Clinical trial NCT03926195
Conditions: Rheumatoid Arthritis Psoriatic Arthritis Ankylosing Spondylitis Non-Radiographical Axial Spondyloarthritis
Sponsor: Galapagos NV
Start date: 2019-05-28; Completion date: 2023-05-10
Enrollment: 109 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The primary objective of this study is to evaluate the effect of filgotinib on semen parameters in adult males with active rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, or non-radiographic axial spondyloarthritis.

Results of this study may be pooled with the results of a separate study being conducted in participants with inflammatory bowel disease (Protocol GS-US-418-4279; NCT03201445) with the same objective.

Detailed description:

Arms: arm 1: Participants received filgotinib 200 milligrams (mg) tablet, orally, once daily up to Week 13 in the double-blind (DB) phase. At Week 13, participants who were arthritis responders, were unblinded and received open-label (OL) treatment filgotinib 200 mg, tablet, orally, once daily up to approximately 143 weeks (until Week 156) in the extension (EXT) phase and participants who were arthritis nonresponders discontinued blinded study drug and started standard of care (SOC) treatment in the EXT phase. Participants on DB treatment or OL filgotinib who entered the monitoring phase (if their sperm parameters met ≥50% decrease threshold in pre-specified semen parameters) discontinued the study drug and started SOC for up to 52 weeks. arm 2: Participants received placebo (matched to filgotinib) tablet, orally, once daily up to Week 13 in the DB phase. At Week 13, participants were unblinded and started SOC treatment in the EXT phase for up to approximately 143 weeks (until Week 156). Participants who entered the monitoring phase (if their sperm parameters met ≥50% decrease threshold in pre-specified semen parameters) continued on SOC treatment.
Interventions: intervention 1: Filgotinib intervention 2: Placebo intervention 3: Standard of Care
Intervention descriptions: intervention 1: 200-mg tablet administered orally once daily intervention 2: Placebo to match filgotinib tablet administered orally once daily intervention 3: Locally approved treatment, accepted by medical experts as a proper treatment for rheumatic conditions, prescribed according to best clinical practice, with no known testicular toxicity.

Protocol documents:
Prot_000.pdf: 
 
 
 
 
 
C LI NI C A L S T U D Y P R O T O C O L  
 
 
St u d y Title:  
A Ra n d o mize d, D o u ble -bli n d, Place b o -c o ntr olle d P hase 2 St u d y t o 
E val uate t he Effect of Fil g oti ni b o n Se me n Para m eters i n A d ult 
Males wit h A cti ve R he u mat oi d Art hritis, Ps oriatic Art hritis, 
A n k yl osi n g S p o n d ylitis or N o n -ra di o gra p hic A xial 
S p o n d yl o art hritis.  
 
 
S p o ns or:  
Gala pa g os N V  
Ge neraal De Wittelaa n L 1 1 A 3  
2 8 0 0 Mec hele n, Bel gi u m  
 
 
 
E u dr a C T N u m ber:  
Cli nic al Tri als. g o v 
I de ntifier: 
2 0 1 8 -0 0 3 9 3 3 -1 4  
 
N C T 0 3 9 2 6 1 9 5  
 
 
I n dic ati o n: 
R he u mat oi d art hritis, ps oriatic art hritis, a n k yl osi n g s p o n d ylitis, or 
n o n -ra di o gra p hical a xial s p o n d yl oart hritis 
 
 
Pr ot oc ol I D:   
G L P G 0 6 3 4 -C L -2 2 7  
 
 
Cli nic al De vel o p me nt 
Le a der : 
 
 
 
Me dic al Le a der : 
 
 
 
Pr ot oc ol 
Versi o n/ D ate:  
Ori gi nal:  0 5 Fe b  2 0 1 9  
A me n d me nt 1: 2 6 Ma y 2 0 2 0  
 
A me n d me nt  2: 0 9 Se p  2 0 2 2  
 
C O N FI D E N TI A LI T Y S T A T E M E N T  
T he i nf or mati o n c o ntai ne d i n t his d oc u me nt is pri vile ge d a n d c o nfi de ntial. It is t he pr o pert y of Gala pa g os N V a n d 
ma y n ot b e use d, discl ose d, re pr o d uce d or ot her wise disse mi nate d wit hi n y o ur or ga nizati o n or c o m m u nicate d t o 
a n y t hir d parties wit h o ut t he e x press writte n a ut h orizati o n of Gala pa g os N V . 
 
P P D
P P D


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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

SAP_001.pdf: 
S T A TI S TI C A L A N A L Y SI S P L A N
St u d y Title:
A Ra n d o mize d, D o u ble -bli n d, Place b o -c o ntr olle d P hase 2 
St u d y  t o E val uate t he Effect of Fil g oti ni b o n Se me n Para meters 
i n A d ult Males wit h Acti ve R he u mat oi d Art hritis, Ps oriatic 
Art hritis, A n k y l osi n g S p o n d ylitis or N o n-ra di o gra p hic A xial 
S p o n d y l oart hritis
N a me of Test Dr u g:
Fil g oti ni b
St u d y N u m ber:
G L P G 0 6 3 4 -C L - 2 2 7
Pr ot oc ol Versi o n ( D ate):
Ori gi nal: 0 5 Fe br uar y  2 0 1 9
A me n d me nt 1: Ma y  2 6, 2 0 2 0
A n al ysis T y pe:
I nteri ms ( Wee k 2 6 a n d Wee k 2 6 pl us Re versi bilit y) a n d 
Fi nal A nal ys is
A n al ysis Pl a n Versi o n:
Versi o n 1. 0
A n al ysis Pl a n D ate:
1 2 Ja n uar y 2 0 2 1
A n al ysis Pl a n A ut h or(s):
C O N FI D E N TI A L A N D P R O P RI E T A R Y I N F O R M A TI O N
P P D


Fil g oti ni b
G L P G 0 6 3 4 -C L -2 2 7
Statistical A nal ysis Pla n
Versi o n 1. 0
C O N FI D E N TI A L
Pa ge 2
1 2 Ja n uar y 2 0 2 1
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 ........................................................................................................................................3
LI S T O F I N - TE X T FI G U R E S ......................................................................................................................................4
LI S T O F A B B R E VI A TI O N S ........................................................................................................................................5
1.
I N T R O D U C TI O N ................................................................................................................................................7
1. 1.
St u d y O bjecti ves ......................................................................................................................................7
1. 2.
St u d y D esi g n ............................................................................................................................................8
1. 3.
Sa m ple Size a n d P o w er ..........................................................................................................................1 1
2.
T Y P E O F P L A N N E D A N A L Y SI S ....................................................................................................................1 2
2. 1.
Data M o nit ori n g C o m mittee A nal yses ...................................................................................................1 2
2. 2.
I nter nal I n de pe n de nt Safet y Re vie w ......................................................................................................1 2
2. 3.
Wee k 2 6 A nal ysis
..................................................................................................................................1 3
2. 4.
Wee k 2 6 pl us Re versi bilit y A nal ysis f or Pre -s pecifie d S per m Decreases U p t o Wee k 2 6 ....................1 3
2. 5.
Fi nal A nal ysis ........................................................................................................................................1 3
3.
G E N E R A L C O N SI D E R A TI O N S F O R D A T A A N A L Y S E S ............................................................................1 4
3. 1.
A nal ysis Sets ..........................................................................................................................................1 4
3. 1. 1.
All Ra n d o mize d A nal ysis Set ...............................................................................................1 4
3. 1. 2.
Se m e n A nal ysis Sets ............................................................................................................1 4
3. 1. 3.
Safet y A nal ysis Sets .............................................................................................................1 5
3. 1. 4.
P har m ac o ki netic A nal ysis Set ..............................................................................................1 5
3. 2.
S u bject Gr o u pi n g ...................................................................................................................................1 6
3. 3.
Strata a n d C o variates ..............................................................................................................................1 7
3. 4.
E xa mi nati o n of S u bject S u b gr o u ps ........................................................................................................1 7
3. 5.
Missi n g Data a n d O utliers ......................................................................................................................1 7
3. 5. 1.
Missi n g Data
........................................................................................................................1 7
3. 5. 2.
O utliers .................................................................................................................................1 7
3. 6.
Data Ha n dli n g C o n ve nti o ns a n d Tra nsf or mati o ns .................................................................................1 7
3. 7.
A nal ysis Visit Wi n d o ws .........................................................................................................................1 8
3. 7. 1.
Defi niti o n of St u d y Da y .......................................................................................................1 8
3. 7. 2.
A nal ysis Visit Wi n d o ws .......................................................................................................1 9
3. 7. 3.
Selecti o n of Data i n t he E ve nt of M ulti ple Rec or ds i n a n A nal ys is Visit 
Wi n d o w ................................................................................................................................2 5
4.
S U BJ E C T DI S P O SI TI O N ..................................................................................................................................2 7
4. 1.
S u bject Ra n d o mizati o n a n d Dis p ositi o n ................................................................................................2 7
4. 2.
E xte nt of St u d y Dr u g E x p os ure a n d A d here nce .....................................................................................3 0
4. 2. 1.
D urati o n of E x p os ure t o St u d y Dr u g ....................................................................................3 0
4. 2. 2.
A d here nce t o St u d y Dr u g .....................................................................................................3 1
4. 3.
Pr ot oc ol De viati o ns ................................................................................................................................3 2
5.
B A S E LI N E C H A R A C T E RI S TI C S ....................................................................................................................3 4
5. 1.
D e m o gra p hics ........................................................................................................................................3 4
5. 2.
Ot her Baseli ne C haracteristics ...............................................................................................................3 4
5. 3.
Me dical Hist or y ......................................................................................................................................3 6
6.
S E M E N A N D H O R M O N E A N A L Y S E S ...........................................................................................................3 7


