A Randomized, Double-blind, Placebo-controlled Phase 2 Study to Evaluate the Testicular Safety of Filgotinib in Adult Males With Moderately to Severely Active Inflammatory Bowel Disease
Phase: PHASE2
Conditions: Inflammatory Bowel Disease
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 Testic ul ar Safet y of Fil g oti ni b i n A d ult  Males wit h 
M o deratel y t o Se verel y Acti ve I nfla m mat or y B o wel Disease 
 
 
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  
 
 
I N D N u m ber: 
E u dr a C T N u m ber:  
Cli nic al Tri als. g o v 
I de ntifier: 
1 2 9 6 4 7  
2 0 1 7 -0 0 0 4 0 2 -3 8  
 
N C T 0 3 2 0 1 4 4 5  
 
 
I n dic ati o n: 
I nfla m mat or y B o wel Dis ease  
 
 
Pr ot oc ol I D:  
G S -U S -4 1 8 -4 2 7 9   
 Me dic al Le a der : 
 
 
 
Pr ot oc ol 
Versi o n/ D ate:  
Ori gi nal:  
3 1 J a n uar y 2 0 1 7  
A me n d me nt 1:  
0 6 J ul y 2 0 1 7  
A me n d me nt 1. 1  ( V H P): 
2 1 Se pte m ber 2 0 1 7  
A me n d me nt 1. 2  ( 
): 
1 5 Oct o ber 2 0 1 8  
A me n d me nt 2:  
2 2  A u g ust 2 0 1 8  
A me n d me nt 3:  
1 8 J a n uar y 2 0 1 9 
A me n d me nt 3. 1 ( 
):  
2 5 J a n uar y 2 0 1 9  
A me n d me nt 4:  
1 7  Marc h  2 0 2 0  
A me n d me nt 4. 1  ( 
):  2 7 Marc h 2 0 2 0  
A me n d me nt 5:  
2 7  J u ne 2 0 2 2  
A me n d me nt 5. 1 ( 
):   2 7 J u ne  2 0 2 2  
A me n d me nt 6:   
0 9 Se pte m ber 2 0 2 2  
A me n d me nt 6. 1 ( 
):   0 9 Se pte m ber 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 d e ntial. I t is t he pr o pert y of 
Gala pa g os N V a n d ma y n ot  be use d , discl ose d, re pr o d uce d  or ot h er wise disse mi nate d wit hi n 
y o ur or ga niz ati 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 writte n a ut h orizati o n of 
Gala pa g os  N V . 
P P D
C CI
C CI
C CI
C CI
C CI

Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  2  
 
0 9 Se pte m ber 2 0 2 2  
T A B L E O F C O N T E N T S  
T A B L E O F C O N T E N T S  .............................................................................................................................................. 2  
LI S T O F I N -T E X T T A B L E S  ........................................................................................................................................ 4  
LI S T O F I N -T E X T FI G U R E S  ...................................................................................................................................... 5  
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  .............................................................................................................. 6  
S U M M A R Y O F C H A N G E S  ......................................................................................................................................... 8  
P R O T O C O L S Y N O P SI S  ............................................................................................................................................ 1 0  
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 5  
1.  
I N T R O D U C TI O N .............................................................................................................................................. 2 9  
1. 1.  
B ac k gr o u n d  ............................................................................................................................................ 2 9  
1. 1. 1.  
Ulcerati ve C olitis  .................................................................................................................. 2 9  
1. 1. 2.  
Cr o h n’s Disease .................................................................................................................... 3 0  
1. 2.  
F il g oti ni b ( G S-6 0 3 4)  .............................................................................................................................. 3 2  
1. 2. 1.  
Ge neral I nf or mati o n  ............................................................................................................. 3 2  
1. 2. 2.  
Precli nical P har mac ol o g y a n d T o xic ol o g y  ........................................................................... 3 2  
1. 2. 3.  
Cli nical Trials of Fil g oti ni b  .................................................................................................. 3 4  
1. 3.  
Rati o nale f or t his St u d y a n d Pr o p ose d I B D P o p ulati o n  ......................................................................... 3 5  
1. 3. 1.  
Rati o nale f or t he O utc o me Me as ures  ................................................................................... 3 7  
1. 3. 2.  
Rati o nale f or t he C h oice of D ose a n d D osi n g I nter val  ......................................................... 3 8  
1. 4.  
Ris k/ Be nefit Assess me nt f or t he St u d y  .................................................................................................. 3 8  
1. 5.  
C o m plia nce  ............................................................................................................................................ 4 0  
2.  
O BJ E C TI V E S  ..................................................................................................................................................... 4 1  
3.  
S T U D Y D E SI G N  ................................................................................................................................................ 4 2  
3. 1.  
St u d y Treat me nts  ................................................................................................................................... 4 8  
3. 2.  
D urati o n of Treat me nt  ............................................................................................................................ 4 8  
3. 3.  
Criteria f or I nterr u pti o n or Dis c o nti n uati o n of St u d y Treat me nt  ........................................................... 4 8  
3. 3. 1.  
St u d y Dr u g I nterr u pti o n C o nsi derati o ns ............................................................................... 4 8  
3. 3. 2.  
St u d y Dr u g Disc o nti n uati o n C o nsi derati o ns  ........................................................................ 4 9  
3. 4.  
Disease W orse ni n g Criteria  .................................................................................................................... 5 1  
3. 5.  
E n d of St u d y  ........................................................................................................................................... 5 2  
3. 6.  
P ost -St u d y Care  ...................................................................................................................................... 5 2  
4.  
S U BJ E C T P O P U L A TI O N  .................................................................................................................................. 5 3  
4. 1.  
N u m ber of S u bj ects a n d S u bj ect Selecti o n  ............................................................................................ 5 3  
4. 2.  
I ncl usi o n Criteria .................................................................................................................................... 5 3  
4. 3.  
E xcl usi o n Criteria ................................................................................................................................... 5 8  
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  ........................................................................................... 6 2  
5. 1.  
Ra n d o mizati o n, Bli n di n g a n d Treat me nt C o des  .................................................................................... 6 2  
5. 1. 1.  
Ra n d o mizati o n  ..................................................................................................................... 6 2  
5. 1. 2.  
Bli n di n g  ................................................................................................................................ 6 2  
5. 1. 3.  
Pr oce d ures f or Brea ki n g Treat me nt C o des  ........................................................................... 6 3  
5. 2.  
Descri pti o n a n d Ha n dli n g of Fil g oti ni b a n d Place b o -t o-Matc h ( P T M)  .................................................. 6 3  
5. 2. 1.  
F or m ulati o n  .......................................................................................................................... 6 3  
5. 2. 2.  
P ac ka gi n g a n d La b eli n g  ....................................................................................................... 6 3  

Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  3  
 
0 9 Se pte m ber 2 0 2 2  
5. 2. 3.  
St ora ge a n d Ha n dli n g  ........................................................................................................... 6 4  
5. 2. 4.  
D osa ge a n d A d mi nistrati o n of Fil g oti ni b  ............................................................................. 6 4  
5. 3.  
Pri or a n d C o nc o mita nt Me dic ati o ns  ....................................................................................................... 6 4  
5. 3. 1.  
All o we d C o nc o mita nt Me dicati o ns  ...................................................................................... 6 5  
5. 3. 2.  
Pr o hi bite d C o nc o mita nt Me dicati o ns  ................................................................................... 6 5  
5. 4.  
Vacci ne G ui deli nes  ................................................................................................................................ 6 7  
5. 5.  
Acc o u nta bilit y f or St u d y Dr u gs  ............................................................................................................. 6 7  
5. 5. 1.  
I n vesti gati o nal Me dici nal Pr o d uct Ret ur n or Dis p osal ......................................................... 6 8  
6.  
S T U D Y P R O C E D U R E S  .................................................................................................................................... 6 9  
6. 1.  
S u bj ect E nr oll me nt a n d Treat me nt Assi g n me nt  ..................................................................................... 6 9  
6. 2.  
Pretreat me nt Assess me nts  ...................................................................................................................... 6 9  
6. 2. 1.  
Scree ni n g Visit  ..................................................................................................................... 6 9  
6. 2. 2.  
Da y 1 Assess me nts  ............................................................................................................... 7 2  
6. 3.  
Ra n d o mizati o n  ....................................................................................................................................... 7 2  
6. 4.  
P art A ( Da y 1 t hr o u g h W ee k 1 3 St u d y Visit) ......................................................................................... 7 3  
6. 5.  
P art B ( After W ee k 1 3 t hr o u g h Wee k 2 6 St u d y Visit)  ........................................................................... 7 3  
6. 6.  
O pe n -La b el Fil g oti ni b P hase ( O pe n -La bel Da y  1  t hr o u g h O p e n-La bel Wee k  1 3 St u d y Visit)  ............. 7 3  
6. 7.  
M o nit ori n g P hase  ................................................................................................................................... 7 3  
6. 8.  
Earl y T er mi nati o n  .................................................................................................................................. 7 4  
6. 9.  
Safet y F oll o w -U p Visit 3 0 Da ys P ost Last D ose ( ± 5 da ys)  ................................................................... 7 4  
6. 1 0.  
L o n g T er m E xte nsi o n  ............................................................................................................................. 7 4  
6. 1 1.  
Safet y a n d T olera bilit y  ........................................................................................................................... 7 4  
6. 1 2.  
Cli nical La b orat or y E val uati o ns  ............................................................................................................. 7 4  
6. 1 3.  
Se me n C ollecti o n Pr oce d ure  .................................................................................................................. 7 5  
6. 1 4.  
Vital Si g ns  .............................................................................................................................................. 7 6  
6. 1 5.  
P h ysical E xa mi nati o n  ............................................................................................................................. 7 6  
6. 1 6.  
P har mac o ki netic Assess me nts  ................................................................................................................ 7 7  
6. 1 7.  
T hr o m b oe m b olic E ve nts  ........................................................................................................................ 7 7  
6. 1 8.  
Ma y o Cli nic Sc ore a n d P artial Ma y o Cli nic Sc ore ................................................................................. 7 7  
6. 1 9.  
Si m ple E n d osc o pic Sc ore f or Cr o h n’s Disease  ...................................................................................... 7 7  
6. 2 0.  
Cr o h n’s Disease Acti vit y I n de x  ............................................................................................................. 7 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 8  
7. 1.  
Defi niti o ns of A d verse E ve nts, A d verse Reacti o ns, a n d Seri o us A d verse E ve nts  ................................. 7 8  
7. 1. 1.  
A d verse E ve nts  ..................................................................................................................... 7 8  
7. 1. 2.  
Seri o us A d verse E ve nts  ........................................................................................................ 7 8  
7. 2.  
Assess me nt of A d verse E ve nts a n d Seri o us A d verse E ve nts  ................................................................. 7 9  
7. 2. 1.  
Assess me nt of Ca usalit y f or St u d y Dr u gs a n d Pr oce d ures  ................................................... 7 9  
7. 2. 2.  
Assess me nt of Se verit y  ........................................................................................................ 8 0  
7. 3.  
I n vesti gat or Re q uire me nts a n d I nstr ucti o ns f or Re p orti n g A d verse E ve nts a n d Seri o us 
A d verse E ve nts t o t he S p o ns or  ............................................................................................................... 8 0  
7. 4.  
S p o ns or Re p orti n g Re q uire me nts  ........................................................................................................... 8 2  
7. 5.  
Cli nical La b orat or y A b n or malities  ......................................................................................................... 8 2  
7. 6.  
T o xicit y Ma na ge me nt  ............................................................................................................................ 8 3  
7. 6. 1.  
Gra d es 1 a n d 2 La b orat or y A b n or malit y or Cli nical E ve nt  .................................................. 8 3  
7. 6. 2.  
Gra d es 3 La b orat or y A b n or malit y or Cli nical E ve nt  ........................................................... 8 3  
7. 6. 3.  
Gra d es 4 La b orat or y A b n or malit y or Cli nical E ve nt  ........................................................... 8 4  
7. 7.  
S pecial Sit uati o ns Re p orts  ...................................................................................................................... 8 4  
7. 7. 1.  
Defi niti o ns of S pecial Sit uati o ns  .......................................................................................... 8 4  
7. 7. 2.  
I nstr ucti o ns f or Re p orti n g S pe cial Sit uati o ns ....................................................................... 8 5  
8.  
S T A TI S TI C A L C O N SI D E R A TI O N S  ................................................................................................................ 8 7  
8. 1.  
A nal ysis O bj ecti ves a n d E n d p oi nts  ........................................................................................................ 8 7  

Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  4  
 
0 9 Se pte m ber 2 0 2 2  
8. 1. 1.  
A nal ysis O bj ecti ves  .............................................................................................................. 8 7  
8. 1. 2.  
Pri mar y E n d p oi nt  ................................................................................................................. 8 7  
8. 1. 3.  
Sec o n dar y E n d p oi nts  ............................................................................................................ 8 8  
8. 1. 4.  
E x pl orat or y E n d p oi nts  .......................................................................................................... 8 8  
8. 2.  
A nal ysis C o n ve nti o ns  ............................................................................................................................. 8 8  
8. 2. 1.  
A nal ysis Sets  ........................................................................................................................ 8 8  
8. 3.  
Data Ha n dli n g C o n ve nti o ns  ................................................................................................................... 8 9  
8. 4.  
De m o gra p hic Data a n d B aseli ne C haracteristics  ................................................................................... 8 9  
8. 5.  
Statistical A nal ysis  ................................................................................................................................. 8 9  
8. 5. 1.  
Pri mar y A nal ysis  .................................................................................................................. 8 9  
8. 5. 2.  
Sec o n dar y A nal yses  ............................................................................................................. 9 0  
8. 5. 3.  
E x pl orat or y A nal yses  ........................................................................................................... 9 0  
8. 5. 4.  
Ot her Safet y A nal ysis  ........................................................................................................... 9 0  
8. 5. 5.  
E xte nt of E x p os ure  ............................................................................................................... 9 0  
8. 5. 6.  
A d verse E ve nts  ..................................................................................................................... 9 1  
8. 5. 7.  
La b orat or y E val uati o ns  ........................................................................................................ 9 1  
8. 6.  
P har mac o ki netic A nal ysis  ...................................................................................................................... 9 1  
8. 7.  
Sa m ple Size  ............................................................................................................................................ 9 1  
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  ......................................................... 9 2  
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)  ................................................... 9 3  
8. 1 0.  
I nter nal I n de p e n de nt Safet y R e vie w ...................................................................................................... 9 3  
8. 1 1.  
U n bli n de d I nteri m A nal ysis  ................................................................................................................... 9 3  
8. 1 2.  
I nte grate d Se me n A nal ysis ..................................................................................................................... 9 4  
9.  
R E S P O N SI BI LI TI E S .......................................................................................................................................... 9 5  
9. 1.  
I n vesti gat or Res p o nsi bilities .................................................................................................................. 9 5  
9. 1. 1.  
G o o d Cli nical Practice .......................................................................................................... 9 5  
9. 1. 2.  
I nstit uti o nal Re vie w B oar d (I R B)/I n de pe n de nt Et hics C o m mittee (I E C) 
Re vie w a n d A p pr o val  ........................................................................................................... 9 5  
9. 1. 3.  
I nf or me d C o nse nt ................................................................................................................. 9 6  
9. 1. 4.  
C o nfi de ntialit y  ...................................................................................................................... 9 6  
9. 1. 5.  
St u d y Files a n d Rete nti o n of Rec or ds  .................................................................................. 9 6  
9. 1. 6.  
Case Re p ort F or ms  ............................................................................................................... 9 8  
9. 1. 7.  
I ns pecti o ns ............................................................................................................................ 9 8  
9. 1. 8.  
Pr ot oc ol C o m plia nce  ............................................................................................................ 9 8  
9. 2.  
S p o ns or Res p o nsi bilities  ........................................................................................................................ 9 8  
9. 2. 1.  
Pr ot oc ol M o dificati o ns  ......................................................................................................... 9 8  
9. 2. 2.  
St u d y Re p ort a n d P u blicati o ns  ............................................................................................. 9 9  
9. 3.  
J oi nt I n vesti gat or/ S p o ns or Res p o nsi bilities ........................................................................................... 9 9  
9. 3. 1.  
P a y me nt Re p orti n g  ............................................................................................................... 9 9  
9. 3. 2.  
Access t o I nf or mati o n f or M o nit ori n g  .................................................................................. 9 9  
9. 3. 3.  
Access t o I nf or mati o n f or A u diti n g or I ns pecti o ns  ............................................................ 1 0 0  
9. 3. 4.  
St u d y Disc o nti n uati o n  ........................................................................................................ 1 0 0  
1 0.  R E F E R E N C E S  ................................................................................................................................................. 1 0 1  
1 1.  A P P E N DI C E S  .................................................................................................................................................. 1 0 4  
 
LI S T O F I N -T E X T T A B L E S  
 
T a ble  5 -1.  
Pr o hi bite d C o nc o mita nt Me dicati o ns  ..................................................................................... 6 6  
T a ble  7 -1.  
Gra di n g of A d verse E ve nt Se verit y  ........................................................................................ 8 0  
 
 

Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  5  
 
0 9 Se pte m ber 2 0 2 2  
LI S T O F I N -T E X T FI G U R E S  
 
Fi g ure  3 -1.  
St u d y Sc he ma  ......................................................................................................................... 4 3  
Fi g ure  3 -2.  
P art A ( Da y  1 t hr o u g h Wee k 1 3 St u d y Visit)  ......................................................................... 4 4  
Fi g ure  3 -3.  
P art B ( After W ee k 1 3  t hr o u g h Wee k 2 6 St u d y Visit) ........................................................... 4 4  
Fi g ure  3 -4.  
O pe n -La b el Fil g oti ni b P hase ( O pe n -La bel Da y  1 t hr o u g h O p e n -La bel Wee k 1 3 
St u d y Visit) ............................................................................................................................. 4 5  
Fi g ure  3 -5.  
M o nit ori n g P hase ( u p t o 5 2 wee ks)  ........................................................................................ 4 6  
Fi g ure  3 -6.  
L o n g T er m E xte nsi o n ( u p t o 1 9 5 wee ks)  ............................................................................... 4 7  
Fi g ure  6 -1.  
Se me n C ollecti o n Sc he ma  ...................................................................................................... 7 6  
 
 
 

Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  6  
 
0 9 Se pte m ber 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 ner al/ C o u ntr y -S pecific  
C S P Versi o n 1. 0  
3 1 -J a n-2 0 1 7  
I nitial C S P Versi o n 
Ge neral  
A me n d me nt # 1  
0 6 -J ul-2 0 1 7  
U p date a n d/ or clarificati o n of st u d y 
desi g n, eli gi bilit y criteria, st u d y 
pr oce d ures, st u d y dr u g 
disc o nti n uati o n c o nsi derati o ns, a n d 
statistical a nal ys es 
Ge neral  
A me n d me nt # 1. 1  
2 1 -Se p -2 0 1 7  
U p date of st u d y desi g n a n d 
clarificati o n of patie nt safet y 
i nf or mati o n 
C o u ntr y -s pecific ( v ol u nt ar y 
har m o nisati o n pr oce d ure c o u ntries)  
A me n d me nt # 1. 2  
1 5 -Oct -2 0 1 8  
I n cl usi o n of s per m ba n ki n g 
rei m b urse me nt la n g ua ge a n d 
details of ne w me dical m o nit or a n d 
st u d y direct or 
C o u ntr y -s pecific ( 
) 
A me n d me nt # 2  
2 2 -A u g -2 0 1 8  
E x pa nsi o n of st u d y p o p ulati o n t o 
i ncl u de s u bjects wit h Cr o h n’s 
disease  a n d u p d ate of eli gi bilit y 
criteria ( n ot e: t his a me n d me nt was 
n ot i m ple me nte d)  
Ge neral  
A me n d me nt # 3  
1 8 -J a n-2 0 1 9  
E x pa nsi o n of st u d y p o p ulati o n t o 
i ncl u de s u bjects wit h Cr o h n’s 
disease a nd u p d ate of eli gi bilit y 
criteria  
Ge neral  
C CI

Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  8  
 
0 9 Se pte m ber 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 6  (0 9 -Se p -2 0 2 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 ntific 
val i 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 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 S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8 ) 
Versi o n  5. 0,  2 7 -J u n-2 0 2 2  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 s pecif y t he dec o m missi o ni n g of t he D ata 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 S afet y M a 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 ble 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. 2  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 I n vesti gat or’s Br 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. 3. 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 S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  9  
 
0 9 Se pte m ber 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 R e vie w  Tea m as of t his a me n d me nt . T he i nter nal i n de pe n d e 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 nt er nal I n d e pe n d e nt Safet y Re vie w T ea m .  
A p plic a ble Secti o n : 8. 1 0  I nter nal I n d e pe n de nt S afet y Re vie w 
A n o ver vie w of t he c h a n ges i ntr o d uce d i n pre vi o us a me n d me nts ca n b e f o u n d i n t he se parat e 
pr ot oc ol a me n d me nt s u m mar y of c h a n ges d oc u me nt f or eac h a me n d me nt.  
 
 

Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  1 0  
 
0 9 Se pte m ber 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 Testic ul ar  Safet y of Fil g oti ni b i n A d ult  Males wit h 
M o deratel y t o Se verel y Acti ve I nfla m mat or y B o wel Disease 
I N D N u m ber: 
E u dr a C T 
N u m ber:  
Cli nic al 
Tri als. g o v 
I de ntifier: 
1 2 9 6 4 7  
2 0 1 7 ‑0 0 0 4 0 2 ‑3 8  
 
N C T 0 3 2 0 1 4 4 5  
St u d y Ce nters 
Pl a n ne d:  
A p pr o xi matel y 1 7 5 ce nters w orl d wi de  
M ai n 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 % decrease 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 % decrease 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 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 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 S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  1 1  
 
0 9 Se pte m ber 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 m o derat el y t o se v erel y acti ve i nfl a m mat or y b o wel 
disease (I B D) w h o ma y b e o n pr ot oc ol -s pecifie d t hera p y.  
U p t o 2 5 0 males bet wee n t he a ge 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 2 6 wee ks of fil g oti ni b 
2 0 0  m g or pla ce b o -t o-m atc h ( P T M) fil g oti ni b 2 0 0  m g o nce dail y.  
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 I B D 
(ie, ulcerati ve c olitis [ U C ] vers us Cr o h n’s disease [C D ]), b y c o n c 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 25  milli o n/ m L  
•  >  2 5  t o 5 0 milli o n/ m L 
•  >  5 0 milli o n/ m L  
St u d y Sc he m a  
 
 
 
C CI

Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  1 2  
 
0 9 Se pte m ber 2 0 2 2  
 
T here  are 5 disti nct p arts t o t he st u d y w hic h s u bjects ma y e nter 
de pe n di n g u p o n t he i n di vi d ual s u bject’s res p o nse of t he u n derl yi n g I B D 
t o assi g ne d tr eat me nt a n d/ or o bser ve d c ha n ges i n s e me n para meters. T he 
5 parts w hic h are des cri b e d i n t he f oll o wi n g s ecti o ns c o m prise of t he 
f oll o wi n g: 
1)  Part A ( Da y 1 t hr o u g h W ee k  1 3 St u d y Visit)  
2)  Part B ( After Wee k  1 3 t hr o u g h Wee k 2 6 St u d y Visit)  
3)  O pe n -La b el Fil g oti ni b P hase  
4)  M o nit ori n g P hase  
5)  L o n g T er m E xte nsi o n  
T he st u d y p arts are descri be d i n t he f oll o wi n g secti o ns.  
P art A ( D a y  1 t hr o u g h Wee k 1 3 St u d y Visit)   
(A p pe n di x  1 1  a n d Fi g ure  3 -2 ) 
I n Part A, all s u bjects will recei ve bli n de d st u d y dr u g f or t he first 
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, I B D res p o nse stat us (ie,  N o n -res p o n der vs 
Res p o n der, see Defi niti o n of Ter ms ) will be det er mi ne d base d o n t he 
partial Ma y o Cli nic Sc ore ( partial M C S) f or s u bjects wit h U C, or t he 
Cr o h n’s  Disease Acti vit y I n d e x ( C D AI) f or s u bjects wit h C D. I n 
a d diti o n, s per m para met ers (see Secti o n 6. 1 3  Se me n C ollecti o n 
Pr oce d ure ) will be e val u ate d t o deter mi ne w het her a n y of t he 
pre -s pecifie d decrease t hres h ol ds (see Defi niti o n of Ter ms ) ha v e bee n 
me t. 
•  S u bjects w h o are Res p o n ders a n d w h os e s per m para meters d o n ot 
meet a pre -s pecifie d decrease t hr es h ol d will c o nti n ue bli n de d st u d y 
dr u g i n Part B.  
•  S u bjects w h o are N o n -res p o n ders a n d w h ose s p er m para meters d o 
n ot meet a pre -s pecifie d decrease t hr es h ol d will disc o nti n ue bli n de d 
st u d y dr u g a n d c o m me nce o pe n-la bel ( O L) fil g oti ni b.  
•  S u bjects w h ose s per m para meters meet a pre -s pecifie d decrease 
t hres h ol d, re gar dless of I B D 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.  
 

Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  1 3  
 
0 9 Se pte m ber 2 0 2 2  
 
P art B ( After W ee k 1 3  t hr o u g h Wee k 2 6 St u d y Visit)  
(A p pe n di x  1 1  a n d Fi g ure  3 -3 ) 
I n Part B, all s u bjects will c o nti n ue bli n de d st u d y dr u g f or u p t o a n 
a d diti o nal 1 3  wee ks. S u bjects ma y e x perie nce Disease W orse ni n g 
(see D efi niti o n of Ter ms) of t heir u n derl yi n g I B D at a n y ti me d uri n g 
bli n de d st u d y dr u g  treat me nt (after Wee k 1 3 t hr o u g h Wee k 2 6). If 
Disease W orse ni n g is c o nfir me d, s per m para meters will be e val uate d t o 
deter mi ne  w het h er a pre -s pecifie d decrease t hr es h ol d has bee n met pri or 
t o a st u d y dr u g c ha n ge (c ha n gi n g fr o m bli n de d st u d y dr u g t o O L  
fil goti ni b). Base d u p o n t he s per m para meters at t his ti me p oi nt, s u bjects 
ma y f oll o w o n e of t he f oll o wi n g pat h w a ys:  
•  All s u bjects w h ose s per m para meters meet a pre -s pecifie d decrease 
t hres h ol d, re gar dless of I B D 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.  
•  S u bjects w h o e x perie nce Disease W orse ni n g after Wee k 1 3 a n d pri or 
t o W ee k 2 6, a n d w h ose s per m para meters d o n ot meet a pre-s pecifie d 
decrease t hr es h ol d will disc o nti n ue bli n de d st u d y dr u g a n d 
c o m me nce O L  fil g oti ni b.  
•  S u bjects w h o d o n ot e x perie nce Diseas e W orse ni n g, a n d are 
Res p o n ders at Wee k 2 6, a n d w h ose s per m para m eters d o n ot meet a 
pre -s pecifie d decrease t hres h ol d, will c o nti n ue bli n de d st u d y dr u g as 
part of t he L o n g T er m E xte nsi o n ( L T E).  
• S u bjects w h o d o n ot e x perie nce Diseas e W orse ni n g, b ut are 
N o n -res p o n d ers at Wee k 2 6, a n d w h ose s per m para meters d o n ot 
meet a pre -s pecifie d decrease t hr es h ol d, will disc o nti n ue bli n de d 
st u d y dr u g a n d c o m plete 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.  
O pe n -L a bel Fil g oti ni b P h ase ( O pe n -L a bel D a y  1 t hr o u g h 
O pe n -L a bel  Wee k 1 3 St u d y Visit)   
(A p pe n di x  1 1  a n d Fi g ure  3 -4 ) 
After e x p os ure t o 1 3 wee ks of O L  fil g oti ni b, t he s u bject’s I B D res p o nse 
stat us will be deter mi ne d a n d s per m para meters will be e val uate d t o 
deter mi ne w het h er a pre -s pecifie d decrease t hres h ol d has bee n met. 
S u bjects will be e val uate d d uri n g t his p hase as f oll o ws:  
•  All s u bjects w h ose s per m para meters meet a pre -s pecifie d decrease 
t hres h ol d, re gar dless of Res p o n der stat us, will disc o nti n ue O L  
fil g oti ni b, c o m plete 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, a n d e nt er t he M o nit ori n g P hase.  

Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  1 4  
 
0 9 Se pte m ber 2 0 2 2  
•  S u bjects w h o e x perie nce Disease W orse ni n g a n d w h ose s per m 
para meters d o n ot meet a pre -s pecifie d decrease t hres h ol d will 
disc o nti n ue O L  fil g oti ni b, c o m plete Earl y T er mi nati o n  (E T ) a n d 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 d o n ot e x perie nce Diseas e W orse ni n g, a n d are 
Res p o n ders at O L Wee k 1 3 after e x p os ure t o 1 3 wee ks of O L 
fil g oti ni b, a n d w h ose s per m para met ers d o n ot meet a pre-s pecifi e d 
decrease t hr es h ol d, ma y c o nti n ue recei vi n g O L fil g oti ni b as part of 
t he L T E. 
•  S u bjects w h o d o n ot e x perie nce Diseas e W orse ni n g, b ut are 
N o n -res p o n d ers aft er e x p os ure t o 1 3 wee ks of O L  fil g oti ni b, a n d 
w h ose s per m para meters d o n ot meet a pre -s pecifi e d decreas e 
t hres h ol d, will disc o nti n ue O L  fil g oti ni b a n d c o m plete 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.  
M o nit ori n g P h ase ( u p t o 5 2 wee ks ) (A p pe n di x  1 1  a n d Fi g ure  3 -5 .) 
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 fr o m t he 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 (see Defi niti o n  of  Ter ms ) is met, 
w hic he ver is ac hie ve d first. S u bjects will be offere d l ocall y a p pr o ve d 
sta n dar d of care (S O C) t hera p y d uri n g t he M o nit ori n g P hase.  
L o n g Ter m E xte nsi o n ( u p t o 1 9 5 wee ks )  
(A p pe n di x  1 1  a n d Fi g ure  3 -6 .) 
All s u bjects w h o e nter t h e L T E will u n der g o sc h e d ule d visits f or safet y 
assess me nts  e ver y 1 3 wee ks fr o m t he start of L T E, f or u p t o 1 9 5 wee ks , 
a n d se me n m o nit ori n g (e ver y 1 3 wee ks) u ntil t h e Wee k 1 3 pri mar y st u d y 
res ults are a nal yz e d. S u bjects will recei ve eit her O L  fil g oti ni b or bli n de d 
st u d y dr u g bas e d o n t he i n di vi d ual’s res p o nse criteria des cri be d a b o v e. If 
a s u bject e x perie nces Dis ease W orse ni n g d uri n g t he L T E, t he treat me nt 
(eit her O L  fil g oti ni b or bli n de d st u d y dr u g) will be disc o nti n ue d a n d t he 
s u bject will c o m plete a n E T visit, f oll o we d b y a s afet y f oll o w-u p visit 3 0 
da ys after l ast st u d y dr u g d ose.  
D at a M o nit ori n g C o m mittee ( D M C) /S p o ns or S afet y M a n a ge me nt 
Te a m ( S S M T)  
A n e xter nal, m u lti 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 ( det ails 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  6 , 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 6 , 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 d er of t he st u d y will c o nti n ue t o be 

Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  1 5  
 
0 9 Se pte m ber 2 0 2 2  
m o nit ore d b y t he S p o ns or me dical lea d er 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. 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.   
Ke y C o nc o mit a nt Me dic ati o n  C o nsi der ati o ns  
S u bjects ma y be treat e d wit h 5 -a mi n osalic ylic aci d ( 5 -A S A), 
c o n ve nti o nal i m m u n o m o d ulat ors, a n d/ or c ortic ost er oi d t hera p y, as 
defi ne d b y t he i ncl usi o n criteria. S u bjects are pr o hi bite d fr o m recei vi n g 
s ulfasalazi ne, be gi n ni n g 2 6 wee ks pri or to Scree ni n g u ntil t he e n d of 
st u d y, as defi ne d b y E x cl usi o n Criteria. 
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 f or 2 0 0 e val ua ble 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 m o deratel y t o 
se verel y acti ve I B D 
D urati o n of 
Treat me nt:  
T he d urati o n of tr eat me nt is a p pr o xi matel y u p t o 2 6 wee ks  of bli n de d 
st u d y dr u g, a n d u p t o 1 3 wee ks of O L  fil g oti ni b (if eli gi ble). 
S u bse q ue ntl y, f or t h ose s u bjects q ualif yi n g, t his will be f oll o we d b y an  
L T E lasti n g u p t o 1 9 5  wee k s. S u bjects w h ose s per m para meters meet a 
pre -s pecifie d decrease t hres h ol d at a n y ti me d uri n g t he st u d y will 
disc o nti n ue st u d y dr u g , a n d s h o ul d be ma na ge d wit h all o we d sta n dar d of 
care t h era p y. T h ese s u bjects will be f oll o we d i n t he M o nit ori n g P hase of 
t he st u d y, f or u p t o 5 2 weeks or u ntil Re versi bilit y 
(see D efi niti o n  of  Ter ms ) of all para m eters meeti n g s per m decreas e 
t hres h ol d is met, w hic 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 Criteri a  
•  Males bet wee n t he a ge 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 nse nt 
•  D oc u me nte d dia g n osis of U C or C D of at least 4  m o nt hs d urati o n. 
D oc u me ntati o n m us t i ncl u de e n d osc o pic a n d hist o pat h ol o gic 
d oc u me ntati o n of eit her U C or C D, as f oll o ws:  

Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  1 6  
 
0 9 Se pte m ber 2 0 2 2  
⎯ U C  
■ Me dical rec or d d oc u m e ntati o n of, or a n e n d osc o p y re p ort 
date d ≥ 4 m o nt hs bef ore ra n d o mizati o n, w hic h s h o ws feat ur es 
c o nsiste nt wit h U C, deter mi ne d b y t he pr o ce d ure p e rf or mi n g 
p h ysicia n, A N D  
■ Me dical rec or d d oc u m e ntati o n of, or a hist o pat h ol o g y re p ort 
i n dicati n g feat ures c o nsiste nt wit h U C as deter mi ne d b y t h e 
pat h ol o gist  
N ote : S u bjects als o nee d t o ha ve mi ni m u m disease e xte nt of 
1 5  c m fr o m t he a n al ver ge  
 
⎯ C D  
■ Me dical rec or d d oc u m e ntati o n of, or a n ile oc ol o n osc o p y 
(f ull c ol o n osc o p y wit h i nt u bati o n of ter mi nal ile u m) re p orte d 
date d ≥ 4 m o nt hs bef ore ra n d o mizati o n, w hic h s h o ws feat ur es 
c o nsiste nt wit h C D, deter mi ne d b y t he pr o ce d ure p erf or mi n g 
p h ysicia n, A N D  
■ Me dic al rec or d d oc u m e ntati o n of, or a hist o pat h ol o g y re p ort 
i n dicati n g feat ures c o nsiste nt wit h, C D as deter mi ne d b y t h e 
pat h ol o gist  
•  M o deratel y t o se verel y acti ve U C, or m o derat el y t o se verel y acti ve 
C D, assesse d l ocall y a n d defi ne d b y:  
⎯  U C  
■ Ma y o Cli nic Sc ore ( M C S; A p pe n di x  3 ) ≥ 6, P h ysicia n’s 
Gl o bal Assess me nt ( P G A) of 2 or 3, a n d e n d osc o pic s u bsc ore 
≥ 2, at Scree ni n g or i n t h e pri or 9 0  da ys  
⎯ C D  
■ C D AI t otal s c ore ( A p pe n di x  9 ) ≥ 2 2 0, A N D  
■ E vi de nce of acti ve i nfla m mati o n, wit h a t otal sc ore of ≥ 6  b y 
t he Si m ple E n d osc o pic Acti vit y Sc ore i n Cr o h n’s Disease 
( S E S-C D; A p pe n di x  1 0 ), O R  if disease is li mite d t o t he ile u m 
a n d/ or ri g ht c ol o n, a c o m bi ne d S E S -C D sc ore ≥ 4 i n t hese 
2  se g me nts, at Scree ni n g or i n t he pri or 9 0  da ys  
 

Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  1 7  
 
0 9 Se pte m ber 2 0 2 2  
 
•  Pre vi o usl y de m o nstrat e d a n i na de q uat e cli nical r es p o nse, l oss of 
res p o nse t o, or i nt olera n ce of at least 1 of t h e f oll o wi n g 5  cl asses of 
a ge nts, as i n di vi d uall y d efi ne d i n Secti o n 4. 2  I ncl usi o n Criteria, # 6 
⎯ C ortic oster oi ds  
⎯ Azat hi o pri ne, 6 -merca pt o p uri ne, or met h otre x ate  
⎯ T N F α a nta g o nists (i nfli xi ma b, a dali m u ma b, g oli m u ma b [ U C 
o nl y], or cert oliz u ma b [ C D o nl y])  
⎯ Ve d oliz u ma b  
⎯ Uste ki n u ma b ( C D o nl y)  
•  T he mea n of 2 s e parate s e me n sa m ples c ollecte d at t he Scree ni n g 
visit 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 4  a n d Fi g ure  6 -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 nc e ntr ati 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 xcl usi o n Criteri a  
•  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  
•  C urre nt use of s ulfasalazi ne or its use wit hi n t he 2 6  wee ks lea di n g u p 
t o 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 
•  C urre nt use of c ortic oster oi ds at a d osa ge of >  2 0  m g/ da y of 
pre d nis o ne or e q ui vale nt at ra n d o mizati o n  
•  Acti ve t u berc ul osis or u ntreate d late nt t u berc ul osis ( Secti o n  4. 2  
I n cl usi o n Criteria, # 1 2) 
I nfecti o n wit h acti ve He p atitis B, He patitis C, or HI V ( Secti o n 4. 3  
E x cl usi o n Criteria, # 3 1 -3 3)  
St u d y Pr oce d ures/  
Fre q u e 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 
P T M fil g oti ni b 2 0 0 m g o nce dail y, f or u p t o 2 6 w ee ks.  
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 a ssess 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 visits. 
S u bjects c o nti n ui n g o n bli n de d st u d y dr u g will ret ur n f or Wee k 2 0 a n d 

Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  1 8  
 
0 9 Se pte m ber 2 0 2 2  
Wee k  2 6 assess me nts, i ncl u di n g se me n s a m ple c ollecti o n d uri n g 
Wee k  2 6 visits. S u bjects w h o are N o n -res p o n ders at Wee k 1 3 or w h o 
s h o w Disease W orse ni n g bet wee n t he Wee k 1 3 a n d Wee k 2 6 St u d y 
Visits will s witc h t o O L fil g oti ni b . After starti n g O L fil g oti ni b, s u bjects 
will ret ur n f or st u d y assess me nts at O L Da y 1, O L Wee k 2, O L Wee k  4, 
O L Wee k 8, a n d O L  Wee k 1 3, i ncl u di n g a se me n sa m ple c ollecti o n at 
O L Wee k 1 3.  S u bjects c o nti n ui n g o n t o t he L T E will u n der g o sc h e d ule d 
visits f or safet y assess me nts a n d se me n sa m ple c ollecti o n, e ver y 
1 3  wee ks u p t o 1 9 5  wee ks.  
S u bjects w h o are Res p o n ders at  Wee k 2 6 or at O L Wee k 1 3 a n d c h o ose 
n ot t o c o nti n ue t o t he L T E, as well as s u bjects w h o disc o nti n ue st u d y 
partici pati o n f or a n y reas o n pri or t o Wee k 2 6, O L Wee k 1 3, reac hi n g 
Re versi bilit y or M o nit ori n g P hase Wee k 5 2 ( w hic he ver occ urs first), or 
L T E Wee k 1 9 5, will c o m plete a n E T visit i n a d diti o n t o a r o uti ne safet 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.  
 
S p arse P l as m a P K S a m ple C ollecti o n: 
I n Parts A a n d B, s parse plas ma P K sa m ples will be c ollecte d at least 
3 0  mi n utes p ost d ose at t he Wee k 2 visit, a n yti me at t he Wee k  4 visit, 
a n d pre d ose d uri n g visits at Wee ks  1 3 a n d 2 6. I n t he O L Fil g oti ni b 
P hase, s parse plas m a P K sa m ples will be c ollecte d at least 3 0 mi n utes 
p ost d ose at t he O L  Wee k  2 visit, a n yti me at t he O L Wee k 4 visit , a n d 
pre d ose d uri n g visits at O L Wee k 1 3.  
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 bjects 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 3 ):  
•  Scree ni n g ( Bas eli ne)  
•  After Part A ( Wee k 1 3 St u d y Visit)  
•  After Part B ( Wee k 2 6 St u d y Visit)  
O R  
F or S u bjects w h o e x perie nce c o nfir me d Diseas e W orse ni n g bet w ee n 
Wee ks 1 3 -2 6 i n Part B, pri or t o be gi n ni n g O L Fil g oti ni b P hase a n d 
at t he O L Wee k  1 3  St u d y Visit  
•  E ver y 1 3 wee ks d uri n g t he M o nit ori n g P hase (if a p plica ble)  
•  E ver y 1 3 wee ks d uri n g t he L T E  
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 ds; i nterc urre nt ill ness or d e h y drati o n at ti me of 

Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  1 9  
 
0 9 Se pte m ber 2 0 2 2  
c ollecti o n; i nc o m plete ca pt 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 ys. All decisi o n s of retesti n g a n y s e me n/s per m 
para meter (ie, o btai ni n g a t hir d  se me 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 he S p o ns or Me di cal M o nit or or desi g n ee 
bef ore t h e 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 fil g oti ni b 2 0 0  m g ta blet orall y o nce 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 i ncl usi o n criteria , a n d 
a d mi nistere d acc or di n g t o t he l ocal pr o d uct la b el.  
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 3 . 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 E s, cli nical 
la b orat or y e v al uati o ns ( h e mat ol o g y, c he mistr y a n d uri nal ysis), p h ysic al 
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 assess e d t hr o u g h o ut t he 
st u d y. 
P har mac o ki netics  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 %  decrease 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 basel i 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 will dis pla y 

Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  2 0  
 
0 9 Se pte m ber 2 0 2 2  
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 on 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 D A’s G ui da nce f or I n d ustr y: 
Testic ular t o xicit y: E v al uati o n D uri n g Dr u g De v el 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 per m c o nce ntrati o n fr o m baseli ne will be calc ul ate 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 nt s 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, 1 st q uartile [ Q 1], 
3 r 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 w ill 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 malities 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 ( Secti o 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 
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 n ce 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 r he u matic diseas es 
( G L P G 0 6 3 4-C L -2 2 7) wit h t he sa me o bjecti ve. T h e 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 trial d ata will be perf or me 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 ne d s u bset(s) of s u bjects, ha ve c o m plete d t he Wee k  1 3 a n d 
Wee k 2 6  ( or O L Wee k 1 3 ) 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 d ata f or all s u bjects w h o e ntere d 
t he M o nit ori n g P hase at t hese ti me p oi nts is a vaila 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 un bli n di n g. T he a nal yses will 

Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  2 1  
 
0 9 Se pte m ber 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 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 m s 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 treat me nt assi g n me nts u ntil t he fi nal a nal ysis w he n t he 
data base h as 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 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 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 S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  2 2  
 
0 9 Se pte m ber 2 0 2 2  
D E FI NI TI O N O F T E R M S  
Disease W orse ni n g  
F or s u bjects wit h U C, Disease W o rse ni n g is defi n e d b y a partial 
M C S after Wee k  1 3 c o nsisti n g of:  
a n i ncrease of ≥ 3 p oi nts t o at least 5 p oi nts fr o m t he Wee k  1 3 
val ue o n 2  c o nsec uti ve visits, O R  
a n i ncrease t o 9 p oi nts fr o m t he Wee k 1 3 val ue o n 2 c o nsec uti ve 
visits, if t he Wee k 1 3 val ue was > 6 p oi nts   
F or s u bjects wit h C D, Disease W orse ni n g is defi n e d b y a t otal 
C D AI s c ore after Wee k 1 3 c o nsisti n g of:  
a sc ore ≥ 2 2 0 o n 2 c o nsec uti ve visits, A N D  
a n i ncrease of ≥ 1 0 0 p oi nts fr o m t he Wee k 1 3 val u e o n 
2  c o nsec uti ve visits  
Disease W orse ni n g is c o nfir me d at t he ti me of t he sec o n d 
c o nsec uti ve visit.  
Ma y o Cli nic Sc ore 
( M C S) 
C o m p osite sc ore of U C acti vit y c o nsisti n g of s u b -sc ores fr o m 
e n d osc o p y, rectal bl ee di n g, st o ol fre q ue nc y, a n d P G A. S u bject 
recall f or t he last 2 4 h o urs will be use d f or t he pati e nt re p orte d 
c o m p o ne nts of t he c o m pl ete M C S.  
Partial Ma y o Cli nic 
Sc ore ( partial M C S)  
C o m p osite sc ore of U C acti vit y c o nsisti n g of s u b -sc ores fr o m 
rectal ble e din g, st o ol fre q ue nc y, a n d P G A. S u bject recall f or t he 
last 2 4 h o urs will be use d f or t he patie nt r e p orte d c o m p o ne nts of 
t he partial M C S. 
Cr o h n’s Disease A cti vit y 
I n d e x ( C D AI) 
C o m p osite sc ore of C D acti vit y c o nsisti n g of gastr oi ntesti nal  
s y m pt o ms (e g, a b d o mi nal pai n), si g ns (e g, a b d o mi nal mass), 
la b orat or y val u es (ie, he mat ocrit), a n d c o m plicati o ns 
(e g, art hritis/art hral gia), a m o n g ot her patie nt attri b utes.   
S u bject recall f or t he last 7 da ys will be use d f or t he patie nt 
re p orte d o utc o m e of t he C D AI. T he C D AI s c ore calc ulati o ns 
s h o ul d n ot be i ncl usi ve of da ys t hat i n v ol ve a n e n d osc o p y 
pr oce d ure or pre parati o n f or t hat pr oce d ure . 
Si m ple E n d osc o pic 
Acti vit y Sc ore i n 
Cr o h n’s Disease 
( S E S-C D)  
C o m p osite sc ore of m uc osal i nfla m mati o n i n C D c o nsisti n g of 
f o ur e n d osc o pi c varia bl es ( ulcer prese nce a n d size; l u mi nal s urface 
c o vere d b y ul cers; l u mi nal s urface wit h disease i n v ol ve me nt; a n d 
ste n osis prese nce a n d se v erit y). 

Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  2 3  
 
0 9 Se pte m ber 2 0 2 2  
M o nit ori n g P hase  
A s u bject w h o e x perie nces a ≥ 5 0 % decrease i n s per m 
c o nce ntr ati 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 o n st u d y dr u g will disc o nti n ue t he st u d y dr u g , c o m plete 
a r o uti ne safet y f oll o w u p visit 3 0 da ys ( ±  5  da ys) after t he l ast 
d ose of st u d y dr u g  a n d st art t he M o nit ori n g P has e. Se me n sa m ples 
will be c ollecte d e v er y 1 3 wee ks fr o m t he date of t he 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 first.  
Res p o n der  
F or U C, a s u bject w h o has a re d ucti o n of ≥ 2 i n partial Ma y o 
Cli nic Sc ore c o m pare d t o baseli ne at t he s pecifie d assess me nt ti me 
(A p pe n di x  2 ). 
F or C D, a s u bject w h o has a re d ucti o n of ≥ 1 0 0 p oi nts i n t otal 
C D AI s c ore c o m pare d t o baseli ne at t he s pecifie d  assess me nt ti me 
(A p pe n di x  2 ). A s u bject wit h a baseli ne t otal C D AI sc ore 
of  ≥ 2 2 0  t o ≤ 2 5 0 will be c o nsi dere d t o be a Res p o n der if a C D AI 
sc ore of <  1 5 0 is attai ne d at t he s pecifie d assess me nt ti me.  
N o n -res p o n d er 
F or U C or C D, a s u bj ect w h o d oes n ot f ulfill t he defi niti o n of 
Res p o n der at t he s pecifie d assess me nt ti me ( A p pe n di x  2 ).  
Pre -s pecifi e d decreas e 
t hres h ol d 
A ≥ 5 0 % decreas e i n s per m c o nce ntr ati 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. T h e mea n of val ues f or 
eac h of t h e s per m para m eters ( meas ure d fr o m 2 s e parat e se me n 
sa m ples) will be use d i n all a nal ys es. Sa m ples will be c ollecte d 
wit hi n a 1 4 -da y peri o 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 . 
Re versi bilit y  
Re versi bilit y is met w he n all s per m para m eter(s) q ualif yi n g t he 
s u bject 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 Baseli 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 (e g, Bas eli ne )]).   
Wee k 1 3  
T he Wee k 1 3 St u d y Visit  occ urs o nce a s u bject c o m pletes t he first 
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.   
Wee k 2 6  
T he Wee k 2 6 St u d y Visit occ urs o nce a s u bject c o m pletes t he 
sec o n d 1 3 wee ks of bli n d e d st u d y, 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.   
O L We e k 1 3  
T he O L Wee k 1 3 St u d y Visit occ urs o nce a s u bject c o m pletes t he 
first 1 3 wee ks of O L  fil g oti ni b, 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.   

Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  2 4  
 
0 9 Se pte m ber 2 0 2 2  
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 bjects 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 bl e s u bjects fr o m St u d y G S -U S -4 1 8 -4 2 7 9 c o m plete 
Wee k 2 6  ( or O L Wee k 1 3 ) or per ma n e ntl y dis c 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 bjects 
reac h Wee k 2 6 a n d all s u bjects wit h a ≥ 5 0 % decrease i n s per m 
c o nce ntr ati 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 
( or O L Wee k 1 3) e nter t h e 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 p ecifie 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 S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  2 5  
 
0 9 Se pte m ber 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  
5 -A S A  
5 -a mi n osalic ylate  
6 -M P  
6 -merca pt o p uri ne  
A b  
anti b o d y  
A E  
a d verse e ve nt  
A L T  
ala ni ne a mi n otra nsferase  
A N C O V A  
a nal ysis of c o varia nce  
A S T  
as partate a mi n otra nsferase  
A U C 0 -Ʈ  
area u n der t he plas ma dr u g c o nce ntrati o n -ti me c ur ve of a d osi n g i nter val 
B U N  
bl o o d urea nitr o ge n  
C Ʈ  
tr o u g h plas ma c o nce ntrati o n (j ust bef ore t he ne xt d osi n g ie, pre d ose sa m ple)  
C C & G  
C oc kcr oft -Ga ult  
C D  
Cr o h n’s disease  
C D AI  
Cr o h n’s Disease Acti vit y I n de x  
C E S  
car b o x ylesterases  
CI  
c o nfi de nce i nter val  
CI A  
c olla ge n -i n d uce d art hritis 
C ma x  
ma xi m u m o bser ve d plas ma c o nce ntrati o n  
C M V  
c yt 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 Researc h Or ga nizati o n  
C R P  
C -reacti ve pr otei n 
C S P  
cli nical st u d y pr ot oc ol  
C S R  
cli nical st u d y re p ort  
C T C A E  
C o m m o n T er mi n ol o g y Criteri a 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 oc hr o me P 4 5 0  
D B P  
diast olic bl o o d press ure  
D M C  
Data M o nit ori n g C o m mittee  
D N A  
de o x yri b o n ucleic aci d  
D S S  
de xtra n s ulfate s o di u m  
E.c oli  
Esc h eric hi a c oli  
E C G  
electr ocar di o gra m 
e C R F  
electr o nic case re p ort f or m  
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 C li nical T rials D ata b ase  

Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  2 6  
 
0 9 Se pte m ber 2 0 2 2  
F D A  
F o o d a n d Dr u g A d mi nistrati o n  
F S H  
follicle -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 B V  
he p atitis B vir us  
H C V  
he p atitis C vir us  
H D P E  
hi g h de nsit y p ol yet h yle ne  
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 G T  
hi g h -le vel gr o u p ter m 
H L T  
hi g h -le vel ter m 
H R  
heart rate 
I A1/ 2  
first/sec o n d u n bli n de d i nteri m a nal ysis 
I B 
In vesti gat or’s B r 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 nisati o n ( of T ec h nical Re q uire me nts f or 
P har mace uticals f or H u ma n Use)  
I E C 
i n de p e n de nt et hics c o m mittee 
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 vesti 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 V 
intra ve n o us  
I W R S 
i nteracti ve we b res p o nse s yste m 
J A K 
j a n us ki nase 
L A M  
lactati o nal a me n orr hea met h o d 
L D L  
l o w de nsit y li p o pr otei n 
L H  
l utei nizi n g h or m o ne 
L L T  
l o w le vel ter m 
L T E  
l o n g ter m e xte nsi o n 
M A C E  
maj or a d verse car di o vasc ular e ve nts  
M C S  
Ma y o Cli nic Sc ore  
M C V  
mea n c or p usc ular v ol u me  
Me d D R A  
Me dical Dicti o nar y f or Re g ul at or y Acti vities  
M T X  
m et h otre xate  

Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  2 7  
 
0 9 Se pte m ber 2 0 2 2  
N O E L  
n o -o bser ve d -effect -le vel 
N S AI Ds  
n o nster oi dal a nti -i nfla m mat or y dr u gs 
O & P  
o va & parasites  
O A Ts  
or ga nic a ni o n tra ns p orters  
O L  
o pe n la bel 
P -g p  
p -gl yc o pr otei n  
P D  
p har mac o d y na mic(s)  
P E G  
p ol yet h yle ne gl yc ol  
P G A  
P h ysicia n’s Gl o bal Assess me nt of disease acti vit y  
P K  
p har mac o ki netic(s)  
P T  
pr ot hr o m bi n ti me  
P T M  
place b o -t o-matc h  
P T T  
partial t hr o m b o plasti n ti me  
Q 1  
1st q uartile  
Q 3  
3r d q uartile  
R A  
r he u mat oi d art hritis 
R N A  
ri b o n ucleic aci d 
R R  
res pirat or y rate 
R T -P C R  
re verse tra nscri pti o n p ol y merase c hai n reacti o n 
S A D R  
seri o us a d verse dr u g reacti o ns 
S A E  
seri o us a d verse e ve nt 
S A P  
statistical a nal ysis pla n 
S B P  
s yst olic bl o o d press ure 
S D  
sta n dar d de viati o n 
S E S -C D  
Si m ple E n d osc o pic Sc ore f or Cr o h n’s Disease  
SI  
i nter nati o nal s yste m of u nits 
S O C  
sta n dar d of care 
S O P  
sta n dar d o perati n g pr oce d ure 
S S M T  
S p o ns or Safet y Ma na ge me nt T ea m  
S T A T  
si g nal tra ns d ucer a n d acti vat or of tra nscri 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 Es  
treat me nt e mer ge nt a d verse e ve nts 
T N F α  
t u m or necr osis fact or al p ha 
T Y K  
t yr osi ne ki nase 
U C  
ulcerati ve c olitis  
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  
vs.  
v ers us  

Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  2 8  
 
0 9 Se pte m ber 2 0 2 2  
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 S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  2 9  
 
0 9 Se pte m ber 2 0 2 2  
1.  
I N T R O D U C TI O N 
1. 1.  
B ac k gr o u n d  
I nfla m mat or y b o wel disease (I B D) c o m prises 2 disti nct pat h ol o gic e ntities, ulcerati ve c olitis 
( U C) a n d Cr o h n’s diseas e ( C D). 
1. 1. 1.  
Ulcer ati ve C olitis  
U C is a c hr o nic, i nter mitte nt, rela psi n g diseas e c haracterize d b y i nfla m mati o n of t he c ol o nic 
m uc osa, w hic h is li mite d t o t he c ol o n a n d rect u m. T he disease c haracteristicall y c o m me nces i n 
t he rect u m a n d ma y e xte n d pr o xi mall y i n a n u ni nt err u pte d patter n i nt o t he c ol o n. It ca n i n v ol ve 
t he e ntire c ol o n ( p a n-c olitis), t he left c ol o n, or is olate d rect o -si g m oi d dise ase, wit h patie nts bei n g 
e q uall y distri b ute d i n t h ose 3 p he n ot y pes. I n t he U nite d States ( U S), t he pre vale nce of U C has 
bee n esti mate d t o be 2 3 8 per 1 0 0, 0 0 0 a d ults { Ka p pel ma n 2 0 0 7 } , w hereas E ur o pe has t he hi g hest 
re p orte d pre vale n ce at 5 0 5  per  1 0 0, 0 0 0 pers o ns f or U C . T he a n n u al i nci de nce of U C is 2 4. 3  per 
1 0 0, 0 0 0  pers o n -years i n E ur o p e a n d 6. 3 p er 1 0 0, 0 0 0  pers o n -years i n Asia { M ol o dec k y 2 0 1 2 } . 
T he i nci de nce a n d pre val e nce of U C a p pear t o be i nc reasi n g o v er ti me gl o ball y.  
T he hall mar k s y m pt o ms of U C are bl o o d y diarr hea, rect al ur ge n c y, a n d te nes m us. T he cli nical 
c o urse te n ds t o w a x a n d wa ne wit h peri o ds of re missi o n i nters perse d wit h peri o ds of acti ve 
disease. U C ma y als o be ass ociate d wit h e xtr a-i ntesti nal ma nifestati o ns i ncl u di n g oc ular lesi o ns, 
s ki n lesi o ns, art hritis, a n d pri mar y scler osi n g c h ol a n gitis. T he e x act pat h o p h ysi ol o g y is n ot 
k n o w n b ut i n ge n eral, ge netic pre dis p ositi o n i n c o nj u ncti o n wit h e n vir o n me ntal a n d s ocial 
fact ors (s u c h as hist or y of t o bacc o us e, me dicati o n hist or y, a n d ge o gra p h y) ma y i m pact 
de vel o p me nt of diseas e. Disc o or di nate d acti vit y of b ot h i n nate a n d a d a pti ve i m m u ne res p o nses 
i n c o m bi nati o n wit h e pit helial barrier defects a n d d ys bi osis lea d t o a n i nfla m mat or y casca de, 
res ulti n g i n cli nical si g ns a n d s y m pt o ms of U C { U n gar o 2 0 1 6 } .   
I n a d diti o n t o a b d o mi nal pai n a n d rectal blee di n g t hat b ot h i m pact acti vities of dail y li vi n g a n d 
q ualit y of life f or patie nts wit h U C, t he disease carries a n i ncrease d ris k of c ol orectal 
ca ncer{ U n gar o 2 0 1 6 } . Wit h p o orl y c o ntr olle d disease, t he rate of d e vel o pi n g c ol or ectal ca ncer 
i ncreas es wit h ti me. T he i nci de nce of c ol orectal ca ncer i n U C p atie nts is decreasi n g o ver ti me, 
partiall y d u e t o better c o ntr ol of i nfla m mati o n a n d c ol o n osc o pic s ur veilla nce { Bea u gerie 2 0 1 5 } . 
O v erall, U C patie nts still e x perie nce a n ele vat e d ris k of c ol orect al ca n cer; i n o ne meta -a n al ysis 
of p o p ulati o n base d c o h orts t he ris k was 2. 4 -f ol d { J ess 2 0 1 2} . T h us, U C re prese nts a seri o us, 
life-t hreat e ni n g dis ease f or w hic h ne w t h era pies are nee d e d t o i nterr u pt t he i nfla m mat or y pr ocess 
t o pre ve nt disease pr o gressi o n, rest ore q ualit y of life, a n d re d uce t he ris k of c ol orectal ca ncer.  
Treat me nt of U C is de p e n de nt o n t he se verit y a n d t he l ocati o n of disease. G oals of treat me nt 
i ncl u de i m pr o ve d q ualit y of life, re d u cti o n i n l o n g-ter m c ortic oster oi d use, a n d mi ni mizati o n of 
ca ncer ris k. Mil d t o m o derate distal c olitis ma y be treate d wit h oral a mi n osalic yl ates, t o pical 
mesala mi ne, or t o pical st er oi ds { K or n bl ut h 2 0 1 0 } . F or m o derate diseas e, oral c ortic oster oi ds a n d 
i m m u n o m o d ulat ors s uc h as azat hi o pri ne a n d 6-merca pt o p uri ne ( 6 -M P) ma y be utilize d { Da nese 
2 0 1 1 } . F or m ore m o d erat e t o se vere disease, p atie nts are c o m m o nl y treat e d wit h a t u m or 

Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  3 0  
 
0 9 Se pte m ber 2 0 2 2  
necr osis fact or  al p ha ( T N F α) a nta g o nist i nf usi o n or i njecti o n, s uc h as i nfli xi ma b ( Re mica de ® ), 
a dali m u ma b ( H u mira ® ), or g oli m u mab ( Si m p o ni ® ). Ve d oliz u ma b ( E nt y vi o® ), a n i njecta ble 
i nte gri n α 4 β 7 m o n o cl o nal a nti b o d y, a n d t of aciti ni b ( Xelja nz® ), a J a n us ki nase (J A K) 
1/ 3  i n hi bit or, are i n dicate d f or a d ults wit h m o derat el y t o se v erel y acti ve U C. Uste ki n u ma b 
( Stelara® , C N T O 1 2 7 5; a n i nterleu ki n (I L) -1 2 a n d I L -2 3 m o n ocl o nal a nti b o d y), u pa daciti ni b 
(J A K i n hi bit or), etr oliz u ma b ( P R O 1 4 5 2 2 3; m o n ocl o nal a nti b o d y t ar geti n g t he β 7 s u b u nit of t he 
heter o di meric i nte gri ns α 4 β 7 a n d α E β 7), risa n kiz u ma b (I L -2 3 a nti b o d y) a n d oza ni m o d 
( R P C 1 0 6 3; selecti ve S 1 P 1 a n d S 1 P 5 rece pt or a g o nist) are c urre ntl y bei n g t este d i n P hase  3 
cli nical trials. Le u k oc yta p heresis t hera p y ma y be use d i n J a pa n { F u k u na ga 2 0 1 2 } . Des pite 
se veral classes of treat me nt o pti o ns f or patie nts wit h U C, t here re mai ns a n u n met me dical nee d, 
partic ularl y i n t he treat me nt of m o derat el y t o se v erel y acti ve dise ase. A ge nts wit h n o vel 
mec ha nis ms of acti o n t hat tar get t he i nfla m mat or y casca d e, wit h oral d osi n g a n d acce pta ble 
i m m u n o m o d ulat or y a n d he mat ol o gic effects, re m ai n t he m ost pr o misi n g o pti o n t o a d dress t hese 
u n met nee ds.  
1. 1. 2.  
Cr o h n’s Dise ase  
C D is a f or m of I B D ca use d b y i nfl a m mati o n of t he l u mi nal s urface of t he gast r oi ntesti nal tract 
t hat, i n c o ntrast t o U C, ca n e xte n d t hr o u g h t he f ull t hic k ness of t he gastr oi ntesti nal wall t o t he 
ser osal s urface. A n y se g me nt of t he gastr oi ntesti nal tract ma y be affecte d, a n d disc o nti n u o us 
re gi o ns of i n v ol ve me nt ma y o cc ur. C D is c h aract erize d b y p h e n ot y p e (i nfl a m mat or y, stri ct uri n g, 
or pe netr ati n g s u bt y pes) a n d b y l o cati o n a n d e xte nt of i n v ol ve me nt. T he i nci de nce a n d 
pre vale n ce of C D h a ve b ee n i ncreasi n g, wit h bi m o dal pea ks affecti n g y o u n g a d ults 
( 1 5 t o 3 5  years of a ge) a n d ol der a d ul ts a ge d 5 0 t o 7 0 years. T he o verall i nci de nce of C D i n t he 
N ort her n H e mis p here ra n ges fr o m 7 t o 2 0 per 1 0 0, 0 0 0 pers o n years, wit h E ur o pe ha vi n g t he 
hi g hest r e p orte d pre vale n ce at 3 2 2  per  1 0 0, 0 0 0 pers o ns.  I n t he U S a n d E ur o pe, u p t o 1. 5 milli o n 
i n di vi d uals ma y be affect e d, a n d C D i nci de nce is risi n g i n parts of Asia a n d t he Mi d dle  East 
{ M ol o dec k y 2 0 1 2 } . 
C D is a rela psi n g a n d re mitti n g dis or der c haracteri ze d b y diarr hea, a b d o mi nal pai n, wei g ht l oss, 
a n d t he passa ge of bl o o d or m uc us per rect u m. Strict ure f or m ati o n ca n res ult i n i ntesti nal 
o bstr ucti o n re q uiri n g s ur gic al ma na ge me nt. O ver ti me, patie nts wit h re peat e d s ur geries are at 
ris k f or de vel o pi n g s h ort b o wel s y n dr o me a n d/ or i ntesti nal fail ure. Pe netr ati n g diseas e is 
c haracteriz e d b y fist ula f or mati o n ( b o wel t o b o wel, b o wel t o s ki n, or b o wel t o a djace nt or ga n 
s uc h as bla d der or va gi na) t hat ma y als o re q uir e s ur gical ma na ge me nt. Pe netrati n g dise ase ca n 
ma nifest wit h i ntra -a b d o mi nal a bscess, a c o n diti o n w hic h ca n b e life t hreat e ni n g if n ot treate d 
earl y wit h s yste mic a nti bi otics. C D ma y affect ot her or ga n s yste ms lea di n g t o ras hes, j oi nt pai n 
a n d stiff ness, fe v er, a n d wei g ht l oss { Ba u m gart 2 0 1 2 } . T he ca us e of C D is p o orl y u n d erst o o d, 
h o we ver a c o m ple x i nter pla y of ge net ic pre dis p ositi o n, a berra nt i m m u ne acti vati o n, a n d earl y 
i nfecti o n d uri n g c hil d h o o d ma y b e i n v ol ve d. T he i m p orta nce of e n vir o n me ntal tri g gers is 
s u g geste d b y i n creasi n g i nci de nce s ee n d uri n g i n d ustrializati o n a n d wit h i m pr o ve d d o mestic 
h y gie n e a n d sa nitati o n. T his “ h y gie n e h y p ot hesis” has als o bee n i m plicate d i n vari o us ot her 
a ut oi m m u ne dis or ders { Ve nt ha m 2 0 1 3 } . 

Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  3 1  
 
0 9 Se pte m ber 2 0 2 2  
T o assess disease s e verit y i n C D, a n u m ber of cli nical sc ori n g s yste ms are utilize d. T he C D AI is 
a o ne s uc h sc ori n g t o ol wit h sc ores ra n gi n g fr o m 0 t o o ver 6 0 0 base d u p o n a c o m p osite of 
s y m pt o ms (e g, a b d o mi nal pai n), si g ns (e g, a b d o mi nal mass), la b orat or y v al ues (ie, he mat o crit), 
a n d c o m plicati o ns (e g, art hritis/art hral gia), a m o n g ot her patie nt attri b utes. I n t his sc ori n g s yste m, 
patie nts wit h a sc ore > 2 2 0 are defi ne d as h a vi n g  m o deratel y t o se verel y acti ve disease; t hese 
patie nts c o m prise t he p o p ulati o n wit h t he greatest u n met me dical nee d. T h e C D AI ca n als o be 
use d t o deter mi ne h o w well a t hera p y is w or ki n g, wit h t hera pe utic re missi o n defi ne d as a C D AI 
of < 1 5 0 p oi nts { Di g n ass 2 0 1 0 } . 
T he Si m ple E n d osc o pic Sc ore f or Cr o h n’s Diseas e ( S E S -C D) was first v ali date d i n 2 0 0 4 a n d has 
bee n use d e xte nsi vel y i n cli nical trials. It m eas ures prese nce a n d size of ulcers, pr o p orti o n of 
s urface affect e d wit h ulcers, pr o p orti o n of s urface affecte d b y ot her l esi o ns, a n d t he pres e nce a n d 
se verit y of ste n otic lesi o ns { Da per n o 2 0 0 4 } . T h e b o wel is di vi de d i nt o se g me nts (ile u m, ri g ht 
c ol o n, tra ns vers e c ol o n, l eft c ol o n, a n d rect u m) a n d eac h se g m e nt is sc ore d i n di vi d uall y, t h e n t he 
se g me nt s c ores are s u m me d f or a t otal sc ore (ra n ge: 0 t o 6 0).  
O ver t he last deca d e, t hera pe utic g oals f or C D ha v e be g u n t o e xte n d be y o n d s y m pt o matic c o ntr ol 
a n d t o i ncl u de l o n g -ter m m uc osal a n d e n d osc o pi c re missi o n { C heifetz 2 0 1 3 }  i n or der t o sl o w 
d o w n or halt disease pr o gressi o n, a v oi di n g s ur geries a n d h os pitalizati o ns. Ris k assess me nt a n d 
pre dicti o n b y m ea ns of c o m ple x cli nical, bi oc he mical, a n d e n d osc o pi c mar kers ha ve b ec o me t h e 
ke y t o p atie nt ma na ge me nt, t hera p y o pti mizati o n, a n d pre dicti o n of t he t h era pe utic o utc o me a n d 
si de effects. C urre ntl y a vaila ble bi ol o gic t hera pies f or C D f oc us o n n e utrali zi n g c yt o ki n e acti vit y 
or alteri n g T -cell differe ntiati o n a n d h o mi n g. T hree m o n ocl o nal a nti b o dies w hic h i n hi bit t u m or 
necr osis fact or  al p ha ( T N F α), are c urre ntl y m ar ket e d f or t he treat me nt of C D: i nfli xi ma b 
( Re mica de® ), a d ali m u ma b ( H u mira®  [a p pr o ve d i n U S a n d E ur o pea n U ni o n { E U } ]), a n d 
cert oliz u ma b pe g ol ( Ci mzia ®  [a p pr o ve d i n U S]). Ve d oliz u ma b ( E nti v y o® ), a m o n ocl o nal 
a nti b o d y a gai nst α 4β 7 i nte gri n is als o a p pr o ve d f or m o deratel y t o se verel y acti ve C D. Rece ntl y, 
uste ki n u ma b ( Stelara ® ), a m o n ocl o nal a nti b o d y directe d a gai nst t he p 4 0 s u b u nit of I L-2 3 a n d a n 
a nta g o nist f or b ot h I L-1 2 a n d I L -2 3 si g nali n g, has bee n a p pr o ve d f or t he treat me nt of C D. 
Le u k o c yta p heresis t hera p y ma y b e use d i n J a pa n { F u k u na ga 2 0 1 2 } . Ot her i n vesti gati o nal 
treat me nt a p pr o ac hes i n cl u de t he a d mi nistrati o n of c yt o ki n es t o sti m ulate i n nate i m m u nit y, t he 
use of pre bi otics t o alter t he g ut fl ora, a n d bl o c ki n g t he I L -6 si g nali n g pat h wa y { It o 2 0 0 4, 
K orze ni k 2 0 1 6 } . Ne w treat me nts bei n g test e d i n cli nical trials i ncl u de J A K i n hi bit ors 
(e g, u pa daciti ni b), a n d ne w bi ol o gic a ge nts s uc h as I L -2 3 p 1 9 a nta g o nists (e g, risa n kiz u ma b) a n d 
a m o n ocl o nal a nti b o d y directe d a gai nst β 7 i nte gri n (e g, etr oliz u ma b). W hile t he i ntr o d ucti o n of 
bi ol o gic t hera pies has si g nifica ntl y i m pr o ve d res p o nse rates i n patie nts wit h m o deratel y t o 
se verel y acti ve C D, l o n g-ter m or d ura ble re missi o n rates are still l o w at a p pr o xi matel y 2 0 %. 
Ma n y p atie nts recei vi n g bi ol o gic t hera pies de v el o p ne utralizi n g a nti b o dies wit h res ulti n g l oss of 
effic ac y. T hes e a ge nts ma y b e ass oci ate d wit h s pecific safet y iss ues i n cl u di n g b ut n ot li mite d t o 
a na p h yla xis, i ncrease d ris k of i nfecti o n i ncl u di n g pr o gressi ve m ultif ocal le u k oe nce p h al o pat h y, 
a n d li ver i nj ur y. Safe a n d effecti ve treat me nt o pti o ns w hic h ma y be c o n v e nie ntl y a d mi nistere d i n 
a c hr o nic s etti n g w o ul d pr o vi de a si g nifica nt treat me nt a d va nce f or p atie nts wit h m o deratel y t o 
se verel y acti ve C D. 

Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  3 2  
 
0 9 Se pte m ber 2 0 2 2  
1. 2.  
Fil g oti ni b  ( G S-6 0 3 4)  
1. 2. 1.  
Ge ner al I nf or m ati o n  
J a n us ki nases (J A Ks) are i ntracell ular c yt o plas mic t yr osi ne ki nas es ( 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 si g nal tra ns d u cer a n d acti vat or of 
tra nscri pti o n ( 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 mator 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 s ets 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 nfl a m mat or y c o n diti o ns i ncl u di n g r he u m at oi d art hritis ( R A) a n d C D. Fil g oti 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 has 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.  
Precli nic al P h ar m ac ol o g y a n d T o xic 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 pote 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 nici t 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 ncli nical P har mac 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 I C5 0 val ues of ≥ 1 7 9  n M, a n d 
de m o nstrates 3 0 -f ol d sel ecti 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 s electi ve f or J A K 1; o nl y 2. 5 % of ki nases were 
i n hi bite d ≥ 5 0 % at 5 0-f ol d hi g her c o nce ntrati o n t h a n I C5 0 f or J A K 1. Br oa d rece pt or pr ofili n g 
( ~ 7 0 rece pt ors, i o n c ha n n els, tra ns p orters a n d e nzy mes) di d n ot re veal a n y off -tar get lia bilities of 
t he c o m p o u n d. Fil g oti ni b de m o nstrate d hi g h p ote nc y i n t he rat c olla ge n-i n d uce d art hritis ( CI A) 
m o del as well as i n t he m o use de xtra n s ulfate s o di u m ( D S S) -i n d uce d c olitis m o del, t he latter of 
w hic h is detai le d bel o w. T he maj or h u ma n meta b olite of fil g oti ni b G S-8 2 9 8 4 5 e x hi bits a si milar 
J A K 1 selecti vit y pr ofile b ut is a p pr o xi matel y 1 0-f ol d less p ote nt as c o m pare d t o pare nt fil g oti ni b 
i n vitr o. 
T he effi cac y of fil g oti ni b was e val uat e d i n a pr o p h yl actic setti n g  of t he c hr o nic m o use D S S 
m o del i n t w o se parate st u dies. B ot h st u dies e val uat e d oral d ose le v els of 1 0 a n d 3 0  m g/ k g o nce 
dail y. I n a d diti o n t o assess me nts of cli nical sc ore ( disease acti vit y i n de x [ D AI] a n d c ol o n lesi o n 
sc ore), s er u m mar kers of i nfla m mati on, i m m u n o hist oc he mical a nal ysis, a n d e x pressi o n of 
vari o us c he m o ki nes a n d c yt o ki nes k n o w n t o be altere d i n C D a n d U C patie nts were als o 
e val uate d i n t he distal c ol o n of t hese mice.  

Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  3 3  
 
0 9 Se pte m ber 2 0 2 2  
I n b ot h st u dies, t he D AI sc ore, w hic h t a kes i nt o acc o u nt b o d y wei g ht l oss, rectal blee di n g, a n d 
st o ol c o nsiste nc y, w as re d uce d b y fil g oti ni b i n a d ose-de pe n d e nt ma n ner, de m o nstrati n g t hat 
fil g oti ni b pr otecte d mic e a gai nst c olitis i n d uce d b y D S S. Hist ol o g y of t he c ol o n re veale d a 
fil g oti ni b-me diate d d ose -relate d re d ucti o n i n c ol o n lesi o n sc ore, c orrelati n g wit h re d ucti o ns i n 
D AI sc ore.  
A d diti o nal e n d p oi nts e val uate d acr oss t he D S S c olitis m o del st u dies c o nfir me d t he s u p pressi o n 
of vari o us i nfla m mat or y mar kers i ncl u di n g ser u m le vels of C -reacti ve pr ot ei n ( C R P) a n d 
m yel o per o xi dase ( M P O) a n d e x pressi o n of I L -6 a n d T N F α ( b y R T -P C R) b y fil g oti ni b. 
I m m u n o hist oc he mical a n al ysis of t he c ol o n c o nfir me d i n hi biti o n of t he J A K-S T A T pat h wa y b y 
fil g oti ni b as e vi de n ce d b y a re d ucti o n of D S S-i n d uce d S T A T 3 p h os p h or yl ati o n. 
1. 2. 2. 2.  
Safet y P h ar mac ol o g y  
Fil g ot i 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 -relate d ge ne [ h E R G] a n d d o g tele m etr y st u dies), a p art fr o m a sli g ht 
n o n -a d vers e i ncrease i n h eart rate a n d arterial press 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 s er 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 nce dail y 
fil g oti ni b. T here were n o rele va 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 pirat or y s yste m a n d ce ntral n er v o us s yste m ( C N S). 
1. 2. 2. 3.  
Ke y N o ncli nical Distri b uti o n, Meta b olis m, a n d E xcreti o n Data  
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 dicat es s o me 
affi nit y f or mela ni n -c o nt ai ni 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 secret i o n of a b o ut 1 5 %. I n t h e d o g, fecal e xcreti 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 diate 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).  

Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  3 4  
 
0 9 Se pte m ber 2 0 2 2  
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. 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 ( IC 5 0: 6 7 µ M). T he cli nical rel e va 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 v al uate d. M A T E 1 was als o w ea 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-g p.  
1. 2. 2. 4.  
N o ncli nical T o xic 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 ( A U C) at t he 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 h e 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 39 -wee k t ar get e d e x p os ure t o xicit y st u d y, res pecti vel y.  
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 g htl 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 C D. 
A d mi nistrati o n of fil g oti ni b di d n ot affect  fe 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 nic al Tri als 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.  

Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  3 5  
 
0 9 Se pte m ber 2 0 2 2  
1. 2. 3. 1.  
P hase 2 S t u d y i n Cr o h n’s Disease ( G L P G 0 6 3 4-C L -2 1 1, FI T Z R O Y)  
A P hase 2, ra n d o mize d, d o u ble -bli n d, place b o -c o ntr olle d, m ultice nte r st u d y wit h fil g oti ni b was 
perf or me d i n s u bje cts wit h acti ve C D wit h e vi de nce of m uc osal ulcerati o n { Ver meir e 2 0 1 7 } . I n 
Part 1, a t otal of 1 7 4 s u bjects were ra n d o mize d ( 3: 1) t o recei ve eit her fil g oti ni b 2 0 0 m g o nce 
dail y or plac e b o f or 1 0 w ee ks. Base d o n t heir cli nical res p o nse i n Part 1, s u bjects i n Part  2 eit her 
c o nti n ue d t heir c urre nt treat me nt or were reassi g n e d t o a differe nt treat me nt f or a n a d diti o nal 
1 0  wee ks.  
T he effi cac y of fil g oti ni b was assesse d b y e val uati n g cli nical  re missi o n ( defi ne d as C D AI 
sc ore <  1 5 0), cli nical r es p o nse ( defi ne d as a d ecrease i n C D AI of at least 1 0 0 p oi nts fr o m 
baseli ne), a n d e n d osc o pi c res p o nse ( defi ne d as a decrease of at least 5 0 % fr o m baseli ne i n t he 
S E S -C D sc ore).  
T he pri mar y e n d p oi nt of t he  st u d y w as met: at Wee k 1 0, 6 0 of 1 2 8 s u bjects ( 4 6. 9 %) w h o 
recei v e d fil g oti ni b ac hie v e d cli nical re missi o n vers us 1 0 of 4 4 s u bjects ( 2 2. 7 %) w h o recei ve d 
place b o, a differe nce of 2 4. 1 % ( p -val ue = 0. 0 0 7 7). Fil g oti ni b treat me nt w as ass ociate d wit h 
i ncreas es in t he pr o p orti o n of s u bjects wit h cli nical re missi o n, cli nical res p o nse, a n d e n d osc o pi c 
res p o nse c o m p are d wit h place b o. 
O verall, t he safet y pr ofil e of fil g oti ni b i n C D s u bjects was c o nsiste nt wit h pri or st u dies.  
F or a d diti o nal details a b o ut t he effic ac y a n d s afet y of fil g oti ni b i n C D, refere nce is ma de t o t he 
I B. 
1. 2. 3. 2.  
P hase 2 b/ 3 S t u dies i n Ulcerati ve C olitis ( G S-U S -4 1 8 -3 8 9 8, S E L E C TI O N)  
T hese are P hase 2 b/ 3, d o u ble -bli n d, ra n d o mize d, place b o -c o ntr olle d st u dies e val uati n g t h e 
effic ac y a n d s afet y of fil g oti ni b i n t he i n d ucti o n a n d mai nte na nce of re missi o n i n s u bjects wit h 
m o deratel y t o se verel y acti ve U C. Pr ot oc ol G S -U S -4 1 8 -3 8 9 8  c o nsists of i n d ucti o n a n d 
mai nte na nce st u dies, e nr olli n g bi ol o gic-n aï ve a n d bi ol o gic -e x perie n ce d s u bjects. T he pri mar y 
e n d p oi nt of t he i n d ucti o n st u d y f or eac h c o h ort is t he effi cac y of fil g oti ni b c o m pare d t o place b o 
i n esta blis hi n g e n d osc o p y/ blee di n g/st o ol re missi o n at Wee k 1 0. T he pri mar y e n d p oi nt of t he 
mai nte na nce st u d y f or eac h c o h ort is t he efficac y of fil g oti ni b at esta blis hi n g 
e n d osco p y/ blee di n g/st o ol re missi o n at Wee k 5 8.  
I n M a y 2 0 1 8, a n i n de p e n de nt Data M o nit ori n g C o m mittee (D M C ) c o n d uct e d a n i nteri m f utilit y 
a nal ysis after 3 5 0  s u bjects ha d c o m plete d t he i n d u cti o n st u dies. T he D M C rec o m me n de d t hat t he 
trial pr ocee d as pla n ne d. 
1. 3.  
R ati o n ale f or t his St u d y a n d Pr o p ose d I B D P o p ul ati o n  
O ver t he last deca d e, c ha n ges i n I B D treat me nt strate gies, acc o m pa nie 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, h a ve greatl y i m pr o ve d t he 
o utc o mes f or s u bjects wit h I B D. Des pite t hese de vel o p me nts, t hera pe utic c halle n ges re mai n. A 
s u bset of patie nts res p o n d t o c urre ntl y a v aila ble bi ol o gic t hera p y w hile ot h ers l ose res p o ns e o ver 

Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  3 6  
 
0 9 Se pte m ber 2 0 2 2  
ti me or are i nt olera nt o ver ti me. T here is a n u n m et 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 b ei n g s afe 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 n ase d ysreg ulate d i n s u bjects wit h i nfla m mat or y 
dis or ders i ncl u di n g I B D. Fil g oti ni b has de m o nstrat e d a fa v ora ble s afet y a n d t olera bilit y pr ofile i n 
a P hase 2 st u d y i n s u bje cts wit h m o deratel y t o se v erel y acti ve C D, w here it was efficaci o us at 
i n d uci n g cli nic al re missi o n at 1 0 wee ks ( Secti o n 1. 2. 3. 1 ). Fil g oti ni b is prese ntl y bei n g e v al uate d 
i n P hase 3 st u dies i n C D, U C, a n d R A. Fil g oti ni b is als o bei n g e val uated i n ps oriatic art hritis, 
a n k yl osi n g s p o n d ylitis, Sj ö gre ns s y n dr o me, c uta ne o us l u p us er yt he mat os 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 m o deratel y t o se verel y acti ve U C or C D, 
t he prese nt st u d y see ks t o e val uate t he i m pact, if a n y, of fil g oti ni b o n s per mat o ge n esis 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 gical c ha n ges i n testes a n d e pi di d y mi des, 
t o get her wit h re d u cti o ns i n s per m c o u nts a n d re d u ce d fertilit y i n t he rat. A mec ha nistic st u d y i n 
t he rat s u g geste d a re v ersi 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 nce 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. 6 7 μ g•h/ m L i n s u bjects 
wit h C D, w hic h re prese nts a n e x p os ure mar gi n of 2. 5, 1. 9, a n d 3. 6 -f ol d w h e n c o nsi deri 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, res pecti vel y. T he prese nt 
st u d y see ks t o assess t he i m pact o n me n of fil g oti ni b at 2 0 0 m g, t he hi g hest pr o p ose d d ose i n t he 
P hase  3 pr o gra m, assesse d b y t he pr o p orti o n of 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 fr o m Baseli ne w h e n c o m pare d wit h place b o after 1 3 -wee ks of t hera p y . T h e 
pr o p ose d st u d y d esi g n a n d s u bject p o p ulati o n f or G S -U S -4 1 8 -4 2 7 9 ha ve b ee 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 ul ati o ns wit h I B D 
a n d ot her c hr o nic i nfla m mat or y dise ases ot her t h a n I B D.   
T he prese nt st u d y ( Gilea d St u d y C o d e G S-U S -4 1 8 -4 2 7 9; Gala pa g os St u d y C o de: 
G L P G 0 6 3 4 -C L -2 2 8 ) has bee n desi g ne d i n acc or da nce wit h F D A’s G ui da n ce f or I n d ustr y: 
Testic ular t o xicit y: E v al uati o n D uri n g Dr u g De v el o p me nt ( Oct o ber 2 0 1 8)  a n d has als o bee n 
g ui de d b y C H M P Scie ntific A d vice E M E A/ H/ S A/ 2 3 8 0/ 1/ F U/ 2/ 2 0 1 6/III, 0 1 A pril 2 0 1 6) a n d 
i n p ut recei ve d b ase d o n disc ussi o ns wit h F D A a n d re g ulat ors i n t he E U. T h e st u d y p o p ulati o n 
will c o nsist of  s u bjects wit h eit her m o deratel y t o s e verel y acti ve U C ( defi n e d as a Ma y o Cli nic 
Sc ore of ≥ 6, wit h e n d osc o pic s u bsc ore ≥ 2 a n d P h ysicia n’s Gl o bal Assess me nt ≥ 2) or 
m o deratel y t o se verel y acti ve C D ( defi ne d as a C D AI sc ore of ≥ 2 2 0 a n d S E S -C D of 
≥ 6  [ or ≥ 4  i n cases of C D li mite d t o t he ile u m a n d/ or ri g ht c ol o n]). S u bjects m ust ha ve 
de m o nstrate d a pri or treat me nt fail ure/i nt olera nce t o U C or C D t hera p y, res pecti vel y 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 ulfasalazi ne w hi c 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 macia & U pj o h n C o 2 0 1 4 } . 
S u bjects will be stratifie d b y bas eli ne s per m c o n ce ntrati o n a n d t y p e of u n derl yi n g I B D 
(ie, U C  vers us C D) . I n a d diti o n, s u bjects will als o be stratifie d b y use of m et h otre x ate 
( M T X; yes or n o) gi ve n its p ote ntial i m pact o n s per mat o ge nesis. T here ha v e bee n case 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 oriasis 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 

Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  3 7  
 
0 9 Se pte m ber 2 0 2 2  
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 
i ncreasi 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 m al, gi ve n t he e x pecte d 
i nci de nce of h y p o g o n a dis m i n t he u p per 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 ale f or t he O utc o me Me as ures  
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{ U. S. De part me nt of Healt h a n d H u ma n Ser vices ( D H H S) 
2 0 1 8 } . S per m c o nce ntr ati o n ma y als o be c o nsi dere d t he m ost i m p orta nt para meter of testic ular 
d ysf u n cti o n { Si k ka 2 0 1 6 } . T he prese 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 b aseli 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 draft g ui da nce. Si g nifica nt variati o ns i n s per m para meters 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 dere d t he a p pr o pri ate t hres h ol d t o acc o u nt f or n or mal varia bilit y 
a n d is c o nsiste 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 { Hellstr o m 
2 0 0 8 , Hellstr o m 2 0 0 3 , J ar vi 2 0 0 8, Si k ka 2 0 1 4 } . S u bsta ntial i ntra- a n d i nter - s u bject variati o n ca 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 u es; in o ne c o h ort, 
s per m c o u nts ra n ge d o ver a n or der of ma g nit u de i n a si n gle h ealt h y  patie 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 s a 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 ve 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 n u m ber are 
mar ke dl y re d u ce d d uri n g peri o ds of hi g h ejac ul ati o n fre q ue n c y { Ol derei d 1 9 8 4 } . Si g nifica nt 
varia bilit y is n ote d e v e n i n healt h y s u bjects { W orl d Healt h O r ga nizati o n ( W H O) 1 9 9 9, W orl d 
Healt h Or ga niz ati o n ( W H O) 2 0 1 0 } . A d diti o nal s per m para meters at 1 3 w ee ks will be e val u ate d 
as sec o n dar y e n d p oi nts i n ali g n me nt wit h t he F D A g ui d a n ce.  
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 
m o deratel y t o se verel y acti ve U C or C D. E n d p oi nts at 2 6 wee ks of t hera p y ha ve bee n c h ose n f or 
sec o n dar y a nal yses t o ass ess i m pact after 2 f ull s per mat o genesis c ycles i n acc or da n ce wit h dr aft 
g ui da n ce, w hic h rec o m m e n ds treat me nt f or 2 6 wee ks f or dr u gs t hat are c hr o nicall 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 h e i m pact of l o n ger -ter m t hera p y o n se m e n 
para 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 he prese nt st u d y, t otal m otilit y, w hic h is c o nsi d ere d t o be m ore c o nsiste ntl y meas ure d acr oss 
o bser vers, will r e mai n as a sec o n dar y e n d p oi nt.   
I n t his st u d y t he Ma y o Cli nic Sc ore ( M C S) will be utilize d t o defi ne m o deratel y t o se v erel y 
acti ve U C f or t he p ur p os e of eli gi bilit y. T he mi ni m u m M C S of 6 (i ncl u di n g e n d os c o pic a n d 
p h ysicia n gl o bal assess me nt sc ores of 2 or 3) e ns ures t hat s u bjects will ha ve e n d o sc o pic e vi de nce 
of disease (i e, acti ve dise ase), ha v e acti ve s y m pt o ms (e g, bl o o d i n t he st o ol or i ncrease d st o ol 

Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  3 8  
 
0 9 Se pte m ber 2 0 2 2  
fre q ue n c y), a n d b e deter mi ne d b y t he pr o vi d er t o ha ve m o deratel y t o se verel y acti ve U C. Aft er 
ra n d o mizati o n, t he partial M C S will be utilize d to deter mi ne Res p o n der, N o n -res p o n der, a n d 
Disease W orse ni n g stat us f or s u bjects wit h U C.  
T he C D AI sc ore a n d S E S -C D will be j oi ntl y use d t o defi ne m o deratel y t o se verel y acti ve C D, 
e ns uri n g t h at s u bjects wit h C D will ha ve acti ve s y m pt o ms of t he c orres p o n di n g se verit y as well 
as e n d osc o pic e vi de nce of acti ve dise ase f or eli gi bilit y. After ra n d o mizati o n, t he C D AI sc ore 
will be use d t o deter mi ne Res p o n der, N o n -res p o n der, a n d Disease W orse ni n g stat us f or s u bj ects 
wit h C D.  
T his st u d y is base d u p o n real -w orl d o u t patie nt cli nical practice, w here ce ntr al e n d osc o p y d oes 
n ot pla y a r ole i n i nitiati o n of t hera p y, a n d w here cli nical 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 d er’s assess me nt are a d e q u ate t o assess t hera pe utic res p o nse or 
n o n -res p o nse. T his a p pro ac h has bee n e n d orse d b y t he T or o nt o C o nse ns us i n 2 0 1 5 { Bressler 
2 0 1 5 } . Safet y a n d t olera bilit y will be assesse d b y t he e val uati o n of a d v erse e ve nts ( A Es), 
selecte d cli nic al la b orat or y p ara m eters, vital si g ns, p h ysical e x a mi nati o ns, a n d E C Gs all of 
w hic h are st a n dar d s afet 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 m or p h ol o g y will be f oll o we d 
f or o ne or m ore s per m at o ge n esis c ycles, u p t o 1 year as nee de d, t o ass ess f or s per m para meter 
re versi bilit y. 
1. 3. 2.  
R ati o n ale f or t he C h oice of D ose a n d D osi n g I nter 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 hes t 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 . I n P hase 2 trials i n R A, p o ole d data wit h a n 
e x p os ure-res p o nse a nal ysis de m o nstrate d a d ose-de pe n de nt i ncreas e i n efficac y u p t o 2 0 0  m g 
t otal dail y d ose. I n t h e P hase 2 st u d y of C D, s u bjects treate d i n t he 2 0 0  m g ar m s h o we d fa v ora ble 
res p o nse a n d re missi o n rates ( 4 7 % re missi o n o ver 2 3 % place b o a n d 5 9 % res p o nse o ver 4 1 % 
place b o). T h ese res ults are c o nsiste nt wit h t he relati o ns hi p o bser ve d bet wee n fil g oti ni b 
e x p os ures a n d i n hi biti o n of p S T A T 1 acti vati o n (e x -vi v o) f oll o wi n g si n gle a n d m ulti ple fil g oti ni b 
d oses, w here ma xi mal i n hi biti o n of p S T A T 1 acti vati o n ( ~ 7 8 %) was ac hie ve d at or a b o v e 2 0 0  m g 
t otal dail y d ose a n d i nter me diate i n hi biti o n ( ~ 4 7 %) at 1 0 0 m g { Na m o ur 2 0 1 5 } . p S T A T 1 data, i n 
c o nj u ncti o n wit h c o nsi derati o ns ar o u n d t he mar gi n f or n o ncli nical testic ular fi n di n gs, s u g gests 
assessi n g d os es a b o ve 2 0 0  m g is n ot i n dicate d.  
1. 4.  
Ris k/ Be nefit Assess me nt f or t he St u d y  
I nfla m mat or y b o wel diseases are pr o gressi ve a n d p ote ntiall y life-t hr eate ni n g dis or ders wit h fe w 
treat me nt o pti o ns, ma n y of w hic h res ult i n pri mar y or sec o n dar y n o nres p o nse. I nfla m mat or y 
b o wel disease ma y l ea d t o i ncreas e d ris k of gastr oi ntesti nal mali g na ncies, i m pair me nt i n q ualit y 
of life, a n d ulti mate nee d f or life -alteri n g s ur ger y. C urre nt treat me nt o pti o ns are li mite d i n t heir 
a bilit y t o esta blis h m uc osal heali n g a n d cli nical re missi o n a n d ha ve si g nifica nt safet y a n d 
effic ac y li mitati o ns; f or e x a m ple, bi ol o gics ha ve si g nifica nt i m m u n o ge ni c ris ks, a n d ster oi ds are 
ass ociate d wit h i ncrease d m or bi dit y a n d m ortalit y. Re missi o n rates are ge nerall y l o w w he n 
c o m pare d t o place b o rates acr oss m ost t hera pies f or I B D. T here re m ai ns s u bsta ntial u n met nee d 

Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  3 9  
 
0 9 Se pte m ber 2 0 2 2  
i n I B D, partic ularl y i n m o derate t o se v ere dis ease. T he lifel o n g nat ure of I B D i ncreases t h e 
pr o ba bilit y t hat s u bjects ha ve c ycl e d t hr o u g h vari o us t hera pies, lea vi n g fe w a p pr o ve d o pti o ns.  
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 ut 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 
re d ucti o n i n fertilit y i n m ale rats. T he d o g was deter 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 mar 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 C D. 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 C F w herei n ris k 
la 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 ot e ntial ris 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 ures ass ociat e d wit h a 2 0 0 m g o nce dail y d ose 
i n C D s u bjects. As a res ult, hi g hly effecti ve c o ntr ace pti o n a n d male c o n d o ms will be re q uire d f or 
male s u bjects wit h fe mal e part ners 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 n hi 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 u b erc ul osis ( T B), a n d s u bjects 
wit h acti ve or u ntreate d l ate nt i nfecti o ns will be e x cl u de d. Mali g na nc y h as bee n re p orte d i n 
s u bjects o n fil g oti ni b; i n t he prese nt trial, s u bjects will be re q uire d t o ha ve u p t o date c ol orectal 
ca ncer s ur veilla n ce i n a cc or da nce wit h l ocal g ui d eli nes, a n d s u bjects wit h rece nt mali g na n cies 
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 n cies, pleas e refere nce t h e I B.  
T he p ote ntial be 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 a n d m uc osal 
a n d e n d osc o pic h eali n g. J A K i n hi biti o n ma y be efficaci o us i n t he treat me nt of I B D base d o n 
res ults fr o m t he P hase 2 st u d y ( FI T Z R O Y) of s u bjects wit h C D. I n FI T Z R O Y, a n i ncrease i n 
mea n he m o gl o bi n c o nce ntrati o n was o bser v e d, wit h o ut differe nce bet wee n fil g oti ni b a n d 
place b o. N o cli nicall y si g nifica nt c ha n ges fr o m baseli ne i n mea n ne utr o p hil c o u nts or li ver 
f u ncti o n tests were o bs er ve d at 1 0 wee ks. Fil g oti ni b treate d s u bjects s h o we d a n i ncrease i n hi g h 
de nsit y li p o pr otei ns ( H D L) a n d n o si g nifica nt c ha n ge i n l o w de nsit y li p o pr otei ns ( L D L). Li pi d 
a n d he m o gl o bi n effects r e prese nt p ote ntial b e nefits i n t his p o p ulati o n . 

Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  4 0  
 
0 9 Se pte m ber 2 0 2 2  
O verall cli nical fi n di n gs a n d la b orat or y c ha n ges re p orte 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 data t he e x pecte d be nefit 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 ociat e d ris ks. I n a dditi 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 n e 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 ysicia n ma y e val uate t he be nefit-ris k pr ofile of 
fil g oti ni b. A lac k of res p o nse c o nti n ge nc 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 
N o n -res p o n d ers at W ee k 1 3 a n d a n y s u bject w h o e x perie nces Diseas e W orse ni n g t hereafter, will 
e na ble earl y access t o acti ve dr u g or sta n dar d of care tr eat me nt w he n cli nicall y i n dicate d. T his 
resc ue a p pr oac h, t he pr o visi o n of best s u p p orti ve care, a n d t he 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 bl e f or t he s p ecifie d d urati o n.    
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 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 6, 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 6, t he D M C will be 
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 Ma na ge me nt Tea 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 ata 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 a P hase 2 cli nical trial i n C D, as well as t he be ne fici al 
fi n di n gs i n n o ncli nical m o dels of disease a n d t he o verall safet y, t olera bilit y, a n d P K 
c haracteristics 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 v el o p me nt as a treat me nt f or U C a n d C D. T he o verall be nefit -ris k bal a nce 
of t his st u d y is c o nsi dere d fa v ora bl e.  
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 nce  
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.  

Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  4 1  
 
0 9 Se pte m ber 2 0 2 2  
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 b as 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 b aseli 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 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 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  
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 ulatin 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 haracteriz e 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  
)  
C CI

Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  4 2  
 
0 9 Se pte m ber 2 0 2 2  
3.  
S T U D Y D E SI G N  
T his i s 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 
m o deratel y t o se verel y acti ve U C , or m o derat el y t o se verel y acti ve C D , w h o ma y b e o n 
pr ot oc ol -s pecifi e d c o nc o mita nt t hera p y.  
U p t o 2 5 0  males bet wee n t he a ge of 2 1 a n d 6 5 ye ars (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 u p t o 2 6 wee ks of fil g oti ni b 2 0 0 m g or place b o -t o-m atc h ( P T M ) fil g oti ni b 
2 0 0  m g o nce dail y, t o e ns ure a p pr o xi matel y 2 0 0 s u bjects are e val ua ble.  
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 I B D (ie, U C vers us C D), b y c o nc urre nt 
use of M T X ( yes or n o), a n d b y s p er m c o n ce ntrati 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 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 m o de ratel y t o se verel y acti ve I B D w h o pr o vi d e writte n i nf or me d c o nse nt will 
be scree ne d t o det er 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 h e Scree ni n g p eri o d will be u p t o 4 5 da ys , a n d ma y be e xte n de d i n 
c o ns ultati o n wit h t he  m e dical m o ni t or. 
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.  

Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  4 3  
 
0 9 Se pte m ber 2 0 2 2  
Fi g ure  3 -1 . 
St u d y Sc he m a  
 
T here are 5 disti nct parts t o t he st u d y w hic h s u bjects ma y e nter de p e n di n g u p o n t he i n di vi d ual 
res p o nse of t he u n d erl yi n g I B D t o assi g ne d treat m e nt a n d/ or o bser ve d c ha n ges i n se m e n 
para meters. T he 5 p arts w hic h are d escri b e d i n t he f oll o wi n g s ecti o ns c o m prise of t he f oll o wi n g:  
1)  Part A ( Da y 1 t hr o u g h W ee k 1 3 St u d y Visit ) 
2)  Part B ( After Wee k 1 3 t hr o u g h Wee k 2 6 St u d y Visit ) 
3)  O pe n -La b el Fil g oti ni b P hase  
4)  M o nit ori n g P hase  
5)  L o n g T er m E xte nsi o n  
T he st u d y p arts are descri be d i n t he f oll o wi n g secti o ns.  
S u bjects will visit t he cli nical st u d y ce nter t o b e e val uate d f or cli nical a n d l a b orat or y assess me nts 
at Scree ni n g, D a y 1, Wee k 2, Wee k 4, Wee k 8, a n d Wee k  1 3 , i ncl u di n g seme n sa m ple c ollecti o n 
d uri n g  Wee k 1 3  visits . S u bjects w h o c o nti n ue o n bli n de d treat me nt after t h e first 1 3 wee ks of 
treat me nt will ret ur n f or Wee k 2 0 a n d Wee k 2 6 assess me nts , i ncl u di n g se m e n sa m ple c ollecti o n 
d uri n g  Wee k 2 6  visits . 

Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  4 6  
 
0 9 Se pte m ber 2 0 2 2  
As a b o ve, after t he first 1 3 wee ks of e x p os ure t o bli n de d st u d y dr u g t h ose s u bjects w h o are 
dee me d N o n -res p o n d ers at W ee k 1 3 or t h ose w h o meet Disease W orse ni n g criteria after 
Wee k  1 3 a n d pri or t o Wee k  2 6 ma y q ualif y f or e ntr y i nt o t he O L Fil g oti ni b P hase a n d ret ur n f or 
st u d y assess me nts at O L Da y 1, O L Wee k 2, O L Wee k 4, O L Wee k 8, a n d O L  Wee k  1 3. After 
e x p os ure t o 1 3  wee ks of O L  fil g oti ni b i n t he O L  Fil g oti ni b  P hase , t he s u bject’s I B D res p o ns e 
stat us will a gai n be d eter mi ne d usi n g t he partial M C S (i n t he case of U C) or C D AI sc ore (i n t he 
case of C D), a n d s per m para meters will be e val u ate d t o deter mi ne w het her a pre -s p ecifie d 
de crease t hr es h ol d has bee n met:  
•  All s u bjects w h ose s per m para meters meet a pre -s pecifie d decrease t hr es h ol d, re gar dless of 
Res p o n der stat us, will disc o nti n ue O L  fil g oti ni b, c o m plete 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,  a n d e nter t he M o nit ori n g P hase.  
•  S u bjects w h o e x perie nce Disease W orse ni n g d uri n g O L  fil g oti ni b treat me nt a n d w h ose 
s per m para m eters d o n ot meet a pre-s pecifie d decrease t hr es h ol d will disc o nti n ue O L  
fil g oti ni b, c o m plete E arl y T er mi nati o n (E T ) a n d a safet y f oll o w -u p vis it 3 0 da ys after l ast 
st u d y dr u g d ose.  
•  S u bjects w h o d o n ot e x perie nce Diseas e W orse ni n g, a n d are R es p o n ders at O L Wee k 1 3 
after e x p os ure t o 1 3  wee ks of O L  fil g oti ni b, a n d w h ose s per m para meters d o n ot meet a 
pre -s pecifie d decrease t hres h ol d, will c o nti n ue recei vi n g O L  fil g oti ni b as p art of t he L T E.  
•  S u bjects w h o d o n ot e x perie nce Diseas e W orse ni n g, b ut are N o n-res p o n ders after e x p os ure 
t o 1 3 wee ks of O L  fil g oti ni b, a n d w h ose s per m p ara meters d o n ot meet a pre-s pecifi e d 
decrease t hr es h ol d, will disc o nti n ue O L  fil g oti ni b a n d c o m plete a s afet 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.  
Fi g ure  3 -5 . 
M o nit ori n g P h ase ( u p t o 5 2 wee ks)  
 
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 
fr o m t he 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 v e d first. S u bjects will be offere d l ocall y a p pr o ve d S O C t hera p y d uri n g t he 
M o nit ori n g P hase . 

Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  4 8  
 
0 9 Se pte m ber 2 0 2 2  
•  E ver y 1 3 wee ks d uri n g t he M o nit ori n g P hase (if a p plica ble)  
•  E ver y 1 3 wee ks d uri n g t he L T E  
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 -assessa 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 ds; 
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 sa m ple;  
a n d/ or sa m ple pr ocessi n g or se me n a n al ysis t hat d e viates fr o m sta n d ar 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 ulati o n free p eri o d of ≥ 4 8 h o urs a n d ≤ 7 da ys . All decisi o n s of  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 me 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 he S p o ns or Me dical M o nit or or desi g nee  bef ore t he retest . 
3. 1.  
St u d y Tre at me nts  
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  ( wit hi n strata) t o recei ve fil g oti ni b 2 0 0 m g 
o nce dail y or P T M fil g oti ni b 2 0 0  m g o nce d ail y.  
3. 2.  
D ur ati o n of Tre at me nt  
T he d urati o n of tr eat me nt is a p pr o xi matel y u p t o 2 6 wee ks of bli n de d st u d y dr u g a n d u p t o 
1 3  wee ks of O L  fil g oti ni b (if eli gi ble). S u bse q ue ntl y, f or s u bjects q ualif yi n g, t his will be 
f oll o we d b y an  L T E lasti n g u p t o  1 9 5  wee k s. S u bjects w h ose s per m para meters meet a 
pre -s pecifie d decrease t hres h ol d at a n y ti me d uri n g t he st u d y will disc o nti n ue st u d y dr u g a n d 
s h o ul d be ma na ge d wit h all o we d sta n dar d of care t hera p y. T hes e s u bjects will be f oll o we d i n t he 
M o nit ori n g P hase of t he st u d y, f or u p t o 5 2 w ee ks or u ntil Re versi bilit y 
(see D efi niti o n  of  Ter ms ) of all para m eters meeti n g s per m decreas e t hres h ol d is met, w hic he ver 
is ac hie ve d first .  
3. 3.  
Criteri a f or I nterr u pti o n or Disc o nti n u ati o n of St u d y Tre at me nt  
3. 3. 1.  
St u d y Dr u g I nterr u pti o n C o nsi der ati o ns  
T he m e dical m o nit or or d esi g nee s h o ul d be 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 he f oll o wi n g cir c 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 o r 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 m e dical m o nit or or desi g n ee.    
•  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 di a g n ostic testi n g a p pr o priate f or a n i m m u n oc 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. 

Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  4 9  
 
0 9 Se pte m ber 2 0 2 2  
•  
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 . 
⎯ 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, i nterr 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 m e dical 
m o nit or or desi g n ee 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 bject s are t o c o nti n ue wit h St u d y Visit  partici pati o n  
a n 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 m e di cal m o nit or or desi g nee . 
T he me dical m o nit or s h o ul d c o ns ult t he me dical lea der as nee de d.  
3. 3. 2.  
St u d y Dr u g Disc o nti n u ati o n C o nsi der ati o ns  
T he m e dical m o nit or or d esi g nee s h o ul d 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.  
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 nfecti o n  
•  A n y s eri o us i nfecti o n t hat re q uires a nti micr o bial t hera p y or h os pitalizati o n, or a n y i nfecti o n 
t hat meets seri o us a d vers e 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, 00 0/ m m 3 

Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  5 0  
 
0 9 Se pte m ber 2 0 2 2  
•  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 nfe cti 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 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 B V 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  
•  A n y t hr o m b o e m b olic e ve nt t ha t meets S A E re p orti n g criteria 
•  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 ( base d o n t h e mea n of 2 se p arat e se me n s a m ples c ollecte d 
at t he Scree ni n g visit ) 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  
•  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  m ay 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 m e dical m o nit or or desi g n ee  
•  W orse ni n g of U C or C D re q uiri n g i nte nsificati o n of t hera p y b e y o n d w hat is all o we d i n t he 
pr ot oc ol or re q uiri n g t he use of a pr o hi bite d me dicati o n  
•  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 ntrall y re p orte d e q ui vale nt 
assa y] T B test a n d 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 dr u g.  
•  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 (refer t o g ui deli nes detaile d i n A p pe n di x  8 ):   
⎯ 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 plat elets/ m m 3)  

Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  5 1  
 
0 9 Se pte m ber 2 0 2 2  
⎯ 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 niti al A S T or A L T ele v ati o n > 3 x t he U L N, at t h e 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 bli n de d st u d y dr u g d ue t o N o n -res p o ns e at Wee k 1 3 or Diseas e 
W orse ni n g aft er Wee k 1 3  t hr o u g h Wee k 2 6,  will be offere d O L  2 0 0 m g o n ce dail y fil g oti ni b, 
a n d t h ose s u bjects s h o ul d be e nc o ura ge d t o c o nti n ue o n st u d y, if d ee me d m e dicall y a p pr o priate 
b y t he i n vesti gat or . S u bje cts w h o per ma n e ntl y st o p st u d y dr u g d ue t o  meeti n g a  pre -s p ecifie d 
dec rease t hr es h ol d i n s per m para met ers ( Secti o n 3. 4 ) will be offere d l ocall y a p pr o ve d sta n d ar d of 
care t h era p y as part of t h e M o nit ori n g P hase . 
S u bject s wit h dra wi n g fr o m t he st u d y s h o ul d c o m plete a n E T visit, f oll o we d b y a s afet y 
f oll o w-u p visit 3 0  da ys after last 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 eff 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 occ ur, t hat ma k es f urt her 
treat me nt of s u bjects i m p ossi ble. I n t his e ve nt, the 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. 
T he me dical m o nit or s h o ul d c o ns ult t he me dical lea der as nee de d.  
3. 4.  
Dise ase W orse ni n g Crit eri a  
S u bjects meeti n g t he f oll o wi n g Disease W orse ni n g criteria , e val uate d after Wee k  1 3  t hr o u g h 
Wee k 2 6 , m ust be disc o nti n ue d fr o m bli n de d treat me nt. T hese s u bjects will be offere d t he o pti o n 
t o c o m me nce O L  fil g oti ni b 2 0 0 m g o nce d ail y , as l o n g as t he y h a ve n ot e x perie nce d a decrease 
of ≥ 5 0 %  fr o m bas eli ne 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 o n c o nfir mati o n of Disease W orse ni n g a n d b ef ore s witc hi n g t o t he O L  Fil g oti ni b P hase, 
2  se me n sa m ples will be c ollecte d. Disease W orse ni n g is c o nfir me d at t he ti me of t he sec o n d 
c o nsec uti ve visit . If t he s ec o n d Diseas e W orse ni n g visit occ urs d uri n g t h e 1 4 -da y se me n 

Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  5 2  
 
0 9 Se pte m ber 2 0 2 2  
c ollecti o n wi n d o w f or t h e Wee k 1 3 or Wee k 2 6 St u d y Visit , t he r o uti ne Wee k 1 3 or Wee k  2 6 
se me n c ollecti o n will s uffice.  
Disease W orse ni n g assess me nts will be dri ve n b y t he patie nt hist or y, p h ysi cal a n d la b orat or y 
e x a mi nati o ns a n d are bas e d o n t he f oll o wi n g criteria:  
F or s u bjects wit h U C, Disease W orse ni n g is defi n e d b y a partial M C S after Wee k  1 3 c o nsisti n g 
of:  
•  A n i ncreas e of ≥ 3 p oi nts t o at least 5 p oi nts fr o m t he Wee k 1 3 val ue o n 2 c o nsec uti ve visits, 
O R  
•  A n i ncreas e t o 9 p oi nts fr o m t he Wee k 1 3 val ue o n 2 c o nsec uti ve visits, if t he Wee k  1 3 val ue 
was > 6 p oi nts   
F or s u bjects wit h C D, Disease W orse ni n g is defi n e d b y a t otal C D AI sc ore after Wee k  1 3 
c o nsisti n g of:  
•  A sc ore ≥ 2 2 0 o n 2 c o nsec uti ve vis its, A N D 
•  A n i ncreas e of ≥ 1 0 0 p oi nts fr o m t he Wee k 1 3 val ue o n 2  c o nsec uti ve visits  
F or all s u bjects , Disease W orse ni n g is f urt her defi ne d b y:  
•  Disease W orse ni n g t o t he e xte nt t hat t he s u bject re q uires me dicati o ns pr o hi bite d b y t he st u d y 
(at i n vesti gat or’s discreti o n, wit h disc ussi o n wit h t he m e dical m o nit or or d esi g nee if 
feasi ble); t hes e s u bjects d o n ot q ualif y t o r ecei v e O L  fil g oti ni b 2 0 0 m g o n ce dail y. 
Disease W orse ni n g visits ma y i ncl u d e U nsc he d ul e d Visits (e g, a St u d y Visit  f oll o we d b y a n 
U nsc he d ule d Visit , or 2 s e q ue ntial U nsc he d ul e d Visits after Wee k  1 3).  
In t he L T E , s u bjects w h o meet Disease W orse ni n g criteria ( p er a b o ve criteri a) , or ha v e Diseas e 
W orse ni n g per i n vesti gat or j u d g me nt , s h o ul d be disc o nti n ue d fr o m st u d y dr u g. T h ese s u bjects 
s h o ul d c o m plete a n E T  visit ( w hic h i ncl u de s se me n c ollecti o n), f oll o we d b y a r o uti ne safet y 
f oll o w-u p visit 3 0  da ys after t he last d ose of st u d y dr u g.  
3. 5.  
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 s u bject c o m plete s t he L T E Wee k 1 9 5 visit, or w he n t he 
last s u bject c o m pletes his  last visit, w hic he ver is s o o ner. 
3. 6.  
P ost -St u d y C are  
U p o n c o m pleti o n of st u d y partici pati o n, t he 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. 

Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  5 3  
 
0 9 Se pte m ber 2 0 2 2  
4.  
S U B J E C T P O P U L A TI O N  
4. 1.  
N u m ber of S u bjects a n d S u b ject Selecti o n 
U p t o 2 5 0 s u bjects wit h m o deratel y t o se verel y acti ve U C or C D will be e nr olle d i n t he st u d y t o 
e ns ure a p pr o xi matel y 2 0 0 s u bjects are e val ua ble at Wee k  1 3 . E nr oll me nt will be e val uate d 
d uri n g t he c o urse of t he st u d y, a n d ma y b e e x pa n d e d if t he dr o p o ut rat e is hi g her t h a n e x pecte d.  
4. 2.  
I ncl usi o n Criteri 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 willi 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 nf or me d c o nse nt f or m (I C F), m ust f ull y u n dersta n d t he 
re q uire me nts of t h e st u d y, a n d m ust be willi n g t o c o m pl y wit h all st u d y visits an 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 s bet wee n t he a ge 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  
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 d e nce of mal n utriti o n as 
deter mi ne d b y t he i n vesti gat or  
4)  D oc u me nte d dia g n osis of U C or C D of at least 4 m o nt hs d urati o n. D oc u me ntati o n m ust 
i ncl u de e n d osc o pic a n d hist o pat h ol o gic d oc u me nt ati o n, as f oll o ws:  
a)  U C  
i) Me dical rec or d  d oc u m e ntati o n of, or a n e n d osc o p y re p ort date d ≥ 4 m o nt hs bef ore 
ra n d o mizati o n, w hic h s h o ws feat ur es c o nsiste nt wit h U C, deter mi ne d b y t he 
pr oce d ure perf or mi n g p h ysicia n, A N D  
ii) Me dical rec or d d oc u m e ntati o n of, or a hist o pat h ol o g y re p ort i n dicati n g feat ures 
c o nsiste nt wit h U C as deter mi ne d b y t he pat h ol o gist, A N D  
N ote : S u bject als o nee ds t o ha ve m i ni m u m disease e xte nt of 1 5 c m fr o m t he a nal 
ver ge  

Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  5 4  
 
0 9 Se pte m ber 2 0 2 2  
b)  C D  
i) Me dical rec or d d oc u m e ntati o n of, or a n ile oc ol o n osc o p y (f ull c ol o n osc o p y wit h 
i nt u bati o n of ter mi nal ile u m) re p orte d d ate d ≥ 4 m o nt hs bef ore ra n d o mizati o n, w hic h 
s h o ws feat ur es c o nsiste nt wit h C D, deter mi ne d b y t he pr oce d ure perf or mi n g 
p h ysicia n, A N D  
ii) Me dical rec or d d oc u m e ntati o n of, or a hist o pat h ol o g y re p ort i n dicati n g feat ures 
c o nsiste nt wit h, C D as deter mi ne d  b y t h e pat h ol o gist  
5)  M o deratel y t o se verel y acti ve U C , or m o derat el y t o se verel y acti ve C D, ass esse d l ocall y a n d 
defi ne d b y:  
a)  U C  
i) Ma y o Cli nic Sc ore ( M C S; A p pe n di x  3 ) ≥ 6, P h ysicia n Gl o bal Assess me nt ( P G A)  of 
2  or 3, a n d e n d osc o pi c  s u bsc ore ≥ 2, at Scree ni n g or i n t he pri or 9 0 da ys  
b)  C D  
i) C D AI t otal s c ore ( A p pe n di x  9 ) ≥ 2 2 0, A N D 
ii) E vi de nce of acti ve i nfla m mati o n, wit h a t otal sc ore of ≥ 6 b y t he Si m ple E n d osc o pic 
Acti vit y Sc ore i n Cr o h n’s Disease ( S E S -C D; A p pe n di x  1 0 ), O R  if disease is li mite d 
t o t he ile u m a n d/ or ri g ht c ol o n, a c o m bi ne d S E S -C D sc ore ≥ 4 i n t hese 2 s e g m e nts,  at 
Scree ni n g or i n t he pri or 9 0 da ys  
6)  Pre vi o usl y de m o nstrat e d a n i na de q uat e cli nica l r es p o nse, l oss of res p o nse t o, or i nt olera nce 
of at  least o ne of t h e f oll o wi n g a ge nts ( de p e n di n g o n c urre nt c o u ntr y treat me nt 
rec o m me n dati o ns/ g ui deli nes): 
a)  C ortic oster oi ds  
i) Acti ve disease d es pite a hist or y of at least a n i n d u cti o n re gi me n of a d os e e q ui val e nt 
t o pre d nis o ne ≥2 0 m g d ail y f or 2  wee ks or i ntra ve n o usl y (I V) f or 1  wee k, O R  
ii) T w o faile d atte m pts t o ta per ster oi ds bel o w a d ose e q ui vale nt of 1 0  m g dail y 
pre d nis o ne, O R  
iii) Hist or y of ster oi d i nt olera nce i ncl u di n g, b ut n ot li mite d t o, C us hi n g’s s y n dr o me, 
os te o pe nia/ oste o p or osis, h y per gl yce mia, i ns o m nia, seri o us i nfecti o ns, de pressi o n, 
aller gic reacti o ns, m o o d dist ur ba nces, or a n y ot her c o n diti o n t hat c o ntri b ute d t o 
disc o nti n uati o n of t he a ge nt  

Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  5 5  
 
0 9 Se pte m ber 2 0 2 2  
b)  I m m u n o m o d ulat ors 
i) Acti ve disease d es pite a hist or y of at least a 1 2 -wee k re gi me n of oral azat hi o pri ne 
( ≥ 2 m g/ k g/ da y) or 6 M P ( ≥ 1 m g/ k g/ da y), or M T X ( 2 5 m g s u b c uta ne o usl y [ S C] or 
i ntra m usc ularl y [I M] per wee k f or i n d ucti o n a n d ≥ 1 5 m g I M per wee k f or 
mai nte na nce), O R  
ii) Hist or y of i nt olera nce t o at least o ne i m m u n o m o d ulat o r i ncl u di n g, b ut n ot li mite d t o, 
seri o us i nfecti o ns, he pat ot o xicit y, c yt o pe nia, p a ncreatitis, t hi o p uri ne 
met h yltra nsf erase ( T P M T) ge netic m utati o n, aller gic reacti o ns, or a n y ot her c o n diti o n 
t hat c o ntri b ute d t o disc o nti n uati o n of t he a ge nt 
c)  T N F α a nta g o nists  
i) Acti ve disease d es pite a n i n d ucti o n re gi me n wit h a T N F α a nta g o nists (i nfli xi ma b, 
a dali m u ma b, g oli m u ma b [ U C o nl y], or cert oliz u ma b [ C D o nl y]), or c orres p o n di n g 
bi osi milar prescri be d at a d ose a n d d urati o n c o nsiste nt wit h t he a p pr o ve d pr o d uct 
la beli n g, O R   
ii) Rec urre n ce of s y m pt o ms d uri n g mai nte na nce t h era p y wit h t he a b o ve a ge nts, O R  
iii) Hist or y of i nt olera nce t o a n y T N F α a nta g o nists i n cl u di n g, b ut n ot li mite d t o, seri o us 
i nfecti o ns, he pat ot o xicit y, heart fail ure, aller gi c reacti o ns, or a n y ot her c o n diti o n t hat 
c ontri b ute d t o disc o nti n uati o n of t he a ge nt  
d)  Ve d oliz u ma b  
i) Acti ve disease d es pite a n i n d ucti o n re gi me n prescri be d i n acc or da n ce wit h t he 
a p pr o ve d pr o d u ct la beli n g, O R  
ii) Rec urre n ce of s y m pt o ms d uri n g mai nte na nce t h era p y wit h ve d oliz u ma b, O R  
iii) Hist or y of i nt olera nce t o ve d oliz u ma b i ncl u di n g, b ut n ot li mite d t o, seri o us i nfecti o ns, 
he pat ot o xicit y, c yt o p e nia, aller gic reacti o ns, or a n y ot her c o n diti o n t hat c o ntri b ute d t o 
disc o nti n uati o n of t he a ge nt  
e)  Uste ki n u ma b [criteri o n a p plica ble o nl y t o s u bjects wit h C D]  
i) Acti ve dise ase d es pite a n i n d ucti o n re gi me n prescri be d i n acc or da n ce wit h t he 
a p pr o ve d pr o d u ct la beli n g, O R  
ii) Rec urre n ce of s y m pt o ms d uri n g mai nte na nce t h era p y wit h uste ki n u ma b, O R  
iii) Hist or y of i nt olera nce t o uste ki n u ma b i ncl u di n g, b ut n ot li mite d t o, seri o us i nfecti o ns,  
aller gic reacti o ns, or a n y ot her c o n diti o n t hat c o ntri b ute d t o disc o nti n uati o n of t he 
a ge nt  

Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  5 6  
 
0 9 Se pte m ber 2 0 2 2  
7)  Ma y b e recei vi n g 1 or m ore of t he f oll o wi n g dr u gs (s u bjects o n t hese t hera pies m ust be 
willi n g t o re mai n o n sta ble d oses f or t he n ote d ti m es):  
a)  5 -a mi n osalic yl ate ( 5 -A S A) c o m p o u n ds pr o vi de d t he d ose prescri be d has b ee n sta ble f or 
at least 4 wee ks pri or t o r a n d o mizati o n; d ose m ust re mai n sta ble f or t he first  1 3  wee ks 
after ra n d o mizati o n  
b)  Azat hi o pri ne, 6 -M P, or M T X pr o vi de d t he d ose prescri be d h as bee n sta ble f or 4  wee ks  
pri or t o ra n d o mizati o n; d ose of M T X m ust re mai n sta ble f or 2 6 wee ks, a n d d ose of 
A Z A/ 6 -M P m ust re mai n sta ble f or t he first 1 3 wee ks , b ut ca n be a dj uste d if i n dicate d 
bet wee n 1 3 a n d 2 6 wee ks.  
c)  C ortic oster oi d t hera p y ( pre d nis o ne pres cri be d at a sta ble d ose ≤ 2 0  m g/ da y or b u des o ni de 
prescri be d at a sta ble d os e of ≤ 9  m g/ d a y); d ose s h o ul d n ot be c ha n ge d d uri n g t he 
first 1 3  wee ks. A ster oi d ta per s h o ul d o nl y c o m me nce aft er Wee k 1 3.  
8)  T he mea n of 2 s e parate se me n sa m ples c ollecte d at t he Scree ni n g  visit  m ust  meet t he 
f oll o wi n g mi ni m u m criteria (in acc or da n ce wit h S ecti o n  6. 1 3  a n d Fi g ure  6 -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 otilit y ≥ 4 0 %, a n d n or mal s per m m or p h ol o g y ≥ 3 0 %  
9)  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 
at Scree ni n g  
1 0)  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  5 , 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 1)  Willi n g ness t o refrai n fr o m recei vi n g li ve atte n u ate d vacci nes wit hi n 3 0 da ys of Da y  1, 
t hr ou g h o ut t he st u d y, a n d f or 1 2 wee ks after t he last d ose of st u d y dr u g 
( Secti o n 5. 4 , Vacci ne  G ui deli nes).  
1 2)  Meet o ne of t he f oll o wi n g 3 t u berc ul osis ( 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 ui 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 or t 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 ecti o n  

Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  5 7  
 
0 9 Se pte m ber 2 0 2 2  
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 pt a ble m ulti-dr u g 
re gi me n). I n t hes e cases, n o Q ua nti F E R O N®  T B -G ol d Pl us I n -T u be t est 
( 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 gra 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  tr eat me nt a n d pr o vi de a p pr o priat e d oc u 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 be 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 Gilea d m e dical m o ni t or or 
desi g nee 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 T B  or u ntr eate 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 oses of cli nical care or f or t he p ur p ose of Scr ee ni n g f or a n ot her 
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 b e use d t o ass ess eli gi bilit y.  
1 3)  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 m3) 
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 oc yt e c o u nt > 7 5 0/ m m 3 
1 4)  Be u p t o date o n c ol orect al ca ncer s ur v eilla nce (p er l ocal g ui deli nes ) pri or t o Scree ni n g.  

Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  5 8  
 
0 9 Se pte m ber 2 0 2 2  
4. 3.  
E xcl usi o n Criteri 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 ucti 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 m acr 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, 
K li nefelter’s s y n dr o me) 
2)  Pri or dia g n osis 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 or 
oral ket oc o naz ole), or treat me nt wit hi n 4 wee ks of Scree ni n g   
7)  C urre nt treat me n t 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)  
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)  
1 0)  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 
1 1)  C urre nt use of 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 ( ma y b e disc usse d wit h Gilea d  m e dical m o nit or or desi g nee)  
1 2)  Treat me nt wit h c ycl os p ori ne or ot her calci ne uri n i n hi bit ors wit hi n 3 0 da ys of Scree ni n g  
1 3)  Use of a n y T N F α a nta g o nist or ve d oliz u ma b wit hi n  8  wee ks pri or t o Scree ni n g, uste ki n u ma b 
wit hi n 1 2 wee ks pri or t o Scree ni n g, or a n y ot her bi ol o gic a ge nt wit hi n  8  wee ks pri or t o 
Scree ni n g or wit hi n 5 ti mes t he half -life of t he bi ol o gic a ge nt pri or t o Scree ni n g, w hic h e ver 
is l o n ger 
1 4)  Use of a n y pr o hi bite d c o nc o mita nt me dicati o n(s) as d escri be d i n Secti o n  5. 3  
1 5)  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  

Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  5 9  
 
0 9 Se pte m ber 2 0 2 2  
1 6)  Prese nce of dis or ders of s per m tra ns p ort  incl 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  
1 7)  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 8)  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 bacc o use (c urre nt use of ≥ 2 pac ks per da y e q ui vale nt)  
1 9)  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)  
2 0)  A n y s e x ual d ysf u ncti o n of a nat ur e t ha t w o ul d pr e 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 diesterase 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 1)  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 2)  Hist or y of t otal c ol ect o m y, s u bt otal c olect o m y, p artial or he mi -c olect o m y, ile ost o m y, 
c ol ost o m y, or a ntici p ate d nee d f or a n y of t hes e  i nter ve nti o ns d uri n g t he st u d y  
2 3)  C urre ntl y h a ve c o m plic ati o ns of C D as a n y of t he f oll o wi n g:  
a)  S y m pt o matic stri ct ur es, O R 
b)  Se vere (i m pass a ble) rect al/a nal ste n osis, O R  
c)  Fist ulae, O R  
d)  S h ort b o wel s y n dr o m e, O R  
e)  A n y ot her c o m plicati o ns w hic h c o ul d precl u de t he use of t he C D AI t o ass ess res p o nse t o 
t hera p y, or w o ul d p ossi bl y c o nf o u n d t he e v al uati o n of be nefit fr o m treat me nt wit h 
fil g oti ni b 
2 4)  Ha ve a n y c urre nt or pri or a bscesses, u nless t he y h a ve bee n drai ne d a n d treate d at least 
6  wee ks pri or t o D a y 1 , a n d are n ot a ntici pat e d t o re q uire s ur ger y  d uri n g t h e st u d y  
2 5)  I n d eter mi nate c olitis, isc he mic c olitis, f ul mi na nt c olitis, is olate d ulcerati ve pr octitis, or t o xic 
me ga -c ol o n  
2 6)  De pe n de n ce o n p are nteral n utriti o n  
2 7)  Hist or y or e vi de nce of i n c o m pletel y resecte d c ol o nic m uc osal d ys pl asia  

Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  6 0  
 
0 9 Se pte m ber 2 0 2 2  
2 8)  Scree ni n g st o ol sa m ple p ositi ve f or Cl ostri di u m difficile (C. difficile ) t o xi n, pat h o ge nic 
Esc heric hi a  c oli (E.  c oli ), S al m o nell a  s pecies (s p p), S hi gell a  s p p, C a m pyl o b acter  s p p or 
Y ersi ni a  s p p, or o va a n d parasites ( O & P), u nless a p pr o ve d b y t he Gilea d m e dical m o nit or or 
desi g nee  
2 9)  C urre nt use of ster oi ds at a d ose >  2 0  m g/ da y of pre d nis o ne e q ui val e nts at ra n d o miz ati o n 
3 0)  A d mi nistrati o n of a li ve atte n uate d vacci ne wit hi n 3 0 da ys of Ra n d o mizati o n (see als o 
Secti o n  5. 4 , Vacci n e G ui deli nes)  
3 1)  A p ositi ve test res ul t f or HI V-1 or HI V -2 ( See A p pe n di x  6 ) 
3 2)  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 dis c 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.  
3 3)  E vi de nce of acti ve H B V i nfecti o n. 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 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 ref le 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. 
3 4)  Prese nce of C hil d -P u g h Class C he patic i m pair me nt  
3 5)  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)  
3 6)  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  
3 7)  Hist or y of treat me nt wit h l y m p h oc yte -d e 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 m i de, t otal l y m p h oi d irra diati o n, or rit u xi ma b 
3 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  
3 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 I n 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  

Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  6 1  
 
0 9 Se pte m ber 2 0 2 2  
4 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)  
4 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  
4 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)  
4 3)  Hist or y of disse mi nate d St a p hyl oc occ us a ure us  i nfecti o n 
4 4)  Hist or y of s y m pt o matic her pes z o ster 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 
ce ntral ner v o us s yste m z oster  
4 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 vice wit hi n 3 0 d a 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. 

Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  6 2  
 
0 9 Se pte m ber 2 0 2 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. 1.  
R a n d o miz ati o n, Bli n di n g a n d Tre at me nt C o des  
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.  
R a n d o miz ati o n  
S u bjects w h o meet ra n d o mizati o n eli gi bilit y criteria will be ra n d o mize d i n a 1: 1 rati o t o 
Fil g oti ni b 2 0 0 m g or P T M fil g oti ni b 2 0 0  m g starti n g o n Da y 1, a n d assi g n e d a s u bject n u m ber. 
Ra n d o miza ti o n will be stratifie d b y t y pe of I B D ( U C vers us C D), 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 ( 1 5 -2 5 milli o n/ m L; > 2 5 t o 5 0 milli o n/ m L; or > 5 0 milli o n/ m L) 
base d o n t he mea n of 2 eli gi ble se me n s a m ples c ollecte d at Scree ni n g . 
5. 1. 2.  
Bli n di n g  
D u ri n g t h e ra n d o mize d 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 me nt. S pecifie d pers o n nel 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 h ar macist, or d esi g nee, 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 netics File A d mi nistrat or, or desi g n ee, i n Bi oa nal yti cal 
O perati o ns a n d/ or Cli nical Data Ma n a ge me nt, w h o facilitates t he data tra nsfer of P K files 
bet 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 ha ve a n U n bli n de d I n v e nt or y M a na ger r ole i n t he 
IW R S s yste m f or p ur p os es of st u d y dr u g i n ve 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 det ecti o n, i n vesti gati o nal ne w dr u g (I N D) s afet 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 be u n bli n de d t o i n di vi d ual case d ata a n d/ or gr o u p l e vel s u m maries. E xter nal 
(ie, C o ntract R esearc h O r ga niz ati o ns [ C R Os]) Bi ostatisticia ns a n d Pr o gra m 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 ostatistic ia n will ser ve as t he e xter nal st atisticia n t o t he D M C. Re g ul at or y Q u alit y a n d 
C o m plia nce pers o n nel i n Researc h a n d De vel o p me nt ma y als o be u n bli n de d f or p ur p oses 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 nc y i ns pe cti 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 treat me nt assi g n me nts u ntil t he 
fi nal a nal ysis w he n t he d ata base h as bee n l o c ke d. P u blicati o n of t he I A 2 data is pla n ne d b y t h e 
S p o ns or. T his p u blicati o n will c o ntai n gr o u p le ve l 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 t ea 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 bef ore I A 2.   

Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  6 3  
 
0 9 Se pte m ber 2 0 2 2  
5. 1. 3.  
Pr oce d ures f or Bre a ki n g Tre at m e nt C o des  
I n t he e ve nt of a me dical e mer ge n c y w here brea ki n g t he bli n d is re q uir e d t o pr o vi de me dical care 
t o t he s u bject, t he i n vesti gat or m a 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 I W R S s yst e m. T he S p o ns or rec o m me n ds, b ut d oes n ot re q uire, t h at t he i n vesti gat or 
c o ntact t he m e dic al m o nit or or desi g nee b ef ore brea ki n g t he bli n d. Treat me nt assi g n me nts 
s h o ul d re mai n bli n de d u nless t hat k n o wle d ge is ne cessar y t o det er mi ne e m er ge nc y me dical care 
f or t he s u bject. T h e rati o nale f or un 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 n d o n t he ele ctr o nic cas e re p ort f or m (e C R F), al o n g wit h t he dat e o n w hi c h t he treat me nt 
assi g n me nt w as u n bli n de d.  T he i n vesti gat or is re q ueste d t o c o ntact t he m e dical m o nit or or 
desi g nee pr o m ptl y i n cas e of a n y tr eat me nt u n bli n di n g.  
Bli n di n g of st u d y tr eat m e nt is critical t o t he i nte grit y of t his cli nical trial a n d t heref ore, 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 bject 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 nless c o nse nt t o d o s o is 
s pecificall y wit h dra 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 f 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 vers e reacti o ns ( S U S A Rs) t o Re g ulat or y A ut h orities.  
5. 2.  
Descri pti o n a n d H a n dli n g of Fil g oti ni b a n d Pl ace b o -t o-M atc h ( P T M)  
5. 2. 1.  
F o r 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 v e 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 
i nacti ve i n gre die nts: micr ocrystalli ne cell ul ose, lact ose m o n o h y drate, f u maric aci d, 
pre gelati nize d starc h, silic o n di o xi de, ma g nesi 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, 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 ( P T M) fil g oti ni b 2 0 0  m g ta blets are i de ntical i n a p peara n ce t o t he acti ve 
ta blets. Place b o -t o-matc h ( P T M) fil g oti ni b 2 0 0  m g ta blets c o ntai n t he f oll o wi n g i nacti ve 
i n gre di e nts: micr ocr ystalli ne cell ul ose, lact ose m o n o h y drate, cr oscar mell ose s o di u m, ma g nesi u m 
stearate, m acr o g ol/p ol yet h yle n e 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. 
5. 2. 2.  
P a c k a gi n g a n d L a beli n g  
Fil g oti ni b a n d P T M fil g oti ni b ta blets are pac k a 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 nt ai 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.  

Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  6 4  
 
0 9 Se pte m ber 2 0 2 2  
St u d y dr u gs t o be distri b ute d t o ce nters i n t he U S a n d ot her partici pati n g c o u ntries s hall be 
la bele d t o meet a p plic a ble re q uir e me nts of t he U nite d States F o o d a n d Dr u g A d mi nistrati o n 
( F D A), E U G ui deli ne t o G o o d Ma n ufact uri n g Practice - A n ne x 1 3 (I n v esti gati o nal Me di ci nal 
Pr o d ucts) a n d/ or  ot her l o cal re g ulati o ns, as a p plica ble.  
5. 2. 3.  
St or a ge a n d H a n dli n g  
Fil g oti ni b a n d P T M fil g oti ni b ta blets, s h o ul d be st ore d at c o ntr olle d r o o m te m perat ur e of 
2 5  °C  ( 7 7 F) . Te m p erat ure vari a bilit y bet w ee 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 ns are s pecifie d o n t he l a bel. 
U ntil dis pe nse d t o t he s u bjects, all 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 s t 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, 
pre 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 os a ge a n d A d mi nistr ati o n of Fil g oti ni b  
Fil g oti ni b a n d P T M fil g oti ni b ta blets will 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 of 
st u d y me dicati o n as s o o n as p ossi ble d uri n g t he s a 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). Misse d d ose (s) or u n use d st u d y dr u g s h o ul d n ot 
be discar de d.  
5. 3.  
Pri or a n d C o nc o mit a nt Me dic ati o ns  
All me dicati o ns ta ke n u p t o 3 0 da ys pri or t o t he Scree 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 st u d y, if p ossi ble. At eac h st u d y visit, t he  
st u d y ce nt er will ca pt ur e 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 he visit (as a p plica ble). C o nc o mita nt me dicati o ns i ncl u de pres cri pti o n, n o n -prescri 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 I n 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 e x cl u de d c o nc o mita nt me dicati o n, t he m e dical m o nit or or desi g nee m ust be c o ns ulte d 
pri or t o i nitiati o n of t he ne w me dicati o n. I n i nsta n ces w here a n e x cl u de 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 he 
is a ware of t he use of t he e x cl u de d me dicati o n.  

Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  6 5  
 
0 9 Se pte m ber 2 0 2 2  
5. 3. 1.  
All o w e d C o nc o mit a nt Me dic ati o ns  
T he all o we d c o n c o mita nt me dicati o n(s) f or U C a n d f or C D m ust be mai ntai ne d at a sta ble d os e 
f or t he n ote d ti me wit h o ut d osi n g alterati o n or disc o nti n uati o n.  
T he all o we d me dicati o ns f or U C a n d f or C D are as f oll o ws:  
•  Oral 5 -A S A c o m p o u n ds , pr o vi de d t he d ose prescri be d has bee n st a ble f or at least 4  wee ks 
pri or t o ra n d o mizati o n; d ose m ust be sta ble f or t he first 1 3 wee ks after ra n d o mizati o n. 
•  Azat hi o pri ne, 6 -M P, or M T X , pr o vi de d t he d ose prescri be d h as bee n sta ble f or 4  wee ks pri or 
t o ra n d o mizati o n; d ose of M T X m ust re mai n sta bl e f or 2 6 wee ks, a n d d os e of A Z A/ 6-M P 
m ust re mai n sta ble f or t h e first 1 3 wee ks , b ut ca n be a dj uste d if i n dicate d bet wee n 1 3  a n d 
2 6  wee ks.  
•  C ortic oster oi d t hera p y ( pre d nis o ne pres cri be d at a sta ble d ose ≤ 2 0  m g/ da y or b u des o ni de 
prescri be d at a sta ble d os e of ≤ 9  m g/ d a y) ; d ose s h o ul d n ot be c ha n ge d d uri n g t he first 
1 3  wee ks. A ster oi d  ta per s h o ul d o nl y c o m me nce after Wee k 1 3. 
C o nc o mit a nt Ster oi d M a n a ge me nt:  
Starti n g at W ee k  1 3, s u bj ects w h o are o n c o n c o mita nt ster oi ds ma y b e gi n ta peri n g st er oi d 
t hera p y at t he discreti o n of t he i n vesti gat or. Ster oi ds ma y b e i ncrease d or restarte d if retur n of 
s y m pt o ms is a p pare nt ( b ut d ose ma y n ot e xcee d 2 0 m g pre d nis o ne e q ui val e nt).  
5. 3. 2.  
Pr o hi bite d C o nc o mit a nt Me dic ati o ns  
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:  

Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  6 6  
 
0 9 Se pte m ber 2 0 2 2  
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 ucers a 
A ntic o n v ulsa nts  
P he n o bar bital, p he n yt oi n, a n d 
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 st u d y  
A nti m yc o bacterials  
Rif a b uti n, rif a pe nti ne, a n d rif a 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 I B D Me dic ati o ns d  
C ortic oster oi ds  
D ose e q ui vale nt t o > 2 0 m g/ da y of 
pre d nis o ne  
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 
( u nless i n M o nit ori n g P hase) 
T N F α a nta g o nist  
I nfli xi ma b, a dali m u ma b, g oli m u ma b, 
cert oliz u ma b, a n d bi osi milar a ge nts  
8 wee ks pri or t o Scree ni n g t hr o u g h t he e n d 
of t he st u d y ( u nless i n M o nit ori n g P hase)  
I nte gri n a nta g o nist 
Ve d oliz u ma b a n d nataliz u ma b  
8 wee ks pri or t o Scree ni n g t hr o u g h t he e n d 
of t he st u d y ( u nless i n M o nit ori n g P hase)  
I nterl e u ki n a nta g o nist 
Uste ki n u ma b  
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 st u d y ( u nless i n M o nit ori n g P hase)  
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 st u d y ( u nless i n M o nit ori n g P hase)  
Fil g oti ni b  
A n y ti me pri 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)  
C ycl os p ori ne, t hali d o mi de, tacr oli m us, 
lefl u n o mi de, a n d a n y i n vesti gati o nal a ge nt 
3 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 st u d y  
Ot her ( bi ol o gic) c 
A n y i n vesti gati o nal bi ol o gic a ge nt  
8 wee ks ( or 5 half -li ves, w hic he ver is 
l o n ger) pri or t o Scree ni n g t hr o u g h t he e n d of 
t he st u d y 
L y m p h oc yte -de pleti n g 
t hera pies 
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, rit u xi ma b, a n d a n y 
ot her l y m p h oc yte d e pleti n g t hera p y  
A n y ti me b ef ore a n d t hr o u g h t he e n d of t he 
st u d y 
S ulf a dr u gs  
S ulf asalazi ne  
C urre nt use of s ulf asalazi ne or use of 
s ulf asalazi ne wit hi n 2 6 wee ks of Scree ni n g . 
S ulf asalazi ne is n ot per mitte d  at a n y p oi nt 
d uri n g t he st u d y  
Ot her P r o hi bite d Me dic ati o ns  
C hr o nic N o nster oi dal 
A nti -i nfla m mat or y 
Dr u gs ( N S AI Ds) b 
As piri n, i b u pr of e n, na pr o xe n, dicl of e nac, 
i n d o met haci n, C O X-2 i n hi bit ors  
Fr o m Scree ni n g t hr o u g h t he e n d of t he st u d y  
a 
Ma y decr ease 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  
Occasi o nal use of N S AI Ds f or tra nsie nt s y m pt o ms a n d dail y use of as piri n u p t o 1 6 2. 5 m g f or t h e p ur p ose of car di o vasc ular 
pr o p h yla xis are per mitte d  
c 
Ot her a p pr o ve d bi ol o gics ( e g, a nti b o d y base d or ot her s yste mi c 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 m e dical 
m o nit or 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  
d  
S u bjects w h o 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, will be offere d l o call y a p pr o ve d S O C  t h era p y; i n t his 
case, c o nc o mita nt me dicati o ns i n t h e a b o ve ta ble ma y be per mitte d u p o n disc ussi o n wit h t h e me dical m o nit or or desi g nee  

Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  6 7  
 
0 9 Se pte m ber 2 0 2 2  
5. 4.  
V acci ne G ui deli nes  
•  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  w ee ks 
after t he l ast  d ose of st u d y dr u g.  
•  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 b e a v oi de d f or t he bel o w state 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 atte 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 va cci 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 va cci 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 vacci 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.  
Acc o u nt a bilit y f or St u d y Dr u gs  
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 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 m e 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  
•  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 

Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  6 8  
 
0 9 Se pte m ber 2 0 2 2  
5. 5. 1.  
I n vesti g ati o n al Me dici n al Pr o d uct Ret ur n or Dis p os al 
T he S p o ns or rec o m me n ds t hat use d a n d u n use d st u d y dr u g s u p plies b e destr o ye d at t he site. If 
t he site has a n a p pr o priat e sta n dar d o perati n g pr oce d ure (S O P ) f or dr u g destr ucti o n as 
deter mi ne d b y t he S p o ns or , t he site ma y destr o y use d (e m pt y or partiall y e m pt y) a n d u n us e d 
st u d y dr u g s u p plies i n acc or da nce wit h t hat site’s a p pr o ve d S O P. A c o p y of t he site’s a p pr o ve d 
S O P will be o btai ne d f or t he S p o ns or’s site files. If st u d y dr u g is destr o ye d o n site, the 
i n vesti gat or m ust mai ntai n acc urate rec or ds f or all st u d y dr u gs destr o ye d. Rec or ds m ust s h o w t he 
i de ntificati o n a n d q ua ntit y of eac h u nit destr o ye d, t he met h o d of destr ucti o n, a n d t he pers o n w h o 
dis p ose d of t he st u d y dr u g. U p o n st u d y c o m pleti o n, c o pies of t he st u d y dr u g acc o u nta bilit y 
rec or ds m ust be file d at t he site. A n ot her c o p y will be ret ur ne d t o t he S p o ns or.  
If t he site d oes n ot ha v e a n a p pr o priate S O P f or dr u g destr u cti o n, use d a n d u n use d st u d y dr u g 
s u p plies are t o be se nt t o t he desi g n ate d dis p osal f acilit y f or destr ucti o n. T h e st u d y m o nit or will 
pr o vi de i nstr ucti o ns f or ret ur n.  
T he st u d y m o nit or will re vie w st u d y dr u g s u p plies a n d ass ociate d rec or ds at peri o dic i nter vals.  
F or b ot h dis p osal o pti o ns liste d a b o ve, t he st u d y m o nit or m ust first perf o r m dr u g acc o u nt a bilit y 
d uri n g a n o n -site m o nit ori n g visit.  

Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  6 9  
 
0 9 Se pte m ber 2 0 2 2  
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 perf 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 bject E nr oll me nt a n d Tre at me nt Assi g n me 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 Scree 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 u bject will 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 P T M fil g oti ni b 
2 0 0 m g  o nce dail y.  
6. 2.  
Pretre at me nt Assess me nts  
6. 2. 1.  
Scree ni n g Visit  
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 Scree ni n g peri o d m ay be exte n de d i n c o ns ult ati o n wit h t he  
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 di x  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  
•  O btai n de m o gra p hics a n d me dical hist or y (i ncl u di n g o nset of I B D, pri or n u m ber of c hil dre n 
fat here d, disease c haract eristics, s m o ki n g ha bits, a vera 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 diseas e) 
•  Re vie w I ncl usi o n / E x cl usi o n Criteria  
•  C o m plete P h ysi cal E x a m ( P E)  as detaile d i n A p pe n di x  7  
•  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  

Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  7 0  
 
0 9 Se pte m ber 2 0 2 2  
•  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 r es 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 i d e ntifie d 
late nt T B d uri n g Scree ni n g  re q uire s p o ns or a p pr o val ( See I n cl usi o n Criteri o n N o. 1 2 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 wee 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 m e dical m o nit or or desi g n ee. If a s u bject ha d a 
Q ua nti F E R O N ®  test f or t he p ur p oses of cli nical care or Scree ni n g f or a n ot h er 
Gilea d -s p o ns ore d st u d y wit hi n 6 0 da ys, t he pri or Gilea d res ult ma y be us e d t o assess 
eli gi bilit y wit h per missi o n of t he me dical m o nit or or desi g n ee.  
•  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  
⎯ Q ua ntitati ve I g s u bclasses  
⎯ E n d ocri ne tests: T h 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 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 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 
•  St o ol C ollecti o n f o r: 
⎯ C. difficile t o xi n, E. c oli, S al m o nell a s p p, S hi gell a s p p, C a m pyl o b acter s p p a n d 
Y ersi ni a  s p p testi n g 
⎯ O va & Parasites ( O & P)  
•  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 seri o us a d v ers e e ve nts ( 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 c o nse nt f or m  
•  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 3 ) 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 baseli ne visit as m uc h as p ossi ble.  

Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  7 1  
 
0 9 Se pte m ber 2 0 2 2  
•  F or s u bjects wit h U C, c ollect t he varia bles t o calc ulate baseli ne M C S ( Defi niti o n  of  Ter ms 
a n d A p pe n di x  3 ), i ncl u di n g perf or mi n g fle xi ble si g m oi d osc o p y u nless perf or me d i n t he 
9 0  da ys pri or t o Scree ni n g. T he M C S is c o m p ose d of s u b -sc ores fr o m e n d osc o p y, rect al 
blee di n g, st o ol fre q ue n c y, a n d P G A. S u bject recall of t he last 2 4 h o urs will be use d f or t h e 
patie nt re p orte d c o m p o ne nts of t he M C S . F or t he c o m plete M C S, P G A will be e val uat e d 
after re vie wi n g t he e n d os c o p y.  
•  F or s u bjects wit h C D, c ollect t he varia bles t o calc ulate baseli ne t otal C D AI sc ore 
( Defi niti o n of  Ter ms a n d A p pe n di x  9 ) a n d t o calc ulate baseli ne S E S-C D ( Defi niti o n of 
Ter ms a n d A p p e n di x  1 0 ), i ncl u di n g perf or mi n g ile oc ol o n osc o p y u nless perf or me d i n t he 
9 0  da ys pri or t o Scree ni n g. S u bject r ecall of t h e last 7 da ys will be use d f or t he patie nt 
re p orte d c o m p o ne nts of t he C D AI. T he C D AI  sc ore cal c ulati o ns s h o ul d n ot be i ncl usi ve of 
da ys t hat i n v ol ve a n e n d osc o p y pr oce d ure or pre p arati o n f or t hat pr o ce d ure . 
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 ni tial 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 or Me dical M o nit or or desi g nee, if t here  is a n e xte n uati n g 
circ u msta nc e 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 S cree ni n g se me n sa m ples is disc usse d i n Secti o n 6. 1 3  
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 n vesti gati o nal 
me dici nal pr o d uct, r ec or d all S A Es, as well as a n y a d v er se e ve nts r elate d t o pr ot oc ol-ma n date d 
pr oce d ures o n t he a d v ers e e ve nts c ase re p ort f or m ( C R F/e C R F). All ot her u nt o war d me dical 
occ urre nces o bser ve 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 c ha n ges i n me di cal 
hist or y are t o be ca pt ure 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 n a ge me nt f or a d diti o nal details.  
6. 2. 1. 1.  
Rescree 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 rescree 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 M o nit or  or 
desi g nee. S u bjects w h o are res cree ne d d o n ot nee 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.  

Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  7 2  
 
0 9 Se pte m ber 2 0 2 2  
6. 2. 2.  
D a y 1 Assess me nts  
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 wil l 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 P T M fil g oti ni b 2 0 0 m g  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 uc h as bl o o d dra ws s h o u l d be d o ne at t he e n d of t h e 
St u d y Visit . T he f oll o wi n g will be perf or me d a n d d oc 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 h ysical e x a mi nati o n, 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)  
•  P h ysicia n’s Gl o b al Assess me nt [ a p plie d o nl y t o s u bjects wit h U C]  
•  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]  
⎯ 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 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  
•  Re vie w c o nc o mita nt me dicati o ns  
•  Rec or d a n y a d vers e e ve nts relate d t o pr ot oc ol ma n date d pr oce d ures a n d all seri o us a d verse 
e ve nts ( S A Es) occ urri n g after si g ni n g of t he c o nse nt f or m.  
6. 3.  
R a n d o miz 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 b e 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 P T M fil g oti ni b 
2 0 0 m g  i n a 1: 1 rati o, wit hi n strata.  
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 I B D ( U C v ers us C D), c o nc urre nt use of 
M T X ( yes or n o), a n d s p er m c o nce ntra ti 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 strata: 
•  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  

Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  7 3  
 
0 9 Se pte m ber 2 0 2 2  
6. 4.  
P a rt  A ( D a y 1 t hr o u g h Wee k 1 3 St u d y Visit)  
All s u bjects will recei ve bli n de d st u d y dr u g f or t he first 1 3 wee ks . 
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 ) 
a n d Fi g ure  3 -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 t he e n d of a St u d y Visit , as 
m uc h as p ossi ble.  
6. 5.  
P a rt B ( After W ee k 1 3 t hr o u g h Wee k 2 6 St u d y Visit)  
S u bjects w h o are Res p o n ders at W ee k 1 3 a n d w h ose s per m para meters d o n ot meet a 
pre -s pecifie d decrease t hres h ol d will c o nti n ue bli n de d st u d y dr u g i n Part 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 ) 
a n d Fi g ure  3 -3 .  
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 t he e n d of a St u d y Visit , as 
m uc h as p ossi ble.  
6. 6.  
O pe n -L a bel Fil g oti ni b P h ase ( O pe n -L a bel D a y  1 t hr o u g h O pe n -L a bel 
Wee k  1 3 St u d y Visit)  
S u bjects w h o are N o n -Res p o n ders  at Wee k 1 3  i n Part A, or ha ve Disease W orse ni n g aft er 
Wee k  1 3 a n d bef ore reac hi n g Wee k  2 6 i n Part B, will disc o nti n ue bli n de d st u d y dr u g a n d 
c o m me nce O L  fil g oti ni b i n t he O L  Fil g oti ni b P has e , if s u bjects’ s per m para meters d o n ot meet a 
pre -s pecifie d decrease t hres h ol d. T w o se parate s e me n sa m ples will be c ollecte d a n d a nal yz e d 
bef ore s witc hi n g a s u bject t o O L  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 ) 
a n d Fi g ure  3 -4 .  
6. 7.  
M o nit ori n g P h ase   
S u bjects w h o se s per m para meters me et a pre -s pecifie d decrease t hres h ol d d uri n g t he st u d y  will 
disc o nti n ue st u d y dr u g , c o m plete a safet y f oll o w-u p visit 3 0 da ys after last d ose of st u d y dr u g,  
a n d e nter t he M o nit ori n g P hase . S u bjects will be offere d S O C t hera p y as part of t he M o nit ori n g 
P hase , a n d u n der g o s p er m e val uati o ns e ver y 1 3  wee ks ( 2  s e parate sa m ples at eac h time p oi nt) 
fr o m t he 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 
(see D efi niti o n of Ter ms), 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 ) 
a n d Fi g ure  3 -5 . 

Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  7 4  
 
0 9 Se pte m ber 2 0 2 2  
6. 8.  
E arl y Ter mi n ati o n  
If a s u bject disc o nti n ues st u d y partici p ati o n f or a n y reas o n pri or t o Wee k 2 6, O L Wee k 1 3, 
reac hi n g Re v ersi bilit y or M o nit ori n g P hase Wee k 5 2  ( w hic he ver occ urs first), or L T E Wee k 1 9 5, 
E T visit 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 ).  
S u bjects w h o are Res p o n ders at W ee k 2 6 a n d at O L  Wee k 1 3 a n d c h o ose n ot t o c o nti n ue t o t he 
L T E will als o c o m plete E T visit a ssess me nts. 
6. 9.  
S afet y F oll o w -U p Visit 3 0 D a ys P ost L ast D ose ( ± 5 d a ys)  
A n y ti me a s u bject disc o nti n ues st u d y dr u g, a s afet y f oll o w -u p visit , 3 0  da ys after t he last d ose of 
st u d y dr u g is re q uire d, e v e n if t he s u bject is e nteri n g t he M o nit ori n g P hase.  
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. 1 0.  
L o n g Ter m E xte nsi o n  
S u bjects w h o are Res p o n ders at eit her Wee k  2 6 ( P art B) or O L Wee k 1 3 ( O L  P hase ), a n d w h os e 
s per m para m eters d o n ot meet a pre-s pecifie d decrease t hr es h ol d, will e nter t he L T E a n d  
c o nti n ue o n t he sa me dr u g t he y w ere res p o n di n g t o  (ie, O L  fil g oti ni b or bli n de d st u d y dr u g). As 
s pecifie 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 Fi g ure  3 -6 , s u bj ects c o nti n ui n g o n t o 
t he L T E will u n der g o sc h e d ule d visits f or safet y assess me nts e ver y 1 3 wee ks, u p t o 1 9 5 wee ks , 
a n d se me n m o nit ori n g will be c ollecte d e v er y 1 3 wee ks u ntil t he Wee k 1 3 pri mar y st u d y res ults 
are a n al yze d .  
S u bjects i n t he L T E w h o m eet Disease W orse ni n g criteria as descri b e d i n Secti o n  3. 4  or ha ve 
Disease W orse ni n g per i n vesti gat or j u d g me nt s h o ul d be disc o nti n ue d fr o m st u d y dr u g. T h ese 
s u bjects s h o ul d c o m plete E T a n d t he safet y f oll o w-u p visit 3 0  da ys after t he last d ose of st u d y 
dr u g.  
6. 1 1.  
S afet y a n d T oler a bilit y  
A Es, P E, vital si g ns, a n d la b orat or y ass ess me nts (sta n dar d he mat 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 be c ollecte d i n acc or da nce wit h 
Secti o n  6. 1 3 . 
6. 1 2.  
Cli nic al L a b or at or y E v al u ati o ns  
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 centr 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 
St u d y Pr oce d ures Ta 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 here li pi d p r ofili n g is 
sc he d ule d.  

Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  7 5  
 
0 9 Se pte m ber 2 0 2 2  
Please refer t o A p p e n di x  6  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 i n dicate d a n d dee me d necessar y b y t he i n vesti gat or.  
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 gat or has c o ns ulte d wit h t he 
me dical m o nit or or desi g nee. 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 aft er 
t he res ults fr o m t he retest are a v aila ble (s ee Secti o n 3. 3  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.   
6. 1 3.  
Se me n C ollecti o n Pr o ce d ure  
Eac h s u bject will pr o vi de 2 se parat e se me n sa m ples c ollecte d wit hi n a 1 4 -d a y p eri o d a n 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 , at t he f oll o wi n g ti me p oi nts:  
•  Scree ni n g ( Bas eli ne)  
•  After Part A ( Wee k 1 3 St u d y Visit ) 
•  After Part B ( Wee k 2 6 St u d y Visit )  
O R  
F or S u bjects w h o e x perie nce c o nfir me d Diseas e W orse ni n g bet w ee n Wee ks 1 3 -2 6 i n Part B, 
p ri or t o be gi n ni n g O L  Fil g oti ni b a n d at t he O L Wee k 1 3  St u d y Visit  
•  E ver y 1 3 wee ks d uri n g t he M o nit ori n g P hase (if a p plica ble)  
•  E ver y 1 3 wee ks d uri n g t he L T E  
All decisi o ns of rete sti n g a n y s e me n/s per m para m eter ( ie, o bt ai ni n g a t hir d se me 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 M o nit or or desi g nee bef ore 
t he retest. S uc h i n q uiries will o nl y b e c o nsi dere d i n select i nsta nces w h ere t he se me n sa m ple 
wit h t he q uest i o ne d val ue(s) is f o u n d t o be n o n -assessa 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 ds; 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 s e 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 peri o d of ≥ 4 8 h o urs a n d ≤ 7 da ys  
(See  Fi g ure  6 -1 ). 

Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  7 6  
 
0 9 Se pte m ber 2 0 2 2  
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 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.  
Fi g ure  6 -1 . 
Se me n C ollecti o n Sc he m a  
 
 
A sta 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 oc all 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 4.  
Vit al Si g ns  
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 St u d y Pr oce d ures Ta 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  7  f or details) a n d will i ncl u de heart rate, res pirat or y rate, s yst olic 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 5.  
P h ysic al E x a mi n ati o n  
A p h ysic al e x a mi nati o n wi ll 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 p e 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 m eas 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 h ysical e x a mi nati o n , as detaile d i n A p pe n di x  7 , will be perf or me d at Scree ni n g , 
o nl y . S y m pt o m-dir ecte d p h ysical e x a ms will be perf or me d at all ot her visits , as nee de d.  

Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  7 7  
 
0 9 Se pte m ber 2 0 2 2  
6. 1 6.  
P h ar m a c o ki netic Assess me nts  
I n Parts A a n d B, bl 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 osi n g at t he Wee k 2 visit, a n 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 visits. I n t he O L  Fil g oti ni b P hase, bl 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 osi n g at t he O L Wee k  2 visit, a n yti me at t he 
O L  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 O L Wee k  1 3 visit. 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.   
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 7.  
T hr o m b oe m b olic E ve nts  
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 8.  
M a y o Cli nic Sc ore a n d P a rti al M a y o Cli nic Sc ore  
M C S a n d partial M C S will be assesse 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 ). T he M C S (A p pe n di x  3 ) is all o we d t o ha ve bee n perf or me d wit hi n t he 9 0 da ys 
p ri or t o Scree ni n g a n d is c o m p ose d of s u b-sc ores fr o m e n d osc o p y, rectal bl ee di n g, st o ol 
fre q ue n c y, a n d P G A. T h e partial M C S i ncl u des t he rect al blee di n g, st o ol fre q ue nc y, a n d 
P G A  s u b-sc ores. S u bject recall of t h e last 2 4 h o urs will be use d f or t he patie nt re p orte d 
c o m p o ne nts of t he M C S a n d partial M C S. F or t he c o m plete M C S, P G A will be e val uate d after 
re vie wi n g t he e n d os c o p y, w hic h will be l ocall y rea d.  
6. 1 9.  
Si m ple E n d osc o pic Sc ore f or Cr o h n’s Dise ase  
S E S -C D will be assesse d at t he ti me p oi nts i n dicate d i n t he S t u d y Pr oce d ures Ta ble 
(A p pe n di x  2 ). T he S E S-C D ( A p pe n di x  1 0 ) is all o we d t o ha ve b ee n perf or me d wit hi n t he 9 0 da ys 
pri or  t o Scree ni n g a n d is a c o m p osite sc ore of m uc osal i nfla m mati o n c o nsisti n g of f o ur 
e n d osc o pic varia bles ( ulc er pres e nce a n d size; l u mi nal s urface c o vere d b y ulcers; l u mi nal s urface 
wit h disease i n v ol ve me nt; a n d ste n osis prese nce a n d se verit y). T he b o wel is di vi de d i nt o 
se g me nts (ile u m, ri g ht c ol o n, tra ns verse c ol o n, left c ol o n, a n d rect u m) a n d eac h se g me nt is 
sc ore d i n di vi d uall y, t h e n t he se g m e nt sc ores are s u m me d f or a t otal sc ore (ra n ge: 0 t o 6 0). T he 
S E S -C D will be l ocall y rea d.  
6. 2 0.  
Cr o h n’s Dise ase Acti vit y I n de x  
C D AI will be assesse 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 bles ( A p pe n di x  2 ). 
T he C D AI ( A p p e n di x  9 ) is a c o m p osite sc ore of C D acti vit y c o nsisti n g of gastr oi ntesti nal 
s y m pt o ms (e g, a b d o mi nal pai n), si g ns (e g, a b d o mi nal mass), la b orat or y v al ues (ie, he mat o crit), 
a n d c o m plicati o n s (e g, art hritis/art hral gia), a m o n g ot her attri b utes. S u bject recall f or t he last 
7  da ys will be use d f or t h e patie nt re p orte d c o m p o ne nts of t he C D AI . T h e C D AI s c ore 
calc ulati o ns s h o ul d n ot be i ncl usi ve of da ys t hat i n v ol ve a n e n d osc o p y pr oce d ure or pre p ar ati o n 
f or t hat pr oce d ure. 

Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  7 8  
 
0 9 Se pte m ber 2 0 2 2  
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.  
Defi niti o ns of A d verse E ve nts, A d verse Re a cti o ns, a n d Seri o us A d verse 
E ve nts  
7. 1. 1.  
A d verse E ve nts  
A n a d vers e e ve nt ( A E) is a n y u nt o w ar d me dical o cc urre nce 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 bl e a n d/ or u ni nte n de d si g n, s y m pt o m, or disease 
te m p orall y ass ociate d wit h t he use of a me di ci nal pr o d uct, w het her or n ot c o nsidere d rel ate d t o 
t he 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 pli cati o ns t hat occ ur as a 
res ult of pr ot oc ol s pecifie d pr oce d ures, la c k of efficac y, o ver d ose, dr u g a b use/ mis use re p orts, or 
occ u pati o nal e x p os ure. Pree xisti n g e ve nts t hat i ncrease i n se v erit y or c h a n ge i n nat ure d uri n g or 
as a c o nse q u e nce of partici pati o n i n t he cli nical st u d y will als o be c o nsi d ere 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 
•  Sit uati o ns w here a n u nt o w ar 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.  
Seri o us A d verse E ve nts  
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 ous” 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 pitalizati o n or pr ol o n gati o n of e xisti n g h os pitaliza ti o n 

Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  7 9  
 
0 9 Se pte m ber 2 0 2 2  
•  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 d e 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.  
Assess me nt of A d verse E ve nts a n d Seri o us A d verse E ve nts  
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 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.  
Assess me nt of C a us alit y f or St u d y Dr u gs a n d Pr oce d ures  
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 asses si n g t h e relati o ns hi p t o 
I M P t hera p y usi n g cli nic al j u d g me nt a n d t h e 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 verse 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 us alit y m ust be pr o vi de d (e g, pre -e xisti n g c o n di ti o n, u n derl yi n g 
disease, 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 n vesti gati o nal me dici nal pr o d uct. 
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 usin 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 verse 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 n ct ure).  

Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  8 0  
 
0 9 Se pte m ber 2 0 2 2  
7. 2. 2.  
Assess me nt of Se verit y  
T he se verit y of A Es w ill be gra de d usi n g t he m o difie d C o m m o n Ter mi n ol o g y Criteria f or 
A d verse E v e nt ( C T C A E ), versi o n 4. 0 3. F or eac h e pis o de, t he hi g hest gra de 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  4 . 
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.  
7. 3.  
I n vesti g at or Re q uire me nts a n d I nstr ucti o ns f or Re p orti n g A d verse E ve nts 
a n d Seri o us A d verse E ve nts t o t he S p o ns 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 d verse e ve nts relate d t o 
pr ot oc ol -ma n date d pr oc e d ures.  
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  3 0 -da ys after last a d mi nistrati o n of st u d y dr u g(s)  m ust be  re p ort e 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 ble, if p ossi ble. 
T he S p o ns or  ma y re q u est 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.  

Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  8 1  
 
0 9 Se pte m ber 2 0 2 2  
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 q uir 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 fr 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 las t d ose of st u d y I M P, re gar dless of ca usalit y, s h o ul d als 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 h as 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 use 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 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.  
Re q uire me nts f or c ollecti o n i n t he M o nit ori n g P hase :  
D uri n g t h e M o nit ori n g P hase, all A Es  rel ate d t o 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).  
Electr o nic Seri o us A d v erse E ve nt (e S A E) Re p orti n g Pr ocess   
•  Site pers o n nel rec or d all S A E data i n t he e C R F data base a n d fr o m t here tra ns mit t he S A E 
i nf or mati o n 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’s k n o wle d ge of t he e ve nt. 
Detaile d i nstr ucti o ns ca n be f o u n d i n t he  e C R F c o m pleti o n g ui deli nes.  
•  If f or a n y reas o n it is n ot p ossi ble t o rec or d t he S A E i nf or mati o n electr o nicall y, ie, t he e C R F 
data base is n ot f u ncti o ni n g, rec or d t h e S A E o n t he pa per seri o us a d v erse e ve nt re p orti n g 
f or m a n d s u b mit wit hi n 2 4 h o urs as descri be d a b o ve.  
E mail:   
M A N T A _safet y @ gl p g. c o m  
•  As s o o n as it is p ossi ble t o d o s o, a n y S A E re p orte d via pa per m ust be tra ns cri be d i nt o t he 
e C R F Data b ase acc or di n g t o i nstr ucti o ns i n t he e C R F c o m pleti o n g ui deli n es.  
•  If a n S A E has b ee n re p orte d via a pa p er f or m b ecause t he e C R F data base h as bee n l oc ke d, 
n o  f urt her acti o n is necessar y. 
•  All A Es a n d S A Es will be rec or de d i n t he e C R F d ata base wit hi n t he ti meli nes o utli ne d i n t he 
e C R F c o m pleti o n g ui d eli ne.  
•  F or fatal or life -t hreate ni n g e v e nts, c o pies of h os pital case re ports, 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 bje ct i de ntifiers.  

Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  8 2  
 
0 9 Se pte m ber 2 0 2 2  
•  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 nt 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. 
7. 4.  
S p o ns or Re p orti n g Re q uire me nts  
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 b e re q uire 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 us pecte d u ne x pecte d seri o us a d verse reacti o ns ( 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 p ecifie d desi g n ee will n otif y w orl d wi de 
re g ulat or y a ge ncies a n d t he rele v a 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 re g ul ati 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 or desi g n ee 
usi n g refere nce safet y i nf or mati o n s pecifie d i n t he I B. Met h otre x ate ma y b e use d as sta n dar d of 
care t h era pi es i n t his st u d y; c o nse q ue ntl y, a n y S A Es t hat are attri b ute d t o me t h otre x ate b y t he 
i n vesti gat or will be f or war de d t o its mar keti n g a ut h orizati 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.  
7. 5.  
Cli nic al L a b or at or y A b n or m alities  
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 n vesti gati o nal me dici nal pr o d uct 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 
well 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 mal ass ess me nts 
(e g, ele ctr ocar di o gra m, X -ra ys, vital si g ns) t hat are ass ociat e 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 descri 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 m alit y is part of a s y n dr o m e, rec or d t he 
s y n dr o me or dia g n osis (i e, a ne mia) n ot t he l a 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 o m m o n Ter mi n ol o g y Criteria f or 
A d verse E v e nts ( 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. 

Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  8 3  
 
0 9 Se pte m ber 2 0 2 2  
7. 6.  
T o xicit y M a n a ge me 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  8  a n d as o utli ne d bel o w.  
Refer t o Secti o n  3. 3 , 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. 3  
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 m e dical m o nit or or desi g n ee s h o ul d 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 bl e.    
7. 6. 1.  
Gr a des 1 a n d 2 L a b or at or y A b n or m alit y or Cli nic al E ve 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 Secti o n  3. 3  ( 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. 3 , 
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 or.  
7. 6. 2.  
Gr a des 3 L a b or at or y A b n or m alit y or Cli nic al E ve 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 Secti o n  3. 3  ( 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. 3 , 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 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 n vesti gati o nal 
me dici nal pr o d uct ma y  b e c o nti n ue d if t he e v e nt is c o nsi dere d t o be u nrelat e d t o 
i n vesti gati o nal me dici nal pr o d uct. 
⎯ 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 n vesti gati o nal me dici n al pr o d uct, 
i n vesti gati o nal me dici nal pr o d uct s h o ul d be wit h hel d u ntil t he t o xicit y ret ur ns 
t o ≤ Gra de  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 n vesti gati o nal 
me dici nal pr o d uct a n d is c o nsi dere d relate d t o i n v es ti gati o nal me dici n al pr o d uct, t he n 
i n vesti gati o nal me dici nal pr o d uct s h o ul d be per ma ne 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. 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 n vesti gati o nal me dici nal pr o d uct ma y n ot re q uire per ma n e nt disc o nti n uati o n.  

Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  8 4  
 
0 9 Se pte m ber 2 0 2 2  
7. 6. 3.  
Gr a des 4 L a b or at or y A b n or m alit y or Cli nic al E ve 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 Secti o n  3. 3  ( 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. 3 , 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 rel ate d t o i n vesti gati o nal me dici nal 
pr o d uct, i n vesti gati o nal me dici nal pr o d uct 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 m alit y ret ur ns t o baseli ne or is ot her wise 
e x plai ne d, w hic he ver occ urs first. A cli nicall y si g nifica nt Gra d e  4 la b orat or y a b n or malit y 
t hat is n ot c o nfir me d b y re peat testi n g s h o ul d be m a na ge d acc or di n g t o t he al g orit h m f or 
t he ne w t o xicit y gra de. 
I n v esti gati o nal me dici nal pr o d uct 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 nifica nt Gra d e 4 l a 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 v ati o n t hat is n o nfasti n g or t hat ca n be 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 n vesti gati o nal me dici n al pr o d uct.  
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 m e dical m o nit or or d esi 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 d eci de t h e 
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 m e dical  m o nit or or 
desi g nee . T he m e dical m o nit or s h o ul d c o ns ult t he me dical lea der as n ee de d. 
7. 7.  
S peci al Sit u ati o ns Re p orts  
7. 7. 1.  
Defi niti o ns of S peci al Sit u ati o ns  
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 o f 
i nfecti o us a ge nts via t he pr o d uct, c o u nterfeit or falsifie d me dici ne, 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 miss e 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; or p ot e ntial me dicati o n err or.  

Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  8 5  
 
0 9 Se pte m ber 2 0 2 2  
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 pri ate 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 ot 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 a me dici nal  pr o d uct.  
Pr o d uct c o m plai nt is defi ne d as c o m pla i 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 me dici nal  pr o d uct wit h a false re pres e ntati o n of: a) its 
i de ntit y, b) its s o urce, or c) its hist or y. 
7. 7. 2.  
I nstr ucti o ns f or Re p orti n g S peci al Sit u ati o ns 
7. 7. 2. 1.  
I nstr u cti o ns f or Re p orti n g Part ner Pre g n a ncies 
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 t he S p o ns or’s or ot her st u d y 
dr u gs m ust be re p orte d a n d rele va nt i nf or m ati o n s h o ul d be s u b mitte d t o 
M A N T A _safet y @ gl p g. c o m  usi n g t he pre g n a nc y a n d pre g na n c 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 n a n c y o cc urs after t he st u d y has bee n c o m plet e d, t he o utc o me s h o ul d be 
re p orte d dir ectl y t o M A N T A _safet y @ gl p g. c o m .  
Ref er t o A p pe n di x  5  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.  

Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  8 6  
 
0 9 Se pte m ber 2 0 2 2  
7. 7. 2. 2.  
Re p orti n g Ot her S pecial Si t uati o ns 
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 M A N T A _s afet y @ gl p g.c o m  wit hi n 2 4 h o urs of t he i n vesti gat or bec 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 dr u g, b ut d o n ot a p pl y t o 
c o nc o mita nt me dicati o ns.  
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 o n ot nee d t o be re p orte d o n t he s peci al 
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 mita 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.  

Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  8 7  
 
0 9 Se pte m ber 2 0 2 2  
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 ysis O bjecti ves a n d E n d p oi nts  
8. 1. 1.  
A n al ysis O bjecti ves  
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 b aseli 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 are:  
•  T o e va l 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 b aseli 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 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 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  
T he e x pl orat or y o bj ecti v es of t his st u d y are:  
•  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 haracteriz e 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  
)  
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 % 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.  
C CI

Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  8 8  
 
0 9 Se pte m ber 2 0 2 2  
8. 1. 3.  
Sec o n d ar y E n d p oi nts  
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 per m c o nce ntrati o n at 
Wee k  2 6  
•  C ha n ge fr o m bas eli ne i n perce nt m otile s per m at Wee ks 1 3 a n d 2 6  
•  C ha n ge fr o m bas eli 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 bas eli ne i n s per m c o nce ntrati o n at Wee ks 1 3 a n d 2 6  
•  C ha n ge fr o m bas eli 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 bas eli 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 nts  
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 %  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  
•  C ha n ge fr o m bas eli ne i 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  
•  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 ysis C o n ve nti o ns  
8. 2. 1.  
A n al ysis Sets  
8. 2. 1. 1.  
All Ra n d o mize d Set  
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.  
Se me n A nal ysis Set  
T he Se me n A nal ys is Set i ncl u des all ra n d o mize d s u bjects w h o ha ve b aseli n e a n d at least o ne 
p ost -baseli ne se 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.  
Safet y A nal ysis Set  
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 n e 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 har mac o ki netic ( P K) A nal ysis Set  
T he P K a nal ysis set i ncl u des all s u bjects i n t he Safet 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 f or 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. 

Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  8 9  
 
0 9 Se pte m ber 2 0 2 2  
8. 3.  
D at a H a n dli n g C o n ve nti o ns  
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 listi n gs. B L Q val u e s 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 o w er li mit of q ua ntitati o n  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 si g nifi ca nt di git, res pecti 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 n e d; if t he res ult o f 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 miza ti o n 
strat u m a n d baseli ne de m o gra p hic c h aracteristics will be s u m marize d. D etails o n ha n dli n g 
missi n g data 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.  
De m o gr a p hic D at a a n d B aseli ne C h ar acteristi cs  
De m o gra p hic a n d baseli n e 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, 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 cate g orical varia bles. 
De m o g ra 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 atistic al A n al ysis  
8. 5. 1.  
Pri m ar y A n al ysis  
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 b aseli 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 per 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 ma 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 f or I n d ustr y ( O ct o ber 2 0 1 8): “ Testic ular t o xicit y: E val uati o n D uri n g Dr u g 
De vel o p me nt”. T h e pr o p orti o n of s u bjects e x perie nci n g at least a 5 0 % d ecrease i n s per m 
c o nce ntr ati o n fr o m baseli ne will be calc ulat e d f or eac h tr eat me nt gr o u p. T h e differe nce bet wee n 
t he fil g oti ni b a n d place b o gr o u ps will be calc ulat e d t o get her wit h t he ass o ciate d 9 5 % c o nfi de nce 
i nter val ( CI). 

Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  9 0  
 
0 9 Se pte m ber 2 0 2 2  
S u bjects w h o ha ve 2 sa m ples a vaila ble at Wee k 1 3 will be i ncl u de d i n t he pri mar y a nal 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 patter 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.  
Sec o n d ar y A n al yses  
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 % decrease fr o m baseli ne 
i n s per m c o nce ntr ati o n at Wee k 2 6, a n d 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.  
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 
Baseli ne a n d 9 5 % CIs.  
A n a nal y sis of c o v aria nce ( A N C O V A) m o del a dj usti n g f or b aseli 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 yses  
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 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 pla 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 her S afet y A n al ysis  
All ot her safet y a n al yses will be perf or me d usi n g t he s afet y a nal ysis set.  
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 h ysical e x a mi nati o ns, vital 
si g ns meas ur e me nts at vari o us ti me p oi nts d uri n g t he st u d y, a n d b y t he d oc u me ntati 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 dr 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 xte nt of E x p os ure  
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 nc l 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.  

Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  9 1  
 
0 9 Se pte m ber 2 0 2 2  
8. 5. 6.  
A d verse E ve nts  
Cli nical a n d la b orat or y a d verse e v e nts  will be c o d e d usi n g t he M e dical Dicti o nar y f or 
Re g ulat or y Acti vities ( Me d D R A). S yst e m Or ga n Class, Hi g h -Le vel Gr o u p Ter m ( H L G T), 
Hi g h -Le vel Ter m ( H L T), Preferre d Ter m ( P T), a n d L o wer -Le vel Ter m ( L L T) will be attac he d t o 
t he cli nical data bas e. 
Treat me nt -E m er ge nt A d verse E ve nts ( T E A Es) are:  
•  A n y A Es wit h a n o nset d ate o n or after t he 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  
•  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 O C 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 relati o ns hi p 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 ns  
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 ha 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 o r 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  4 . 
8. 6.  
P h ar m a c o ki netic A n al ysis  
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 statistics (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, sta n dar d de viati o n ( S D), me dia n, mi ni m u m, a n d 
ma xi m u m). Plas ma c o nce ntrati 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 b e pl otte d i n 
se mi l o garit h mic a n d li near f or mats as mea n  sta n dar d de viati o n. 
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 ple Size  
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 % c o nfi de n ce i nter val wi dt h t hat is reas o na bl y narr o w f or 
t he perce nta 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. T his sa m ple size is s u g geste d i n F D A’s g ui da nce o n 
testic ular t o xicit y st u dies { U. S. De part me nt of Healt h a n d H u ma n Ser vices ( D H H S) 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 bjec ts per ar m ma y be 
e nr olle d.  

Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  9 2  
 
0 9 Se pte m ber 2 0 2 2  
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 r he u matic diseases ( G L P G 0 6 3 4-C L -2 2 7) wit h t he sa me o bjecti ve . T he t otal 
pla n ne d n u m ber of e nr oll e d 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 mittee /S p o ns or S afet y M a n a ge me nt Te a m  
A n e xter nal 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 
data 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 he r t he n at 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 mo 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 
t he 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 
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 h e 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 will 
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 ve l o p t he sa me ( b y preferre d ter m) relate d, Gra de 4, u n e x pecte d a d verse e v e nt 
( A E) i n t he i nfecti o ns a n d i nfestati o ns s yste m or ga n class; 
•  ≥ 2 s u bjects de vel o p a n y relate d, Gra de 4, t hr o m b oe m b olic e ve nt t hat has b ee 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 6 , i ncl u di n g t he dat a f or 
I A 2. As of a m e n d me nt 6 , 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 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 m e 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 de d, safet y iss ues will be escalate d t o t he S S M T 
per i nter nal sta n d ar d pr o ce d ures , i n cl u di n g t he or ga nizati o n of a d h o c meeti n gs if re q uir e d. T he 
S S M T ca n c o ns ult e xt er nal e x perts, if dee me d necessar y, a n d ca n re vie w d ata i n a n  u n bli n de d 
fas hi o n. 

Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  9 3  
 
0 9 Se pte m ber 2 0 2 2  
8. 9.  
C ar di o v asc ul ar S af et y E n d p oi nt A dj u dic ati o n C o m mittee ( 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 infarcti o n  
•  Str o ke  
•  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 nter n al I n de pe n de nt S afet y Re vie w 
A Gilea d 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 
Gilea d i nter nal u n bli n de d tea m ma y be gra nte d t he access t o bli n de d a n d 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 
Gilea d 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 nte r 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 6, 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 de d I nteri m A n al ysis  
U n bli n de d i nteri m a nal ys es of t he cli nical trial d ata will be perf or me d b y t h e S p o ns or 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  ( or O L Wee k 1 3 ) ass ess 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 v ersi 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 hese 
ti me p oi nts is a vaila ble (I A 2; see Defi niti o n  of  Ter ms ). A Data I nt e grit y a n d C o m m u nicati o n 

Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  9 4  
 
0 9 Se pte m ber 2 0 2 2  
Pla n f or t he i nteri m a nal ysis will be de vel o pe d pri or t o u n bli n di n g . T he a n al yses will be 
c o n d ucte d pri maril y t o e val uate t he testic ular s afet y a n d f urt her details will be descri b e d i n t he 
S A P .  
F or o n g oi n g s u bjects, t he st u d y tea m s 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 treat me nt assi g n me nts u ntil t he 
fi nal anal ysis w he n t he d ata base h as bee n l o c ke d.  P u blicati o n of t he I A 2 data is pla n ne d b y t h e 
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 t ea 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 bef ore I A 2.  
8. 1 2.  
I nte gr ate d Se me n A n al ysis  
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, G S-U S -4 1 8 -4 2 7 9, will be c o m bi ne d wit h si milar data fr o m a 
se parat e st u d y b ei n g c o n d ucte d i n s u bjects wit h r he u matic disease. T h e a n al yses will be 
c o n d ucte d pri maril y t o e val uate t he testic ular s afet y. F urt her details of t he i nte grate d a n al 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. 

Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  9 5  
 
0 9 Se pte m ber 2 0 2 2  
9.  
R E S P O N SI BI LI TI E S  
9. 1.  
I n vesti g at or Res p o nsi bilities 
9. 1. 1.  
G o o d Cli nic al Pr a ctice  
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 nisati 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 ur o pea n U n i o n 
( E U) Cli nical Trials Dir ecti ve 2 0 0 1/ 2 0/ E C a n d G o o d Cli nical Practice 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 o o d Cli nical Practice, as 
o utli ne 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 nter ests 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 nstit uti o n al Re vie w B o ar d (I R B)/I n de pe n de nt Et hics C o m mittee (I E C) 
Re vie 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 nf or me d c o ns e nt f or m, a n d a n y acc o m p a n yi n g mat erial t o be pr o vi de d t o t he s u bject 
(s uc h as a d v ertise me nts, s u bject i nf or mati o n s heets, or descri 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 o c u m e nte d a n d pr o vi de d as a l etter 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 will 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 mme 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.  

Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  9 6  
 
0 9 Se pte m ber 2 0 2 2  
9. 1. 3.  
I nf or me d C o nse nt 
T he i n vesti gat or is res p o nsi ble f or o b tai 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 derta ki n g a n y st u d y -relate d pr oce d ures. T h e 
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 de nti alit y  
T he i n vesti gat or m u st 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 r ec 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 res 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 trial. S u bject data will be pr ocesse d i n acc or da nce 
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 B, 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 mati o 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 he 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 na 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 Files a n d Rete nti o n of Rec or ds  
T he i n vesti gat or m ust mai ntai n a de q uate a n d acc urate r ec 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 ntal a p pr o val wit h c orres p o n de nce, i nf or me d c o ns e 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 pria te d oc u m e nts a n d c orres p o n de n ce. 

Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  9 7  
 
0 9 Se pte m ber 2 0 2 2  
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 cri teria, ie, hist or y, p h ysi cal e x a mi nati o n, a n d 
c o nfir mati o n of dia g n osis (t o s u p p ort i ncl 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  
•  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 usse 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 pecific pr oce d ures were p erf or me d;  
•  Res ults of efficac y para meters, as r e 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 d v erse e ve nts a n d ot her safet y p ara meters (start a n d e n d dat e, a n d i ncl u di n g 
ca usalit y a n d se v erit 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 ose c ha 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 keti n g a p plicati o n i n 
a n I C H re gi o n (i e, U nite d S tates, 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  years 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 vesti gat or m ust n otif y t he S p o ns or bef ore d estr 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 pr o vi de f or t his arc hi vi n g re q uire me nt at t he st ud 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 ource 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.  

Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  9 8  
 
0 9 Se pte m ber 2 0 2 2  
9. 1. 6.  
C ase Re p ort F or ms  
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. T he  e C R F s h o ul d 
be c o m plete d o n t he d a 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 dat a. T he Eli gi bilit y Criteri a e C R F s h o ul d be 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 E D C s yste m.  Ori gi nal 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 data base l oc 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 vie we d, a n d t hat t he e ntri es acc uratel y reflect 
t he i nf or mati on i n t he s o urce d oc u m e nts.  T he e C R F ca pt ur es t he data re q uire 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 uerie s will be iss ue d t o t he 
i n vesti gati ve site staff as data discre p a ncies are i d e ntifie d b y t h e m o nit or or data ma na g eme nt  
staff, w h o r o uti nel 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 h e site 
c o or di nat or is res p o nsi bl e 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 data 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, dat a e ntr y err or). At t he c o n cl usi o n of t he trial, 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 dat a e ntere d b y t h at site.  T his arc hi ve m ust be st ore d i n 
acc or da nce wit h t he rec or ds rete nti o n re q uir e me nts o utli ne d i n Secti o n  9. 1. 5 .  
9. 1. 7.  
I ns pecti o ns 
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 trial t o t he 
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 oc ol C o m pli a nce  
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 ns or Res p o nsi bilities  
9. 2. 1.  
Pr ot oc ol M o dific ati o ns  
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 IR 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.  

Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  9 9  
 
0 9 Se pte m ber 2 0 2 2  
9. 2. 2.  
St u d y Re p ort a n d P u blic ati o ns  
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 bstract, ma n uscri pt, or pres e 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 pres e ntati o n.  
•  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 n ces 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 ol d p u blicati 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 m e d necessar y.  
9. 3.  
J oi nt I n vesti g at or/ S p o ns or Res p o nsi bilities  
9. 3. 1.  
P a y me nt Re 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 I n v esti gat or's Meeti n gs . If re q uir e d u n der t h e 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 trial pa y m e nts, meal, tra v el 
e x pe nses or rei m b urse me nts, c o ns ulti n g fe es, a n d a n y ot h er tra nsfer of val u e.  
9. 3. 2.  
Access 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 t o 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 ble 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.  

Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  1 0 0  
 
0 9 Se pte m ber 2 0 2 2  
9. 3. 3.  
Access t o I nf or m ati o n f or A u diti n g or I ns pecti o ns  
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 u ct 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 m e di cal m o nit or or desi g n ee i m me diatel y. T he i n vesti gat or 
a grees t o pr o vi d e t o re prese ntati ves of a re g ulat or y a ge nc y or t h e S p o ns or access t o rec or ds, 
facilities, a n d pers o n n el f or t he effecti ve c o n d uct of a n y i ns pecti o n or a u dit. 
9. 3. 4.  
St u d y Disc 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 S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  1 0 1  
 
0 9 Se pte m ber 2 0 2 2  
1 0.  
R E F E R E N C E S  
Ara uj o A B, O' D o n n ell A B, Bra m billa DJ, Si m ps o n W B, L o n gc o pe C, Mats u m ot o A M, et al. 
Pre vale nce a n d i nci de n ce of a n dr o ge n d eficie nc y i n mi d dle -a ge d a n d ol der me n: 
esti mates fr o m  t he Massa c h usetts Male A gi n g St u d y. J Cli n E n d ocri n ol Meta b 2 0 0 4; 8 9 
( 1 2): 5 9 2 0-6.  
Ba u m gart D C, Sa n d b or n WJ. Cr o h n's disease. La n cet 2 0 1 2; 3 8 0 ( 9 8 5 3): 1 5 9 0 -6 0 5.  
Bea u gerie L, Itz k o witz S H. Ca ncers C o m plicati n g I nfla m mat or y B o wel Disease. N E n gl J Me d 
2 0 1 5; 3 7 2 ( 1 5): 1 4 4 1-5 2.  
Bressler B, M ars hall J K, Ber nstei n C N, Bitt o n A, J o nes J, Le o ntia dis GI, et al. Cli nical practice 
g ui deli nes f or t he me dical ma na ge me nt of n o n h os pitalize d ulcerati ve c olitis: t he T or o nt o 
c o nse ns us. Gastr o e nter ol o g y 2 0 1 5; 1 4 8 ( 5): 1 0 3 5 -5 8 e 3.  
C h eifetz A S. Ma na ge me nt of acti ve Cr o h n diseas e. J A M A 2 0 1 3; 3 0 9 ( 2 0): 2 1 5 0 -8.  
C oc kcr oft D W, Ga ult M H. Pre dicti o n of creati ni ne cleara nce fr o m s er u m creati ni ne. Ne p hr o n 
1 9 7 6; 1 6: 3 1 -4 1.  
Da nese S, Fi occ hi C. Ulcerati ve c olitis. N E n gl J Me d 2 0 1 1; 3 6 5 ( 1 8): 1 7 1 3 -2 5.  
Da per n o M, D' Hae ns G, Va n Assc he G, Baert F, B ul ois P, Ma u n o ur y V, et al. De vel o p me nt a n d 
vali dati o n of a ne w, si m plifie d e n d osc o pic acti vit y sc ore f or Cr o h n's disease: t he S E S -
C D. Gastr oi ntesti nal e n d osc o p y 2 0 0 4; 6 0 ( 4): 5 0 5 -1 2.  
Di g nass A, Va n Ass c he G, Li n dsa y J O, Le ma n n M, S o der h ol m J, C ol o m bel J F, et al. T he sec o n d 
E ur o pea n e vi de nce -bas e d C o nse ns us o n t he dia g n osis a n d ma na ge me nt of Cr o h n's 
disease: C urre nt ma n a ge me nt. J o ur nal of Cr o h n's & c olitis 2 0 1 0; 4 ( 1): 2 8 -6 2.  
El -Be h eir y A, El -Ma ns y E, Ka mel N, Sala m a N. Met h otre x ate a n d fertilit y i n me n. Arc h A n dr ol 
1 9 7 9; 3 ( 2): 1 7 7 -9.  
F u k u na ga K, Mats u m ot o T. C urre nt stat us a n d f ut ure pers pecti ves of le u k o c yt a p heresis f or 
i nfla m mat or y b o wel disease. J Gastr oe nter ol H e pat ol 2 0 1 2; 2 7 ( 6): 9 9 7-1 0 0 3.  
Hellstr o m WJ, Gittel ma n  M, J ar o w J, Stei dle C, Mc M urra y J, Talle y D, et al. A n e val uati o n of 
se me n c haract eristics i n me n 4 5 years of a ge or ol der aft er dail y d osi n g wit h ta dalafil 
2 0 m g: res 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 oll e d, 9 -m o nt h 
st u d y. E ur o pea n ur ol o g y 2 0 0 8; 5 3 ( 5): 1 0 5 8 -6 5.  
Hellstr o m WJ, O verstreet J W, Y u A, Sai kali K, S he n W, Beasle y C M, Jr., et al. 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. J Ur ol 2 0 0 3; 1 7 0 
( 3): 8 8 7-9 1.  

Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  1 0 2  
 
0 9 Se pte m ber 2 0 2 2  
It o H, T a kaz oe M, F u k u d a Y, Hibi T, K us u ga mi K, A n d o h A, et al. A pil ot ra n d o mize d trial of a 
h u ma n a nti -i nterle u ki n-6 rece pt or m o n ocl o nal a nti b o d y i n acti ve Cr o h n's disease. 
Gastr oe nter ol o g y 2 0 0 4; 1 2 6 ( 4): 9 8 9 -9 6; disc ussi o n 4 7.  
J ar vi K, D ula E, Dre h o bl M, Pr y or J, S ha pir o J, Se ger M. 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 ne le v els. J Ur ol 2 0 0 8; 1 7 9 ( 3): 1 0 6 0 -5.  
J ess T, R u n g oe C, Pe yri n-Bir o ulet L. Ris k of C ol orectal Ca n cer i n Patie nts Wit h Ulcera ti ve 
C olitis: A Meta -a nal ysis of P o p ulati o n -Base d C o h ort St u dies. Cli n Gastr oe nter ol He pat ol 
2 0 1 2; 1 0 ( 6): 6 3 9 -4 5.  
Ka p pel ma n M D, Rifas -S hi ma n S L, Klei n ma n K, Olle n d orf D, B o us var os A, Gra n d RJ, et al. T he 
pre vale n ce a n d ge o gra p hic distri b uti o n of Cr o h n's dis ease a n d ulcerati ve c olitis i n t he 
U nite d States. Cli n Gastr oe nter ol He p at ol 2 0 0 7; 5 ( 1 2): 1 4 2 4 -9.  
Keel B A. Wit hi n - a n d bet wee n -s u bject variati o n i n se me n para meters i n i nfertile me n a n d 
n or mal se me n d o n ors. Fertilit y a n d sterilit y 2 0 0 6; 8 5 ( 1): 1 2 8 -3 4.  
K or n bl ut h A, Sac har D B. Errat u m: Ulcerati ve C olitis Practice G ui deli nes i n A d ults: A merica n 
C olle ge of Gastr oe nt er ol o g y, Practice Para meters C o m mittee. T he A merica n J o ur nal of 
Gastr oe nter ol o g y 2 0 1 0.  
K orze ni k J R. I n vesti gati o nal t hera pies i n t he me dical ma na ge me n t of Cr o h n disease. A vaila bl e 
at: w w w. u pt o date.c o m/c o nte nts/ 4 0 7 6. U p T o Date 2 0 1 6.  
M ol o dec k y N A, S o o n I S, Ra bi D M, G hali W A, Ferris M, C her n off G, et al. I n creasi n g i n ci de nce 
a n d pre val e nce of t he i nfl a m mat or y b o wel diseas es wit h ti me, base d o n s yste matic 
re vie w. G astr oe nter ol o g y 2 0 1 2; 1 4 2 ( 1): 4 6-5 4 e 4 2; q uiz e 3 0.  
M ulli ga n T, Fric k M F, Z ura w Q C, Ste m ha ge n A, Mc W hirter C. Pre vale nce of h y p o g o na dis m i n 
males a ge d at least 4 5 years: t he HI M st u d y. I nt J Cli n Pract 2 0 0 6; 6 0 ( 7): 7 6 2-9.  
Na m o ur F, Di deric hs e n P M, C o x E, Va yssiere B, Va n der Aa A, Tasset C, et al. 
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. Cli n 
P har mac o ki net 2 0 1 5; 5 4 ( 8): 8 5 9 -7 4.  
Ol derei d N B,  G or d ela dze J O, Kir k h us B, P ur vis K. H u ma n s per m c h aract eristics d uri n g fre q u e nt 
ejac ulati o n. J Re pr o d Fertil 1 9 8 4; 7 1 ( 1): 1 3 5 -4 0.  
P har macia & U pj o h n C o. Az ulfi di ne ® Ta blets c o ntai n s ulfasalazi ne, 5 0 0 m g, f or oral 
a d mi nistrati o n. U S Prescri bi n g I nf o mati o n. 2 0 1 4:  
Sa n d b or n WJ, Fea ga n B G, Ha na u er S B, L o c hs H, L of ber g R, M o di glia ni R, et al. A re vie w of 
acti vit y i n dices a n d efficac y e n d p oi nts f or cli nical trials of me dical t hera p y i n a d ults wit h 
Cr o h n's diseas e. Gastr o e nter ol o g y 2 0 0 2; 1 2 2 ( 2): 5 1 2 -3 0.  

Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  1 0 3  
 
0 9 Se pte m ber 2 0 2 2  
Si k ka S C, C h e n C, Al mas M, D ula E, K na p p L E, Hellstr o m WJ. Pre ga 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. Pai n Pract 2 0 1 4.  
Si k ka S C, Hellstr o m WJ. C urre nt u p dates o n la b orat or y t ec h ni q ues f or t he dia g n osis of male 
re pr o d ucti ve fail ure. Asia n J A n dr ol 2 0 1 6. 
S uss ma n A, Le o n ar d J M. Ps oriasis, met h otre x ate, a n d oli g os per mia. Arc h Der mat ol 1 9 8 0; 1 1 6 
( 2): 2 1 5-7.  
U. S. De part me nt of Healt h a n d H u ma n Ser vices ( D H H S), F o o d a n d Dr u g A d mi nistr ati o n 
( F D A), Ce nter f or Dr u g E val uati o n a n d Researc h ( C D E R). Testic ular T o xicit y: 
E val uati o n D uri n g Dr u g De vel o p me nt G ui da nce f or I n d ustr y.  2 0 1 8.  
U n gar o R, Me ha n dr u S, Alle n P B, Pe yri n -Bir o ulet L, C ol o m bel J F. Ulcerati ve c olitis. La n cet 
2 0 1 6: 1 -1 5.  
Ve nt ha m  N T, K e n ne d y N A, Ni m m o E R, Satsa n gi J. Be y o n d ge n e disc o ver y i n i nfla m mat or y 
b o wel disease: t he e mer gi n g r ole of e pi ge n etics. Gastr oe nter ol o g y 2 0 1 3; 1 4 5 ( 2): 2 9 3 -3 0 8.  
Ver meir e S, Sc hrei ber S, Petr y ka R, K ue h bac her T, He b uter ne X, R o bli n X, et al. Cli nical 
remissi o n i n patie nts wit h m o derate -t o-s e vere Cr o h n's diseas e treate d wit h fil g oti ni b (t he 
FI T Z R O Y st u d y): res ults fr o m a p hase 2, d o u ble -bli n d, ra n d o mise d, place b o -c o ntr olle d 
trial. La ncet 2 0 1 7; 3 8 9: 2 6 6-7 5.  
W orl d Healt h Or ga niz ati o n ( W H O). 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 per m-cer vical m uc us i nterati 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). W H O La b orat or y m a n ual f or t h e 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.  
 
