni b  
 
Pr ot oc ol  G L P G 0 6 3 4 -C L -2 2 7  
Fi nal  
Gala pa g os  
A me n d me nt 2  
C O N FI D E N TI A L  
P a ge  5  
0 9 Se p 2 0 2 2  
R ati o n ale:  C riteri o n f or disc o nti n uati o n f or t hr o m b oe m b olis m has bee n a d de d t o a d dress 
c o m me nts of t he 
 
A p plic a ble Secti o n : 3. 7. 2  St u d y Dr u g Disc o nti n u ati o n C o nsi derati o ns  
R ati o n ale:  Te xt was c orrecte d.  
A p plic a ble Secti o n : 4. 3  E x cl usi o n Criteria  
R ati o n ale:  Ne w secti o n was a d d e d t o clarif y bli n di n g pr oce d ures i n li ne wit h t he pr ot o c ol 
te m plate u p date. 
A p plic a ble Secti o n : 5. 1. 1  Bli n di n g  
R ati o n ale: Te xt was re vise d t o descri b e t hat all u n use d a n d e m pt y I M P s u p plies nee d t o b e 
ret ur ne d t o t he ware h o use a n d t hat l ocal destr u cti o n is n ot all o we d, a n d t o ali g n wit h t he p r ot o c ol 
te m plate u p date, w hic h re m o ves Secti o n 9. 1. 7 a n d i nc or p orates t he i nf or m ati o n i n t his secti o n. 
A p plic a ble Secti o n : 5. 5. 1  I n v esti gati o nal Me dici nal Pr o d uct Ret ur n or Dis p osal 
R ati o n ale: Te xt was a d d e d  t o a v oi d c o nf usi o n. 
A p plic a ble Secti o n : 6. 8  Safet y F oll o w -U p Visit 3 0 Da ys P ost D ose ( ± 5 D a ys)  
R ati o n ale: Te xt was a d de d t o a d dress c o m me nts of t he  
. T he l a n g ua ge was a d de d t o 
g ui de t he ma n a ge me nt of s u bjects w h o de vel o p a t hr o m b oe m b olic e ve nt w hile u n der  st u d y, 
e ns uri n g cli nical ma na ge me nt is a d dresse d a n d cli nical ris k fact ors are ca pt ure d.  
A p plic a ble Sect i o n: 6. 9. 1  T hr o m b oe m b olic E ve nts  
R ati o n ale: Te xt was re vise d  wit h a m ore ge n eral descri pti o n t o a v oi d c o nf usi o n . 
A p plic a ble Secti o n : 6. 1 1  Se me n C ollecti o n Pr oce d ure  
R ati o n ale: Te xt was u p date d t o ali g n wit h t he  pr ot oc ol te m plate u p date. 
A p plic a ble Secti o ns:  7. 7  S pecial Sit uati o ns Re p orts  
7. 7. 1  D efi niti o ns of S pecial Sit uati o ns  
7. 7. 2  I nstr u cti o ns f or Re p orti n g S pecial Sit uati o ns 
R ati o n ale: A cr iteri o n t o tri g ger a n a d h o c D M C meeti n g relate d t o a t hr o m b oe m b olic e ve nt 
was a d de d t o a d dress c o m me nts of t he 
 
A p plic a ble Secti o n : 8. 8  Data M o nit ori n g C o m mittee  
R ati o n ale: Te xt was a d de d t o des cri be a C V E A C t hat t he S p o ns or is est a blis hi n g t o a d dress 
c o m me nts of t he 
 
A p plic a ble Secti o n : 8. 9  Car di o vasc ular Safet y E n d p oi nt A dj u dicati o n C o m mittee ( C V E A C)  
C CI
C CI
C CI
C CI

Fil g oti ni b  
 
Pr ot oc ol  G L P G 0 6 3 4 -C L -2 2 7  
Fi nal  
Gala pa g os  
A me n d me nt 2  
C O N FI D E N TI A L  
P a ge  6  
0 9 Se p 2 0 2 2  
R ati o n ale: Te xt was re vise d a n d a d de d t o ali g n wit h t he G S -U S -4 1 8 -4 2 7 9  pr ot oc ol.  
A p plic a ble Secti o n s: S y n o psis  
8. 1 0  I nter nal D e pe n de nt Safet y R e vie w 
R ati o n ale: Te xt was re m o ve d t o ali g n wit h t he pr ot oc ol te m plate u p date , w hic h re m o ves t his 
secti o n a n d inc or p orates t he i nf or mati o n i n o ne  place i n Secti o n 5. 5. 1 . 
A p plic a ble Secti o n : 9. 1. 7 I M P Acc o u nta bilit y a n d Ret ur n  
R ati o n ale: A f o ot n ote w as a d de d t o pr o vi de m or e details o n t he Safet y f oll o w -u p visit.  
A p plic a ble Secti o n : A p pe n di x 2 , St u d y Pr oce d ure Ta ble –  D o u ble -b li n d Treat me nt Phase  
R ati o n ale:  T he 1 2 -l ea d E C G asse ss me nt has bee n re m o ve d i n (t he l ast sc he d ule d visit of) the 
M o nit ori n g P hase  si nce t he patie nt i s n ot o n fil g oti ni b a n y m ore; t heref ore, this assess me nt is n ot 
nee de d f or safet y reas o ns.  
A p plic a ble Secti o n : A p pe n di x 2 , St u d y P r oce d ure Ta ble - M o nit ori n g p hase  
R ati o n ale: F o ot n otes ha ve bee n u p d ate d f or acc urate ness a n d t o a v oi d c o nf usi o n.  
A p plic a ble Secti o n: A p pe n di x 2, St u d y Pr oce d ure Ta ble - E xte nsi o n p has e  
R ati o n ale: T e x t was a d de d t o s pecif y t hat i n t he E xte nsi o n P hase E C G f or safet y assess me nt is 
o nl y re q uire d f or s u bjects o n st u d y dr u g ( o pe n -la bel fil g oti ni b) a n d n ot f or s u bjects o n Sta n dar d 
of Care  treat me nt. T he E C G i n s u bjects o n Sta n dar d of Care tr eat me nt is see n as re d u n d a nt a n d 
t heref ore re m o ve d t o re d uce t he patie nt b ur d e n. 
A p plic a ble Secti o n : A p pe n di x 2 , St u d y Pr oce d ure Ta ble - E xte nsi o n p has e  
 
 

Fil g oti ni b  
 
Pr ot oc ol  G L P G 0 6 3 4 -C L -2 2 7  
Fi nal  
Gala pa g os  
A me n d me nt 2  
C O N FI D E N TI A L  
P a ge  7  
0 9 Se p 2 0 2 2  
T A B L E O F C O N T E N T S  
C LI NI C A L S T U D Y P R O T O C O L HI S T O R Y  ........................................................................................................ 2  
S U M M A R Y O F C H A N G E S  ................................................................................................................................... 3  
T A B L E O F C O N T E N T S  ........................................................................................................................................ 7  
LI S T O F I N -T E X T T A B L E S  ................................................................................................................................ 1 0  
LI S T O F I N -T E X T FI G U R E S  .............................................................................................................................. 1 0  
P R O T O C O L  S Y N O P SI S  ...................................................................................................................................... 1 1  
D E FI NI TI O N O F T E R M S  .................................................................................................................................... 2 2  
G L O S S A R Y O F A B B R E VI A TI O N S A N D D E FI NI TI O N  O F T E R M S  .............................................................. 2 3  
1.  
I N T R O D U C TI O N ........................................................................................................................................ 2 8  
1. 1.  
B a c k gr o u n d  ....................................................................................................... 2 8  
1. 1. 1.  
R h e u m at oi d Art hriti s  ........................................................................... 2 8  
1. 1. 2.  
P s ori ati c Art hriti s ................................................................................. 2 9  
1. 1. 3.  
A n k yl o si n g S p o n d yliti s  ........................................................................ 3 0  
1. 1. 4.  
N o n -r a di o gr a p hi c al A xi al S p o n d yl o art hriti s ......................................... 3 1  
1. 2.  
Fil g oti ni b ( G S -6 0 3 4)  .......................................................................................... 3 2  
1. 2. 1.  
G e n er al I nf or m ati o n  ............................................................................ 3 2  
1. 2. 2.  
Pr e cli ni c al P h ar m a c ol o g y a n d T o xi c ol o g y  ........................................... 3 2  
1. 2. 3.  
Cli ni c al St u di e s of Fil g oti ni b  ................................................................ 3 4  
1. 3.  
R ati o n al e f or t hi s St u d y a n d Pr o p o s e d St u d y P o p ul ati o n  ................................... 3 5  
1. 3. 1.  
R ati o n al e f or t h e O ut c o m e M e a s ur e s  ................................................. 3 6  
1. 3. 2.  
R ati o n al e f or t h e C h oi c e of D o s e a n d D o si n g I nt er v al  ......................... 3 7  
1. 4.  
Ri s k/ B e n efit A s s e s s m e nt f or t h e St u d y  .............................................................. 3 7  
1. 5.  
C o m pli a n c e  ....................................................................................................... 3 9  
2.  
O BJ E C TI V E S  ............................................................................................................................................... 3 9  
3.  
S T U D Y D E SI G N  .......................................................................................................................................... 4 0  
3. 1.  
D o u bl e -bli n d Tr e at m e nt P h a s e ( D a y  1 t hr o u g h W e e k  1 3 St u d y Vi sit)  ................ 4 2  
3. 2.  
E xt e n si o n P h a s e ................................................................................................ 4 3  
3. 3.  
M o nit ori n g P h a s e ( u p t o 5 2  w e e k s)  ................................................................... 4 4  
3. 4.  
S e m e n C oll e cti o n a n d a n al y si s:  ......................................................................... 4 4  
3. 5.  
St u d y Tr e at m e nt s  .............................................................................................. 4 5  
3. 6.  
D ur ati o n of Tr e at m e nt  ........................................................................................ 4 5  
3. 7.  
Crit eri a f or I nt err u pti o n or Di s c o nti n u ati o n of St u d y Tr e at m e nt ........................... 4 5  
3. 7. 1.  
St u d y Dr u g I nt err u pti o n C o n si d er ati o n s  .............................................. 4 5  
3. 7. 2.  
St u d y Dr u g Di s c o nti n u ati o n C o n si d er ati o n s:  ....................................... 4 6  
3. 7. 3.  
St u d y Di s c o nti n u ati o n  ......................................................................... 4 8  
3. 8.  
E n d of St u d y  ...................................................................................................... 4 8  
3. 9.  
P o st -St u d y C ar e  ................................................................................................ 4 8  
4.  
S U BJ E C T P O P U L A TI O N  ............................................................................................................................ 4 8  
4. 1.  
N u m b er of S u bj e ct s a n d S u bj e ct S el e cti o n  ........................................................ 4 8  

Fil g oti ni b  
 
Pr ot oc ol  G L P G 0 6 3 4 -C L -2 2 7  
Fi nal  
Gala pa g os  
A me n d me nt 2  
C O N FI D E N TI A L  
P a ge  8  
0 9 Se p 2 0 2 2  
4. 2.  
I n cl u si o n Crit eri a ................................................................................................ 4 8  
4. 3.  
E x cl u si o n Crit eri a  ............................................................................................... 5 2  
5.  
I N V E S TI G A TI O N A L M E DICI N A L P R O D U C T S  ..................................................................................... 5 4  
5. 1.  
R a n d o mi z ati o n, Bli n di n g a n d Tr e at m e nt C o d e s  ................................................. 5 4  
5. 1. 1.  
Bli n di n g  .............................................................................................. 5 4  
5. 1. 2.  
Pr o c e d ur e s f or Br e a ki n g Tr e at m e nt C o d e s  ......................................... 5 5  
5. 2.  
D e s cri pti o n a n d H a n dli n g of Fil g oti ni b a n d Pl a c e b o  ........................................... 5 5  
5. 2. 1.  
F or m ul ati o n  ........................................................................................ 5 5  
5. 2. 2.  
P a c k a gi n g a n d L a b eli n g  ..................................................................... 5 6  
5. 2. 3.  
St or a g e a n d H a n dli n g  ......................................................................... 5 6  
5. 2. 4.  
D o s a g e a n d A d mi ni str ati o n of Fil g oti ni b a n d Pl a c e b o  ......................... 5 6  
5. 3.  
Pri or a n d C o n c o mit a nt M e di c ati o n s  ................................................................... 5 7  
5. 3. 1.  
All o w e d C o n c o mit a nt M e di c ati o n s  ...................................................... 5 7  
5. 3. 2.  
Pr o hi bit e d C o n c o mit a nt M e di c ati o n s  ................................................... 5 8  
5. 4.  
V a c ci n e G ui d eli n e s  ............................................................................................ 6 0  
5. 5.  
A c c o u nt a bilit y f or St u d y Dr u g s  ........................................................................... 6 0  
5. 5. 1.  
I n v e sti g ati o n al M e di ci n al Pr o d u ct R et ur n or Di s p o s al ......................... 6 1  
6.  
S T U D Y P R O C E D U R E S  .............................................................................................................................. 6 1  
6. 1.  
S u bj e ct E nr oll m e nt a n d Tr e at m e nt A s si g n m e nt  ................................................. 6 1  
6. 2.  
Pr etr e at m e nt A s s e s s m e nt s  ................................................................................ 6 1  
6. 2. 1.  
S cr e e ni n g Vi sit  ................................................................................... 6 1  
6. 2. 2.  
D a y 1 A s s e s s m e nt s  ............................................................................ 6 3  
6. 3.  
R a n d o mi z ati o n  .................................................................................................. 6 4  
6. 4.  
D o u bl e -bli n d Tr e at m e nt P h a s e ( D a y 1 T hr o u g h W e e k 1 3 St u d y Vi sit)  ............... 6 4  
6. 5.  
E xt e n si o n P h a s e ................................................................................................ 6 5  
6. 6.  
M o n it ori n g P h a s e ............................................................................................... 6 5  
6. 7.  
E arl y T er mi n ati o n  .............................................................................................. 6 5  
6. 8.  
S af et y F oll o w -U p Vi sit 3 0 D a y s P o st D o s e ( ± 5 d a y s)  ......................................... 6 6  
6. 9.  
S af et y a n d T ol er a bilit y  ....................................................................................... 6 6  
6. 9. 1.  
T hr o m b o e m b oli c E v e nt s  ..................................................................... 6 6  
6. 1 0.  Cli ni c al L a b or at or y E v al u ati o n s  .......................................................................... 6 6  
6. 1 1.  S e m e n C oll e cti o n Pr o c e d ur e  ............................................................................. 6 7  
6. 1 2.  Vit al Si g n s  ......................................................................................................... 6 8  
6. 1 3.  P h y si c al E x a mi n ati o n  ........................................................................................ 6 8  
6. 1 4.  P h ar m a c o ki n eti c A s s e s s m e nt s  .......................................................................... 6 8  
6. 1 5.  Hi g h S e n siti vit y S er u m C -R e a cti v e Pr ot ei n  ........................................................ 6 9  
6. 1 6.  6 6/ 6 8 -J oi nt C o u nt ( P s A) a n d 2 8 -J oi nt C o u nt ( R A) ( u s e d f or D A P S A a n d 
C D AI)  ................................................................................................................ 6 9  
6. 1 7.  P h y si ci a n Gl o b al A s s e s s m e nt of Di s e a s e A cti vit y ( P h G A D A)  ............................ 6 9  
6. 1 8.  P ati e nt Gl o b al A s s e s s m e nt of Di s e a s e A cti vit y ( Pt G A D A) ( u s e d f or C D AI 
a n d D A P S A)  ...................................................................................................... 6 9  
6. 1 9.  P ati e nt’ s Gl o b al A s s e s s m e nt of P ai n I nt e n sit y ( P P AI N) ( u s e d f or D A P S A)  ........ 7 0  
6. 2 0.  B A S D AI  ............................................................................................................. 7 0  
7.  
A D V E R S E E V E N T S A N D T O XI CI T Y M A N A G E M E N T  ......................................................................... 7 0  
7. 1.  
D efi niti o n s of A d v er s e E v e nt s, A d v er s e R e a cti o n s, a n d S eri o u s A d v er s e 
E v e nt s  ............................................................................................................... 7 0  
7. 1. 1.  
A d v er s e E v e nt s  .................................................................................. 7 0  
7. 1. 2.  
S eri o u s A d v er s e E v e nt s  ..................................................................... 7 1  

Fil g oti ni b  
 
Pr ot oc ol  G L P G 0 6 3 4 -C L -2 2 7  
Fi nal  
Gala pa g os  
A me n d me nt 2  
C O N FI D E N TI A L  
P a ge  9  
0 9 Se p 2 0 2 2  
7. 2.  
A s s e s s m e nt of A d v er s e E v e nt s a n d S eri o u s A d v er s e E v e nt s  ............................ 7 1  
7. 2. 1.  
A s s e s s m e nt of C a u s alit y f or St u d y Dr u g s a n d Pr o c e d ur e s  ................. 7 1  
7. 2. 2.  
A s s e s s m e nt of S e v erit y  ...................................................................... 7 2  
7. 3.  
I n v e sti g at or R e q uir e m e nt s a n d I n str u cti o n s f or R e p orti n g A d v er s e E v e nt s 
a n d S eri o u s A d v er s e E v e nt s t o t h e S p o n s or  ...................................................... 7 3  
7. 4.  
S p o n s or R e p orti n g R e q uir e m e nt s  ...................................................................... 7 4  
7. 5.  
Cli ni c al L a b or at or y A b n or m aliti e s a n d Ot h er A b n or m al A s s e s s m e nt s  ................ 7 5  
7. 6.  
T o xi cit y M a n a g e m e nt  ........................................................................................ 7 5  
7. 6. 1.  
Gr a d e s 1 a n d 2 L a b or at or y A b n or m alit y or Cli ni c al E v e nt  ................... 7 5  
7. 6. 2.  
Gr a d e s 3 L a b or at or y A b n or m alit y or Cli ni c al E v e nt  ............................. 7 5  
7. 6. 3.  
Gr a d e s 4 L a b or at or y A b n or m ali t y or Cli ni c al E v e nt ............................. 7 6  
7. 7.  
S p e ci al Sit u ati o n s R e p ort s  ................................................................................. 7 6  
7. 7. 1.  
D efi niti o n s of S p e ci al Sit u ati o n s  .......................................................... 7 6  
7. 7. 2.  
I n str u cti o n s f or R e p orti n g S p e ci al Sit u ati o n s ....................................... 7 7  
8.  
S T A TI S TI C A L C O N SI D E R A TI O N S  .......................................................................................................... 7 8  
8. 1.  
A n al y si s O bj e cti v e s a n d E n d p oi nt s  .................................................................... 7 8  
8. 1. 1.  
A n al y si s O bj e cti v e s  ............................................................................ 7 8  
8. 1. 2.  
Pri m ar y E n d p oi nt  ................................................................................ 7 9  
8. 1. 3.  
S e c o n d ar y E n d p oi nt s  ......................................................................... 7 9  
8. 1. 4.  
E x pl or at or y E n d p oi nt s  ........................................................................ 8 0  
8. 2.  
A n al y si s C o n v e nti o n s  ........................................................................................ 8 0  
8. 2. 1.  
A n al y si s S et s  ...................................................................................... 8 0  
8. 3.  
D at a H a n dli n g C o n v e nti o n s  ............................................................................... 8 0  
8. 4.  
D e m o gr a p hi c D at a a n d B a s eli n e C h ar a ct eri sti c s  ............................................... 8 1  
8. 5.  
St ati sti c al A n al y si s  ............................................................................................. 8 1  
8. 5. 1.  
Pri m ar y A n al y si s  ................................................................................. 8 1  
8. 5. 2.  
S e c o n d ar y A n al y s e s  ........................................................................... 8 1  
8. 5. 3.  
E x pl or at or y A n al y s e s  .......................................................................... 8 2  
8. 5. 4.  
Ot h er S af et y A n al y si s  ......................................................................... 8 2  
8. 5. 5.  
E xt e nt of E x p o s ur e  ............................................................................. 8 2  
8. 5. 6.  
A d v er s e E v e nt s  .................................................................................. 8 2  
8. 5. 7.  
L a b or at or y E v al u ati o n s  ....................................................................... 8 3  
8. 6.  
P h ar m a c o ki n eti c A n al y si s  .................................................................................. 8 3  
8. 7.  
S a m pl e Si z e  ...................................................................................................... 8 3  
8. 8.  
D at a M o nit ori n g C o m mitt e e/ S p o n s or S af et y M a n a g e m e nt T e a m  ...................... 8 3  
8. 9.  
C ar di o v a s c ul ar S af et y E n d p oi nt A dj u di c ati o n C o m mitt e e ( C V E A C)  ................... 8 4  
8. 1 0.  I nt er n al I n d e p e n d e nt S af et y R e vi e w .................................................................. 8 5  
8. 1 1.  U n bli n d e d I nt eri m A n al y si s  ................................................................................ 8 5  
8. 1 2.  I nt e gr at e d S e m e n A n al y si s ................................................................................ 8 5  
9.  
R E S P O N SI BI LI TI E S .................................................................................................................................... 8 6  
9. 1.  
I n ve sti g at or R e s p o n si biliti e s  .............................................................................. 8 6  
9. 1. 1.  
G o o d Cli ni c al Pr a cti c e  ........................................................................ 8 6  
9. 1. 2.  
I R B/I E C R e vi e w a n d A p pr o v al ............................................................ 8 6  
9. 1. 3.  
I nf or m e d C o n s e nt ............................................................................... 8 6  
9. 1. 4.  
C o nfi d e nti alit y  ..................................................................................... 8 7  
9. 1. 5.  
St u d y Fil e s a n d R et e nti o n of R e c or d s  ................................................. 8 7  
9. 1. 6.  
C a s e R e p ort F or m s  ............................................................................ 8 8  
9. 1. 7.  
I n s p e cti o n s ......................................................................................... 8 9  
9. 1. 8.  
Pr ot o c ol C o m pli a n c e  .......................................................................... 8 9  

Fil g oti ni b  
 
Pr ot oc ol  G L P G 0 6 3 4 -C L -2 2 7  
Fi nal  
Gala pa g os  
A me n d me nt 2  
C O N FI D E N TI A L  
P a ge  1 0  
0 9 Se p 2 0 2 2  
9. 2.  
S p o n s or R e s p o n si biliti e s  ................................................................................... 8 9  
9. 2. 1.  
Pr ot o c ol M o difi c ati o n s  ........................................................................ 8 9  
9. 2. 2.  
St u d y R e p ort a n d P u bli c ati o n s ............................................................ 8 9  
9. 3.  
J oi nt I n v e sti g at or/ S p o n s or R e s p o n si biliti e s  ........................................................ 9 0  
9. 3. 1.  
P a y m e nt R e p orti n g  ............................................................................. 9 0  
9. 3. 2.  
A c c e s s t o I nf or m ati o n f or M o nit ori n g  ................................................... 9 0  
9. 3. 3.  
A c c e s s t o I nf or m ati o n f or A u diti n g or I n s p e cti o n s  ............................... 9 0  
9. 3. 4.  
St u d y Di s c o nti n u ati o n  ......................................................................... 9 0  
1 0.  R E F E R E N C E S  ............................................................................................................................................. 9 1  
1 1.  A P P E N DI C E S  .............................................................................................................................................. 9 3  
 
LI S T O F I N -T E X T T A B L E S  
T a bl e  5 -1.  
Pr o hi bit e d C o n c o mit a nt M e di c ati o n s  ................................................................ 5 8  
T a bl e  7 -1.  
Gr a di n g of A d v er s e E v e nt S e v erit y  .................................................................. 7 2  
 
LI S T O F I N -T E X T FI G U R E S  
Fi g ur e  3 -1.  St u d y S c h e m e .................................................................................................. 4 1  
Fi g ur e  3 -2.  D o u bl e -bli n d Tr e at m e nt P h a s e –  W e e k  1 3 E v al u ati o n  ..................................... 4 2  
Fi g ur e  3 -3.  E xt e n si o n P h a s e –  E v al u ati o n  .......................................................................... 4 3  
Fi g ur e  3 -4.  M o nit ori n g P h a s e - E v al u ati o n  ......................................................................... 4 4  
Fi g ur e  6 -1.  S e m e n C oll e cti o n S c h e m a  ............................................................................... 6 8  
 

Fil g oti ni b  
 
Pr ot oc ol  G L P G 0 6 3 4 -C L -2 2 7  
Fi nal  
Gala pa g os  
A me n d me nt 2  
C O N FI D E N TI A L  
P a ge  1 1  
0 9 Se p 2 0 2 2  
P R O T O C O L S Y N O P SI S  
G al a p a g os N V Ge ner a al De Wittel a a n L 1 1 A 3 2 8 0 0 Mec hele n, Bel gi u m  
St u d y Title:  
A Ra n d o mize d, D o u ble -bli n d, Place b o -c o ntr olle d P hase  2 St u d y t o 
E val uate t he Effect of Fil g oti ni b o n Se me n Para m eters i n A d ult Males 
wit h Acti ve R he u mat oi d Art hritis, Ps oriatic Art hritis, A n k yl osi n g 
S p o n d ylitis or N o n -ra di o gra p hic A xial S p o n d yl o art hritis.  
E u dr a C T 
N u m ber:  
Cli nic al Tri als. g o v 
I de ntifier: 
2 0 1 8 -0 0 3 9 3 3 -1 4  
  
N C T 0 3 9 2 6 1 9 5  
St u d y Ce nters 
Pl a n ne d:  
A p pr o xi matel y 1 5 0  ce nters w orl d wi de  
O bjecti ves:  
T he pri mar y o bjecti ve of t his st u d y is:  
•  T o e val uate t he effect of fil g oti ni b o n testic ular f u ncti o n as defi ne d 
b y t he pr o p orti o n of s u bjects wit h a ≥5 0 % decreas e fr o m Baseli ne  i n 
s per m c o nce ntrati o n at Wee k 1 3  
T he sec o n d ar y o bjecti ves of t his st u d y i ncl u de:  
•  T o e val uate t he effect of fil g oti ni b  o n testic ular f u ncti o n as defi ne d 
b y t he pr o p orti o n of s u bjects wit h a ≥5 0 % decreas e fr o m Baseli ne  i n 
s per m c o nce ntrati o n at Wee k 2 6  
•  T o e val uate t he effect of fil g oti ni b o n s per m t otal m otilit y at 
Wee ks  1 3 a n d 2 6  
•  T o e val uate t he effect of fil g oti ni b o n t o tal s per m c o u nt at Wee ks 1 3 
a n d 2 6 
•  T o e val uate t he effect of fil g oti ni b o n t he c ha n ge fr o m Baseli ne  i n 
s per m c o nce ntrati o n at Wee ks 1 3 a n d 2 6  
•  T o e val uate t he effect of fil g oti ni b o n ejac ulat e v ol u me at Wee ks  1 3 
a n d 2 6 
•  T o e val uate t he effect of fil g oti ni b o n s per m m or p h ol o g y at 
Wee ks  1 3 a n d 2 6  

Fil g oti ni b  
 
Pr ot oc ol  G L P G 0 6 3 4 -C L -2 2 7  
Fi nal  
Gala pa g os  
A me n d me nt 2  
C O N FI D E N TI A L  
P a ge  1 2  
0 9 Se p 2 0 2 2  
 
T he e x pl orat or y o bj ecti v es of t his st u d y i ncl u de:  
•  T o e val uate t he re versi bilit y of o bser ve d effects of fil g oti ni b o n 
testic ular f u ncti o n i n s u bjects w h o e x perie nce a ≥5 0 % decrease i n 
s per m c o nce ntrati o n, a n d/ or m otilit y a n d/ or m or p h ol o g y 
•  T o e val uate t he effect of fil g oti ni b o n se x h or m o nes, i ncl u di n g 
l utei nizi n g h or m o ne ( L H), f ollicle sti m ulati n g h or m o ne ( F S H), 
i n hi bi n B, a n d t otal test oster o ne at Wee ks  1 3 a n d 2 6  
•  T o e val uate t he s afet y a n d t olera bilit y of fil g oti ni b  
•  T o c haracterize t he plas ma p har mac o ki n etics ( P K) of fil g oti ni b a n d 
its meta b olite ( G S-8 2 9 8 4 5, f or merl y  
)  
St u d y Desi g n:  
T his is a ra n d o mize d, d o u ble -bli n d, place b o -c o ntr olle d, P hase  2 st u d y i n 
a d ult males wit h acti ve r he u mat oi d art hritis ( R A), ps ori atic art hritis 
( Ps A), a n k yl osi n g s p o n d ylitis ( A S) or n o n-ra di o gra p hic a xial 
s p o n d yl oart hritis ( nr A x S p A) w h o ha v e ha d a n i n a de q uate res p o nse t o 
pri or art hritis t hera p y as o utli ne d i n t he i ncl usi o n criteria , a n a d verse 
pr o g n osis of t heir c o n diti o n per t he i n vesti gat or, a n d w h o ma y b e nefit 
fr o m treat me nt wit h a J a n us Ki nase (J A K)-i n hi bit or.  
U p t o  2 5 0  males bet wee n t he a ges of 2 1 a n d 6 5  years (i ncl usi ve) at t he 
ti me of c o nse nt will be ra n d o mize d t o recei ve fil g oti ni b 2 0 0 m g or 
place b o o nce dail y f or  1 3  wee ks , after w hic h a n E xte nsi o n P hase will 
start.  
Ra n d o mizati o n will be stratifie d acc or di n g t o t he t y p e of r he u m atic 
c o n diti o n ( R A  or S p o n d yl oart hritis  [Ps A, A S, nr A x S p A ]), b y c o nc urre nt 
use of met h otre x ate ( M T X; yes or n o), a n d b y s p er m c o nce ntr ati o n 
meas ure d at Scree ni n g (“ Baseli ne”) acc or di n g t o t he f oll o wi n g str ata:  
•  1 5 t o 2 5  milli o n/ m L  
•  > 2 5 t o 5 0 milli o n/ m L  
•  > 5 0  milli o n/ m L  
C CI

Fil g oti ni b  
 
Pr ot oc ol  G L P G 0 6 3 4 -C L -2 2 7  
Fi nal  
Gala pa g os  
A me n d me nt 2  
C O N FI D E N TI A L  
P a ge  1 3  
0 9 Se p 2 0 2 2  
 
St u d y Sc he m e  
 
T here are 3  disti nct parts t o t he st u d y : 
1)  D o u ble – bli n d Treat me nt P hase ( Da y  1 t hr o u g h W ee k  1 3 St u d y Visit)  
2)  E xte nsi o n  P hase ( After Wee k  1 3 St u d y Visit a n d u p t o Wee k  1 5 6)  
3)  M o nit ori n g P hase ( u p t o 5 2  wee ks)  
After f ulfilli n g all selecti o n criteria, s u bjects will be ra n d o mize d t o 
fil g oti ni b or place b o ( 1: 1) at Da y 1 a n d e nter t h e D o u ble -bli n d 
T reat me nt P hase. Bas e d o n t he o utc o mes of t he  Wee k  1 3 as sess me nts 
(ie, i n di vi d ual s u bject’s res p o nse of t he u n derl yi n g r he u matic c o n diti o n 
t o t he assi g ne d tr eat me nt a n d/ or t he o bser ve d c ha n ges i n s per m 
para meters d uri n g t he d o u ble bli n d treat me nt p has e) , su bjects ma y e nt er 
t he E xte nsi o n or M o nit ori n g P hase .  
D o u ble -bli n d Tre at me nt  P h ase  (D a y  1 t hr o u g h Wee k  1 3 St u d y Visit)  
(Fi g ure  3 -2 ) 
D uri n g t h e D o u ble -bli n d T reat me nt P hase,  all s u bjects will recei ve 
bli n de d st u d y dr u g f or 1 3  wee ks  starti n g fr o m t he Da y 1/ Ra n d o mizati o n 
St u d y Visit.  At t he Wee k  1 3 st u d y visit, s per m para me ters (s ee “ Se m e n 
C ollecti o n a n d A nal ysis”) will be e val uate d t o d eter mi ne w het her  t he y 
meet a n y of t he  pre -s p ecifie d decreas e t hres h ol ds (see Defi niti o n of 
Ter ms ). I n a d diti o n, art hritis res p o nse stat us ( Art hritis N o n -res p o n der vs 
A rt hritis Res p o n der, see Defi niti o n of Ter ms ) will be deter mi ne d. As 
s o o n as Wee k 1 3 se me n res ults are a v aila ble t o t he i n vesti gat or a n d ha ve 
bee n e v al uate d , s u bjects are assi g ne d t o o n e of t he f oll o wi n g: 
•  S u bjects w h ose s per m para meters meet a n y of t h e  pre -s pecifie d 
decrease t hr es h ol d s, re gar dless of art hritis res p o ns e stat us, will 
disc o nti n ue st u d y dr u g a n d e nter t he M o nit ori n g P hase.  T hese 
s u bjects will als o ha ve a safet y f oll o w-u p visit 3 0  da ys after l ast 
st u d y dr u g d ose. 

Fil g oti ni b  
 
Pr ot oc ol  G L P G 0 6 3 4 -C L -2 2 7  
Fi nal  
Gala pa g os  
A me n d me nt 2  
C O N FI D E N TI A L  
P a ge  1 4  
0 9 Se p 2 0 2 2  
•  S u bjects w h o are Art hritis N o n -res p o n ders a n d w h ose se me n 
para meters d o n ot meet a n y of t he pre -s p ecifie d d ecreas e t hres h ol ds 
will disc o nti n ue  bli n de d st u d y dr u g a n d st art Sta n dar d of Care 
treat me nt (see Defi niti o n of Ter ms ) d uri n g t he E xte nsi o n P hase. 
T hese s u bjects will als o ha ve a  safet y f oll o w-u p visit 3 0  da ys after 
last st u d y dr u g d ose. 
•  S u bjects w h o are A rt hritis Res p o n ders a n d w h ose se me n para meters 
d o n ot meet a n y of t he  pre -s pecifi e d decrease t hres h ol ds will be 
u n bli n de d b y t he i nteracti ve we b res p o ns e s yste m (I W R S) a n d e nt er 
t he E xte nsi o n P hase. S u bjects o n fil g oti ni b will c o n vert t o o pe n -la bel 
fil g oti ni b a n d s u bjects r ecei vi n g pl ace b o will s witc h t o S ta n dar d of 
C are treat me nt. 
E xte nsi o n P h ase ( After Wee k 1 3 t hr o u g h Wee k  1 5 6  St u d y Visit)  
(Fi g ure  3 -3 ) 
I n t he E xte nsi o n P hase, s u bjects will recei v e o pe n-la bel treat me nt 
(fil g oti ni b or Sta n dar d of Care) a n d h a ve a st u d y visit e ver y 1 3  wee ks 
t hat i ncl u des se me n a n al ysis. T he first sc he d ule d visit of t he E xte nsi o n 
P hase occ urs at Wee k  2 6.  
I n case s e me n para meters at a n y visit (i ncl u di n g Wee k 1 5 6) meet a n y of 
t he pre-s pecifie d d ecreas e t hres h ol ds, s u bjects will e nter t he M o nit ori n g 
P hase.  
D uri n g t h e E xte nsi o n P hase, Sta n dar d of C are a n d bac k gr o u n d tr eat me nt 
c o nc o mita nt t o fil g oti ni b ma y b e o pti mize d at t he discreti o n of t he 
i n vesti gat or, ta ki n g i nt o c o nsi derati o n t he pr ot oc ol restricti o ns 
( Secti o ns 5. 3  a n d 5. 4 ). 
I n case a s u bject nee ds t o be treate d wit h a pr o hi bite d me dicati o n  (see 
Ta ble  5 -1 ), f or i nsta nce t o c o ntr ol t heir r he u matic c o n diti o n, t he s u bject 
will disc o nti n ue t he st u d y a n d c o m plete a n E arl y Ter mi nati o n ( E T) visit 
(i ncl u di n g se m e n c ollecti o n). F or s u bjects o n fil g oti ni b, t his will be 
f oll o we d b y a safet y f oll o w-u p visit 3 0  da ys afte r last st u d y dr u g d ose.  
All s u bjects w h o di d n ot e nter t he M o nit ori n g P hase will c o nti n ue t he 
st u d y u ntil t he Wee k 1 5 6 visit.  
M o nit ori n g P h ase ( u p t o 5 2  wee ks)  (Fi g ure  3 -4 ) 
S u bjects w h ose s per m  para meters  me et a n y of t h e pre-s pecifie d decrease 
t hres h ol ds will s witc h t o t he M o nit ori n g P hase i m me diatel y. S u bjects o n 
d o u ble -bli n d treat me nt or  o pe n -la bel fil g oti ni b w h o e nter t he M o nit ori n g 
P hase will disc o nti n ue st u d y dr u g a n d start Sta n dar d of Care. T h ese 
s u bjects will als o ha ve a safet y f oll o w-u p visit 3 0  da ys after l ast st u d y 
dr u g d os e.  S u bjects o n Sta n dar d of Care will c o nti n ue treat me nt.  

Fil g oti ni b  
 
Pr ot oc ol  G L P G 0 6 3 4 -C L -2 2 7  
Fi nal  
Gala pa g os  
A me n d me nt 2  
C O N FI D E N TI A L  
P a ge  1 5  
0 9 Se p 2 0 2 2  
All s u bjects  w h o e nter t h e  M o nit ori n g P hase will u n der g o se me n 
e val uati o ns e ver y 1 3  wee ks  starti n g fr o m t heir e ntr y i nt o t he M o nit ori n g 
P hase, f or u p t o 5 2  wee ks or u ntil Re versi bilit y (see Defi niti o n of 
Ter ms ) is met, w hic he v er is ac hie ve d first.  
I n case a s u bject nee ds t o be treate d wit h a pr o hi bite d me dicati o n  (see 
Ta ble  5 -1 ), f or i nsta nce t o c o ntr ol t heir r he u matic c o n diti o n, t he s u bject 
will disc o nti n ue t he st u d y a n d c o m plete a n E T visit (i ncl u di n g se me n 
c ollecti o n).  
D at a M o nit ori n g C o m mittee ( D M C) /S p o ns or S af et y M a n a ge me nt 
Te a m ( S S M T)   
A n e xter nal, m ulti disci pli nar y D M C, i ncl u di n g a n e x pert i n male 
fertilit y, will re vie w t he pr o gress of t he st u d y a n d perf or m i nteri m 
u n bli n de d re vie ws of s afet y d ata, if nee de d ( details i n Secti o n  8. 8 ).  
T he D M C  has m o nit ore d t he st u d y u ntil t he date of pr ot oc ol 
a me n d me nt  2 , i ncl u di n g t he data f or t he sec o n d u n bli n de d i nteri m 
a nal ysis (I A 2) . As of a m e n d me nt 2 , the D M C will be dec o m missi o ne d.  
T he safet y a n d pr o gress of t he re mai n d er of t he st u d y will c o nti n ue t o be 
m o nit ore d b y t he S p o ns or  Me dical Lea der a n d Me dical M o nit or  or 
desi g nee , pr o vi di n g u p dates d uri n g  re g ular S p o ns or me dical m o nit ori n g 
o versi g ht meeti n gs acr oss t he fil g oti ni b pr o gra m . If nee d e d, safet y iss ues 
will be escalate d t o t he S S M T  per i nter nal sta n dar d pr oce d ures . T he 
S S M T ca n c o ns ult e xter nal e x perts, if dee me d necessar y, a n d ca n re vie w 
data i n a n  u n bli n de d fas hi o n.  
 
I nter n al I n de pe n de nt S afet y Re vie w Te a m 
A  S p o ns or i nter nal u n bli n de d tea m, i n de pe n d e nt of t he bli n de d st u d y 
tea m will be asse m ble d. T he S p o ns or i nter nal u n bli n de d tea m ma y  be 
gra nte d access t o  bli n de d a n d  u n bli n de d cli nical d ata i ncl u di n g tr eat me nt 
assi g n me nt t o cl osel y m o nit or se me n para m eters  i n real-ti me. T his 
i nter nal tea m will be s u p p orte d b y a n e xter nal e x pert i n male fertilit y. T o 
miti gate t he ris k of i na d verte n tl y releasi n g treat me nt assi g n me nt t o sites 
a n d s u bjects, t he i nter nal tea m will kee p t he u n bli n de d i nf or mati o n 
c o nfi de ntial a n d will n ot c o m m u nicate a n y i nf or mati o n t o t he bli n de d 
st u d y tea m, site staff or s u bjects. Data u n bli n di n g d ue t o me dical 
e mer ge n c y will f oll o w sta n dar d S p o ns or  pr oce d u res. Pri or t o a n y 
u n bli n di n g of t he c o m mittee, t he I nter nal I n de p e n d e nt Safet y Re vie w 
c o m mittee’s s pecific acti vities will be defi ne d b y a m ut uall y a gree d 
u p o n c harter, w hic h will defi ne t he c o m mittee me m bers hi p, c o n d uct, 
a n d meeti n g sc he d ule.  
As of a me n d m e nt 2, t he I nter nal I n de p e n de nt Safet y Re vie w T ea m  will 
be dec o m missi o ne d. Safet y re vi e ws will be c o v ere d b y t he S S M T.  

Fil g oti ni b  
 
Pr ot oc ol  G L P G 0 6 3 4 -C L -2 2 7  
Fi nal  
Gala pa g os  
A me n d me nt 2  
C O N FI D E N TI A L  
P a ge  1 6  
0 9 Se p 2 0 2 2  
Ke y C o nc o mit a nt Me dic ati o n C o nsi der ati o ns:  
If usi n g c o n ve nti o nal s y nt hetic disease -m o dif yi n g a ntir he u matic dr u g 
(cs D M A R D ) t hera p y pri or t o t he st u d y , s u bjects are per mitte d t o 
c o nti n ue t he f oll o wi n g dr u gs d uri n g t he st u d y, al o ne or i n c o m bi nati o n 
( wit h t he e x ce pti o n of t he M T X-lefl u n o mi de [ L E F] c o m bi nati o n) a n d 
m ust ha ve bee n o n a st a ble d ose of t he dr u g f or at least 4  wee ks pri or t o 
Scree n i n g a n d re mai n o n a sta ble d ose d uri n g t he D o u ble -bli n d 
Treat me nt P hase  of t he st u d y (sta bl e d ose i n all cases is defi ne d as n o 
c ha n ge i n pr escri pti o n):  
a. M T X oral or pare nteral u p t o 2 5  m g/ wee k ( pl us c o nc o mita nt use of 
f olic or f oli nic aci d s u p pl e me ntatio n as per l o cal S ta n dar d of C are)  
b.  L efl u n o mi de ( LE F ) u p t o 2 0  m g/ da y orall y  
c. H y dr o x yc hl or o q ui ne u p t o 4 0 0  m g/ da y or c hl or o q ui ne u p t o 
2 5 0  m g/ da y  
d.  A pre milast orall y u p t o 3 0  m g t wice d ail y  
Oral c ortic oster oi ds ma y be use d at ≤1 0  m g/ da y ( of pre d nis o ne or 
e q ui vale nt), pr o vi de d t h at t he prescri pti o n has bee n sta ble f or at least 
4  wee ks  pri or t o D a y  1  a n d u p t o t he Wee k  1 3 visit . F or s u bjects 
c o nti n ui n g o n o pe n -l a bel fil g oti ni b after t h e Wee k 1 3  visit, t he s u bject's 
ster oi d d ose ca n b e re d u ce d base d o n i n vesti gat or j u d g me nt (a n d ma y 
als o be a dj uste d bac k u p as nee de d), b ut s h o ul d N O T e x cee d t he sta ble 
d ose prescri be d at Baseli ne ( Ra n d o mizati o n/ Da y  1 ). F or s u bjects 
c o nti n ui n g Sta n dar d of Care  tr eat me nt, t he d ose of c ortic oster oi ds ca n 
als o be re d u ce d or i ncrease d b ut s h o ul d n ot e x cee d 2 0  m g / da y ( of 
pre d nis o ne or e q ui vale nt).  
If a n o n -ster oi dal a nti-i nfla m mat or y dr u g (N S AI D ) or c ycl o o x y ge nase -2 
(C O X -2 ) i n hi bit or is use d, it m ust n ot e x cee d t he ma xi m u m d ose 
per mitte d as per l ocal la b el a n d m ust ha ve bee n us e d at a sta ble d os e f or 
at least 2  wee ks pri or t o Da y  1 a n d re mai n o n a st a ble d ose d uri n g t he 
D o u ble -bli n d Treat me nt P hase  of  t he st u d y. 
S u bjects s h o ul d n ot recei ve s ulfasalazi ne at a n y ti me, be gi n ni n g 
2 6  wee ks pri or t o Scree ni n g u ntil t he e n d of st u d y .  
A list of per mitte d a n d pr o hi bite d me dicati o ns is pr o vi de d i n t he 
e x cl usi o n criteria a n d Secti o n  5. 3 . 
N u m ber of 
S u bjects 
Pla n ne d:  
U p t o 2 5 0  s u bjects t o ha ve 2 0 0 e val ua bl e s u bjects  
Tar get 
P o p ulati o n:  
Males bet wee n t he a ges of 2 1  a n d 6 5 years (i ncl usi ve) wit h acti ve R A, 
Ps A, A S or nr A x S p A  

Fil g oti ni b  
 
Pr ot oc ol  G L P G 0 6 3 4 -C L -2 2 7  
Fi nal  
Gala pa g os  
A me n d me nt 2  
C O N FI D E N TI A L  
P a ge  1 7  
0 9 Se p 2 0 2 2  
D urati o n of 
Treat me nt:  
T he d urati o n of  bli n de d  treat me nt is a p pr o xi matel y 1 3  wee ks , f oll o we d 
b y a n o p e n -la b el E xte nsi o n P hase of u p t o 1 4 3  wee ks . S u bjects e nteri n g 
t he M o nit ori n g P hase will be f oll o we d f or u p t o 5 2 wee ks or u ntil 
Re versi bilit y (see Defi niti o n  of  Ter ms ) is met, w hi c he ver is ac hie ve d 
first.  
Dia g n osis a n d 
Mai n Eli gi bilit y 
Criteria:  
F or a c o m plete list of st u d y i ncl usi o n a n d e x cl usi o n criteria, please refer 
t o Secti o ns  4. 2  a n d 4. 3 . 
Ke y i ncl usi o n criteria:  
•  
Males bet wee n t he a ges of 2 1 a n d 6 5  (i ncl usi ve) o n t he da y of 
si g ni n g i nf or me d c o ns e nt  
•  
Dia g n osis of R A , Ps A, A S, or nr A x S p A f or at least 1 2  wee ks  pri or 
t o S cree ni n g, meeti n g t he c orres p o n di n g s pecific classificati o n 
criteria:  
⎯ R A, A merica n C olle ge of R he u m at ol o g y ( A C R)/ E ur o pea n 
Lea g ue A gai nst R he u matis m ( E U L A R) 2 0 1 0  
⎯ Ps A, Classificati o n criteria f or Ps oriatic Art hritis ( C A S P A R) 
criteria  
⎯ A S or nr A x S p A, Assess me nt of S p o n d yl oart hritis I nter nati o nal 
S ociet y ( A S A S) criteria f or a xial s p o n d yl o art hritis  
•  
F or  R A, Ps A, A S, or nr A x S p A, s u bject meets t he f oll o wi n g criteria:  
⎯ R A  
■ I n a de q uat e res p o ns e or  i nt olera nt t o ≥1 2 -wee ks ’ c o urse of 
cs D M A R D or bi ol o gi cal D M A R D ( b D M A R D) t h era p y f or 
R A  
■ Ha ve a n Cli nical Dise ase Acti vit y I n de x ( C D AI) > 1 0 at 
scree ni n g 
⎯ Ps A  
■ I n a de q uat e res p o ns e or  i nt olera nt t o ≥1 2 -wee ks ’ c o urse of 
cs D M A R D or b D M A R D t hera p y f or Ps A  
■ Ha ve a Disease Acti vit y i n Ps oriatric Art hritis ( D A P S A) 
sc ore > 1 4 at S cree ni n g  
⎯ A xial S p o n d yl oart hritis (a p plica ble t o t h ose wit h dia g n osis of A S 
or nr A x S p A)  
■ I n a de quat e res p o ns e or  i nt olera nt t o at least 2 N S AI Ds, 
w hic h ma y i ncl u de C O X -2 i n hi bit ors pres cri be d f or a t otal 
peri o d of ≥4  wee ks O R t o a n ≥1 2  wee k c o urse of cs D M A R D 
or bi ol o gical disease m o dif yi n g a nti -r he u matic dr u g 
(b D M A R D ) t hera p y f or s p o n d yl oart hritis 

Fil g oti ni b  
 
Pr ot oc ol  G L P G 0 6 3 4 -C L -2 2 7  
Fi nal  
Gala pa g os  
A me n d me nt 2  
C O N FI D E N TI A L  
P a ge  1 8  
0 9 Se p 2 0 2 2  
■ Ha ve a Bat h A n k yl osi n g S p o n d ylitis Diseas e Acti vit y I n de x 
( B A S D AI) ≥4 at S cree ni n g  
■ At S cree ni n g, s u bjects s h o ul d ha ve a hi g h -se nsiti vit y 
C -reacti ve pr otei n (hs C R P) > 0. 3  m g/ d L O R sacr oiliitis 
acc or di n g t o t he m o difie d Ne w Y or k ( N Y) criteri a O R a 
hist or y of acti ve i nfla m m ati o n o n ma g n etic res o n a nce 
i ma gi n g ( M RI) c o nsiste nt wit h  sacr oiliitis wit hi n 2  year s of 
scree ni n g 
•  
T he mea n of 2  s e parate s e me n sa m ples c ollecte d at Scree ni n g m ust 
meet t he f oll o wi n g mi ni m u m criteria  (i n acc or da nce wit h 
Secti o n  6. 1 1 ): se me n v ol u me ≥1. 5 m L, t otal s per m/ejac ulate 
≥3 9  milli o n, s per m c o nce ntrati o n ≥1 5  milli o n/ m L, s per m t otal 
m otilit y ≥4 0 %, a n d n or mal s per m m or p h ol o g y ≥3 0 %  
Ke y E x cl usi o n Criteria  
•  
Pre vi o usl y or c urre ntl y d oc u me nte d pr o ble ms wit h male 
re pr o d ucti ve h ealt h i ncl u di n g b ut n ot li mite d t o pri mar y 
h y p o g o na dis m, sec o n dar y h y p o g o na dis m, or re d u ce d fertilit y  
•  
Use of a n y pr o hi bite d c o nc o mita nt me dicati o n(s)  as descri be d i n 
Secti o n  5. 3  (a n d Ta ble  5 -1 ) 
•  
Acti ve t u berc ul osis ( T B) or u ntreate d l ate nt T B  (Secti o n  4. 2  
I n cl usi o n Criteria, 1 0 ) 
•  
I nfecti o n wit h He p atitis B, He p atitis C or h u ma n i m m u n o deficie nc y 
vir us ( HI V)  (Secti o n  4. 3 , E x cl usi o n Criteria, #2 2 -2 4 ) 
St u d y 
Pr o ce d ures/  
Fre q ue nc y:  
After writte n i nf or me d c o nse nt is o btai ne d, Scree ni n g  pr oce d ures will 
c o m me nce , i ncl u di n g b ut n ot li mite d t o, e val uati o n of eli gi bilit y criteria,  
me dical hist or y, r o uti ne bl o o d a n d uri ne c ollecti o n f or la b orat or y 
a nal ys es a n d s e me n sa m ple c ollecti o n. All s u bjects meeti n g eli gi bilit y 
criteria will be ra n d o mize d 1: 1 t o recei v e fil g oti ni b 2 0 0  m g o nce dail y or 
place b o o nce dail y f or 1 3  wee ks , i n a bli n de d fas hi o n .  
All s u bjects will ret ur n t o t he cli nical st u d y ce nter t o be e val uate d f or 
cli nical a n d la b orat or y assess me nts at Wee k  2, Wee k  4, Wee k  8 a n d 
Wee k  1 3 , i ncl u di n g se me n sa m ple c ollecti o n d uri n g Wee k  1 3 visit.   
S u bjects e nteri n g t he E xte nsi o n P hase ( o n o pe n -l a bel fil g oti ni b or o n 
Sta n dar d of Care) will u n der g o sc he d ul e d visits f or safet y ass ess me nts 
(i ncl u di n g se m e n a nal ysis) e ver y 1 3 wee ks u p t o Wee k  1 5 6.  
S u bjects e nteri n g t he M o nit ori n g P hase ( o n Sta n d ar d of Care) will 
u n der g o sc he d ul e d visi ts f or safet y assess me nts e v er y 1 3 wee ks u p t o 
Wee k  5 2 or u ntil Re versi bilit y is met.  