Fil g oti ni b
G L P G 0 6 3 4 -C L -2 2 7
Statistical A nal ysis Pla n
Versi o n 1. 0
C O N FI D E N TI A L
Pa ge 3
1 2 Ja n uar y 2 0 2 1
6. 1.
Ge neral C o nsi derati o ns ..........................................................................................................................3 7
6. 2.
P ri mar y A nal ysis of Pri mar y a n d Sec o n dar y E n d p oi nts ........................................................................3 8
6. 3.
S u b gr o u p A nal ysis f or S per m C o nce ntrati o n Para meter at Wee k 1 3 .....................................................3 9
6. 4.
S u p p orti ve A nal ysis f or Pri mar y a n d Sec o n dar y E n d p oi nts at Wee k 1 3 ...............................................3 9
6. 5.
Ot her Dis pla ys of S per m/ Se me n Data ....................................................................................................4 1
6. 5. 1.
Wee k 2 6 b y Treat me nt Se q ue nce a n d Res p o n der/ N o n -Res p o n der at Wee k 
1 3 Dis pla ys ...........................................................................................................................4 1
6. 5. 2.
Treat me nt Se q ue nce Dis pla ys at/ after Wee k 3 9 ...................................................................4 1
6. 5. 3.
Pr e -S pecifie d S per m Decrease T hres h ol d Criteria a n d C o nfir me d Se me n  
A b n or m alities .......................................................................................................................4 2
6. 6.
E x pl orat or y E n d p oi nts ...........................................................................................................................4 3
6. 6. 1.
Defi niti o n of t he E x pl orat or y E n d p oi nts ..............................................................................4 3
6. 6. 2.
Re versi bilit y A nal ysis ..........................................................................................................4 3
6. 6. 3.
H or m o nes .............................................................................................................................4 4
6. 7.
C ha n ges t o Pr ot oc ol -S pecifie d A nal yses of Se me n a n d H or m o ne Data ................................................4 5
7.
A S S E S S M E N T O F R E S P O N D E R/ N O N -R E S P O N D E R A N D DI S E A S E W O R S E NI N G ...............................4 6
8.
S A F E T Y A N A L Y S E S ........................................................................................................................................4 7
8. 1.
A d verse E ve nts a n d Deat hs ....................................................................................................................4 7
8. 1. 1.
A d verse E ve nt Dicti o nar y ....................................................................................................4 7
8. 1. 2.
A d verse E ve nt Se verit y ........................................................................................................4 7
8. 1. 3.
Relati o ns hi p of A d verse E ve nts t o St u d y Dr u g ....................................................................4 8
8. 1. 4.
Seri o us A d verse E ve nts ........................................................................................................4 8
8. 1. 5.
Treat me nt- E mer ge nt A d verse E ve nts ...................................................................................4 8
8. 1. 6.
S u m maries of A d verse E ve nts a n d Deat hs ...........................................................................5 1
8. 1. 7.
A d verse E ve nts of I nterest ...................................................................................................5 3
8. 2.
La b orat or y E val uati o ns ..........................................................................................................................5 6
8. 2. 1.
S u m maries of N u meric La b o rat or y Res ults .........................................................................5 6
8. 2. 2.
Gra de d La b orat or y Val ues ...................................................................................................5 7
8. 2. 3.
Li ver -relate d La b orat or y E val uati o ns...................................................................................5 8
8. 3.
B o d y  Wei g ht a n d Vital Si g ns.................................................................................................................5 8
8. 4.
Pri or a n d C o nc o mita nt Me dicati o ns .......................................................................................................5 9
8. 4. 1.
Pri or Me dicati o ns .................................................................................................................5 9
8. 4. 2.
C o nc o mita nt Me dicati o ns .....................................................................................................5 9
8. 5.
Electr ocar di o gra m ( E C G) Res ults ..........................................................................................................6 0
9.
P H A R M A C O KI N E TI C A N A L Y S E S ................................................................................................................6 1
1 0.
R E F E R E N C E S ...................................................................................................................................................6 2
1 1.
S O F T W A R E .......................................................................................................................................................6 3
1 2.
S A P R E VI SI O N ..................................................................................................................................................6 4
1 3.
A P P E N DI C E S ....................................................................................................................................................6 5
A p pe n di x 1.
St u d y Pr oce d ures Ta ble – D o u ble -bli n d Treat me nt P hase .....................................................6 6
A p pe n di x 2.
Calc ulati o n of t he Differe nce i n Pr o p orti o ns a n d 9 5 % CI ( Strat u m -A dj uste d Ma ntel -
Hae nszel Pr o p orti o ns) ............................................................................................................7 3
LI S T O F I N -T E X T T A B L E S
Ta ble 3- 1.
A nal ysis Visit Wi n d o ws f or Uri nal ysis, P h G A D A, a n d Li pi d Pr ofile ...................................2 1


Fil g oti ni b
G L P G 0 6 3 4 -C L -2 2 7
Statistical A nal ysis Pla n
Versi o n 1. 0
C O N FI D E N TI A L
Pa ge 4
1 2 Ja n uar y 2 0 2 1
Ta ble 3- 2.
A nal ysis Visit Wi n d o ws f or hs -C R P, Vital Si g ns, Wei g ht, He mat ol o g y, a n d 
C he mistr y La b orat ories ..........................................................................................................2 2
Ta ble 3- 3.
A nal ysis Visit Wi n d o ws f or L H, F S H, I n hi bi n B, a n d T otal Test oster o ne ............................2 3
Ta ble 3- 4.
A nal ysis Visit Wi n d o ws f or O n -Treat m e nt Se me n Para meters ..............................................2 4
Ta ble 3- 5.
A nal ysis Visit Wi n d o ws f or Se me n Para meters i n M o nit ori n g P hase  ( Calc ulate d 
fr o m Last D ose Date of A n y St u d y Dr u g/ E n d of E xte nsi o n P hase f or t h ose o n 
Sta n dar d of Care i n E xte nsi o n P hase) ....................................................................................2 4
Ta ble 6- 1.
Defi niti o ns f or t he Pri mar y a n d Sec o n dar y E n d p oi nts ...........................................................3 7
Ta ble 6- 2. 
Se m e n Para meter Eli gi bilit y Criteria ......................................................................................3 7
Ta ble 6- 3.
H y p ot hetical Pr o p orti o n of S u bjects W h o Met Re versi bilit y Criteria  f or S per m 
C o nce ntrati o n b y Treat me nt Gr o u p a n d M o nit ori n g P hase Visit ( S u bjects wi t h a 
≥5 0 % Decrease i n S per m C o nce ntrati o n at/ pri or t o Wee k 1 3) ..............................................4 4
LI S T O F I N -T E X T FI G U R E S
Fi g ure 1- 1.
St u d y Sc he ma ...........................................................................................................................9


Fil g oti ni b
G L P G 0 6 3 4 -C L -2 2 7
Statistical A nal ysis Pla n
Versi o n 1. 0
C O N FI D E N TI A L
Pa ge 5
1 2 Ja n uar y 2 0 2 1
L I S T O F A B B R E VI A TI O N S
A E
a d verse e ve nt
A E Is
a d verse e ve nt s of i nterest
A L T
ala ni ne a mi n otra nsferase
A S
a n k yl osi n g sp o n d ylitis
A S T
as partate a mi n otra nsferase
A T C
A nat o mical T hera pe utic C he mical
B A S D AI
Bat h A n k yl osi n g S p o n d ylitis Disease Acti vit y I n de x
B L Q
bel o w  t he li mit of q ua ntitati o n
B MI
b o d y mass i n de x
C D AI
Cli nical Disease Acti vit y I n de x
CI
co nfi de nce i nter val
C O VI D -1 9
C or o na vir us Disease 2 0 1 9
cs D M A R D
c o n ve nti o nal s y nt hetic disease m o dif yi n g a nti -r he u matic dr u g
C S R
cli nical st u d y re p ort
C T C A E
C o m m o n Ter mi n ol o g y Criteria f or A d verse E ve nts
C V E A C
Car di o vasc ular E ve nt A dj u dicati o n C o m mittee
D A P S A
Disease Acti vit y i n Ps oriatic Art hritis
D M C
Data M o nit ori n g C o m mittee 
D V T
dee p vei n t hr o m b osis
E AI R
ex p os ure -a dj uste d i nci de nce rate
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 X T
e xte nsi o n p hase
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
F U
f oll o w-u p
G L P G
Gala pa g os , N V
H L G T
hi g h -le vel gr o u p ter m
H L T
h i gh- le vel ter m
hs C R P
hi g h -se nsiti vit y C-Reacti ve Pr otei n
I C
i ncl usi o n criteria
I D
Ide ntificati o n
I P D
i mp orta nt pr ot oc ol de viati o n
I T T
I nte nt-t o-Treat
I U T
I nter nal U n bli n de d Tea m
I W R S
i nteracti ve we b res p o nse s yste m
J A K
Ja n us Ki nase


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L H
l utei nizi n g h or m o ne
L L T
lo w  le vel ter m
L O Q
li mit of q ua ntitati o n
M
M illi o n
M A C E
maj or a d verse car diac e ve nts
M A R
missi n g at ra n d o m
Me d D R A
Me dical Dicti o nar y f or Re g ulat or y Affairs
M H
Ma ntel- Hae nszel
MI
m ulti ple i m p utati o n , m y ocar dial i nfarcti o n
M P
M o nit ori n g P hase
M S T
Me d D R A searc h t er m
M T X
M et h otre xate
nr A x S p A
n o n- ra di o gra p hic a xial s p o n d yl oart hritis
OI
o p p ort u nistic i nfecti o n
P E
p ul m o nar y e m b oli s m
P h G A D A
P h y sicia n’s Gl o bal Assess me nt of Disease Acti vit y
P K
p har mac o ki netics
Ps A
ps oriatic art hritis
P T
preferre d ter m
P T M
place b o -t o-matc h
P Y E
p atie nt -years of e x p os ure
Q 1
first q uartile
Q 3
t hir d q uartile
R A
r he u mat oi d art hritis
S A E
seri o us a d verse e ve nt
S A P
Statistical A nal ysis Pla n
S D
sta n dar d de viati o n
S E
sta n dar d err or
S M Q
sta n dar dize d Me d D R A q uer y
S O C
s yste m or ga n class
T E A Es
treat me nt e mer ge nt a d verse e ve nts
T F L s
ta bles, fi g ures a n d listi n gs
U L N
u p per li mit of n or mal
U S
U nite d States
V A S
vis ual a nal o g ue scale
V T E
ve n o us t hr o m b oe m b olis m e ve nt
W H O
W orl d Healt h Or ga nizati o n


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1.
I N T R O D U C TI O N
T his statistical a nal y sis pla n ( S A P) descri bes t he statistical a nal ysis met h o ds a n d data 
prese ntati o ns t o be use d i n ta bles, fi g ures, a n d listi n gs ( T FLs) f or St u d y  G L P G 0 6 3 4-C L - 2 2 7
[ M A N T A-R A y ]. T his S A P is base d o n A me n d me nt 1 of t he pr ot oc ol date d 2 6 Ma y
2 0 2 0 a n d t he 
electr o nic case re p ort f or m (e C R F). T he S A P will be fi nalize d pri or t o u n bli n di n g f or t he 
Wee k
2 6 i nteri m a nalys is 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 [ M A N T A] a n d G L P G 0 6 3 4 -C L -2 2 7 [ M A N T A -R A y ] c o m plete Wee k 1 3; a n d 
e val ua ble s u bjects fr o m St u d y  G LP G 0 6 3 4 -C L -2 2 7 c o m plete Wee k 2 6 or per ma ne ntl y 
disc o nti n ue fr o m st u d y  dr u g. A n y c ha n ges ma de after t he fi nal izati o n of t he S A P will be 
d oc u me nte d i n t he cli nical st u d y re p ort (C S R ).
1. 1. 
St u d y O bjecti ves
T he pri m ar y o bjecti ve of t he st u d y is as f oll o ws:

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 he st u d y are as f oll o ws:

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 ulate 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 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
T he e x p l or at or y o bjecti ves of t he st u d y are as f oll o ws:

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 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 safet y a n d t olera bilit y of fil g oti ni b

T o c harac terize t he plas ma p har mac o ki netics ( 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


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1. 2.
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 
r he u mat oi d art hritis ( R A), ps oriatic art hritis ( Ps A), a n k yl osi n g s p o n d ylitis ( A S) or 
n o n- ra di o gra p hic a xial s p o n d yl oart hritis ( nr A x S p A) w h o ha ve ha d a n i na de q uate res p o nse t o 
pri or art hritis t hera p y as o utli ne d i n t he i ncl usi o n criteria, ha ve a n a d verse pr o g n osis of t heir 
c o n diti o n per t he i n vesti ga t or, a nd w h o ma y  be nefit fr o m treat me nt wit h a Ja n us Ki nase 
(J A K)-i n hi bit or. S u bjects ma y be o n pr ot oc ol-s pecifie d c o nc o mita nt t hera p y.
U p t o 2 5 0 males were pla n ne d t o be ra n d o mize d i n a 1: 1 rati o t o recei ve fil g oti ni b 2 0 0 m g or 
place b o -t o-matc h ( P T M) o nce dail y f or 1 3 wee ks, after w hic h a n e xte nsi o n p hase was t o start.
S u bjects w h o met a pre -s pecifie d s per m decrease t hres h ol d (e g, ≥ 5 0 % decrease i n s per m 
c o nce ntrati o n or m otilit y or m or p h ol o g y) at a n y ti me d uri n g t he st u d y w ere t o be f oll o we d 
off -st u d y dr u g f or re versi bilit y i n t he M o nit ori n g P hase.
Ra n d o mizati o n w as stratifie d acc or di n g t o t he ty pe of r he u mat ol o gic c o n diti o n ( R A or
S p o n d y l oart hritis [Ps A, A S, nr A x S p A ]), b y  c o nc urre nt use of met h otre xate ([ M T X ], yes or n o), 
a n d b y s per m c o nce ntrati o n ( mea n of 2 eval ua ble sa m ples) c ollecte d at t he scree ni n g visit
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]/ m L