 

Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  1 0 4  
 
0 9 Se pte m ber 2 0 2 2  
1 1.  
A P P E N DI C E S  
A p pe n di x  1.  
S p o ns or a n d I n vesti gat or Si g nat ure P a ge  
A p pe n di x  2.  
St u d y Pr oce d ures T a bles  
A p pe n di x  3.  
Ma y o Sc ori n g S yste m * f or Asse ss me nt of Ulcerati ve C olitis Acti vit y 
A p pe n di x  4.  
C T C A E Gra di n g Scale f or Se verit y of A d verse E ve nts  
A p pe n di x  5.  
Pre g na nc y Preca uti o ns, Defi niti o n f or Fe male of C hil d beari n g P ote ntial, a n d 
C o ntrace pti ve Re q uire me nts  
A p pe n di x  6.  
Cli nical La b orat or y Assess me nt T a ble  
A p pe n di x  7.  
Pr oce d ures a n d S pecificati o ns  
A p pe n di x  8.  
Ma na ge me nt of Cli nical a n d L a b orat or y A d verse E ve nts  
A p pe n di x  9.  
Cr o h n’s Disease Acti vit y I n de x ( C D AI)  
A p pe n di x  1 0.  
Si m ple E n d osc o pic Sc ore f or Cr o h n’s Disease ( S E S -C D)  
A p pe n di x  1 1.  
St u d y Fl o w  
 

Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9 ( G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  1 0 5  
 
0 9 Se pte m ber 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 Testic ular 
Safet y of Fil g oti ni b i n A d ult  Males  wit h M o derat el y t o Se verel y Acti ve I nfla m mat or y B o wel 
Disease   
G S -U S -4 1 8 -4 2 7 9 , A me n d me nt # 6 , 0 9 Se pte m ber  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 ocu 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 E N 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 pl ete 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 Gala pa g os N V . 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 m e 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 S -U S -4 1 8 -4 2 7 9  (G L P G 0 6 3 4 -C L -2 2 8)  
 
Fi nal  
Gala pa g os N V  
 
A me n d me nt 6  
C O N FI D E N TI A L  
 
P a ge  1 0 6  
 
0 9 Se pte m ber 2 0 2 2  
A p pe n di x  2 . 
St u d y Pr oce d ures T a bles  
St u d y Pr o ce d ure  
Scree ni n g  
P art A  
( Secti o n 6. 4 ) 
P art B  
( Secti o n 6. 5 ) 
O pe n -L a bel Fil g oti ni b P h ase  
( Secti o n 6. 6 ) 
L o n g  Ter m 
E xte nsi o n  
( Secti o n 6. 1 0 ) 
3 0 D a y S afet y  
F oll o w -u p e 
E T f 
D a y 
1  
W k 
2  
W k 
4  
W k 
8  
W k 
1 3 a  
W k 
2 0  
W k 
2 6 a  
S per m 
P ar a meter 
Eli gi bilit y 
C o nfir m ati o n b 
O L 
D a y 
1  
O L 
W k 
2  
O L 
W k 
4  
O L 
W k 
8  
O L 
W k 
1 3 c 
L T E Wee k  1 3 
t hr o u g h L T E 
Wee k  1 9 5 d  
4 5  
d a ys  
 
± 5  
d a ys  
± 5  
d a ys  
± 5  
d a ys  
+  5  
d a ys  
± 5  
d a ys  
+  5  
d a ys  
 
 
± 5  
d a ys  
± 5  
d a ys  
± 5  
d a ys  
+  5  
d a ys  
± 1 0  d a ys  
± 5  
d a ys  
 
I nf or me d C o nse nt 
X  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Me dical Hist or y, N u m ber 
of ti mes s u bj ect 
i m pre g nate d w o me n, I B D 
Hist or y, a n d 
De m o gra p hics  
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 g  
X  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
S y m pt o m -directe d 
P h ysical E xa m, as nee de d  
 
X  
X  
X  
X  
X  
X  
X  
 
X  
X  
X  
X  
X  
X  
X  
X  
Vital Si g ns g a n d W ei g ht  
X  
X  
X  
X  
X  
X  
X  
X  
 
X  
X  
X  
X  
X  
X  
X  
X  
Hei g ht  
X  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1 2 -lea d E C Gg  
X  
 
 
 
 
 
 
X  
 
 
 
 
 
X  
X h 
 
X  
Fle xi ble Si g m oi d osc o p y i 
X  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Ile oc ol o n osc o p yi 
X  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
C o m plete Ma y o Cli nic 
Sc ore  (c o m plete M C S)j 
X  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
P artial Ma y o Cli nic Sc ore   
( partial M C S)j 
 
X  
X  
X  
X  
X  
X  
X  
 
X  
X  
X  
X  
X  
X  
 
X  

Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9  (G L P G 0 6 3 4 -C L -2 2 8)  
 
Fi nal  
Gala pa g os N V  
 
A me n d me nt 6  
C O N FI D E N TI A L  
 
P a ge  1 0 7  
 
0 9 Se pte m ber 2 0 2 2  
St u d y Pr o ce d ure  
Scree ni n g  
P art A  
( Secti o n 6. 4 ) 
P art B  
( Secti o n 6. 5 ) 
O pe n -L a bel Fil g oti ni b P h ase  
( Secti o n 6. 6 ) 
L o n g  Ter m 
E xte nsi o n  
( Secti o n 6. 1 0 ) 
3 0 D a y S afet y  
F oll o w -u p e 
E T f 
D a y 
1  
W k 
2  
W k 
4  
W k 
8  
W k 
1 3 a  
W k 
2 0  
W k 
2 6 a  
S per m 
P ar a meter 
Eli gi bilit y 
C o nfir m ati o n b 
O L 
D a y 
1  
O L 
W k 
2  
O L 
W k 
4  
O L 
W k 
8  
O L 
W k 
1 3 c 
L T E Wee k  1 3 
t hr o u g h L T E 
Wee k  1 9 5 d  
4 5  
d a ys  
 
± 5  
d a ys  
± 5  
d a ys  
± 5  
d a ys  
+  5  
d a ys  
± 5  
d a ys  
+  5  
d a ys  
 
 
± 5  
d a ys  
± 5  
d a ys  
± 5  
d a ys  
+  5  
d a ys  
± 1 0  d a ys  
± 5  
d a ys  
 
Si m ple E n d osc o pic Sc ore 
f or Cr o h n’s Disease 
( S E S-C D)  
X  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Cr o h n’s Disease Acti vit y 
I n de x ( C D AI)k  
X  
X  
X  
X  
X  
X  
X  
X  
 
X  
X  
X  
X  
X  
X  
 
X  
T B ( Q ua nti F E R O N ® ) T est 
X l 
 
 
 
 
 
 
 
 
 
 
 
 
 
X m  
 
 
C hest X -ra yn  
X  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Uri nal ysis o  
X  
X  
 
 
 
X  
 
X  
 
X  
 
 
 
X  
X  
 
X  
Uri ne dr u g scree n o 
X  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
He mat ol o g y a n d 
C he mistr y o  
X  
X  
X  
X  
X  
X  
X  
X  
 
X  
X  
X  
X  
X  
X  
X  
X  
Li pi d pr ofile (fasti n g) o  
 
X  
 
 
 
X  
 
X  
 
X  
 
 
 
X  
X p 
 
 
Ser u m I m m u n o gl o b uli n o  
X  
 
 
 
 
X  
 
X  
 
 
 
 
 
X  
X  
 
 
E n d ocri ne: T S H, H b A 1c o  
X  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
L H, F S H, i n hi bi n B, t otal 
T est oster o ne o 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  
 
X  
 
X  
 
X  
 
X  
 
X  
 
X  
X  
X  
X  
St o ol o  
X  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
C o nc o mita nt Me dicati o ns  
X  
X  
X  
X  
X  
X  
X  
X  
 
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  
 
X  
X  
X  
X  
X  
X  
X  
X  

Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9  (G L P G 0 6 3 4 -C L -2 2 8)  
 
Fi nal  
Gala pa g os N V  
 
A me n d me nt 6  
C O N FI D E N TI A L  
 
P a ge  1 0 8  
 
0 9 Se pte m ber 2 0 2 2  
St u d y Pr o ce d ure  
Scree ni n g  
P art A  
( Secti o n 6. 4 ) 
P art B  
( Secti o n 6. 5 ) 
O pe n -L a bel Fil g oti ni b P h ase  
( Secti o n 6. 6 ) 
L o n g  Ter m 
E xte nsi o n  
( Secti o n 6. 1 0 ) 
3 0 D a y S afet y  
F oll o w -u p e 
E T f 
D a y 
1  
W k 
2  
W k 
4  
W k 
8  
W k 
1 3 a  
W k 
2 0  
W k 
2 6 a  
S per m 
P ar a meter 
Eli gi bilit y 
C o nfir m ati o n b 
O L 
D a y 
1  
O L 
W k 
2  
O L 
W k 
4  
O L 
W k 
8  
O L 
W k 
1 3 c 
L T E Wee k  1 3 
t hr o u g h L T E 
Wee k  1 9 5 d  
4 5  
d a ys  
 
± 5  
d a ys  
± 5  
d a ys  
± 5  
d a ys  
+  5  
d a ys  
± 5  
d a ys  
+  5  
d a ys  
 
 
± 5  
d a ys  
± 5  
d a ys  
± 5  
d a ys  
+  5  
d a ys  
± 1 0  d a ys  
± 5  
d a ys  
 
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 3 )q  
X r 
 
 
 
 
X  
 
X  
X s 
 
 
 
 
X t 
X  
 
X  
Date a n d ti me of m ost 
rece nt ej ac ulati o nu  
X  
 
 
 
 
X  
 
X  
X  
 
 
 
 
X  
X  
 
X  
HI V, He p atitis B, a n d 
He p atitis C v  
X  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
H B V D N A w  
 
 
 
 
 
X  
 
X  
 
 
 
 
 
X  
X  
 
 
Ra n d o mizati o n  
 
X  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
St u d y Dr u g 
Acc o u nta bilit y  
 
 
 
X  
X  
X  
X  
X  
 
X  
 
X  
X  
X  
X  
 
X  
St u d y Dr u g Dis pe nsati o n  
 
X  
 
X  
X  
X  
X  
X  
 
X  
 
X  
X  
X  
X  
 
 
P K c ollecti o n (s parse)  
 
 
X x  
X y  
 
X z 
 
X z 
 
 
X x  
X y  
 
X z 
 
 
 
I n-Cli nic D osi n g aa  
 
X  
X  
 
 
X  
 
X  
 
 
X  
 
 
X  
 
 
 
a 
Wee ks 1 3 a n d 2 6 m ust o cc ur after 1 3 wee ks a n d 2 6 wee ks of dr u g e x p os ure, res pecti vel y . T heref ore, visit wi n d o w f or t h ese visits are + 5 da ys  
b  
S u bjects o n bli n de d st u d y dr u g meeti n g criteria as a n o n -res p o n der ( Wee k 1 3) or f or Disease W orse ni n g (after Wee k 1 3 t hr o u g h 2 6), a n d n ot meeti n g  t h e pre-s pecifie d 
decrease t hres h ol d i n s per m para meters,  are eli gi ble f or o pe n -la bel fil g oti ni b (refer A p pe n di x  1 1  a n d Secti o n 3 ). F or defi niti o ns of I B D res p o nse stat us, Disease W orse ni n g, 
a n d/ or pre -s pecifie d decrease t hres h ol d i n s per m para meters pleas e refer t o Defi niti o n  of  Ter ms a n d Secti o n 3. 4 . 
c 
O L Wee k 1 3 m ust o cc ur after 1 3 we e ks of starti n g o pe n -la bel fil g oti ni b. T heref ore, visit wi n d o w is + 5 da ys. 
d  
S u bjects i n t he L T E will u n der g o sc he d ule d visits f or safet y assess me nts a n d se me n sa m ple c ollecti o n e ver y 1 3 we e ks, starti n g  wit h L T E We e k  1 3 . S e me n m o nit ori n g will be 
c ollecte d u ntil t he Wee k 1 3 pri mar y st u d y res ults are a nal yze d . 
e 
A n y ti me a s u bject disc o nti n ues st u d y dr u g, a safet 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 is re q uire d, e ve n if t h e s u bject is e nteri n g  t he 
M o nit ori n g P hase  
f 
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 2 6, O L Wee k 1 3, reac hi n g re versi bilit y or M o nit ori n g P hase Wee k 5 2  ( w hic he ver occ urs first), or 
L T E We e k 1 9 5, a n E T Visit is re q uire d . S u bjects w h o are Res p o n der s at Wee k 2 6 or at O L Wee k 1 3 a n d c h o ose n ot t o c o nti n ue i n t h e L T E ar e als o re q uire d t o c o m plete E T 
visit assess me nts.  
g  
As detaile d i n A p pe n di x  7  

Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9  (G L P G 0 6 3 4 -C L -2 2 8)  
 
Fi nal  
Gala pa g os N V  
 
A me n d me nt 6  
C O N FI D E N TI A L  
 
P a ge  1 0 9  
 
0 9 Se pte m ber 2 0 2 2  
h  
1 2 -Lea d E C G will be perf or me d at L T E Wee k 1 9 5 or E T, w hic he ver occ urs s o o ner  
i 
Fle xi ble Si g m oi d osc o p y ( U C p atie nts) or ile oc ol o n osc o p y ( C D p atie nts) is o nl y re q uire d if it has n ot bee n d o ne i n t he last 9 0  da ys.  
j 
P artial M C S i ncl u des all parts of t h e c o m plete M C S e xce pt e n d osc o p y. F or defi niti o ns of I B D res p o nse stat us, please refer t o Defi niti o n of Ter ms ; f or defi niti o ns of Disease 
W orse ni n g, please refer t o Secti o n 3. 4  a n d Defi niti o n of Ter ms. S u bject recall f or t h e last 2 4 h o urs will be use d f or t h e patie nt re p orte d c o m p o ne nts of t h e c o m plet e M C S a n d 
partial M C S. S u bjects o n bli n de d st u d y dr u g meeti n g criteria f or N o n -Res p o n der at Wee k 1 3 or Disease W or se ni n g after Wee k 1 3 t hr o u g h Wee k 2 6 (a n d n ot meeti n g t h e 
pre -s pecifie d decrease t hres h ol d i n s per m para meters) will be eli gi ble f or o pe n -la bel fil g oti ni b (see Secti o n 3 ). M C S a n d partial M C S will be c ollecte d f or U C patie nts. 
P h ysicia n Gl o bal Assess me nt is a c o m p o ne nt of M C S a n d partial M C S.  
k  
C D AI will be c ollecte d f or C D p atie nts. S u bject recall f or t h e last 7 da ys will be use d f or t h e patie nt re p or te d o utc o mes of t h e C D AI.  T h e C D AI sc ore calc ulati o ns s h o ul d n ot 
be i n cl usi ve of da ys t h at i n v ol ve a n e n d osc o p y pr oce d ure or pre parati o n f or t hat pr oce d ure.  
l 
Pr o of of n o acti ve or u ntreate d late nt 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 a t scree ni n g m ust i nitiate a n a de q uate c o urse of pr o p h yla 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 after c o ns ulta ti o n wit h t h e m e dical m o nit or or desi g nee.  
m  
I n t h e L T E s u bjects m ust h a ve ye arl y Q ua nti F E R O N®  testi n g. Yearl y T B testi n g be gi ns 1  year fr o m t h e scree ni n g T B test date. If yearl 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  ye ar 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 
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 treate d f or T B wit h a c o m plete a n d a de q ua te co urse of t h era p y as 
per l o cal sta n dar d of care a n d as v erifie d b y t h e 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 be 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 st u d y.  
n  
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 v aila ble f or i n vesti gat or re vie w) wit h o ut 
e vi d e nce of acti v e or late nt T B i nfe cti o n  
o  
As detaile d i n A p pe n di x  6 . F or visits t hat 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. 
p  
Li pi d pr ofile s h o ul d be perf or me d e ver y 2 6 we e ks  
q  
Se me n sa m ples will be c ollecte d o n t he visit da y a n d/ or after t he visit. T h ose meeti n g t h e pre -s pecifi e d decrease t hres h ol d i n s per m para meters (as defi n e d i n t he Defi niti o n of 
Ter ms) m ust e nter t he M o nit ori n g P hase (see sc he d ule b el o w).  
r 
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) visit as m uc h as p ossi ble.  
s 
At ti me of c o nfir mati o n of N o n -res p o n der stat us/ Disease W orse ni n g a n d pri or t o i nitiati o n of o pe n-la bel fil g oti ni b, Se me n A nal ysis m ust c o nfir m s u bject di d n ot meet t h e pre-
s pecifie d decreas e t hres h ol d i n s per m para meters.  
t 
At ti me of c o nfir mati o n of N o n -res p o n der stat us/ Disease W orse ni n g a n d pri or t o e ntr y i nt o t he L T E, Se me n A nal ysis m ust c o nfir m s u bject di d n ot meet t h e pre -s pecifie d 
decrease t hres h ol d i n s per m para meters.  
u  
T his q uesti o n will be as ke d pri or t o eac h se me n c ollecti o n.  
v  
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 p atitis 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 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 h e 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 u ire 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 de 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 trea t 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 or 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 he 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. 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 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 g at or j u d g me nt. 
w  
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 
x  
S parse plas ma P K sa m ples ar e c ollecte d at least 3 0 mi n utes p ost -d ose.   
y  
S parse plas ma P K sa m ples c a n b e c ollecte d at a n y ti me wit h o ut re gar d t o d osi n g.   
z 
S parse plas ma P K sa m ples ar e c ollecte d pre -d ose.  
aa  
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, 1 3, a n d 2 6, a n d O L Wee ks 2 a n d 1 3, su bje cts 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 visit, as detaile d i n 
Secti o n 6. 1 6 . 

Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9  (G L P G 0 6 3 4 -C L -2 2 8)  
 
Fi nal  
Gala pa g os N V  
 
A me n d me nt 6  
C O N FI D E N TI A L  
 
P a ge  1 1 0  
 
0 9 Se pte m ber 2 0 2 2  
St u d y Pr o ce d ure  
M o nit ori n g P h ase  
( Secti o n 6. 7 ) 
E T a  
Visits occ ur e ver y 1 3 w ee ks ( ± 5 d a ys)  
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 b a n d W ei g ht  
X  
X  
1 2 -lea d E C G 
 
X  
P artial Ma y o Cli nic Sc ore  
( partial M C S)c 
 
X  
Cr o h n’s Disease Acti vit y I n de x ( C D AI) d  
 
X  
Uri nal ysis e  
X  
X  
He mat ol o g y a n d C he mistr y e  
X  
X  
L H, F S H, i n hi bi n B, t otal T est oster o ne e  
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 f 
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 3 )g  
X  
 
Date  a n d ti me of m ost rece nt ej ac ulati o n h  
X  
 
a 
N ot re q uire d if Re versi bilit y is met or if s u bject c o m pletes Wee k 5 2  
b  
As detaile d i n A p pe n di x  7  
c 
P artial M C S i ncl u des all parts of t h e c o m plete M C S e xce pt e n d osc o p y. F or defi niti o ns of I B D res p o nse stat us, please refer t o Defi niti o n of Ter ms; f or defi niti o ns of Disease 
W orse ni n g, please refer t o Secti o n 3. 4  a n d Defi niti o n of Ter ms. S u bject recall f or t h e last 2 4 h o urs will be use d f or t h e patie nt re p orte d c o m p o ne nts of t h e c o m plet e M C S a n d 
partial M C S. M C S a n d partial M C S will be c ollecte d f or U C p atie nts. P h ysicia n Gl o bal Assess me nt is a c o m p o ne nt of M C S a n d par tial M C S. 
d  
C D AI will be c ollecte d f or C D p atie nts. S u bject recall f or t h e last 7 da ys will be use d f or t h e patie nt re p orte d o utc o me s of t h e C D AI . T h e C D AI sc ore calc ulati o ns s h o ul d n ot 
be i n cl usi ve of da ys t h at i n v ol ve a n e n d osc o p y pr oce d ure or pre parati o n f or t hat pr oce d ure.  
e 
As detaile d i n A p pe n di x  6  
f 
As detaile d i n Secti o n 7. 3  
g  
Se me n sa m ples will be c ollecte d o n t he visit da y a n d/ or after t he visit  
h  
T his q uesti o n will be as ke d pri or t o eac h se me n c ollecti o n  

Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9  (G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  1 1 1  
 
0 9 Se pte m ber 2 0 2 2  
A p pe n di x  3 . 
M a y o Sc ori n g S yste m * f or Assess me nt of Ulcer ati ve C olitis Acti vit y 
St o ol Fre q ue nc y * * –  E ac h s u bject serves as his 
or her o w n c o ntr ol t o est a blis h t he de gree of 
a b n or m ality of t he st o ol fre q ue n cy  
 
0  
N or mal n u m ber of st o ols f or s u bj ect  
 
1  
1 t o 2 st o ols per da y m ore t ha n n or mal  
 
2  
3  t o 4 st o ols m ore t ha n n or mal 
 
3  
≥ 5 st o ols m ore t ha n n or mal  
Rect al Blee di n g * * –  T he d aily blee di n g sc ore 
re prese nts t he m ost severe blee di n g of t he d ay. 
 
0  
N o bl o o d see n  
 
1  
Strea ks of bl o o d wit h st o ol less t ha n half t he ti me  
 
2  
O b vi o us bl o o d wit h st o ol half or m ore t ha n half of 
 
t he ti me 
 
3  
Bl o o d al o ne passes  
E n d osc o pic fi n di n gs –  Assesse d b y L ocal 
Rea der (i ncl u de o nl y f or M C S assess me nt *)  
 
0  
N or mal or i nacti ve disease  
 
1  
Mil d Disease (eryt he m a, decr e ase d v asc ul ar 
p atter n)  
 
2  
M o derate Disease ( m arke d er yt he m a, l ack of 
 
v asc ul ar p atter n, fri a bility, er osi o ns)  
 
3  
Se vere Disease (s p o nt a ne o us blee di n g, ulcer ati o n) 
P h ysici a n's Gl o b al Assess me nt –  T he 
p hysici a n’s gl o b al assess me nt ack n o wle d ges t he 
t hree ot her criteri a, t he s u bject’s d aily 
rec ollecti o n of a b d o mi n al disc o mf ort a n d ge ner al 
se nse of well-bei n g, a n d ot her o bserv ati o n, s uc h 
as p hysic al fi n di n gs a n d t he s u bject’s 
perf or m a nce st at us.  
 
0  
N or mal  
 
1  
Mil d disease  
 
2  
M o derate disease  
 
3  
Se vere disease  
*  
T he partial Ma y o Cli nic Sc ore ( partial M C S; ra n ge: 0 - 9) uses t he 3 n o n -i n vasi ve s u b-sc ores fr o m, a n d o mits t h e 
e n d osc o pic s u b -sc ore of, t h e f ull Ma y o Cli nic Sc ore (ra n ge: 0 - 1 2)  
* *  S u bject recall f or t h e last 2 4 h o urs will be use d f or t h e patie nt re p orte d c o m p o ne nts of t h e c o m plete M C S a n d partial M C S  

Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9  (G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  1 1 2  
 
0 9 Se pte m ber 2 0 2 2  
A p pe n di x  4 . 
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 o m m o n Ter mi n ol o g y Criteri a f or A d verse E ve nts ( C T C A E) Versi o n  4. 0 3, 
w hic h ca n b e f o u n d at:  
htt ps://e vs. nci. ni h. g o v/ft p 1/ C T C A E / C T C A E _ 4. 0 3/ 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 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.  
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 Ter 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 S -U S -4 1 8 -4 2 7 9  (G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  1 1 3  
 
0 9 Se pte m ber 2 0 2 2  
A p pe n di x  5 . 
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 -fetal a ni mal de vel o p me nt st u dies res ulte d i n 
decrease d n u m bers of via ble rat fet uses, i n crease 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 ot e 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 d e ntifie d. Pre g na n c 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 fe m ale se 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 wit 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  
a.  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 S -U S -4 1 8 -4 2 7 9  (G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  1 1 4  
 
0 9 Se pte m ber 2 0 2 2  
b.  C o ntr 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 ntial 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 ntr 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 part 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 fertilizati 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 xp 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 onsi 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 S -U S -4 1 8 -4 2 7 9  (G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  1 1 5  
 
0 9 Se pte m ber 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 h o d ( L A M). Fe male 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 f or 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 S -U S -4 1 8 -4 2 7 9  (G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  1 1 6  
 
0 9 Se pte m ber 2 0 2 2  
A p pe n di x  6 . 
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 ysi s 
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 ul oc yte c o u nt  
Mea n c or p usc ular v ol u me 
( M C V) 
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 otassi u m  
S o di u m  
Creati ne p h os p h o ki nase 
( C P K) 
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)  
 
Fecal (st o ol)  
Bacterial St o ol C ult ure  
C -Diff T o xi n  
O va a n d P arasites ( O & P)  
 
P har mac o ki netics ( P K)  
Ser u m I m m u n o gl o b uli n  
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 (I N 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) 
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 
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 S -U S -4 1 8 -4 2 7 9  (G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  1 1 7  
 
0 9 Se pte m ber 2 0 2 2  
A p pe n di x  7 . 
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 h ysical e x a mi nati o n s h o ul d i ncl u de s o urce d oc u m e ntati o n of ge n eral 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 h est (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 gical.  
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 ole n u m ber o n a n a ut o matic de vi ce. 
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 oft -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 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 S -U S -4 1 8 -4 2 7 9  (G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  1 1 8  
 
0 9 Se pte m ber 2 0 2 2  
A p pe n di x  8 . 
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  
 
 
N O T E : Re peat la bs s h o ul d occ ur wit hi n 3 t o 7 da ys of t he i nitial a b n or m al la b val ue (e x ce pt f or 
creati ni ne cleara nce, w hi c h s h o ul d be re p eate d wit hi n 7 t o 1 4 da ys of t he i nitial a b n or mal val ue). 
A n u nsc he d ule d visit (ie, se q ue ntial visit) s h o ul d be utilize d t o o btai n t he re peat l a b v al ues.  
 
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 

Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9  (G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  1 1 9  
 
0 9 Se pte m ber 2 0 2 2  
A p pe n di x  9 . 
Cr o h n’s Dise ase Acti vit y I n de x ( C D AI)  
T he C D AI will be calc ul ate d as f oll o ws:  
V ari a ble  n o.  
V ari a ble  
V ari a ble descri pti o n  
M ulti plier  
1  
Li q ui d or ver y s oft st o ol *  
Dail y st o ol c o u nt is s u m me d f or 7  da ys  
2  
2  
A b d o mi nal pai n *  
S u m of 7 da ys of dail y rati n gs as  
0 = n o ne, 1 = mil d, 2 = m o derate, 
3  =  se vere 
5  
3  
Ge neral well bei n g *  
S u m of 7 da ys of dail y rati n gs as  
0 = ge nerall y well, 1 = sli g htl y bel o w 
par, 2  =  p o or, 3  =  ver y p o or, 
4  =  terri ble 
7  
4  
C o m plicati o ns  
N u m ber of liste d c o m plicati o ns:  
Art hritis or art hral gia  
Er yt he ma n o d os u m, p y o der ma 
ga n gre n os u m or a p h t h o us st o matitis 
Iritis or u veitis 
A nal fiss ures or fist ulae or a bscess  
Ot her fist ula  
Fe ver o ver 3 7. 8  ℃ [ 1 0 0 ℉] d uri n g past 
wee k  
2 0 eac h  
5  
Use of a nti -dia rr heal me dicati o ns 
Use of di p he n o x ylate or l o pera mi de or 
ot her o piate f or diarr hea  
0 = N o, 1 = Yes  
3 0  
6  
A b d o mi nal mass  
0 = n o ne, 2 = q uesti o na ble, 5  = defi nite  
1 0  
7  
He mat ocrit †  
Males: 4 7 –  Hct [ %]  
Fe males: 4 2 –  Hct [ %]  
† Res ult m ust be greater t ha n or e q ual 
t o 0. If ne gati ve res ult e nter 0  
6 × differe nce  
8  
W ei g ht ‡  
P erce nta ge de viati o n fr o m sta n dar d 
wei g ht  
[1 –  (c urre nt wei g ht / sta n dar d wei g ht) ] 
× 1 0 0  
‡ Li mit of -1 0  
1  
C D AI sc ore  
 
 
T O T A L  
C D AI = Cr o h n’s Disease Acti vit y I n de x; Hct = he mat o crit  
{ Sa n d b or n 2 0 0 2 }  
*  
S u bject recall f or t h e last 7 da ys will be use d f or t h e patie nt re p orte d c o m p o ne nts of t h e C D AI . T he C D AI s c ore calc ulati o ns 
s h o ul d n ot be i ncl usi ve of da ys t h at i n v ol ve a n e n d osc o p y pr oce d ure or pre parati o n f or t hat pr oce d ure.  

Fil g oti ni b  
Pr ot oc ol G S -U S -4 1 8 -4 2 7 9  (G L P G 0 6 3 4 -C L -2 2 8)  
Fi nal  
Gala pa g os N V  
A me n d me nt 6  
C O N FI D E N TI A L  
P a ge  1 2 0  
 
0 9 Se pte m ber 2 0 2 2  
A p pe n di x  1 0 . 
Si m ple E n d osc o pic Sc ore f or Cr o h n’s Dise ase ( S E S -C D)  
V ari a bles  
Sc ore  
0  
1  
2  
3  
Size of ulcers (c m)  
N o ne  
A p ht h o us ulcers  
( dia meter 0. 1-0 .5)  
Lar ge ulcers  
( dia meter 0. 5-2)  
Ver y lar ge ulcers  
( dia meter > 2) 
Ulcerate d surface ( %)  
N o ne  
< 1 0  
1 0 -3 0  
> 3 0  
Affecte d s urface ( %)  
U naffecte d 
se g me nt 
< 5 0  
5 0 -7 5  
> 7 5  
Prese nce of narr o wi n gs  
N o ne  
Si n gle,  
ca n be passe d  
M ulti ple,  
ca n be passe d  
Ca n n ot be passe d  
T otal S E S -C D (ra n ge: 0 -6 0): s u m of t h e val u es of t h e 4 varia bles f or t h e 5 b o wel se g me nts. V al u es are gi ve n t o eac h varia ble a n d 
f or e ver y e xa mi n e d b o wel se g me nt (e g, rect u m, left c ol o n, tra ns verse c ol o n, ri g ht c ol o n, a n d ile u m) { Da per n o 2 0 0 4 }  

Si g nat ure Pa ge f or gl p g 0 6 3 4-cl- 2 2 8- pr ot oc ol-a me n d # 6 2 4 2 3 6
Si g nat ure Pa ge f or gl p g 0 6 3 4-cl- 2 2 8- pr ot oc ol-a me n d # 6 4 3 9 5 2 _ 7 7 4 9 8 _ 1 0 4 3 1 7
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 6: 2 6 G M T + 0 0 0 0
P P D