Fil g oti ni b  
 
Pr ot oc ol  G L P G 0 6 3 4 -C L -2 2 7  
Fi nal  
Gala pa g os  
A me n d me nt 2  
C O N FI D E N TI A L  
P a ge  1 9  
0 9 Se p 2 0 2 2  
S p arse Pl as m a P K S a m ple C ollecti o n  
S parse plas ma P K sa m pl es will be c ollecte d fr o m all s u bjects at least 
3 0  mi n utes p ost d ose at t he Wee k  2 visit, at a n y ti me at t he Wee k  4 visit 
a n d pri or t o st u d y dr u g d osi n g at t he Wee k  1 3 visit. At t he Wee k  2 6 
visit, o nl y s u bjects o n o pe n -la bel fil g oti ni b will pr o vi de a P K sa m ple 
pri or t o st u d y dr u g a d mi nistrati o n.  
Se me n C ollecti o n a n d A n al ysis : 
At eac h of t h e f oll o wi n g ti me p oi nts, s u b jects will pr o vi de 2 se me n 
sa m ples c ollecte d wit hi n a 1 4-da y peri o d. Eac h s e me n sa m ple m ust be 
c ollecte d wit h a n ejac ulati o n free p eri o d of  ≥4 8  h o urs a n d ≤7  da ys 
( Secti o n 6. 1 1 ):  
•  Scree ni n g ( Bas eli ne)  
•  After t he D o u bl e-bli n d Treat me nt P hase ( Wee k 1 3 st u d y visit)  
•  E ver y 1 3  wee ks d uri n g t he E xte nsi o n P hase  
•  E ver y 1 3  wee ks d uri n g t he M o nit ori n g P hase  
•  At t he Earl y Ter mi n ati o n Visit 
I n s elect i nsta nces w here t he se me n sa m ple wit h q uesti o ne d val ue(s) is 
f o u n d t o be n o n -assess a ble or i n vali d ( e g, c ollecti o n wit h o ut a d here nce 
t o ejac ulati o n-free p eri o d; i nterc urre nt ill ness or d e h y drati o n at ti me of 
c ollecti o n; i nc o m plete ca p t ure of se me n s a m ple; a n d/ or sa m ple 
pr ocessi n g or se m e n a nal ysis t hat de viates fr o m sta n dar dize d pr oce d ure ), 
a t hir d se me n sa m ple , w he n i n dicate d, m ust be c ollecte d wit hi n 1 4  da ys 
of t he pri or sa m ple , wit h a n ejac ul ati o n free p eri o d of  ≥4 8  h o urs a n d 
≤7  da y s. All de cisi o ns o n retesti n g a n y se me n/s per m para meter 
(ie, o btai ni n g a t hir d se m e n sa m ple at a n y of t he a b o ve ti me p oi nts) m ust 
be a p pr o ve d b y t h e S p o ns or  Me dical Lea der  or desi g nee b ef ore t he 
retest. 
Test Pr o d uct, 
D ose, a n d M o de of 
A d mi nistr ati o n:  
2 0 0 -m g fil g oti ni b ta blet orall y o n ce dail y  
Refere nce 
T her a p y, D ose, 
a n d M o de of 
A d mi nistr ati o n:  
Place b o -t o-matc h  t a blet orall y o n ce dail y 
Re q uire d 
B ac k gr o u n d 
Me dic ati o n:  
Per mitte d me dicati o n as descri be d i n t he c o nc o mita nt me dicati o ns 
secti o n  

Fil g oti ni b  
 
Pr ot oc ol  G L P G 0 6 3 4 -C L -2 2 7  
Fi nal  
Gala pa g os  
A me n d me nt 2  
C O N FI D E N TI A L  
P a ge  2 0  
0 9 Se p 2 0 2 2  
Criteri a f or 
E v al u ati o n:  
 
Safet y:  
Se me n sa m ples will be c ollecte d as o utli ne d i n Secti o n  6. 1 1 . Se x 
h or m o nes i ncl u di n g L H , F S H , i n hi bi n B a n d t otal test oster o ne will be 
meas ure d at vari o us ti me p oi nts d uri n g t his st u d y.  
Ot her as pects of safet y will be assesse d b y t he re p orti n g of a d verse 
e ve nts ( A Es), cli nical la b orat or y e v al uati o ns ( he m at ol o g y, c h e mistr y, 
a n d uri nal ysis), p h ysical e x a mi nati o n , vital si g ns a n d at vari o us ti me 
p oi nts d uri n g t he st u d y. C o nc o mita nt me dicati o n usa ge will als o be 
assesse d t hr o u g h o ut t he st u d y  
P K : 
Plas ma c o nce ntr ati o ns of fil g oti ni b a n d its meta b olite ( G S -8 2 9 8 4 5) will 
be a nal yz e d.  
St atistic al 
Met h o ds:  
T he pri mar y e n d p oi nt is t he pr o p orti o n of s u bjects wit h a ≥5 0 % decreas e 
i n s per m c o nce ntr ati o n fr o m Baseli ne  at Wee k  1 3.  
A c u m ulati ve distri b uti o n pl ot f or t he perce nt c ha n ge fr o m Baseli ne  i n 
s per m c o nce ntrati o n at Wee k 1 3 f or eac h treat me nt gr o u p will be 
c o nstr ucte d. T he x -a xis will dis pla y p erce nt c ha n ges fr o m Baseli ne  
s per m c o nce ntrati o n ra n gi n g fr o m 1 0 0 % decreas e (ie, -1 0 0 % or 
az o os per mia) t o t he ma xi mal o bser ve d i ncreas e. T he y -a xis wi ll dis pla y 
t he pr o p orti o n of s u bjects w h o e x perie nce d a perce nta ge c h a n ge i n 
s per m c o nce ntrati o n e q u al t o or less t ha n t he c orres p o n di n g x -a xis val ue 
at W ee k  1 3. T his met h o d is s u g geste d i n F o o d a n d Dr u g 
A d mi nistrati o n’s ( F D A)  G ui da nce f or I n d ustr y: T estic ular t o xicit y: 
E val uati o n D uri n g Dr u g De vel o p me nt” ( Oct o ber 2 0 1 8 ).  
T he pr o p orti o n of s u bjects e x perie nci n g at least a 5 0 % decrease i n s p er m 
c o nce ntr ati o n fr o m Baseli ne  will be calc ulate d t o get her wit h t he 
ass ociate d 9 5 % c o nfi de n ce i nter val f or t he differe nce bet w ee n t he 
fil g oti ni b a n d place b o gr o u ps. A d diti o nal assess me nts of se me n 
para meters ma y be c o n d ucte d.  
All c o nti n u o us e n d p oi nts will be s u m marize d usi n g a n 8 -n u m ber 
s u m mar y ( n, mea n, sta n d ar d de viati o n [ S D], me dia n, 1st q uartile [ Q 1], 
3r d q uartile [ Q 3 ], mi ni m u m, ma xi m u m) b y treat me nt gr o u p. All 
cate g orical e n d p oi nts will be s u m marize d b y t he n u m ber a n d perce nt a ge 
of s u bjects w h o meet t he e n d p oi nt defi niti o n.  
Safet y e n d p oi nts will be a nal yze d b y t h e n u m ber a n d perce nt of s u bjects 
wit h e ve nts or a b n or mal ities f or cate g orical val u es or 8-n u m ber 
s u m mar y ( n, mea n, S D, me dia n, Q 1, Q 3, mi ni m u m, ma xi m u m) f or 
c o nti n u o us data b y d osi n g gr o u p.  
A sa m ple siz e of 1 0 0  e val ua ble s u bjects per gr o u p, w here e val ua ble is 
defi ne d as s u bjects i n t he Se me n A nal ysis Set  ( Sectio n  8. 2. 1. 2 ), is 
a de q uate f or t he p ur p os es of esti mati n g c u m ulati v e distri b uti o n c ur ves 

Fil g oti ni b  
 
Pr ot oc ol  G L P G 0 6 3 4 -C L -2 2 7  
Fi nal  
Gala pa g os  
A me n d me nt 2  
C O N FI D E N TI A L  
P a ge  2 1  
0 9 Se p 2 0 2 2  
a n d pr o d uci n g a 9 5 % c o nfi de nce i nter val wi dt h t hat is reas o na bl y 
narr o w f or t he perce nt a ge of s u bjects i n eac h gr o u p w h o e x perie nce a 
≥5 0 % decrease i n s per m c o nce ntr ati o n c o m pare d t o Baseli ne . Ass u mi n g 
a 2 0 % rat e of n o n -e val ua ble s u bjects at Wee k  1 3, u p t o  1 2 5  s u bjects per 
ar m ma y be e nr olle d.  
Res ults of t his st u d y ma y be p o ole d wit h t he res ults of a se parate st u d y 
bei n g c o n d ucte d i n s u bjects wit h i nfla m mat or y b o wel disease ( Pr ot o c ol 
G S -U S -4 1 8 -4 2 7 9) wit h t he sa me o bjecti ve. T he t otal pla n ne d n u m ber of 
s u bjects i n b ot h st u dies c o m bi ne d will be a p pr o xi matel y 2 5 0  s u bjects. 
U n bli n de d i nteri m a nal ys es of t he cli nical st u d y data will be perf or m e d 
b y t he S p o ns or f or re g ul at or y s u b missi o ns w he n 2 0 0 s u bjects 
(e g, p o ole d data fr o m G S -U S -4 1 8 -4 2 7 9 a n d G L P G 0 6 3 4 C L -2 2 7), a n d/ or 
w he n s o me defi n e d s u bset(s) of s u bj ects, h a ve c o m plete d t he Wee k  1 3 
a n d Wee k 2 6 assess me nts  (first u n bli n de d i nteri m a nal ysis [I A 1]), a n d 
w he n c o m plete re versi bilit y data f or all s u bjects w h o e ntere d t he 
M o nit ori n g P hase at t hes e ti me p oi nts is a vai la ble (I A 2; see 
Defi niti o n  of  Ter ms ). A Data I nte grit y a n d C o m m u nicati o n Pla n f or t he 
i nteri m a nal ysis will be d e vel o pe d pri or t o u n bli n di n g. T he a nal yses will 
be c o n d ucte d pri maril y t o e val uate t he testic ul ar safet y a n d f urt her 
details will be descri be d i n t he statistical a nal ysis pla n (S A P ).  
F or o n g oi n g s u bjects, the st u d y tea ms a n d st u d y st aff at t he sites a n d all 
ot her staff directl y i n v ol ve d i n t he c o n d uct of t he st u d y will re mai n 
bli n de d t o t he d o u ble -bli n d p hase treat me nt assi g n me nts u ntil t he fi nal 
a nal ysis w h e n t he dat a base has bee n l o c ke d.  P u blicati o n of t he I A 2 d ata 
is pla n ne d b y t he S p o ns or. T his p u blicati o n will c o ntai n gr o u p le vel data 
f or t he e ntire st u d y p o p ul ati o n, b ut will u n bli n d t he st u d y tea ms a n d staff 
directl y i n v ol ve d i n t he c o n d uct of t he st u d y t o t he i n di vi d ual baseli ne 
treat me nt assi g n me nt of s u bjects w h o c o m plete d t he st u d y b ef ore I A 2.  
 
T his st u d y will be c o n d u cte d i n acc or da n ce wit h t he g ui d eli nes of G o o d Cli nical Practice ( G C P)  
i ncl u di n g arc hi vi n g of esse ntial d oc u me nts. 

Fil g oti ni b  
 
Pr ot oc ol  G L P G 0 6 3 4 -C L -2 2 7  
Fi nal  
Gala pa g os  
A me n d me nt 2  
C O N FI D E N TI A L  
P a ge  2 2  
0 9 Se p 2 0 2 2  
D E FI N I TI O N O F T E R M S 
M o nit ori n g P hase  
A s u bj ect w h o e x perie nces a ≥5 0 % decrease i n s per m c o nce ntrati o n, a n d/ or 
m otilit y, a n d/ or m or p h ol o g y at a n y ti me after 1 3  wee ks will start t he M o nit ori n g 
P hase. Se me n sa m ples will be c ollecte d e ver y 1 3  wee ks starti n g fr o m t heir e ntr y 
i nt o t he M o nit ori n g P hase, f or u p t o 5 2 wee ks or u ntil Re versi bilit y is met, 
w hic he ver is ac hie ve d first.  
Art hritis Res p o n der  
F or R A, Ps A, A S or nr A x S p A - i m pr o ve me nt i n p h ysicia n’s gl o bal assess me nt 
( P h G AD A ) of at least 2 0 % c o m pare d t o Baseli ne  ( Da y 1)  at t he s pecifie d 
assess me nt ti me   
Art hritis N o n -res p o n der 
F or R A, Ps A, A S or nr A x S p A, a s u bj ect w h o d oes n ot f ulfill t he defi niti o n of 
Art hritis Res p o n der at t he s pecifie d assess me nt ti me p oi nt (refer t o A p pe n di x  2 )  
Pre -s pecifie d decrease 
t hres h ol d 
A ≥5 0 % decrease i n s per m c o nce ntrati o n, a n d/ or m otilit y, a n d/ or m or p h ol o g y i n 
c o m paris o n t o Baseli ne  ( Screeni n g) . T he mea n of val ues f or eac h of t he s per m 
para meters ( meas ure d fr o m 2  se parate se me n sa m ples) will be use d i n all 
a nal yses. Sa m ples will be c ollecte d wit hi n a 1 4 -da y peri o d a n d wit h a n 
ej ac ulati o n-free peri o d of ≥4 8  h o urs a n d ≤7  da ys.  
Re versi bilit y  
Re versi bilit y is met w he n all s e me n para meter(s) q ualif yi n g t he s u bj ect t o e nter 
i nt o t he M o nit ori n g P hase ret ur n(s) t o greater t ha n 5 0 % of B aseli ne (ie, t o 
greater t ha n [ 0. 5 0 x mea n of 2 s per m c ollecti o ns c ollecte d at t he Scree ni n g visit 
(ie, B aseli ne )]).  
W ee k 1 3  
T he W ee k 1 3 St u d y Visit occ urs o nce a s u bj ect c o m pletes 1 3  wee ks of bli n de d 
st u d y dr u g, a n d is i ncl usi ve of all st u d y assess me nts perf or me d at t he cli nic visit 
a n d t he se me n sa m ple c ollecti o n visits ass ociate d wit h t his ti me p oi nt.  
W ee k 2 6  
T he  W ee k 2 6 St u d y Visit occ u rs o nce a s u bj ect c o m pletes  1 3  wee ks of o pe n -
la bel fil g oti ni b or Sta n dar d of Care treat me nt d uri n g t he E xt e nsi o n P hase, a n d is 
i ncl usi ve of all st u d y assess me nts perf or me d at t he cli nic visit a n d t he se me n 
sa m ple c ollecti o n visits ass oci ate d wit h t his ti me p oi nt.  
Sta n dar d of Care  
L ocall y a p pr o ve d treat me nt, a cce pte d b y me dical e x perts as a pr o per treat me nt 
f or r he u matic c o n diti o ns, pres cri be d acc or di n g t o best cli nic al practice, wit h n o 
k n o w n testic ular t o xicit y. Sta n dar d of Care w ill be rei m b urse d b y t he s p o ns or 
u ntil t he W ee k  1 5 6 visit of t he E xte nsi o n P hase or u ntil a s u bj ect c o m pletes t he 
M o nit ori n g P hase.  
St u d y Dr u g  
St u d y dr u g is defi ne d as bli n d e d fil g oti ni b or place b o d uri n g t he D o u ble -bli n d 
Treat me nt P hase a n d o pe n -la bel fil g oti ni b d uri n g t he E xte nsi o n P hase. 
First  u n bli n de d  i nteri m 
a nal ysis (I A 1)  
U n bli n de d Wee k 2 6 a nal ysis t o be perf or me d after at least 2 0 0  e val ua ble 
s u bj ects p o ole d acr oss st u dies G S-U S -4 1 8 -4 2 7 9 (G L P G 0 6 3 4 -C L -2 2 8)  a n d 
G L P G 0 6 3 4 -C L -2 2 7 c o m plete Wee k 1 3 a n d e val ua ble s u bj ects fr o m St u d y 
G L P G 0 6 3 4 -C L -2 2 7 c o m plete Wee k 2 6 or per ma ne ntl y disc o nti n ue fr o m st u d y 
dr u g. Referre d t o as ‘ Wee k 2 6 A nal ysis’ i n t he S A P.  
Sec o n d  u n bli n de d  i nteri m 
a nal ysis (I A 2)  
U n bli n de d Wee k 2 6 a nal ysis t o be perf or me d after all s u bj ects reac h Wee k 2 6 
a n d all s u bj ects wit h a ≥ 5 0 % decrease i n s per m c o nce ntrati o n, a n d/ or m otilit y, 
a n d/ or m or p h ol o g y u p t o Wee k 2 6 e nter t he M o nit ori n g P hase a n d eit her meet 
re versi bilit y criteria or are f oll o we d off-treat me nt f or 5 2 wee ks, w hic he ver 
occ urs first. Referre d t o as ‘ Wee k 2 6 a n d Re versi bilit y A nal ysis f or 
Pre -s pecifie d S per m Decreases U p t o Wee k 2 6’ i n t he S A P.  
 

Fil g oti ni b  
 
Pr ot oc ol  G L P G 0 6 3 4 -C L -2 2 7  
Fi nal  
Gala pa g os  
A me n d me nt 2  
C O N FI D E N TI A L  
P a ge  2 3  
0 9 Se p 2 0 2 2  
G L O S S A R Y O F A B B R E VI A TI O N S A N D D E FI NI TI O N O F T E R M S  
A b  
anti b o d y  
A C R ( 2 0/ 5 0/ 7 0)  
A merica n C olle ge  of R he u mat ol o g y ( 2 0/ 5 0/ 7 0 % i m pr o ve me nt)  
A E  
a d verse e ve nt  
A L T  
ala ni ne a mi n otra nsferas e  
A N C  
a bs ol ute ne utr o p hil c o u nt  
A N C O V A  
a nal ysis of c o varia nce  
A S  
a n k yl osi n g s p o n d ylitis  
A S A S  
Assess me nt of S p o n d yl o art hritis I nt er nati o nal S ociet y  
A S T  
as partate a mi n otra nsferas e  
A U C  
area u n d er t he pl as ma dr u g c o n ce ntr ati o n -ti me c ur ve 
B A S D AI  
Bat h A n k yl osi n g S p o n d ylitis Disease Acti vit y  
b D M A R D  
bi ol o gical diseas e -m o dif yi n g a ntir he u m atic dr u g  
B L Q  
bel o w t he li mit of q ua ntitati o n  
B U N  
bl o o d urea nitr o ge n  
C A S P A R  
Classificati o n criteria f or Ps oriatic Art hritis  
C C & G  
C oc kcr oft -G a ult  
C D  
Cr o h n’s disease  
C D AI  
Cli nical Disease Acti vit y I n d e x  
C E S  
car b o x ylesterases  
CI  
c o nfi de nce i nter val  
C ma x  
ma xi m u m o bser ve d plas ma c o nce ntr ati o n  
C M V  
cyt o me gal o vir us  
C N S  
ce ntral ner v o us s yste m  
Cr Cl  
creati ni ne cleara nce  
C R O  
c o ntract r esearc h or ga nizati o n  
C R P  
C -reacti ve pr otei n 
C O X -2  
c ycl o o x y ge nas e -2  
cs D M A R D  
c o n ve nti o nal s y nt h etic disease -m o dif yi n g a ntir he u matic dr u g  
C S P  
cli nical st u d y pr ot o c ol  
C S R  
cli nical st u d y re p ort  
C T C A E  
C o m m o n Ter mi n ol o g y Criteria f or A d verse E ve nts  
C V E A C  
Car di o vasc ular Safet y E n d p oi nt A dj u dicati o n C o m mittee  
C X R  
c hest x -ra y 
C Y P  
c yt o c hr o me P 4 5 0  

Fil g oti ni b  
 
Pr ot oc ol  G L P G 0 6 3 4 -C L -2 2 7  
Fi nal  
Gala pa g os  
A me n d me nt 2  
C O N FI D E N TI A L  
P a ge  2 4  
0 9 Se p 2 0 2 2  
D A P S A  
Disease A cti vit y i n Ps oriatric Art hritis  
D A S 2 8  
Disease A cti vit y Sc ore 2 8  j oi nts 
D B P  
diast olic bl o o d press ure  
D M C  
D ata M o nit ori n g C o m mittee  
D N A  
de o x yri b o n ucleic aci d  
E C G  
electr ocar di o gra m 
e C R F 
electr o nic case re p ort f or m  
E R A P  
e n d o plas mic retic ul u m a mi n o pe pti dase  
E T  
earl y ter mi nati o n  
E U  
E ur o pea n U ni o n  
E u dra C T  
E ur o pea n U ni o n Dr u g Re g ul ati n g A ut h orities Cli nical Trials Data base  
E U L A R  
E ur o pea n Lea g ue A gai nst R he u matis m  
F D A  
F o o d a n d Dr u g A d mi nistrati o n  
F S H  
f ollicle sti m ulati n g h or m o ne 
G C P  
G o o d Cli nical Practice  
GI  
g astr oi ntesti nal  
G L P  
Gala pa g os, N V  
H Bs A g  
h e patitis B s urface a nti ge n 
H B V  
he patitis B vir us  
H C V  
he patitis C vir us  
H D P E  
hi g h de nsit y p ol yet h yl e n e  
H D L  
hi g h de nsit y li p o pr otei n  
h E R G  
h u ma n et her -a-g o -g o relate d ge ne  
HI V  
h u ma n i m m u n o deficie nc y vir us  
H L A -B 2 7  
h u ma n le u k oc yte a nti ge n B 2 7  
H L G T  
h i g h le vel g r o u p ter m  
H L T  
h i g h le vel ter m 
hs C R P  
hi g h se nsiti vit y C -reacti v e pr otei n 
I A 1/ 2 
first/sec o n d u n bli n de d i nteri m a nal ysis 
I B 
I n v esti gat or’s Br oc h ure 
I B D 
i nfla m mat or y b o wel disease 
I C5 0 
half ma xi mal i n hi bit or y c o nce ntrati o n  
I C F 
i nf or me d c o nse nt f or m 
I C H 
I nter nati o nal C o u ncil f or Har m o nizati o n ( of Tec h nical Re q uire me nts f or 
P har mace uticals f or H u m a n Use)  
I E C 
I n d e pe n de nt Et hics C o m mittee 

Fil g oti ni b  
 
Pr ot oc ol  G L P G 0 6 3 4 -C L -2 2 7  
Fi nal  
Gala pa g os  
A me n d me nt 2  
C O N FI D E N TI A L  
P a ge  2 5  
0 9 Se p 2 0 2 2  
I F N 
i nterfer o n 
I F Nγ 
i nterfer o n ga m ma 
I g 
i m m u n o gl o b uli n 
I L 
interle u ki n  
I M P 
i n vesti gati o nal me dici nal pr o d uct 
I N D 
I n v esti gati o nal ne w dr u g 
I N R 
i nter nati o nal n or malize d rati o 
I R B 
I nstit uti o nal Re vie w B oar d 
I W R S 
i nteracti ve w e b res p o ns e s yste m 
J A K 
J a n us ki nase 
L D L  
l o w de nsit y li p o pr otei n 
L E F  
lefl u n o mi de  
L H  
l utei nizi n g h or m o ne 
L L O Q  
l o wer li mit of q ua ntitati o n 
L L T  
l o w le vel ter m 
L T B R  
l y m p h ot o xi n beta rece pt or 
M A C E  
maj or a d vers e car di o vasc ular e ve nts  
M A T E 1  
m ulti dr u g a n d t o xi n e xtr usi o n pr otei n 1  
Me d D R A  
Me dical Dicti o nar y f or R e g ul at or y Acti vities  
M C P  
m o n oc yte c he m oattr acta nt pr otei n  
M C V  
mea n c or p us c ular v ol u m e  
M H C  
maj or hist oc o m pati bilit y c o m ple x  
M M P  
matri x metall o pe pti dase  
M RI  
ma g n etic res o n a nce i ma gi n g  
M T X  
m et h otre x ate  
N O A E L  
n o o bser ve d a d v erse effect le vel  
N O E L  
n o o bser ve d effect le vel  
nr A x S p A  
n o n -ra di o gra p hical a xial s p o n d yl oart hritis 
N S AI D  
n o n -ster oi dal a nti-i nfla m mat or y dr u g 
N Y  
Ne w Y or k  
O A T  
or ga nic a ni o n tra ns p orter  
O C T  
or ga nic cati o n tra ns p orter  
P C P  
p ne u m oc ystis p ne u m o nia  
P E  
p h ysical e x a mi nati o n  
P E G  
p ol yet h yle n e gl yc ol  
P -g p  
P -gl yc o pr ot ei n  

Fil g oti ni b  
 
Pr ot oc ol  G L P G 0 6 3 4 -C L -2 2 7  
Fi nal  
Gala pa g os  
A me n d me nt 2  
C O N FI D E N TI A L  
P a ge  2 6  
0 9 Se p 2 0 2 2  
P h G A D A  
P h ysicia n Gl o bal Ass ess me nt of Disease Acti vit y  
P K  
p har mac o ki netic (s) 
Ps A  
ps oriatic art hritis  
p S T A T  
p h os p h o si g nal tra ns d u cer a n d acti vat or of tra ns cri pti o n  
P T  
preferre d t er m  
Pt G A D A  
Patie nt Gl o bal Assess me nt of Disease Acti vit y  
P T T  
partial t hr o m b o plasti n ti me  
Q 1  
1 st q uartile  
Q 3  
3 r d q uartile  
R A  
r he u mat oi d art hritis 
S A D R  
seri o us a d vers e dr u g reacti o ns 
S A E  
seri o us a d vers e e v e nt 
S A P  
statistical a nal ysis pla n 
S B P  
s yst olic bl o o d press ur e 
S D  
sta n dar d de viati o n 
S D AI  
Si m plifie d Disease Acti vit y I n de x  
SJ C 2 8  
s w olle n j oi nt c o u nt 2 8 j oi nts 
SJ C 6 6  
s w olle n j oi nt c o u nt 6 6 j oi nts 
S O P  
sta n dar d o perati n g pr oce d ure 
S p A  
sp o n d yl oart hritis  
S S M T  
S p o ns or Safet y M a na ge me nt Tea m  
S S Z  
sulfalazi ne  
S T A T  
si g nal tra ns d u cer a n d acti vat or of tra ns cri pti o n 
S U S A R  
s us pecte d u ne x pecte d seri o us a d verse reacti o ns 
T B  
tu berc ul osis  
T E A E  
treat me nt-e mer ge nt a d verse e ve nt  
TI M P  
tiss ue i n hi bit or of metall o pe pti dase 
TJ C 2 8  
te n der j oi nt c o u nt 2 8 
TJ C 6 8  
te n der j oi nt c o u nt 6 8 
T M F  
trial master file 
T N F α  
t u m or necr osis fact or al p ha 
T N Fi  
t u m or necr osis fact or i n hi bit or 
T N F R S F 1 A  
t u m or necr osis fact or rece pt or s u perfa mil y me m b er 1 A 
T S H  
t h yr oi d sti m ulati n g h or m o ne 
T Y K  
t yr osi ne ki nas e 
U C  
ulcerati ve c olitis  

Fil g oti ni b  
 
Pr ot oc ol  G L P G 0 6 3 4 -C L -2 2 7  
Fi nal  
Gala pa g os  
A me n d me nt 2  
C O N FI D E N TI A L  
P a ge  2 7  
0 9 Se p 2 0 2 2  
U G T  
uri di ne 5’ -dis p h os p hate gl uc ur o n os yltra nsferase  
U L N  
u p per li mit of n or mal  
U S  
U nite d States  
V A S  
vis ual a nal o g u e scale  
W B C  
w hite bl o o d cell  
W H O  
W orl d Healt h Or ga nizati o n  
 

Fil g oti ni b  
 
Pr ot oc ol  G L P G 0 6 3 4 -C L -2 2 7  
Fi nal  
Gala pa g os  
A me n d me nt 2  
C O N FI D E N TI A L  
P a ge  2 8  
0 9 Se p 2 0 2 2  
1.  
I N T R O D U C TI O N 
1. 1.  
B a c k gr o u n d  
1. 1. 1.  
R h e u m at oi d Art hriti s  
R he u mat oi d art hritis ( R A) is a c hr o nic, s yste mic i nfla m mat or y disease t h at affects a p pr o xi matel y 
1. 3 milli o n a d ults i n t he U nite d States ( U S). R A  ma nifests pri nci pall y as a n attac k o n peri p h eral 
j oi nts a n d ma y lea d t o m ar ke d destr u cti o n a n d def or mit y of j oi nts, wit h c o nsi dera ble disa bilit y 
a n d i m pact o n q ualit y of life. It is c h aracterize d b y t he pr o d ucti o n of a ut oa nti b o dies, s y n o vial 
i nfla m mati o n wit h f or mati o n of pa n n us tiss ue, a n d er osi o n of u n derl yi n g cartila ge a n d b o ne. 
Alt h o u g h pe o ple of a n y a ge ca n b e affect e d, t he o nset of R A is m ost fre q ue nt bet wee n t he a ges 
of 4 0 a n d 5 0  years, a n d w o me n are affecte d 3  ti m es m ore ofte n t ha n m e n. W hile t he ca use of R A 
is still n ot c o m pletel y u n derst o o d, a berra nt B-cell acti vati o n, T -cell c o -sti m ulati o n, oste oclast 
di ffere ntiati o n, a n d c yt o ki ne releas e all ha ve b ee n i m plicate d i n its pat h o ge nesis. 
Treat me nt of R A is de p e n de nt o n se verit y, t he patie nt’s c o -m or bi dities a n d i nitial res p o nse t o 
t hera p y. Met h otre x ate ( M T X) is a c o n ve nti o nal s yste mic dise ase -m o dif yi n g a ntir h e u matic dr u g 
(cs D M A R D) a n d c o nti n u es t o be t he c or nerst o ne of R A t hera p y. Patie nts wit h a n i na de q uate 
res p o nse t o cs D M A R D(s) are ofte n treate d wit h bi ol o gic t hera pies s uc h as t u m or necr osis fact or 
i n hi bit ors ( T N Fi) as a n i nitial sec o n d li ne t hera p y. H o we ver, a p pr o xi matel y 2 8 % t o 5 8 % of 
patie nts wit h R A wit h i na de q uate res p o nse t o M T X fail T N Fi as re vie we d i n  ( Re dlic h, et al., 
2 0 0 3) . I n t his setti n g, treat me nt g ui deli nes rec o m me n d eit her s witc hi n g t o a n ot her T N Fi, 
alter nate bi ol o gic, or t o a s mall m olec ule dr u g. Des pite si g nifica nt a d va nces i n disease 
ma na ge me nt i n rece nt years, t here re mai ns a n ee d f or ne w treat me nts, si nce n ot all patie nts 
res p o n d a de q u atel y t o c urre nt t hera pies, ha v e c o-m or bi dities a n d s o me patie nts e x perie nce 
t o xicities a n d/ or i nt olera nce t hat li mit t he use of a p pr o ve d t hera pies. 
I n N o ve m ber 2 0 1 2, t ofaciti ni b ( Xelja nz® ) beca me t he first J a n us Ki nase (J A K) i n hi bit or t o 
recei v e F o o d a n d Dr u g A d mi nistrati o n ( F D A) a p pr o val f or t he treat me nt of a d ult patie nts wit h 
R A. T he dr u g pr o ve d t o be effi caci o us i n treati n g t he si g ns a n d s y m pt o ms of R A. H o we ver, t he 
o bser ve d si de  effects a n d ris k pr ofile of t ofaciti ni b are si milar t o t h ose of se veral e xisti n g 
a ntir he u matic a ge nts wit h c yt o p e nias, ele vate d le vels of li ver f u ncti o n e nz y m es, i ncreas e d t otal 
c h olester ol le vels, wit h i ncreas es i n l o w de nsit y li p o pr otei n ( L D L) t y picall y e x cee di n g t h ose f or 
hi g h de nsit y li p o pr otei n ( H D L), a n d i ncreas e d ris k f or i nfecti o ns i ncl u di n g seri o us a n d 
o p p ort u nistic i nfecti o ns. At hi g her d oses,  t ofaciti ni b treat me nt was ass o ciat e d wit h a ne mia, 
w hic h is t h o u g ht t o be li n ke d t o i n hi biti o n of J A K 2. W hile t he pa n J A K i n hi bit or t ofaciti ni b has 
s h o w n a n earl y o ns et of acti o n a n d l o n g ter m effi cac y i n R A as m o n o t hera p y a n d i n c o m bi nati o n 
wit h bac k gr o u n d cs D M A R D t hera p y, d ose le vels were li mite d b y si de effects p ote ntiall y 
me diate d b y its effect o n J A K 2 a n d J A K 3. A n ot her J A K i n hi bit or, baraciti ni b ( Ol u mia nt ®) has 
bee n a p pr o ve d i n t he E ur o pea n U ni o n ( E U ) i n Fe br uar y 2 0 1 7 as a sec o n d -li ne t hera p y f or 
m o derate t o se v ere acti ve r he u mat oi d art hritis i n a d ults, eit her al o ne or i n c o m bi nati o n 
wit h  met h otre x ate  ( wit h t he e x ce pti o n of t he M T X-lefl u n o mi de [ L E F] c o m bi nati o n). T his was 
f oll o we d, i n Ma y 2 0 1 8, b y t he F D A a p pr o val f or t he treat me nt of a d ult patie nts  wit h m o deratel y 
t o se verel y acti ve r he u m at oi d art hritis w h o ha ve h a d a n i na de q u ate res p o nse t o o ne or m ore T N F 
a nta g o nist t hera pies . Bari citi ni b is a selecti ve a n d re versi ble i n hi bit or of J A K 1 a n d J A K 2 a n d 
t here b y acts b y re d uci n g t he p h os p h or yl ati o n a n d acti vati o n of si g n al tra ns d ucers a n d acti vat ors 

Fil g oti ni b  
 
Pr ot oc ol  G L P G 0 6 3 4 -C L -2 2 7  
Fi nal  
Gala pa g os  
A me n d me nt 2  
C O N FI D E N TI A L  
P a ge  2 9  
0 9 Se p 2 0 2 2  
of tra nscri pti o n ( S T A Ts ). O bser ve d si de effects a n d ris k pr ofile of baraciti ni b is c o nsiste nt wit h 
u nselecti ve J A K/ S T A T pat h wa y i n hi biti o n. Ele vate d le vels of li ver f u ncti o n e nz y mes, i ncrease d 
t otal c h olesterol le vels, i ncreas e d ris k f or i nfecti o ns i ncl u di n g seri o us a n d o p p ort u nistic 
i nfecti o ns. J A K 2 i n hi biti o n s pecific hae mat ol o gical si de effects  s uc h as a n e mia, ne utr o pe nia, 
l y m p h oc yt o pe nia a n d t hr o m b oc yt osis wit h i ncreas e d ris k f or dee p vei n t hr o m b osis/ p ul m o nar y 
e m b olis m  ha ve als o bee n re p orte d.  
T his hi g hli g hts t he nee d f or m ore sele cti ve a n d tar get e d t hera pi es wit h i m pr o ve d 
i m m u n o m o d ulat or y a n d he mat ol o gic effects. J A K 1 is t h o u g ht t o be a n i nte gral part of R A 
pat h o ge nesis d ue its r ole i n tra ns mitti n g i nfla m m at or y c yt o ki n e si g n ali n g. He nce, tar gete d 
i n hi biti o n of J A K 1 has great p ote ntial f or t he treat me nt of R A wit h a n i m pr o ve d safet y a n d si de 
effect pr ofile.  
1. 1. 2.  
P s ori ati c Art hriti s  
Ps oriatic art hritis ( Ps A) is a n i nfla m mat or y j oi nt disease ass oci ate d wit h ps orias is a n d 
c haracteriz e d b y heter o ge ne o us m usc ul os keletal p he n ot y p es t hat i n v ol ve m ulti ple d o mai ns 
i ncl u di n g t he peri p heral j oi nts, a xial s kelet o n, te n d o n a n d li ga m e nt i nserti o n sites (e nt hesitis), 
a n d di gits ( dact ylitis). Ps A occ urs i n a p pr o xi matel y 3 0 % of ps oriasis patie nts. I n t he maj orit y of 
cases ( 7 5 %) ps oriasis pr ece des j oi nt disease, b ut i n s o me cases ( 1 5 %) t he o nset is s y nc hr o n o us 
a n d i n 1 0 % art hritis prece des ps oriasis.  
Ps A occ urs j ust as fre q ue ntl y i n males a n d fe males. T he art hritis i n Ps A c o m m o nl y i n v ol ves 
distal j oi nts a n d has t he te n de nc y t o distri b ute i n a ra y patter n, s o t hat all t he sa me j oi nts of a 
si n gle di git are m or e li kel y t o be affecte d ( d act ylitis). T he de gree of er yt he ma o ver t he affecte d 
j oi nts, t he prese nce of as y m metric al s pi nal i n v ol ve me nt, t he pres e nce of e nt hesitis a n d a l o wer 
le vel of te n der ness are als o t y pical f eat ur es of Ps A. Ps A bel o n gs t o t he gr o u p of 
s p o n d yl oart hr o pat hies beca use of t h e pres e nce of s p o n d ylitis i n u p t o 4 0 % of patie nts. T he e xtra -
artic ular feat ur es o bser v e d i n Ps A are si milar t o ot her s p o n d yl o art hr o p at hies i ncl u di n g m uc o us 
me m bra ne lesi o ns, iritis, uret hritis, diarr hea a n d a ortic r o ot dilatati o n, a n d ass ociati o n wit h 
h u ma n le u k oc yte a nti ge n B 2 7 ( H L A -B 2 7).  
First -li ne treat me nt tra diti o nall y c o nsists of n o n-st eroi dal a nti -i nfla m mat or y dr u gs ( N S AI Ds) a n d 
cs D M A R Ds s uc h as s ulfalazi ne ( S S Z), M T X, a n d lefl u n o mi de ( L E F). T hes e dr u gs re mai n a 
mai nsta y of t h era p y w h ere t here is li mite d access t o bi ol o gical a ge nts. T he arri val of T N F i a ge nts 
o ver a deca d e a g o dra maticall y i ncreas e d t he treat me nt ar ma me ntari u m f or Ps A lea di n g t o m uc h 
i m pr o ve d o utc o mes f or b ot h s ki n a n d j oi nt disease. Ne vert hel ess, T N Fi a ge nts d o n ot w or k i n all 
patie nts a n d ma y l ose res p o nse o ver ti me, partl y b eca use of i m m u n o ge nicit y. A ge nts wit h 
differe n t mec ha nis m of acti o ns t hat tar get t he i nterle u ki n (I L)-2 3/I L -1 7 pat h wa ys t hat pr o m ote 
s ki n a n d j oi nt i nfla m mati o n ha ve bec o me a v aila ble a n d m ore are c urre ntl y u n der e val u ati o n i n 
cli nical st u dies. T hese a ge nts i ncl u de t he I L -1 2/I L -2 3 i n hi bit ors uste ki n u ma b; t he I L -2 3 
i n hi bit ors g usel k u ma b, til dra kiz u ma b, a n d risa n kiz u ma b; t he I L-1 7 rece pt or A i n hi bit ors s uc h  as 
sec u ki n u ma b a n d i x e kiz u ma b; t he I L-1 7 rece pt or A/ F i n hi bit or bi me kiz u ma b ; a n d t he 
p h os p h o diesterase E 4 i n hi bit or a pre milast. T he t hera pe utic res p o n se of t hes e ne w a ge nts is m ost 
e vi de nt i n ps oriasis, res ulti n g i n mar ke d pla q ue cleara nce; t he res ults i n Ps A f or t hese  a ge nts are 
si milar t o t h ose o bser ve d wit h T N Fi a ge nts. I L-1 7 bl oc ka de is als o effecti ve f or a xial disease a n d 
i n hi bits ra di o gra p hic pr o gressi o n. T he oral a ge nt a pre milast offers a m o dest res p o nse i n t he s ki n 

Fil g oti ni b  
 
Pr ot oc ol  G L P G 0 6 3 4 -C L -2 2 7  
Fi nal  
Gala pa g os  
A me n d me nt 2  
C O N FI D E N TI A L  
P a ge  3 0  
0 9 Se p 2 0 2 2  
a n d j oi nts, wit h fe w safet y si g nals a n d is n ot i n dicate d i n patie nts w h o de m o nstrate ra di o gra p hic 
da ma ge or a xial i n v ol ve me nt.  
Se veral ke y c yt o ki n es i n t he I L -2 3/I L -1 7 p at h wa ys pr o m ote  s ki n a n d j oi nt i nfla m mati o n si g nal 
t hr o u g h t he J A K fa mil y of rece pt or-ass ociate d t yr osi ne ki nases (T Y Ks ). Acti vate d J A Ks recr uit 
a n d acti vate S T A Ts w hi c h i n t ur n dri ve ge ne tr a ns cri pti o n. T he s pecifi c J A K -S T A T acti vati o n 
de pe n ds o n t he c yt o ki ne si g nal w hi c h i ncl u d es i nterfer o n (I F N) a n d its relate d c yt o ki n es, t he 
c o m m o n γ-c hai n c yt o ki n es a n d t he I L -6 t y p e c yt o ki nes. St u dies ha ve de m o nstrate d i ncrease d 
p h os p h o S T A T 3 ( p S T A T 3) a n d p S T A T 1 e x pressi o n i n ps oriasis s ki n a n d ha ve s h o w n t hat 
i nterfer o n ga m ma (I F Nγ), I L-6 a n d I L -2 2 ca n i n d uce p S T A T 1 or p S T A T 3 i n kerati n oc ytes. 
T ofaciti ni b, a n orall y a d mi nistere d J A K 1/J A K 3 i n hi bit or, is re gistere d i n U S a n d E ur o pe f or t he 
treat me nt of m o derate t o se vere ps oriatic art hritis. It has b ee n s h o w n t o d ecrease p S T A T 3, 
p S T A T 1, N F -κ B, p 6 5, a n d i n d uce S O C S 3 a n d PI A S 3 e x pressi o n i n Ps A s y n o vial fi br o blasts. I n 
Ps A s y n o vial bi o ps y c ult ures, t ofaciti ni b si g nifi ca ntl y decreas e d s p o nta ne o us secreti o n of I L -6, 
I L-8, m o n oc yte c h e m oattracta nt pr ot ei n 1 ( M C P -1 ), matri x metall o pe pti dase 
(M M P )9/ M M P 2/ M M P 3 a n d decreas e d  t he M M P 3/tiss ue i n hi bit or of metall o pr otei nase (TI M P )3 
rati o. Res ults fr o m a pr o of of c o nce pt st u d y  wit h t he J A K 1 selecti ve i n hi bit or fil g oti ni b ha ve 
de m o nstrate d t he effic ac y of t he c o m p o u n d i n ps oriatic art hritis. U p ad aciti ni b, a J A K 1/J A K 3 I,  
i n hi bit or is c urre ntl y b ei n g teste d i n P hase 3. 
1. 1. 3.  
A n k yl o si n g S p o n d yliti s  
A n k yl osi n g s p o n d ylitis ( A S) is a c hr o nic, i nfla m mat or y a ut oi m m u ne disease, w hic h bel o n gs t o a 
gr o u p of c o n diti o ns k n o w n as s p o n d yl o art hr o pat hies. A S is mai nl y c haracterize d b y 
i nfla m mati o n of t he sacr oiliac j oi nts a n d a xial s kelet o n. E xtra-a xial i n v ol ve me nt ca n occ ur i n u p 
t o half of patie nts a n d ma nifest as peri p heral art hritis, e nt hesitis, a n d dact ylitis. Ac ute a nteri or 
u veitis is t he m ost c o m m o n e xtra -artic ular ma nifestati o n, wit h lifeti me pre v ale nce of 3 0 -4 0 %. 
Ps oriasis occ urs i n a b o ut 1 0 % a n d i nfla m mat or y b o wel disease (I B D), m or e c o m m o nl y Cr o h n’s 
disease ( C D), h as bee n re p orte d i n 5 -1 0 % of A S p atie nts; h o we ver, micr osc o pic i nfla m mat or y 
lesi o ns fr o m t he c ol o n or distal ile u m bi o psies ha ve bee n re p orte d m or e c o m m o nl y. Oste o p or osis 
of t he s pi ne a n d peri p heral b o nes is fre q u e ntl y prese nt, lea di n g t o i ncrease d s pi nal fract ur e rat es 
i n t hese patie nts. 
First s y m pt o ms i n dicati v e of A S te n d t o de vel o p i n a d olesce nts, a ge d 2 0 -3 0  years. T he dis ease 
occ ur s 3 ti mes m ore oft e n i n y o u n g me n c o m p are d t o y o u n g w o me n, wit h a pre val e nce of 
0. 1 5 -0. 8 % i n t he ge neral p o p ulati o n. Alt h o u g h t he e x act ca use of A S is u n k n o w n, a str o n g 
ge n etic pre dis p ositi o n is k n o w n, wit h > 9 0 % of t he disease ris k deter mi ne d ge n eticall y. T he 
str o n gest a n d m ost esta blis he d ass ociati o n has bee n f o u n d wit h t he H L A-B 2 7 ge n e. M ore rece nt 
w h ole ge n o me ass o ciati o n st u dies ha ve i de ntifie d f urt her l oci i n n o n -maj or hist oc o m pati bilit y 
c o m ple x ( M H C) ge n es or ge netic re gi o ns t hat i nfl ue nce s usce pti bil it y t o A S; t hese l oci c o nfer 
e n d o plas mic retic ul u m a mi n o pe pti dase 1 ( E R A P -1), I L -2 3 R, l y m p h ot o xi n beta rece pt or ( L T B R), 
a n d t u m or necr osis f act or rece pt or s u perfa mil y me m ber 1 A ( T N F R S F 1 A).  
T he pri mar y g oals of A S treat me nt are t o re d u ce s y m pt o ms, i m pr o ve a n d mai ntai n s pi nal 
fle xi bilit y a n d n or mal p ost ure, re d uce f u ncti o nal li mitati o n wit h t he ai m t o mai ntai n t he a bilit y t o 
w or k, a n d decrease l o n g -ter m c o m plicati o ns ass ociate d wit h A S. T he first-li ne treat me nt of mil d 

Fil g oti ni b  
 
Pr ot oc ol  G L P G 0 6 3 4 -C L -2 2 7  
Fi nal  
Gala pa g os  
A me n d me nt 2  
C O N FI D E N TI A L  
P a ge  3 1  
0 9 Se p 2 0 2 2  
A S are N S AI Ds, pr o vi di n g a s u bsta ntial r elief of bac k pai n a n d stiff n ess i n a p pr o xi matel y 
7 0 -8 0 % of A S patie nts.  
I n case N S AI D treat me nt d oes n ot a de q uatel y c o ntr ol s y m pt o ms s ufficie ntl y, treat me nt wit h 
c ortic oster oi ds c a n be c o nsi dere d, w hic h h o we ver c o ul d i ncreas e t he ris k of s pi nal oste o p or os is. 
W hile use d wi del y i n R A treat me nt, cs D M A R Ds are ge nerall y i neffecti ve f or treat me nt of A S, 
alt h o u g h peri p heral j oi nt s y m pt o ms ma y effecti vel y be tr eate d wit h S S Z.  
T N F i treat me nt has bee n a maj or pr o gress i n treat me nt o pti o ns f or p o orl y c o ntr olle d A S, 
im pr o vi n g disease acti vit y, s pi nal m o bilit y, p h ysic al f u ncti o n, a n d pai n. T N F i i ncl u de t he 
m o n ocl o nal a nti b o dies i nfli xi ma b, a dali m u ma b, cert oliz u ma b pe g ol a n d g oli m u ma b, as well as 
t he T N F al p ha ( T N F α) bi n di n g rec o m bi na nt rece pt or eta nerce pt. H o we ver, serio us i nfecti o ns 
s uc h as t u berc ul osis ( T B), aller gic reacti o ns a n d a ut oi m m u ne reacti o ns ca n res ult fr o m treat me nt. 
A d diti o nall y, T N F i a ge nts are o nl y effecti ve i n a b o ut 4 0 % of patie nts a n d patie nts ma y l ose 
res p o nse o ver ti me beca use of i m m u n o ge ni cit y. 
Rece n t st u dies s u g gest t hat I L-2 3/I L -1 7 p at h wa ys ma y h a ve a r ole i n t he pat h o ge n esis of A S. 
Ne w c o m p o u n ds t hat tar get t hes e pat h wa ys h a ve bec o me a v aila ble a n d a d diti o nal c o m p o u n ds are 
c urre ntl y u n der e val u ati o n i n cli nical st u dies. T hese a ge nts i ncl u de t he, t h e  I L-2 3 i n hi bit or 
til dra kiz u ma b; t he I L-1 7 A i n hi bit ors s uc h as sec u ki n u ma b a n d i x e kiz u ma b; t he I L 1 7 A a n d F 
i n hi bit or bi me kiz u ma b; se veral k e y c yt o ki nes i n t he I L-2 3/I L -1 7 pat h wa ys si g nal t hr o u g h t he 
J A K fa mil y of rece pt or-ass ociate d T Y Ks.  
Se veral ke y c yt o ki n es i n t he I L -2 3/I L -1 7 p at h wa ys si g nal t hr o u g h t he J A K fa mil y of rece pt or -
ass ociate d T Y Ks , t heref ore i n hi biti o n of J A K si g nali n g ma y b e efficaci o us  i n t he treat me nt of 
t hese diseases.  
1. 1. 4.  
N o n -r a di o gr a p hi c al A xi al S p o n d yl o art hriti s 
T he ter m n o n -ra di o gra p hic a xial s p o n d yl o art hritis ( nr A x S p A) is rece ntl y bei n g i ntr o d uce d t o 
i de ntif y patie nts s ufferi n g fr o m t he earl y p h ase of A S, w here t he sta n d ar d dia g n osis, hist oricall y 
base d o n t he prese nce of sacr oiliitis o n X -ra y, is i m p ossi ble d ue t o t he a bse nce of ra di o gra p hic 
c ha n ges.  
A st u d y de m o nstr ate d t hat t he fre q u e nc y of ra di o gra p hic sacr oiliitis i ncreases i n parallel wit h 
disease d urati o n a n d a p pr o xi matel y 6 0 % of patie nts will re q uire at least 1 0 or m ore years of 
acti ve diseas e t o de m o nstrate its ra di o gra p hic feat ures see n i n “classical ” A S ( Sa hi d-Na hal, 
Miceli -Ric har d, & Bert h el ot, 2 0 0 0) . 
T heref ore t o da y, p atie nts prese nti n g wit h a cli nical pict ure of A S b ut wit h o ut its ra di ol o gical  
hall mar k, will be dia g n os e d wit h nr A x S p A.  
T his disti ncti o n is i m p orta nt as a ge nts effecti ve i n alle viati n g cli nical s y m pt o ms a n d si g ns of A S 
c o ul d be use d m uc h earl i er i n t he c o urse of t he dis ease a n d t h eref ore m a y pre ve nt str uct ur al 
da ma ge a n d c o m plicati o ns  ( R u d waleit, et al., 2 0 0 9). 

Fil g oti ni b  
 
Pr ot oc ol  G L P G 0 6 3 4 -C L -2 2 7  
Fi nal  
Gala pa g os  
A me n d me nt 2  
C O N FI D E N TI A L  
P a ge  3 2  
0 9 Se p 2 0 2 2  
1. 2.  
Fil g oti ni b ( G S -6 0 3 4)  
1. 2. 1.  
G e n er al I nf or m ati o n  
J A Ks are i ntracell ular c yt o plas mic T Y Ks t hat tra ns d uce c yt o ki ne si g nali n g fr o m me m bra ne 
rece pt ors t hr o u g h S T A T t o t he n ucle us of cells. J A K i n hi bit ors bl oc k t he si g nali n g of vari o us 
c yt o ki nes, gr o wt h fact ors, a n d h or m o nes, i ncl u di n g t he pr o -i nfla m mat or y c yt o ki ne I L-6. F o ur 
differe nt t y pes of J A Ks are k n o w n, J A K 1, J A K 2, J A K 3, a n d T Y K 2 w hic h i nteract wit h differe nt 
sets of me m bra ne rece pt ors. I n hi biti o n of J A Ks is a pr o misi n g t hera pe utic o pti o n f or a ra n ge of 
i nfla m mat or y c o n diti o ns i ncl u di n g R A a n d C D. Fil g o ti ni b ( G S-6 0 3 4, f or merl y k n o w n as 
G L P G 0 6 3 4)  is a p ote nt a n d selecti ve i n hi bit or of J A K 1. T he c o m p o u n d h as s h o w n g o o d 
preli mi nar y efficac y i n s u bjects wit h R A a n d t h ose wit h C D i n P hase  2 st u dies.   
F or f urt her i nf or m ati o n o n fil g oti ni b, refer t o t he c urre nt  I n vesti gat or’s Br oc h ure (I B). 
1. 2. 2.  
Pr e cli ni c al P h ar m a c ol o g y a n d T o xi c ol o g y   
Fil g oti ni b a n d its meta b olite, G S -8 2 9 8 4 5, ha ve bee n e xte nsi vel y c h aracteri ze d i n n o ncli nical 
st u dies. T his pr o gra m i ncl u des cell ular ass a ys d e m o nstrati n g p ote nc y a n d selecti vit y of t he  
c o m p o u n d a gai nst J A K 1; efficac y st u dies i n rats a n d mice; re peat  d ose t o xicit y st u dies ( u p t o 
2 6  wee ks i n t he rat a n d 3 9  wee ks i n t he d o g), i n vitr o a n d i n vi v o safet y p har mac ol o g y a n d 
ge n etic t o xic ol o g y st u dies, carci n o ge nicit y st u dies i n rats a n d i n tra ns ge nic ( T gras H 2) mice, a n d 
re pr o d ucti ve t o xic ol o g y st u dies i n rats a n d ra b bits. A d diti o nal t o xic ol o g y st u dies c o n d ucte d 
i ncl u de p h ot ot o xicit y st u dies a n d d ose-ra n ge fi n di n g st u dies i n s u p p ort of a defi niti ve rat j u ve nile 
t o xicit y st u d y. A d efi niti ve j u ve nile t o xic ol o g y st u d y i n rats is o n g oi n g.  
1. 2. 2. 1.  
N o n cli ni c al P h ar m a c ol o g y  
I n cell ular assa ys, fil g oti ni b i n hi bits J A K 1 si g nali n g wit h half ma xi m u m i n hi bit or y c o nce ntrati o n 
(I C5 0) val ues of ≥1 7 9 n M, a n d de m o nstrates 3 0 -f ol d selecti vit y o ver J A K 2 i n a h u ma n w h ole 
bl o o d assa y. Fil g oti ni b has bee n pr ofile d a gai nst 4 5 1  ki nases a n d it is hi g hl y selecti ve f or J A K 1; 
o nl y 2. 5 % of ki n ases were i n hi bite d ≥ 5 0 % at 5 0 -f ol d hi g her c o nce ntrati o n t ha n I C5 0 f or J A K 1.  
1. 2. 2. 2.  
S af et y P h ar m a c ol o g y  
Fil g oti ni b a n d G S -8 2 9 8 4 5 ha d n o rele va nt effects o n car di o vas c ular para m eters 
( h u ma n et her -a-g o g o [ h E R G] a n d d o g tele metr y st u dies), a part fr o m a sli g ht n o n -a d verse 
i ncreas e i n heart rate a n d arterial pr ess ure wit h G S-8 2 9 8 4 5 at e x p os ures 8 -f ol d t hat of t he pea k 
ser u m c o nce ntrati o n (C ma x ) i n s u bjects wit h C D treate d wit h 2 0 0 m g o n ce d ail y fil g oti ni b. T here 
were n o rele v a nt effects o n electr ocar di o gra m ( E C G) a n d Q T. Fil g oti ni b a n d G S -8 2 9 8 4 5 ha d n o 
effects o n t he res pir at or y s yste m a n d ce ntral n er v o us s yste m ( C N S).  