> 2 5 t o 5 0 M / m L

> 5 0 M / m L
T he mai n i ncl usi o n criteria rele va nt t o t his st u d y  were :

Male s u bjects bet wee n t he a ge s 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

T he mea n of 2 se parate e val ua ble se me n sa m ples c ollecte d at t he scree ni n g visit m ust ha ve 
met t he f oll o wi n g mi ni m u m criteria (se me n v ol u me ≥ 1. 5 m L , t otal s per m/ejac ulate 
≥3 9 M/ejac ulate , s per m c o nce ntrati o n ≥ 1 5 M / 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 % ( m or p h ol o g y  usi n g W orl d Healt h Or ga nizati o n [ W H O ] 1 9 9 2 
criteria { W orl d Healt h Or ga nizati o n ( W H O) 1 9 9 2 }; all ot her para meters usi n g W H O 2 0 1 0 
criteria{ C o o per 2 0 1 0 , W orl d Healt h Or ga nizati o n ( W H O) 2 0 1 0 })
T he mai n e xcl usi o n criteri o n rele va nt t o t his st u d y wa s:

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 healt 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 yp o g o na dis m, or re d uce d fertilit y


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A c o m plete list of eli gi bilit y  criteria is pr o vi de d i n Secti o ns 4. 2 a n d 4. 3 of t he St u d y Pr ot oc ol. 
Male s u bjects wit h a r he u mat ol o gic c o n diti o n w h o pr o vi de d writte n i nf or me d c o nse nt w ere
scree ne d t o deter mi ne eli gi bilit y. T he Scree ni n g peri o d was u p t o 4 5 da y s pri or t o ra n d o mizati o n 
a n d c o ul d ha ve bee n e xte n de d i n c o ns ultati o n wit h t he me dical m o nit or.
T he assess me nts pla n ne d 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 1 ). A sc he matic of t he st u d y desi g n is pr o vi de d bel o w.
Fi g ure 1- 1.
St u d y Sc he m a
T here are 3 disti nct parts t o t he st u d y:
1)
D o u ble -bli n d Treat me nt P hase ( Da y 1 t hr o u g h Wee k 1 3 st u d y visit)
2)
E xte nsi o n P hase ( After Wee k 1 3 St u d y  Visit a n d u p t o Wee k 1 5 6)
3)
M o nit ori n g P hase
( u p t o 5 2 wee ks)
After f ulfilli n g all selecti o n criteria, s u bjects w ere t o be ra n d o mize d t o fil g oti ni b 2 0 0 m g or P T M 
i n a 1: 1 rati o at Da y 1 a n d e nter t he Do u ble -bli n d Treat me nt P hase. Base d o n t he o utc o mes of t he 
Wee k 1 3 assess me nts (ie, i n di vi d ual s u bject’s res p o nse of t he u n derl y i n g r he u matic c o n diti o n t o 
t he assi g ne d treat me nt a n d/ or o bser ve d c ha n ges i n s per m para meters d uri n g t he D o u ble-bli n d 
Treat me nt P hase), s u bjects ma y  e nter t he E xte nsi o n or M o nit ori n g P hase. 


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D o u ble -bli n d Tre at me nt P h ase ( D a y 1 t hr o u g h Wee k 1 3 St u d y Visit)
D uri n g t he D o u ble -bli n d Treat me nt P hase, all s u bjects recei ve d bli n de d st u d y  dr u g f or 1 3 wee ks 
starti n g fr o m t he Da y 1/ Ra n d o mizati o n St u d y  Visit. At t he Wee k 1 3 st u d y visit, s per m 
para meters w ere e val uate d t o deter mi ne w het her t he s u bject ha d met a n y of t he pre -s pecifie d 
s per m decrease t hres h ol ds ( e g, ≥5 0 % decrease i n s per m c o nce ntrati o n a n d/ or m otilit y  a n d/ or 
m or p h ol o g y ). I n a d diti o n, art hritis res p o nse stat us ( Art hritis Res p o n der [ defi ne d as i m pr o ve me nt 
i n p h ysicia n’s gl o bal assess me nt of disea se acti vit y ( P h G A D A) of at least 2 0 % c o m pare d t o 
Baseli ne ( Da y 1) at t he s pecifie d assess me nt ti me] vs Art hritis N o n- res p o n der [ defi ne d as d oes 
n ot meet Art hritis Res p o n der defi niti o n] ) was deter mi ne d. Base d o n t hese assess me nts, s u bjects 
were assi g ne d t o o ne of t he f oll o wi n g:

S u bjects w h ose se me n para meters met a n y  of t he pre-s pecifie d s per m decrease t hres h ol ds, 
re gar dless of art hritis res p o nse stat us, disc o nti n ue d st u d y dr u g a n d e ntere d t he M o nit ori n g 
P hase.

S u bjects w h o were art hritis n o n- res p o n ders a n d w h ose se me n para meters d i d n ot meet a n y  of 
t he pre-s pecifie d s per m decrease t hres h ol ds disc o nti n ue d bli n de d st u d y  dr u g a n d starte d
Sta n dar d of Care treat me nt d uri n g t he E xte nsi o n P hase.

S u bjects w h o were Art hritis Res p o n ders a n d w h ose se me n para meters d i d n ot meet a n y of 
t he pre-s pecifie d s per m decrease t hres h ol ds w ere u n bli n de d b y  t he i nteracti ve we b res p o nse 
s yste m (I W R S) a n d e ntere d t he E xte nsi o n P hase. S u bjects o n fil g oti ni b were c o n vert t o 
o pe n -la bel fil g oti ni b a n d s u bjects w h o rece i ve d place b o s witc h e d t o Sta n dar d of Care 
treat me nt.
E xte nsi o n P h ase ( After Wee k 1 3 t hr o u g h Wee k 1 5 6 St u d y Visit)
I n t he E xte nsi o n P hase, s u bjects will recei ve o pe n-la bel treat me nt (fil g oti ni b or Sta n dar d of 
Care) a n d ha ve a st u d y  visit e ver y 1 3 wee ks t hat i ncl u des se me n a nalys is. T he first sc he d ule d 
visit of t he E xte nsi o n P hase occ urs at Wee k 2 6.
I n case se me n para meters at a n y visit (i ncl u di n g Wee k 1 5 6) meet a n y of t he pre-s pecifie d s per m 
decrease t hres h ol ds, s u bjects will e nter t he M o nit ori n g P hase.
D uri n g t he E xte nsi o n P hase, Sta n dar d of Care a n d bac k gr o u n d treat me nt c o nc o mita nt t o 
fil g oti ni b ma y be o pti mize d at t he discreti o n of t he i n vesti gat or, ta ki n g i nt o c o nsi derati o n t he 
pr ot oc ol restricti o ns (see Secti o ns 5. 3 a n d 5. 4 of t he st u d y  pr ot oc ol).
I n case a s u bject nee ds t o be treate d wit h a pr o hi bite d me dicati o n (see Ta ble 5. 1 fr o m t he st u d y  
pr ot oc ol), f or i nsta nce t o c o ntr ol t heir r he u matic c o n diti o n, t he s u bject will disc o nti n ue t he st u d y  
a n d c o m plete a n Earl y Ter mi nati o n ( E T) visit (i ncl u di n g se me n c o llecti o n). F or s u bjects o n 
fil g oti ni b, t his will be f oll o we d b y a safety f oll o w -u p visit 3 0 da y s after last st u d y dr u g d ose.  
All s u bjects w h o di d n ot e nter t he M o nit ori n g P hase will c o nti n ue t he st u d y u ntil t he Wee k 1 5 6 
visit.


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wee k s)
S u bjects w h ose se me n para meters meet a n y of t he pre -s pecifie d s per m decrease t hres h ol ds will 
s witc h t o t he M o nit ori n g P hase i m me diatel y. S u bjects o n d o u ble- bli n d treat me nt or o pe n-la bel 
fil g oti ni b w h o e nter t he M o nit ori n g P hase will disc o nti n ue st u d y  dr u g a n d start Sta n dar d of Care. 
T hese s u bjects will als o ha ve a safet y f oll o w -u p visit 3 0 da y s after t he last st u d y dr u g d ose. 
S u bjects o n Sta n dar d of Care i n t he e xte nsi o n p hase will c o nti n ue ta ki n g a Sta n dar d of Care 
re gi me n i n t he M o nit ori n g P hase. 
All s u bjects w h o e nter t he M o nit ori n g P hase will u n der g o se me n e val uati o ns e ver y  1 3 wee ks 
starti n g fr o m t heir e ntr y i nt o t he M o nit ori n g P hase, f or u p t o 5 2 wee ks or u ntil re versi bilit y 
( defi ne d as a ret ur n t o > 0. 5 x [ mea n of 2 e val ua ble sa m ples c ollecte d at scree ni n g visit] f or all
s per m para meter[s] q ualif yi n g t he s u bject f or t he m o nit ori n g p hase —base d o n 2 e val ua ble 
sa m ples c ollecte d at t he m o nit ori n g p hase visit) is met, w hic he ver is ac hie ve d first.
1. 3. 
S a m ple Size a n d P o wer
Res ults of t his st u d y  will be p o ole d wit h t he res ults of a se parate st u d y bei n g c o n d ucte d i n 
s u bjects wit h i nfla m mat or y b o wel disease ( G S-U S - 4 1 8- 4 2 7 9 [ M A N T A]) wit h t he sa me 
o bjecti ve s. T he t otal pla n ne d n u m ber of s u bjects i n b ot h st u dies c o m bi ne d will be u p t o 
a p pr o xi matel y 2 5 0 s u bjects.
A sa m ple size of a p pr o xi matel y  1 0 0 e val ua ble s u bjects per gr o u p (ie, 1 0 0 s u bjects i n t he 
fil g oti ni b 2 0 0 m g gr o u p a n d 1 0 0 s u bjects i n t he place b o gr o u p) is a de q uate f or t he p ur p oses of 
esti mati n g c u m ulat i 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 nce i nter val ( CI) wi dt h 
t hat is reas o na bly narr o w f or t he pr o p orti o n 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 ntrati o n c o m pare d t o baseli ne. A n e val ua ble s u bject is defi ne d a s 
a s u bject wit h 2 se me n sa m ples at b ot h baseli ne a n d at Wee k 1 3 t hat are eli gi ble f or mea n 
calc ulati o n f or s per m c o nce ntrati o n wit h visit wi n d o w assi g n me nt f or t he mea n calc ulati o n base d 
o n t he date of t he first of 2 e val ua ble sa m ple c ollecti o ns. T his 2 0 0 s u bject 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 bjects at Wee k 1 3, u p 
t o 2 5 0 s u bjects ma y be e nr olle d t o o btai n 2 0 0 e val ua ble s u bjects.