Fil g oti ni b  
 
Pr ot oc ol  G L P G 0 6 3 4 -C L -2 2 7  
Fi nal  
Gala pa g os  
A me n d me nt 2  
C O N FI D E N TI A L  
P a ge  3 3  
0 9 Se p 2 0 2 2  
1. 2. 2. 3.  
K e y N o n cli ni c al Di str i b uti o n, M et a b oli s m, a n d E x cr eti o n D at a 
Fil g oti ni b de m o nstrates g o o d oral bi oa vaila bilit y i n mice, rats, d o gs, a n d mi ni -pi gs b ut less i n 
m o n ke ys. Plas ma pr otei n bi n di n g is l o w ( < 7 0 %) i n all s pecies, i ncl u di n g h u ma ns.  
T he p har mac o ki netics ( P K) of fil g oti ni b  is ge n erall y d ose pr o p orti o nal wit h o ut ge n d er 
differe n ces. N o acc u m ulati o n occ urs wit h re p eate d d osi n g. T he mea n ter mi nal half -life after oral 
a d mi nistrati o n is 4  h o urs a n d 5  h o urs i n rats a n d d o gs, res pecti vel y.  
I n t he rat, fil g oti ni b s h o we d a ra pi d a n d e ve n distri b uti o n t hr o u g h o ut t he b o d y. Hi g h 
c o nce ntr ati o ns were o bs er ve d o nl y i n t he gastr oi ntesti nal ( GI) tract a n d uri nar y bla d der. 
Fil g oti ni b d oes n ot pe netrate i nt o C N S tiss ues. T he distri b uti o n of fil g oti ni b i n dicates s o me 
affi nit y f or mela ni n -c o nt ai n i n g tiss ues. 
E x creti o n is nearl y c o m plete wit hi n 2 4  h o urs (rat) a n d 4 8  h o urs ( d o g) p ost -d osi n g. I n t he rat, 
fecal a n d uri nar y e x creti o n acc o u nte d f or 4 0 % a n d 5 3 % of t he a d mi nistere d d ose, res pecti vel y, 
wit h a bile secreti o n of a b o ut 1 5 %. I n t h e d o g, fecal e x creti o n was t he pri m ar y r o ute of e x creti o n, 
acc o u nti n g f or 5 9 % of t h e a d mi nistere d d ose, wit h uri nar y e x creti o n acc o u nti n g f or 2 5 %.  
I n vitr o met a b olis m st u dies i n all s pecies re veal e d o ne maj or meta b olite ( G S-8 2 9 8 4 5). T he 
f or mati o n of G S-8 2 9 8 4 5 is me diat e d b y car b o x yl esterases ( C E S) a n d is n ot de pe n de nt o n 
c yt o c hr o me P 4 5 0 ( C Y P).  
I n vitr o e x peri me nts ha ve s h o w n t hat dr u g-dr u g i nteracti o ns wit h fil g oti ni b a n d G S -8 2 9 8 4 5 are 
u nli kel y. T here is n o i n hi biti o n or i n d ucti o n of C Y Ps or uri di ne 5’ -di p h os p h o -
gl uc ur o n os yltra nsferase  ( U G Ts), a n d n o rele va nt i n hi biti o n of ke y dr u g tr a ns p orters, i ncl u di n g 
or ga nic a ni o n tra ns p orters ( O A Ts), b y fil g oti ni b or G S -8 2 9 8 4 5. Or ga ni c cati o n tra ns p orter 2 
( O C T 2) was i n hi bite d b y b ot h fil g oti ni b (I C5 0: 8. 7 µ M) a n d G S -8 2 9 8 4 5 ( I C5 0: 6 7  µ M). T he 
cli nical rele v a nce of t he I C5 0 val ues f or i n hi biti o n of O C T 2 will be f urt her e val uate d. M ulti dr u g 
a n d t o xi n e xtr usi o n pr otei n 1 ( M A T E 1) was als o wea kl y i n hi bite d b y fil g oti ni b ( I C5 0: 9 4 µ M) 
a n d G S-8 2 9 8 4 5 ( I C5 0: > 1 0 0 µ M). Fil g oti ni b was f o u n d t o  be a s u bstrate of P -gl yc o pr ot ei n 
( P-g p).  
1. 2. 2. 4.  
N o n cli ni c al T o xi c ol o g y  
I n re peat oral d ose t o xicit y st u dies i n b ot h rats a n d d o gs, t he pri mar y tar get tiss ues i de ntifie d f or 
fil g oti ni b were t he l y m p h oi d tiss ues w hic h are e x pecte d bas e d o n t he p har mac ol o g y of J A K 
i n hi biti o n. A d diti o nal fil g oti ni b-rel ate d fi n di n gs were o bs er ve d i n t he mal e re pr o d ucti ve or ga ns 
of b ot h s pecies, a n d i n t h e i ncis or teet h of rats o nl y. Effects o n t he l y m p h oi d s yste m were f ull y 
re versi ble. Testic ular t o xicit y de m o nstrat e d partial re versi bilit y; h o w e ver, s per m c o u nts 
re mai ne d l o w. W he n usi n g t he mea n e x p os ure (area u n der t h e plas ma dr u g c o nce ntr ati o n -ti me 
c ur ve [ A U C]) at t he n o o bser ve d a d v erse effect le vels ( N O A E Ls) f or t he m ost se nsiti ve s pecies 
(t he d o g), t he e x p os ure mar gi ns c o m pare d t o a 2 0 0 m g o nce dail y d ose of fil g oti ni b i n C D 
s u bjects are 2. 5, 1. 9, a n d 3. 6-f ol d f or t he 2 6-wee k a n d 3 9 -wee k c hr o ni c t o xicit y st u dies a n d t he 
3 9 -wee k tar gete d e x p os ure t o xicit y st u d y, res pecti vel y.  

Fil g oti ni b  
 
Pr ot oc ol  G L P G 0 6 3 4 -C L -2 2 7  
Fi nal  
Gala pa g os  
A me n d me nt 2  
C O N FI D E N TI A L  
P a ge  3 4  
0 9 Se p 2 0 2 2  
G S -8 2 9 8 4 5 -relat e d fi n di n gs i n ge n eral i n t he re peat-d ose t o xicit y st u dies w ere ge n erall y si milar 
t o t h ose of t he pare nt fil g oti ni b, h o we ver n o testic ular t o xicit y was n ote d f oll o wi n g 
a d mi nistrati o n of G S -8 2 9 8 4 5.  
Fil g oti ni b a n d G S -8 2 9 8 4 5 were n o n -ge n ot o xic w he n e val uat e d i n t he bacterial m uta ge nicit y 
assa y, t he i n vitr o m o use l y m p h o ma m uta ge nicit y assa y, a n d t he rat b o ne m arr o w micr o n ucle us 
assa y.  
I n e m br y ofet al de vel o p m e nt st u dies, fil g oti ni b a n d G S-8 2 9 8 4 5 ca use d e m br y olet halit y a n d 
terat o ge nicit y i n rats a n d ra b bits. Terat o ge nicit y was o bser ve d at e x p os ures sli ghtl y hi g her or 
si milar t o t he h u ma n e x p os ure at 2 0 0 m g o nce  d ail y of fil g oti ni b i n s u bjects wit h R A. 
A d mi nistrati o n of fil g oti ni b di d n ot affect f e male fertilit y b ut i m paire d fertilit y was o bser v e d i n 
male rats at e x p os ures a p pr o xi matel y 1 2 -f ol d t he h u ma n e x p os ure at 2 0 0  m g of fil g oti ni b i n 
s u bjects wit h C D. G S-8 2 9 8 4 5 di d n ot ha ve a n y effects o n fertilit y para met ers i n eit her male or 
fe male rats. 
I n a n i n vitr o p h ot ot o xicit y st u d y i n 3 T 3 cells, t he meta b olite G S-8 2 9 8 4 5 was p ositi ve f or 
p h ot ot o xic p ote ntial a n d res ults wit h fil g oti ni b were e q ui v ocal. A f oll o w -u p i n vi v o rat 
p h ot ot o xicit y assa y re veale d a lac k of p h ot ot o xic p ote ntial f or b ot h c o m p o u n ds.  
1. 2. 3.  
Cli ni c al St u di e s  of Fil g oti ni b  
A n o ver vie w of e x p os ure a n d cli nical st u dies c o n d ucte d wit h fil g oti ni b is a vaila ble i n t he I B.  
I n t w o 2 4-wee k, P hase  2 b, ra n d o mize d, d o u ble -bli n d, place b o -c o ntr olle d st u dies i n 
5 9 4  ( St u d y G L P G 0 6 3 4 -C L -2 0 3) a n d 2 8 3  s u bjects ( St u d y G L P G 0 6 3 4-C L -2 0 4) wit h m o deratel y 
t o se verel y acti ve R A w h o ha d i ns ufficie nt r es p o nse t o M T X, fil g oti ni b a d de d t o a sta ble d ose of 
bac k gr o u n d M T X or a d mi nistere d as m o n ot hera p y was efficaci o us i n a d ose -de pe n d e nt ma n ner 
i n treati n g t he si g ns a n d s y m pt o ms of acti ve R A ( West h o ve ns, et al., 2 0 1 6; Ka va na u g h, et al., 
2 0 1 7) . I n St u d y G L P G 0 6 3 4-C L -2 0 3, a n A merica n C olle ge of R he u m at ol o g y 2 0 ( A C R 2 0 ) 
res p o nse was ac hie v e d b y a statisticall y si g nifica ntl y hi g h er perce nta ge of s u bjects i n t he 1 0 0-m g 
o nce  dail y, 2 0 0 -m g o nce -dail y, a n d 1 0 0 -m g fil g oti ni b t wice  dail y gr o u ps ( 6 3. 5 %, 6 8. 6 %, a n d 
7 8. 6 %, res pecti vel y) c o m pare d wit h place b o ( 4 4. 2 %) ( p  =  0. 0 4 3 5, 0. 0 0 6 8, a n d < 0. 0 0 0 1, 
res pecti vel y). I n St u d y G L P G 0 6 3 4-C L -2 0 4, a n A C R 2 0 res p o nse at Wee k  1 2 was ac hie ve d b y a 
statisticall y si g nifica ntl y hi g her perce nta ge of s u bj ects i n all fil g oti ni b d ose gr o u ps c o m pare d 
wit h place b o ( 6 6. 7 %, 6 5. 7 %, a n d 7 2. 5 % i n t he 5 0 -m g o nce -dail y, 1 0 0 -m g o nce -dail y, a n d 
2 0 0 -m g fil g oti ni b o nce -d ail y gr o u ps, res pecti vel y, c o m pare d wit h 2 9. 2 % o n place b o) ( p  < 0. 0 0 0 1 
f or all c o m paris o ns). I n b ot h st u dies, t he A C R 2 0 a p peare d t o plat ea u at Wee k 8 a n d was 
mai ntai ne d t hr o u g h Wee k  2 4. I n a d diti o n, at Wee k  1 2, fil g oti ni b s h o we d a be neficial effect 
acr oss t he f oll o wi n g sec o n dar y efficac y para meters: A C R 5 0, A C R 7 0, A C R -N, Diseas e Acti vit y 
Sc ore 2 8  j oi nts ( D A S 2 8) (C -reacti ve pr otei n [C R P ]), Cli nical Disease Acti vit y I n de x ( C D AI), 
a n d Si m plifie d Disease Acti vit y I n de x ( S D AI). A d ose -de p e n de nt f ast o nset of effi cac y was 
re p orte d, a n d t he res p o ns es were mai ntai ne d or c o nti n ue d t o i m pr o ve t hr o u g h 2 4 wee ks. N o 
si g nifica nt differe nce i n effic ac y w as o bser ve d bet wee n 1 0 0-m g a n d 2 0 0 -m g o nce  dail y d osi n g 
re gi me ns. 

Fil g oti ni b  
 
Pr ot oc ol  G L P G 0 6 3 4 -C L -2 2 7  
Fi nal  
Gala pa g os  
A me n d me nt 2  
C O N FI D E N TI A L  
P a ge  3 5  
0 9 Se p 2 0 2 2  
Safet y i n t he pr o of of c o nce pt st u dies i n Ps A a n d A S was i n li ne wit h t he safet y pr ofile re p ort e d 
fr o m pre vi o us st u dies wit h fil g oti ni b i n R A a n d n o u ne x pecte d safet y si g nals were i de ntifie d.  
1. 3.  
R ati o n al e f or t hi s St u d y a n d Pr o p o s e d St u d y  P o p ul ati o n  
O ver t he last deca d e, c ha n ges i n  tr eat me nt strate gi es f or r he u matic diseas es , acc o m pa ni e d b y 
a d va nces i n dr u g de vel o p me nt a n d t he a d diti o n of tar gete d bi ol o gical t hera pies, ha ve greatl y 
i m pr o ve d t he o utc o mes f or patie nts . Des pite t hese de vel o p me nts, t hera p e utic c halle n ges re mai n. 
O nl y a s u bs et of patie nts res p o n ds t o c urre ntl y a vaila ble bi ol o gic t hera p y w hile ot hers l ose 
res p o nse o ver ti me or bec o me i nt olera nt o ver ti me. T here is a n u n met me dical nee d f or si m ple, 
orall y a d mi nistere d t hera pies wit h n o vel a n d tar gete d mec ha nis ms of acti o n t hat ca n effecti vel y 
i m pr o ve t he disease c o urse w hile bei n g safe a n d well t olerate d. Fil g oti ni b is a n orall y 
a d mi nistere d, s mall m olec ule i n hi bit or of J A K 1 , a n i ntracell ular t yr osi ne ki nase d ysre g ul ate d i n 
s u bjects wit h i nfla m mat or y dis or d ers i ncl u di n g R A, Ps A, A S a n d nr A x S p A . Fil g oti ni b has 
de m o nstrate d a fa v ora ble safet y a n d t olera bilit y pr ofile i n a P hase  2 st u d y i n s u bjects wit h 
m o deratel y t o se verel y acti ve  R A.  Fil g oti ni b is prese ntl y b ei n g e val uat e d i n P hase  3 st u dies i n 
C D, ulcerati ve c olitis ( U C ), a n d R A. Fil g oti ni b is als o bei n g e val uate d i n, Sj ö gre ns s y n dr o me, 
c uta ne o us l u p us er yt he m at os us, n o ni nfecti o us u veitis a n d l u p us me m bra n o us ne p hritis.  
W hile pr o vi di n g a treat me nt o pti o n f or s u bjects wit h R A, Ps A, A S a n d nr A x S p A, t he prese nt 
st u d y see ks t o e val uate t h e i m pact, if a n y, of fil g oti ni b o n s per mat o ge nesis i n h u ma ns . T he 
o bser ve d effects of fil g oti ni b o n t he testes are c o nsiste nt acr oss t he n o n cli nical  s pecies teste d, 
wit h o bser vati o ns of hist o pat h ol o gic al c ha n ges i n testes a n d e pi di d y mi d es, t o get her wit h 
re d ucti o ns i n s per m c o u nts a n d re d uce d fertilit y i n t he rat. A mec h a nistic st u d y i n t he rat 
s u g geste d a re versi ble direct i m pact o n t he ge n es i n v ol ve d i n cell c ycle. A d ose of 2 0 0  m g o n ce 
dail y of fil g oti ni b res ults i n a n esti mate d mea n cli nical  A U C of 2. 8 μ g∙h/ m L i n s u bjects  wit h R A , 
w hic h re prese nts a n e x p os ure mar gi n of 2. 3, 1. 8, a n d 3. 4 -f ol d w he n c o nsi d eri n g t he mea n A U C 
i n male d o gs at t he n o o bser ve d effect le vels ( N O E Ls) i n t he 2 6-wee k a n d 3 9 -wee k c hr o nic 
t o xicit y st u dies, a n d 3 9-wee k tar gete d e x p os ure t o xicit y st u d y, r es pecti vel y. T he prese nt st u d y 
see ks t o assess t he i m pact of fil g oti ni b at 2 0 0 m g, t he hi g hest pr o p os e d d os e i n t he P hase  3 
pr o gra m, assess e d b y t he pr o p orti o n of  male s u bjects w h o e x perie nce a ≥5 0 % decrease  i n s p er m 
c o nce ntr ati o n  fr o m Baseli ne  w he n c o m pare d wit h place b o after 1 3 wee ks of t hera p y. T he 
pr o p ose d st u d y desi g n a n d s u bject p o p ulati o n f or G L P G 0 6 3 4 -C L -2 2 7  ha ve bee n selecte d t o 
ge n erat e cli nical safet y d ata w hic h w o ul d be br oa dl y a p plica ble t o patie nt p o p ulati o ns treate d 
wit h fil g oti ni b . 
T he prese nt st u d y has b ee n desi g n e d i n acc or da nce wit h F D A G ui d a nce f or I n d ustr y:  T estic ular 
T o xicit y: E val uati o n D uri n g Dr u g De vel o p me nt ( Oct o ber 2 0 1 8 ).  
T he st u d y p o p ulati o n will c o nsist of males wit h acti ve R A ( defi ne d as a C D AI sc ore > 1 0), acti ve 
Ps A ( defi ne d as D A P S A sc ore > 1 4) or acti ve A S or nr A x S p A ( defi ne d as Bat h A n k yl osi n g 
S p o n d ylitis Diseas e Acti vit y [ B A S D AI ] ≥4). S u bjects m ust ha ve de m o nstr ate d a pri or tr eat me nt 
fail ure/i nt olera n ce t o disease s pecifi c t hera pies b ut will be all o we d t o re mai n o n per mitte d 
t hera p y, wit h t he e x ce pti o n of S S Z  w hic h will be pr o hi bite d d ue t o k n o w n ris ks of oli g os per mia 
a n d i nfertilit y { P har m aci a & U pj o h n C o 2 0 1 4 } . S u bjects will be stratifie d b y Baseli ne  s p er m 
c o nce ntr ati o n a n d t y p e of u n derl yi n g r he u matic disease  ( R A or s p o n d yl o ar hritis). I n a d diti o n, 
su bjects will als o be stratifie d b y us e of M T X  ( yes or n o) gi ve n its p ote ntial i m pact o n 

Fil g oti ni b  
 
Pr ot oc ol  G L P G 0 6 3 4 -C L -2 2 7  
Fi nal  
Gala pa g os  
A me n d me nt 2  
C O N FI D E N TI A L  
P a ge  3 6  
0 9 Se p 2 0 2 2  
s per mat o ge nesis. There h a ve bee n cas e re p orts of re versi ble oli g os per mia a n d az o os per mia wit h 
treat me nt wit h M T X { S uss ma n 1 9 8 0 } , t h o u g h a s mall case seri es i n 2 6  me n wit h ps oriasi s a ge d 
3 3  t o 5 2 treate d wit h M T X at a d ose of 2 5  m g wee kl y di d n ot re veal a n y i m pact of M T X o n 
mea n s per m c o u nt m otilit y a n d m or p h ol o g y  { El -Be heir y 1 9 7 9 } . 
S u bjects wit h mil dl y decrease d t est oster o ne will als o be i ncl u de d i n t he st u d y. T he i n ci de nce of 
l o w test oster o ne i ncreases wit h i ncreasi n g a ge. T h e cr u de i n ci de nce of a n dr o ge n d eficie nc y i n 
1  lar ge c o h ort (t he Massa c h usetts Male A gi n g St u d y) was 1 2. 3 % o verall, b ut i ncrease d wit h 
increasi n g a ge: 5. 9 % at 4 0 t o 4 9  years, 1 1. 2 % at 5 0 t o 5 9  years, a n d 2 3. 3 % at 6 0 t o 7 0  years 
{ Ara uj o 2 0 0 4 } . O ne c o h ort de m o nstrate d a pre val e nce of h y p o g o na dis m i n me n a ge d 4 5 a n d 
ol der ( base d o n t otal test oster o ne < 3 0 0 n g/ d L) of 3 8. 7 % { M ulli ga n 2 0 0 6 } . T he prese nt st u d y will 
i ncl u de me n wit h test oster o ne le vels at or a b o ve 8 0 % of n or mal, gi ve n t he e x pecte d i nci de nce of 
h y p o g o na dis m i n t he u p p er a ge ra n ge of t he st u d y p o p ulati o n.  
1. 3. 1.  
R ati o n al e f or t h e O ut c o m e M e a s ur e s  
W hile n o si n gle s per m para meter ca n pre dict fertilit y p ote ntial, s per m c o nce ntrati o n ma y b e 
c o nsi dere d t he m ost relia bl y q ua ntifia ble para meter t hat has p ote ntial utilit y i n pr o vi di n g 
i nf or mati o n a b o ut male fertilit y ( F D A G ui da n ce o n Testic ular T o xicit y; Oct o ber 2 0 1 8). S per m 
c o nce ntr ati o n ma y als o b e c o nsi dere d t he m ost i m p orta nt para m eter of testi c ular d ysf u ncti o n 
( Si k ka & Hellstr o m, C urre nt u p dates o n la b orat or y tec h ni q ues f or t he di a g n osis of male 
re pr o d ucti ve fail ure., 2 0 1 6). T he pres e nt st u d y will e val uate t he re d ucti o n i n s per m c o nce ntrati o n 
of ≥5 0 % or m ore fr o m Baseli ne  at 1 3 wee ks as t h e pri mar y e n d p oi nt i n acc or da nce wit h t he F D A 
g ui da n ce. Si g nifi ca nt variati o ns i n s per m para met ers are e x pecte d i n me n; a t hres h ol d of a 
≥5 0 %  re d ucti o n is c o nsi d ere d t he a p pr o priat e t hres h ol d t o acc o u nt f or n or m al varia bilit y a n d is 
c o nsi ste nt wit h pri or st u dies e val uati n g i m pact of p ote ntial testic ular t o xi ns ( Si k ka, et al., 2 0 1 4; 
Hellstr o m, et al., 2 0 0 8; Hellstr o m, et al., 2 0 0 3; J ar vi, et al., 2 0 0 8) . S u bsta ntial i ntra- a n d i nter - 
s u bject variati o n c a n occ ur partic ularl y i n s per m c o u nt i n patie nts wit h a n d wit h o ut 
fertilit y iss ues; i n o ne c o h ort, s per m c o u nts ra n ge d o ver a n or der of m a g nit u de i n a 
si n gle healt h y  p atie nt o ver ti me ( Keel, 2 0 0 6). T w o se me n sa m ples will be c ollecte d f or 
e val uati o n at eac h ti me p oi nt d uri n g t his st u d y, wit h c o ntr olle d  a bsti ne nce peri o ds bef ore eac h 
sa m ple c ollecti o n; l o n ger or s h orter a bsti ne n ce peri o ds ma y ha v e a n i m pact o n q ualit y of sa m ple. 
Ejac ulate v ol u me a n d s p er m c o u nt are mar k e dl y re d uce d d uri n g p eri o ds of hi g h ejac ulati o n 
fre q ue n c y ( Ol derei d, G or dela dze, Kir k h us, & P ur vis, 1 9 8 4). Si g nifica nt varia bilit y is n ote d e ve n 
i n healt h y s u bjects ( W orl d Healt h Or ga nizati o n ( W H O), La b orat or y M a n ual f or t he e x a mi nati o n 
of h u ma n se me n a n d s p er m -cer vical m uc us i nteracti o n. F o urt h E diti o n., 1 9 9 9; W orl d Healt h 
Or ga niz ati o n ( W H O), La b orat or y ma n ual f or t he E x a mi nati o n a n d pr ocessi n g of h u ma n s e me n. 
Fift h E diti o n., 2 0 1 0) . A d diti o nal s per m para meters at 1 3 wee ks will be e v al uate d as sec o n d ar y 
e n d p oi nts i n ali g n me nt wit h t he F D A G ui da n ce o n Testic ular T o xicit y ( Oct o ber 2 0 1 8) .  
T he pri mar y e n d p oi nt at Wee k  1 3 will e na ble a direct assess me nt vers us pl ace b o i n s u bjects wit h 
R A , PsA , A S, a n d nr A x S p A . E n d p oi nts at 2 6 wee ks of t hera p y h a ve bee n c h ose n f or sec o n dar y  
a n d e x pl orat or y a nal yses t o assess i m pact after 2  f ull s per mat o ge nesis c ycl es i n acc or da nce wit h 
T he F D A G ui da nce o n T estic ular T o xicit y ( Oct o ber 2 0 1 8) , w hic h rec o m me n ds treat me nt f or 
2 6  wee ks f or dr u gs t hat are c hr o ni call y d ose d. T he 2 6 -wee k e n d p oi nt will als o all o w assess me nt 
of t he i m pact of l o n ger -ter m t hera p y o n se me n p ara meters, gi ve n t he e x pectati o n f or c hr o nic 
d osi n g of t hera p y i n t he real w orl d setti n g. Fi nall y, i n t h e prese nt st u d y, t ot al m otilit y, w hic h is 

Fil g oti ni b  
 
Pr ot oc ol  G L P G 0 6 3 4 -C L -2 2 7  
Fi nal  
Gala pa g os  
A me n d me nt 2  
C O N FI D E N TI A L  
P a ge  3 7  
0 9 Se p 2 0 2 2  
c o nsi dere d t o be m ore c o nsiste ntl y m eas ure d acr oss o bser vers, will re m ai n as a sec o n d ar y 
e n d p oi nt.  
I n t his st u d y t he A C R/E U L A R  ( 2 0 1 0) criteria will be use d t o defi ne a di a g n osis of R A, t he 
C A S P A R criteria will be use d t o defi ne a di a g n osis of Ps A, a n d t he Assess me nt of 
S p o n d yl o art hritis I nter n ati o nal S ociet y ( A S A S) criteria f or will be use d t o defi ne a dia g n osis of 
a xial s p o n d yl oart hritis ( A S or n o n -ra di o gra p hical a xial s p o n d yl oart hritis [ nr A x S p A]) f or t he 
p ur p ose of eli gi bilit y.  
S u bjects wit h R A a n d Ps A will be re q uire d t o h a v e a n i na de q u ate res p o nse or i nt olera nce t o at 
least a 1 2-w ee k c o urse of cs D M A R D or bi ol o gical D M A R D ( b D M A R D) t h era p y f or t heir 
art hritis. S u bjects wit h A S a n d n r A x S p A will be re q uire d t o ha ve a n i na de q uate res p o ns e or 
i nt olera nt t o at least 2 N S AI Ds (see S ecti o n 4. 2 ). 
At t he Wee k  1 3  Visit , P h ysicia n Gl o b al Assess me nt of Di sease Acti vit y (P h G A D A ) will be use d 
t o deter mi ne art hritis Res p o n der, a n d art hritis N o n -res p o n der stat us. D uri n g t he E xte nsi o n P hase, 
i n di vi d ual s u bject res p o nse t o treat me nt has t o be e val uate d at eac h visit i n acc or da nce wit h g o o d 
r he u mat ol o g y practice. 
T his st u d y is base d u p o n real  w orl d o ut patie nt cli nical practice, w here cli ni cal si g ns/s y m pt o ms 
(a n d la bs as a p plica ble) a n d a pr o vi der’s assess me nt are a d e q uate t o ass ess t hera pe utic res p o nse 
or n o n -res p o ns e. Safet y a n d t olera bilit y will be ass esse d b y the e v al uati o n of a d verse e ve nts 
( A Es), sele cte d cli nical l a b orat or y p ara met ers, vital si g ns, p h ysical e xa mi nati o ns, a n d E C Gs  all 
of w hic h are sta n dar d safet y e val uati o ns i n cli nical de vel o p me nt. All s u bjects w h o e x perie nce a 
≥5 0 % decrease i n s per m c o nce ntr ati o n a n d/ or t otal m otilit y a n d/ or n or mal m or p h ol o g y will be 
f oll o we d f or o n e or m ore s per mat o ge nesis c ycles, u p t o 5 2  wee ks  as nee de d, t o assess f or s per m 
para meter re v ersi bilit y.  
1. 3. 2.  
R ati o n al e f or t h e C h oi c e of D o s e a n d D o si n g I nt er v al  
T he 2 0 0  m g o n ce  dail y d ose le vel of fil g oti ni b is c urre ntl y t he hi g hest cli nical d ose bei n g 
e val uate d i n P hase  3 st u dies of R A, U C, a n d C D.   
1. 4.  
Ri s k/ B e n efit A s s e s s m e nt f or t h e St u d y  
O ver t he last deca d e, c ha n ges i n R A a n d Ps A tr eat me nt strate gies, acc o m pa nie d b y a d va nces i n 
dr u g d e vel o p me nt a n d t h e a d diti o n of tar get e d t hera pies, ha v e i m pr o ve d patie nt o utc o mes. 
Des pite t hese de v el o p me nts, t hera pe utic c h alle n ges re mai n. C urre nt cs D M A R Ds a n d b D M A R Ds 
ma y pr o d uce o nl y partial res p o nses i n s o me patie nts a n d ma y b e ass ociat e d wit h si g nif ica nt 
safet y a n d t olera bilit y c o ncer ns. T here is a n o n g oi n g nee d f or orall y a d mi nistere d t hera pies wit h 
n o vel a n d tar get e d mec h a nis ms of acti o n t hat ca n m ore effecti vel y i m pr o ve t he disease c o urse.  
N o ncli nical st u dies i n rats a n d d o gs i de ntifie d l y m p h oi d tiss ues a n d testes as tar get or ga ns f or 
fil g oti ni b i n l o n g-ter m re peat-d ose t o xicit y st u dies. Alt h o u g h decrease d l y m p h oc yte n u m b ers 
o bser ve d i n n o ncli nical st u dies ha ve n ot bee n s ee n i n cli nical st u dies, he mat ol o gical assess me nt 
will be perf or me d t hr o u g h o u t t he prese nt st u d y t o e ns ure t his p ote ntial ris k is a p pr o priatel y 
m o nit ore d. I n b ot h r ats a n d d o gs, micr osc o pic fi n di n gs i n t he testes i ncl u d e d ger m cell de pleti o n 
a n d de ge n erati o n, wit h re d uce d s per m c o nte nt a n d i ncreas e d cell de bris i n t he e pi di d y mis a n d 

Fil g oti ni b  
 
Pr ot oc ol  G L P G 0 6 3 4 -C L -2 2 7  
Fi nal  
Gala pa g os  
A me n d me nt 2  
C O N FI D E N TI A L  
P a ge  3 8  
0 9 Se p 2 0 2 2  
re d ucti o n i n fertilit y i n m ale rats. T he d o g was det er mi ne d t o be t he m ost se nsiti ve s pecies. W he n 
usi n g t he A U C at t he N O A E Ls f or d o gs i n t he 2 6 -wee k a n d 3 9 -wee k c hr o nic t o xicit y st u dies, 
a n d t he 3 9-wee k tar gete d e x p os ure t o xicit y st u d y, t he e x p os ure ma r gi ns c o m pare d wit h t he 
hi g hest pr o p os e d cli nical d ose of 2 0 0  m g o n ce  d ail y are 2. 5, 1. 9, a n d 3. 6 -f ol d res pecti vel y, i n 
s u bjects wit h R A . T o assess t his p ote ntial ris k t o male fertilit y, t he m ale safet y cli nical st u d y 
descri be d h erei n is pla n n e d t o e x a mi ne  t he effect of fil g oti ni b (if a n y) o n s per m/ejac ulat e 
para meters. Male s u bjects w h o e nr oll will be a p pr o priatel y c o nse nte d vi a t he i nf or me d c o ns e nt 
f or m (I C F) w herei n ris k l a n g u a ge is hi g hli g hte d. I m paire d s per mat o ge nesis is c o nsi dere d t o be a 
p ote ntial ri s k f or fil g oti ni b. Refer t o t he I B f or f urt her i nf or mati o n a b o ut n o ncli nical a n d cli nical 
testic ular fi n di n gs. 
Fil g oti ni b has s h o w n a n i ncreas e d ris k i n e m br y ofetal malf or mati o ns i n rats a n d ra b bits at 
e x p os ures si milar t o, or sli g htl y hi g her t ha n, e x p os ur es ass ociat e d wit h a 2 0 0  m g o nce  dail y d ose 
i n s u bjects wit h R A. As a res ult, hi g hl y effecti ve c o ntrace pti o n a n d mal e c o n d o ms will be 
re q uire d f or male s u bjects wit h fe male part n ers of c hil d beari n g p ote ntial, w hic h is e x pecte d t o 
miti gate t his ris k.  
J A K i nhi biti o n is e x pecte d t o i ncrease t h e ris k of i nfecti o n base d o n m ec ha nis m of acti o n. Acr oss 
t he gl o bal st u dies i n fil g oti ni b, i n ge neral, acti ve tr eat me nt ar ms ha v e i ncrease d i nci de nces of 
i nfecti o n versus place b o. I n t he prese nt pr ot oc ol, treat me nt i nterr u pti o n a n d disc o nti n uati o n 
c o nsi derati o ns s urr o u n di n g i nfecti o ns are i n c or p orate d, a n d sites a n d i n v esti gat ors will be trai n e d 
re gar di n g s uc h circ u msta nces. All s u bjects will be scree n e d f or T B, a n d s u bjects wit h acti ve 
i nfecti o ns will be e x cl u de d. Mali g n anc y has b ee n re p orte d i n s u bjects o n fil g oti ni b; i n t he 
prese nt st u d y, s u bjects wit h rece nt mali g na nci es will be e x cl u de d as o utli ne d i n t he i ncl usi o n 
criteria. F or f urt her details a b o ut i nfecti o ns a n d mali g na nci es, please refere n ce t he I B.  
T he p ote ntial b e nefits of J A K i n hi biti o n i ncl u de i m pr o ve me nt i n cli nical s y m pt o ms. J A K 
i n hi biti o n ma y b e efficaci o us i n t he treat me nt of R A, Ps A, A S a n d nr A x S p A  base d o n res ults 
fr o m t he P hase 2 st u dies of s u bjects wit h Ps A, a n d A S . Fil g oti ni b is c urre ntl y i n P hase  3 st u dies 
f or R A. 
O verall , cli nical fi n di n gs a n d la b orat or y c ha n ges ass ociate d wit h fil g oti ni b are c o nsiste nt wit h 
J A K 1 i n hi biti o n. Base d o n P hase 2 a n d P hase 3  d ata t he e x pecte d be n efit of usi n g fil g oti ni b as 
pr o p ose d i n t his st u d y is c o nsi dere d t o o ut wei g h a n y ass o ciate d ris ks. I n a d diti o n, t he s u bject 
p o p ulati o n i n t he prese nt st u d y will c o nse nt t o a ris k of p ote ntiall y per ma ne nt i nfertilit y, t h us 
i n di vi d ual male s u bjects i n c o nj u ncti o n wit h t he treati n g p h ysici a n ma y e v al uate t he be nefit -ris k 
pr ofile of fil g oti ni b. A lac k of res p o ns e c o nti n ge n c y fr o m Wee k  1 3 o n war d i n t he c urre nt st u d y, 
tar geti n g art hritis  N o n -res p o n ders at Wee k 1 3, will e na ble earl y access t o acti ve dr u g or S ta n dar d 
of C are tr eat me nt w he n cli nicall y i n dicate d. T his r esc ue a p pr oac h, t he p r o visi o n of best 
s u p p orti ve care d uri n g t h e e xte nsi o n p hase , a n d t h e li mite d st u d y d urati o n, ma kes t he use of 
place b o et hicall y acce pta ble f or t he s pecifie d d urati o n.  
A n e xter nal m ulti disci pli nar y Data M o nit ori n g C o m mittee ( D M C ), i ncl u di n g a n e x pert i n male 
fertilit y, will be a p p oi nte d t o m o nit or t he st u d y.  
T he D M C  has  m o nit or e d  t he st u d y u ntil t he date of pr ot oc ol a me n d me nt 2, i ncl u di n g t he dat a f or 
t he sec o n d u n bli n de d i nteri m a nal ysis (I A 2). As of a me n d me nt 2, t he D M C will be  

Fil g oti ni b  
 
Pr ot oc ol  G L P G 0 6 3 4 -C L -2 2 7  
Fi nal  
Gala pa g os  
A me n d me nt 2  
C O N FI D E N TI A L  
P a ge  3 9  
0 9 Se p 2 0 2 2  
dec o m missi o ne d. Details o n t he D M C’s r ole ha v e bee n descri be d i n a s pecific c harter. T h e 
D M C’s r ole will be tra nsferre d t o t he i nter nal S p o ns or  Safet y M a na ge me nt T ea m  ( S S M T). T he 
S S M T is  n ot i n v ol ve d i n t he c o n d uct of t he st u d y a n d will e val uate safet y d a ta t hr o u g h o ut t he 
re mai n der of t he st u d y as part of c o nti n u o us safet y o versi g ht acr oss t he fil g oti ni b pr o gra m. 
Ta ki n g all of t hese c o nsi derati o ns i nt o acc o u nt wit h res pect t o t he fil g oti ni b pr o gra m, t he earl y 
si g nals f or effi cac y d e m o nstrate d i n P hase  2  a nd P hase  3  cli nical st u dies of R A , A S a n d Ps A , as 
well as t he be neficial fi n di n gs i n n o ncli nical m o d els of disease a n d t he o verall safet y, 
t olera bilit y, a n d P K c h aracteristics of fil g oti ni b el uci date d t o date, t here is a fa v ora ble be n efit -
ris k pr ofile f or t his a ge nt i n c o nti n ue d de vel o p me nt as a treat me nt f or R A, Ps A, A S, a n d 
nr A x S p A . T he o verall be nefit -ris k bala nce of t his st u d y is c o nsi dere d fa v ora ble. 
F or a d diti o nal i nf or mati o n a b o ut t he ris ks of fil g oti ni b, refere nce t h e latest versi o n of t he 
fil g oti ni b I B. 
1. 5.  
C o m pli a n c e  
T his st u d y will be c o n d u cte d i n c o m plia nce wit h t his pr ot oc ol,  G o o d Cli nical Practice  (G C P ), 
a n d all a p plica ble re g ulat or y re q uire m e nts.  
2.  
O B J E C TI V E S  
T he pri mar y o bje cti ve of t his st u d y is:  
•  
T o e val uate t he effect of fil g oti ni b o n testic ular f u ncti o n as defi ne d b y t he pr o p orti o n of 
s u bjects wit h a ≥ 5 0 % decreas e fr o m Bas eli ne  i n s per m c o nce ntrati o n at Wee k  1 3  
T he sec o n d ar y o bjecti ves of t his st u d y i ncl u de:  
•  
T o e val uate t he effect of fil g oti ni b o n testic ular f u ncti o n as defi ne d b y t he pr o p orti o n of 
s u bjects wit h a ≥ 5 0 % decreas e fr o m Bas eli ne  i n s per m c o nce ntrati o n at Wee k 2 6  
•  
T o e val uate t he effect of fil g oti ni b o n s per m t otal m otilit y at Wee ks  1 3 a n d 2 6  
•  
T o e v al uate t he effect of fil g oti ni b o n t otal s per m c o u nt at Wee ks  1 3 a n d 2 6  
•  
T o e val uate t he effect of fil g oti ni b o n t he c ha n ge fr o m Baseli ne  i n s p er m c o nce ntrati o n at 
Wee ks  1 3 a n d 2 6  
•  
T o e val uate t he effect of fil g oti ni b o n ejac ulat e v ol u me at Wee ks  1 3 a n d 2 6  
•  
T o e val uate t he effect of fil g oti ni b o n s per m m or p h ol o g y at Wee ks  1 3 a n d 2 6  
T he e x pl orat or y o bj ecti v es of t his st u d y i ncl u de: 
•  
T o e val uate t he re versi bilit y of o bser ve d effects of fil g oti ni b o n testic ular f u ncti o n i n 
s u bjects w h o e x perie nce a ≥ 5 0 % decreas e i n s per m c o nce ntrati o n, a n d/ or m otilit y , a n d/ or 
m or p h ol o g y  

Fil g oti ni b  
 
Pr ot oc ol  G L P G 0 6 3 4 -C L -2 2 7  
Fi nal  
Gala pa g os  
A me n d me nt 2  
C O N FI D E N TI A L  
P a ge  4 0  
0 9 Se p 2 0 2 2  
•  
T o e val uate t he effect of fil g oti ni b o n se x h or m o nes, i ncl u di n g l utei nizi n g h or m o ne ( L H), 
f ollicle sti m ulati n g h or m o ne ( F S H), i n hi bi n B, a n d t otal test oster o ne at Wee ks 1 3 a n d  2 6  
•  
T o e val uate t he s a fet y a n d t olera bilit y of fil g oti ni b 
•  
T o c haracteriz e t he plas ma P K of fil g oti ni b a n d  its meta b olite ( G S-8 2 9 8 4 5, f or merl y 
 
3.  
S T U D Y D E SI G N  
T his is a ra n d o mize d, d o u ble -bli n d, place b o -c o ntr olle d, P hase  2 st u d y i n a d ult males wit h acti ve 
R A, Ps A, A S or nr A x S p A w h o ha ve h a d a n i na de q uate res p o ns e t o pri or art hritis t hera p y as 
o utli ne d i n t he i ncl usi o n criteria, a n a d verse pr o g n osis of t heir c o n diti o n per t he i n vesti gat or a n d 
ma y b e nefit fr o m treat me nt wit h a J A K i n hi bit or.  
U p t o 2 5 0  males bet wee n t he a ges of 2 1 a n d 6 5  years (i ncl usi ve) at t he ti me of c o nse nt will be 
ra n d o mize d t o recei ve fil g oti ni b 2 0 0 m g or pl ace b o o nce  dail y  f or 1 3 wee ks .  
Ra n d o mizati o n will be stratifie d acc or di n g t o t he t y p e of r he u m atic c o n diti o n ( R A  or 
S p o n d yl o art hrit is [Ps A, A S, nr A x S p A ]), b y c o n c urre nt use of M T X ( yes or n o), a n d b y s per m 
c o nce ntr ati o n meas ure d at Scree ni n g  (“Bas eli ne ”) acc or di n g t o t he f oll o wi n g strat a:  
•  
1 5 t o 2 5  milli o n/ m L  
•  
>  2 5 t o 5 0 milli o n/ m L  
•  
>  5 0  milli o n/ m L  
Male s u bjects wit h R A , Ps A, A S  or  nr A x S p A w h o pr o vi de writte n i nf or m e d c o nse nt will be 
scree n e d t o deter mi ne eli gi bilit y as p er t he i ncl usi o n a n d e x cl usi o n criteria (see Secti o n  4. 2  
a n d 4. 3 , res pecti vel y).  
T he Scree ni n g  p eri o d will be u p t o 4 5  da ys a n d ma y  b e e xte n de d i n c o ns ultati o n wit h t he 
S p o ns or  M e dical M o nit or.  D uri n g t he Scree ni n g p eri o d, s u bjects will pr o vi de 2  se me n sa m ples 
wit hi n a 1 4 -da y peri o d as detaile d i n Secti o n  6. 1 1  (ie, t he Scree ni n g [“ Bas eli ne”] sa m ple). 
T he assess me nts t o be perf or me d at eac h visit are detaile d i n t he st u d y pr oce d ures ta ble 
(A p pe n di x  2 ). A sc he matic of t he st u d y d esi g n is pr o vi de d bel o w. 
C CI

Fil g oti ni b  
 
Pr ot oc ol  G L P G 0 6 3 4 -C L -2 2 7  
Fi nal  
Gala pa g os  
A me n d me nt 2  
C O N FI D E N TI A L  
P a ge  4 1  
0 9 Se p 2 0 2 2  
Fi g ure  3 -1 . St u d y Sc he m e 
 
T here are 3  disti nct parts t o t he st u d y:  
1)  D o u ble – bli n d Treat me nt P hase ( Da y  1 t hr o u g h W ee k  1 3 St u d y Visit ) 
2)  E xte nsi o n P hase ( After Wee k  1 3 St u d y Visit a n d u p t o Wee k  1 5 6)  
3)  M o nit ori n g  P hase ( u p t o 5 2  wee ks)  
After f ulfilli n g all selecti o n criteria, s u bjects will be ra n d o mize d t o fil g oti ni b or place b o ( 1: 1) at 
Da y  1 a n d e nt er t he D o u ble -bli n d Treat me nt P has e. Bas e d o n t he o utc o mes of t he Wee k  1 3 
assess me nts (ie, i n di vi d ual s u bject’s res p o ns e of t he u n derl yi n g r he u m atic c o n diti o n t o t he 
assi g ne d treat me nt a n d/ or t he  o bser ve d c ha n ges i n s per m para m eters d uri n g t he d o u ble -bli n d 
treat me nt p hase), s u bjects ma y e nt er t he E xte nsi o n or M o nit ori n g P hase.  

Fil g oti ni b  
 
Pr ot oc ol  G L P G 0 6 3 4 -C L -2 2 7  
Fi nal  
Gala pa g os  
A me n d me nt 2  
C O N FI D E N TI A L  
P a ge  4 2  
0 9 Se p 2 0 2 2  
3. 1.  
D o u bl e -bli n d Tr e at m e nt P h a s e ( D a y  1 t hr o u g h W e e k 1 3 St u d y 
Vi sit)  
Fi g ure  3 -2 . D o u ble -bli n d Tre at me nt P h ase –  W ee k  1 3 E v al u ati o n  
 
  
D uri n g t h e D o u ble -bli n d Treat me nt P hase , all s u bjects will recei ve bli n de d st u d y dr u g f or 
1 3  wee ks  starti n g fr o m t he Da y 1/ Ra n d o mizati o n St u d y Visit . S u bjects will visit t he cli nical 
st u d y ce nt er t o be e val uat e d f or cli nic al a n d la b orat or y ass ess me nts at Da y 1, Wee k  2, Wee k  4, 
Wee k  8, a n d Wee k  1 3.  At t he Wee k  1 3 st u d y visit,  sper m  para m eters (s ee S e me n c ollecti o n a n d 
A nal ysis)  will be e val uat e d t o det er mi ne w het her t he y m eet a n y of t h e pre -s pecifie d decrease 
t hres h ol ds (see D efi niti o n of Ter ms ). I n a d diti o n, art hritis res p o nse stat us ( Art hritis N o n-
res p o n der vs Art hritis Res p o n der, see Defi niti o n of Ter ms ) will be det er mi ne d. As s o o n as t he 
Wee k 1 3 se m e n res ults are a vaila bl e t o t he i n vesti gat or a n d ha v e bee n e val uate d , s u bjects are 
assi g ne d t o o n e of t he f oll o wi n g : 
•  S u bjects w h ose se me n para meters meet a n y of t h e pre -s pecifie d decrease t hres h ol ds, 
re gar dl ess of art hritis res p o nse stat us, will disc o nti n ue bli n de d st u d y dr u g a n d e nter t he 
M o nit ori n g P hase.  T hes e s u bjects will als o ha ve a safet y f oll o w -u p visit 3 0  da ys after l ast 
st u d y dr u g d ose. 
•  S u bjects w h o are art hritis N o n -res p o n d ers a n d w h ose sper m  para meters d o n ot meet a n y of 
t he pre-s pecifie d d ecreas e t hres h ol ds will disc o nti n ue bli n de d st u d y dr u g a n d start Sta n dar d 
of Care tr eat me nt (see D efi niti o n of Ter ms ) d uri n g t he E xte nsi o n P hase. T hese s u bjects will 
als o ha ve a s afet y f oll o w -u p visit 3 0  da ys after last st u d y dr u g d ose.  
•  
S u bjects w h o are A rt hritis Res p o n ders a n d w h ose sper m  para m eters d o n ot meet a n y of t he  
pre -s pecifie d decrease t hres h ol ds will be u n bl in de d b y t he I W R S s yste m a n d e nter t he 
E xte nsi o n P hase. S u bjects o n fil g oti ni b will c o n vert t o o pe n -la bel fil g oti ni b a n d s u bjects 
recei vi n g pla ce b o will s witc h t o Sta n dar d of Care treat me nt. 
Bli n de d 
Treat me nt  
S per m  
effect  
M o nit ori n g 
P has e 
Res p o n der  
O pe n -la bel 
Fil g oti ni b 
Yes  
N o  
St a n dar d of 
Care  
U n bli n d  
N o  
Yes  
Fil g oti ni b 
Place b o  
D o u ble -bli n d Treat me nt P hase –  Wee k 1 3 E val uati o n  

Fil g oti ni b  
 
Pr ot oc ol  G L P G 0 6 3 4 -C L -2 2 7  
Fi nal  
Gala pa g os  
A me n d me nt 2  
C O N FI D E N TI A L  
P a ge  4 3  
0 9 Se p 2 0 2 2  
3. 2.  
E xt e n si o n P h a s e  
Fi g ure  3 -3 . E xte ns i o n P h ase –  E v al u ati o n  
 
* O pe n -la bel treat me nt wit h fil g oti ni b or Sta n dar d of Care . A dj ust me nt of bac k gr o u n d treat me nt wit h n o n -pr o hi bite d me dicati o n 
all o we d at a n y ti me d uri n g t h e E xte nsi o n P hase  
I n t he E xte nsi o n P hase, s u bjects will recei v e o pe n-la bel treat me nt (fil g oti ni b or Stan dar d of 
Care) a n d h a ve a st u d y visit e ver y 1 3  wee ks t hat i ncl u des se me n a n al ysis.  T he first  sc he d ule d 
visit of t he E xte nsi o n P hase occ urs at Wee k  2 6.   
I n case s p er m para meters at a n y visit (i ncl u di n g Wee k  1 5 6) meet a n y of t he pre -s pecifie d 
decrease t hr es h ol ds, s u bjects will e nter t he M o nit ori n g P hase.  
D uri n g t h e E xte nsi o n p hase,  S ta n dar d of C are a n d bac k gr o u n d tr eat me nt c o nc o mita nt t o 
fil g oti ni b ma y b e o pti mize d at t he discreti o n of t he i n vesti gat or, ta ki n g i nt o c o nsi derati o n t he 
pr ot oc ol restricti o ns.  
I n case a s u bject ne e ds t o be treate d wit h a pr o hi bite d me dicati o n  (see Ta bl e  5 -1 ), f or i nsta nce t o 
c o ntr ol t heir r he u matic c o n diti o n, t he s u bject will disc o nti n ue t he st u d y a n d c o m plete a n Earl y 
Ter mi nati o n ( E T) visit (i ncl u di n g se me n c ollecti o n). F or s u bjects o n fil g oti ni b, t his will be 
f oll o we d b y a safet y f oll o w-u p visit 3 0  da ys after last st u d y dr u g d ose.  
All s u bjects w h o di d n ot e nter t he M o nit ori n g P hase will c o nti n ue t he st u d y u ntil t he Wee k  1 5 6 
visit.  
In t he E xte nsi o n P hase, s u bjects m ust ha ve yearl y Q ua ntifer o n ®  testi n g. Yearl y T B testi n g be gi ns 
1 year fr o m t he scree ni n g T B test date. If yearl y T B testi n g falls bet wee n st u d y visits, t he yearl y 
T B testi n g s h o ul d b e perf or me d at t he visit pri or t o 1 year fr o m t he scree ni n g T B test date. 
S u bjects wit h ne wl y p ositi ve (c o n vert e d) Q ua ntifer o n ®  ( or ce ntr all y re p ort e d e q ui vale nt assa y) 
T B test s h o ul d be disc o nti n ue d fr o m t he st u d y. S u bjects w h o were pre vi o usl y treate d f or T B wit h 
a c o m plete a n d a de q uat e c o urse of t hera p y as per l ocal Sta n dar d of Care a n d as verifie d b y t he 
i n vesti gat or d o n ot nee d t o ha ve yearl y tests.  
O pe n -la bel * 
S per m  
effect  
M o nit ori n g P hase  
Nee d f or 
Pr o hi bit e d 
C o n c o mit a nt 
Tr eat m e nt 
C o nti n ue O pe n -
la bel Treat me nt 
N o  
Yes  
N o  
Yes  
E xte nsi o n P hase –  E val uati o n  
C o n d uct E arl y 
T er mi nati o n Visit  

Fil g oti ni b  
 
Pr ot oc ol  G L P G 0 6 3 4 -C L -2 2 7  
Fi nal  
Gala pa g os  
A me n d me nt 2  
C O N FI D E N TI A L  
P a ge  4 4  
0 9 Se p 2 0 2 2  
3. 3.  
M o nit ori n g P h a s e ( u p t o 5 2  w e e k s)  
Fi g ure  3 -4 . M o nit ori n g P h ase - E v al u ati o n  
 
* A dj ust me nt of bac k gr o u n d treat me nt wit h n o n -pr o hi bite d me dicati o n all o we d at a n y ti me d uri n g t he M o nit ori n g P hase  
S u bjects w h ose s per m para meters meet a n y of  t h e pre-s pecifie d decrease t hres h ol ds will s witc h 
t o t he M o nit ori n g P hase i m me diatel y. S u bjects o n d o u ble -bli n de d treat me nt or o pe n -la bel 
fil g oti ni b w h o e nter t h e M o nit ori n g P hase will disc o nti n ue st u d y dr u g a n d start Sta n dar d of Care. 
T hese s u bjects will als o ha ve a safet y f oll o w -u p visit 3 0  da ys after last st u d y dr u g d os e. S u bjects 
o n Sta n dar d of Care will c o nti n ue treat me nt.  
A ll s u bjects w h o e nter t h e M o nit ori n g P hase will u n der g o se me n e val uati o ns e ver y 1 3  wee ks  
starti n g fr o m t heir e ntr y i nt o t he M o nit ori n g P hase, f or u p t o 5 2 wee ks or u ntil Re versi bilit y (see 
Defi niti o n of Ter ms ) is met , w hic he ver is ac hie ve d first.  
I n case a s u bject ne e ds t o be treate d wit h a pr o hi bite d me dicati o n  (see Ta bl e  5 -1 ), f or i nsta nce t o 
c o ntr ol t heir r he u matic c o n diti o n, t he s u bject will disc o nti n ue t he st u d y a n d c o m plete a n E T visit 
(i ncl u di n g se m e n c ollecti o n).  
3. 4.  
S e m e n C oll e cti o n a n d a n al y s i s: 
At eac h of t h e f oll o wi n g ti me p oi nts, s u bjects will pr o vi de 2  se parate se m e n sa m ples c ollecte d 
wit hi n a 1 4 -da y peri o d. E ac h se me n s a m ple m ust be c ollecte d wit h a ≥4 8  h o urs a n d ≤7  da ys 
ejac ulati o n free peri o d  ( S ecti o n 6. 1 1 ) at t he f oll o wi n g ti me p oi nts.  
•  
Scree ni n g ( Bas eli ne ) 
•  
After t he D o u bl e -bli n d Treat me nt P hase ( Wee k  1 3 st u d y visit)  
•  
E ver y 1 3  wee ks d uri n g t he E xte nsi o n P hase  
•  
E ver y 1 3  wee ks d uri n g t he M o nit ori n g P hase  
•  
At t he Earl y Ter mi nati o n Visit  
St a n dar d of 
Care 
M o nit ori n g 
P has e *  
S per m 
Para met ers 
Re verse d  
E n d of St u d y  
Nee d f or 
Pr o hi bit e d 
C o n c o mit a nt 
Tr eat m e nt  
C o nti n ue St a n dar d 
of Care Treat me nt 
N o  
Yes  
N o  
Yes  
M o nit ori n g P hase - E val uati o n  
C o n d uct E arl y 
T er mi nati o n Visit  

Fil g oti ni b  
 
Pr ot oc ol  G L P G 0 6 3 4 -C L -2 2 7  
Fi nal  
Gala pa g os  
A me n d me nt 2  
C O N FI D E N TI A L  
P a ge  4 5  
0 9 Se p 2 0 2 2  
I n s elect c ases w h ere t he se me n sa m ple wit h q uesti o ne d val ue(s) is f o u n d t o be n o n -assess a ble or 
i n vali d (e g, c ollecti o n wit h o ut a d here nce t o ejac ulati o n -free peri o d; i nterc urre nt ill ness or 
de h y drati o n at ti me of c ollecti o n; i nc o m plete ca pt ure of se me n s a m p le; a n d/ or sa m ple pr ocessi n g 
or se me n a n al ysis t hat de viates fr o m sta n dar dize d pr oce d ure ), a t hir d se me n sa m ple, w he n 
i n dicate d, m ust be c ollect e d wit hi n 1 4  da ys of t he pri or sa m ple a n d wit h a n ejac ulati o n free 
peri o d of  ≥4 8  h o urs a n d ≤7  da ys. All decisi o n s o n retesti n g a n y se me n/s per m para meters 
(ie, o btai ni n g a t hir d se m e n sa m ple at a n y of t he a b o ve ti me p oi nts) m ust be c o nfir me d  b y t h e 
S p o ns or  Me dical Lea d er or desi g n ee b ef ore t he ret est.  
3. 5.  
St u d y Tr e at m e nt s  
U p t o 2 5 0  s u bjects will be ra n d o mize d i n a 1: 1 rati o t o recei ve fil g oti ni b 2 0 0 m g o nce  dail y  or 
place b o o nce  dail y.  
3. 6.  
D ur ati o n of Tr e at m e nt  
T he d ur ati o n of bli n de d treat me nt is a p pr o xi matel y 1 3  wee ks f oll o we d b y a n o pe n -la bel 
E xte nsi o n P hase of u p t o 1 4 3  wee ks . S u bjects e nteri n g t he M o nit ori n g  P has e  will be  f oll o we d f or 
u p t o 5 2  wee ks or u ntil Re versi bilit y (s ee Defi niti o n of Ter ms ) is met, w hic he ver is ac hie ve d 
first.  
3. 7.  
Crit eri a f or  I nt err u pti o n or Di s c o nti n u ati o n of St u d y Tr e at m e nt  
3. 7. 1.  
St u d y Dr u g I nt err u pti o n C o n si d er ati o n s  
T he S p o ns or Me dical Lea der or desi g n ee s h o ul d b e c o ns ulte d pri or t o st u d y dr u g i nterr u pti o n 
w he n me dicall y feasi ble. St u d y dr u g i nterr u pti o n s h o ul d be c o nsi dere d i n t h e f oll o wi n g 
circ u msta nces : 
•  
I nterc urre nt ill ness t hat w o ul d, i n t he j u d g me nt of t he i n vesti gat or, affect assess me nts of 
cli nical stat us t o a si g nifi ca nt de gree.  
•  
S u bject is sc he d ule d f or electi ve or e mer ge n c y s ur ger y (e x cl u di n g mi n or s ki n pr oce d ures 
u n der l ocal or n o a nest hesia); ti mi n g of st u d y dr u g i nterr u pti o n s h o ul d be deter mi ne d i n 
c o ns ultati o n wit h t he S p o ns or M e dical Lea der or desi g nee .   
•  
A n y s u bject w h o de v el o ps a ne w i nfecti o n d uri n g t he st u d y s h o ul d u n der g o pr o m pt a n d 
c o m plete dia g n ostic testi n g a p pr o priate f or a n i m m u n o c o m pr o mise d i n di vi d ual, a n d t he 
s u bject s h o ul d be cl osel y m o nit ore d. 
•  
After bec o mi n g a ware of a la b orat or y c ha n ge re prese nti n g m o derate re nal fail ure (esti mate d  
creati ni ne cleara nce [ Cr Cl] ≥3 5 m L/ mi n a n d < 6 0 m L/ mi n per C oc kcr oft -Ga ult [C C & G ] 
f or m ula) at a n y ti me d uri n g t he st u d y, t he f oll o wi n g acti o ns s h o ul d be ta ke n a n d 
d oc u me nte d : 
⎯ Esta blis h p ossi ble u n derl yi n g c o n diti o n a n d i nitiate a p pr o pri ate acti o n t o res ol ve . 
⎯ Retest Cr Cl  wit hi n 8 wee ks . 