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2.
T Y P E O F  P L A N N E D A N A L Y SI S
2. 1.  
D at a M o nit ori n g C o m mittee A n al yses
A n e xter n al D M C re vi e w s t he pr o gress of t he st u d y, perf or m s u n bli n de d i nteri m re vie ws of 
safety data , a n d pr o vi des a rec o m me n dati o n t o t he S p o ns or w het her t he nat ure, fre q ue nc y , a n d 
se verity of a d verse effects ass ociate d wit h st u d y treat me nt warra 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 he st u dy s h o ul d c o nti n ue as pla n ne d, or 
t he st u d y s h o ul d c o nti n ue wit h m o dificati o ns. T he i nitial u n bli n de d data re vie w meeti n g
occ urre d after a p pr o xi matel y t he first 5 0 s u bjects c o m plete d t he Wee k 1 3 visit. F oll o wi n g t his, 
s u bse q ue nt u n bli n de d data re vie w meeti n gs w ere t o 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). P o ole d s per m/se me n data fr o m S t u dies G S -U S - 4 1 8- 4 2 7 9 
[ M AN T A] pl us G L P G 0 6 3 4 -C L -2 2 7 [ M A N T A-R A y ] were re vie we d after a p pr o xi matel y 
1 0 0 s u bjects c o m pleted Wee k 1 3.
T he D M C ma y  a d diti o nall y re q uest t o re vie w bli n de d s per m/se me n data pri or t o t he first 
u n bli n de d D M C meeti n g a n d/ or i n bet wee n u n bli n de d re vie w meeti n g s. A d - h oc D M C meet i n gs 
ma y  be sc he d ule d as nee de d. A d-h oc D M C meeti n gs ma y  be tri g gere d f or reas o ns o utli ne d i n t he 
D M C C harter a n d/ or pr ot oc ol.
T he D M C’s r ole a n d res p o nsi bilities a n d t he sc o pe of a nal ys is t o be pr o vi de d t o t he D M C are 
pr o vi de d i n a m ut u all y a gree d u p o n c harter, w hic h defi nes t he D M C me m bers hi p, meeti n g 
l o gistics, a n d meeti n g fre q ue nc y.
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 t he 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 retains 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. 
2. 2. 
I nter n al I n de pe n de nt S afet y Re vie w
A S p o ns or I nter nal U n bli n de d Tea m (I U T), i n de pe n de nt of t he bli n de d st u d y  tea m, will be 
asse m ble d. T he S p o ns or I U T will m o nit or bli n de d c u m ulati ve i nter val s per m/se me n data a n d 
ma y be gra nte d access t o u n bli n de d cli nical data at pre -s pecifie d ti me p oi nts t o re vie w 
s per m/se me n data. T his i nter nal re vie w tea m will be s u p p orte d b y a n e xter nal Ur ol o g y e x pert. T o 
miti gate t he ris k of i na d verte ntl y  releasi n g treat ment assi g n me nt t o sites a n d s u bjects, t he i nter nal 
tea m will kee p 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. T o date, t he S p o ns or I U T has n ot bee n u tilize d t o 
re vie w u n bli n de d se me n data at pre -s pecifie d ti me p oi nts t o m o nit or safet y ( D M C has perf or me d 
t his d ut y). If t he S p o ns or I U T is utilize d t o re vie w u n bli n de d data f or p ur p oses of m o nit ori n g 
safety pri or t o u n bli n di n g of t he st u d y , t he c o m mittee’s s pecific acti vities will be defi ne d b y a 
m ut uall y  a gree d u p o n c harter, w hic h will defi ne t he c o m mittee me m bers hi p, c o n d uct, a n d 
meeti n g sc he d ule. Data u n bli n di n g d ue t o me dical e mer ge nc y  will f oll o w sta n dar d S p o ns or
pr oce d ures .


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2. 3.
Wee k 2 6
A n al ysis
T he u n bli n de d Wee k 2 6 a nal ys is of St u d y  G L P G 0 6 3 4-C L - 2 2 7 will 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 [ M A N T A] a n d 
G L P G 0 6 3 4 -C L - 2 2 7 [ M A N T A-R A y ] c o m plete Wee k 1 3 a n d e val ua ble s u bjects fr o m St u d y 
G L P G 0 6 3 4 -C L -2 2 7 c o m plete Wee k 2 6 or per ma ne ntl y disc o nti n ue fr o m st u d y dr u g. T his 
a nal ys is will be c o n d ucte d i n or der t o f ulfill e x -U S re g ulat or y c o m mit me nts.
A Data I nte grit y  a n d C o m m u nicati o n Pla n will be de vel o pe d pri or t o u n bli n di n g f or a n y i nteri m 
a nal ys is. T he G L P G 0 6 3 4 -C L - 2 2 7 st u d y tea m will re mai n bli n de d t o d o u ble -bli n d treat me nt 
assi g n me nts ( w here p ossi ble b y st u d y desi g n) u ntil t he fi nal a nal ys is w he n t he data base has bee n 
l oc ke d, an d t he st u d y  has bee n c o m pletely u n bli n de d . 
2. 4.
Wee k 2 6 pl us Re versi bilit y A n al ysis f or Pre-s pecifie d S per m Decre ases U p t o 
Wee k 2 6
A se parate u n bli n de d Wee k 2 6 a nal ys is of St u d y G LP G 0 6 3 4 -C L -2 2 7 will 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 % decli ne i n s pe r m c o nce ntrati o n a n d/ or 
m otilit y  a n d/ or m or p h ol o g y u p t o Wee k 2 6 e nter t he m o nit ori n g p hase a n d eit her meet 
re versi bilit y criteria, or are foll o we d off -treat me nt f or 5 2 wee ks, w hic he ver occ urs s o o ner. T his 
a nal ys is will be c o n d ucte d at t he re q uest of t he US F o o d a n d Dr u g A d mi nistrati o n.
T he Data I nte grity a n d C o m m u nicati o n Pla n will c o nti n ue t o be i n place, a n d t he 
G L P G 0 6 3 4 -C L -2 2 7 st u d y  tea m will re mai n bli n de d t o d o u ble- bli n d treat me nt assi g n me nts 
( w here p ossi ble b y st u d y desi g n) u ntil t he fi nal a nal y sis whe n t he data base has bee n l oc ke d a n d 
t he st u d y has bee n c o m pletel y u n bli n de d.
2. 5.
Fi n al A n al ysis
After all s u bjects ha ve c o m plete d t he st u d y (e g, c o m plete d Wee k 1 5 6 a n d di d n ot meet 
pre -s pecifie d s per m decrease t hres h ol d [≥ 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]; met pre -s pecifie d s per m decrease t hres h ol d(s) a n d eit her met re versi bilit y 
criteria or c o m plete d 5 2 wee ks of off -st u d y dr u g f oll o w-u p f or re versi bilit y; or pre mat urel y 
disc o nti n ue d fr o m st u d y ), o utsta n di n g data q ueries h a ve bee n res ol ve d or a dj u dicate d as 
u nres ol va ble , a n d t he data ha ve bee n clea ne d a n d fi nalize d , the st u d y bli n d will be br o ke n a n d 
t he fi nal a nalys is of t he data will be perf or me d.


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3.
G E N E R A L  C O N SI D E R ATI O N S F O R D A T A  AN A L Y S E S
A nal y sis res ults will be prese nte d usi n g descri pti ve statistics. F or cate g orical varia bles, t he 
n u m ber a n d perce nta ge of s u bjects i n eac h cate g or y will be prese nte d; f or c o nti n u o us varia bles, 
t he n u m ber of s u bjects ( n), mea n, sta n dar d de viati o n (S D ) or sta n dar d err or (S E ), me dia n, 
first q u artile (Q 1 ), t hir d q uartile (Q 3 ), mi ni m u m, a n d ma xi m u m will be prese nte d.
All statistical tests will be 2 -si de d a n d perf or me d at t he 5 % si g nifica nce le vel u nless ot her wise 
s pecifie d.
B y -s u bject listi n gs will be prese nte d f or all s u bjects i n t he All Ra n d o mize d A nal y sis Set a n d 
s orte d b y s u bject I D n u m ber, visit date, a n d ti me (if a p plica ble). Data c ollecte d o n l o g f or ms, 
s uc h as A Es, will be prese nte d i n c hr o n ol o gical or der wit hi n t he s u bject. T he treat me nt gr o u p t o 
w hic h s u bje cts were ra n d o mize d , d o uble -bli n d treat me nt a n d res p o n der/ n o n -res p o n der stat us at 
Wee k 1 3, or treat me nt se q ue nce will be prese nte d i n t he listi n gs, as a p pr o priate. A ge, se x, race, 
et h nicit y, start a n d e n d date of t he d o u ble -bli n d st u d y  dr u g a n d o pe n-la bel fil g oti ni b or start a n d 
e n d date of e xte nsi o n p hase (f or s u bjects w h o were s witc he d t o sta n dar d of care i n t he e xte nsi o n 
p hase ) will be i ncl u de d i n t he listi n gs, as s pace per mits. A b y -s u bject listi n g will be pr o vi de d f or 
s u bjects wit h a n y visits or assess me nts i m pacte d b y C or o navir us Disease 2 0 1 9 ( C O VI D -1 9) . 
3. 1.
A n al ysis Sets
A nal y sis sets defi ne t he s u bjects t o be i ncl u de d i n a n anal ys is. A nal ys is sets a n d t heir defi niti o ns 
are pr o vi de d i n t his secti o n. T he a nal ys is set will be i de ntifie d a n d i ncl u de d as a s u btitle of eac h 
ta ble, fi g ure, a n d listi n g.
F or eac h a nal ys is set, the n u m ber a n d perce nta ge of s u bjects eli gi ble f or i ncl usi o n will be 
s u m marize d b y  treat me nt gr o u p.
A listi n g of reas o ns f or e xcl usi o n fr o m a nal y sis sets will be pr o vi de d b y s u bject.
3. 1. 1.
All R a n d o mize d A n al ysis Set
T he All Ra n d o mize d A nal y sis Set i ncl u des all su bjects w h o w ere ra n d o mize d i n t he st u d y. T his 
is t he pri mar y a nalys is set f or ra n d o mizati o n s u m maries a n d b y -s u bject listi n gs.
3. 1. 2.
Se me n A n al ysis Set s
T he Se me n A nal ys is Set i ncl u des all ra n d o mize d a n d treate d (≥ 1 d ose of d o u ble -bli n d st u d y  
dr u g) s u bjects w h o ha ve 2 se me n sa m ples t hat are eli gi ble f or mea n calc ulati o n at b aseli ne a n d at 
t he Wee k 1 3
a nal ys is visit wit h t he date of t he first c hr o n ol o gic se me n sa m ple use d f or p ur p oses 
of assi g ni n g a nal ys is visit wi n d o ws. 