Fil g oti ni b  
 
Pr ot oc ol  G L P G 0 6 3 4 -C L -2 2 7  
Fi nal  
Gala pa g os  
A me n d me nt 2  
C O N FI D E N TI A L  
P a ge  4 6  
0 9 Se p 2 0 2 2  
⎯ Caref ull y c o nsi der i n di vi d ual be nefit/ris k of c o nti n uati o n of fil g oti ni b 2 0 0  m g o nce dail y 
i n relati o n t o t he o bser vati o n. 
⎯ If c o nti n uati o n of fil g oti ni b 2 0 0  m g o nce d ail y is n ot c o nsi dere d a p pr o priate, interr u pt 
treat me nt u ntil retest c o nfir ms Cr Cl ≥6 0 m L/ mi n. 
⎯ T he pri nci pal i n vesti gat or/ de p ut y s h o ul d ass ess i n di vi d ual patie nt be nefit/ris k wit h 
re gar ds t o re-i nitiati o n of treat me nt after re p eat or pr ol o n ge d i nterr u pti o ns, or if 
re-i nitiati o n is n ot c o nsi dere d a p pr o priate. C o ns ult ati o n wit h t he S p o ns or me dical 
m o nit or or desi g nee is pr eferre d i n t hese sit uati o ns. 
D uri n g t h e ti me of st u d y dr u g i nterr u pti o n, s u bjects are t o c o nti n ue wit h st u d y visit partici pati o n 
an d c o m plete st u d y  pr oce d ures a n d assess me nts, dee me d me dicall y a p pr o priate b y t he 
i n vesti gat or. 
After st u d y dr u g i nterr u pti o n, pri or t o res u m pti o n of st u d y dr u g, t h e i n vesti gat or s h o ul d disc uss 
t he case wit h t he S p o ns or Me dical  Lea der or desi g nee.  
3. 7. 2.  
St u d y Dr u g Di s c o nti n u ati o n C o n si d er ati o n s : 
T he S p o ns or Me dical Lea der  or desi g n ee s h o ul d b e c o ns ulte d pri or t o st u d y dr u g disc o nti n uati o n 
w he n me dicall y feasi ble.  
St u d y dr u g s h o ul d be per ma ne ntl y disc o nti n ue d i n t he f oll o wi n g i nsta nces:  
•  A n y o p p ort u nistic i nfect i o n 
•  A n y s eri o us i nfecti o n t hat re q uires p are nt eral/ i ntra ve n o us a nti micr o bial t h era p y or 
h os pitaliz ati o n, or a n y i nfecti o n t hat meets  seri o us a d verse e ve nt (S A E ) re p orti n g criteria. 
•  Fe brile n e utr o pe nia (te m perat ur e > 3 8. 3° C or a s ustai ne d te m perat ur e of > 3 8° C f or m ore t ha n 
1  h o ur) wit h a bs ol ute ne utr o p hil c o u nt of < 1, 0 0 0/ m m 3 
•  S y m pt o matic a ne mia (e g,  si g ns/s y m pt o ms i ncl u di n g pall or, s h ort ness of breat h, ne w h eart 
m ur m ur, pal pitati o ns, let har g y, fati g ue) wit h he m o gl o bi n < 7. 5  g/ d L, or if tra nsf usi o n is 
i n dicate d re gar dless of h e m o gl o bi n val ue 
•  C o m plicate d her pes z oster i nfecti o n ( wit h m ulti -der mat o mal, disse mi nate d, o p ht hal mic, or 
C N S i n v ol ve me nt) 
•  E vi de nce of acti ve H e patitis C vir us ( H C V ) d uri n g t he st u d y, as e vi de nce d b y H C V R N A 
p ositi vit y  
•  E vi de nce of acti ve H e patitis B vir us ( H B V ) d uri n g t he st u d y, as e vi de nce d b y H B V 
de o x yri b o n ucleic aci d ( D N A ) p ositi vit y  
•  A n y t hr o m b o e m b olic e ve nt t hat meets S A E re p orti n g criteria  

Fil g oti ni b  
 
Pr ot oc ol  G L P G 0 6 3 4 -C L -2 2 7  
Fi nal  
Gala pa g os  
A me n d me nt 2  
C O N FI D E N TI A L  
P a ge  4 7  
0 9 Se p 2 0 2 2  
•  U nacce pta ble t o xicit y, or t o xicit y t hat, i n t he j u d g me nt of t he i n vesti gat or, c o m pr o mises t he 
a bilit y t o c o nti n ue st u d y s pecific pr oce d ures or is c o nsi dere d t o n ot be i n t h e s u bject’s best 
i nterest 
•  A  ≥5 0 % decreas e  fr o m Baseli ne ( bas e d o n t he mea n of 2 se parate s e me n sa m ples c ollecte d at 
t he Scree ni n g Visit) i n s p er m c o nce ntrati o n a n d/ or m otilit y a n d/ or m or p h ol o g y   
•  S u bject re q uest t o disc o nti n ue f or a n y reas o n  
•  S u bject n o nc o m plia nce  t o t he pr ot oc ol 
•  Disc o nti n uati o n of t he st u d y at t he re q uest of t h e S p o ns or, a re g ulat or y a ge nc y or a n 
i nstit uti o nal re vie w b oar d or i n de pe n de nt et hics c o m mittee (I R B/I E C) 
•  S u bject ’s use of pr o hi bite d  c o nc urre nt t hera p y will tri g ger st u d y disc o nti n uati o n; c o ns ultati o n 
s h o ul d be ma de wit h t he S p o ns or M e dical Lea d er or desi g n ee  
•  S u bjects wit h ne wl y p ositi ve (c o n vert e d) Q ua nti F E R O N ®  T B test ( or ce ntr all y re p orte d 
e q ui vale nt assa y) a n d/ or a n y s u bject wit h acti ve T B  
•  A n y of t he bel o w d escri b e d a b n or mal la b orat or y c ha n ges occ urri n g at a n y o ne ti me, a n d 
c o nfir me d b y re peat testi n g ( A p pe n di x  1 1 ):   
⎯ 2  se q ue ntial ne utr o p hil c o u nts < 0. 7 5 x 1 0 9 cells/ L ( 7 5 0 ne utr o p hils/ m m 3)  
⎯ 2  se q ue ntial platelet c o u nts < 7 5. 0 x 1 0 9 cells/ L (7 5, 0 0 0 platelets/ m m 3)  
⎯ 2 se q ue ntial as part ate a mi n otra nsferase ( A S T) or ala ni ne a mi n otra nsferase ( A L T) 
ele vati o ns > 3 x t he u p per li mit of n or mal ( U L N) a n d at least 1  of t he f oll o wi n g c o nfir me d 
val ues: a) t otal bilir u bi n > 2 x U L N, b) i nter nati o nal n or malize d rati o (I N R) > 1. 5, or 
c) acc o m pa nie d b y s y m pt o ms c o nsiste nt wit h he patic i nj ur y . F or a n y s u bject wit h a n 
i nitial A S T or A L T el e vati o n > 3 x t he U L N, at t he ti me of t he  sec o n d c o nfir mat or y dra w, 
a n I N R, pr ot hr o m bi n ti me ( P T) a n d partial t hr o m b o plasti n ti me ( P T T) m ust als o be 
dra w n.   
⎯ 2  se q ue ntial A S T or A L T ele vati o ns > 5 x U L N  
⎯ 2 se q ue ntial val ues f or  esti mate d Cr Cl  < 3 5  m L/ mi n base d o n t he C C & G  f or m ula 
•  S u bjects w h o per ma ne ntl y st o p st u d y dr u g d ue t o pre -s pecifie d decrease i n s per m para m eter s 
( Secti o n 6. 1 1 ) will be offere d  sta n d ar d of care as p art of t he M o nit ori n g P hase . 
•  S u bjects w h o are u n bli n d e d pri or t o Wee k  1 3.  

Fil g oti ni b  
 
Pr ot oc ol  G L P G 0 6 3 4 -C L -2 2 7  
Fi nal  
Gala pa g os  
A me n d me nt 2  
C O N FI D E N TI A L  
P a ge  4 8  
0 9 Se p 2 0 2 2  
3. 7. 3.  
St u d y Di s c o nti n u ati o n  
S u bjects wit h dra wi n g fr o m t he st u d y s h o ul d ma ke e ver y eff ort t o c o m plet e a n E T visit ; f or 
s u bjects o n bli n de d treat me nt or o n  fil g oti ni b, t his will be f oll o we d b y a safet y f oll o w-u p  visit  
3 0  da ys after l ast d ose  of st u d y dr u g .  
S u bjects are free t o wit h dra w fr o m t he st u d y at a n y ti me wit h o ut pr o vi di n g reas o n(s) f or 
wit h dra wal a n d wit h o ut prej u dice t o f urt h er me di cal treat me nt. T h e reas o n(s) f or wit h dr a wal will 
be d oc u me nte d i n t he ele ctr o nic cas e re p ort f or m (e C R F).  
Reas o na ble ef f orts will b e ma de t o c o ntact s u bjects w h o are l ost t o f oll o w-u p. All c o ntacts a n d 
c o ntact atte m pts m ust be d oc u me nte d i n t he s u bject’s file.  
T he S p o ns or has t he ri g ht t o ter mi nate t he st u d y at a n y ti me i n case of safet y c o n cer ns or if 
s pecial cir c u msta nces c o ncer ni n g t he st u d y dr u g or t he c o m pa n y itself occ ur, ma ki n g f urt her 
treat me nt of s u bjects i m p ossi ble. I n t his e ve nt, t he i n vesti gat or(s) a n d rele va nt a ut h orities will be 
i nf or me d of t he reas o n f or st u d y ter mi nati o n. 
3. 8.  
E n d of St u d y  
E n d of St u d y is reac he d w he n t he last sc he d ul e d st u d y visit occ urre d. T his ca n be a Wee k  1 5 6 
visit, a F oll o w -u p visit, or t he last visit of a M o nit ori n g P hase.  
3. 9.  
P o st -St u d y C ar e  
U p o n c o m pleti o n of  st u d y partici pati o n, the l o n g -ter m care of s u bjects will re mai n t he 
res p o nsi bilit y of t heir pri mar y treati n g p h ysicia n.  
4.  
S U B J E C T P O P U L A TI O N  
4. 1.  
N u m b er of S u bj e ct s a n d S u bj e ct S el e cti o n  
U p t o 2 5 0  s u bjects wit h acti ve R A, Ps A, A S or nr A x S p A  will be ra n d o mize d i n t he st u d y t o 
e ns ure 2 0 0  s u bjects are e val ua ble at Wee k 1 3. E nr oll me nt ma y be e x pa n de d if t he dr o p o ut rate is 
hi g her t h a n e x pecte d a n d will be e val uate d d uri n g t he c o urse of t h e st u d y.  
4. 2.  
I n cl u si o n Crit eri a 
S u bjects m ust meet all of t he f oll o wi n g i ncl usi o n criteria t o be eli gi ble f or p artici pati o n i n t his 
st u d y.  
1)  A ble t o u n dersta n d a n d will i n g t o si g n t he i nf or m e d c o nse nt as a p pr o ve d b y t he I R B/I E C. 
Writte n c o nse nt m ust be pr o vi de d bef ore i nitiati n g a n y Scree ni n g  e val uati o ns. S u bjects m ust 
ha ve rea d a n d u n d erst o o d t he I C F, m ust f ull y u n d ersta n d t he re q uire me nts of t he st u d y, a n d 
m ust be will i n g t o c o m pl y wit h all st u d y visits a n d assess me nts; s u bjects w h o ca n n ot rea d or 
u n dersta n d t he I C F ma y n ot be e nr olle d i n t he st u d y b y a g u ar dia n or a n y ot her i n di vi d ual  
2)  Male bet wee n t he a ges of 2 1 a n d 6 5 (i ncl usi ve) o n t he da y of si g ni n g i nf or m e d c o nse nt  

Fil g oti ni b  
 
Pr ot oc ol  G L P G 0 6 3 4 -C L -2 2 7  
Fi nal  
Gala pa g os  
A me n d me nt 2  
C O N FI D E N TI A L  
P a ge  4 9  
0 9 Se p 2 0 2 2  
3)  B o d y mass i n de x ( k g/ m 2) of ≥1 8. 5 t o ≤4 0 at Scree ni n g , wit h n o e vi de n ce of mal n utriti o n as 
deter mi ne d b y t he i n vesti gat or  
4)  Dia g n osis of R A , Ps A, A S, or nr A x S p A f or at least 1 2  wee ks pri or t o S cree ni n g, meeti n g t he 
c orres p o n di n g s pecific cl assificati o n criteri a:  
a)  R A, A C R/ E ur o pea n Lea g ue A gai nst R he u matis m ( E U L A R) 2 0 1 0  
b)  Ps A, Classificati o n criteria f or Ps oriatic Art hritis ( C A S P A R) criteria  
c)  A S or nr A x S p A, Assess me nt of S p o n d yl oart hritis I nter nati o nal S ociet y ( A S A S) 
criteria f or a xial s p o n d yl oart hritis  
5)  F or R A, Ps A, A S, or nr A x S p A, meets t he f oll o wi n g criteria:  
a)  R A  
i. I n a de q uat e res p o ns e or i nt olera nt t o a n ≥1 2 -wee k s’ c o urse of cs D M A R D or 
b D M A R D t hera p y f or R A  
ii. Ha ve a n C D AI > 1 0 at S cree ni n g  
b)  Ps A  
i. I n a de q uat e res p o ns e or i nt olera nt ≥1 2 -wee ks’ c o urse of cs D M A R D or 
b D M A R D t hera p y f or Ps A  
ii. Ha ve a Disease Acti vit y i n Ps oriatric Art hritis ( D A P S A) sc ore > 1 4 at 
S cree ni n g  
c)  A xial S p o n d yl oart hritis (a p plica ble t o t h ose wit h dia g n osis of A S or nr A x S p A) 
i. I n a de q uat e res p o ns e or i nt olera nt t o at least 2 N S AI Ds, w hic h ma y i ncl u d e 
c ycl o o x y ge nas e -2 ( C O X -2 i n hi bit ors) prescri be d f or a t otal peri o d of ≥4 
wee ks O R t o a n at least 1 2 -wee ks’ c o urse of cs D M A R D or b D M A R D t hera p y 
f or s p o n d yl o art hritis 
ii. Ha ve a B A S D AI ≥4 at S cree ni n g  
iii. At S cree ni n g, s u bjects s h o ul d ha ve a hi g h -se nsiti vit y C -reacti ve pr ot ei n 
(hs C R P) > 0. 3  m g/ d L O R sacr oiliitis acc or di n g t o t he m o difie d Ne w Y or k 
( N Y) criteria O R a hist or y of acti ve i nfla m mati o n o n ma g n etic res o n a nce 
i ma gi n g ( M RI) c o nsiste nt wit h sacr oiliitis wit hi n 2  year s of scree ni n g  
6)  If usi n g cs D M A R D t hera p y, s u bjects are p er mitte d t o use o ne of t he f oll o wi n g dr u gs, al o n e 
or i n c o m bi nati o n ( wit h t he e x ce pti o n of t he M T X-L E F c o m bi nati o n) a n d m ust ha ve bee n o n 
a sta ble d ose of t he dr u g  f or at least 4 wee ks pri or t o Scree ni n g a n d re mai n o n  a sta ble d ose 
d uri n g t he D o u ble -bli n d Treat me nt P hase  of  t he st u d y (sta bl e d ose i n all cases is defi ne d as 
n o c ha n ge i n pr escri pti o n) : 

Fil g oti ni b  
 
Pr ot oc ol  G L P G 0 6 3 4 -C L -2 2 7  
Fi nal  
Gala pa g os  
A me n d me nt 2  
C O N FI D E N TI A L  
P a ge  5 0  
0 9 Se p 2 0 2 2  
a)  M T X oral or pare nteral u p t o 2 5  m g/ wee k ( pl us c o nc o mita nt use of f olic or f oli nic 
aci d s u p ple me ntati o n as per l ocal S tan dar d of C are) 
b)  Lefl u n o mi de  ( L E F) u p t o 2 0  m g/ da y orall y  
c)  H y dr o x yc hl or o q ui ne u p t o 4 0 0  m g/ da y or c hl or o q ui ne u p t o 2 5 0  m g/ da y orall y  
d)  A pre milast orall y u p t o 3 0  m g t wice d ail y  
N ote t hat S S Z  is n ot per mitte d at a n y ti me, be gi n ni n g 2 6  wee ks pri or t o S cree ni n g u ntil 
t he e n d of t he st u d y, a n d ca n n ot be i ncl u de d i n t he Sta n dar d of C are art hritis re gi me n, d ue 
t o its p ote ntial i m pact o n se me n para meters. 
7)  T he mea n of 2  s e parate s e me n sa m ples c ollecte d at Scree ni n g  m ust meet t he f oll o wi n g 
mi ni m u m criteria (i n acc or da nce wit h Secti o n  6. 1 1 ): se me n v ol u me ≥1. 5  m L, t otal s per m per 
ejac ulate ≥3 9  milli o n, s per m c o nce ntrati o n ≥1 5  milli o n per m L, s per m t otal m oti lit y ≥4 0% 
a n d n or mal s per m m or p h ol o g y ≥3 0 %  
8)  L H, F S H, i n hi bi n B, a n d t otal test oster o ne val ues wit hi n 2 0 % of la b orat or y refere nce ra n ges 
d uri n g Scree ni n g  
9)  S u bjects w h o e n ga ge i n h eter ose x ual i nterc o urse m ust a gree t o use pr ot o c ol -s pecifie d 
met h o d(s) of c o ntr ace pti o n as descri be d i n A p pe n di x  1 0  i ncl u di n g use of c o n d o ms d uri n g t he 
st u d y a n d f or 9 0 da ys aft er t he last d ose of st u d y dr u g  
1 0)  Willi n g ness t o refrai n fr o m recei vi n g li ve a n d atte n uate d vacci nes wit hi n 3 0  da ys of Da y  1, 
t hr o u g h o ut t he st u d y, a n d f or 1 2 wee ks aft er t he last d ose of st u d y dr u g ( Secti o n  5. 4 , Vacci n e 
G ui deli nes ). 
1 1)  M eet o ne of t he f oll o wi n g 3  T B Scree ni n g  criteria:  
a)  N o e vi de nce of acti ve or late nt T B:  
⎯ A ne gati ve Q u a nti F E R O N ®  T B -G ol d Pl us I n-T u b e test at Scree ni n g, A N D  
⎯ A c hest ra di o gra p h ( vie ws as per l ocal g u i deli nes) ta ke n at Scree ni n g or wit hi n t he 
3  m o nt hs pri or t o Scree ni n g ( wit h t he re p ort or fil ms a vaila ble f or i n vesti gat or 
re vie w) wit h o ut e vi de nce of acti ve or l ate nt T B i nf ecti o n, A N D 
⎯ N o hist or y of eit her u ntreate d or i na de q u atel y treate d late nt T B i nf e cti o n  
b)  Pre vi o usl y treate d f or T B:  
⎯ A s u bject w h o has pr e vi o usl y recei ve d a n a d e q uat e c o urse of t hera p y as per l ocal 
sta n dar d of care f or eit her late nt T B (e.g . 9  m o nt hs of is o niazi d i n a l ocati o n w here 
rates of pri mar y m ulti-dr u g resista nt T B i nf ecti o ns are  < 5 %, or a n alter nati ve re gi me n 
acc or di n g t o l ocal c o u ntr y g ui deli nes) or acti ve T B (acce pta ble m ulti -dr u g re gi me n). 

Fil g oti ni b  
 
Pr ot oc ol  G L P G 0 6 3 4 -C L -2 2 7  
Fi nal  
Gala pa g os  
A me n d me nt 2  
C O N FI D E N TI A L  
P a ge  5 1  
0 9 Se p 2 0 2 2  
I n t hes e cases, n o Q ua nti F E R O N®  T B -G ol d  P L us  I n-T u be test ( or a ce ntrall y re p orte d 
e q ui vale nt assa y) nee ds t o be o btai ne d.  
⎯ A c hest ra di o gr a p h m ust be o btai ne d if n ot d o ne wit hi n 3  m o nt hs pri or t o Scree ni n g  
( wit h t he re p ort or fil ms a vaila ble f or i n vesti gat or re vie w).  
⎯ It is t he res p o nsi bilit y of t he i n vesti gat or t o v erif y t he a de q uac y of pre vi o us a nti-T B  
treat me nt a n d pr o vi d e a p pr o priate d ocu m e ntati o n.  
c)  Ne wl y i de ntifie d late nt T B d uri n g Scree ni n g :  
⎯ A s u bject w h o has a n e wl y i de ntifie d p ositi ve dia g n ostic T B test res ult ( defi ne d as a 
p ositi ve Q ua nti F E R O N ®  T B -G ol d Pl us I n -T u b e test or e q ui vale nt assa y) i n w hic h 
acti ve T B has bee n r ule d o ut a n d f or w hic h a p pr o priate, o n g oi n g treat me nt f or late nt 
T B has b ee n i nitiate d f or at least 4  wee ks pri or t o t he first  a d mi nistrati o n of st u d y 
dr u g.  
⎯ A de q uate treat me nt f or l ate nt T B is defi ne d acc or di n g t o l ocal c o u ntr y g ui deli nes f or 
i m m u n oc o m pr o mise d patie nts . 
Cases falli n g u n d er cate g or y “ b” a n d “c” m ust be a p pr o ve d b y t he S p o ns or Me dical Lea der 
or desi g n ee pri or t o e nr oll me nt i n t he st u d y. N o s u bject wit h c urre ntl y acti ve or u ntreate d 
late nt T B ma y b e e nr olle d i n t he st u d y. If a s u bject ha d a Q ua nti F E R O N®  T B -G ol d Pl us I n-
T u be test f or t he p ur p os es of cli nical care or f or t h e p ur p ose of Scree ni n g f or a n ot her 
Gala pa g os - or Gilea d -s p o ns ore d st u d y wit hi n 6 0 da ys, t he pri or res ult ma y be use d t o assess 
eli gi bilit y.  
1 2)  La b orat or y p ara m eters n ee d t o be met as p er bel o w : 
a)  He patic pa n el ( A S T, A L T, t otal bilir u bi n) ≤ 2 X  t he U L N 
b)  Esti mate d Cr Cl ≥ 4 0  m L/ mi n as calc ulate d b y t he C C & G  e q uati o n  
c)  He m o gl o bi n ≥8  g/ d L  
d)  A bs ol ute ne utr o p hil c o u nt ( A N C) ≥ 1. 5 × 1 0 9/ L ( 1, 5 0 0/ m m 3) 
e)  Platelets ≥1 0 0 × 1 0 9/ L 
f) W hite bl o o d cells ( W B C) ≥3. 0 x 1 0 9/ L 
g)  A bs ol ute L y m p h o c yt e c o u nt > 7 5 0/ m m 3 

Fil g oti ni b  
 
Pr ot oc ol  G L P G 0 6 3 4 -C L -2 2 7  
Fi nal  
Gala pa g os  
A me n d me nt 2  
C O N FI D E N TI A L  
P a ge  5 2  
0 9 Se p 2 0 2 2  
4. 3.  
E x cl u si o n Crit eri a  
S u bjects w h o meet  a ny  of t he f oll o wi n g e x cl usi o n criteria are n ot t o be e nr olle d i n t his st u d y  
( N ote: “ Scree ni n g” refers t o t he first da y of Scree ni n g). 
1)  Pre vi o usl y d oc u me nt e d pr o ble ms wit h male re pr o d u cti ve healt h i ncl u di n g, b ut n ot li mite d t o , 
k n o w n h y p ot hal a mic -pit uitar y dis or d ers (e .g . pit uitar y macr oa de n o mas, pit uitar y i nf arcti o n, 
h y per pr ola cti ne mia, pa n h y p o pit uitaris m), pri mar y h y p o g o na dis m (e .g . cr y pt orc hi dis m, 
Kli nefelter’s s y n dr o me)  
2)  Pri or dia g n o sis of male i nfertilit y (i ncl u di n g re d u ce d fertilit y), or hist or y of a nti -s per m 
a nti b o dies  
3)  Cli nicall y si g nifica nt ( per j u d g me nt of i n v esti gat or) varic o cele or s per m at ocele  
4)  Hist or y of ra diati o n t o t he testicles  
5)  Hist or y of cli nicall y si g nifica nt tra u ma t o, or s ur ger y o n, t he testicles, i ncl u di n g vasect o m y  
6)  C urre nt treat me nt wit h a ntia n dr o ge n t hera p y  (i ncl u di n g b ut n ot li mite d t o s pir o n olact o ne, 
oral ket oc o naz ole , or c y pr oter o ne acet ate), or tr eat me nt wit hi n 4 wee ks of Scree ni n g  
7)  C urre nt treat me nt wit h  test oster o ne re place me nt t h era p y, or treat me nt wit hi n 1 2  wee ks of 
Scree ni n g  
8)  C urre nt treat me nt wit h 5 -α re d uct ase i n hi bit ors  (i ncl u di n g b ut n ot li mite d t o fi nasteri de a n d 
d utasteri de ), or treat me nt wit hi n 4 wee ks of Scree ni n g  
9)  C urre nt treat me nt wit h al p ha -1  bl oc kers (i ncl u di n g b ut n ot li mite d t o ta ms ul osi n, d o x az osi n, 
praz osi n) , or treat me nt wit hi n 4 wee ks of Scree ni n g  
1 0)  C urre nt use of S S Z  or us e of S S Z wit hi n 2 6  wee ks of Scree ni n g; S S Z is n ot per mitte d at a n y 
p oi nt d uri n g t he st u d y  
1 1)  C urre nt use of  wit h al k yl at i n g a ge nts or a n y rec o g nize d testic ular t o xi n, or treat me nt wit hi n 
2 6  wee ks pri or t o Scree ni n g  ( ma y be disc usse d wit h S p o ns or Me dical Lea d er or desi g nee)  
1 2)  C urre nt treat me nt wit h T N F α a nta g o nist (i ncl u di n g b ut n ot li mite d t o i nfli xi ma b, 
a dali m u ma b n eta nerce p t, g oli m u ma b, cert oliz u ma b, a n d bi osi milar a ge nts), or treat me nt 
wit hi n 4  wee ks of Scree ni n g  
1 3)  Use of a n y  pr o hi bite d c o nc o mita nt me dicati o n (s) as descri be d i n Secti o n 5. 3 )  
1 4)  K n o w n h y p erse nsiti vit y t o fil g oti ni b, its meta b olites, or f or m ulati o n e xci pie nts  
1 5)  Prese nce of dis or ders of s per m tra ns p ort i ncl u di n g , b ut n ot li mite d t o retr o gra de ej ac ulati o n 
a n d i m m otile cilia s y n dr o me  

Fil g oti ni b  
 
Pr ot oc ol  G L P G 0 6 3 4 -C L -2 2 7  
Fi nal  
Gala pa g os  
A me n d me nt 2  
C O N FI D E N TI A L  
P a ge  5 3  
0 9 Se p 2 0 2 2  
1 6)  Cli nicall y si g nifica nt uri nar y tract i nfecti o n, pr ost atitis, e pi di d y mitis, i ncl u di n g se x uall y 
tra ns mitte d i nfecti o n wit hi n 4 wee ks of Scree ni n g  
1 7)  P ositi ve uri ne test f or a m p heta mi nes or c o cai ne; p ositi ve test t o o pi oi ds wit h o ut a 
prescri pti o n, or hea v y t o bac c o use (c urre nt use of ≥2 pac ks per da y e q ui vale nt)  
1 8)  U nc o ntr olle d t h yr oi d d ysf u ncti o n (e g, u ntreate d h y p ot h yr oi dis m or h y pert h yr oi dis m)  
1 9)  A n y s e x ual d ysf u ncti o n of a nat ur e t hat w o ul d pre ve nt s per m c ollecti o n i n acc or da nce wit h 
pr ot oc ol g ui da n ce ( p h os p h o dies terase i n hi bit ors, h o we ver, are p er mitte d d uri n g t he st u d y) 
2 0)  Hist or y of m aj or s ur ger y or tra u ma wit hi n 3 0  da ys pri or t o Scree ni n g , or a ntici pate d nee d f or 
maj or s ur ger y d uri n g t he st u d y  
2 1)  Vacci n ati o n wit h li ve atte n uate d vacci ne(s) wit hi n 3 0  da ys of Da y  1 (see als o Secti o n 5. 4 , 
Vacci n e G ui deli nes)  
2 2)  A p ositi ve test res ult f or h u ma n i m m u n o deficie nc y vir us ( HI V )-1 or HI V -2 ( See 
A p pe n di x  1 2 ) 
2 3)  E vi de nce of acti ve H C V i nfecti o n. S u bjects wit h p ositi ve H C V a nti b o d y ( A b) at Scree ni n g , 
re q uire refle x testi n g f or H C V R N A. S u bjects wit h p ositi ve H C V R N A at Scree ni n g  will be  
e x cl u de d. S u bjects wit h p ositi ve H C V A b, b ut ne gati ve H C V R N A are eli gi ble per 
i n vesti gat or j u d g me nt. S u bjects wit h acti ve H C V d uri n g t he st u d y, as e vi de nce d b y H C V 
R N A p ositi vit y will be disc o nti n ue d fr o m st u d y dr u g as o utli ne d i n t he pr ot oc ol.  
2 4)  E vi de nce of acti ve H B V i nfecti o n. S u bjects wit h p ositi ve H e patitis B s urface a nti ge n 
( H Bs A g) at Scree ni n g are e x cl u de d fr o m t he st u d y. S u bjects wit h p ositi ve H B V c ore A b a n d 
ne gati ve H Bs A g, re q uire refle x testi n g f or H B V D N A. S u bjects wit h p ositi ve H B V D N A at 
Scree ni n g will be e x cl u de d. S u bjects wit h p ositi ve H B V c ore A b a n d n e gati ve H B V D N A 
are eli gi ble per i n vesti gat or j u d g me nt, b ut ma y re q uire pr o p h ylactic tr eat me nt i n acc or da n ce 
wit h H B V treat me nt g ui deli nes/l ocal sta n dar d of care a n d re q uir e o n g oi n g m o nit ori n g wit h 
bl o o d tests f or H B V D N A e ver y 3  m o nt hs. S u bjects wit h e vi de nce of acti v e he patitis  B 
d uri n g t he st u d y, as e vi de nce d b y H B V D N A p ositi vit y, will be disc o nti n u e d fr o m st u d y dr u g 
as o utli ne d i n t he pr ot oc ol.  
2 5)  Prese nce of C hil d -P u g h Class C he patic i m pair m e nt 
2 6)  Hist or y of m ali g na n c y wit hi n t he past 5  years pri or t o Scree ni n g , (e x ce pti o n will be ma de f or 
a de q uatel y tr eate d b asal cell carci n o ma or n o n -m etastatic s q ua m o us cell carci n o ma of t h e 
s ki n, wit h n o e vi de nce of rec urre nce) 
2 7)  Hist or y of l y m p h o pr oliferati ve dis or der, l y m p h o m a, le u ke mia, m yel o pr oliferati ve dis or der, 
or m ulti ple m yel o ma  
2 8)  Hist or y of l e u k oc yta p heresis ≤6  m o nt hs pri or t o Scree ni n g  

Fil g oti ni b  
 
Pr ot oc ol  G L P G 0 6 3 4 -C L -2 2 7  
Fi nal  
Gala pa g os  
A me n d me nt 2  
C O N FI D E N TI A L  
P a ge  5 4  
0 9 Se p 2 0 2 2  
2 9)  A n y c hr o nic me dical c o n diti o n (i ncl u di n g, b ut n ot li mite d t o, car diac or p ul m o nar y dis ease, 
or s u bsta nce a b use) or ps yc hi atric pr o ble m t hat, i n t he o pi ni o n of t he in vesti gat or, w o ul d 
ma ke t he s u bject u ns uita ble f or t he st u d y or w o ul d pre ve nt c o m plia nce wit h t he st u d y 
pr ot oc ol pr oce d ures  
3 0)  Acti ve cli nicall y si g nifi ca nt i nfecti o n, or a n y i nf ecti o n re q uiri n g h os pitalizati o n or treat me nt 
wit h i ntra ve n o us a nti -i nf ecti ves wit hi n 3 0  da ys of Scree ni n g ( or 8 wee ks of Da y 1) ; or a n y 
i nfecti o n re q uiri n g oral a nti-i nfecti ve t hera p y wit hi n 2  wee ks of  Scree ni n g ( or 6  wee ks of  
Da y  1)  
3 1)  Hist or y of o p p ort u nistic i nfecti o n or i m m u n o defici e nc y s y n dr o me  
3 2)  C urre ntl y o n a n y s yste mic ( oral or i ntra ve n o us) a nti -i nfecti ve t hera p y f or c hr o nic i nfecti o n 
(s uc h as p ne u m o c ystis p ne u m o nia [P C P ], c yt o me gal o vir us ( C M V), her pes z oster, at y pical 
m yc o b acteri a)  
3 3)  Hist or y of disse mi nate d St a p hyl oc occ us a ure us  i nfecti o n 
3 4)  Hist or y of s y m pt o matic her pes z oster or her pes si m ple x wit hi n 1 2  wee ks of Scree ni n g , or 
a n y hist or y of disse mi nate d her pes si m ple x, disse mi nate d her pes z oster, o p ht hal mic z oster, or 
C N S  z oster 
3 5)  Partici pati o n i n a n y cli nical st u d y of a n i n vesti gati o nal de vic e wit hin 3 0  da ys, i n vesti gati o nal 
n o n -bi ol o gic dr u g wit hi n 3 0  da ys, or i n vesti gati o nal bi ol o gic dr u g wit hi n 8  wee ks (or 
5  half -li ves, w hic he v er is l o n ger), pri or t o Scree ni n g.  
5.  
I N V E S TI G A TI O N A L M E DICI N A L P R O D U C T S  
5. 1.  
R a n d o mi z ati o n, Bli n di n g a n d Tr e at m e nt C o d e s  
A n I nteracti ve We b Res p o nse S yste m (I W R S) will be e m pl o ye d t o ma na ge s u bject 
ra n d o mizati o n a n d treat me nt assi g n me nts. It is t he res p o nsi bilit y of t he i n v esti gat or t o e ns ure t hat 
t he s u bject is eli gi ble f or t he st u d y pri or t o e nr oll me nt. S u bjects will be assi g ne d a Scree ni n g 
n u m ber at t he ti me of c o nse nt.  
5. 1. 1.  
Bli n di n g  
D uri n g t h e ra n d o mize d D o u ble -bli n d Treat me nt P hase , s u bjects a n d all pers o n nel directl y 
i n v ol ve d i n t he c o n d uct of t he st u d y will be bli n de d t o treat me nt assi g n m e nt. S pecifie d pers o n nel 
n ot directl y i n v ol ve d i n t he st u d y c o n d uct ma y be u n bli n de d base d o n t heir st u d y r ole. St u d y 
dr u g will be dis pe nse d b y t he st u d y p har macist, or desi g n ee, i n a bli n de d fas hi o n t o t he s u bjects. 
T he P har mac o ki n etics File A d mi nistrat or, or desi g nee, i n Bi oa nal yti cal O p er ati o ns a n d/ or 
Cli nical Data Ma na ge me nt, w h o facilitates t he dat a tra nsfer of P K files b et wee n t he S p o ns or a n d 
ve n d ors, will re mai n u n bli n de d. I n di vi d uals i n Cli nical Pac ka gi n g & La b eli n g or Cli nical S u p pl y 
Ma na ge me nt w h o h a ve a n U n bli n de d I n ve nt or y Ma na ger  r ole i n t he I W R S s yst e m f or p ur p os es 
of st u d y dr u g i n v e nt or y ma na ge me nt will re mai n u n bli n de d. I n di vi d uals r es p o nsi ble f or safet y 
si g nal detecti o n, I n vesti gati o nal Ne w Dr u g (I N D) safet y re p orti n g a n d/ or e x pe dite d re p orti n g of 
s us pecte d u ne x pecte d seri o us a d verse reacti o ns ( S U S A Rs) ma y b e u n bli n de d t o i n di vi d ual case 

Fil g oti ni b  
 
Pr ot oc ol  G L P G 0 6 3 4 -C L -2 2 7  
Fi nal  
Gala pa g os  
A me n d me nt 2  
C O N FI D E N TI A L  
P a ge  5 5  
0 9 Se p 2 0 2 2  
data a n d/ or gr o u p l e v el s u m maries. E xter nal (i e, c o ntract res earc h or ga nizati o ns  [ C R Os]) 
bi ostatisticia ns a n d p r o gram mers will be u n bli n de d t o pr o d uce ta bles, fi g ures, a n d listi n gs f or 
u n bli n de d re vie w at D M C meeti n gs, a n d t he e xter nal bi ostatisticia n will ser ve as t he e xter nal 
statisticia n t o t he D M C. Re g ulat or y Q ualit y a n d C o m plia nce pers o n nel i n Researc h a n d 
De vel o p m e nt ma y als o b e u n bli n de d f or p ur p os es of s u p p orti n g Q ualit y Ass ura nce acti vities 
a n d/ or Re g ulat or y A ge n c y i ns pecti o ns.  
F or o n g oi n g s u bjects, t he st u d y tea ms a n d st u d y st aff at t he sites a n d all ot her staff directl y 
i n v ol ve d i n t he c o n d uct of t he st u d y will re m ai n bli n de d t o t he d o u ble -bli n d p hase treat me nt 
assi g n me nts u ntil t he fi n al a nal ysis w he n t he data base has bee n l oc ke d. P u blicati o n of t he I A 2 
data is pla n ne d b y t he S p o ns or. T his p u blicati o n will c o ntai n gr o u p le vel data f or t he e ntire st u d y 
p o p ulati o n, b ut will u n bli n d t he st u d y tea ms a n d staff directl y i n v ol ve d i n t h e c o n d uct of t he 
st u d y t o t he i n di vi d ual baseli ne treat me nt assi g n m e nt of s u bjects w h o c o m plete d t he st u d y b ef ore 
I A 2.   
5. 1. 2.  
Pr o c e d ur e s f or Br e a ki n g Tr e at m e nt C o d e s  
After  Wee k  1 3 of t h e D o u b le-bli n d Treat me nt P hase, s u bjects w h o are Art hritis Res p o n ders a n d 
w h ose s per m para meters d o n ot meet a n y of t he pre -s pecifi e d decrease t hres h ol ds will be 
u n bli n de d b y t he I W R S s yste m  a n d e nter t he E xte nsi o n P hase . 
Bli n di n g of st u d y tr eat m e nt u ntil t he Wee k  1 3 visit is critical t o t he i nte grit y of t his cli nical 
st u d y. T heref ore, t reat me nt assi g n me nts s h o ul d re mai n bli n de d u ntil t he se me n a nal ysis res ults 
relate d t o t he Wee k 1 3 visit are k n o w n , u nless t hat k n o wle d ge is necessar y t o deter mi ne 
e mer ge n c y me dical care f or t he s u bject. I n t h e e ve nt of a me dical e m er ge n c y w here brea ki n g t he 
bli n d  pri or t o c o m pleti o n of t he Wee k  1 3 visit  pr oce d ures  is r e q uire d t o pr o vi de me dical care t o 
t he s u bject, t he i n vesti gat or ma y o btai n t he i n di vi d ual s u bject treat me nt assi g n me nt directl y fr o m 
t he IW R S s yste m . T he S p o ns or  rec o m me n ds, b ut d oes n ot re q uire , t hat t he i n vesti gat or c o ntacts 
t he S p o ns or M e dical Lea der or desi g nee bef ore brea ki n g t he bli n d.  
T he i n vesti gat or h o we v er m ust c o ntact t he S p o ns or Me dical Lea der or desi g nee pr o m ptl y after 
u n bli n di n g pri or t o t he Wee k  1 3 visit. T he rati o nal e f or u n bli n di n g m ust be clearl y e x plai ne d i n 
s o urce d oc u m e ntati o n a nd o n t he e C R F, al o n g wit h t he date o n w hic h t he tr eat me nt assi g n me nt 
was u n bli n de d . If a s u bject’s treat me nt assi g n me nt is discl ose d t o t he i n vesti gat or, t he s u bj ect 
will ha ve st u d y dr u g disc o nti n ue d. All s u bjects will be f oll o we d u ntil st u d y c o m pleti o n u n less 
c o nse nt t o d o s o is s pecificall y wit h dr a w n b y t he s u bject.  
T he S p o ns or  ma y i n de pe n de ntl y u n bli n d cas es pri or t o t he Wee k  1 3 visit f or e x pe dite d re p orti n g 
of S U S A Rs  t o Re g ulat or y A ut h orities. 
5. 2.  
D e s cri pti o n a n d H a n dli n g  of Fil g oti ni b  a n d Pl a c e b o  
5. 2. 1.  
F or m ul ati o n  
Fil g oti ni b is a vaila ble as 2 0 0  m g stre n gt h ta blets. Fil g oti ni b 2 0 0 m g t a blets are bei ge,  de b osse d 
wit h “ G SI” o n o ne si de a n d “ 2 0 0” o n t he ot her , ca ps ule-s ha pe d, bic o n ve x, fil m-c oate d ta blets f or 
cli nical use. Eac h t a blet c o ntai ns t he e q ui vale nt  of 2 0 0 m g fil g oti ni b free b ase i n t he f or m of 
fil g oti ni b maleate. I n a d diti o n t o t he acti ve i n gre die nt, fil g oti ni b ta blets c o ntai n t he f oll o wi n g 

Fil g oti ni b  
 
Pr ot oc ol  G L P G 0 6 3 4 -C L -2 2 7  
Fi nal  
Gala pa g os  
A me n d me nt 2  
C O N FI D E N TI A L  
P a ge  5 6  
0 9 Se p 2 0 2 2  
i nacti ve i n gre die nts: micr ocr ystalli ne cell ul ose, lact ose m o n o h y drate, f u maric aci d, 
pre gelati nize d starc h, si lic o n di o xi de, ma g nesi u m stearate, m acr o g ol/p ol yet h yle ne gl yc ol ( P E G ) 
3 3 5 0, p ol y vi n yl alc o h ol, talc, tita ni u m di o xi de, ir o n o xi de yell o w, a n d ir o n o xi de re d.  
Place b o  t o matc h ta blets are i de ntic al i n a p peara n ce t o t he acti ve ta blets. Place b o ta bl ets c o ntai n 
t he f oll o wi n g i na cti ve i n gre die nts: micr ocr ystalli ne cell ul ose, lact os e m o n o h y drate, 
cr oscar mell ose s o di u m, ma g n esi u m stearate, m acr o g ol/ P E G 3 3 5 0, p ol y vi n yl alc o h ol, tal c, 
tita ni u m di o xi de, ir o n o xi de yell o w, a n d ir o n o xi de re d. 
5. 2. 2.  
P a c k a gi n g a n d L a b el i n g  
Fil g oti ni b 2 0 0  m g a n d p l ace b o ta bl ets are p ac ka ge d i n w hite, hi g h de nsit y p ol yet h yle ne ( H D P E) 
b ottles. Eac h b ottle c o ntai ns 3 0  ta blets, silica gel d esicca nt a n d p ol yester pac ki n g mat erial. Eac h 
b ottle is e ncl ose d wit h a w hite, c o nti n u o us t hrea d, c hil d -resista nt p ol y pr o p yl e n e scre w ca p fitte d 
wit h a n i n d ucti o n -seale d, al u mi n u m -face d li ner.  
St u d y  dr u gs t o be distri b ute d t o ce nters i n t he p artici pati n g c o u ntri es s hall be la bele d t o meet 
a p plica ble re q uire me nts of t he E U G ui deli ne t o G o o d Ma n ufact uri n g Pr actice –  A n ne x  1 3 
(I n vesti gati o nal Me dici n al Pr o d ucts) a n d/ or ot her l ocal re g ulati o ns, as a p pli ca ble.  
5. 2. 3.  
St or a g e a n d H a n dli n g   
Fil g oti ni b 2 0 0  m g  a n d p l ace b o ta bl ets, s h o ul d be st ore d at c o ntr olle d r o o m t e m perat ur e of  
2 5 °C  ( 7 7F) . Te m p erat ur e varia bilit y b et wee n 1 5 C  a n d 3 0 C ( 5 9 F  t o 8 6 F)  are per mitte d a n d 
are n ot c o nsi dere d e x c ursi o ns . St ora ge c o n diti o n s are s pecifie d o n t he la b el. 
U ntil dis pe nse d t o t he s u bjects, a ll dr u g pr o d ucts s h o ul d be st ore d i n a sec urel y l o c ke d area, 
accessi ble  o nl y t o a ut h ori ze d site pers o n nel. T o e ns ure t he sta bilit y of t h e st u d y dr u g a n d t o 
e ns ure pr o per pr o d u ct i de ntificati o n, t he dr u g pr o d uct s h o ul d n ot be st ore d i n a c o ntai ner ot her 
t ha n t he c o ntai ner i n w hi c h t he y are s u p plie d. C o nsi derati o n s h o ul d be gi v e n t o ha n dli n g, 
pr e parati o n, a n d dis p osal t hr o u g h me as ures t hat mi ni mize dr u g c o ntact wit h t he b o d y. 
A p pr o priate preca uti o ns s h o ul d be f oll o we d t o a v oi d direct e ye c o ntact or e x p os ure w he n 
ha n dli n g.  
5. 2. 4.  
D o s a g e a n d A d mi ni str ati o n  of Fil g oti ni b  a n d Pl a c e b o  
Fil g oti ni b  2 0 0  m g t a blets or p lace b o w ill be a d mi nistere d o nce d ail y wit h or wit h o ut f o o d. Eac h 
s u bject m ust be gi ve n i nstr ucti o ns t o mai ntai n a p pr o xi matel y t he s a me dail y d osi n g i nter val 
bet wee n st u d y dr u g d os es.  
F or misse d d ose(s) of st u d y me dicati o n, s u bjects s h o ul d be i nstr ucte d t o ta ke t he misse d d ose(s) 
of st u d y me dicati o n as s o o n as p ossi ble d uri n g t he sa me da y. S u bjects s h o ul d n ot ta ke t he misse d 
d ose wit h t he ne xt da y’s d ose ( ie d o u ble d ose). M isse d d ose(s) or u n us e d st u d y dr u g, s h o ul d n ot 
be discar de d.  

Fil g oti ni b  
 
Pr ot oc ol  G L P G 0 6 3 4 -C L -2 2 7  
Fi nal  
Gala pa g os  
A me n d me nt 2  
C O N FI D E N TI A L  
P a ge  5 7  
0 9 Se p 2 0 2 2  
5. 3.  
Pri or a n d C o n c o mit a nt M e di c ati o n s  
All me dicati o ns ta ke n u p t o 3 0  da ys pri or t o t he S cree ni n g visit t hr o u g h t he e n d of s u bject’s 
partici pati o n i n t he st u d y nee d t o be rec or de d i n t he s o urce d o c u me nts a n d o n t he e C R F. T here 
s h o ul d be n o variati o n i n d ose or re gi me n d uri n g t he D o u ble -bli n d Treat me nt P hase of t he  st u d y, 
if p ossi ble. At eac h st u d y visit, t he st u d y ce nter will ca pt ure a n y a n d all me dicati o ns ta ke n b y t he 
s u bject si nce t he last visit or d uri n g t h e visit (as a p plica ble). C o nc o mita nt me dicati o ns i ncl u de 
prescri pti o n  a n d n o n -pres cri pti o n me dicati o ns, dietar y s u p ple me nts, a n d mi nerals.  
Effecti ve c urre nt t hera pi es s h o ul d n ot be disc o nti n ue d f or t he s ole p ur p ose of partici pati n g i n t his 
st u d y. S u bjects ma y recei ve me dicati o ns as s u p p orti ve care or t o treat A Es as dee me d necessar y 
b y t he in vesti gat or or t he s u bject’s p h ysi cia n. S h o ul d s u bjects ha ve a n ee d t o i nitiate treat me nt 
wit h a n y pr o hi bite d c o nc o mita nt me dicati o n, t he S p o ns or Me dical Lea d er or desi g n ee s h o ul d be 
c o ns ulte d pri or t o i nitiati o n of t he ne w me dicati o n , if p ossi ble. I n i nsta nces w here a pr o hi bite d 
me dicati o n is i nitiate d pri or t o disc ussi o n wit h t he S p o ns or, t he  in vesti gat or m ust n otif y t h e 
S p o ns or as s o o n as he/s h e is a ware  of t he us e of t he e x cl u de d me dicati o n .  
5. 3. 1.  
All o w e d C o n c o mit a nt M e di c ati o n s  
If usi n g cs D M A R D t hera p y pri or t o t he st u d y , s u bjects are p er mitte d t o c o nti n ue o ne of  t he 
f oll o wi n g dr u gs d uri n g t he st u d y, al o ne or i n c o m bi nati o n ( wit h t he e x ce pti o n of t he M T X-L E F 
c o m bi nati o n ), a n d m ust ha ve bee n o n a sta ble d os e of t he dr u g f or at least 4  wee ks pri or t o 
Scree ni n g a n d re mai n o n a sta ble d ose d uri n g t he D o u ble -bli n d Treat me nt P hase of t he st u d y 
(sta ble d ose i n all cas es is defi ne d as n o c ha n ge i n prescri pti o n): 
a)  M T X oral or pare nteral u p t o 2 5  m g/ wee k ( pl us c o nc o mita nt use of f olic or f oli nic aci d 
s u p ple me ntati o n as per l ocal Sta n dar d of Care)  
b)  Lefl u n o mi de u p t o 2 0  m g/ da y orall y  
c)  H y dr o x yc hl or o q ui ne u p t o 4 0 0  m g/ da y or c hl or o q ui ne u p t o 2 5 0  m g/ da y  
d)  A pre milast orall y u p t o 3 0  m g t wice d ail y  
Oral c ortic oster oi ds ma y be use d at ≤1 0  m g/ da y ( of pre d nis o ne or e q ui vale nt), pr o vi de d t hat t he 
prescri pti o n has bee n sta ble f or at least 4  wee ks  pri or t o Da y  1  a n d u p t o t h e Wee k  1 3 visit . F or 
s u bjects c o nti n ui n g o n o pe n-la bel fil g oti ni b after t he Wee k 1 3 visit, t he s u bject's ster oi d d ose ca n 
be re d uce d bas e d o n i n vesti gat or j u d g me nt (a n d m a y als o be a dj uste d b ac k u p as nee de d), b ut 
s h o ul d N O T e x cee d t he sta ble d ose i de ntifie d at Baseli ne ( Ra n d o mizati o n/ Da y 1) . F or s u bjects 
c o nti n ui n g Sta n dar d of Care tr eat me nt, t he d ose of c ortic oster oi ds c a n als o be re d uce d or 
i ncreas e d b ut s h o ul d n ot e x cee d 2 0 m g / d a y ( of pre d nis o ne or e q ui vale nt; t h e pre d nis o ne 
c o n versi o n ta ble is pr o vi de d i n A p pe n di x  1 3 ). 
If a n N S AI D or C O X-2 i n hi bit or is use d, it m ust n ot e xcee d t he ma xi m u m d ose per mitte d as per 
l ocal la bel a n d m ust ha ve bee n use d at a sta ble d os e f or at least 2 wee ks pri or t o Da y  1  a n d u p t o 
t he Wee k 1 3 visit. 