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A n i n di vi d ual se me n sa m ple is eli gi ble f or mea n calc ulati o n if c ollecte d ≥ 4 8 h o urs a n d ≤7 d a y s 
after t he pre vi o us ejac ulati o n date/ti me; a n d c ollecte d wit hi n 1 4 da y s of t he pre vi o us c hr o n ol o gic 
se me n sa m ple c ollecti o n at t he visit w he n t he sa m ple is n ot t he first c ollecti o n at t he visit. T hree 
s u bjects ( 1 0 5 4 5-6 0 6 9 5, 1 2 8 5 8 - 6 0 7 0 6, 1 5 9 2 2-6 0 6 8 4) ha d a t hir d se me n sa m ple c ollecte d at 
Wee k
1 3 t hat was 3 5, 2 2, a n d 2 4 da y s, res pecti vel y, after t he sec o n d se me n sa m ple (t he first 
2 se me n sa m ples were c ollecte d wit hi n 1 4 da y s) d ue t o dela ys i n a nalys is ti me. T hese sa m ples 
will be c o nsi dere d t o be a n e xce pti o n a n d will be “eli gi ble f or mea n calc ulati o n”.
T he Wee k 2 6 Se me n A nal y sis Set i ncl u des all s u bjects treate d (≥ 1 d ose of o pe n -la bel fil g oti ni b
or sta n dar d of care i n t he e xte nsi o n p hase) w h o ha ve 2 e val ua ble sa m ples at baseli ne a n d at
Wee k 2 6.
T he At/ After Wee k 3 9 Se me n A nal ys is Set i ncl u des all s u bjects treate d (≥ 1 d ose of o pe n -la bel 
fil g oti ni b or sta n dar d of care i n t he e xte nsi o n p hase) w h o h a ve 2 e val ua ble sa m ples at baseli ne 
a n d at ≥ 1 p ost baseli ne a nal ysis visit wi n d o w o n/after Wee k 3 9. T he first of 2 e val ua ble se me n 
sa m ples f or t he p ost baseli ne ti me p oi nt will be utilize d t o assi g n t he p ost baseli ne a nal ys is visit 
wi n d o w. 
T h ese are t he prim ar y  a nal ysis sets f or all se me n a n d h or m o ne -relate d para meters.
T he pri mar y  a nalys is of se me n data f or pri mar y a n d sec o n dar y e n d p oi nts at d o u ble-bli n d 
Wee k
1 3 will be base d o n t he Se me n A nalys is Set a n d s u bjects wit h 2 e val ua ble se me n sa m ples 
w hic h are re q uire d at eac h se me n sa m ple c ollecti o n ti me p oi nt. A s u p p orti ve a nal ys is (see 
Secti o n 6. 4 of t his S A P)  will als o be perf or me d f or s u bjects i n t he f oll o wi n g a nalys is set:
T he I nte nt-t o-Treat (IT T) 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 
2 se me n sa m ples t hat are eli gi ble f or mea n calc ulati o n at Baseli ne.
Si nce all s u bjects w h o wer e ra n d o mize d t o o k at least 1 d ose of st u d y  dr u g a n d als o ha d 
2 e val ua ble se me n sa m ples at baseli ne, t he I nte nt-t o-Treat Se me n A nal ys is Set will i ncl u de t he 
sa me s u bjects as t he Safet y A nalys is Set.
3. 1. 3. 
S afet y A n al ysis Sets
T he S afet y A nal y sis S et i ncl u des all ra n d o mize d s u bjects w h o t o o k ≥1 d ose of d o u ble -bli n d 
st u d y dr u g. T his is t he a nal ysis set f or safet y  d uri n g t he d o u ble-bli n d p hase of t he st u d y .
T he E xte nsi o n P hase Safet y  A nalys is Set i ncl u des all s u bjects w h o t o o k ≥ 1 d ose of o pe n -la bel 
fil g oti ni b or sta n dar d of care i n t he e xte nsi o n p hase of t he st u d y. T h is is t he a nalys is set f or 
safety d uri n g t he e xte nsi o n p hase of t he st u d y.
3. 1. 4.
P h ar m ac o ki netic A n al ysis Set
T he P har mac o ki netic ( P K ) Anal ys is S et i ncl u des all ra n d o mize d s u bjects w h o t o o k ≥ 1 d ose of 
fil g oti ni b w h o ha ve at least 1 n o n missi n g p ost d ose c o nce ntrati o n val ue f or fil goti 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 nalys is set f or all P K a nal ys es.


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3. 2.
S u bject Gr o u p i n g
F or a nal y ses base d o n t he All Ra n d o mize d a n d IT T Se me n A nal ys is Sets, s u bjects will be 
gr o u pe d acc or di n g t o t he ir ra n d o mize d treat me nt. F or all ot her a nal ys is sets, s u bjects will be 
gr o u pe d acc or di n g t o t he act ual treat me nt recei ve d. T he act ual treat me nt recei ve d will differ 
fr o m t he ra n d o mize d treat me nt o nl y w he n t he act ual treat me nt differs fr o m ra n d o mize d 
treat me nt f or t he e ntire treat me nt d urati o n of t he st u d y  dr u g a d mi nistrati o n peri o d.
T he f oll o wi n g s u bject gr o u pi n gs will be a p plie d t o t he se me n a n d h or m o ne data acc or di n g t o t he 
act ual treat me nt recei ve d:

F or t he d o u ble -bli n d treat me nt p hase , data will be s u m marize d b y d o u ble-bli n d treat me nt 
gr o u p (ie, fil g oti ni b 2 0 0 m g a n d place b o) .

F or t he Wee k 2 6 visit, se me n a n d h or m o ne data will be s u m marize d b y  treat me nt se q ue nce 
a n d R he u matic Disease Res p o n der/ N o n -res p o n der stat us at Wee k 1 3 (ie, fil g oti ni b 
res p o n ders w h o s witc h t o o pe n-la bel fil g oti ni b, fil g oti ni b n o n-res p o n ders at Wee k 1 3 w h o 
s witc h t o sta n dar d of care, place b o res p o n ders w h o s witc h t o sta n dar d of care, a n d place b o 
n o n- res p o n ders w h o s witc h t o sta n dar d of care).

S e me n a n d h or m o ne data c ollecte d at/after Wee k 3 9 i n t he e xte nsi o n p hase will be 
s u m marize d b y treat me nt se q ue nce (ie, d o u ble-bli n d fil g oti ni b t o o pe n -la bel fil g oti ni b, 
d o u ble -bli n d fil g oti ni b t o sta n dar d of care, a n d place b o t o sta n dar d of care) f or s u bjects wit h 
baseli ne a n d ≥1 visit at/after Wee k 3 9.

S u bjects wit h a decrease of ≥ 5 0 % 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 
fr o m baseli ne w hile o n d o u ble - bli n d treat me nt or o pe n-la bel fil g oti ni b will ha ve st u d y dr u g 
st o p pe d a n d a n i n vesti gat or selecte d sta n dar d of care treat me nt t hat meets pr ot oc ol-s pecifie d 
criteria starte d. S u bjects meeti n g a s per m decrease w hile o n sta n dar d of care i n e xte nsi o n 
p hase will c o nti n ue o n a sta n dar d of care re gi me n. Se me n sa m ples will be c ollecte d off -st u d y 
dr u g /c o ntr ol (e g, sta n dar d of care i n e xte nsi o n p hase) e ver y 1 3 wee ks d uri n g t he M o nit ori n g 
P hase u ntil re versi bilit y  is met or f or u p t o 5 2 wee ks , w hic he ver occ urs first . Re versi bilit y is 
met w he n all s per m para meter(s) q ualif y i n g t he s u bject t o e nter t he M o nit ori n g P hase ret ur n 
t o greater t ha n 5 0 % of t he baseli ne val ue (ie , greater t ha n 0. 5 x [ mea n of 2 e val ua ble sa m ples 
c ollecte d at t he scree ni n g visit ]). Data w ill be s u m marize d f or eac h s per m para meter meeti n g
a pre -s pecifie d s per m decrease t hres h ol d at t he visit w he n st u d y dr u g was st o p pe d. T he 
n u m ber ( perce nt) w h o met re versi bilit y  criteria a n d t he c u m ulati ve n u m ber ( perce nt) w h o 
met re versi bilit y  criteria at eac h M o nit ori n g P hase visit will be prese nte d se parately f or 
s u bjects w h o met pre -s pecifie d sper m para meter decreases at Wee k 1 3 (s u m marize d b y  
d o u ble -bli n d treat me nt gr o u p) ; f or s u bjects meeti n g pre-s pecifie d s per m para meter decrease 
t hres h ol ds at Wee k 2 6 (s u m marize d b y treat me nt se q ue nce a n d r he u matic disease 
res p o n der/ n o n -res p o n der stat us at Wee k 1 3) a n d at or after Wee k 3 9 (s u m marize d b y 
treat me nt se q ue nce).
F or t he safet y a nal yses, s u bjects will be gr o u pe d b y  d o u ble-bli n d treat me nt gr o u p (ie, fil g oti ni b 
2 0 0 m g or place b o) f or safet y e ve nts re p orte d d uri n g t he d o u ble -bli n d p hase of t he st u d y . 


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S afet y e ve nts re p orte d d uri n g t he e xte nsi o n p has e will be s u m marize d b y treat me nt se q ue nce 
( d o u ble- bli n d fil g oti ni b t o o pe n-la bel fil g oti ni b, d o u ble-bli n d fil g oti ni b t o sta n dar d of care, a n d 
place b o t o sta n dar d of care).
3. 3.
Str at a a n d C o v ari ates
S u bjects will be ra n d o ml y assi g ne d t o treat me nt gr o u ps via t he I WR S i n a 1: 1 rati o usi n g a 
stratifie d ra n d o mizati o n sc he d ule. S tratificati o n will be base d o n t he f oll o wi n g varia ble s:

T y pe of r he u mat ol o gic c o n diti o n ( R A , S p o n d y l oart hritis [Ps A , A S, nr A x S p A])

C o nc urre nt use of M T X ( Yes , N o)

S per m c o nce ntrati o n ( mea n of 2 e val ua ble sa m ples) meas ure d at t he Scree ni n g visit : 1) 1 5 t o
2 5
M / m L; 2) > 2 5 t o 5 0 M / m L; 3) > 5 0 M / m L
If t here are discre pa ncies i n stratificati o n fact or val ues bet wee n t he I WR S a n d t he cli nical 
data base, t he val ues rec or de d i n t he cli nical d ata base will be use d f or a nal ysi s.
3. 4.
E x a mi n ati o n of S u bject S u b gr o u ps
S u b gr o u p a nal ys es f or t he pri mar y  e n d p oi nt are s pecifie d i n Secti o n 6. 3.
3. 5.
Missi n g D at a a n d O utliers
3. 5. 1.  
Missi n g D at a
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. E xce pti o ns are prese nte d i n t his d oc u me nt.
F or mis si n g last d osi n g date of st u d y  dr u g, i m p utati o n r ules are descri be d i n Secti o n 4. 2. 1 . T he 
ha n dli n g of missi n g or i nc o m plete dates f or A E o nset is descri be d i n Secti o n 8. 1. 5. 2 , a n d f or
pri or a n d c o nc o mita nt me dicati o n s i n Secti o n 8. 4 .
3. 5. 2.  
O utliers
O utliers will be i de ntifie d d uri n g t he data ma na ge me nt a n d data a nal ys is pr ocess . All data, 
i ncl u di n g o utliers, will be i ncl u de d i n data a nal ys es.
3. 6.  
D at a H a n dli n g C o n ve nti o ns a n d Tr a nsf or m ati o ns
I n ge neral, a ge (i n years) o n t he date of t he first d ose of a n y st u d y dr u g will be use d f or a nalys es 
a n d prese ntati o n i n listi n gs. If a ra n d o mize d s u bject was n ot d ose d wit h a n y st u d y dr u g, t he 
ra n d o mizati o n date will be use d i nstea d of t he first d osi n g da te of st u dy dr u g f or a ge calc ulati o n. 
F or scree n fail ures, t he date t he i nf or me d c o nse nt was si g ne d will be use d f or a ge calc ulati o n. If 
o nl y  t he birt h y ear is c ollecte d o n t he e C R F, “ 0 1 J ul y” will be use d f or t he u n k n o w n birt h da y  
a n d m o nt h f or p ur p oses of a ge calc ulati o n. If o nly birt h y ear a n d m o nt h are c ollecte d, “ 1 5 ” will 
be use d f or t he u n k n o w n birt h da y .


Fil g oti ni b
G L P G 0 6 3 4 -C L -2 2 7
Statistical A nal ysis Pla n
Versi o n 1. 0
C O N FI D E N TI A L
Pa ge 1 8
1 2 Ja n uar y 2 0 2 1
N o n -P K 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 wer li mit of q ua ntitati o n ( L O Q)
or a b o ve t he u p per L O Q will be i m p ute d as f oll o ws:

A val ue t hat is 1 u nit less t ha n t he L O Q will be use d t o calc ulate descri pti ve statistics if t he 
dat u m is re p orte d i n t he f or m of “ x” ( w here x is c o nsi dere d t he L O Q ). F or e xa m ple, if t he 
val ues are re p orte d as < 5 0 a n d < 5. 0, val ues of 4 9 a n d 4. 9 , res pecti vel y, will be use d t o 
calc ulate s u m mar y statistics. A n e xce pti o n t o t his r ule is a ny val ue re p orte d as < 1 or < 0. 1, 
etc. F or val ues re p orte d as < 1 or < 0. 1, a val ue of 0. 9 or 0. 0 9 , res pecti vel y, will be use d t o 
calc ulate s u m mar y statistics.