Fil g oti ni b  
 
Pr ot oc ol  G L P G 0 6 3 4 -C L -2 2 7  
Fi nal  
Gala pa g os  
A me n d me nt 2  
C O N FI D E N TI A L  
P a ge  5 8  
0 9 Se p 2 0 2 2  
5. 3. 2.  
Pr o hi bit e d C o n c o mit a nt  M e di c ati o n s  
T he pr o hi bite d me dicati o ns w hile o n st u d y are as f oll o ws:  
T a ble  5 -1 . Pr o hi bite d C o nc o mit a nt Me dic ati o ns  
Dr u g Cl ass  
A ge nts Dis all o w e d  
Pr o hi bite d Peri o d  
Str o n g P -g p I n d ucersa 
A ntic o n v ulsa nts  
I ncl u di n g, b ut n ot li mite d t o P he n o bar bital, 
p he n yt oi n, car ba maze pi ne  
2 1 da ys pri or t o Scree ni n g t hr o u g h 
t he e n d of t he D o u ble -bli n d 
T reat me nt P hase of t he  st u d y a n d 
t hr o u g h t he e n d of t he E xte nsi o n 
P hase f or s u bj ects o n o pe n -la bel 
fil g oti ni b 
A nti m yc o bacterials  
I ncl u di n g, b ut n ot li mite d t o Rifa b uti n, 
rifa p e nti ne, rifa m pi n 
Her bal/ Nat ural S u p ple me nts  
St. J o h n’s w ort a n d da ns he n ( Sal via 
Milti orr hiza)  
Pr o hi bite d M e dic ati o ns  f or R he u m atic C o n diti o ns 
C ortic oster oi ds  
D ose e q ui vale nt t o > 1 0  m g/ da y of 
pre d nis o ne or e q ui vale nt ( oral)  
F or s u bj ects o n Sta n dar d of Care treat me nt: 
d ose e q ui vale nt t o > 2 0 m g/ da y of  
pre d nis o ne  or e q ui vale nt  ( oral) 
All pare nteral c ortic oster oi ds are pr o hi bite d  
D uri n g t he E xte nsi o n a n d M o nit ori n g 
P has e, s u bj ects ma y recei ve a ma xi m u m of 
3 i ntra -artic ular i nj ecti o ns of c ortic oster oi d 
e ver y 
1 2  m o nt hs; T he d ose of c ortic oster oi d 
i nj ecte d s h o ul d n ot e xcee d t he e q ui vale nt 
d ose of tria mci n ol o ne 4 0 -m g s us pe nsi o n; 
T he d ose a n d v ol u me s h o ul d be a dj uste d 
d o w n war d as a p pr o priate t o t he size of t he 
j oi nt 
Ra n d o mizati o n t hr o u g h t he e n d of 
t he st u d y  
 
T N F α a nta g o nist  
I ncl u di n g, b ut n ot li mite d t o: i nfli xi ma b, 
a d ali m u ma b, eta nerce pt, g oli m u ma b, 
cert oliz u ma b, a n d bi osi milar a ge nts  
4  wee ks pri or t o Scree ni n g t hr o u g h 
t he e n d of t he D o u ble -Bli n d 
Treat me nt P has e of t he st u d y a n d 
t hr o u g h t he e n d of t he E xte nsi o n 
P hase f or s u bj ects o n o pe n-la bel 
fil g oti ni b  
 
I nterle u ki n a nta g o nists 
I ncl u di n g, b ut n ot li mite d t o: uste ki n u ma b, 
t ociliz u ma b, sec u ki n u ma b, a na ki nara, 
1 2 wee ks pri or t o Scree ni n g 
t hr o u g h t he e n d of t he D o u ble -
Bli n d Treat me nt P hase  of t he 
st u d y a n d t hr o u g h t he e n d of t he 
E xte nsi o n P hase f or s u bj ects o n 
o pe n -la bel fil g oti ni b  
J A K i n hi bit or 
A n y J A K i n hi bit or ot her t ha n fil g oti ni b  
9 0 da ys pri or t o Scree ni n g t hr o u g h 
t he e n d of t he D o u ble -Bli n d 
Treat me nt P has e of t he st u d y a n d 
t hr o u g h t he e n d of t he E xte nsi o n 
P has e f or s u bj ects o n o pe n -la bel 
fil g oti ni b  

Fil g oti ni b  
 
Pr ot oc ol  G L P G 0 6 3 4 -C L -2 2 7  
Fi nal  
Gala pa g os  
A me n d me nt 2  
C O N FI D E N TI A L  
P a ge  5 9  
0 9 Se p 2 0 2 2  
Dr u g Cl ass  
A ge nts Dis all o w e d  
Pr o hi bite d Peri o d  
Fil g oti ni b  
A n y ti me p ri or t o Ra n d o mizati o n  
i n t his st u d y 
Ot her ( n o n -bi ol o gic) 
D M A R Ds  
I ncl u di n g, b ut n ot li mite d t o: c ycl os p ori ne 
(a n d ot her calci ne uri n i n hi bit ors), 
t hali d o mi de, tacr oli m us, m yc o p he n olate, 
azat hi o pri ne, g ol d salts,  ( N O T E: a pre milast 
is per mitte d d uri n g t he st u d y) 
4 wee ks  pri or t o Scree ni n g t hr o u g h 
t he e n d of t he D o u ble -Bli n d 
Treat me nt P hase of t he st u d y a n d 
t hr o u g h t he e n d of t he e xte nsi o n 
p hase f or s u bj ects o n o pe n -la b el 
fil g oti ni b 
Ot her ( bi ol o gic)  
A n y i n vesti gati o nal bi ol o gic a ge nt  
8 wee ks pri or t o Scree ni n g ( or 5 
half -li ves, w hic he ver is l o n ger) 
t hr o u g h t he e nd of t he st u d y  
L y m p h oc yte -de pleti n g 
t hera pies 
I ncl u di n g, b ut n ot li mite d t o: ale mt uz u ma b, 
c ycl o p h os p ha mi de, t otal l y m p h oi d 
irra diati o n, a n d a n y ot her l y m p h oc yte-
de pleti n g t hera p y    
A n y ti me bef ore a n d t hr o u g h t he 
e n d of t he st u d y  
Ot her L y m p h oc yte -de pleti n g 
t hera pies 
Rit u xi ma b  
1 2 m o nt hs pri or t o scree ni n g a n d 
t hr o u g h t he e n d of t he st u d y 
S ulfa dr u gs  
S ulfasalazi ne  
C urre nt use of s ulfasalazi ne or use 
of s ulfasalazi ne wit hi n 2 6  wee ks 
of Scree ni n g. S ulfasalazi ne is n ot 
per mitte d at a n y p oi nt d uri n g t he 
st u d y 
Al k ylati n g a ge nts or a n y 
rec o g nize d testic ular t o xi n 
 
Wit hi n 2 6  wee ks of Scree ni n g a n d 
t hr o u g h t he e n d of t he st u d y ( ma y 
be disc usse d wit h S p o ns or Me dical 
Lea der or desi g nee)  
Pr o hi bite d M e dic ati o ns f or Ot her I n dic ati o ns  
Ot her bi ol o gics b 
A nti b o d y base d or ot her s yste mic bi ol o gics, 
e.g . de n os u ma b, trast uz u ma b  
Re q uires S p o ns or Me dical Le a d er 
c o ns ultati o n  
A l p ha-1 bl oc kers  
I ncl u di n g b ut n ot li mite d t o ta ms ul osi n, 
d o xaz osi n, praz osi n  
4  wee ks pri or t o Scree ni n g a n d 
t hr o u g h t he e n d of t he st u d y 
5 -α re d uctase i n hi bit ors  
I ncl u di n g, b ut n ot li mite d t o, fi nasteri de a n d 
d utasteri de  
4  wee ks pri or t o Scree ni n g a n d 
t hr o u g h t he e n d of t he st u d y 
A ntia n dr o ge n t hera p y  
I ncl u di n g b ut n ot li mite d t o:  s pir o n olact o ne 
or oral ket oc o naz ole, c y pr oter o ne  acetate  
4  wee ks pri or t o Scree ni n g a n d 
t hr o u g h t he e n d of t he st u d y 
T est oster o ne re place me nt 
t hera p y 
 
1 2  wee ks pri or t o Scree ni n g a n d 
t hr o u g h t he e n d of t he st u d y 
a Ma y decrease st u d y dr u g e x p os ure a n d are e xcl u de d t o a v oi d p ote ntial re d ucti o n i n st u d y dr u g acti vit y.  
P K res ults i n dicate fil g oti ni b is a P -g p s u bstrate, as a si n gle d ose of 2 0 0 m g itrac o naz ole (a p ote nt P -g p i n hi bit or) i ncrease d 
fil g oti ni b Cma x  b y 6 4 % a n d A U C i nf b y 4 5 % a n d ha d n o effect o n t he maj or, acti ve meta b olite G S -8 2 9 8 4 5.  
b Ot her a p pr o ve d bi ol o gics (e .g . a nti b o d y base d or ot h er s yste mic bi ol o gics) ma y be all o we d wit h t h e a p pr o val of t h e  S p o ns or 
Me dical Lea der or desi g nee  w h o will als o s pecif y t h e c orres p o n di n g pr o hi bite d peri o d . 

Fil g oti ni b  
 
Pr ot oc ol  G L P G 0 6 3 4 -C L -2 2 7  
Fi nal  
Gala pa g os  
A me n d me nt 2  
C O N FI D E N TI A L  
P a ge  6 0  
0 9 Se p 2 0 2 2  
5. 4.  
V a c ci n e G ui d eli n e s  
•  Pri or t o st u d y partici pati o n, it is rec o m me n de d t h at t he s u bject’s vacci nati o ns be br o u g ht u p 
t o date acc or di n g t o l ocal vacci nati o n sta n dar ds. 
•  Li ve atte n uate d v acci n es (i ncl u di n g, b ut n ot li mite d t o varicella a n d i ntra nasal i nfl ue nza 
vacci nes ) are pr o hi bite d wit hi n 3 0 da ys of Da y  1, t hr o u g h o ut t he st u d y,  a n d f or 1 2  wee ks 
after t he l ast  d ose of st u d y dr u g.  
It s h o ul d be n ote d t h at t he i n vesti gat or m ust re mi n d t he s u bject at t he F oll o w-u p Visit t hat 
vacci nati o n wit h li ve c o m p o ne nts are n ot all o we d u ntil 1 2  wee ks after t h e last d ose of st u d y 
me dicati o n . 
•  S u bjects s h o ul d be a d vise d t o a v oi d r o uti ne h o use h ol d c o ntact wit h pers o ns vacci nate d wit h 
li ve/atte n uate d vacci ne c o m p o ne nts. Ge neral g ui d eli nes s u g gest t hat a st u d y s u bject’s 
e x p os ure t o h o use h ol d c o ntacts s h o ul d be a v oi de d f or t he bel o w stat e d ti me peri o ds:  
⎯ Varicella or li ve atte n uat e d  ( oral) t y p h oi d vacci nes  –  a v oi d c o ntact f or 4  wee ks f oll o wi n g 
h o use h ol d c o ntact va cci n ati o n  
⎯ Li ve atte n uate d ( oral) p oli o vacci ne –  a v oi d c o ntact f or 6  wee ks f oll o wi n g h o use h ol d 
c o ntact va cci nati o n  
⎯ Li ve a tte n uate d r ot a vir us vacci ne –  a v oi d c o ntact f or 1 0  da ys f oll o wi n g h o use h ol d 
c o ntact vacci nati o n  
⎯ Li ve atte n uate d (i ntra nas al) i nfl ue nza  vacci ne –  a v oi d c o ntact f or 1  wee k f oll o wi n g 
h o use h ol d c o ntact vacci n ati o n  
•  I n acti vate d v acci n es (s uc h as i nacti vate d i nfl ue nza v acci nes) s h o ul d be a d mi nistere d 
acc or di n g t o l ocal vacci nati o n sta n dar ds w he n e ver me dicall y a p pr o pri ate; h o we ver, t here are 
n o a vaila ble data o n t he c o nc urre nt use of fil g oti ni b a n d its i m pact o n i m m u ne res p o nses 
f oll o wi n g vacci nati o n. 
5. 5.  
A c c o u nt a bilit y f or S t u d y Dr u g s 
T he i n vesti gat or is res p o nsi ble f or e ns uri n g a d e q u ate acc o u nta bilit y of all use d a n d u n use d st u d y 
dr u gs . T his i ncl u des ac k n o wle d ge me nt of recei pt of eac h s hi p me nt of st u d y dr u gs ( q ua ntit y a n d 
c o n diti o n). All use d a n d u n use d st u d y dr u gs dis pe nse d  t o s u bjects m ust be ret ur ne d t o t he site. 
St u d y dr u g acc o u nta bilit y rec or ds will be pr o vi de d t o eac h st u d y site t hr o u g h I W R S t o: 
•  Rec or d t he dat e recei ve d a n d q ua ntit y of st u d y dr u g 
•  Rec or d t he dat e, s u bject n u m ber, t he i n vesti gati o nal me dici nal pr o d uct (I M P) n u m ber 
dis pe nse d  
•  Rec or d t he dat e, q ua ntit y of use d a n d u n use d I M P ret ur ne d, al o n g wit h t he i nitials of t he 
pers o n rec or di n g t he i nf or mati o n  

Fil g oti ni b  
 
Pr ot oc ol  G L P G 0 6 3 4 -C L -2 2 7  
Fi nal  
Gala pa g os  
A me n d me nt 2  
C O N FI D E N TI A L  
P a ge  6 1  
0 9 Se p 2 0 2 2  
•  Dis pe nsi n g rec or ds will i ncl u de t he i nitials of t he pers o n dis pe nsi n g t h e st u d y dr u g or 
s u p plies 
5. 5. 1.  
I n v e sti g ati o nal M e di ci n al Pr o d u ct R et ur n or Di s p o s al  
U se d a n d u n use d I M P s u p plies m ust be ret ur ne d t o t he desi g n ate d dis p osal facilit y f or 
destr ucti o n. T he st u d y m o nit or will pr o vi de i nstr ucti o ns f or ret ur n. Dr u g destr ucti o n at t he site is 
n ot all o we d.  
I M P ma y be ret u r ne d o n a n o n g oi n g b asis d uri n g t he st u d y if a p pr o priat e. At t he e n d of t he 
st u d y, f oll o wi n g fi nal I M P i n ve nt or y rec o nciliati o n b y t he st u d y m o nit or, t he st u d y site will 
ret ur n all u n use d I M P s u p plies, i ncl u di n g e m pt y c o ntai ners, acc or di n g t o t hese pr oce d ures. U p o n 
st u d y c o m pleti o n, c o pies of t he I M P acc o u nta bilit y re p orts m ust be file d at t he site . A n ot her 
c o p y will be ret ur n e d t o t he S p o ns or.  
T he st u d y m o nit or will re vie w I M P s u p plies a n d ass ociate d rec or ds at peri o dic i nter vals. T he 
st u d y m o nit or m ust first perf or m I M P  acc o u nta bilit y d uri n g a n o n -site m o nit ori n g visit. 
6.  
S T U D Y P R O C E D U R E S  
T he st u d y assess me nts as descri be d b el o w will be pe rf or me d at t he ti me p oi nts s pecifie d i n t he 
St u d y Pr oce d ures Ta ble ( A p pe n di x  2 ).  
T he i n vesti gat or m ust d oc u me nt a n y de viati o n fr o m pr ot oc ol pr oce d ures a n d n otif y t he s p o ns or 
or C R O . 
6. 1.  
S u bj e ct E nr oll m e nt a n d Tr e at m e nt A s si g n m e nt  
S u bject eli gi bilit y will be esta blis he d at t he c o n cl usi o n of t he S cree ni n g e v al uati o ns. T he  s u bject 
I D will be assi g ne d f or eac h s u bject b y I W R S.  
It is t he res p o nsi bilit y of t he i n vesti gat or t o e ns ure t hat eac h s u bject is eli gi ble f or t he st u d y 
bef ore ra n d o mizati o n  a n d t he start of treat me nt . A s ubject w ill be c o nsi dere d e nr olle d o n ce t he y 
ha ve bee n ra n d o mize d. 
S u bjects w h o meet pr ot o c ol criteria will be ra n d o mize d t o fil g oti ni b 2 0 0 m g or place b o  o n ce 
dail y .  
6. 2.  
Pr etr e at m e nt A s s e s s m e nt s  
6. 2. 1.  
S cr e e ni n g Vi sit  
S u bjects will be scree ne d wit hi n 4 5  d ays bef ore r a n d o miz ati o n t o deter mi ne eli gi bility f or 
p artici p ati o n i n t he st u dy . T he 4 5 -d ay S cree ni n g p er i o d m ay be exte n de d i n c o ns ult ati o n wit h t he 
S p o ns or M e dic al M o nit or . Refer t o t he St u dy Pr oce d ure T a bles i n A p pe n dix  2  f or a c o m plete list 
of assess me nts t o be  perf or me d a n d d oc u me nte d at Scree ni n g : 
•  O btai n writte n i nf or me d c o nse nt  

Fil g oti ni b  
 
Pr ot oc ol  G L P G 0 6 3 4 -C L -2 2 7  
Fi nal  
Gala pa g os  
A me n d me nt 2  
C O N FI D E N TI A L  
P a ge  6 2  
0 9 Se p 2 0 2 2  
•  O btai n de m o gra p hics a n d me dical hist or y ( i ncl u di n g R A/ Ps A/ A S/ nr A x S p A hist or y ), pri or 
n u m ber of c hil dre n fat here d, disease c haract eristics  (rele va nt f or dise ase cl assificati o n a n d 
disease se verit y) , s m o ki n g ha bits, a v era ge wee kl y alc o h ol c o ns u m pti o n, a n d fa mil y hist or y of 
pre mat ure c or o nar y heart disease)  
•  Re vie w  I ncl usi o n / E x cl usi o n Criteria  
•  C o m plete p h ysical e x a mi nati o n ( P E)  as detaile d i n A p pe n di x  1 2  
•  V ital si g ns, wei g ht, a n d h ei g ht  
•  Perf or m sta n dar d 1 2 -Lea d E C G  
•  Q ua nti F E R O N test a n d c hest X -ra y ( C X R) (if a p plica ble). Q ua nti F E R O N p ositi ve or 
ne gati ve res ults m ust n ot be re peate d. A n i n det er mi nate res ult s h o ul d be re p eate d o nce a n d 
t he sec o n d res ult (if p ositi ve or ne gati ve) will be acce pte d. T w o se q ue ntial i n deter mi nate 
res ults c o nstit ute a scree n fail ure. S u bjects wit h pre vi o usl y tr eate d T B or n e wl y di a g n ose d 
late nt T B d uri n g S cree ni n g re q uire s p o ns or a p pr oval ( See I n cl usi o n Criteri o n # 1 0  f or 
details). S u bjects w h o are dia g n ose d wit h late nt T B at Scree ni n g  m ust i nitiate a n a d e q uate 
c o urse of pr o p h yl a xis acc or di n g t o  l ocal c o u ntr y g ui deli nes f or i m m u n oc o m pr o mise d 
patie nts  f or a mi ni m u m of 4 w ee ks pri or t o ra n d o mizati o n. S u bject ma y i nitiate st u d y dr u g 
d osi n g o nl y after c o ns ult ati o n wit h t he S p o ns or  Me dical Lea der or desi g nee . If a s u bject ha d 
a Q ua nti F E R O N t est f or t he p ur p oses of cli nical care or Scree ni n g f or a n ot her Gala pa g os - or 
Gilea d -s p ons ore d st u d y wit hi n 6 0  da ys, t he pri or res ult ma y b e use d t o ass ess eli gi bilit y wit h 
per missi o n of S p o ns or  Me dical Lea der or desi g nee .  
•  C hest X -ra y 
•  Uri nal ysis, i ncl u di n g a uri ne dr u g s cree n  
•  O btai n bl o o d sa m ples f or:  
⎯ He mat ol o g y a n d ser u m c he mistr y  
⎯ Ser ol o g y  
⎯ Ser u m hs C R P  
⎯ E n d ocri ne tests: th yr oi d sti m ulati n g h or m o ne ( T S H), H b A 1c  
⎯ Se x h or m o nes, i nc l u di n g L H, F S H, i n hi bi n B, a n d t otal test oster o ne t o be c ollecte d 
bet wee n 0 7: 0 0 –  1 1: 0 0 i n t he m or ni n g if p ossi ble  
•  Re vie w a n d c ollecti o n of c o nc o mita nt me dicati o ns  
•  Rec or d all S A Es a n d a n y A Es relate d t o pr ot o c ol -ma n date d pr oce d ures occ urri n g after 
si g ni n g of t he I C F 

Fil g oti ni b  
 
Pr ot oc ol  G L P G 0 6 3 4 -C L -2 2 7  
Fi nal  
Gala pa g os  
A me n d me nt 2  
C O N FI D E N TI A L  
P a ge  6 3  
0 9 Se p 2 0 2 2  
•  Se me n c ollecti o n ( 2  se p arate c ollecti o ns i n acc or da nce wit h Secti o n  6. 1 1 ) a n d rec or d date 
a n d ti me of last ejac ulati o n pri or t o sa m ple. Se me n c ollecti o n s h o ul d be c ollecte d t o c oi nci de 
wit h  Da y  1  (Baseli ne  visit ) as m uc h as p ossi ble.  
•  Disease S pecific scal es a n d q uesti o n naires  
A si n gle retest of a ny excl usi o n ary scree ni n g l a b ( n o n -se me n s a m pl es) is per mitte d: 
•  at t he discreti o n of t he i n vesti gat or, if t h e i nitial e xcl usi o nar y val ue is i n vali d d ue t o a 
d oc u me nte d err or i n sa m ple c ollecti o n or la b orat or y pr ocessi n g, O R  
•  u p o n t he a p pr o val of t h e S p o ns o r Me dical Lea d er or desi g n ee, if t here is a n e xte n uati n g 
circ u msta nce ar o u n d t he e x cl usi o nar y val u e.  
Retesti n g of e x cl usi o nar y para meters i n Scree ni n g se me n sa m ples is disc usse d i n Secti o n 6. 1 1 . 
S u bjects meeti n g all of t he i ncl usi o n criteri a a n d n o ne of t he excl usi o n criteri a will ret ur n t o t he 
cli nic after Scree ni n g, f or r a n d o miz ati o n i nt o t he st u dy.  
Fr o m t he ti me of o btai ni n g i nf or m e d c o nse nt t hr o u g h t he first a d mi nistrati o n of I M P, rec or d all 
S A Es, as well as a n y A Es relate d t o pr ot oc ol -m a n date d pr oce d ures o n t he A Es case re p ort f or m 
( C R F/e C R F). All ot her u nt o war d me dical o cc urre nces o bser v e d d uri n g t he Scree ni n g peri o d, 
i ncl u di n g e x acer bati o n or cha n ges i n me dical hist or y are t o b e ca pt ur e d o n t he me dical hist or y 
C R F/e C R F. See Secti o n  7  A d verse E v e nts a n d T o xicit y Ma na ge me nt f or a d diti o nal details.  
6. 2. 1. 1.  
R e s cr e e ni n g  
S u bjects w h o d o n ot meet t he eli gi bilit y criteria will  n ot be ra n d o mize d, b ut  ma y b e c o nsi dere d 
f or a si n gle r escree ni n g after c o ns ultati o n wit h  a n d a p pr o val b y t he S p o ns or  Me dical Lea der or 
desi g nee.  S u bjects w h o are res cree ne d d o n ot  n ee d t o ha ve a re peat Q u a nti F E R O N  a n d/ or C X R, 
if t hese were perf or me d wit hi n 9 0 da ys of writte n c o nse nt f or rescree ni n g, u nless a re peat is 
dee me d a p pr o priate b y t h e i n vesti gat or.  
6. 2. 2.  
D a y 1  A s s e s s m e nt s  
O n Da y 1 , after t he s u bject’s eli gi bilit y f or t he st u d y has b ee n c o nfir me d, t he s u bject will be 
ra n d o mize d i nt o t he st u d y t o recei ve fil g oti ni b 2 0 0 m g  or place b o  o nce dail y . St u d y dr u g will be 
dis pe nse d  as assi g ne d b y t he I W R S s yste m . T he s u bject will ta ke t he first d ose i n cli nic. I n vasi ve 
st u d y pr oce d ures s uch as bl o o d dra ws s h o ul d be d o ne at t he e n d of a st u d y visit. T he f oll o wi n g 
will be perf or me d a n d d o c u me nte d at D a y 1 pri or t o d osi n g:  
•  Re vie w i ncl usi o n / e x cl usi o n Criteria  
•  S y m pt o m -dri ve n  P E , as nee de d 
•  Vital si g ns  (resti n g bl o o d press ure, res pirat or y rate, p ulse a n d te m perat ure) 
•  Wei g ht  ( wit h o ut s h oes)  

Fil g oti ni b  
 
Pr ot oc ol  G L P G 0 6 3 4 -C L -2 2 7  
Fi nal  
Gala pa g os  
A me n d me nt 2  
C O N FI D E N TI A L  
P a ge  6 4  
0 9 Se p 2 0 2 2  
•  O btai n bl o o d sa m ples f or:  
⎯ He mat ol o g y a n d ser u m c he mistr y 
⎯ Li pi d pr ofile (fasti n g)  [t otal c h olester ol a n d s u bfracti o ns]  
⎯ Ser u m hs C R P  
⎯ Se x h or m o nes, i ncl u di n g L H, F S H, in hi bi n B, a n d t otal test oster o ne t o be c ollecte d 
bet wee n 0 7 :0 0 –  1 1 :0 0 i n t he m or ni n g if p ossi ble  
•  Uri nal ysis  
•  Disease S pecific scal es a n d q uesti o n naires  
•  Re vie w c o nc o mita nt me dicati o ns  
•  Rec or d a n y A Es  relate d t o pr ot oc ol-ma n date d pr oce d ures a n d all S A Es  occ ur ri n g after 
si g ni n g of t he c o ns e nt f or m. 
6. 3.  
R a n d o mi z ati o n  
S u bjects will be ra n d o ml y all ocate d t o d osi n g gr o u p acc or di n g t o a pre -s p ecifie d ra n d o mizati o n 
sc he me pre pare d b y a n i n de pe n de nt statisticia n. O nce c o nfir me d eli gi ble  f or t he st u d y, s u bjects 
will be ra n d o mize d usi n g a c o m p uterize d I W R S s yste m t o fil g oti ni b 2 0 0 m g or place b o i n a 
1 : 1 rati o.  
Ra n d o mizati o n will be stratifie d acc or di n g t o t he t y p e of r he u m atic c o n diti o n ( R A  or 
S p o n d yl art hritis [ Ps A, A S, nr A x S p A ]), c o nc urre nt use of M T X ( yes or n o) a n d s per m 
c o nce ntr ati o n meas ure d at Scree ni n g  (“Bas eli ne ”) acc or di n g t o t he f oll o wi n g strat a:  
•  1 5 t o 2 5 milli o n/ m L  
•  >  2 5 t o 5 0 milli o n/ m L 
•  >  5 0 milli o n/ m L  
6. 4.  
D o u bl e -bli n d Tr e at m e nt P h a s e  ( D a y 1 T hr o u g h W e e k 1 3 St u d y 
Vi sit)  
All s u bjects  will recei ve bli n de d st u d y dr u g u ntil c o m pleti o n of all Wee k 1 3 assess me nts.  
St u d y assess me nts will be c o m plete d as s p ecifie d i n t he St u d y Pr oce d ures Ta ble ( A p pe n di x  2 ).  
I n v asi ve st u d y pr oce d ures s uc h as bl o o d dra ws s h o ul d be d o ne at the e n d of a st u d y visit , as 
m uc h as p ossi ble .  

Fil g oti ni b  
 
Pr ot oc ol  G L P G 0 6 3 4 -C L -2 2 7  
Fi nal  
Gala pa g os  
A me n d me nt 2  
C O N FI D E N TI A L  
P a ge  6 5  
0 9 Se p 2 0 2 2  
T he e n d of t he D o u ble -Bli n d Treat me nt P hase is w he n t he Wee k 1 3 se me n res ult s are a vaila ble 
t o t he i n vesti gat or a n d ha ve bee n e val uate d. Bas e d o n t his e val uati o n, s u bjects are assi g n e d t o 
e nter t he M o nit ori n g P hase or t he E xte nsi o n P hase.  
6. 5.  
E xt e n si o n P h a s e  
I n t he E xte nsi o n P hase, s u bjects will recei v e o pe n-la bel treat me nt (fil g oti ni b or Sta n dar d of 
Care) a n d h a ve a st u d y visit e ver y 1 3  wee ks t hat i ncl u des se me n a n al ysis.  T he first  sc he d ule d 
visit of t he  E xte nsi o n P hase occ urs at Wee k  2 6.  
I n case s p er m para meters at a n y visit (i ncl u di n g Wee k 1 5 6) meet a n y of t he pre -s pecifie d 
decrease t hr es h ol ds, s u bjects will e nter t he M o nit ori n g P hase.  
D uri n g t h e E xte nsi o n p hase, Sta n dar d of C are a n d c o nc o mita nt treat me nt ma y b e o pti mize d at 
t he discreti o n of t he i n vesti gat or ta ki n g i nt o c o nsi derati o n t he pr ot oc ol r estricti o ns (see 
Secti o n  5. 3 ).  
I n case a s u bject ne e ds t o be treate d wit h a pr o hi bite d me dicati o n t o c o ntr ol t heir r he u matic 
c o n diti o n  (see Ta ble  5 -1 ), t he s u bject will disc o nti n ue t he st u d y a n d c o m plete a n E T visit 
(i ncl u di n g se m e n c ollecti o n). F or s u bjects o n fil g oti ni b, t his will be f ollo we d  b y a s afet y f oll o w -
u p visit 3 0  da ys after last st u d y dr u g d ose.  
All s u bjects w h o di d n ot e nter t he M o nit ori n g P hase will c o nti n ue t he st u d y u ntil t he Wee k  1 5 6 
visit.  
S u bjects wit h ne wl y p ositi ve (c o n vert e d) Q ua nti F E R O N ®  [ or ce ntr all y re p orte d e q ui vale nt 
assa y] T B test s h o ul d be disc o nti n ue d fr o m st u d y dr u g. S u bjects w h o were pre vi o usl y tr eate d f or 
T B wit h a c o m plet e a n d a de q uate c o urse of t hera p y as p er l ocal sta n dar d of care a n d as verifie d 
b y t he i n vesti gat or d o n ot nee d t o ha ve yearl y Q ua nti F E R O N ®  tests. S u bjects pre vi o usl y treate d 
f or T B s h o ul d b e scree ne d at least yearl y f or si g ns a n d s y m pt o ms c o nsiste nt wit h reacti vati o n of 
T B . A n y s u bject wit h acti ve T B s h o ul d be disc o nti n ue d fr o m t he st u d y.  
St u d y assess me nts will be c o m plete d as s p ecifie d i n t he St u d y Pr oce d ures Ta ble ( A p pe n di x  2 ). 
6. 6.  
M o nit ori n g P h a s e  
S u bjects o n fil g oti ni b w h o e nter t he M o nit ori n g P hase will disc o nti n ue st u d y dr u g a n d start 
St a n dar d of Care. S u bjects o n Sta n dar d of Care will c o nti n ue treat me nt.  
All s u bjects w h o e nter t h e M o nit ori n g P hase will u n d er g o se me n e val uati o ns e ver y 1 3  wee ks 
starti n g fr o m t heir e ntr y i nt o t he M o nit ori n g P hase, f or u p t o 5 2  wee ks or u ntil Re versi bilit y (see 
Defi niti o n of Ter ms ) is met, w hic he ver is ac hie ve d first.  
St u d y assess me nts will be c o m plete d as s p ecifie d i n t he St u d y Pr oce d ures Ta ble ( A p pe n di x  2 ). 
6. 7.  
E arl y T er mi n ati o n  
S u bjects w h o disc o nti n ue st u d y partici p ati o n f or a n y reas o n pri or t o Wee k  1 5 6 i n t he E xte nsi o n 
P hase , pri or t o  reac hi n g Re versi bilit y or Wee k  5 2 i n t he M o nit ori n g P hase ( w hic he ver occ urs 
first) will c o m plete a n E T Visit. S u bjects o n  bli n de d st u d y dr u g or o pe n -l a bel fil g oti ni b will als o 
u n der g o a r o uti ne s afet y f oll o w -u p visit 3 0  da ys ( ± 5  da ys) after t he last d ose of st u d y dr u g.  

Fil g oti ni b  
 
Pr ot oc ol  G L P G 0 6 3 4 -C L -2 2 7  
Fi nal  
Gala pa g os  
A me n d me nt 2  
C O N FI D E N TI A L  
P a ge  6 6  
0 9 Se p 2 0 2 2  
6. 8.  
S af et y  F oll o w -U p Vi sit 3 0 D a y s P o st D o s e  (± 5  d a y s)   
All s u bjects will c o m plete a safet y f oll o w -u p visit 3 0 da ys after t h e last d ose of st u d y dr u g 
(bli n de d [fil g oti ni b or place b o] or o pe n-la bel [fil g oti ni b]). 
St u d y assess me nts will be c o m plete d as s p ecifie d i n t he St u d y Pr oce d ures Ta ble ( A p pe n di x  2 ). 
6. 9.  
S af et y a n d T ol er a bilit y  
A Es , P E , vital si g ns, E C Gs,  a n d la b orat or y assess me nts (sta n dar d he m at ol o g y, ser u m/ plas ma 
c he mistr y, a n d uri nal ysis)  will be c ollecte d . Se me n sa m ples will b e c ollect e d i n acc or da nce wit h 
S ecti o n 6. 1 1 . 
6. 9. 1.  
T hr o m b o e m b oli c E v e nt s  
S u bjects e x perie nci n g a t hr o m b oe m b olic e ve nt s h o ul d be e val uate d f or t he o verall ris k of 
rec urre nt t hr o m b oe m b olis m a n d referre d t o a s pecialist f or f urt her testi n g as a p pr o priate 
(i ncl u di n g b ut n ot li mite d t o e val uati o n f or a n u n derl yi n g i n herite d h y perc oa g ul a ble state). 
6. 1 0.  
Cli ni c al L a b or at or y E v al u ati o n s   
T he he mat ol o g y a n d ser u m  c he mistr y la b orat or y a nal yses will be perf or me d at a ce ntr al 
la b orat or y. Refere n ce ra n ges will be s u p plie d b y t he ce ntr al la b orat or y a n d will be use d b y t he 
i n vesti gat or t o ass ess t he la b orat or y dat a f or cli nical si g nifica nce a n d pat h ol o gical c ha n ges. 
Bl o o d sa m ples will be c ollecte d b y ve ni p u nct ure i n t he ar m at t he ti me  p oi nts i n dicate d i n t he 
S t u d y P r oce d ures T a ble ( A p pe n di x  2 ). I n a d diti o n, uri ne sa m ples f or t he cli nical la b orat or y 
assess me nts will be c ollecte d. S u bjects o nl y n ee d t o be faste d o n da ys w h ere li pi d pr ofili n g is 
sc he d ule d.  
Please refer t o A p p e n di x  1 1  f or ta ble of cli nical la b orat or y tests. 
T he la b orat or y v al ues o utsi de t he n or mal ra n ge will be fla g ge d a n d cli nical rele va n ce will be 
assesse d b y t he i n vesti gat or. M ore fre q ue nt sa m pli n g as w ell as a d diti o nal tests ma y b e 
perf or me d as dee me d necessar y b y t he i n vesti gat or as i n dicate d.  
N ote t hat  i n t he case w here cli nicall y si g nifica nt la b orat or y test res ults are a p ote ntial reas o n f or 
disc o nti n uati o n fr o m t he st u d y dr u g a n d wit h dra wal fr o m t he st u d y, retesti n g of t he affecte d 
para meter(s) s h o ul d be pr o m pt ( wit hi n 3 t o 7  da ys) after t h e i n vesti ga t or has c o ns ulte d wit h t he 
S p o ns or  M e dical Lea d er or desi g n ee . A decisi o n re gar di n g s u bject disc o nti n uati o n s h o ul d be 
ma de after t he res ults fr o m t he retest are a vaila bl e (see Secti o n  3. 7  f or a d diti o nal i nf or mati o n). 
T he details of sa m ple h a n dli n g a n d s hi p me nt i nstr ucti o ns will be pr o vi de d i n a se parate 
la b orat or y ma n u al.  

Fil g oti ni b  
 
Pr ot oc ol  G L P G 0 6 3 4 -C L -2 2 7  
Fi nal  
Gala pa g os  
A me n d me nt 2  
C O N FI D E N TI A L  
P a ge  6 7  
0 9 Se p 2 0 2 2  
6. 1 1.  
S e m e n C oll e cti o n Pr o c e d ur e  
At eac h of t h e f oll o wi n g ti me p oi nts, s u bjects will  pr o vi de 2 se parate  se m e n sa m ples c ollecte d 
wit hi n a 1 4 -da y peri o d. E ac h se me n s a m ple m ust be c ollecte d wit h a ≥4 8  h o urs a n d ≤7  da ys 
ejac ulati o n free peri o d at t he f oll o wi n g ti me p oi nts.  
•  Scree ni n g (Bas eli ne ) 
•  After t he D o u bl e -bli n d Treat me nt P hase ( Wee k  1 3  st u d y visit) 
•  E ver y 1 3  wee ks d uri n g t he E xte nsi o n P hase  
•  E ver y 1 3  wee ks d uri n g t he M o nit ori n g P hase  
•  At t he Earl y Ter mi nati o n Visit  
T he 2 ti me -p oi nts f or t he se me n sa m ple c ollecti o n will be sc he d ule d i n a gree me nt wit h t he 
i n vesti gat or o n t he st u d y visit da y  a n d/ or as s o o n as p ossi ble after t he visit da y.  
All decisi o ns of retesti n g a n y s e me n/s per m para m eter (i .e. o bt ai ni n g a t hir d sa m ple at a n y of t he 
a b o ve ti me p oi nts), m ust be a p pr o ve d b y t h e S p o ns or  Me dical Lea der or desi g nee b ef ore t he 
retest. S uc h i n q uiries will o nl y be c o nsi dere d i n sel ect i nsta nces w h ere t h e s e me n sa m ple wit h 
t he q uesti o ne d val ue(s) is f o u n d t o be n o n -assess a ble or i n vali d (e .g . c ollecti o n wit h o ut 
a d here n ce t o ej ac ulati o n -free p eri o d; i nterc urre nt ill ness or de h y drati o n at ti me of c ollecti o n; 
i nc o m plete ca pt ur e of se me n sa m ple; a n d/ or sa m ple pr ocessi n g or se me n a nal ysis t hat d e viates 
fr o m sta n dar dize d pr oce d ure). T he t hir d se me n sa m ple, w he n i n dicate d, m ust be c ollecte d wit hi n 
1 4  da ys of t he pri or s a m ple a n d wit h a n ejac ulati o n free p er i o d of ≥4 8 h o urs a n d ≤7 da ys ( See 
Fi g ure  6 -1 ). 
At eac h ti me p oi nt, t he mea n of 2  se p arat e se me n s a m ples f or eac h para met er will be use d f or t he 
assess me nt  of st u d y eli gi bilit y, e ntr y  i nt o t he E xte nsi o n P hase, e ntr y i nt o t he M o nit ori n g P hase, 
a n d e xit fr o m t he M o nit ori n g P hase . 
T he res ults of t he se m e n a nal ysis  will be e val uate d a n d disc usse d  wit h t he s u bject a n d he  will be 
i nf or me d a b o ut t he a p pr o priate ne xt ste ps t o be ta ke n i n t he st u d y.  

Fil g oti ni b  
 
Pr ot oc ol  G L P G 0 6 3 4 -C L -2 2 7  
Fi nal  
Gala pa g os  
A me n d me nt 2  
C O N FI D E N TI A L  
P a ge  6 8  
0 9 Se p 2 0 2 2  
Fi g ure  6 -1 . Se me n C ollecti o n Sc he m a  
 
 
A s ta n dar dize d pr oce d ure f or se me n c ollecti o n a n d a nal ysis will be pr o vi d e d t o sites i n a se parate 
ma n ual . Se me n will be assesse d l ocall y f or all para meters  ( m otilit y, c o n ce ntrati o n , c o u nt, a n d 
v ol u me) , e x ce pt m or p h ol o g y, w hic h will be assess e d ce ntr all y. 
6. 1 2.  
Vit al Si g n s  
Vital si g ns will be meas ure d at t he ti me  p oi nts i n dicate d i n t he S t u d y P r oce d ures T a ble 
(A p pe n di x  2 ).  
Vital si g ns s h o ul d be ta k e n after t he s u bject has b ee n resti n g f or 5  mi n utes  ( please refer t o 
A p pe n di x  1 2  f or details) a n d will i ncl u de heart rat e, res pirat or y rate, s yst oli c bl o o d press ure 
(S B P ), diast olic bl o o d press ure ( D B P ), a n d b o d y t e m perat ur e. 
6. 1 3.  
P h y si c al E x a mi n ati o n  
A P E  will be perf or me d at t he ti me  p oi nts i n dicate d i n t he St u d y Pr oce d ures Ta ble  (A p pe n di x  2 ).  
A n y c ha n ges fr o m Baseli ne will be rec or de d. Hei g ht will be meas ure d at Scree ni n g o nl y.  Wei g ht 
wit h o ut s h oes is meas ure d at all visits.  
A  c o m plete P E , as detail e d i n A p pe n di x  1 2 , will be perf or me d at Scree ni n g o nl y . S y m pt o m -
directe d p h ysic al e x a ms s h o ul d be perf or m e d at all ot her visits , as nee de d.  
6. 1 4.  
P h ar m a c o ki n eti c A s s e s s m e nt s  
B l o o d sa m ples f or P K a n al ysis will be c ollecte d at least 3 0 mi n utes p ost -st u d y dr u g d os i n g at t he 
Wee k 2  visit , an yti me at t he Wee k 4 visit , a n d pri or t o st u d y dr u g d osi n g at  t he Wee k  1 3  a n d 2 6 
( o nl y f or s u bjects o n o pe n-la bel fil g oti ni b i n t he E xte nsi o n P hase) visits . S u bjects s h o ul d be 
i nstr ucte d n ot t o ta ke t heir st u d y dr u g o n t h ese visit da ys (e x ce pt f or t he Wee k  4 visit) a n d bri n g 
it wit h t he m t o t he cli nic i nstea d.  

Fil g oti ni b  
 
Pr ot oc ol  G L P G 0 6 3 4 -C L -2 2 7  
Fi nal  
Gala pa g os  
A me n d me nt 2  
C O N FI D E N TI A L  
P a ge  6 9  
0 9 Se p 2 0 2 2  
S u bjects will be i nstr ucte d w he n t o ta ke t heir d os e d uri n g t heir s c he d ule d visit at t he st u d y site.  
Plas ma c o nce ntr ati o ns of fil g oti ni b a n d its meta b olite, G S -8 2 9 8 4 5 , will be a nal yze d . 
6. 1 5.  
Hi g h S e n siti vit y S er u m C -R e a cti v e Pr ot ei n  
T he s u bject’s ser u m C R P will be meas ure d usi n g a hs C R P test at t he ti me p oi nts i n dicate d i n t he 
st u d y acti vities ta ble  (A p pe n di x  2 ).  
P ost -B aseli ne C R P res ults will be bli n de d u p t o a n d i ncl u di n g Wee k  1 3 t o t he i n vesti gat or u ntil 
data base l oc k.  
6. 1 6.  
6 6/ 6 8 -J oi nt C o u nt  ( P s A) a n d 2 8 -J oi nt C o u nt ( R A)  (u s e d f or D A P S A 
a n d C D AI)  
F or  s u bjects e nr olle d wit h Ps A, t he 6 6/ 6 8 j oi nt c o u nt will be use d t o calc ul ate t he D A P S A sc ore. 
F or s u bjects e nr olle d wit h R A, t he 2 8  j oi nt c o u nt will be use d t o calc ulate t he C D AI sc ore. 
Eac h of 6 6 / 2 8 j oi nts will be e val uat e d f or s w elli n g (s w olle n j oi nt c o unt 6 6 / 2 8 j oi nts 
[ SJ C 6 6/ SJ C 2 8]) a n d eac h of 6 8/ 2 8 j oi nts will be e val uate d f or te n der ness (te n der j oi nt c o u nt 6 8 
/ 2 8 j oi nts [ TJ C 6 8/ TJ C 2 8]) (A p pe n di x  3 ) at ti me p oi nts descri be d i n t he St u d y Pr oce d ures T a ble 
(A p pe n di x  2 ).  
T he 6 8 / 2 8 te n der j oi nt c o u nt s h o ul d be perf or me d b y sc ori n g t h e pres e nce or a bse nce of 
te n der ness as assesse d b y press ure a n d j oi nt ma ni p ulati o n.  
T he 6 6 / 2 8 s w olle n j oi nt c o u nt s h o ul d be perf or me d b y sc ori n g t h e pres e nce or a bse nce of 
sy n o vial fl ui d a n d/ or s oft tiss ue s welli n g (b ut n ot b o n y o ver gr o wt h ) as assesse d b y press ure a n d 
j oi nt ma ni p ulati o n.  
6. 1 7.  
P h y si ci a n Gl o b al A s s e s s m e nt of Di s e a s e A cti vit y ( P h G A D A ) 
Gl o bal assess me nt of t he s u bject’s disease acti vit y will be perf or me d b y dra wi n g a  p er pe n dic ular 
li ne o n t he vis ual a nal o gue  scale ( V A S), a n d m eas uri n g  t he dista nce bet w ee n t he “ n o diseas e 
acti vit y” a nc h or a n d t he mar k o n t he 1 0 -c m li ne i n m m.  
T he P h G A D A  will be rec or de d at t he ti me p oi nts i n dicate d i n t he St u d y Pr oce d ures T a ble 
(A p pe n di x  2 ) a n d is pr o vi de d i n A p pe n di x  4 .  
6. 1 8.  
P ati e nt Gl o b al A s s e s s m e nt of Di s e a s e A cti vit y ( Pt G A D A ) ( u s e d f or 
C D AI a n d D A P S A ) 
F or s u bjects wit h R A a n d Ps A, t he patie nt’s gl o bal assess me nt of t heir art hritis disease acti vit y 
will be rec or de d o n a 0 t o 1 0 0 m m V A S. A per pe n dic ular li ne will be dra w n o n t he V A S, a n d 
wit h a r uler, t he dista nce bet wee n t he b e gi n ni n g of t he li ne a n d t he mar k o n t he 1 0 -c m li ne i n 
m m will be t he sc ore fr o m 0 -1 0 0. A sc ore of 0 i n dicates “ ver y well” a n d 1 0 0 i n dicates “ ver y 
p o or” t o t he q uesti o n “ C o nsi deri n g all t he wa ys ps oriatic art hritis affects y o u, please dra w a 

Fil g oti ni b  
 
Pr ot oc ol  G L P G 0 6 3 4 -C L -2 2 7  
Fi nal  
Gala pa g os  
A me n d me nt 2  
C O N FI D E N TI A L  
P a ge  7 0  
0 9 Se p 2 0 2 2  
vertical mar k ( | ) o n t he h oriz o ntal li ne bel o w f or h o w well y o u h a ve b ee n d oi n g o ver t he last 
wee k.  
T he Pt G A D A  will be rec or de d at t he ti me p oi nts i n dicate d i n t he St u d y Pr oce d ures T a ble 
(A p pe n di x  2 ) a n d is pr o vi de d A p pe n di x  5 . 
6. 1 9.  
P ati e nt’ s Gl o b al A s s e s s m e nt of P ai n I nt e n sit y  ( P P AI N) ( us e d f or 
D A P S A)  
F or s u bjects wit h Ps A, t he patie nt’s assess me nt of pai n is a set of 2  q uesti o ns o n pai n o n t he 
n u merical r ati n g scale.  
T he Patie nt’s Gl o bal Ass ess me nt of Pai n I nte nsit y as relate d t o art hritis will be rec or de d at t he 
ti me p oi nts i n dicate d in t he St u d y Pr oce d ures T a ble ( A p pe n di x  2 ) a n d is pr o vi de d i n A p pe n di x  6 . 
6. 2 0.  
B A S D AI  
F or s u bjects wit h A S or nr A x S p A , t he patie nt-re p orte d art hritis acti vit y will be meas ure d  at 
Scree ni n g  usi n g B A S D AI. T his is a 6 -ite m i n de x (fati g u e, s pi nal pai n, peri p heral art hritis, 
e nt hesitis, i nte nsit y a n d d urati o n of m or ni n g stiff ness) i n w hic h t he ite ms will be rec or de d o n a 0 
t o 1 0 n u merical rati n g scale . T he t otal sc ore will ra n ge fr o m 0-1 0.  
T he B A S D AI will be ass esse d at t he ti me p oi nts i n dicate d i n t he St u d y Pr oce d ures T a ble 
(A p pe n di x  2 ) a n d is pr o vi de d i n A p pe n di x  7 . 
7.  
A D V E R S E E V E N T S A N D T O XI CI T Y M A N A G E M E N T  
7. 1.  
D efi niti o n s of A d v er s e E v e nt s, A d v er s e R e a cti o n s, a n d S eri o u s 
A d v er s e E v e nt s  
7. 1. 1.  
A d v er s e E v e nt s  
A n A E is a n y u nt o war d me dical occ urre n ce i n a  cli nical st u d y s u bject a d mi nistere d a me dici nal 
pr o d uct, w hic h d oes n ot necessaril y h a ve a ca us al relati o ns hi p wit h t he treat me nt. A n A E ca n 
t heref ore be a n y u nfa v ora ble a n d/ or u ni nte n de d si g n, s y m pt o m, or disease t e m p orall y ass ociate d 
wit h t he use of a m e dici n al pr o d uct, w het her or n ot c o nsi dere d relate d t o t h e me dici nal pr o d uct. 
A Es ma y als o i ncl u de pre - or p ost -treat me nt c o m plicati o ns t hat occ ur as a res ult of pr ot oc ol 
s pecifie d pr oce d ures, lac k of effic ac y, o v er d ose, dr u g a b use/ mis use re p orts, or occ u p ati o nal 
e x p os ure. Pre-e xisti n g e v e nts t hat i ncreas e i n se verit y or c ha n ge i n n at ure d uri n g or as a 
c o nse q ue nce of partici pati o n i n t he cli nical st u d y will als o be c o nsi dere d A Es.  
A n A E d oes n ot i ncl u de t he f oll o wi n g:  
•  Me dical or s ur gic al pr oce d ures s uc h as s ur ger y, e n d osc o p y, t o ot h e xtracti o n, a n d tra nsf usi o n. 
T he c o n diti o n t hat le d t o t he pr oce d ure ma y b e a n a d verse e ve nt a n d m ust b e re p ort e d.  
•  Pre -e xisti n g diseases, c o n diti o ns, or la b orat or y a b n or malities prese nt or det ecte d bef ore t h e 
Scree ni n g  visit t hat d o n ot w orse n  

Fil g oti ni b  
 
Pr ot oc ol  G L P G 0 6 3 4 -C L -2 2 7  
Fi nal  
Gala pa g os  
A me n d me nt 2  
C O N FI D E N TI A L  
P a ge  7 1  
0 9 Se p 2 0 2 2  
•  Sit uati o ns w here a n u nt o war d me dical occ urre n ce has n ot occ urre d ( e.g . h os pitalizati o n f or 
electi ve s ur ger y, s ocial a n d/ or c o n ve nie nce a d missi o ns)  
•  O ver d ose wit h o ut cli nical se q uelae (see Secti o n  7. 7. 1 ) 
•  A n y me di cal c o n diti o n or cli nicall y si g nifica nt la b orat or y a b n or malit y wit h a n o nset date 
bef ore t h e c o nse nt f or m is si g ne d a n d n ot relate d t o a pr ot oc ol -ass o ciate d pr oce d ure is n ot a n 
A E.  It is c o nsi dere d t o be pre-e xisti n g a n d s h o ul d be d oc u me nte d o n t he m e dical hist or y 
C R F.  
7. 1. 2.  
S eri o u s A d v er s e E v e nt s  
A seri o us a d verse e v e nt ( S A E) is defi ne d as a n e ve nt t hat, at a n y d ose, res ults i n t he f oll o wi n g: 
•  Deat h  
•  Lif e -t hreate ni n g ( N ote: T he ter m “life-t hreat e ni n g” i n t he defi niti o n of “seri o us” refers t o a n 
e ve nt i n w hic h t he s u bject was at ris k of deat h at t he ti me of t he e ve nt; it d oes n ot refer t o a n 
e ve nt t hat h y p ot heticall y mi g ht ha ve ca use d d eat h if it were m ore s e vere.)  
•  I n-patie nt h os pitali zati o n or pr ol o n gati o n of e xisti n g h os pitalizati o n  
•  Persiste nt or si g nifica nt disa bilit y/i nca pacit y  
•  A c o n ge nital a n o mal y/ birt h defect  
•  A me dicall y i m p orta nt e ve nt or reacti o n: s uc h e v e nts ma y 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 ma y je o par dize t he s u bject or ma y 
re q uire i nter ve nti o n t o pr e ve nt o ne of t he ot h er o utc o mes c o nstit uti n g S A Es. Me dical a n d 
scie ntific j u d g m e nt m ust be e x ercise d t o deter mi ne w het her s u c h a n e ve nt is a re p orta bl e 
u n der e x pe dite d re p orti n g r ules.  E x a m ples of me dicall y i m p orta nt e ve nts i ncl u de i nte nsi ve 
treat me nt i n a n e mer ge nc y r o o m or at h o me f or aller gic br o n c h os pas m; bl o o d d yscrasias or 
c o n v ulsi o ns t hat d o n ot res ult i n h os pitalizati o n; a n d de vel o p me nt of dr u g de pe n de n c y or 
dr u g a b use. F or t he a v oi da nce of d o u bt, i nfecti o ns res ulti n g fr o m c o nta mi nate d me dici nal 
pr o d uct will be c o nsi dere d a me dicall y i m p orta nt e ve nt a n d s u bject t o e x pe dite d re p orti n g 
re q uire me nts. 
7. 2.  
A s s e s s m e nt of A d v er s e E v e nt s a n d S eri o u s A d v er s e E v e nt s  
T he i n vesti gat or or q ualifi e d s u bi n vesti gat or is r es p o nsi ble f or assessi n g A Es a n d S A Es f or 
ca usalit y a n d se v erit y, a n d f or fi nal r e vie w a n d c o nfir mati o n of acc urac y of e ve nt i nf or mati o n 
a n d assess me nts.  
7. 2. 1.  
A s s e s s m e nt of C a u s alit y f or St u d y Dr u g s a n d Pr o c e d ur e s  
T he i n vesti gat or or q ualifie d s u bi n vesti gat or is r es p o nsi ble f or assessi n g t h e relati o ns hi p t o I M P 
t hera p y usi n g cli nical j u d g me nt a n d t h e f oll o wi n g c o nsi derati o ns: 

Fil g oti ni b  
 
Pr ot oc ol  G L P G 0 6 3 4 -C L -2 2 7  
Fi nal  
Gala pa g os  
A me n d me nt 2  
C O N FI D E N TI A L  
P a ge  7 2  
0 9 Se p 2 0 2 2  
N o : E vi de nce e xists t hat t he a d vers e e ve nt h as a n eti ol o g y ot her t ha n t h e st u d y dr u g . F or S A Es, 
a n alter nati ve ca usalit y m ust be pr o vi de d (e g, pre -e xisti n g c o n diti o n, u n derl yi n g dise ase, 
i nterc urre nt ill ness, or c o nc o mita nt me dicati o n). 
Yes : T here is reas o n a ble p ossi bilit y t hat t he e v e nt ma y h a ve bee n ca use d b y t he I M P. 
It s h o ul d be e m p hasize d t hat i neffecti ve treat me nt s h o ul d n ot be c o nsi dere d as ca usall y relate d i n 
t he c o nte xt of a d verse e v e nt re p orti n g.  
T he relati o ns hi p t o st u d y pr oce d ures (e g, i n v asi ve pr oce d ures s uc h as v e ni p u nct ure or bi o ps y) 
s h o ul d be assesse d usi n g t he f oll o wi n g c o nsi d erati o ns: 
N o: E vi de nce  e xists t hat t he a d vers e e ve nt h as a n eti ol o g y ot her t ha n t h e st u d y pr oce d ure.  
Yes:  T he a d vers e e ve nt o cc urre d as a res ult of pr ot oc ol pr oce d ures, (e g, ve ni p u nct ure).  
7. 2. 2.  
A s s e s s m e nt of S e v erit y  
T he se verit y of A Es will be gra de d usi n g t he m o difie d  C o m m o n Ter m i n ol o g y Criteria f or 
A d verse E v e nts  (C T C A E ), Versi o n 4. 0 3. F or eac h e pis o de, t he hi g h est gra d e attai ne d s h o ul d be 
re p orte d. 
If a C T C A E criteri o n d oes n ot e xist, t he i n vesti gat or s h o ul d use t he gra d e or a djecti ves: 
Gra de  1  ( mil d), Gra d e 2 ( m o derate), Gra d e  3 (se v ere), Gra de  4 (life -t hr eate ni n g) or 
Gra de  5  (fatal) t o descri b e t he ma xi m u m i nte nsit y of t he a d verse e v e nt. F or p ur p oses of 
c o nsiste nc y wit h t he C T C A E, t hese i nte nsit y gra des are d efi ne d i n T a ble  7 -1  a n d A p pe n di x  9 . 
T a ble  7 -1 . Gr a di n g of A d verse E ve nt Se verit y  
Gr a de  
A djecti ve  
Descri pti o n  
Gra d e 1  
Mil d  
As y m pt o matic or mil d s y m pt o ms; cli nical or dia g n ostic o bser vati o ns o nl y; 
i nter ve nti o n n ot i n dicate d  
Gra d e 2  
M o derate  
L ocal or n o ni n vasi ve i nter ve nti o n i n dicate d; li miti n g a ge -a p pr o priate 
i nstr u me ntal A D L*   
Gra d e 3  
Se vere  
Se vere or me dicall y si g nifica nt b ut n ot i m me diatel y life -t hreate ni n g; 
h os pitalizati o n or pr ol o n gati o n of h os pitalizati o n i n dicate d; disa bli n g; li miti n g 
self-care A D L * *   
Gra d e 4  
Life -t hreate ni n g 
Ur ge nt i nter ve nti o n i n dicate d  
Gra d e 5  
Deat h  
Deat h -relate d A E  
*  
Acti vities of Dail y Li vi n g ( A D L) I nstr u me ntal A D L refer t o o pe ni n g pre pari n g meals, s h o p pi n g f or gr oceries or cl ot hes, 
usi n g t h e tele p h o ne, ma na gi n g m o ne y, etc.  
* *  Self -car e A D L refer t o bat hi n g, dressi n g a n d u n dressi n g, fee di n g self, usi n g t h e t oilet, ta ki n g me dicati o ns, a n d n ot 
be dri d de n.  