A val ue t h at is 1 u nit a b o ve t he L O Q will be use d t o calc ulate descri pti ve statistics if t he 
dat u m is re p orte d i n t he f or m of “ > x” ( w here x is c o nsi dere d t he L O Q ). Val ues wit h deci mal 
p oi nts will f oll o w t he sa me l o gic as a b o ve.

T he L O Q will be use d t o calc ulate descri pti ve statistics if t he dat u m is re p orte d i n t he f or m of 
“≤ x” or “ ≥ x” ( w here x is c o nsi dere d t he L O Q ).
Plas ma c o nce ntrati o n val ues t hat are 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 he c o nce ntrati o n data listi n g.
3. 7.
A n al ysis Visit Wi n d o ws
3. 7. 1.
Defi niti o n of St u d y D a y
T he First D osi n g Date of D o u ble- Bli n d Fil g oti ni b/ P lace b o is defi ne d as t he date w he n s u bjects 
ta ke t heir first d ose of d o u ble -bli n d fil g oti ni b/ place b o as rec or de d o n t he St u d y Dr u g 
A d mi nistrati o n e C R F .
T he Last D osi n g Date of D o u ble - Bli n d Fil g oti ni b/ Place b o is defi ne d as t he date w he n s u bjects 
ta ke t heir last d ose of d o u ble -bli n d fil g oti ni b/ place b o as rec or de d i n t he St u d y  Dr u g 
A d mi nistrati o n e C R F.
T he Last D osi n g Date of A n y  Fil g oti ni b is defi ne d as t he date w he n a s u bject ta kes t heir last d ose 
of d o u ble -bli n d or o pe n -la bel fil g oti ni b as rec or de d i n t he St u d y Dr u g A d mi nistrati o n e C R F.
T he Start Date of E xte nsi o n P hase is defi ne d as t he first d ose date of o pe n -la bel fil g oti ni b (f or 
r he u matic disease res p on ders ra n d o mize d t o fil g oti ni b w h o c o nti n ue d o n o pe n-la bel filg ot i ni b i n 
e xte nsi o n p hase ) fr o m t he st u d y dr u g a d mi nistrati o n e C R F or last d ose date of d o u ble-bli n d 
st u d y dr u g + 1 da y f or s u bjects w h o ha ve a n o n-missi n g sta n dar d of care start date i n t he 
e xte nsi o n p hase of t he st u d y. I n s o me c o u ntries, it ta kes ti me t o o btai n a ne w sta n dar d of care 
dr u g f or r he u matic disease w he n s u bjects u n der g o a me dicati o n s witc h (es pecially f or bi ol o gics ), 
s o t he “sta n dar d of care” is t o c o nti n ue bac k gr o u n d me dicati o ns al o ne or i n rare cases, t o ta ke n o 
r he u matic disease me dicati o n u ntil t he ne w re gi me n is a vaila ble.


Fil g oti ni b
G L P G 0 6 3 4 -C L -2 2 7
Statistical A nal ysis Pla n
Versi o n 1. 0
C O N FI D E N TI A L
Pa ge 1 9
1 2 Ja n uar y 2 0 2 1
T he E n d Date of E xte nsi o n P hase is defi ne d as last d ose date of o pe n-la bel fil g oti ni b as rec or de d 
o n t he S t u d y Dr u g A d mi nistrati o n e C R F f or s u bjects o n o pe n- la bel fil g oti ni b i n t he E xte nsi o n 
P hase . T he en d date f or sta n dar d of care i n e xte nsi o n p hase will be 1 da y  pri or t o t he date t he 
s u bject we nt i nt o t he M o nit ori n g P hase (ie, date t he site was n otifie d of s u bject meeti n g a 
pres pecifie d s per m decrease t hres h ol d). S u bjects w h o d o n ot partici pate i n M o nit ori n g P hase b ut
ha ve a St u d y C o m pleti o n e C R F t hat states t hat t he s u bject has eit her c o m plete d st u d y or 
pre mat urel y disc o nti n ue d st u d y will ha ve t he last date of sta n dar d of care esti mate d usi n g t he last 
of t he f oll o wi n g dates: last C o va nce la b date, last e C R F visit date, date of last s per m sa m ple
c ollecti o n, a n d deat h date (if s u bject die d).
St u d y  D a y will be calc ulate d fr o m t he first d osi n g date of d o u ble -bli n d fil g oti ni b/ place b o a n d 
deri ve d as f oll o ws:

F or p ost d ose st u d y da ys : Assess me nt Date – O n -Fil g oti ni b/ Place b o St u d y  D a y 1 + 1

F or da y s pri or t o t he first d ose: Assess me nt Date – O n -Fil g oti ni b/ Place b o St u d y  Da y 1
F oll o w -u p ( F U) Da y will be calc ulate d fr o m last st u d y dr u g ( d o u ble-bli n d st u d y  dr u g or 
o p e n-la bel fil g oti ni b) d osi n g date or e n d date of e xte nsi o n p hase f or s u bjects o n sta n dar d of care .
T he F U da y  is deri ve d as Assess me nt Date – Last D ose Date of st u d y  dr u g/e n d date of e xte nsi o n 
p hase f or s u bjects o n sta n dar d of care
T heref ore, F oll o w - u p Da y 1 is t he first da y  after per ma ne nt disc o nti n uati o n of all st u d y dr u gs or 
e n d of E xte nsi o n P hase f or s u bjects o n sta n dar d of care i n e xte nsi o n p hase.
Baseli ne is defi ne d as t he last a vaila ble o bser vati o n ta ke n o n or pri or t o t he first d ose date of 
d o u ble - bli n d fil g oti ni b/ place b o st u d y dr u g.
F or se me n para meters, incl u di n g s per m c o nce ntrati o n, t otal s per m c o u nt, ejac ulate v ol u me, 
s per m t otal m otilit y , a n d s per m m or p h ol o g y, t he baseli ne val ue is t he mea n of 2 e val ua ble 
sa m ples fr o m t he scree ni n g visit . T he baseli ne val ue f or s per m para meters is use d t o deter mi ne
w het her s u bjects ha ve met a s per m para meter decrease t hres h ol d (ie, ≥ 5 0 % decrease fr o m 
baseli 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). 
3. 7. 2.
A n al ysis Visit Wi n d o ws
S u bject visit s mi g ht n ot occ ur o n pr ot oc ol-s pecifie d da ys. T heref ore, f or t he p ur p oses of a nal y sis, 
o bser vati o ns will be assi g ne d t o a nal ys is visit wi n d o ws.
T he a nal ys is visit wi n d o ws f or u ri nalys is, P h G A D A , a n d li pi d pr ofiles are pr o vi de d i n Ta ble 3- 1 . 
T he a nal ys is visit wi n d o ws f or hi g h -se nsiti vit y C- reacti ve pr otei n (hs C R P), vital si g ns, wei g ht, 
he mat ol o g y a n d c he mistr y  la b orat ories are pr o vi de d i n Ta ble 3- 2 . T he a nal y sis visit wi n d o ws f or 
L H, F S H, i n hi bi n B, a n d t otal test oster o ne are pr o vi de d i n Ta ble 3- 3 . T he a nal ysis wi n d o ws f or 
se me n para meters are pr o vi de d i n Ta ble 3- 4 a n d Ta ble 3 - 5, res pecti vely.


Fil g oti ni b
G L P G 0 6 3 4 -C L -2 2 7
Statistical A nal ysis Pla n
Versi o n 1. 0
C O N FI D E N TI A L
Pa ge 2 0
1 2 Ja n uar y 2 0 2 1
Visit Wi n d o w R ules f or D o u ble -Bli n d P hase Dis pla y s
Data c ollecte d d uri n g t he d o u ble -bli n d p hase of t he st u d y  will ha ve visit wi n d o ws assi g ne d base d 
o n st u d y  da y calc ulate d fr o m first d ose date of d o u ble-bli n d st u d y dr u g.
Visit Wi n d o w R ules f or E xte nsi o n P hase Dis pla y s
Data c ollecte d d uri n g t he e xte nsi o n p hase of t he st u d y  will ha ve visit wi n d o ws assi g ne d base d o n 
st u d y da y calc ulate d fr o m first d ose date of d o u ble-bli n d st u d y  dr u g.
Visit Wi n d o w R ules f or F U - 4 Visit (la bs [i ncl u di n g h or m o nes], vital si g ns, hei g ht, wei g ht, B MI)
Pri or t o pr ot oc ol a me n d me nt 1, all s u bjects were t o ha ve a 3 0 -d a y  safet y f oll o w-u p visit after 
t heir last d ose date of a n y fil g oti ni b (last of d o u ble -bli n d /o pe n -la bel) or d o u ble -bli n d place b o. 
U n der pr ot oc ol a me n d me nt 1, res p o n ders assi g ne d t o place b o will n o l o n ger be re q uire d t o 
atte n d a safet y f oll o w -u p visit after Wee k 1 3. F or s u bjects i n t he fil g oti ni b 2 0 0 m g t o O L 
fil g oti ni b gr o u p, t he f oll o w-u p visit will occ ur after t he e xte nsi o n p hase (ie, F U da ys); f or 
r he u matic disease n o nres p o n ders c o nti n ui n g o n sta n dar d of care i n e xte nsi o n p hase, t he 
f oll o w-u p visit will be wi n d o we d base d o n da y s i n e xte nsi o n p hase (ie E X T da ys) si nce s u bjects 
will be off of st u d y dr u g b ut o n sta n dar d of care i n e xte nsi o n p hase. S u bjects w h o meet a s per m 
decrease t hres h ol d at Wee k 1 3 or pre mat urel y disc o nti n ue fr o m d o u ble -bli n d st u d y  dr u g will 
ha ve t he F oll o w -U p Wee k 4 visit calc ulate d fr o m t he last d ose date of d o u ble- bli n d st u d y  dr u g.
Visit Wi n d o w R ules f or M o nit ori n g P hase S per m Para meters
Se me n a n d h or m o ne data c ollecte d i n t he M o nit ori n g P hase will ha ve visit wi n d o ws calc ulate d 
fr o m t he ma xi m u m of last d ose date of a ny st u d y dr u g ( d o u ble -bli n d dr u g or o pe n -la bel 
fil g oti ni b) or date s u bject w e nt i nt o M o nit ori n g P hase (t he date t he site recei ves n otificati o n of 
t he s u bject meeti n g a s per m decrease t hres h ol d) f or s u bjects o n sta n dar d of care i n e xte nsi o n 
p hase . 