Fil g oti ni b  
 
Pr ot oc ol  G L P G 0 6 3 4 -C L -2 2 7  
Fi nal  
Gala pa g os  
A me n d me nt 2  
C O N FI D E N TI A L  
P a ge  7 3  
0 9 Se p 2 0 2 2  
7. 3.  
I n v e sti g at or R e q uir e m e nt s a n d I n str u cti o n s f or R e p orti n g A d v er s e 
E v e nt s a n d S eri o u s A d v er s e E v e nt s t o t h e S p o n s or  
Re q uire me nts f or c ollecti o n pri or t o st u d y dr u g i nitiati o n:  
After i nf or m e d c o nse nt, b ut pri or t o i nitiati o n of st u d y dr u g , t he f oll o wi n g t y pes of e ve nts s h o ul d 
be re p ort e d o n t he case re p ort f or m ( C R F/e C R F): all S A Es a n d A Es  relate d t o pr ot oc ol-ma n date d 
pr oce d ures.  All S A E’s s h o ul d als o be re p orte d vi a t he pa per S A E f or ms.  
A d verse E v e nts  
F oll o wi n g i nitiati o n of st u d y dr u g , c ollect all A Es, re gar dl ess of ca us e or relati o ns hi p, u ntil  t he 
last st u d y visit m ust be re p orte d t o t he C R F/e C R F data base as i nstr ucte d.  
All A Es s h o ul d be f oll o we d u p u ntil res ol uti o n or u ntil t he a d verse e v e nt is sta bl e, if p ossi ble. 
T he s p o ns or  ma y re q uest t hat certai n A Es b e f oll o we d be y o n d t he pr ot oc ol -defi ne d f oll o w -u p 
peri o d.  
Seri o us A d verse E v e nts  
All S A Es, re gar dless of ca use or relati o ns hi p, t hat occ urs after t he s u bject first c o nse nts t o 
partici pate i n t he st u d y (i e, si g ni n g t he i nf or m e d c o nse nt) a n d t hr o u g h o ut t he d urati o n of t he 
st u d y, i ncl u di n g t h e pr ot oc ol-re quir e d p ost -treat me nt f oll o w-u p peri o d, m ust be re p orte d t o t he 
C R F/e C R F data base a n d t he S p o ns or as i nstr ucte d. T his als o i ncl u des a n y S A Es res ulti n g f r o m 
pr ot oc ol -ass ociat e d pr oce d ures perf or me d after i nf or me d c o nse nt is si g ne d.  
A n y S A Es a n d d eat hs t hat occ ur d uri n g a n y p orti o n of t he st u d y or after st u d y disc o nti n uati o n 
b ut wit hi n 3 0 -da ys of t he last d ose of st u d y I M P, re gar dless of ca usalit y, s h o ul d a ls o be re p orte d.  
I n v esti gat ors are n ot o bli gat e d t o acti vel y see k S A Es after t he pr ot oc ol defi ne d f oll o w u p peri o d 
h o we ver, if t h e i n vesti gat or lear ns of a n y S A Es t hat occ ur after st u d y p artici pati o n has c o ncl u de d 
a n d t he e ve nt is dee me d rele va nt t o t he u se of I M P, he/s he s h o ul d pr o m ptl y d oc u me nt a n d re p ort 
t he e ve nt t o t he S p o ns or. 
All A Es a n d S A Es will be rec or de d i n t he C R F/e C R F data bas e a n d all S A E’s s h o ul d als o be 
re p orte d via t h e pa per S A E f or m wit hi n t he ti meli nes o utli ne d i n t he C R F/e C R F c o m pleti o n  
g ui deli ne.  
D uri n g t h e M o nit ori n g P hase, all A Es relate d t o t he pr ot oc ol -ma n date d pr oce d ures, a n d all S A Es 
(re gar dless of relate d ness) s h o ul d be re p ort e d o n t he case re p ort f or m ( C R F/e C R F).  
Seri o us A d verse E v e nt Pa per Re p orti n g Pr ocess  
I n case of a seri o us a d verse e ve nt ( S A E) t h e i n vesti gat or m ust re p ort t his i m me diatel y, a n d u n der 
n o circ u msta nces later t h a n 2 4 h o urs f oll o wi n g t he k n o wle d ge of t he S A E t o:  
 

Fil g oti ni b  
 
Pr ot oc ol  G L P G 0 6 3 4 -C L -2 2 7  
Fi nal  
Gala pa g os  
A me n d me nt 2  
C O N FI D E N TI A L  
P a ge  7 4  
0 9 Se p 2 0 2 2  
E -mail: 
 
or  
 Me dical Affairs S A E Fa x #: 
 
 
F or fatal or life -t hreate ni n g e v e nts, c o pies of h os pital case re p orts, a ut o ps y re p orts, a n d ot her 
d oc u me nts are als o t o be s u b mitte d b y e -mail or fa x w he n re q ueste d a n d a p plica ble. 
Tra ns missi o n of s uc h d o c u me nts s h o ul d occ ur wit h o ut pers o nal s u bject i de ntificati o n, 
mai ntai ni n g t he tracea bilit y of a d o c u me nt t o t he s u bject i de ntifiers.  
A d diti o nal i nf or mati o n ma y b e re q u este d t o e ns ure t he ti mel y c o m pleti o n of acc urate s afet y 
re p orts. 
A n y me di cati o ns necessar y f or treat me n t of t he S A E m ust be rec or de d o nt o t he c o nc o mita nt 
me dicati o n secti o n of t he s u bject’s C R F/e C R F a n d t he e ve nt descri pti o n secti o n of t he S A E 
f or m. 
After t he last St u d y Dr u g i nta ke, a n d f or all patie nts u n der Sta n dar d of Care , t he i n vesti gat or is 
hi g hl y e nc o ura ge d t o re p ort a n y A E/ S A E c o nsi dere d as rel ate d t o t he Sta n dar d of Care 
me dicati o n directl y t o t he mar keti n g a ut h orizati o n h ol der a n d/ or its Nati o nal C o m pete nt 
A ut h orit y.  
I n or der t o a v oi d d u plicati o n i n t he re p orti n g of s uc h e ve nts, t he S p o ns or will n o t re p ort t hese 
e ve nts si m ulta ne o usl y.  
7. 4.  
S p o n s or R e p orti n g R e q uir e m e nt s  
De pe n di n g o n rele va nt l o cal le gislati o n or re g ulati o ns, i ncl u di n g t he a p plica ble U S F D A C o d e of 
Fe deral Re g ulati o ns, t he E U Cli nical Trials Directi ve ( 2 0 0 1/ 2 0/ E C) a n d rel e va nt u p dates, a n d 
ot her c o u ntr y -s p ecific le gislati o n or re g ul ati o ns, t he s p o ns or ma y be re q uir e d t o e x pe dite t o 
w orl d wi de re g ul at or y a ge ncies re p orts of S A Es, s eri o us a d verse dr u g reacti o ns ( S A D Rs), or 
S U S A Rs . I n acc or da n ce wit h t he E U Cli nical Trials Directi ve ( 2 0 0 1/ 2 0/ E C), t he s p o ns or or a 
s pecifie d desi g nee will n otif y w orl d wi d e re g ulator y a ge nci es a n d t he rele va nt I E C i n c o ncer ne d 
Me m ber States of a p plica ble S U S A Rs as o utli ne d i n c urre nt r e g ulati o ns.  
Assess me nt of e x pecte d n ess f or fil g oti ni b S A Es will be deter mi ne d b y t he S p o ns or usi n g 
refere nce safet y i nf or mati o n s pecifie d i n t he i n vesti gat or's br oc h ure. M et h otre x ate ma y b e use d 
as sta n dar d of care t hera pies i n t his st u d y; c o ns e q u e ntl y, a n y S A Es t hat are attri b ute d t o 
met h otre x ate  or a n y ot her c o nc o mita nt treat me nt will be f or war de d b y t he i n vesti gat or t o its 
res pecti ve m ar keti n g a ut h or iz ati o n h ol der. 
All i n vesti gat ors will recei ve a safet y letter n otif yi n g t he m of rele va nt S U S A R re p orts ass ociat e d 
wit h a n y st u d y I M P. T he i n vesti gat or s h o ul d n otif y t he I R B or I E C of S U S A R re p orts as s o o n as 
is practical, w h ere t his is re q uire d b y l ocal re g ulat or y a ge nci es, a n d i n acc or da nce wit h t he l ocal 
i nstit uti o nal p olic y.  
C CI
C CI
C CI

Fil g oti ni b  
 
Pr ot oc ol  G L P G 0 6 3 4 -C L -2 2 7  
Fi nal  
Gala pa g os  
A me n d me nt 2  
C O N FI D E N TI A L  
P a ge  7 5  
0 9 Se p 2 0 2 2  
7. 5.  
Cli ni c al L a b or at or y A b n or m aliti e s a n d Ot h er A b n or m al 
A s s e s s m e nt s  
La b orat or y a b n or malities are us uall y n ot rec or de d as A Es or S A Es. H o we v er, la b orat or y 
a b n or malities (e g, cli nic al c he mistr y, h e mat ol o g y, a n d uri nal ysis) i n de pe n d e nt of t he 
u n derl yi n g  me di cal c o n diti o n t hat re q uire me dical or s ur gical i nter v e nti o n or lea d t o I M P 
i nterr u pti o n or disc o nti n uati o n m ust be rec or de d as a n A E, as w ell as a n S A E, if a p plica ble. I n 
a d diti o n, la b orat or y or ot her a b n or m al assess me nts (e g,  electr ocar di o gra m, X -ra ys, vital si g ns) 
t hat are ass o ciate d wit h si g ns a n d/ or s y m pt o ms m ust be rec or de d as a n A E or S A E if t he y meet 
t he defi niti o n of a n A E ( or S A E) as des cri be d i n Secti o ns 7. 1. 1  a n d 7. 1. 2 . If t he la b orat or y 
a b n or malit y is part of a s y n dr o me, rec or d  t he s y n dr o me or dia g n osis (ie, a n e mia) n ot t he 
la b orat or y res ult (ie, decrease d he m o gl o bi n). 
Se verit y s h o ul d be rec or de d a n d gra d e d acc or di n g t o t he C T C A E . 
F or A Es ass ociate d wit h la b orat or y a b n or malities, t he e ve nt s h o ul d be gra d e d o n t he basis of t he 
cli nical se verit y i n t he c o nte xt of t he u n derl yi n g c o n diti o ns; t his ma y or ma y  n ot be i n a gree m e nt 
wit h t he gra di n g of t he la b orat or y  a b n or malit y.  
7. 6.  
T o xi cit y M a n a g e m e nt  
All cli nical a n d cli nicall y si g nifica nt la b orat or y t o xicities will be ma na ge d acc or di n g t o u nif or m 
g ui deli nes det aile d i n A p pe n di x  1 4  a n d as o utli ne d bel o w.  
Refer t o Secti o n 3. 7 , Criteria f or St u d y Dr u g I nterr u pti o n or Disc o nti n uati o n, f or a d diti o nal 
s pecific disc o nti n uati o n criteria. S pecific t o xicit y disc o nti n uati o n criteria i n Secti o n 3. 7  
s u perse de b el o w ge n eral t o xicit y g ui deli nes, a n d i n ge n eral, w h ere discre p a nc y is pr ese nt, t he 
m ore c o nser vati ve criteri a a p pl y. T he S p o ns or  Me dical Lea d er or desi g n ee s h o uld be c o ns ulte d 
pri or t o st u d y  dr u g disc o nti n uati o n w he n me dicall y feasi ble .  
7. 6. 1.  
Gr a d e s 1 a n d 2 L a b or at or y A b n or m alit y or Cli ni c al E v e nt  
C o nti n ue st u d y dr u g at t h e discreti o n of t he i n vesti gat or.  
•  F or st u d y s pecifi c i nterr u pti o n a n d st o p pi n g criteri a, please refer t o S ecti o n  3. 7  ( Criteria f or 
I nterr u pti o n or Disc o nti n uati o n of St u d y Treat me nt) 
•  F or Gra des 1 a n d 2 La b orat or y A b n or m alit y or Cli nical E ve nt n ot s pecifie d i n Secti o n 3. 7 , 
c o nti n ue st u d y dr u g at t he discreti o n of t he i n vesti gat o r. 
7. 6. 2.  
Gr a d e s 3 L a b or at or y A b n or m alit y or Cli ni c al E v e nt  
•  F or st u d y s pecifi c i nterr u pti o n a n d st o p pi n g criteri a, please refer t o S ecti o n  3. 7  ( Criteria f or 
I nterr u pti o n or Disc o nti n uati o n of St u d y Treat me nt) 
•  F or Gra des 3 La b orat or y A b n or malit y or Cli nical E ve nt n ot s pecifie d i n Secti o n  3. 7 , t he 
f oll o wi n g t o xicit y m a na ge me nt g ui d eli nes a p pl y: 

Fil g oti ni b  
 
Pr ot oc ol  G L P G 0 6 3 4 -C L -2 2 7  
Fi nal  
Gala pa g os  
A me n d me nt 2  
C O N FI D E N TI A L  
P a ge  7 6  
0 9 Se p 2 0 2 2  
⎯ F or Gra de  3 cli nicall y si g nifica nt la b orat or y a b n or malit y or cli nical e ve nt, I M P ma y be 
c o nti n ue d if t he e ve nt is c o nsi dere d t o be u nrel ate d t o I M P. 
⎯ F or a Gra d e  3 cli nical e v e nt, or cli nicall y si g nifi ca nt la b orat or y a b n or m alit y c o nfir me d b y 
re peat testi n g, t hat is c o nsi dere d t o be relate d t o I M P, I M P s h o ul d be wit h hel d u ntil t he 
t o xicit y ret ur ns t o ≤ Gra d e  2.  
If a la b orat or y a b n or malit y rec urs t o ≥Gra de  3 f oll o wi n g re -c h alle n ge wit h I M P a n d is 
c o nsi dere d relate d t o I M P, t he n I M P s h o ul d be per ma ne ntl y dis c o nti n ue d a n d t he s u bject 
ma na ge d acc or di n g t o l o cal cli nical pr actice. Rec urre nce of la b orat or y a b n or malities 
c o nsi dere d u nrelate d t o I M P ma y n ot re q uir e per ma ne nt disc o nti n uati o n.  
7. 6. 3.  
Gr a d e s 4 L a b or at or y A b n or m alit y or Cli ni c al E v e nt  
•  F or st u d y s pecifi c i nterr u pti o n a n d st o p pi n g criteri a, please refer t o S ecti o n  3. 7  ( Criteria f or 
I nterr u pti o n or Disc o nti n uati o n of St u d y Treat me nt). 
•  F or Gra de 4 La b orat or y A b n or malit y or Cli nical E ve nts n ot s pecifie d i n Secti o n  3. 7 , t he 
f oll o wi n g t o xicit y m a na ge me nt g ui d eli nes a p pl y: 
⎯ F or a Gra d e  4 cli nical e v e nt or cli nicall y si g nifi ca nt Gra de  4 la b orat or y a b n or malit y 
c o nfir me d b y re peat testi n g t hat is c o nsi dere d relat e d t o I M P, I M P s h o ul d be per ma n e ntl y 
disc o nti n ue d a n d t he s u bject ma na ge d acc or di n g t o l ocal cli nical practice. T he s u bject 
s h o ul d be f oll o we d as cli nicall y i n dicat e d u ntil t he la b orat or y a b n or malit y ret ur ns t o 
Baseli ne  or is ot her wise e x plai ne d, w hic he ver  o cc urs first. A cli nicall y si g nifica nt 
Gra de  4 la b orat or y a b n or malit y t hat is n ot c o nfir m e d b y re peat testi n g s h o ul d be 
ma na ge d acc or di n g t o t h e al g orit h m f or t he ne w t o xicit y gra d e.  
IM P  ma y be c o nti n ue d wit h o ut d ose i nterr u pti o n f or a cli nicall y n o n -si g nifi ca nt Gra d e 4 
la b orat or y a b n or malit y (e g, Gra de 4 C K after stre n u o us e x ercise or tri gl yceri de ele vati o n t hat is 
n o nfasti n g or t hat ca n b e me dicall y ma na ge d) or a cli nical e ve nt c o nsi dere d u nrelate d t o I M P. 
Treat me nt -e mer ge nt t o xicities will be n ote d b y t h e i n vesti gat or a n d br o u g ht t o t he atte nti o n of 
t he S p o ns or  M e dical Lea der or desi g nee , w h o will ha ve a disc ussi o n wit h t he i n vesti gat or a n d 
deci de t he a p pr o priate c o urse of acti o n. W het her or n ot c o nsi dere d tr eat me nt -relate d, all s u bjects 
e x perie nci n g A Es  m ust be m o nit ore d peri o dicall y u ntil s y m pt o ms s u bsi de, a n y a b n or mal 
la b orat or y val u es ha ve res ol ve d or ret ur n e d t o Bas eli ne  le vels or t he y are c o nsi dere d irre versi ble, 
or u ntil t here is a satisfact or y e x pla nati o n f or t he c ha n ges o bser v e d.  
A n y q u esti o ns re gar di n g t o xicit y ma na ge me nt s h o ul d be directe d t o t he S p o ns or  Me dical  Lea der 
or desi g n ee . 
7. 7.  
S p e ci al Sit u ati o n s R e p ort s  
7. 7. 1.  
D efi niti o n s of S p e ci al Sit u ati o n s  
S pecial sit uati o n re p orts i ncl u de all re p orts of me dicati o n err or, a b use, mis use, o ver d ose, pr o d uct 
c o m plai nts, occ u pati o nal e x p os ure,  dr u g i nteracti o ns, u ne x pecte d be nefit, tra ns missi o n of 

Fil g oti ni b  
 
Pr ot oc ol  G L P G 0 6 3 4 -C L -2 2 7  
Fi nal  
Gala pa g os  
A me n d me nt 2  
C O N FI D E N TI A L  
P a ge  7 7  
0 9 Se p 2 0 2 2  
i nfecti o us a ge nts via t he pr o d uct, c o u nterfeit or falsifie d me dicine, e x p os ure via breastfee di n g , 
a n d part ner pre g n a nc y re p orts re gar dl ess of a n ass ociate d A E .  
Me dicati o n err or is a n y u ni nte nti o nal err or i n t he prescri bi n g, dis pe nsi n g, pre parati o n f or 
a d mi nistrati o n or a d mi nistrati o n of a me dici nal pr o d uct w hile t he me dicati o n is i n t he c o ntr ol of 
t he healt h care pr ofessi o nal, patie nt , or c o ns u mer. Me dicati o n err ors ma y b e classifie d as a 
me dicati o n err or wit h o ut a n A E, w hic h i ncl u des sit uati o ns of misse d d ose; me dicati o n err or wit h 
a n A E; i nterce pte d me dic ati o n err or; o r p ot e ntial me dicati o n err or. 
A b use is defi ne d as persiste nt or s p ora dic i nte nti o nal e xcessi ve use of a m e dici nal pr o d uct b y a 
s u bject. 
Mis use is defi ne d as a n y i nte nti o nal a n d i na p pr o priate use of a m e dici nal pr o d uct t hat is n ot i n 
acc or da nce wit h t he pr o t oc ol i nstr ucti o ns or t he l ocal pres cri bi n g i nf or mati o n. 
A n o ver d ose is defi ne d as a n acci d e ntal or i nte nti o nal a d mi nistrati o n of a q ua ntit y of a m e dici nal 
pr o d uct gi v e n per a d mi nistrati o n or c u m ulati vel y w hic h is a b o ve t he ma xi m u m rec o m me n de d 
d ose as per pr ot oc ol or i n t he pr o d uct la belli n g (as it a p plies t o t he dail y d os e of t he s u bject i n 
q uesti o n). I n cas es of a discre pa n c y i n dr u g acc o u nta bilit y, o v er d ose will be esta blis he d o nl y 
w he n it is clear t hat t he s u bject has ta ke n t he e x cess d ose(s). O ver d ose ca n n ot be esta blis he d 
w he n t he s u bject c a n n ot acc o u nt f or t he discre pa n c y e x ce pt i n cases i n w hi c h t he i n vesti gat or has 
reas o n t o s us pect t hat t he s u bject has ta ke n t he a d diti o nal d ose(s). 
Occ u pati o nal e x p os ure is defi ne d as e x p os ure t o a me dici nal pr o d uct  as a res ult of o ne's 
pr ofessi o nal or n o n -pr ofessi o nal occ u pati o n.  
Dr u g i nteracti o n is defi ne d as a n y dr u g/ dr u g, dr u g/f o o d, or dr u g/ de vice i nt eracti o n.  
U ne x pecte d be nefit is defi ne d as a n u ni nte n d e d t hera pe utic effect w h ere t h e res ults are j u d ge d t o 
be desira ble a n d be n efici al.  
Tra ns missi o n of i nfecti o us a ge nts is defi ne d as a n y s us pecte d tra ns missi o n of a n i nfecte d a ge nt 
t hr o u g h an I M P . 
Pr o d uct c o m plai n t is defi ne d as c o m plai nts arisi n g fr o m p ote ntial de viati o ns i n t he ma n ufact ur e, 
pac ka gi n g, or distri b uti o n of t he me dici nal pr o d u ct .  
C o u nterfeit or falsifie d m e dici ne: A n y i n vesti gati o nal pr o d uct wit h a false re prese nt ati o n of: a) 
its i de ntit y, b) its s ource, or c) its hist or y.  
7. 7. 2.  
I n str u cti o n s f or R e p orti n g S p e ci al Sit u ati o n s 
7. 7. 2. 1.  
I n str u cti o n s f or R e p orti n g P art n er Pr e g n a n ci e s  
Pre g n a ncies of fe mal e part ners of male st u d y s u bj ects e x p ose d t o st u d y dr u g m ust be re p orte d 
u ntil 9 0  da ys aft er t he last st u d y dr u g i nta k e a n d rele va nt i nf or mati o n s h o ul d be s u b mitte d t o  t he 
S p o ns or  usi n g t he pre g n a nc y a n d pr e g n a nc y o utc o me f or ms wit hi n 2 4  h o urs. If t he e n d of t h e 
pre g na nc y o cc urs after t he st u d y h as bee n c o m plete d, t he o utc o me s h o ul d b e re p ort e d directl y t o : 

Fil g oti ni b  
 
Pr ot oc ol  G L P G 0 6 3 4 -C L -2 2 7  
Fi nal  
Gala pa g os  
A me n d me nt 2  
C O N FI D E N TI A L  
P a ge  7 8  
0 9 Se p 2 0 2 2  
E -mail: 
 
or  
 Me dical Affairs S A E Fa x #: 
 
After 9 0  da ys fr o m t he last St u d y Dr u g i nta ke, a n d if t he patie nt is u n der Sta n dar d of Care  
treat me nt, t he i n vesti gat or is hi g hl y e nco ura ge d t o re p ort a n y Pre g na nc y c o nsi dere d as relate d t o 
t his Sta n dar d of Care tr eat me nt directl y t o t he mar keti n g a ut h orizati o n h ol der a n d/ or it s Nati o nal 
C o m pete nt A ut h orit y.  
I n or der t o a v oi d d u plicati o n i n t he re p orti n g of s uc h e ve nts, t he s p o ns or will n ot re p ort t hese 
Pre g n a ncies si m ulta ne o usl y.  
Refer t o A p pe n di x  1 0  f or Pre g n a nc y Preca uti o ns, Defi niti o n of Fe m ales of C hil d beari n g 
P ote ntial  a n d C o ntrace pti ve Re q uire me nts.  
7. 7. 2. 2.  
R e p orti n g Ot h er S p e ci al Sit u ati o n s  
All ot her s pecial sit uati o n re p orts m ust be re p orte d o n t he s pecial sit uati o ns re p ort f or m a n d 
f or war de d t o t he S p o ns or wit hi n 2 4  h o urs of t he i n vesti gat or b ec o mi n g a ware of t he sit uati o n.  
T hese re p orts m ust c o nsist of sit uati o ns t hat i n v ol ve st u d y I M P.  
S pecial sit uati o ns i n v ol vi n g c o n c o mita nt me dicati o ns d oes n ot nee d t o be re p orte d o n t he s pecial 
sit uati o ns re p ort f or m; h o we ver, f or s pecial sit uati o ns t hat res ult i n A Es d ue t o a c o nc o mit a nt 
me dicati o n, t he A E s h o ul d be re p ort e d o n t he A E f or m.  
A n y i na p pr o priate us e of c o nc o mita nt me dicati o ns pr o hi bite d b y t his pr ot oc ol s h o ul d n ot be 
re p orte d as “ mis use,” b ut ma y b e m ore a p pr o priat el y d o c u me nte d as a pr ot oc ol de viati o n. 
Refer t o Secti o n  7. 3  a n d t he C R F/e C R F c o m pleti o n g ui deli nes f or f ull i nstr ucti o ns o n t he 
mec ha nis m of s peci al sit uati o ns re p orti n g.  
All cli nical se q uelae i n r elati o n t o t hese s pecial sit uati o n re p orts will be re p orte d as A Es or S A Es 
at t he sa me ti me usi n g t h e A E C R F/e C R F a n d/ or t he S A E re p ort f or m. Det ails of t he s y m pt o ms 
a n d si g ns, cli nic al ma na ge me nt, a n d o utc o me will be re p ort e d, w he n a vaila ble.  
8.  
S T A TI S TI C A L C O N SI D E R A TI O N S  
8. 1.  
A n al y si s O bj e cti v e s a n d E n d p oi nt s  
8. 1. 1.  
A n al y si s O bj e cti v e s  
T he pri mar y o bje cti ve of t his st u d y is:  
•  
T o e val uate t he effect of fil g oti ni b o n testic ular f u ncti o n as defi ne d b y t he pr o p orti o n of 
s u bjects wit h a ≥5 0 % decrease fr o m Baseli ne  i n s p er m c once ntrati o n at Wee k  1 3  
C CI
C CI
C CI

Fil g oti ni b  
 
Pr ot oc ol  G L P G 0 6 3 4 -C L -2 2 7  
Fi nal  
Gala pa g os  
A me n d me nt 2  
C O N FI D E N TI A L  
P a ge  7 9  
0 9 Se p 2 0 2 2  
T he sec o n d ar y o bjecti ves of t his st u d y i ncl u de:  
•  
T o e val uate t he effect of fil g oti ni b o n testic ular f u ncti o n as defi ne d b y t he pr o p orti o n of 
s u bjects wit h a ≥5 0 % decrease fr o m Baseli ne  i n s p er m c o nce ntrati o n at Wee k 2 6 
•  
T o e val uate t he effect of fil g oti ni b o n s per m t otal m otilit y at Wee ks  1 3 a n d 2 6  
•  
T o e val uate t he effect of fil g oti ni b o n t otal s per m c o u nt at Wee ks  1 3 a n d 2 6  
•  
T o e val uate t he effect of fil g oti ni b o n t he c ha n ge fr o m Baseli ne  i n s p er m c o nce ntrati o n at 
Wee ks 1 3 a n d 2 6  
•  
T o e v al uate t he effect of fil g oti ni b o n ejac ulat e v ol u me at Wee ks  1 3 a n d 2 6  
•  
T o e val uate t he effect of fil g oti ni b o n s per m m or p h ol o g y at Wee ks  1 3 a n d 2 6   
T he e x pl orat or y o bj ecti v es of t his st u d y i ncl u de: 
•  
T o e val uate t he re versi bilit y of o bser ve d effects of fil g oti ni b o n testic ular f u ncti o n i n 
s u bjects w h o e x perie nce a ≥5 0 % decreas e i n s per m c o nce ntrati o n, a n d/ or m otilit y, a n d/ or 
m or p h ol o g y   
•  
T o e val uate t he effect of fil g oti ni b o n se x h or m o nes, i ncl u di n g L H , F S H , i n hi bi n B, a n d t otal 
test oster o ne at W ee ks 1 3 a n d 2 6  
•  
T o e val uate t he s afet y a n d t olera bilit y of fil g oti ni b  
•  
T o c haracteriz e t he plas ma P K of fil g oti ni b a n d  its meta b olite ( G S-8 2 9 8 4 5, f or merl y 
) 
8. 1. 2.  
Pri m ar y E n d p oi nt  
T he pri mar y e n d p oi nt is t he pr o p orti o n of s u bjects wit h a ≥5 0 % dec reas e fr o m Baseli ne  i n s per m 
c o nce ntr ati o n at W ee k  1 3.  
8. 1. 3.  
S e c o n d ar y E n d p oi nt s  
T he sec o n d ar y e n d p oi nts are:  
•  
T he pr o p orti o n of s u bjects wit h a ≥5 0 % decrease fr o m Baseli ne  i n s p er m c o nce ntrati o n at 
Wee k  2 6  
•  
C ha n ge fr o m Baseli ne  in perce nt m otile s per m at Wee ks  1 3 a n d 2 6  
•  
C ha n ge fr o m  Baseli ne  i n t otal s per m c o u nt at Wee ks 1 3 a n d 2 6  
•  
C ha n ge fr o m Baseli ne  i n s per m c o nce ntrati o n at Wee ks 1 3 a n d 2 6  
C CI

Fil g oti ni b  
 
Pr ot oc ol  G L P G 0 6 3 4 -C L -2 2 7  
Fi nal  
Gala pa g os  
A me n d me nt 2  
C O N FI D E N TI A L  
P a ge  8 0  
0 9 Se p 2 0 2 2  
•  
C ha n ge fr o m Baseli ne  i n ejac ulate v ol u me at Wee ks 1 3 a n d 2 6  
•  
C ha n ge fr o m Baseli ne  i n perce nt n or mal s per m m or p h ol o g y at Wee ks 1 3 a n d 2 6  
8. 1. 4.  
E x pl or at or y E n d p oi nt s  
T he e x pl orat or y e n d p oi nts are:  
•  
Perce nt of s u bjects w h o ac hie ve re versi bilit y a m o n g s u bjects w h o e x perie nce a ≥5 0 % 
decrease i n s per m c o nce ntrati o n , a n d/ or m otilit y, a n d/ or m or p h olo g y   
•  
C ha n ge fr o m Baseli ne  i n se x h or m o nes, i ncl u di n g L H, F S H, in hi bi n B, a n d t otal test oster o ne 
at W ee ks 1 3 a n d 2 6  
•  
P K c haracteristics f or fil g oti ni b a n d its meta b olite G S -8 2 9 8 4 5  
8. 2.  
A n al y si s C o n v e nti o n s  
8. 2. 1.  
A n al y si s S et s  
8. 2. 1. 1.  
All R a n d o mi z e d S et  
T he All Ra n d o mize d Set i ncl u des all s u bjects w h o were ra n d o mize d.  
8. 2. 1. 2.  
S e m e n A n al y si s S et  
T he Se me n A nal ysis Set i ncl u des all ra n d o mize d s u bjects w h o  ha ve Bas eli ne  a n d at least o ne 
p ost -Baseli ne  s e me n sa m ple. T his is t he pri mar y a nal ysis set f or se me n-relate d para met ers.  
8. 2. 1. 3.  
S af et y A n al y si s S et  
T he Safet y A n al ysis Set i ncl u des all s u bjects w h o recei v e d at least o ne d ose of st u d y dr u g.  T his 
is t he pri mar y a nal ysis set f or safet y e n d p oi nts. 
8. 2. 1. 4.  
P h ar m a c o ki n eti c  A n al y si s S et  
T he P K  a nal ysis set incl u des all s u bjects i n t he S afet y A nal ysis Set w h o ha v e at least 
1  n o n missi n g p ost d ose c o nce ntrati o n val ue  for fil g oti ni b a n d/ or its meta b olite G S -8 2 9 8 4 5 . T his 
is t he pri mar y a nal ysis set f or all P K a nal yses. 
8. 3.  
D at a H a n dli n g C o n v e nti o n s  
P K c o nce ntrati o n val u es a n d P K para m eter val u es bel o w t he li mit of q ua ntitati o n ( B L Q) will be 
prese nte d as “ B L Q” i n t h e data list i n gs. B L Q val u es t hat occ ur pri or t o t he first d ose will be 
treate d as 0, B L Q v al ues at all ot her ti me  p oi nts will be treate d as 1/ 2 of t he l o wer li mit of 
q ua ntitati o n ( L L O Q).  
La b orat or y d ata t hat are c o nti n u o us i n nat ure b ut are less t ha n t he L L O Q  or a b o ve t he u p per li mit 
of q ua ntitati o n will be i m p ute d t o t he val ue of t he l o wer or u p p er li mit mi n us or pl us o ne 

Fil g oti ni b  
 
Pr ot oc ol  G L P G 0 6 3 4 -C L -2 2 7  
Fi nal  
Gala pa g os  
A me n d me nt 2  
C O N FI D E N TI A L  
P a ge  8 1  
0 9 Se p 2 0 2 2  
si g nifica nt di git, res p ecti vel y (e g, if t he res ult of a c o nti n u o us la b orat or y test is  < 2 0, a val ue of 
1 9 will be assi g ne d; if t h e res ult of  a c o nti n u o us la b orat or y test is < 2 0. 0, a val ue of 1 9. 9 will be 
assi g ne d).  
I n ge neral, missi n g data will n ot be i m p ute d u nless met h o ds f or ha n dli n g missi n g data are 
s pecifie d. T o ass ess missi n g se me n d ata patter ns, missi n g ness b y treat me nt ar m, ra n d o mizati o n 
strat u m a n d Bas eli ne  de m o gra p hi c c haracteristics will be s u m marize d. A d diti o nal details o n 
ha n dli n g missi n g d ata a n d se nsiti vit y a nal yses will be pr o vi de d i n t he statistical a nal ysis pla n 
( S A P). 
8. 4.  
D e m o gr a p hi c D at a a n d B a s eli n e  C h ar a ct eri sti c s  
De m o gra p hic a n d Baseli ne  c haracteristics will be s u m marize d  b y treat me nt gr o u p  usi n g sta n d ar d 
descri pti ve statistics i ncl u di n g sa m ple siz e, mea n, sta n dar d de viati o n (S D ), me dia n, Q 1, Q 3, 
mi ni m u m, a n d ma xi m u m f or c o nti n u o us varia bl es a n d n u m bers a n d p erce nta ges f or cat e g orical 
varia bles.  
De m o gra p hic d ata will i ncl u de se x, race, et h nicit y, a n d a ge.  
Baseli ne c haracteristics ma y i ncl u d e s per m c o n ce ntrati o n, ejac ulate v ol u m e, t otal s per m per 
ejac ulate, a n d ot her v aria bles of i nterest .  
8. 5.  
St ati sti c al A n al y si s  
8. 5. 1.  
Pri m ar y A n al y si s   
T he pri mar y e n d p oi nt is t he pr o p orti o n of s u bjects wit h a ≥5 0 % decreas e fr o m Baseli ne  i n s per m 
c o nce ntr ati o n at W ee k  1 3. A c u m ulati ve distri b uti o n pl ot f or t he perce nt c ha n ge fr o m Bas eli ne  i n 
s per m c o nce ntrati o n at Wee k 1 3 f or eac h treat me nt gr o u p will be  c o nstr ucte d. T he x -a xis will 
dis pla y perce nt c ha n ges fr o m Baseli ne  i n s p er m c o nce ntrati o n ra n gi n g fr o m 1 0 0 %  decrease 
(ie, -1 0 0 %  or az o os per mia) t o t he m a xi mal o bser ve d i ncrease. T he y -a xis will dis pla y t he 
pr o p orti o n of s u bjects w h o e x perie nce d a p erce nt a ge c h a n ge i n s per m c o n ce ntrati o n e q u al t o or 
less t ha n t he c orres p o n di n g x-a xis val ue at Wee k  1 3. T his met h o d is s u g geste d i n F D A’s 
G ui da nce o n  T estic ular t o xicit y  (O ct o ber 2 0 1 8 ). T he pr o p orti o n of s u bjects e x perie nci n g at least 
a 5 0%  decrease i n s per m c o nce ntr ati o n fr o m Baseli ne  will be calc ulate d  f or eac h tr eat me nt 
gr o u p. T h e differe n ce bet wee n t he fil g oti ni b a n d place b o gr o u ps will be cal c ulate d t o get her wit h 
t he ass ociate d 9 5 % c o nfi de nce i nter val. 
S u bjects w h o ha ve t w o s a m ples a vaila ble at Wee k  1 3, wil l be i ncl u de d i n t he pri mar y a n al ysis. 
Se nsiti vit y a n al ys es will be perf or me d t o e val u ate t he i m pact of differe nt missi n g data pa tter ns 
o n t he pri mar y a n al ysis.  Details of t he se nsiti vit y a nal ys es will be pr o vi de d i n t he S A P.  
8. 5. 2.  
S e c o n d ar y A n al y s e s  
T he sec o n d ar y e n d p oi nts i ncl u de t he pr o p orti o n of s u bjects wit h a ≥5 0 % decreas e fr o m Bas eli ne  
i n s per m c o nce ntr ati o n at Wee k 2 6, c ha n ges fr o m Baseli ne  at Wee ks 1 3 a n d 2 6 i n s per m 
c o nce ntr ati o n, t otal s per m c o u nt, ejac ulate v ol u m e, perce nt m otile s per m, a n d perce nt n or mal 
s per m m or p h ol o g y.  

Fil g oti ni b  
 
Pr ot oc ol  G L P G 0 6 3 4 -C L -2 2 7  
Fi nal  
Gala pa g os  
A me n d me nt 2  
C O N FI D E N TI A L  
P a ge  8 2  
0 9 Se p 2 0 2 2  
T he c o nti n u o us e n d p oi nts will be s u m marize d  ( n, mea n, S D, me dia n, Q 1, Q 3, mi ni m u m, a n d 
ma xi m u m) b y treat me nt gr o u p at W ee ks 1 3 a n d 2 6 al o n g wit h c orres p o n di n g c h a n ge fr o m 
Basel i ne a n d 9 5 % CIs. All cate g orical e n d p oi nts will be s u m marize d b y t h e n u m ber a n d 
perce nt a ge of s u bjects w h o meet t he e n d p oi nt defi niti o n . 
A n a nal ysis of c o v aria nce ( A N C O V A) m o del a dj usti n g f or Bas eli ne  val ue a n d stratificati o n 
fact ors will be use d t o esti mate treat me nt differe n ces ( 9 5 % CI) f or t he c o nti n u o us e n d p oi nts. T he 
cate g orical e n d p oi nt at Wee k  2 6 will be s u m marize d descri pti vel y . 
8. 5. 3.  
E x pl or at or y A n al y s e s  
T he e x pl orat or y a nal yses of se x h or m o nes will use t he sa me a n al ysis met h o ds use d as f or t he 
c o nti n u o us sec o n dar y e n d p oi nts. F or re v ersi bilit y, t he n u m ber a n d perce nta ge a n d c u m ulati ve 
n u m ber a n d perce nt a ge of s u bjects w h o ac hie ve re versi bilit y will be dis p la ye d b y s p er m 
para meter a n d m o nit ori n g p has e visit f or t h ose s u bjects wit h a ≥5 0 % decrease i n t he s per m 
para meter(s) q u alif yi n g t he m f or e ntr y i nt o t he m o nit ori n g p hase.  
8. 5. 4.  
Ot h er S af et y A n al y si s  
All ot her safet y a n al yses will be perf or me d usi n g t he S afet y A n al ysis S et.  
Safet y will be e val uat e d b y ass ess me nt of cli nical la b orat or y tests, P Es , E C G a n d vital si g ns 
meas ure me nts at v ari o us ti me  p oi nts d uri n g t he st u d y, a n d b y t h e d oc u me nt ati o n of A Es.  
All safet y data c ollecte d o n or after t h e first d ose of st u d y d r u g a d mi nistrati o n u p t o 3 0 da ys after 
t he last d ose of st u d y dr u g, u nless s pecifie d ot her wise, will be s u m marize d b y treat me nt gr o u p 
acc or di n g t o t he st u d y dr u g recei v e d.  
8. 5. 5.  
E xt e nt of E x p o s ur e  
A s u bject’s e xte nt of e x p os ure t o st u d y dr u g will be ge nerate d fr o m t he st u d y dr u g 
a d mi nistrati o n pa ge of t h e e C R F . E x p os ure data will be s u m marize d b y treat me nt gr o u p.  
D urati o n of e x p os ure t o st u d y dr u g will be e x press e d as t he n u m ber of wee ks bet wee n t he 
first a n d last d ose of t he st u d y dr u g, i ncl usi ve, re gar dless of  te m p orar y i nterr u pti o ns i n st u d y 
dr u g a d mi nistrati o n a n d s u m mariz e d b y treat me nt gr o u p.  
8. 5. 6.  
A d v er s e E v e nt s  
Cli nical a n d la b orat or y A Es  will be c o de d usi n g t h e Me dical Dicti o nar y f or Re g ulat or y 
Acti vitie s ( Me d D R A). S yste m Or ga n Class, Hi g h-Le vel Gr o u p Ter m ( H L G T), Hi g h-Le v el Ter m 
( H L T), P T, a n d L o w er Le vel Ter m ( L L T) will be attac he d t o t he cli nical data base.  
T E A Es are:  
•  
A n y A Es wit h a n o nset d ate of o n or after t h e st u d y dr u g start date a n d n o l ater t ha n 3 0 da ys  
after per ma ne nt disc o nti n uati o n of st u d y dr u g or  

Fil g oti ni b  
 
Pr ot oc ol  G L P G 0 6 3 4 -C L -2 2 7  
Fi nal  
Gala pa g os  
A me n d me nt 2  
C O N FI D E N TI A L  
P a ge  8 3  
0 9 Se p 2 0 2 2  
•  
A n y A Es  lea di n g t o pre m at ure disc o nti n uati o n of st u d y dr u g. 
S u m maries ( n u m ber a n d perce nt a ge of s u bjects) of T E A Es b y s yste m or ga n class a n d P T will be 
pr o vi de d b y treat me nt gr o u p . T E A Es will als o be s u m marize d b y rel ati o ns hip t o st u d y dr u g a n d 
se verit y. I n a d diti o n, T E A Es lea di n g t o pre mat ure disc o nti n uati o n of st u d y dr u g will be 
s u m marize d a n d liste d. 
8. 5. 7.  
L a b or at or y E v al u ati o n s  
Selecte d la b orat or y data will be s u m marize d ( n, mea n, S D, me dia n, Q 1, Q 3, mi ni m u m, a n d  
ma xi m u m) b y treat me nt gr o u p a n d st u d y visit  al o n g wit h c orres p o n di n g c h a n ge fr o m  Bas eli ne . 
T he i nci de nce of treat me nt -e mer ge nt gra de d la b orat or y a b n or malities will be s u m marize d 
si milarl y. 
Gra de d la b orat or y a b n or malities will be defi ne d usi n g C T C A E 4. 0 3 gra di n g scale i n  A p pe n di x  9 . 
8. 6.  
P h ar m a c o ki n eti c A n al y si s  
Plas ma c o nce ntr ati o ns of fil g oti ni b a n d its meta b olite ( G S -8 2 9 8 4 5 ) will be liste d a n d 
s u m marize d f or all s u bjects usi n g des cri pti ve sta tistics (e g, s a m ple siz e, arit h metic mea n, 
ge o m etric mea n, %  c o efficie nt of variati o n, S D , m e dia n, mi ni m u m, a n d ma xi m u m). P las ma 
c o nce ntr ati o ns of t he fil g oti ni b a n d G S -8 2 9 8 4 5  o ver ti me ma y be pl otte d i n se mi l o garit h mic a n d 
li near f or mats as mea n  S D.  
E x p os ure -res p o nse a n al yses ma y b e perf or me d. 
8. 7.  
S a m pl e Si z e  
A sa m ple siz e of a p pr o xi matel y 1 0 0  e val ua ble s u bjects per gr o u p, w here e v al ua ble is defi ne d as 
s u bjects i n t he Se me n A n al ysis Set, is a de q uat e f or t he p ur p oses of esti mati n g c u m ulati ve 
distri b uti o n c ur ves a n d pr o d uci n g a 9 5 % CI wi dt h t hat is reas o na bl y narr o w f or t he perce nt a ge of 
s u bjects i n eac h gr o u p w h o e x perie nce a ≥5 0 % decreas e i n s per m c o n ce ntr ati o n c o m pare d t o 
Baseli ne . T his sa m ple siz e is s u g gest e d i n F D A G ui da nce o n Testic ul ar T o xicit y  ( Oct o ber 2 0 1 8). 
Ass u mi n g a 2 0 % rate of n o n -e val ua ble s u bj ects at Wee k  1 3, u p t o 1 2 5 s u bjects per ar m ma y be 
e nr olle d.  
Res ults of t his st u d y ma y be p o ole d wit h t he res ults of a se parate st u d y bei n g c o n d u cte d i n 
s u bjects wit h I B D ( Pr ot oc ol G S-U S -4 1 8 -4 2 7 9) wit h t he sa me o bjecti ve . T he t otal pla n ne d 
n u m ber of s u bjects i n b ot h st u dies c o m bi ne d will be u p t o a p pr o xi matel y 2 5 0  s u bjects. 
8. 8.  
D at a M o nit ori n g C o m mitt e e /S p o n s or S af et y M a n a g e m e nt T e a m   
A n e xter na l D M C will re vie w t he pr o gress of t he st u d y a n d p erf or m i nteri m re vie ws of safet y 
dat a a n d pr o vi de rec o m me n dati o n t o  t he S p o ns or w het her t he nat ure, fre q u e nc y, a n d se v erit y of 
a d verse effects ass oci ate d wit h st u d y treat me nt w arra nt t he earl y ter mi nati o n of  t he st u d y i n t he 
best i nterests of t he partici pa nts, w het her t h e st u d y s h o ul d c o nti n ue as pl a n ne d, or t he st u d y 
s h o ul d c o nti n ue wit h m o dificati o ns. T he i nitial meeti n g is pla n n e d t o occ ur after a p pr o xi matel y 
the first 5 0  s u bjects reac h Wee k 1 3. F oll o wi n g t his, s u bse q ue nt meeti n gs will occ ur 

Fil g oti ni b  
 
Pr ot oc ol  G L P G 0 6 3 4 -C L -2 2 7  
Fi nal  
Gala pa g os  
A me n d me nt 2  
C O N FI D E N TI A L  
P a ge  8 4  
0 9 Se p 2 0 2 2  
a p pr o xi matel y e ver y 4 m o nt hs (if e nr oll me nt s u p p orts t he nee d). A d diti o nal D M C meeti n gs ma y 
be sc he d ule d as nee d e d.  
T he D M C’s s pecifi c acti vities will be defi ne d b y a m ut uall y a gree d u p o n c harter, w hi c h wi ll 
defi ne t he D M C’s me m b ers hi p, c o n d uct a n d m eeti n g sc he d ule.  
W hile t he D M C will be as ke d t o a d vise t he s p o ns or re gar di n g f ut ure c o n d uct of t he st u d y, 
i ncl u di n g p ossi ble earl y st u d y ter mi nati o n, t he S p o ns or retai ns fi nal decisi o n-ma ki n g a ut h orit y 
o n all as pects of t he st u d y.  
A n a d -h oc D M C meeti n g ma y b e tri g gere d b y t he f oll o wi n g c o n diti o ns or base d u p o n re vi e w of 
e mer gi n g se me n d ata:  
•  
≥2 s u bjects de vel o p t he s a me ( b y preferre d ter m) relate d, Gra de  4, u ne x pect e d A E  i n t he 
i nfecti o ns a n d i nfestati o ns S yst e m O r ga n Class; 
•  
≥2 s u bjects de vel o p a n y relate d, Gra de 4, t hr o m b o e m b olic e ve nt t hat has bee n p ositi vel y 
a dj u dicate d b y t he a dj u dicati o n c o m mittee (see Secti o n 8. 9 ); 
•  
an y s u bject de vel o ps a Gra de 5, relate d, u n e x pecte d A E. T he d efi niti o n of a n u ne x pecte d A E 
will be base d o n t he Refere nce Safet y I nf or mati o n t hat is o n file at t he ti me t he e ve nt occ urs . 
T he D M C has m o nit ore d t he st u d y u ntil t he date of pr ot oc ol a me n d me nt  2 , incl u di n g t he dat a f or 
I A 2. As of a m e n d me nt 2, t he D M C will be dec o m missi o ne d. T he safet y a n d pr o gress of t he 
re mai n der of t he st u d y will c o nti n ue t o be m o nit ore d b y t h e S p o ns or  M e dical L ea der a n d 
M e dical M o nit or , or desi g nee, pr o vi di n g u p dates d uri n g  re g ular S p o ns or me dical m o nit ori n g 
o versi g ht meeti n gs acr oss t he fil g oti ni b pr o gra m . If nee d e d, safet y iss ues will be escalate d t o t he 
S S M T  per i nter nal sta n dar d pr oce d ures , i n cl u di n g t he or ga nizati o n of a d h oc meeti n gs if 
re q uire d. T h e S S M T  ca n c o ns ult exter nal e x perts, if dee me d necessar y, a n d ca n re vi e w data i n a n 
u n bli n de d fas hi o n.  
8. 9.  
C ar di o v a s c ul ar S af et y E n d p oi nt A dj u di c ati o n C o m mitt e e ( C V E A C)  
A n i n de pe n de nt a dj u dic ati o n c o m mittee will be f or me d t o peri o dicall y re vie w a n d a dj u dicate all 
p ote ntial maj or a d vers e car di o vasc ular e ve nts ( M A C E) a n d t hr o m b oe m b olic e ve nts i n a bli n de d 
ma n ner.  
T he C V E A C’s s pecifi c acti vities will be g o ver ne d b y a m ut uall y a gree d c h arter , w hi c h will 
defi ne t he C V E A C’s me m bers hi p, c o n d uct a n d m eeti n g s c he d ule.  
T he f oll o wi n g e ve nts will be a dj u dicate d a n d classifie d b y t he C V E A C:  
•  Car di o vasc ular d eat h  
•  M y ocar dial i nfarcti o n  
•  Str o ke  

Fil g oti ni b  
 
Pr ot oc ol  G L P G 0 6 3 4 -C L -2 2 7  
Fi nal  
Gala pa g os  
A me n d me nt 2  
C O N FI D E N TI A L  
P a ge  8 5  
0 9 Se p 2 0 2 2  
•  Arterial t hr o m b oe m b olis m  
•  Ve n o us t hr o m b oe m b olis m (e g, d ee p v e n o us t hr o m b osis, p ul m o nar y e m b olis m)  
F urt her details will be s pecifie d i n t he C V E A C C harter.  
8. 1 0.  
I nt er n al I n d e p e n d e nt S af et y R e vi e w 
A S p o ns or i nter nal u n bli n de d tea m, i n de pe n d e nt of t he bli n de d st u d y tea m, will be asse m ble d. 
T he S p o ns or i nter nal u n bli n de d tea m ma y  be gra nte d t he access t o u n bli n de d cli nical data 
i ncl u di n g treat me nt assi g n me nt t o cl osel y m o nit or se me n para meters i n real-ti me. T his i nter nal 
tea m will be s u p p orte d b y a n e xter nal e x pert i n male fertilit y. T o miti gate t he ris k of 
i na d verte ntl y rele asi n g tr eat me nt assi g n me nt t o sites a n d s u bjects, t he i nter nal tea m will kee p t he 
u n bli n de d i nf or mati o n c o nfi de ntial a n d will n ot c o m m u nicate a n y i nf or mati o n t o t he bli n de d 
st u d y tea m, site staff or s u bjects. Data u n bli n di n g d ue t o me dical e mer ge nc y will f oll o w  sta n dar d 
S p o ns or  pr oce d ures.  Pri or t o a n y u n bli n di n g of t he c o m mittee, t he I nter nal I n de pe n de nt Safet y 
Re vie w c o m mittee’s s pecific acti vities will be defi ne d b y a m ut uall y a gree d u p o n c harter, w hic h 
will defi ne t he c o m mittee me m bers hi p, c o n d u ct, a n d meeti n g sc he d ule.  
As of a me n d me nt 2, t he I nter nal I n de p e n de nt Safet y Re vie w T ea m  will be dec o m missi o ne d. 
Safet y re vie ws will be c o vere d b y t he S S M T.  
8. 1 1.  
U n bli n d e d I nt eri m A n al y si s 
U n bli n de d i nteri m a nal ys es of t he cli nical st u d y data will be perf or m e d b y t he S p o ns o r f or 
re g ulat or y s u b missi o ns w he n 2 0 0  s u bjects (e g, p o ole d data fr o m G S-U S -4 1 8 -4 2 7 9 a n d 
G L P G 0 6 3 4 -C L -2 2 7), a n d/ or w he n s o me defi ne d s u bset(s) of s u bjects, ha v e c o m plete d t he 
Wee k  1 3 a n d Wee k 2 6 assess me nts  (first u n bli n de d i nteri m a nal ysis [I A 1]), a n d w he n c o m plet e 
re versi bilit y d ata f or all s u bjects w h o e ntere d t he Mo nit ori n g P hase  at t hes e ti me  p oi nts is 
a vaila ble (I A 2; see D efi niti o n  of  Ter ms ). A Data I nte grit y a n d C o m m u nicati o n Pla n f or t he 
i nteri m a nal ysis will be d e vel o pe d pri or t o u n bli n di n g. T he a nal yses will be c o n d ucte d pri maril y 
t o e val uate t he testic ular safet y a n d f urt her details will be descri be d i n t he S A P.  
F or o n g oi n g s u bjects, t h e st u d y tea ms a n d st u d y st aff at t he sites a n d all ot her staff directl y 
i n v ol ve d i n t he c o n d uct of t he st u d y will re m ai n bli n de d t o t he d o u ble -bli n d p hase treat me nt 
assi g n me nts  u ntil t he fi n al a nal ysis w he n t he data base has bee n l oc ke d . P u blicati o n of t he I A 2 
data is pla n ne d b y t he S p o ns or. T his p u blicati o n will c o ntai n gr o u p le vel data f or t he e ntire st u d y 
p o p ulati o n, b ut will u n bli n d t he st u d y tea ms a n d staff directl y i n v ol ve d i n t h e c o n d uct of t he 
st u d y t o t he i n di vi d ual baseli ne treat me nt assi g n m e nt of s u bjects w h o c o m plete d t he st u d y b ef ore 
I A 2.  
8. 1 2.  
I nt e gr at e d S e m e n A n al y si s  
As part of t he male s afet y ass ess me nt of fil g oti ni b, i nte grate d a n al ys es ma y be p erf or me d i n 
w hic h data fr o m t he pres e nt st u d y, will be c o m bi n e d wit h si milar data fr o m a se parate st u d y 
G S -U S -4 1 8 -4 2 7 9 bei n g c o n d ucte d i n males wit h i nfla m mat or y b o wel disease. T he a n al ys es will 

Fil g oti ni b  
 
Pr ot oc ol  G L P G 0 6 3 4 -C L -2 2 7  
Fi nal  
Gala pa g os  
A me n d me nt 2  
C O N FI D E N TI A L  
P a ge  8 6  
0 9 Se p 2 0 2 2  
be c o n d ucte d pri maril y t o e val uate t he testic ul ar safet y. F urt her details of t he i nte grate d a nal ysis 
will be descri be d i n t he I nte grate d Se me n a n d H or m o ne S A P. 
9.  
R E S P O N SI BI LI TI E S  
9. 1.  
I n v e sti g at or R e s p o n si biliti e s 
9. 1. 1.  
G o o d Cli ni c al Pr a cti c e  
T he i n vesti gat or will e ns ure t hat t his st u d y is c o n d ucte d i n acc or da n ce wit h t he pri nci ples of t he 
Declarati o n of Helsi n ki, I nter nati o nal C o u ncil f or  Har m o ni zati o n (I C H) g ui deli nes, or wit h t he 
la ws a n d re g ul ati o ns of t he c o u ntr y i n w hic h t he researc h is c o n d ucte d, w hic he ver aff or ds t he 
greater pr otecti o n t o t he st u d y s u bject. T h ese sta n d ar ds are c o nsiste nt wit h t he E U  Cli nical Trials 
Directi ve 2 0 0 1/ 2 0/ E C a n d G C P  Directi ve 2 0 0 5/ 2 8/ E C.  
T he i n vesti gat or will e ns ure a d here n ce t o t he basi c pri nci ples of G C P , as o utline d i n 
2 1  C F R  3 1 2, s u b part  D, “ Res p o nsi bilities of S p o ns ors a n d I n vesti gat ors, ” 2 1  C F R, part  5 0, a n d 
2 1  C F R, part  5 6 . 
T he i n vesti gat or a n d all a p plica ble s u bi n vesti gat ors will c o m pl y wit h 2 1  C F R, Part  5 4, pr o vi di n g 
d oc u me ntati o n of t heir fi na ncial i nterest  or arra n ge me nts wit h t he s p o ns or, or pr o prietar y 
i nterests i n t he i n vesti gati o nal dr u g u n d er st u d y. T his d oc u me ntati o n m ust be pr o vi de d pri or t o 
t he i n vesti gat or’s (a n d a n y s u bi n vesti gat or’s) parti ci pati o n i n t he st u d y. T he i n vesti gat or a n d 
s u bi n vesti gat or a gree t o n otif y t he s p o ns or of a n y c ha n ge i n r e p orta ble i nterests d uri n g t h e st u d y 
a n d f or 1 year f oll o wi n g c o m pleti o n of t he st u d y. St u d y c o m pleti o n is defi ne d as t he date w he n 
t he last s u bject c o m pletes t he pr ot oc ol-defi n e d acti vities.  
9. 1. 2.  
I R B/IE C  R e vi e w a n d A p pr o v al  
T he i n vesti gat or ( or s p o ns or as a p pr o priate acc or di n g t o l ocal r e g ulati o ns) will s u b mit t his 
pr ot oc ol, I C F, a n d a n y acc o m pa n yi n g m aterial t o be pr o vi de d t o t he s u bject (s uc h as 
a d vertise me nts, s u bject i nf or mati o n s heets, or des cri pti o ns of t he st u d y use d t o o btai n i nf or me d 
c o nse nt) t o a n  I R B/I E C. T he i n vesti gat or will n ot be gi n a n y st u d y s u bject acti vities u ntil 
a p pr o val fr o m t he  I R B/I E C has bee n d oc u me nt e d a n d pr o vi de d as a letter t o t he i n vesti gat or.  
Bef ore i m ple me ntati o n, t he i n vesti gat or wil l s u b mit t o a n d recei ve d oc u me nte d a p pr o val fr o m 
t he I R B/I E C a n y m o dificati o ns ma de t o t he pr ot oc ol or a n y acc o m pa n yi n g material t o be 
pr o vi de d t o t he s u bject after i nitial  I R B/I E C a p pr o val, wit h t he e x ce pti o n of t h ose necessar y t o 
re d uce i m me diat e ris k t o st u d y s u bjects. 
I nitial s u b missi o n a n d s u bsta ntial a me n d me nt(s) s h o ul d be a p pr o ve d b y t he nati o nal c o m pete nt 
a ut h orities bef ore starti n g of e nr oll me nt a n d/ or i m ple me ntati o n of c ha n ges . 
9. 1. 3.  
I nf or m e d C o n s e nt 
T he i n vesti gat or is res p o nsi ble f or o btai ni n g writte n i nf or me d c o ns e nt fr o m eac h i n di vi d ual 
partici pati n g i n t his st u d y after a de q uat e e x pla nati o n of t he ai ms, met h o ds, o bjecti ves, a n d 
p ote ntial hazar ds of t he st u d y a n d b ef ore u n dert a ki n g a n y st u d y-relate d pr oce d ures. T h e 

Fil g oti ni b  
 
Pr ot oc ol  G L P G 0 6 3 4 -C L -2 2 7  
Fi nal  
Gala pa g os  
A me n d me nt 2  
C O N FI D E N TI A L  
P a ge  8 7  
0 9 Se p 2 0 2 2  
i n vesti gat or m ust use t he m ost c urre nt I R B/I E C a p pr o ve d c o nse nt f or m f or d oc u me nti n g writte n 
i nf or me d c o nse nt. E ac h i nf or me d c o ns e nt ( or ass e nt as a p plica ble) will be a p pr o priatel y si g ne d 
a n d date d b y t he s u bject a n d  t he pers o n c o n d ucti n g t he c o nse nt disc ussi o n, a n d als o b y a n 
i m partial wit ness if re q uire d b y I R B/ I E C or l ocal re q uire me nts. T h e c o nse nt f or m will i nf or m 
s u bjects a b o ut ge n o mic t esti n g a n d s a m ple rete nti o n, a n d t heir ri g ht t o recei ve cli nicall y rele va nt 
ge n o mic a nal ysis res ults.  
9. 1. 4.  
C o nfi d e nti alit y  
T he i n vesti gat or m ust ass ure t hat s u bjects’ a n o n y mit y will be strictl y mai ntai ne d a n d t hat t heir 
i de ntities are pr otecte d fr o m u na ut h orize d parties. O nl y s u bject i nitials, date of birt h, a n ot her 
u ni q ue i de ntifier (as all o we d b y l ocal la w) a n d a n i de ntificati o n c o de will be rec or de d o n a n y 
f or m or bi ol o gic al sa m pl e s u b mitte d t o t he S p o ns or, I R B/I E C, or la b orat or y. La b orat or y 
s peci me ns m ust be la bele d i n s uc h a wa y as t o pr otect s u bject i de ntit y w hile all o wi n g t he re s ults 
t o be rec or de d t o t he pr o per s u bject. Refer t o s pecific la b orat or y i nstr ucti o ns. N O T E: T he 
i n vesti gat or m ust kee p a Scree ni n g  l o g s h o wi n g c o des, na mes, a n d a d dress es f or all s u bjects 
scree n e d a n d f or all s u bjects e nr olle d i n t he st u d y. S u bject data will be pr ocesse d i n acc or da n ce 
wit h all a p plica ble re g ul ati o ns.  
T he i n vesti gat or a grees t hat all i nf or mati o n recei v e d fr o m t he s p o ns or, i ncl u di n g b ut n ot li mite d 
t o t he i n vesti gat or br o c h ure, t his pr ot oc ol, C R F/e C R F, t he I M P, a n d a n y ot her st u d y i nf or matio n, 
re mai n t he s ole a n d e x cl usi ve pr o pert y of t he s p o ns or d uri n g t h e c o n d uct of t he st u d y a n d 
t hereafter. T his i nf or mati o n is n ot t o be discl ose d t o a n y t hir d part y (e x ce pt e m pl o yees or a ge nts 
directl y i n v ol ve d i n t he c o n d uct of t he st u d y or as re q uire d b y  la w) wit h o ut pri or writte n c o nse nt 
fr o m t he s p o ns or. T he i n vesti gat or f urt her a grees t o ta ke all reas o n a ble preca uti o ns t o pre ve nt t he 
discl os ure b y a n y e m pl o yee or a ge nt of t he st u d y site t o a n y t hir d part y or ot her wise i nt o t he 
p u blic d o mai n.  
9. 1. 5.  
St u d y Fil e s a n d R et e nti o n of R e c or d s  
T he i n vesti gat or m ust mai ntai n a de q uate a n d acc urate rec or ds t o e na bl e t he c o n d uct of t he st u d y 
t o be f ull y d oc u m e nte d a n d t he st u d y data t o b e s u bse q ue ntl y v erifie d. T h es e d oc u me nts s h o ul d 
be classifie d i nt o at least t he f oll o wi n g t w o cate g ories: ( 1)  i n vesti gat or’s st u d y file, a n d 
( 2) s u bject cli nical s o ur ce d oc u me nts. 
T he i n vesti gat or’s st u d y file will c o ntai n t he pr ot oc ol/a me n d me nts, C R F a n d q uer y f or ms, I R B/ 
I E C a n d g o ver n me nt al a p pr o val wit h c orres p o n de nce, i nf or me d c o nse nt, dr u g rec or ds, staff 
c urric ul u m vitae a n d a ut h orizati o n f or ms, a n d ot her a p pr o priate d oc u m e nts a n d c orres p o n de n ce.  
T he re q uir e d s o urce data s h o ul d i ncl u de se q ue ntial n otes c o ntai ni n g at least t he f oll o wi n g 
i nf or mati o n f or eac h s u bj ect: 
•  
S u bject i de ntificati o n ( na me, date of birt h, ge n d er)  
•  
D oc u me ntati o n t hat s u bject meets eli gi bilit y criteria, ie, hist or y, P E , a n d c o nfir mati o n of 
dia g n osis (t o s u p p ort i n cl usi o n a n d e x cl usi o n criteria)  
•  
D oc u me ntati o n of t he reas o n(s) a c o ns e nte d s u bject is n ot e nr olle d  

Fil g oti ni b  
 
Pr ot oc ol  G L P G 0 6 3 4 -C L -2 2 7  
Fi nal  
Gala pa g os  
A me n d me nt 2  
C O N FI D E N TI A L  
P a ge  8 8  
0 9 Se p 2 0 2 2  
•  
Partici pati o n i n  st u d y (i n cl u di n g st u d y n u m ber) 
•  
St u d y dis c uss e d a n d d ate of i nf or me d c o ns e nt  
•  
Dates of all visits  
•  
D oc u me ntati o n t hat pr ot oc ol s pe cific pr oce d ures were p erf or me d  
•  
Res ults of efficac y para mete rs, as re q uire d b y t h e pr ot oc ol 
•  
Start a n d e n d date ( i ncl u di n g d ose re gi me n) of I M P, i ncl u di n g dates of dis pe nsi n g a n d ret ur n  
•  
Rec or d of all A Es  a n d ot her safet y p ara meters (st art a n d e n d d ate, a n d i n cl u di n g ca usalit y 
a n d se verit y)  
•  
C o nc o mita nt me dicati o n (i ncl u di n g start a n d e n d d ate, d ose if rele va nt; d os e cha n ges)  
•  
Date of st u d y c o m pleti o n a n d reas o n f or earl y disc o nti n uati o n, if it occ urs  
All cli nical st u d y d oc u m e nts m ust be retai ne d b y t he i n vesti gat or u ntil at least 2  years or 
acc or di n g t o l ocal la ws, w hic he ver is l o n ger, aft er t he last a p pr o val of a mar ke ti n g a p plicati o n i n 
a n I C H re gi o n ( i e, U nite d States, E ur o pe, or Ja pa n) a n d u ntil t here are n o pe n di n g or pla n ne d 
mar keti n g a p plicati o ns i n a n I C H re gi o n; or, if n o a p plicati o n is file d or if t he a p plicati o n is n ot 
a p pr o ve d f or s uc h i n dicati o n, u ntil 2  yea rs after t h e i n vesti gati o n is disc o nti n ue d a n d re g ul at or y 
a ut h orities ha ve bee n n otifie d. I n vesti gat ors ma y b e re q uir e d t o retai n d oc u me nts l o n ger if 
s pecifie d b y re g ulat or y re q uire me nts, b y l ocal r e g ulati o ns, or b y a n a gree m e nt wit h t he s p o ns or. 
T he i n ves ti gat or m ust n otif y t he s p o ns or b ef ore destr o yi n g a n y cli nical st u d y rec or ds.  
S h o ul d t he i n vesti gat or wis h t o assi g n t he st u d y rec or ds t o a n ot her part y or m o ve t he m t o a n ot her 
l ocati o n, t he s p o ns or m ust be n otifie d i n a d va nce.  
If t he i n vesti gat or ca n n ot pro vi de f or t his arc hi vi n g re q uire me nt at t he st u d y site f or a n y or all of 
t he d oc u me nts, s pecial arra n ge me nts m ust be ma d e bet wee n t he i n vesti gat or a n d t he s p o ns or t o 
st ore t hese rec or ds s ec urel y a wa y fr o m t he site s o t hat t he y ca n be ret ur n e d seale d t o t he  
i n vesti gat or i n case of a n i ns pecti o n. W he n s o urce d oc u me nts are re q uir e d f or t he c o nti n ue d care 
of t he s u bject, a p pr o priat e c o pies s h o ul d be ma d e f or st ora ge a wa y fr o m t h e site.  
9. 1. 6.  
C a s e R e p ort F or m s  
F or eac h s u bject c o nse nt e d, a n e C R F will be c o m plete d b y a n a ut h orize d st u d y staff me m ber 
w h ose trai ni n g f or t his f u ncti o n is d oc u me nte d acc or di n g t o st u d y pr oce d ures. e C R F s h o ul d be 
c o m plete d o n t he da y of t he s u bject visit t o e na ble t he s p o ns or t o perf or m ce ntral m o nit ori n g of 
safet y data. T he Eli gi bilit y Criteria e C R F s h o ul d b e c o m plete d o nl y aft er all data relat e d t o 
eli gi bilit y ha v e bee n recei ve d. S u bse q ue nt t o data e ntr y, a st u d y m o nit or will perf or m s o urce data 
verificati o n wit hi n t he el ectr o nic dat a ca pt ur e  s yst e m. Ori gi n al e ntries as well as a n y c ha n ges t o 
data fiel ds will be st ore d i n t he a u dit trail of t he s yste m . Pri or t o dat a base l o c k ( or a n y i nteri m 
ti me p oi nts as descri be d i n t he cli nical data ma na ge me nt pla n), t he i n vesti gat or will use his/ her 
l o g i n cre de ntials t o c o nfir m t hat t he f or ms ha ve b ee n re vi e we d, a n d t hat t he e ntries acc uratel y 

Fil g oti ni b  
 
Pr ot oc ol  G L P G 0 6 3 4 -C L -2 2 7  
Fi nal  
Gala pa g os  
A me n d me nt 2  
C O N FI D E N TI A L  
P a ge  8 9  
0 9 Se p 2 0 2 2  
reflect t he i nf or mati o n i n t he s o urce d o c u me nts. T he e C R F ca pt ures t he d ata re q uir e d per t he 
pr ot oc ol St u d y Pr oce d ures Ta ble  (A p pe n di x  2 ). S yste m -ge nerate d or ma n ual q ueries will be 
iss ue d t o t he i n vesti gati v e site staff as d ata discre pa ncies are i de ntifie d b y t he m o nit or or i nter nal 
s p o ns or staff, w h o r o uti n el y re vie w t he data f or c o m plete ness, c orrect ness, a n d c o nsiste nc y . T he 
site c o or di nat or is res p o nsi ble f or res p o n di n g t o t he q ueries i n a ti mel y ma n ner, wit hi n t he 
s yste m, eit her b y c o nfir mi n g t he dat a as c orrect or u p dati n g t he ori gi nal e ntr y, a n d pr o vi di n g t he 
reas o n f or t he u p date (e g, data e ntr y err or) . At t he c o ncl usi o n of t he st u d y, t he s p o ns or will 
pr o vi de t he site wit h a rea d -o nl y arc hi ve c o p y of t he data e nt ere d b y t hat site . T his arc hi ve m ust 
be st ore d i n acc or da n ce wit h t he rec or ds rete nti o n re q uire me nts o utli ne d  i n Secti o n 9. 1. 5 .  
9. 1. 7.  
I n s p e cti o n s 
T he i n vesti gat or will ma ke a vaila ble all s o urce d o c u me nts a n d ot her rec or ds f or t his st u d y t o 
S p o ns or’s  a p p oi nte d st u d y m o nit ors, t o I R Bs/I E Cs, or t o re g ulat or y a ut h orit y or healt h a ut h orit y 
i ns pect ors. 
9. 1. 8.  
Pr ot o c ol C o m pli a n c e  
T he i n vesti gat or is res p o nsi ble f or e ns uri n g t he st u d y is c o n d u cte d i n acc or da nce wit h t he 
pr oce d ures a n d e v al uati o ns descri be d i n t his pr ot oc ol.  
9. 2.  
S p o n s or R e s p o n si biliti e s  
9. 2. 1.  
Pr ot o c ol M o difi c ati o n s  
Pr ot oc ol m o dificati o ns, e x ce pt t h ose i nte n de d t o re d uce i m me diate ris k t o st u d y s u bjects, ma y b e 
ma de o nl y b y t h e s p o ns or. T he i n vesti gat or m ust s u b mit all pr ot oc ol m o dificati o ns t o t he 
I R B/I E C i n acc or da n ce wit h l ocal re q uire m e nts a n d recei v e d oc u me nte d  I R B/I E C a p pr o val 
bef ore m o dificati o ns ca n be i m ple me nte d.  
9. 2. 2.  
St u d y R e p ort a n d P u bli c ati o n s  
A cli nical st u d y re p ort ( C S R) will be pre pare d a n d pr o vi de d t o t he re g ulat or y a ge nc y( i es). T he 
s p o ns or will e ns ure t hat t he re p ort meets t he sta n d ar ds set o ut i n t he I C H G ui deli ne f or Str uct ure 
a n d C o nte nt of Cli nical St u d y Re p orts (I C H  E 3). N ote t hat a n a b bre viate d re p ort ma y be 
pre pare d i n certai n cas es.  
I n v esti gat ors i n t his st u d y ma y c o m m u nicate, orall y pres e nt, or p u blis h i n scie ntific j o ur nals or 
ot her sc h olarl y me dia o nl y after t he f oll o wi n g c o n diti o ns ha ve bee n met:  
•  
T he res ults of t he st u d y i n t heir e ntiret y ha v e bee n p u blicl y discl ose d b y or wit h t he c o nse nt 
of t he s p o ns or i n a n a bstr act, ma n uscri pt, or prese ntati o n f or m or t he st u d y has bee n 
c o m plete d at  all st u d y sit es f or at least 2  years  
•  
T he i n vesti gat or will s u b mit t o t he s p o ns or a n y pr o p ose d p u blicati o n or prese ntati o n al o n g 
wit h t he res pecti ve s cie ntific j o ur nal or prese ntati o n f or u m at least 3 0  da ys  bef ore 
s u b missi o n of t he p u blicati o n or prese ntati o n.  

Fil g oti ni b  
 
Pr ot oc ol  G L P G 0 6 3 4 -C L -2 2 7  
Fi nal  
Gala pa g os  
A me n d me nt 2  
C O N FI D E N TI A L  
P a ge  9 0  
0 9 Se p 2 0 2 2  
•  
N o s uc h c o m m u nicati o n, prese ntati o n, or p u blicati o n will i ncl u de t he s p o ns or’s c o nfi de ntial 
i nf or mati o n (see Secti o n 9. 1. 4 ). 
•  
T he i n vesti gat or  will c o m pl y wit h t he s p o ns or’s re q uest t o delete refere nces t o its 
c o nfi de ntial i nf or mati o n ( ot her t ha n t he st u d y res ults) i n a n y pa p er or prese ntati o n a n d 
a grees t o wit h h o l d p u blic ati o n or prese ntati o n f or a n a d diti o nal 6 0 da ys i n or der t o o btai n 
pate nt pr otecti o n if dee me d necessar y.  
9. 3.  
J oi nt I n v e sti g at or/ S p o n s or R e s p o n si biliti e s  
9. 3. 1.  
P a y m e nt R e p orti n g  
I n v esti gat ors a n d t heir st u d y staff ma y be as ke d t o pr o vi de ser vices perf or me d u n der t his 
pr ot oc ol, e g, atte n da n ce at in vesti gat or's M eeti n gs . If re q uir e d u n der t he a p plica ble stat ut or y a n d 
re g ulat or y re q uire me nts, t he s p o ns or will ca pt ure a n d discl ose t o Fe d eral a n d State a ge ncies a n y 
e x pe nses pai d or rei m b urse d f or s uc h s er vices, i n cl u di n g a n y cli nical st u d y pa y m e nts, meal, 
tra vel e x pe nses or rei m b urse me nts, c o ns ulti n g fees, a n d a n y ot her tr a nsfer of val ue. 
9. 3. 2.  
A c c e s s t o I nf or m ati o n f or M o nit ori n g  
I n acc or da n ce wit h re g ul ati o ns a n d g ui deli nes, t h e st u d y m o nit or m ust ha ve direct access to t he 
i n vesti gat or’s s o urce d o c u me ntati o n i n or der t o verif y t h e acc urac y of t he d ata rec or de d i n t he 
C R F/e C R F.  
T he m o nit or is res p o nsi ble f or r o uti ne re vie w of t he C R F/e C R F at re g ular i nter vals t hr o u g h o ut 
t he st u d y t o verif y a d here nce t o t he pr ot oc ol a n d t h e c o m plete ness, c o nsiste nc y, a n d acc urac y of 
t he data bei n g e nt ere d o n t he m. T he m o nit or s h o ul d ha ve access t o a n y s u bj ect rec or ds nee de d t o 
verif y t he e ntri es o n t he C R F/e C R F. T he i n vesti gat or a grees t o c o o perate wit h t he m o nit or t o 
e ns ure t hat a n y pr o b le ms detecte d t hr o u g h a n y t y p e of m o nit ori n g (ce ntr al, o n site) are res ol ve d. 
9. 3. 3.  
A c c e s s t o I nf or m ati o n f or A u diti n g or I n s p e cti o n s  
Re prese ntati ves of re g ulat or y a ut h orities or of t he s p o ns or ma y c o n d uct i ns pecti o ns or a u dits of 
t he cli nical st u d y. If t he i n vesti gat or is n otifie d of a n i ns pecti o n b y a re g ulat or y a ut h orit y t he 
i n vesti gat or a grees t o n otif y t he S p o ns or  M e di cal Lea der or desi g nee  i m me diatel y. T h e 
i n vesti gat or a grees t o pr o vi de t o re pres e ntati ves of a re g ulat or y a ge n c y or t he s p o ns or access t o 
rec or ds, facilities, a n d pers o n nel f or t he effecti ve c o n d uct of a n y i ns pe cti o n or a u dit. 
9. 3. 4.  
St u d y Di s c o nti n u ati o n  
B ot h t he s p o ns or a n d t he i n vesti gat or reser ve t he ri g ht t o ter mi nate t he st u d y at a n y ti me. S h o ul d 
t his be necessar y, b ot h parties will arra n ge disc o nti n uati o n pr oce d ures a n d n otif y t he a p pr o priate 
re g ulat or y a ut h orit y(i es), I R Bs, a n d I E Cs. I n t er mi nati n g t he st u d y, t he s p o ns or a n d t he 
i n vesti gat or will ass ure t hat a de q uat e c o nsi derati o n is gi ve n t o t he pr otecti o n of t he s u bjects’ 
i nterests. 

Fil g oti ni b  
 
Pr ot oc ol  G L P G 0 6 3 4 -C L -2 2 7  
Fi nal  
Gala pa g os  
A me n d me nt 2  
C O N FI D E N TI A L  
P a ge  9 1  
0 9 Se p 2 0 2 2  
1 0.  
R E F E R E N C E S  
( Oct o ber 2 0 1 8). F D A’s G ui d a nce f or I n d ustry: T estic ul ar t oxicity: Ev al u ati o n D uri n g Dr u g 
Devel o p m e nt ”.   
Ge n o vese, M., K al u nia n, K., Wal ker, D., G otte n b er g, J. -E., de Vla m, K., & M ozaffaria n, N. 
( 2 0 1 8, Oct o ber 0 4). Safet y a n d effi cac y of fil g oti ni b i n a P hase 3 trial of patie nts wit h 
acti ve t he u mat oi d art hritis a n d i na de q uate res p o ns e or i nt olera n ce t o bi ol o gic D M A R Ds. 
A bstr act L 0 6 . 
Hellstr o m, W., Gittel ma n, M., J ar o w, J., Stei dle, C., Mc M urra y, J., & Talle y, D. ( 2 0 0 8). A n 
e val uati o n of se me n c haracteristics i n me n 4 5 years of a ge or ol d er after dail y d osi n g 
wit h ta dalafil 2 0 m g: r es ults of a m ultice nter, ra n d o mize d, d o u ble -bli n d, place b o -
c o ntr olle d, 9 -m o nt h st u d y. . 5 3 ( 5) ( 1 0 5 8-6 5.).  
Hellstr o m, W., O verstreet, J., Y u,  A., Sai kali, K., S he n, W., & Beasle y C M Jr. ( 2 0 0 3). Ta dalafil 
has n o detri me ntal effect o n h u ma n s per mat o ge n esis or re pr o d ucti ve h or m o nes. 1 7 0 
( 3)( 8 8 7-9 1).  
J ar vi, K., D ula, E., Dre h o bl, M., Pr y or, J., S ha pir o, J., & Se ger, M. ( 2 0 0 8). Dail y v ar de n afil f or 6 
m o nt hs has n o detri me ntal effects o n se me n c haracteristics or re pr o d ucti ve h or m o nes i n 
me n wit h n or mal baseli n e le vels. 1 7 9 ( 3) ( 1 0 6 0-5).  
Ka va na u g h, A., Kre mer, J., P o nce , L., Cse uz, R., Res het o k o, O., Sta nisla vc h u k, M., . . . 
Harris o n, P. ( 2 0 1 7). Fil g oti ni b ( G L P G 0 6 3 4/ G S -6 0 3 4), a n oral s electi ve J A K 1 i n hi bit or, 
is effecti ve as m o n ot hera p y i n patie nts wit h acti ve r he u mat oi d art hritis: res ults fr o m a 
ra n d o mise d, d ose-fi n di n g st u d y ( D A R WI N 2). A n n R he u m Dis , 7 6( 6): 9 9 8-1 0 0 8.  
Keel, B. ( 2 0 0 6). Wit hi n - a n d bet wee n -s u bject v ari ati o n i n se me n para m eters i n i nfertile me n a n d 
n or mal se me n d o n ors. . 8 5 ( 1) ( 1 2 8-3 4).  
Mease, P., C oates, L., H elli well, P., St nisla vc h u k, M., R yc hle ws k a -Ha ncze ws ka, A., D u de k, A., . 
. . Gla d ma n n, D. ( 2 0 1 8). Efficac y a n d safet y of fil g oti ni b, a selecti ve J a n us ki nase 1 
i n hi bit or, i n patie nts wit h acti ve ps oriatic art hritis ( E Q U A T O R): res ults fr o m a 
ra n d o mise d, place b o-c o ntr olle d, p hase 2 trial. T he L a ncet , 3 9 2( 1 0 1 6 2): 2 3 6 7-2 3 7 7.  
Na m o ur, F., Di derc hs e n, P., C o x, E., Va yssiere, B., Va n der Aa, A., & Tass et, C. ( 2 0 1 5). 
P har mac o ki netics a n d P h ar mac o ki netic/ P har mac o d y na mic M o d eli n g of Fil g oti ni b 
( G L P G 0 6 3 4), a Sele cti ve J A K 1 I n hi bit or, i n S u p p ort of P hase II B D os e Selecti o n. . 5 4 
( 8)( 8 5 9-7 4).  
Ol derei d, N., G or dela dze, J., Kir k h us, B., & P ur vis, K. ( 1 9 8 4). H u ma n s per m c haracteristics 
d uri n g fre q ue nt ejac ulati o n. 7 1 ( 1) ( 1 3 5-4 0).  
Re dlic h, K., Sc hett, G., Stei ner, G., Ha yer, S., Wa g ner , E.,  & S m ole n, J. ( 2 0 0 3). R he u mat oi d 
art htritis t hera p y aft er t u m or necr osis fact or a n d i nterle u ki n -1 bl oc ka d e. Art hritis R he u m , 
4 8 ( 1 2): 3 3 0 8 -1 9.  

Fil g oti ni b  
 
Pr ot oc ol  G L P G 0 6 3 4 -C L -2 2 7  
Fi nal  
Gala pa g os  
A me n d me nt 2  
C O N FI D E N TI A L  
P a ge  9 2  
0 9 Se p 2 0 2 2  
R u d waleit, M., va n der Heij de, D., La n de wé, R., Listi n g, J., A k k oc, N., Bra n dt, J., . . . Sie per, J. 
( 2 0 0 9). T he d e vel o p me nt of Assess me nt of S p o n d yl o Art hritis i nter nati o nal S ociet y 
classificati o n criteria f or a xial s p o n d yl oart hritis ( part II): v ali dati o n a n d fi n al selecti o n. 
A n n R he u m Dis , 7 7 7-8 3.  
Sa hi d -Na hal, R., Miceli -Ric har d, C., & Bert h el ot, J. ( 2 0 0 0). T he f a mi li al f or m of 
s p o n dyl art hr o p at hy: a cli nic al st u dy of 1 1 5 m ulti plex f a milies. Gr o u pe Fr a n cç ais d' Et u de 
Gé néti q ue des S p o n d yl o art hr o p at hies.  Art hritis R he u m.  
Sc h oels, M., Aleta ha, D., F u n o vits, J., Ka va na u g h, A., Ba k er, D., & S m ole n, J. ( 2 0 1 0). 
A p plicati o n o f t he D A R E A/ D A P S A sc ore f or ass ess me nt of disease acti vit y i n ps oriatic 
art hritis. A n n R he u m Dis , 6 9( 8): 1 4 4 1-7.  
Sie per, J., R u d waleit, M., Baralia k os, X., Bra n dt, J., Bra u n , J., B ur g os -Var gas, R., . . . va n d er 
Heij de, D. ( 2 0 0 9). T he Assess me nt of S p o n d yl o Art hritis i nter nati o nal S ociet y ( A S A S) 
ha n d b o o k: a g ui de t o ass ess s p o n d yl oart hritis. A n n R he u m Dis. , 6 8 S u p pl 2:ii 1-4 4.  
Si k ka, S., & Hellstr o m, W. ( 2 0 1 6). C urre nt u p dat es o n la b orat or y tec h ni q u es f or t he dia g n osis of 
male re pr o d ucti ve fail ure.  
Si k ka, S ., C he n, C., Al mas, M., D ula, E., K na p p, L., & Hellstr o m, W. ( 2 0 1 4). Pre ga v bali n d oes 
n ot affect s per m pr o d ucti o n i n healt h y v ol u nteers: a ra n d o mize d, d o u ble -bli n d, place b o -
c o ntr olle d, n o ni nferi orit y st u d y.  
va n der Heij de, D., Baralia k os, X., Ge nsler, L., M a ks y m o w yc h, W., Tsel u y k o, V., 
Na das h ke vic h, O., . . . La n de wé, R. ( 2 0 1 8). Efficac y a n d safet y of fil g oti ni b, a selecti ve 
J a n us ki nase 1 i n hi bit or, i n patie nts wit h acti ve a n k yl osi n g s p o n d ylitis ( T O R T U G A): 
res ults fr o m a ra n d o mise d, place b o-c o ntr olle d, p h a se 2 trial. L a ncet , 3 9 2( 1 0 1 6 2): 2 3 7 8-
2 3 8 7.  
West h o ve ns, R., Ta yl or, P., Alte n, R., Pa vl o va, D., E nri q uez -S osa, F., Maz ur, M., . . . Harris o n, 
P. ( 2 0 1 6). Fil g oti ni b ( G L P G 0 6 3 4/ G S -6 0 3 4), a n oral J A K 1 selecti ve i n hi bit or, is effecti ve 
i n c o m bi nati o n wit h met h otre x ate ( M T X) i n patie nts wit h acti ve r he u mat oi d art hritis a n d 
i ns ufficie nt res p o nse t o M T X: res ults fr o m a ra n d o mise d, d ose-fi n di n g st u d y ( D A R WI N 
1). A n n R he u m Dis , 7 6: 9 9 8– 1 0 0 8.  
W orl d Healt h Or ga niz ati o n ( W H O). ( 1 9 9 9). La b orat or y Ma n ual f or t he e x a mi nati o n of h u ma n 
se me n a n d s per m-cer vical m uc us i nteracti o n. F o urt h E diti o n.  
W orl d Healt h Or ga niz ati o n ( W H O). ( 2 0 1 0). La b orat or y ma n ual f or t he E x a mi nati o n a n d 
pr ocessi n g of h u ma n s e me n. Fift h E diti o n.  
 

Fil g oti ni b  
 
Pr ot oc ol  G L P G 0 6 3 4 -C L -2 2 7  
Fi nal  
Gala pa g os  
A me n d me nt 2  
C O N FI D E N TI A L  
P a ge  9 3  
0 9 Se p 2 0 2 2  
1 1.  
A P P E N DI C E S  
A p p e n di x  1.   S p o n s or a n d I n v e sti g at or Si g n at ur e P a g e  
A p p e n di x  2.  St u d y Pr o c e d ur e s T a bl e –  D o u bl e -bli n d Tr e at m e nt P h a s e ( S e cti o n 6. 4)  
A p p e n di x  3.  6 6/ 6 8 -j oi nt Co u nt ( S J C 6 6/ T J C 6 8)  
A p p e n di x  4.  P h y si ci a n’ s Gl o b al A s s e s s m e nt of Di s e a s e A cti vit y ( P h G A D A)  
A p p e n di x  5.  P ati e nt’ s Gl o b al A s s e s s m e nt of Di s e a s e A cti vit y ( Pt G A D A)  
A p p e n di x  6.  P ati e nt’ s Gl o b al A s s e s s m e nt of P ai n I nt e n sit y  
A p p e n di x  7.  B at h A n k yl o si n g S p o n d yliti s Di s e a s e A cti vit y I n d e x ( B A S D AI)  
A p p e n di x  8.  Di s e a s e S p e cifi c Cl a s sifi c ati o n Crit eri a  
A p p e n di x  9.  C T C A E Gr a di n g S c al e f or S e v erit y of A d v er s e E v e nt s  
A p p e n di x  1 0.  
Pr e g n a n c y Pr e c a uti o n s, D efi niti o n f or F e m al e of C hil d b e ari n g 
P ot e nti al, a n d C o ntr a c e pti v e  R e q uir e m e nt s  
A p p e n di x  1 1.  
Cli ni c al L a b or at or y A s s e s s m e nt T a bl e  
A p p e n di x  1 2.  
Pr o c e d ur e s a n d S p e cifi c ati o n s  
A p p e n di x  1 3.  
Pr e d ni s o n e C o n v er si o n T a bl e  
A p p e n di x  1 4.  
M a n a g e m e nt of Cli ni c al a n d L a b or at or y A d v er s e E v e nt s  
 
 

Fil g oti ni b  
 
Pr ot oc ol  G L P G 0 6 3 4 -C L -2 2 7  
Fi nal  
Gala pa g os  
A me n d me nt 2  
C O N FI D E N TI A L  
P a ge  9 4  
0 9 Se p 2 0 2 2  
A p pe n di x  1 . S p o ns or a n d I n vesti g at or Si g n at ure P a g e 
 
G A L A P A G O S N V G E N E R A A L D E WI T T E L A A N L 1 1 A 3 2 8 0 0 M E C H E L E N, 
B E L GI U M  
 
S T U D Y A C K N O W L E D G E M E N T  
 
A Ra n d o mize d, D o u ble -bli n d, Place b o -c o ntr olle d P hase 2 St u d y t o E val uate t he Effect of 
Fil g oti ni b o n Se me n Para meters i n A d ult Males wit h acti ve R he u mat oi d Art hritis , Ps oriatic 
Art hritis, A n k yl osi n g S p o n d ylitis or N o n -ra di o gra p hic A xial S po n d yl oart hritis  
A me n d me nt 2 , Fi n al 0 9 Se p 2 0 2 2  
T his pr ot oc ol has bee n a p pr o ve d b y Gal a pa g os N V . T he f oll o wi n g si g n at ure d oc u me nts t his 
a p pr o val.  
 
 
A n electr o nic si g n at ure of t he s p o ns or’s 
res p o nsi ble pers o n is pr o vi de d at t he e n d of 
t he d oc u me nt. 
 ( Cli nical De vel o p me nt 
Lea der) i n a bse n ce of 
 
(Me dical Lea der ) 
 
Si g nat ure  
 
 
 
 
Date  
 
 
 
I N V E S TI G A T O R S T A T E M EN T  
I h a ve rea d t he pr ot oc ol, i ncl u di n g all a p p e n dices, a n d I a gree t hat it c o ntai ns all necessar y 
details f or me a n d m y staff t o c o n d uct t his st u d y as descri be d. I will c o n d uct t his st u d y as 
o utli ne d herei n a n d will ma ke a reas o na bl e eff ort t o c o m plete t he st u d y wit hi n t he ti me 
desi g nat e d.  
I will pr o vi de all st u d y p ers o n nel u n der m y s u p er visi o n c o pies of t he pr ot o c ol a n d access t o all 
i nf or mati o n pr o vi de d b y t he s p o ns or. I will disc uss t his material wit h t he m t o e ns ure t hat t he y are 
f ull y i nf or me d a b o ut t he dr u gs a n d t he st u d y. 
 
 
 
Pri nci pal I n v esti gat or Na me ( Pri nte d)  
 
Si g nat ure  
 
 
 
 
Date  
 
Site N u m ber  
P P D
P P D

Fil g oti ni b  
 
Pr ot oc ol G L P G 0 6 3 4 -C L -2 2 7  
Fi nal  
Gala pa g os  
A me n d me nt 2  
C O N FI D E N TI A L  
P a ge  9 5  
0 9 Se p 2 0 2 2  
A p pe n di x  2 .  St u d y Pr oce d ures T a ble  –  D o u ble -bli n d Tre at me nt P h ase  ( Secti o n 6. 4 ) 
E V E N T  
Scree ni n g  
 
E T b  
 
S afet y f oll o w -u p c  
St u d y d a ys ( D)/ w ee ks ( W) a 
D a y  1  
W 2  
( ± 5 d a ys)  
W 4  
( ± 5 d a ys)  
W 8  
( ± 5 d a ys)  
W 1 3 * *  
(+ 5  d a ys)  
3 0 D a ys after l ast 
d ose of st u d y dr u g  
( ± 5 d a ys)  
I nf or me d C o nse nt  
X  
 
 
 
 
 
 
 
De m o gra p hics a n d Me dical 
Hist or y( Disease C haracteristics, 
R A/ Ps A/ A S/ nr A x S p A Hist or y, 
N u m ber of C hil dre n Fat here d , 
S m o ki n g Ha bits, A vera ge 
W ee kl y Alc o h ol C o ns u m pti o n, 
a n d Fa mil y Hist or y of C or o nar y 
Heart Disease)  
X  
 
 
 
 
 
 
 
I ncl usi o n/e xcl usi o n criteria 
re vie w 
X  
X  
 
 
 
 
 
 
C o m plete P h ysical E xa m c 
X  
 
 
 
 
 
X  
X  
S y m pt o m -directe d P h ysical 
E xa m, as nee de d  
 
X  
X  
X  
X  
X  
 
 
Vital Si g ns c a n d W ei g ht  
X  
X  
X  
X  
X  
X  
X  
X  
Hei g ht  
X  
 
 
 
 
 
 
 
1 2 -lea d E C G 
X  
 
 
 
 
X  
X  
 
T e n der J oi nt C o u nt 2 8 ( TJ C 2 8) 
(f or R A s u bj ects o nl y)  
X  
 
 
 
 
 
 
 
S w olle n J oi nt C o u nt 2 8 ( SJ C 2 8) 
(f or R A s u bj ects o nl y) 
X  
 
 
 
 
 
 
 
T e n der J oi nt C o u nt 6 8 ( TJ C 6 8) 
(f or Ps A s u bj ects o nl y) 
X  
 
 
 
 
 
 
 
S w olle n J oi nt C o u nt 6 6 ( SJ C 6 6) 
(f or Ps A s u bj ects o nl y) 
X  
 
 
 
 
 
 
 

Fil g oti ni b  
 
Pr ot oc ol G L P G 0 6 3 4 -C L -2 2 7  
Fi nal  
Gala pa g os  
A me n d me nt 2  
C O N FI D E N TI A L  
P a ge  9 6  
0 9 Se p 2 0 2 2  
E V E N T  
Scree ni n g  
 
E T b  
 
S afet y f oll o w -u p c  
St u d y d a ys ( D)/ w ee ks ( W) a 
D a y  1  
W 2  
( ± 5 d a ys)  
W 4  
( ± 5 d a ys)  
W 8  
( ± 5 d a ys)  
W 1 3 * *  
(+ 5  d a ys)  
3 0 D a ys after l ast 
d ose of st u d y dr u g  
( ± 5 d a ys)  
P atie nt Gl o bal Assess me nt of 
Disease Acti vit y ( Pt G A D A)  (f or 
R A a n d Ps A s u bj ects o nl y)  
X  
 
 
 
 
 
 
 
P h ysicia n’s Gl o bal Assess me nt 
of Disease Acti vit y ( P h G A D A) d 
(f or all s u bj ects) 
X  
X  
 
 
 
X  
 
 
P atie nt’s Gl o bal Assess me nt of 
P ai n I nte nsit y ( P P ai n) (f or Ps A 
s u bj ects o nl y) 
X  
 
 
 
 
 
 
 
B at h A n k yl osi n g 
S p o n d yl oart hritis Disease 
Acti vit y I n de x ( B A S D AI) (f or 
A S/ nr A X S p A s u bj ects o nl y)  
X  
 
 
 
 
 
 
 
T B ( Q ua ntifer o n ® )T est e 
X  
 
 
 
 
 
 
 
C hest X -ra yf 
X  
 
 
 
 
 
 
 
Uri nal ysis g  
X  
X  
 
 
 
X  
X  
X  
Uri ne dr u g scree n g  
X  
 
 
 
 
 
 
 
He mat ol o g y a n d Ser u m 
C he mistr y g  
X  
X  
X  
X  
X  
X  
X  
X  
Li pi d pr ofile (fasti n g) (T otal 
c h olester ol a n d s u bfracti o ns )g  
 
X  
 
 
 
X  
 
 
Ser u m hs C R P  
X  
X  
X  
X  
X  
X  
 
 
E n d ocri ne: T S H, H b A 1c g  
X  
 
 
 
 
 
 
 

Fil g oti ni b  
 
Pr ot oc ol G L P G 0 6 3 4 -C L -2 2 7  
Fi nal  
Gala pa g os  
A me n d me nt 2  
C O N FI D E N TI A L  
P a ge  9 7  
0 9 Se p 2 0 2 2  
E V E N T  
Scree ni n g  
 
E T b  
 
S afet y f oll o w -u p c  
St u d y d a ys ( D)/ w ee ks ( W) a 
D a y  1  
W 2  
( ± 5 d a ys)  
W 4  
( ± 5 d a ys)  
W 8  
( ± 5 d a ys)  
W 1 3 * *  
(+ 5  d a ys)  
3 0 D a ys after l ast 
d ose of st u d y dr u g  
( ± 5 d a ys)  
L H, F S H, i n hi bi n B, t otal 
T est oster o ne c ollecti o n ti me 
bet wee n 0 7: 0 0 -1 1: 0 0 i n t he 
m or ni n g g  
X  
X  
 
X  
 
X  
X  
X  
P K c ollecti o n (s parse) h  
 
 
X  
X  
 
X  
 
 
C o nc o mita nt Me dicati o ns  
X  
X  
X  
X  
X  
X  
X  
X  
Assess me nt of A d verse E ve nts  
X  
X  
X  
X  
X  
X  
X  
X  
Se me n C ollecti o n  
( 2 sa m ples as p er c ollecti o n 
i nstr ucti o ns i n Secti o n 6. 1 1 )i 
X  
 
 
 
 
X  
X j 
 
Date a n d ti me of m ost rece nt 
ej ac ulati o n k 
X  
 
 
 
 
X  
X  
 
HI V, He p atitis B, a n d 
He p atitis  C l 
X  
 
 
 
 
 
 
 
H B V D N A l, m 
 
 
 
 
 
X  
 
 
Ra n d o mizati o n  
 
X  
 
 
 
 
 
 

Fil g oti ni b  
 
Pr ot oc ol G L P G 0 6 3 4 -C L -2 2 7  
Fi nal  
Gala pa g os  
A me n d me nt 2  
C O N FI D E N TI A L  
P a ge  9 8  
0 9 Se p 2 0 2 2  
E V E N T  
Scree ni n g  
 
E T b  
 
S afet y f oll o w -u p c  
St u d y d a ys ( D)/ w ee ks ( W) a 
D a y  1  
W 2  
( ± 5 d a ys)  
W 4  
( ± 5 d a ys)  
W 8  
( ± 5 d a ys)  
W 1 3 * *  
(+ 5  d a ys)  
3 0 D a ys after l ast 
d ose of st u d y dr u g  
( ± 5 d a ys)  
St u d y Dr u g Acc o u nta bilit y  
 
 
 
X  
X  
X  
X  
 
St u d y Dr u g Dis pe nsati o n n 
 
X  
 
X  
X  
X o  
 
 
I n-cli nic D osi n g n  
 
X  
X  
 
 
X  
 
 
a 
Visits c orrelate wit h t he n u m ber of da ys/ wee ks o n dr u g. 
b  
A n y ti me a s u bject disc o nti n ues partici p ati o n i n t h e st u d y pri or t o Wee k  1 3 a n Earl y Ter mi n ati o n ( E T) Visit is re q uire d. S u bjects w h o are Res p o n ders at Wee k 1 3 a n d c h o ose 
n ot t o c o nti n ue i n t he E xte nsi o n P hase are als o re q uire d t o c o m plete E T visit assess me nts.  
c 
All s u bjects will ha ve a 3 0 -da y safet y f oll o w -u p visit after disc o nti n ui n g bli n de d st u d y dr u g, e xce pt Art hritis Res p o n ders at Wee k 1 3 w h o are c o nti n ui n g i n  t he E xte nsi o n 
P hase of t h e st u d y . 
c 
As detaile d i n A p pe n di x  1 2 . 
d  
F or defi niti o ns of  A rt hritis Res p o n der/ N o n -res p o n der stat us please refer t o Defi niti o n of Ter ms .  
e 
Pr o of of n o acti ve or u ntreate d late nt t u berc ul osis (T B ) at Scree ni n g . S u bjects w h o are dia g n ose d wit h late nt T B at Scree ni n g  m ust i nitiate a n a de q uate c o urse of pr o p h yl a xis 
as per l o cal sta n dar d of care f or a mi ni m u m of 4  we e ks pri or t o ra n d o mizati o n. S u bject ma y i nitiate st u d y dr u g d osi n g o nl y aft er c o ns ultati o n wit h t h e S p o ns or  Me dical 
Lea der or desi g nee . 
f 
C hest x -ra y ( vie ws as p er l o cal g ui d eli nes) ta ke n at Scree ni n g or wit hi n t h e 3 m o nt hs pri or t o Scree ni n g ( wit h t h e re p ort or fil ms a vaila ble f or i n vesti gat or re vie w) wit h o ut 
e vi d e nce of acti ve or late nt T B i nfe cti o n . 
g  
As detaile d i n A p pe n di x  1 1 . F or visits t h at re q uire fasti n g, s u bjects s h o ul d n ot ha ve a n y f o o d or dri n k (e xce pt water) f or at least 8  h o urs bef ore t h e visit.  
h  
S parse plas ma p har mac o ki n etic ( P K ) sa m ples at Wee k 2 are c ollecte d at 3 0  mi n utes p ost  d ose. T he P K sa m ple at Wee k  4 ca n be c ollecte d at a n y ti me wit h o ut re gar d t o 
d osi n g. T he P K sa m ple at Wee k 1 3 is c ollecte d pri or t o st u d y dr u g a d mi nist rati o n. Please refer t o Secti o n 6. 1 4  f or details o n st u d y dr u g a d mi nistrati o n.  
i 
T he Scree ni n g  se me n sa m ple c ollecti o n s h o ul d c oi n ci d e wit h t he Da y 1 ( Baseli ne ) visi t as m uc h as p ossi ble. Se me n sa m ples will be c ollecte d o n t he visit da y a n d/ or as s o o n 
as p ossi ble after t he visit  da y .  
j 
Se me n c ollecti o n will be c o m plete d at E T visit o nl y if pre vi o us se me n sa m p les were n ot c ollecte d wit hi n 2 wee ks of E T . 
k  
T his q uesti o n will be as ke d pri or t o eac h se me n c ollecti o n.  
l 
A n HI V -1/ HI V -2 a nti ge n/a nti b o d y test, a He patitis C vir us a nti b o d y test, a He patitis B s urface a nti ge n, a He patitis B s urface a nti b o d y a n d  a He patitis c ore a nti b o d y test will 
be c o n d ucte d o n all s u bj ects; S u bjects wit h p ositi ve He patitis B s urface a nti ge n ( H Bs A g) at Scree ni n g are e xcl u de d fr o m  t he st u dy . S u bjects wit h p ositi ve H B V c ore A b a n d 
ne gati ve H Bs A g, re q uire refle x testi n g f or H B V D N A. S u bjects wit h p ositi ve H B V D N A at Scree ni n g will be e xcl u d e d. S u bjects wit h p ositi ve H B V c ore A b a n d ne gati ve 
H B V D N A are eli gi ble p er i n vesti gat or j u d g me nt, b ut ma y  re q uire pr o p h ylactic treat me nt i n acc or da nce wit h H B V treat me nt g ui d eli nes/l ocal sta n dar d of care a n d re q uire 
o n g oi n g m o nit ori n g wit h bl o o d tests f o r H B V D N A e ver y 3 m o nt hs. S u bjects wit h e vi d e nce of acti ve He patitis  B d uri n g t h e st u d y , as e vi d e nce d b y H B V D N A  p ositi vit y , 
will be disc o nti n ue d fr o m st u d y  dr u g  as o utli ne d i n t h e pr ot oc ol. S u bjects wit h p ositi ve H C V a nti b o d y ( A b) at Scree ni n g, re q uire re fle x testi n g f or H C V R N A. S u bjects wit h 
p ositi ve H C V R N A at Scree ni n g will be e xcl u de d. S u bjects wit h p ositi ve H C V A b, b ut ne gati ve H C V R N A  are eli gi ble per i n vesti gat or j u d g me nt.  
m  
S u bjects wit h p ositi ve H B V c ore A b a n d ne gati ve H B V D N A at Scree ni n g re q ui re o n g oi n g m o nit ori n g wit h bl o o d tests f or H B V D N A e ver y 3 m o nt hs. 
n  
T he s u bject will ta ke t h e first d ose ( Da y  1 ) i n t he cli nical st u d y ce nter. F or P K c ollecti o n p ur p oses, at Wee ks 2 a n d 1 3, s u bjects s h o ul d be i nstr ucte d n ot t o ta ke t h eir st u d y 
dr u g, b ut rat her t o bri n g it wit h t he m t o t h e cli nic. S u bjects will be i nstr ucte d t o ta ke t h eir d ose d uri n g t h eir sc he d ule d v isit, as detaile d i n Secti o n 6. 1 4 . 
o  
O nl y f or s u bjects c o nti n ui n g o n o pe n -la bel fil g oti ni b i n t he E xte nsi o n P hase. 
* * Wee k 1 3 visit m ust o cc ur after 1 3 wee ks of dr u g e x p os ure. T heref ore, visit wi n d o w f or t his visit  is + 5 da ys.  T he e n d of t h e D o u ble -Bli n d Treat me nt P hase is w he n t he Wee k 1 3 
se me n res ults are a vaila ble t o  t h e i n vesti gat or a n d ha ve bee n e val u ate d . Base d o n t his e val u ati o n, s u bjects are assi g ne d t o e nter t he M o nit ori n g P hase or t h e E xte nsi o n P hase.  