Fil g oti ni b
G L P G 0 6 3 4 -C L -2 2 7
Statistical A nal ysis Pla n
Versi o n 1. 0
C O N FI D E N TI A L
Pa ge 2 1
1 2 Ja n uar y 2 0 2 1
T a ble 3- 1.  
A n al ysis Visit Wi n d o ws f or Uri n al ysis, P h G A D A , a n d Li pi d Pr ofile
A n al ysis Visit
N o m i n al D a y
( St u d y D a y)
L o wer Li mit
( St u d y D a y)
U p per Li mit
( St u d y D a y)
Baseli ne * #
1
N o ne
1
Wee k 1 3 * #
9 2
2
1 3 7
Wee k 2 6
#
1 8 3
1 3 8
2 2 8
Wee k 3 9
#
2 7 4
2 2 9
3 1 9
Wee k 5 2
3 6 5
3 2 0
4 1 0
Wee k 6 5
#
4 5 6
4 1 1
5 0 1
Wee k 7 8
5 4 7
5 0 2
5 9 2
Wee k 9 1
#
6 3 8
5 9 3
6 8 3
Wee k 1 0 4
7 2 9
6 8 4
7 7 4
Wee k 1 1 7
#
8 2 0
7 7 5
8 6 5
Wee k 1 3 0
9 1 1
8 6 6
9 5 6
Wee k 1 4 3
#
1 0 0 2
9 5 7
1 0 4 7
Wee k 1 5 6
1 0 9 3
1 0 4 8
≥1 0 9 3
F U - 4^
Last D ose Date O L fil g oti ni b
(fil g o t o O L fil g o); last d ose
date D B dr u g, ot her w ise
+ 3 0 Da ys
Last D ose Date O L fil g oti ni b
(fil g o t o O L fil g o); last d ose
date D B dr u g, ot her w ise
+ 8 Da ys
Last D ose Date O L fil g oti ni b
(fil g o t o O L fil g o); last d ose
date D B dr u g *, ot her wise
+ 3 5 Da ys
* P h G A D A is o nl y assesse d at t he Baseli ne a n d Wee k 1 3
a nal ysis visit wi n d o w. P h G A D A is o nl y c ollecte d t o deter mi ne w het her 
t he s u bject is a res p o n der or n o n-res p o n der at t he e n d of t he d o u ble -bli n d p hase. # Li pi d pr ofile is c ollecte d at baseli ne, 
a n d at Wee ks 1 3, 2 6, 3 9, 6 5, 9 1, 1 1 7 , a n d 1 4 3.
^ F U -4 visit c ollecte d base d o n da ys fr o m last d ose of o pe n -la bel fil g oti ni b (fil g oti ni b 2 0 0 m g t o O L fil g oti ni b); E X T da ys f or all 
( pri or t o A me n d me nt 1) s u bjects / o nl y n o n-res p o n ders (after A me n d me nt 1) w h o s witc he d t o sta n dar d of care i n e xte nsi on 
p hase; a n d fr o m last d ose date of d o u ble -bli n d st u d y dr u g f or t h ose meeti n g s per m decrease t hres h ol d at Wee k 1 3 or pre mat urel y 
disc o nti n ue d i n/at e n d of d o u ble - bli n d p hase. Pr ot oc ol s pecifie d a n u p per b o u n d of + 5 da ys. F U-4 visit wi n d o w is a p plica ble f or 
uri nal ysis.


Fil g oti ni b
G L P G 0 6 3 4 -C L -2 2 7
Statistical A nal ysis Pla n
Versi o n 1. 0
C O N FI D E N TI A L
Pa ge 2 2
1 2 Ja n uar y 2 0 2 1
T a ble 3- 2.  
A n al ysis Visit Wi n d o ws f or hs -C R P, Vit al Si g ns, Wei g ht, He m at ol o g y ,
a n d C he mistr y L a b or at ories 
A n al ysis Visit
N o m i n al D a y
( St u d y D a y)
L o wer Li mit
( St u d y D a y)
U p per Li mit
( St u d y D a y)
Baseli ne
1
N o ne
1
Wee k 2
1 5
2
2 2
Wee k 4
2 9
2 3
4 3
Wee k 8
5 7
4 4
7 4
Wee k 1 3
9 2
7 5
1 3 7
Wee k 2 6
1 8 3
1 3 8
2 2 8
Wee k 3 9
2 7 4
2 2 9
3 1 9
Wee k 5 2
3 6 5
3 2 0
4 1 0
Wee k 6 5
4 5 6
4 1 1
5 0 1
Wee k 7 8
5 4 7
5 0 2
5 9 2
Wee k 9 1
6 3 8
5 9 3
6 8 3
Wee k 1 0 4
7 2 9
6 8 4
7 7 4
Wee k 1 1 7
8 2 0
7 7 5
8 6 5
Wee k 1 3 0
9 1 1
8 6 6
9 5 6
Wee k 1 4 3
1 0 0 2
9 5 7
1 0 4 7
Wee k 1 5 6
1 0 9 3
1 0 4 8
≥1 0 9 3
F U -4 *
Last D ose Date O L fil g oti ni b
(fil g o t o O L fil g o); last d ose
d ate D B dr u g * , ot her wise
+ 3 0 Da ys
Last D ose Date O L fil g oti ni b
(fil g o t o O L fil g o); last d ose
date D B dr u g * , ot her wise
+ 8 Da ys
Last D ose Date O L fil g oti ni b
(fil g o t o O L fil g o); last d ose
date D B dr u g * , ot her wise
+ 3 5 Da ys
N ote: Data will be i ncl u de d f or “ o n -treat me nt” visits u p t o t he last d ose date of sta n dar d of care i n t he e xte nsi o n p hase 
(if n o n -missi n g) or u p t o last d ose date of a n y st u d y dr u g + 7 da ys.
* F U -4 visit c ollecte d base d o n da ys fr o m last d ose of o pe n -la bel fil g oti ni b (fil g oti ni b 2 0 0 m g t o O L fil g oti ni b); E X T da ys f or all
( pri or t o A me n d me nt 1) s u bjects / o nl y n o n-res p o n ders (after A men d me nt 1) w h o s witc h e d t o sta n dar d of care i n e xte nsi o n 
p has e; a n d fr o m last d ose date of d o u ble-bli n d st u d y dr u g f or t h ose meeti n g s per m decrease t hres h ol d at Wee k 1 3 or pre mat urel y 
d isc o nti n ue d i n/at e n d of d o u ble-bli n d p hase . Pr ot oc ol s pecifie d a n u p per b o u n d of + 5 da ys. F U -4 visit wi n d o w is a p plica ble f or 
he mat ol o g y, c he mistr y, vitals , a n d wei g ht.


Fil g oti ni b
G L P G 0 6 3 4 -C L -2 2 7
Statistical A nal ysis Pla n
Versi o n 1. 0
C O N FI D E N TI A L
Pa ge 2 3
1 2 Ja n uar y 2 0 2 1
T a ble 3- 3.  
A n al ysis Visit Wi n d o ws f or L H, F S H, I n hi bi n B, a n d T ot al
Test oster o ne
A n al ysis Visit
N o m i n al D a y
( St u d y D a y)
L o wer Li mit
( St u d y D a y)
U p per Li mit
( St u d y D a y)
Baseli ne
1
N o ne
1
Wee k 4
2 9
2
8 4
Wee k 1 3
9 2
8 5
1 1 2
Wee k 2 6
1 8 3
1 7 0
2 6 0
Wee k 3 9
2 7 4
2 6 1
3 5 1
Wee k 5 2
3 6 5
3 5 2
4 4 2
Wee k 6 5
4 5 6
4 4 3
5 3 3
Wee k 7 8
5 4 7
5 3 4
6 2 4
Wee k 9 1
6 3 8
6 2 5
7 1 5
Wee k 1 0 4
7 2 9
7 1 6
8 0 6
Wee k 1 1 7
8 2 0
8 0 7
8 9 7
Wee k 1 3 0
9 1 1
8 9 8
9 8 8
Wee k 1 4 3
1 0 0 2
9 8 9
1 0 7 9
Wee k 1 5 6
1 0 9 3
1 0 8 0
≥1 0 9 3
F U -4 *
Last D ose Date O L fil g oti ni b
(fil g o t o O L fil g o); last d ose
date D B dr u g * , ot her wise
+ 3 0 Da ys
Last D ose Date O L fil g oti ni b
(fil g o t o O L fil g o); last d ose
date D B dr u g * , ot her wise
+ 8 Da ys
Last D ose Date O L fil g oti ni b
(fil g o t o O L fil g o); last d ose
date D B dr u g * , ot her wise
+ 3 5 Da ys
N ote: Data will be i ncl u de d f or “ o n -treat me nt” visits u p t o t he last d ose date of sta n dar d of care i n t he e xte nsi o n p hase 
(if n o n -missi n g) or u p t o last d ose date of a n y st u d y dr u g + 7 da ys.
* F U -4 visit c ollecte d base d o n da ys fr o m last d ose of o pe n -la bel fil g oti ni b (fil g oti ni b 2 0 0 m g t o O L fil g oti ni b); off st u d y dr u g b ut 
i n E X T p hase f or all ( pri or t o A me n d me nt 1) s u bjects / o nl y n o n- res p o n ders (after A me n d me nt 1) w h o s witc he d t o sta n dar d of 
care i n e xte nsi o n p hase; a n d fr o m last d ose date of d o u ble -bli n d st u d y dr u g f or t h ose meeti n g s per m decrease t hres h ol d at 
Wee k
1 3 or pre mat urel y d isc o nti n ue d i n/at e n d of d o u ble-bli n d p hase. Pr ot oc ol s pecifie d a n u p per b o u n d of + 5 da ys.


Fil g oti ni b
G L P G 0 6 3 4 -C L -2 2 7
Statistical A nal ysis Pla n
Versi o n 1. 0
C O N FI D E N TI A L
Pa ge 2 4
1 2 Ja n uar y 2 0 2 1
T a ble 3- 4.  
A n al ysis Visit Wi n d o ws f or O n -Tre at me nt Se me n P ar a meters
A n al ysis Visit
N o m i n al D a y
( St u d y D a y)
L o wer Li mit
( St u d y D a y)
U p per Li mit
( St u d y D a y)
Baseli ne
1
N o ne
1
Wee k 1 3
9 2
8 5
1 1 2
Wee k 2 6
1 8 3
1 7 0
2 6 0
Wee k 3 9
2 7 4
2 6 1
3 5 1
Wee k 5 2
3 6 5
3 5 2
4 4 2
Wee k 6 5
4 5 6
4 4 3
5 3 3
Wee k 7 8
5 4 7
5 3 4
6 2 4
Wee k 9 1
6 3 8
6 2 5
7 1 5
Wee k 1 0 4
7 2 9
7 1 6
8 0 6
Wee k 1 1 7
8 2 0
8 0 7
8 9 7
Wee k 1 3 0
9 1 1
8 9 8
9 8 8
Wee k 1 4 3
1 0 0 2
9 8 9
1 0 7 9
Wee k 1 5 6
1 0 9 3
1 0 8 0
≥1 0 9 3
N ote: Pri mar y a nal ysis i ncl u des data u p t o first d ose date of o pe n -la bel fil g oti ni b/first date i n e xte nsi o n p hase (if n o n -missi n g) or
t o last d ose date of d o u ble- bli n d dr u g + 7 da ys (f or t h ose n ot c o nti n ui n g i n E xte nsi o n P hase).
Sec o n dar y a nal ysis i ncl u des all “ o n-treat me nt” data u p t o t he last d ose date i n e xte nsi o n p hase (if n o n-missi n g) or t o last d ose 
date of a n y st u d y dr u g + 7 da ys .
T a ble 3- 5.
A n al ysis Visit Wi n d o ws f or Se me n P ar a meters i n M o nit ori n g P h ase 
( C alc ul ate d fr o m L ast D ose D ate of A n y St u d y Dr u g/E n d of E xte nsi o n 
P h ase f or t h ose o n S t a n d ar d of C are i n E xte nsi o n P h ase)
A n al ysis Visit
N o m i n al D a y
( F U D a y)
L o wer Li mit
( F U D a y)
U p per Li mit
( F U D a y)
M P Wee k 1 3
9 1
8
1 0 4
M P Wee k 2 6
1 8 2
1 0 5
1 9 5
M P Wee k 3 9
2 7 3
1 9 6
2 8 6
M P Wee k 5 2
3 6 4
2 8 7
3 7 7
M P = M o nit ori n g P hase; F U = F oll o w -U p.
N O T E: All visit wi n d o ws f or m o nit ori n g p hase will be calc ulate d fr o m last d ose date of a n y st u d y dr u g/ e n d date i n E xte nsi o n 
P hase ( date site recei ves c o nfir mati o n of s u bject meeti n g s per m para meter decrease t hres h ol d) f or s u bjects ta ki n g sta n dar d of 
care i n e xte nsi o n p hase w h o met pre -s pecifie d s per m decrease t hres h ol d s.
F U Da y = visit date – last d ose date of a n y st u d y dr u g/last date i n exte nsi o n p hase.