Fil g oti ni b  
 
Pr ot oc ol G L P G 0 6 3 4 -C L -2 2 7  
Fi nal  
Gala pa g os  
A me n d me nt 2  
C O N FI D E N TI A L  
P a ge  9 9  
0 9 Se p 2 0 2 2  
M o nit ori n g P h ase ( Secti o n  6. 6 ) 
E V E N T  
M o nit ori n g P h ase ( ± 5  d a ys)  
E T   
St u d y d a ys ( D)/ w ee ks ( W)  
Visits occ ur e ver y 1 3 w ee ks st arti n g fr o m t heir 
e ntr y i nt o t he M o nit ori n g P h ase (f or u p t o 5 2 w ee ks 
or u ntil R e versi bilit y is met, w hic he ver is s o o ner )  
 
S y m pt o m -directe d P h ysical E xa m, as nee de d  
X  
X  
Vital Si g ns a a n d W ei g ht  
X  
X  
Uri nal ysis a  
X  
X  
He mat ol o g y a n d C he mistr y a  
X  
X  
Ser u m hs C R P  
X  
 
L H, F S H, i n hi bi n B, t otal T est oster o ne a c ollecti o n ti me 
bet wee n 0 7: 0 0 -1 1: 0 0 i n t he m or ni n g  
X  
X  
C o nc o mita nt Me dicati o ns  
X  
X  
Assess me nt of A d verse E ve nts b 
X  
X  
Se me n C ollecti o n c 
( 2 sa m ples as p er c ollecti o n i nstr ucti o ns i n Secti o n 6. 1 1 ) 
X  
X e 
Date a n d ti me  of m ost rece nt ej ac ulati o n d 
X  
 
a 
A s detaile d i n A p pe n di x  1 2 . 
b  
As detaile d i n Secti o n  7. 3 . 
c 
Se me n sa m ples will be c ollecte d e ver y 1 3  wee ks fr o m t h e da y of st u d y dr u g disc o nti n uati o n, f or u p t o 5 2 wee ks or u ntil Re versi bilit y is met, w hic he ver is ac hie ve d s o o ner. 
Re versi bilit y is met w he n all s per m para meter(s) q ualif yi n g t h e s u bject t o e nter t he M o nit ori n g P hase ret ur n(s) t o greater t ha n 5 0 % of Baseli n e (ie, t o greater t ha n [ 0. 5 0 x 
Baseli ne]).  
d  
T his q uesti o n will be as ke d pri or t o se me n c ollecti o n n ot at t h e site visit.  
e 
Se me n c ollecti o n will be c o m plete d at E T visit o nl y if pre vi o us se me n sa m ples were n ot c ollecte d wit hi n 2  wee ks of E T.  

Fil g oti ni b  
 
Pr ot oc ol G L P G 0 6 3 4 -C L -2 2 7  
Fi nal  
Gala pa g os  
A me n d me nt 2  
C O N FI D E N TI A L  
P a ge  1 0 0  
0 9 Se p 2 0 2 2  
E xte nsi o n P h ase ( Secti o n 6. 5  ) 
E V E N T  
E xte nsi o n P h ase   
E T b  
S afet y f oll o w -u p   
St u d y d a ys ( D)/ w ee ks ( W)  
Wee k 2 6 u p t o 1 5 6 w ee ks
a   
( ± 1 0 d a ys) 
3 0 D a ys after l ast d ose of st u d y dr u g  
( ± 5 d a ys) 
S y m pt o m -directe d P h ysical E xa m, as nee de d  
X  
X  
X  
Vital Si g ns a n d W ei g ht  
X  
X  
X  
T B Q ua nti F E R O N c 
X  
 
 
Uri nal ysis d  
X  
X  
X  
He mat ol o g y a n d C he mistr y d  
X  
X  
X  
Li pi d pr ofile (fasti n g) [ T otal c h olester ol a n d 
s u bfracti o ns] d, e 
X  
 
 
Ser u m hs C R P  
X  
 
 
L H, F S H, i n hi bi n B, t otal T est oster o ne d c ollecti o n 
ti me bet wee n 0 7: 0 0-1 1: 0 0 i n t he m or ni n g  
X  
 
 
C o nc o mita nt Me dicati o ns  
X  
X  
X  
Assess me nt  of A d verse E ve nts  
X  
X  
X  
Se me n C ollecti o n  
 ( 2 sa m ples as per c ollecti o n i nstr ucti o ns i n 
Secti o n 6. 1 1 ) 
X  
X l 
 
Date a n d ti me of m ost rece nt ej ac ulati o n f 
X  
 
 
St u d y Dr u g Acc o u nta bilit y g  
X  
X  
 
St u d y Dr u g Dis pe nsati o n g  
X  
 
 
1 2 -lea d E C Gh  
X  
X  
 
P K c ollecti o n (s parse)  
X i 
 
 
H B V D N A j, k 
X  
 
 
I n-cli nic d osi n g  
X ( Wee k 2 6)  
 
 
a 
S u bjects i n t he E xte nsi o n P hase ( E P) will c o m plete E P Wee k  2 6 visit a n d e ver y  1 3  wee ks t h ereafter u p t o 1 5 6  wee ks.  

Fil g oti ni b  
 
Pr ot oc ol G L P G 0 6 3 4 -C L -2 2 7  
Fi nal  
Gala pa g os  
A me n d me nt 2  
C O N FI D E N TI A L  
P a ge  1 0 1  
0 9 Se p 2 0 2 2  
b  
A n y ti me a s u bject disc o nti n ues partici p ati o n i n t h e st u d y pri or t o Wee k 1 5 6 i n t he E xte nsi o n P hase,  a n Earl y Ter mi n ati o n ( E T) Visit is re q uire d.  
c 
I n t h e E P  s u bjects m ust h a ve yearl y Q ua nti F E R O N testi n g. Yearl y T B t esti n g be gi ns 1 year fr o m t h e scree ni n g T B test date. If ye arl y T B testi n g falls bet we e n st u d y visits, t h e 
yearl y T B testi n g s h o ul d be perf or me d at t h e visit pri or t o 1 year fr o m t h e scree ni n g T B test date. S u bjects wit h ne wl y p ositi ve (c o n verte d) Q ua nti F E R O N ® [ or ce ntrall y r e p orte d 
e q ui vale nt  assa y] T B test s h o ul d be disc o nti n ue d fr o m st u d y dr u g. S u bjects w h o were pre vi o usl y tre ate d f or T B wit h a c o m plete a n d a de q ua te c o urse of t h era p y as per l o cal 
Sta n dar d of C are a n d as verifie d b y t h e i n vesti gat or d o n o t nee d t o ha ve yearl y Q ua nti F E R O N ® tests. S u bjects pre vi o usl y treate d f or T B s h o ul d be scree ne d at least ye arl y f or 
si g ns a n d s y m pt o ms c o nsiste nt wit h reacti vati o n of T B. A n y s u bject wit h acti ve T B s h o ul d be disc o nti n ue d fr o m st u d y.  
d  
As detaile d i n A p pe n di x  1 2 . F or visits t h at re q uire fasti n g, s u bjects s h o ul d n ot ha ve a n y f o o d or dri n k (e xce pt water) f or at least 8 h o urs bef ore t h e vi sit. 
e 
Li pi d pr ofile s h o ul d be perf or me d  at Wee ks 2 6, 3 9, 6 5, 9 1, 1 1 7 a n d 1 4 3 . 
f 
T his q uesti o n will be as ke d pri or t o se me n c ollecti o n n ot at t h e site visit.  
g  
O nl y a p plica ble f or s u bjects o n fil g oti ni b.   
h  
E C G will be perf or me d at Wee k 1 5 6 or E T  (f or s u bjects o n o pe n-la bel fil g oti ni b o nl y).  
i 
A s parse plas ma P K sa m ple is c ollecte d at Wee k  2 6 pri or t o st u d y dr u g a d mi nistrati o n  (f or s u bjects o n o pe n la bel fil g oti ni b o nl y). Please refer t o Secti o n  6. 1 4  f or details o n 
st u d y dr u g a d mi nistrati o n.  
j 
A n HI V -1/ HI V -2 a nti ge n/a nti b o d y test, a He patitis C vir us a nti b o d y test, a He patitis B s urface a nti ge n, a He patitis B s urface a nti b o d y a n d  a He patitis c ore a nti b o d y test will 
be c o n d ucte d o n all s u bjects; S u bjects wit h e vi d e nce of acti ve He patitis  B d uri n g t h e st u d y , as e vi d e nce d b y H B V D N A  p ositi vit y , will be disc o nti n ue d fr o m st u d y dr u g  as o utli ne d 
i n t he pr ot o c ol.  
k  
S u bjects wit h p ositi ve H B V c ore A b a n d ne gati ve H B V D N A at Scree ni n g re q uire o n g oi n g m o nit ori n g wit h bl o o d tests f or H B V D N A e ver y 3 m o nt hs.  
l 
Se me n c ollecti o n will be c o m plete d at E T visit o nl y if pre vi o us se me n sa m ples were n ot c ollecte d wit hi n 2  wee ks of E T.  

Fil g oti ni b  
 
Pr ot oc ol G L P G 0 6 3 4 -C L -2 2 7  
Fi nal  
Gala pa g os  
A me n d me nt 2  
C O N FI D E N TI A L  
P a ge  1 0 2  
0 9 Se p 2 0 2 2  
A p pe n di x  3 . 6 6/ 6 8 -j oi nt C o u nt ( S J C 6 6/ T J C 6 8) 
A n o ver vie w of t he j oi nts t o be assesse d is pr o vi de d bel o w ( s u bject’s left a n d ri g ht): 
− 
Te m p or o ma n di b ular  
− 
Ster n ocla vic ular  
− 
Acr o mi ocla vic ular  
− 
S h o ul der ( *)  
− 
El b o w ( *)  
− 
Wrist ( *)  
− 
Metacar p o p hala n geal: first, sec o n d, t hir d, f o urt h, fift h ( *)  
− 
Pr o xi mal i nter p hala n geal: first, sec o n d, t hir d, f o urt h, fift h ( *)  
− 
Distal i nter p hala n geal: sec o n d, t hir d, f o urt h, fift h  
− 
Hi p (assesse d f or te n der ness o nl y, n ot i ncl u de d i n SJ C)  
− 
K nee ( *)  
− 
A n kle  
− 
Tars us  
− 
Metatars o p hala n geal: first, sec o n d, t hir d, f o urt h, fift h  
− 
Pr o xi mal i nter p hala n geal: first, sec o n d, t hir d, f o urt h, fift h  
Re place d ( or ot her wise n ot assessa ble) j oi nts s h o ul d be d oc u me nte d at S cree ni n g a n d o mitte d 
fr o m f urt her e val uati o n d uri n g t he st u d y. Pare nteral c ortic oster oi ds are n ot r o uti nel y per mitte d 
d uri n g t he st u d y; if t he s u bject re q uir es a j oi nt i njecti o n f or A E of art hritis flare, t he i njecte d  j oi nt 
s h o ul d be mar ke d as “ n on -assessa ble ” f or t h e re m ai n der of t he st u d y.  
J oi nts fla g ge d wit h a n ( *) are use d i n t he 2 8 -j oi nt c o u nts (TJ C 2 8/ SJ C 2 8 ). 
N ote: T he TJ C 6 8 / TJ C 2 8 a n d SJ C 6 6 / SJ C 2 8 are use d t o deri ve t he D A P S A  a n d C D AI.  

Fil g oti ni b  
 
Pr ot oc ol G L P G 0 6 3 4 -C L -2 2 7  
Fi nal  
Gala pa g os  
A me n d me nt 2  
C O N FI D E N TI A L  
P a ge  1 0 3  
0 9 Se p 2 0 2 2  
A p pe n di x  4 . P h ysici a n’s Gl o b al A ssess me nt of Dise ase Acti vit y ( P h G A D A) 
T he P h G A D A  will be rec or de d o n a 0 -1 0 0 m m V A S, wit h 0 i n dicati n g “ n o disease acti vit y” a n d 
1 0 0 i n dicati n g “e xtre me disease acti vit y”  as relates t o t he s u bject’s art hritis . T he e val uati n g 
p h ysicia n a n d t he s u bject s h o u l d c o m plete t he gl o bal assess me nts i n de pe n d e ntl y of eac h ot h er, as 
m uc h as p ossi ble . 
I nstr u cti o ns are pr o vi de d bel o w. 
C o nsi deri n g all t he wa ys art hritis affects y o ur pati e nt, dra w a li ne o n t h e scale f or h o w well his 
or her c o n diti o n is t o da y.  
 
 
 
 
0  
 
 
 
 
 
 
 
1 0 0  
 
N o Disease A cti vit y   
 
 
 
E xtre me Disease Acti vit y  
N ote: T he V A S scal e m ust be 1 0 0  m m l o n g.  
 
 
 
 

Fil g oti ni b  
 
Pr ot oc ol G L P G 0 6 3 4 -C L -2 2 7  
Fi nal  
Gala pa g os  
A me n d me nt 2  
C O N FI D E N TI A L  
P a ge  1 0 4  
0 9 Se p 2 0 2 2  
A p pe n di x  5 . P ati e nt’s Gl o b al Assess me nt of Dise ase Acti vit y ( Pt G A D A ) 
I n R A a n d Ps A, t he Pt G AD A  will be rec or de d o n a 0 -1 0 0 m m V A S, wit h 0 i n dicati n g “ v er y 
well” a n d 1 0 0 i n dicati n g “ ver y p o or”. T he e val uati n g p h ysicia n a n d t he s u bj ect s h o ul d c o m plete 
t he gl o bal assess me nts i n de pe n de ntl y of eac h ot her. 
I nstr u cti o ns: 
C o nsi deri n g all t he wa ys art hritis  affects y o u, please dra w  a vertical mar k ( | ) o n t h e h oriz o ntal 
li ne bel o w f or h o w well y o u ha v e bee n d oi n g o v er t he last wee k . 
 
 
0  
 
 
 
 
 
 
 
1 0 0  
 
Ver y Well  
 
 
 
 
 
 
 
Ver y P o or  
N ote: T he V A S scal e m ust be 1 0 0  m m l o n g.  
N ote: T he Pt G A D A  is part of t he D A P S A a n d C D AI.  
 
− 
S o urce: A S A S Ha n d b o o k ( Sie per, et al., 2 0 0 9) 
 

Fil g oti ni b  
 
Pr ot oc ol G L P G 0 6 3 4 -C L -2 2 7  
Fi nal  
Gala pa g os  
A me n d me nt 2  
C O N FI D E N TI A L  
P a ge  1 0 5  
0 9 Se p 2 0 2 2  
A p pe n di x  6 . P ati e nt’s Gl o b al Assess me nt of P ai n I nte nsit y  
I n Ps A: ( P P ai n)  
T he Patie nt’s Gl o bal Ass ess me nt of Pai n I nte nsit y will be rec or de d o n a  0 -1 0 0 m m V A S, wit h 0 
i n dicati n g “ n o p ai n” a n d 1 0 0 i n dicati n g “ u n b eara ble pai n”.  
I nstr u cti o ns: 
Please i n dicate wit h a v ertical mar k ( | ) t hr o u g h t h e h oriz o ntal li ne t he m ost pai n y o u h a d fr o m 
y o ur art hritis o ver t he last wee k . 
 
 
 
 
0  
 
 
 
 
 
 
 
1 0 0  
 
N o pai n  
 
 
 
 
 
 
U n beara ble pai n  
 
N ote: t he V A S scale m ust be 1 0 0 m m l o n g.  
 
Patie nt pai n assess me nt will be use d t o calc ulate t he D A P S A sc ore: D A P S A = TJ C 6 8 + SJ C 6 6 + 
Pt G A D A (c m) + P Pai n ( c m) + C R P ( m g/ d L).  
 
− 
S o urce: A S A S Ha n d b o o k ( Sie per, et al., 2 0 0 9; Sc h oels, et al., 2 0 1 0) 
 

Fil g oti ni b  
 
Pr ot oc ol G L P G 0 6 3 4 -C L -2 2 7  
Fi nal  
Gala pa g os  
A me n d me nt 2  
C O N FI D E N TI A L  
P a ge  1 0 6  
0 9 Se p 2 0 2 2  
A p pe n di x  7 . B at h A n k yl osi n g S p o n d ylitis Dise ase Acti vit y I n de x ( B A S D AI)  
Please tic k t he b o x w hic h re pres e nts y o ur a ns w er.  
All q uesti o ns refer t o t he last wee k.  
1. F A TI G U E  
H o w w o ul d y o u d escri b e t he o verall le vel of fati g ue/tire d ness y o u ha ve e x perie nce d?  
0  
1  
2  
3  
4  
5  
6  
7  
8  
9  
1 0  
 
N o ne   
 
 
 
 
 
 
 
Ver y se v ere  
2. S PI N A L P AI N  
H o w w o ul d y o u d escri b e t he o verall le vel of A S nec k, bac k or hi p pai n y o u ha ve ha d?  
0  
1  
2  
3  
4  
5  
6  
7  
8  
9  
1 0  
 
N o ne   
 
 
 
 
 
 
 
Ver y se v ere  
3. P E RI P H E R A L A R T H RI TI S  
H o w w o ul d y o u d escri b e t he o verall le vel of pai n/s welli n g i n j oi nts ot her t ha n nec k, b ac k or hi ps 
y o u ha v e ha d?  
0  
1  
2  
3  
4  
5  
6  
7  
8  
9  
1 0  
 
N o ne   
 
 
 
 
 
 
 
Ver y se v ere  
4. E N T H E SI TI S  
H o w w o ul d y o u d escri b e t he o verall le vel of disc o mf ort y o u h a ve ha d fr o m a n y areas te n der t o 
t o uc h or press ur e? 
0  
1  
2  
3  
4  
5  
6  
7  
8  
9  
1 0  
 
N o ne   
 
 
 
 
 
 
 
Ver y se v ere  
5. I N T E N SI T Y O F M O R NI N G S TI F F N E S S  
H o w w o ul d y o u d escri b e t he o verall le vel of m or ni n g stiff ness y o u h a ve ha d fr o m t he ti me y o u 
wa ke u p?  

Fil g oti ni b  
 
Pr ot oc ol G L P G 0 6 3 4 -C L -2 2 7  
Fi nal  
Gala pa g os  
A me n d me nt 2  
C O N FI D E N TI A L  
P a ge  1 0 7  
0 9 Se p 2 0 2 2  
0  
1  
2  
3  
4  
5  
6  
7  
8  
9  
1 0  
 
N o ne   
 
 
 
 
 
 
 
Ver y se v ere  
6. D U R A TI O N O F M O R NI N G S TI F F N E S S  
H o w l o n g d o es y o ur m or ni n g stiff ness last fr o m t he ti me y o u wa ke u p?  
0  
1  
2  
3  
4  
5  
6  
7  
8  
9  
1 0  
 
0 h  
 
 
 
 
  1 h  
 
 
 
2 or m ore h  
− 
S o urce: A S A S Ha n d b o o k ( Sie per, et al., 2 0 0 9) 
 
N ote: T he B A S D AI is part of t he A S A S C ore Set. T he t otal sc ore is c alc ulat e d as f oll o ws:  
𝐵𝐴𝑆𝐷𝐴𝐼=
𝑄1 + 𝑄2 + 𝑄3 + 𝑄4 + (𝑄5 + 𝑄6 )
2
5
 
 

Fil g oti ni b  
 
Pr ot oc ol G L P G 0 6 3 4 -C L -2 2 7  
Fi nal  
Gala pa g os  
A me n d me nt 2  
C O N FI D E N TI A L  
P a ge  1 0 8  
0 9 Se p 2 0 2 2  
A p pe n di x  8 . Dise ase S pecific Cl assific ati o n Criteri a  
 
T he 2 0 1 0 A meric a n C olle ge of R he u m at ol o g y – E ur o pe a n Le a g ue A g ai nst 
R he u m atis m C oll a b or ati ve I niti ati ve Cl assific ati o n Criteri a f or R he u m at oi d Art hritis  
 
T ar g et p o p ul ati o n ( W h o s h o ul d b e t est e d ?): P ati e nts 
w h o h a v e at l e ast 1 j oi nt wit h d efi nit e cli nic al 
s y n o vitis (s w elli n g) a  wit h t h e s y n o vitis n ot b ett er 
e x pl ai n e d b y a n ot h er dis e as e b  
 
Cl assific ati o n crit eri a f or R A (sc or e -b as e d al g orit h m: 
a d d sc or e of c at e g ori es A - D;  a sc or e of ≥ 6/ 1 0 is 
n e e d e d f or cl assific ati o n of a p ati e nt as h a vi n g 
d efi nit e R A) c 
 
A. J oi nt i n v ol v e m e nt d 
 
1 l ar g e j oi nt e  
0  
2 -1 0 l ar g e j oi nts  
1  
1 -3 s m all j oi nts ( wit h or wit h o ut i n v ol v e m e nt 
of l ar g e j oi nts) f  
2  
4 -1 0 s m all j oi nts ( wit h or wit h o ut 
i n v ol v e m e nt of l ar g e j oi nts)  
3  
> 1 0 j oi nts ( at l e ast 1 s m all j oi nt) g  
5  
B. S er ol o g y ( at l e ast 1 t est r es ult is n e e d e d 
f or cl assific ati o n)h 
 
N e g ati v e R F a n d n e g ativ e A C P A  
0  
L o w-p ositi v e R F or l o w -p ositi v e A C P A  
2  
Hi g h -p ositi v e R F or hi g h -p ositi v e A C P A  
3  
C. Ac ut e -p h as e r e act a nts ( at l e ast 1 t est 
r es ult is n e e d e d f or cl assific ati o n)i 
 
N or m al C R P a n d n or m al E S R  
0  
A b n or m al C R P or a b n or m al E S R  
1  
D. D ur ati o n of s y m pt o ms j 
 
< 6 w e e ks  
0  
≥6 w e e ks 1  
≥6 w e e ks 1  

Fil g oti ni b  
 
Pr ot oc ol G L P G 0 6 3 4 -C L -2 2 7  
Fi nal  
Gala pa g os  
A me n d me nt 2  
C O N FI D E N TI A L  
P a ge  1 0 9  
0 9 Se p 2 0 2 2  
 
a T he criteria are ai me d at classifi cati o n of ne wl y prese nti n g patie nts. I n a d diti o n, patie nts wit h er osi v e disease t y pical of  
r he u mat oi d art hritis ( R A) wit h a hist or y c o m pati ble wit h pri or f ulfill me nt of t h e 2 0 1 0 criteria s h o ul d be classifie d as h a vi n g  
R A. P atie nts wit h l o n gsta n di n g disease, i n cl u di n g t h ose w h ose disease is i nacti ve ( wit h or wit h o ut treat me nt ) w h o, base d o n 
retr os pecti vel y a vaila ble d ata, ha ve pre vi o usl y f ulfille d t h e 2 0 1 0 criteria s h o ul d be classifie d as h a vi n g R A.  
b Differe ntial dia g n oses var y a m o n g patie nts wit h differ e nt prese ntati o ns, b ut ma y i n cl u de c o n diti o ns s uc h as s yste mic l u p us  
er ythe mat os us, ps oriatic art hritis, a n d g o ut. If it is u nclear a b o ut t h e rele va nt differe ntial dia g n oses t o c o nsi der, a n e x pert  
r he u mat ol o gist s h o ul d be c o ns ulte d. 
c Alt h o u g h patie nts wit h a sc ore of < 6/ 1 0 are n ot classifia ble as ha vi n g R A, t h eir stat us ca n be  reassesse d a n d t h e criteria 
mi g ht be f ulfille d c u m ulati vel y o ver ti me.  
d J oi nt i n v ol ve me nt refers t o a n y s w olle n or te n der j oi nt o n e xa mi n ati o n, w hic h ma y be c o nfir me d b y i ma gi n g e vi d e nce of 
s y n o vitis. Distal i nter p hala n geal j oi nts, first car p o meta car pal j oi nts, a n d first metatars o p hala n geal j oi nts are excl u de d fr o m  
assess me nt . Cate g ories of j oi nt distri b uti o n are classifie d acc or di n g t o t he l o cati o n a n d n u m ber of i n v ol ve d j oi nts, wit h 
place me nt i nt o t h e hi g hest cate g or y p ossi ble b ase d o n t he patter n of j oi nt i n v ol ve me nt.  
e " Lar ge j oi nts" refers t o s h o ul d ers, el b o ws, hi ps, k nees, a n d a n kles.  
f " S mall j oi nts" refers t o t h e meta car p o p hala n geal j oi nts, pr o xi mal i nter p hala n geal j oi nts, sec o n d t hr o ug h  
fift h metatars o p hala n geal j oi nts, t h u m b i nter p hala n geal j oi nts, a n d wrists. 
g I n t his cate g or y, at least 1 of t h e i n v ol ve d j oi nts m ust b e a s mall j oi nt; t h e ot h er j oi nts ca n i ncl u de a n y c o m bi n ati o n of lar ge 
a n d a d diti o nal s mall j oi nts, as well as ot h er j oi nts n ot s pecificall y liste d else w here (e g, te m p or o ma n di b ular, 
acr o mi o cla vic ular, ster n ocla vic ular).  
h Ne gati ve refers t o I U val u es t h at are less t h a n or e q ual t o t h e u p per li mit of n or mal ( U L N) f or t h e la b orat or y a n d assa y;  
l o w-p ositi ve refers t o I U val ues t h at are hi g her t ha n t he U L N b ut ≤3 ti mes t h e U L N f or t h e la b orat or y a n d assa y;  
hi g h -p ositi ve refers t o I U val u es t h at are > 3 ti mes t h e U L N f or t h e la b orat or y a n d assa y. W here r he u mat oi d fact or ( R F)  
i nf or mati o n is o nl y a vaila ble as p ositi ve or ne gati ve, a p ositi ve res ult s h o ul d be sc ore d as l o w-p ositi ve f or R F.  
A C P A = a nti -citr ulli n ate d pr otei n a nti b o d y.  
i N or mal/a b n or mal is d eter mi n e d b y l o cal la b orat or y sta n dar ds. C R P = C-reacti ve pr otei n; E S R = er yt hr oc yte se di me ntati o n 
rate. 
j D urati o n of s y m pt o ms refers t o patie nt self-re p ort of t h e d urati o n of si g ns or s y m pt o ms of s y n o vitis (e g, pai n, s welli n g, 
te n der ness) of j oi nts t hat are cli nicall y i n v ol ve d at t h e ti me of assess me nt, re gar dless of treat me nt stat us. 
 
 

Fil g oti ni b  
 
Pr ot oc ol G L P G 0 6 3 4 -C L -2 2 7  
Fi nal  
Gala pa g os  
A me n d me nt 2  
C O N FI D E N TI A L  
P a ge  1 1 0  
0 9 Se p 2 0 2 2  
C A S P A R Cl assific ati o n Criteri a f or Ps ori ati c Art hritis  
T he classificati o n of Ps A base d o n t he C A S P A R criteria re q uires t he prese n ce of est a blis he d 
i nfla m mat or y art hritis (j oi nts, s pi ne, or e nt h uses) wit h at least 3 p oi nts fr o m t he f oll o wi n g 
5  feat ur es: 
•  
C urre nt ps oriasis, O R  
A hist or y of ps oriasis,  O R  
A fa mil y hist or y of ps oriasis  
•  
C urre nt or pri or hist or y of dact ylitis  
•  
Ra di o gra p hic e vi de n ce of j u xta -artic ular ne w -b o n e f or mati o n  
•  
A bse nce of ser u m r h e u m at oi d fact or  
•  
Nail d ystr o p h y  
C urre nt ps oriasis is assi g ne d 2 p oi nts, w hile all ot her cli nical f eat ur es  are assi g ne d 1 p oi nt  

Fil g oti ni b  
 
Pr ot oc ol G L P G 0 6 3 4 -C L -2 2 7  
Fi nal  
Gala pa g os  
A me n d me nt 2  
C O N FI D E N TI A L  
P a ge  1 1 1  
0 9 Se p 2 0 2 2  
A S A S Cl assific ati o n Criteri a f or A xi al S p A  
 
 
T he classificati o n of A S base d o n t he m o difie d Ne w Y or k criteria re q uires o ne of t he f oll o wi n g 
cli nical criteria A N D o n e of t he ra di ol o gical criteri a.  
Cli nical Criteria  
L o w b ac k pai n ≥3 m o nt hs, i m pr o ve d b y e x ercise a n d n ot relie ve d b y rest  
Li mitati o n of l u m bar s pi ne i n sa gittal a n d fr o ntal pla nes  
Li mitati o n of c hest e x pa nsi o n (relati ve t o n or mal val ues c orrecte d f or a ge a n d se x)  
Ra di ol o gical criteria  
Bilateral gra de 2 -4 sacr oiliitis O R  
U ni lateral gra de 3-4 s acr oiliitis  
 

Fil g oti ni b  
 
Pr ot oc ol G L P G 0 6 3 4 -C L -2 2 7  
Fi nal  
Gala pa g os  
A me n d me nt 2  
C O N FI D E N TI A L  
P a ge  1 1 2  
0 9 Se p 2 0 2 2  
A p pe n di x  9 . C T C A E Gr a di n g Sc ale f or Se verit y of A d verse E ve nts  
Please refer t o t he C T C A E  Versi o n  4. 0 3, w hic h ca n be f o u n d at:  
htt p://e vs. nci. ni h. g o v/ft p 1/ C T C A E/ C T C A E _ 4. 0 3 _ 2 0 1 0 -0 6 -1 4 _ Q uic k Refere nce _ 8. 5 x 1 1. p df.  
F or A Es ass ociate d wit h la b orat or y a b n or malities, t he e ve nt s h o ul d be gra d e d o n t he basis of t he 
cli nical se verit y i n t he c o nte xt of t he u n derl yi n g c o n diti o ns; t his ma y or m a y n ot be i n a gree m e nt 
wit h t he gra di n g of t he la b orat or y a b n or malit y.  
T he o nl y m o dificati o n t o t he C T C A E criteria is t he a d diti o n of a Gra d e 1 u p per res pir at or y 
i nfecti o n as f oll o ws: 
C T C A E 
v 4. 0 Ter m  
Gr a de 1  
Gr a de 2  
Gr a de 3  
Gr a de 4  
Gr a de  5  
C T C A E v 4. 0 3 
A E T er m 
Defi niti o n  
U p per 
res pirat or y 
i nfecti o n 
Mil d 
s y m pt o ms; 
s y m pt o matic 
relief 
(e g, c o u g h 
s u p pressa nt, 
dec o n gesta nt)  
M o derate 
s y m pt o ms; 
oral 
i nter ve nti o n 
i n dicate d 
(e g, a nti bi otic, 
a ntif u n gal, 
a nti viral)  
I V a nti bi otic, 
a ntif u n gal, or 
a nti viral 
i nter ve nti o n 
i n dicate d; 
ra di ol o gic, 
e n d osc o pic, or 
o perati ve 
i nter ve nti o n 
i n dicate d 
Life -
t hreate ni n g 
c o nse q ue nces; 
ur ge nt 
i nter ve nti o n 
i n dicate d 
Deat h  
A dis or der 
c haracterize d b y 
a n i nfecti o us 
pr ocess 
i n v ol vi n g t he 
u p per res pirat or y 
tract 
( n ose, para nasal 
si n uses, 
p har y n x, lar y n x, 
or trac hea).  
 

Fil g oti ni b  
 
Pr ot oc ol G L P G 0 6 3 4 -C L -2 2 7  
Fi nal  
Gala pa g os  
A me n d me nt 2  
C O N FI D E N TI A L  
P a ge  1 1 3  
0 9 Se p 2 0 2 2  
A p pe n di x  1 0 .  Pre g n a nc y Prec a uti o ns, Defi niti o n f or Fe m ale of C hil d be ari n g P ote nti al, a n d 
C o ntr ace pti ve Re q uire me nts   
T he a d mi nistrati o n of fil g oti ni b i n e m br y o fet al a ni mal de vel o p me nt st u dies res ulte d i n decreas e d 
n u m bers of via ble rat fet uses, i ncreas e d res or pti o ns, a n d visceral a n d s keletal malf or mati o ns . 
Si milar effects w ere n ote d i n t he ra b bit. A safet y mar gi n relati ve t o h u ma n e x p os ure has n ot bee n 
i de ntifie d. P re g na nc y is c o ntrai n dicate d d uri n g use of fil g oti ni b. 
F or partici pati o n i n t his st u d y, me n m ust a gree t o use c o n d o ms d uri n g t he st u d y a n d f or 9 0  da ys 
after t he l ast d ose  of st u d y dr u g . Fe m ale se x ual part ners of c hil d beari n g p ot e ntial, defi ne d bel o w, 
s h o ul d als o c o nsi der use of hi g hl y effecti ve c o ntr ace pti o n as o utli ne d bel o w.  
1)  Defi niti o ns  
a)  Defi niti o n of C hil d be ari n g P ote nti al (f or F e m ale S e x u al P art ners of M ale S u bjects)  
F or t he p ur p os es of t his st u d y, a fe male -b or n part ner is c o nsi dere d of c hil d b eari n g p ote ntial 
f oll o wi n g t he i nitiati o n of p u bert y ( Ta n ner sta ge 2) u ntil bec o mi n g p ost-me n o pa usal, u nless 
per ma ne ntl y sterile or wit h me dicall y d o c u me nte d o varia n fail ure .  
W o me n are c o nsi dere d t o be i n a p ost me n o pa usal state w he n t he y are  ≥ 5 4  years of a ge wi t h 
cessati o n of pre vi o usl y o cc urri n g me ns es f or ≥ 1 2 m o nt hs wit h o ut a n alter nati ve ca use.  
Per ma ne nt steriliz ati o n i ncl u des h yst erect o m y, bilateral o o p h or ect o m y, or bilateral 
sal pi n gect o m y i n a fe mal e s u bject of a n y a ge. 
b)  Defi niti o n of M ale Fertilit y  
F or t he  p ur p os es of t his st u d y, a mal e -b or n s u bject is c o nsi dere d fertile aft er t he i nitiati o n of 
p u bert y u nless per ma n e ntl y steriliz e d b y bilateral orc hi dect o m y or has me dical d oc u me ntati o n of 
per ma ne nt male i nfertilit y.  
2)  C o ntr ace pti o n f or Fe m ale Se x u al P art ners of M ale S u bjects  
1.  St u d y Dr u g Effects o n Pre g n a nc y a n d H or m o n al C o ntr ace pti o n  
Fil g oti ni b is c o ntrai n dicate d i n pre g na nc y as t here is a p ossi bilit y of h u ma n 
terat o ge nicit y/fet ot o xicit y i n e arl y pre g n a nc y b ase d o n n o n-cli nical data. Data fr o m a dr u g -dr u g 
i nteracti o n st u d y of fil g oti ni b a n d h or m o nal c o ntrace pti ves ( G S -U S -4 1 7 -3 9 1 6) ha ve 
de m o nstrate d c o -a d mi nistrati o n wit h fil g oti ni b di d n ot alter t he p har m ac o ki netics of 
re pres e ntati ve h or m o nal c o ntrace pti ves  (le v o n or gestrel/et hi n yl estra di ol). F or male s u bjects, 
male c o n d o m s h o ul d be use d; f or t heir fe male part ners of c hil d beari n g p ote ntial a n acce pte d 
c o ntrace pti ve met h o d s h o ul d als o be c o nsi dere d . Details are o utli ne d bel o w.  
Please refer t o t he latest versi o n of t he fil g oti ni b I B f or a d diti o nal i nf or mati o n.  

Fil g oti ni b  
 
Pr ot oc ol G L P G 0 6 3 4 -C L -2 2 7  
Fi nal  
Gala pa g os  
A me n d me nt 2  
C O N FI D E N TI A L  
P a ge  1 1 4  
0 9 Se p 2 0 2 2  
2.  C o nt r ace pti o n f or Fe m ale Se x u al P art ners of C hil d be ari n g P ote nti al  
Male s u bjects i n t his st u d y wit h fe m ale se x ual part ners of c hil d beari n g p ote ntial m ust a gree t o 
use a c o n d o m. Male s u bj ects m ust s hare t he f oll o wi n g i nf or m ati o n wit h fe male se x ual part ners 
re gar di n g w hi c h c o ntrace pti ve met h o ds are rec o m me n de d, starti n g at t he ti me of Scree ni n g u ntil 
9 0 da ys f oll o wi n g t he l ast d ose of st u d y dr u g i n t h e male s u bject.  
C o ntrace pti ve Met h o ds i ncl u de:  
C o m plete a bsti ne nce fr o m se x ual i nterc o urse of re pr o d ucti ve p ote nti al wit h t he male s u bject. 
A bsti ne nce is a n acce pta ble met h o d of c o ntrace pti o n o nl y w he n it is i n li ne wit h t he fe male 
se x ual part ner a n d male s u bject’s preferre d a n d us ual lifest yle.  
O R  
C o nsiste nt a n d c orrect us e of 1 of t he f oll o wi n g m et h o ds of birt h c o nt r ol liste d bel o w.  
I ntr a uteri ne d e vice (I U D) wit h a fail ure rate of < 1 % per year 
T u bal steriliz ati o n  
Ess ure micr o -i nsert s yste m ( pr o vi de d c o nfir m ati o n of s uccess 3 m o nt hs aft er pr oce d ure) 
H or m o nal met h o ds (eac h met h o d m ust be use d wit h a c o n d o m i n t he male  p art ner)  
⎯ Oral c o ntrace pti ves (eit h er c o m bi ne d or pr o gester o ne o nl y)  
⎯ I nje cta ble pr o gester o n e 
⎯ I m pla nts of le v o n or gestr el 
⎯ Tra ns der m al c o ntrace pti ve patc h  
⎯ C o ntrace pti ve va gi n al ri n g  
All fe male se x ual part ners of male s u bjects s h o ul d refrai n fr o m i n vitr o fert ilizati o n wit h e x p ose d 
male’s s per m d uri n g mal e s u bject st u d y p artici pati o n a n d u ntil at least 9 0 da ys after t h e last  d ose 
of st u d y dr u g i n t he mal e part ner.  
3)  C o ntr ace pti o n f or M ale S u bjects  
It is t he oreticall y p ossi ble t hat a rel e va nt c o nce ntr ati o n of st u d y dr u g ma y be ac hie ve d i n a 
fe male part ner fr o m e x p os ure t o t he male s u bject’s se mi nal fl ui d. T heref ore, male s u bjects wit h 
fe male part ners of c hil d beari n g p ote ntial m ust use c o n d o ms d uri n g st u d y p artici pati o n a n d f or 
9 0  da ys after t h e last st u d y dr u g d os e . Fe male part ners of male st u d y s u bjects s h o ul d c o nsi der 
usi n g o ne  of t h e a b o ve m et h o ds of c o ntrace pti o n as well. Male s u bjects m ust als o refrai n fr o m 
s per m d o nati o n d uri n g treat me nt a n d u ntil at least 9 0 da ys after t h e last st u d y dr u g d osi n g . 

Fil g oti ni b  
 
Pr ot oc ol G L P G 0 6 3 4 -C L -2 2 7  
Fi nal  
Gala pa g os  
A me n d me nt 2  
C O N FI D E N TI A L  
P a ge  1 1 5  
0 9 Se p 2 0 2 2  
4)  U n acce pt a ble Birt h C o ntr ol Met h o ds  
Birt h c o ntr ol met h o ds t h at are u n acce pta ble i ncl u de peri o dic a bsti ne n ce (e g,  cale n dar, o v ulati o n, 
s y m pt ot her mal, p ost -o v ulati o n met h o ds), wit h dra wal (c oit us i nterr u pt us), s per mici des o nl y, a n d 
lactati o nal a me n orr hea m et ho d . Fe mal e c o n d o m a n d male c o n d o m s h o ul d n ot be use d t o get her. 
5)  Pr o ce d ures t o be F oll o w e d i n t he E ve nt of Pre g n a nc y i n a Fe m ale Se x u al P art ner  
S u bjects will be i nstr ucte d t o n otif y t he i n vesti gat or if t heir fe m ale part n er bec o mes pre g na nt at 
a n y ti me d uri n g t he st u d y, or if s he bec o mes pre g n a nt wit hi n 9 0 da ys of his last st u d y dr u g d ose. 
S u bjects w h o ha ve se x ual part ners w h o b ec o me pre g n a nt or w h o s us pect t hat t he y are pre g n a nt 
d uri n g t he st u d y m ust re p ort t he i nf or mati o n t o t he i n vesti gat or.  
I nstr u cti o ns for re p orti n g part ner pre g na n c y a n d p art ner pre g na n c y o utc o m e are o utli ne d i n 
Secti o n  7. 7. 2. 1 . 

Fil g oti ni b  
 
Pr ot oc ol G L P G 0 6 3 4 -C L -2 2 7  
Fi nal  
Gala pa g os  
A me n d me nt 2  
C O N FI D E N TI A L  
P a ge  1 1 6  
0 9 Se p 2 0 2 2  
A p pe n di x  1 1 . Cli nic al L a b or at or y Assess me nt T a ble  
He m at ol o g y  
C he mistr y  
Uri n al ysis  
Ot her  
He mat ocrit  
He m o gl o bi n  
Platelet c o u nt  
Re d bl o o d cell  ( R B C) 
c o u nt  
W hite bl o o d cell ( W B C ) 
c o u nt  
Differe ntials (a bs ol ute a n d 
perce nta ge), i ncl u di n g:  
L y m p h oc ytes  
M o n oc ytes  
Ne utr o p hils  
E osi n o p hils  
B as o p hils  
Retic u l ocyte c o u nt  
Mea n c or p usc ular v ol u me 
( M C V) 
 
 
E n d ocri ne  
(at Scree ni n g O nl y ) 
H b A 1c  
T S H  
Se x H or m o nes  
L utei nizi n g h or m o ne ( L H ) 
F ollicle sti m ulati n g 
h or m o ne ( F S H  
T est oster o ne (t otal)  
I n hi bi n B 
Al kali ne p h os p hatase  
As partate 
a mi n otra nsferase ( A S T)  
Ala ni ne a mi n otra nsferase 
( A L T) 
T otal bilir u bi n  
Direct a n d i n direct 
bilir u bi n  
T otal pr otei n  
Al b u mi n  
Bicar b o nate  
Bl o o d urea nitr o ge n 
( B U N) 
Calci u m  
C hl ori de  
Ser u m creati ni ne  
Creati ni ne cleara nce  
( Cr Cl) 
Gl uc ose  
P h os p h or us  
Ma g nesi u m  
P ota ssi u m 
S o di u m  
Creati ne p h os p h o ki nase 
( C P K) 
c-Reacti ve Pr otei n  
 
A p peara nce:  
Bl o o d  
C ol or  
Gl uc ose  
Le u k oc yte esterase  
p H  
Pr otei n  
Ur o bili n o ge n  
Ket o nes  
Bilir u bi n  
Nitrite  
S pecific Gra vit y  
Micr osc o pic  
Uri ne dr u g scree n f or:  
A m p heta mi nes  
C ocai ne  
Bar bit urates  
O piates  
Be nz o diaze pi nes  
Q ua nti F E R O N ®  T B –  G ol d 
Pl us I n-T u be  A nal ysis 
(w he n  re q uire d per 
i ncl usi o n criteria) 
 
 
 
P har mac o ki netics ( P K)  
Pr ot hr o m bi n Ti me ( P T ) 
P artial t hr o m b o plasti n ti me 
(P T T ) 
I nter nati o nal N or malize d 
Rati o ( IN R ) 
Ser ol o g y  
He p atitis B S urface A g 
He p atitis B S urface A b  
He p atitis B C ore A b 
He p atitis C A b  
HI V A g/ A b  
Refle x he patitis B D N A 
( w he n i n dicate d) 
Refle x he patitis C R N A 
( w he n i n dicate d) 
F asti n g Li pi ds  
Tri gl yceri des  
C h olester ol a n d its  
s u bfracti o ns 
( hi g h-de nsit y  
li p o pr otei n [ H D L] a n d 
l o w 
de nsit y li p o pr otei n 
[ L D L]) 
 

Fil g oti ni b  
 
Pr ot oc ol G L P G 0 6 3 4 -C L -2 2 7  
Fi nal  
Gala pa g os  
A me n d me nt 2  
C O N FI D E N TI A L  
P a ge  1 1 7  
0 9 Se p 2 0 2 2  
A p pe n di x  1 2 . Pr o ce d ures a n d S pecific ati o ns  
C o m plete P h ysic al E x a mi n ati o n  
A c o m plete P E  s h o ul d i ncl u de s o urce d oc u me ntati o n of ge neral a p peara n ce, a n d t he f oll o wi n g 
b o d y s yste ms: Hea d, nec k a n d t h yr oi d; e yes, ears, n ose, t hr oat, m o ut h a n d t o n g ue; c hest 
(e x cl u di n g breasts); res pirat or y; car di o vasc ular; l y m p h n o des, a b d o me n; s ki n, hair, nails; 
m usc ul os keletal; a n d ne ur ol o gic al.  
Vit al Si g ns  
Assess me nt of vital si g ns s h o ul d i ncl u de meas ure me nt of resti n g bl o o d press ure, p ulse, 
res pirat or y rate, a n d t e m perat ur e. 
Bl o o d press ur e s h o ul d be meas ure d usi n g t he f oll o wi n g sta n d ar dize d pr ocess:  
S u bject s h o ul d be resti n g f or  5 mi n utes wit h feet flat o n t he fl o or a n d meas ure me nt ar m 
s u p p orte d s o t hat t he mi d p oi nt of t he ma n o meter c uff is at heart le vel;  
Use a merc ur y s p h y g m o ma n o meter or a ut o matic bl o o d press ure de vi ce wit h a n a p pr o priat el y 
siz e d c uff wit h t he bla d d er ce nt ere d o v er t he brac hial arter y; 
Meas ure a n d rec or d t he bl o o d press ure t o t he nearest 2 m m H g mar k o n t h e ma n o meter or t o t he 
nearest w h ol e n u m ber o n a n a ut o matic de vice.  
Cre ati ni ne Cle ar a nce  
Creati ni ne cleara n ce is c alc ulate d b y t he C oc k cr o ft-Ga ult e q uati o n { C oc kcr oft 1 9 7 6 }  usi n g 
act ual b o d y wei g ht ( B W).  
Male:   
C r Cl ( m L/ mi n) =  [1 4 0  - a ge ( years)]  B W( k g)  
 
 
 
 
 
 
7 2   S cr 
 
S cr = ser u m creati ni ne ( m g/ d L)  
1 2 -Le a d E C G  
S u bjects s h o ul d rest i n a s u pi ne p ositi o n f or 5  mi n utes pri or t o ma ki n g a rec or di n g.   
T he i n vesti gat or ( or q ualifie d desi g nee) s h o ul d re vie w t he E C G traces  (i ncl u di n g heart rat e, P R-
i nter val, Q R S-i nter val, Q T-i nter val) rec or de d i n real ti me f or cli nicall y si g nifica nt a b n or malities.  
 

Fil g oti ni b  
 
Pr ot oc ol G L P G 0 6 3 4 -C L -2 2 7  
Fi nal  
Gala pa g os  
A me n d me nt 2  
C O N FI D E N TI A L  
P a ge  1 1 8  
0 9 Se p 2 0 2 2  
A p pe n di x  1 3 . Pre d nis o ne C o n versi o n T a ble  
T he f oll o wi n g t a ble will be use d f or c o n verti n g n o n -pre d n is o ne me dicati o ns t o pre d nis o ne 
e q ui vale nt:  
Ex a m ple: P atie nt is t aki n g 8 m g of Met hyl pre d nis ol o ne or ally d aily. T o get t he e q uiv ale nt d ose 
of pre d nis o ne: 8 m g Met hyl pre d nis ol o ne = ( 5 * 8)/ 4 = 1 0 m g pre d nis o ne.  
C ortic oster oi ds N a me  
E q ui v ale nt D ose ( m g) t o 5  
m g Pre d nis o ne  
B eta met has o ne  
0. 7 5  
B eta met has o ne 
Di pr o pi o nate  
0. 7 5  
B eta met has o ne S o di u m 
P h os p hate  
0. 7 5  
C ortis o ne  
2 0  
De xa met has o ne  
0. 7 5  
De xa met has o ne 
P al mitate  
0. 7 5  
De xa met has o ne 
P h os p hate  
0. 7 5  
De xa met has o ne 
S o di u m P h os p hate  
0. 7 5  
H y dr oc ortis o ne  
2 0  
Me pre d nis o ne  
4  
Met h yl pre d nis ol o ne  
4  
Met h yl pre d nis ol o ne 
Acetate  
4  
Met h yl pre d nis ol o ne 
S o di u m S ucci nate  
4  
Pre d nis o ne  
5  
Pre d nis ol o ne  
5  
Pre d nis ol o ne 
Far nes ylate  
5  
Pre d nis ol o ne S o di u m 
S ucci nate  
5  
Tria mci n ol o ne  
4  
 
 

Fil g oti ni b  
 
Pr ot oc ol G L P G 0 6 3 4 -C L -2 2 7  
Fi nal  
Gala pa g os  
A me n d me nt 2  
C O N FI D E N TI A L  
P a ge  1 1 9  
0 9 Se p 2 0 2 2  
A p pe n di x  1 4 . M a n a ge me nt of Cli nic al a n d L a b or at or y A d verse E ve nts  
 
 
 
Gr a de 1  
Gr a de 4  
Gr a de 3  
Gr a de 2  
M a y c o nti n ue 
d osi n g at t he 
discreti o n of t he 
i n vesti g at or 
Re pe at l a b t o 
c o nfir m t o xicit y 
gr a de  
Re pe at l a b t o 
c o nfir m t o xicit y  
gr a de  
If c o nfir me d a n d p ossi bl y a n d/ or pr o b a bl y rel ate d t o 
i n vesti g ati o n al me dici n al pr o d ucts: 
 
1.
Wit h h ol d i n vesti g ati o n al me dici n al pr o d ucts u ntil  
 Gr a de 2  
2.
Rest art all i n vesti g ati o n al me dici n al pr o d ucts at f ull d ose  
If c o nfir me d a n d u nrel ate d t o 
i n vesti g ati o n al me dici n al 
pr o d ucts, d osi n g m a y c o nti n ue at 
t he discreti o n of t he i n vesti g at or 
If c o nfir me d a n d 
p ossi bl y or pr o b a bl y 
rel ate d t o 
i n vesti g ati o n al 
me dici n al pr o d ucts , 
disc o nti n ue 
i n vesti g ati o n al 
me dici n al pr o d ucts  
d osi n g per m a ne ntl y 
a n d f oll o w at 
peri o dic i nter v als at 
le ast w ee kl y u ntil a 
ret ur n t o b aseli ne or 
is ot her wise 
e x pl ai ne d  
If Gr a de 3 or 4 rec urre nce t h at is c o nfir me d a n d p ossi bl y or 
pr o b a bl y rel ate d t o i n vesti g ati o n al me dici n al pr o d ucts, 
disc o nti n ue all i n vesti g ati o n al me dici n al pr o d ucts d osi n g 
per m a ne ntl y  
If Gr a de 3 or 4 rec urre nce t h at is c o nsi dere d u nrel ate d t o 
i n vesti g ati o n al me dici n al pr o d ucts, c o nti n ue all 
i n vesti g ati o n al me dici n al pr o d ucts at t he s a me d ose at t h e 
discreti o n of t he i n vesti g at or  

Si g nat ure Pa ge f or gl p g 0 6 3 4-cl- 2 2 7- pr ot oc ol 2 3 0 3 2
Si g nat ure Pa ge f or gl p g 0 6 3 4-cl- 2 2 7- pr ot oc ol 4 3 9 5 2 _ 4 4 1 3 7 _ 1 0 4 3 1 2
A p pr o val
o p me nt Lea der
Cli nical De vel o p me nt
0 9- Se p- 2 0 2 2 1 2: 2 7: 0 4 G M T + 0 0 0 0
P P D