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Versi o n 1. 0
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I n vesti gat or Assess me nt of Electr ocar di o gra m (E C G ) Visit Assi g n me nt
N o mi nal visits fr o m t he cli nical data base will be use d t o assi g n ti me p oi nts f or t he i n ve sti gat or’s 
assess me nt of E C G . Baseli ne will use t he n o mi nal visit “ Scree ni n g”; Wee k 1 3 or Earl y 
Ter mi nati o n will use a n o mi nal visit of “ Wee k 1 3” or “ E arl y ter mi nati o n ” if s u bject pre mat urely 
disc o nti n ue d d o u ble -bli n d st u d y dr u g ; a n d L T E Wee k 1 5 6 or Earl y ter mi nati o n visit f or s u bjects 
i n t he fil g oti ni b 2 0 0 m g t o o pe n-la bel fil g oti ni b 2 0 0 m g gr o u p will use n o mi nal visits of 
“E xte nsi o n Wee k 1 5 6 ” or “ Earl y ter mi nati o n ” f or s u bjects w h o earl y ter mi nate d after starti n g 
o pe n -la bel fil g oti ni b ( per pr ot oc ol A me nd me nt 1 s u bjects ta ki n g sta n dar d of care i n e xte nsi o n 
p hase are n o l o n ger re q uire d t o c o m plete a n E C G at Wee k 1 5 6 or earl y ter mi nati o n).
3. 7. 3.
Selecti o n of D at a i n t he E ve nt of M ulti ple Rec or ds i n a n A n al ysis Visit 
Wi n d o w
De pe n di n g o n t he statistical a nal ys is met h o d utilize d , si n gle val ues ma y be re q uire d fr o m eac h 
a nal ys is wi n d o w. F or e xa m ple, c ha n ge fr o m baseli ne b y visit us ually re q uires a si n gle val ue, 
w hereas a ti me -t o-e ve nt a nal ys is w o ul d n ot re q uire 1 val ue per a nalys is wi n d o w. 
If m ulti ple vali d, n o n missi n g, c o nti n u o us meas ure me nts e xist i n a n a nal ysis wi n d o w, rec or ds 
will be c h ose n base d o n t he f oll o wi n g r ules if a si n gle val ue is nee de d. 

I n ge neral, t he baseli ne val ue will be t he last n o n missi n g val ue o n or pri or t o t he first d osi n g 
date of st u d y dr u g , u nless s pecifie d differe ntly. 

If m ulti ple meas ure me nts occ ur o n t he sa me da y, t he last n o n missi n g val ue pri or t o t he ti me 
of first d osi n g of st u d y dr u g will be c o nsi dere d as t he baseli ne val ue. If t hese m ulti ple 
meas ure me nts occ ur at t he sa me ti me or t h e ti me is n ot a vaila ble, t he a vera ge of t hese 
meas ure me nts (f or c o nti n u o us data) will be c o nsi dere d t he baseli ne val ue.

F or p ost baseli ne val ues:

T he rec or d cl osest t o t he n o mi nal da y  f or t hat visit will be selecte d.

If t here are 2 rec or ds t hat are e q ui dista nt fr o m t he n o mi nal da y, t he later rec or d will be 
selecte d.

If t here is m ore t ha n 1 rec or d o n t he selecte d da y, t he a vera ge will be ta ke n, u nless 
ot her wise s pecifie d.
If m ulti ple vali d, n o n missi n g, cate g orical meas ure me nts e xist i n a n a nal ysis wi n d o w, recor ds 
will be c h ose n base d o n t he f oll o wi n g r ules if a si n gle val ue is nee de d:

F or baseli ne, t he last a vaila ble rec or d o n or pri or t o t he date of t he first d ose of st u d y dr u g 
will be selecte d. If t here are m ulti ple rec or ds wit h t he sa me ti me or n o ti me rec o r de d o n t he 
sa me da y, t he val ue wit h t he l o west se verity will be selecte d (e g, n or mal will be selecte d o ver 
a b n or mal f or safet y fi n di n gs).

F or p ost baseli ne visits, if t here are m ulti ple rec or ds wit h t he sa me ti me or n o ti me rec or de d 
o n t he sa me da y , t he val ue wit h t he w orst se verit y wit hi n t he wi n d o w will be selecte d 
(e g, a b n or mal will be selecte d o ver n or mal f or safet y  fi n di n gs).


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G L P G 0 6 3 4 -C L -2 2 7
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Versi o n 1. 0
C O N FI D E N TI A L
Pa ge 2 6
1 2 Ja n uar y 2 0 2 1
F or se me n data, si nce 2 e val ua ble se me n sa m ples are re q uire d at eac h se me n sa m ple c ollecti o n 
ti me p oi nt , t he a vera ge of t he measure me nts will be ta ke n a n d t he st u d y da y ass ociate d wit h t he 
earliest vali d meas ure me nt will be use d f or assi g n me nt of t he visit t o a n a nal ysis visit wi n d o w. 
F or t he s u p p orti ve a nal ys is of s per m c o nce ntrati o n at Wee k 1 3 t hat i ncl u des s u bjects wit h o nl y 
1 e val ua ble meas ure me nt at a c ollecti o n ti me p oi nt, t he date of t he si n gle s a m ple will be use d t o 
calc ulate t he st u d y d a y f or assi g n me nt t o a nal ys is visit wi n d o w. If m ulti ple c ollecti o n ti me p oi nts 
fall wit hi n a visit wi n d o w , t he a b o ve r ule will be a p plie d.


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4.
S U B J E C T DI S P O SI TI O N
4. 1.
S u bject R a n d o miz ati o n a n d Dis p ositi o n
S u m maries descri be d u n der t his secti o n will be base d o n t he All Ra n d o mize d A nal ysis Set a n d
ra n d o mize d treat me nt gr o u ps.
A s u m mar y  of s u bject ra n d o mizati o n will be pr o vi de d b y ra n d o mize d treat me nt a nd o verall f or 
eac h c o u ntr y, a n d i n vesti gat or wit hi n a c o u ntr y. T he s u m mar y will prese nt t he n u m ber a n d 
perce nta ge of s u bjects ra n d o mize d. F or eac h c ol u m n, the de n o mi nat or f or t he perce nta ge 
calc ulati o n will be t he t otal n u m ber of s u bjects a nal yze d f or t hat c ol u m n.
A si milar ra n d o mizati o n ta ble will be pr o vi de d by ra n d o mizati o n strat u m. T he de n o mi nat or f or 
t he perce nta ge of s u bjects i n t he strat u m will be t he t otal n u m ber of ra n d o mize d s u bjects. If t here 
are discre pa ncies i n t he val ue use d f or stratificati o n assi g n me nt bet wee n t he I WR S a n d t he 
cli nical data base, t he val ue c ollecte d i n t he cli nical data base will be use d f or t he s u m mar y . A 
listi n g of s u bjects wit h discre pa ncies i n t he val ue use d f or stratificati o n assi g n me nt bet wee n t he 
I WR S a n d t he cli nical data base at t he ti me of data fi nalizati o n will be pr o vi de d.
T he ra n d o mizati o n sc he d ule use d f or t he st u d y will be pr o vi de d as a n a p pe n di x t o t he C S R.
T he fl o w t hr o u g h t he st u d y  f or a n i n di vi d ual s u bject will be deter mi ne d by t he res p o nse of t he 
u n derl y i n g r he u mat ol o gic c o n diti o n t o assi g ne d treat me nt a n d by t he s u bject meeti n g a 
pre -s pecifie d s per m decrease t hre s h ol d (e g, a ≥ 5 0 % decrease i n s per m c o nce ntrati o n a n d/ or 
m otilit y  a nd/ or m or p h ol o g y  fr o m baseli ne) . S u bjects meeti n g a pre -s pecifie d s per m decrease 
thres h ol d will st o p st u d y  dr u g a n d e nter t he M o nit ori n g P hase of t he st u d y. T he mea n val ue at a 
st u d y visit f or eac h of t he s per m parameters ( meas ure d fr o m 2 se parate e val ua ble s per m 
c ollecti o n sa m ples) will be use d t o deter mi ne w het her a pre -s pecifie d s per m decrease t hres h ol d 
has bee n met. I n t he s pecial case w here t he 2 se me n c ollecti o ns at a visit are e val ua ble, b ut data 
f or a n i n di vi d ual s per m para meter (ie, m otilit y is n ot e val ua ble d ue t o tec h nical pr o ble ms w he n 
perf or mi n g se me n a nal ys is) is n ot e val ua ble, t he 1 e val ua ble val ue will be use d t o deter mi ne 
w het her a pre -s pecifie d s per m decrease t hres h ol d was met f or t hat s per m para meter, w hile t he 
mea n of t he 2 sa m ples will be use d f or s per m para meters wit h 2 e val ua ble c ollecti o ns.
A s u m mar y  of s u bject dis p ositi o n will be pr o vi de d b y ra n d o mize d treat me nt gr o u p a n d o verall. 
T his s u m mar y  will prese nt t he n u m ber of s u bjects scree ne d (rescree ns are c o u nte d o nl y  o nce) , 
t he n u m ber of s u bjects ra n d o mize d, a n d t he n u m ber of s u bjects i n t he safet y a nal ysis set. I n 
a d diti o n, t he n u m ber a n d perce nta ge of s u bjects i n eac h cate g or y  bel o w will be s u m marize d:
D o u ble - Bli n d St u d y Dr u g C o m pleti o n St at us T hr o u g h Wee k 1 3

C o m plete d bli n de d st u d y dr u g t hr o u g h Wee k 1 3

S witc he d t o M o nit ori n g P hase after Wee k 1 3 ( s u bject met pre-s pecifie d s per m decrease 
t hres h ol d[s])

S witc he d t o O pe n -La bel Fil g oti ni b after Wee k 1 3 ( R es p o n der o n d o u ble -bli n d fil g oti ni b , 
s u bject di d n ot meet pre -s pecifie d s per m decrease t hres h ol d [s])


Fil g oti ni b
G L P G 0 6 3 4 -C L -2 2 7
Statistical A nal ysis Pla n
Versi o n 1. 0
C O N FI D E N TI A L
Pa ge 2 8
1 2 Ja n uar y 2 0 2 1

S witc he d t o Sta n dar d of Care after Wee k 1 3 ( N o n -res p o n der o n d o u ble -bli n d fil g oti ni b;
or ra n d o mize d t o place b o i n d o u ble-bli n d p hase , s u bject di d n ot meet pre -s pecifie d s per m 
decrease t hres h ol d [s])

Has Wee k 1 3 Se me n Sa m ple/ Ter mi nate d fr o m St u d y . S u bject I D 1 5 9 1 5 -6 0 6 0 9 
c o m plete d d o u ble-bli n d st u d y dr u g at Wee k 1 3 a n d ha d 2
e val ua ble se me n sa m ples
c ollecte d. He  s u bse q ue ntl y  early ter mi nate d fr o m st u d y  a n d di d n ot e nter e xte nsi o n p hase 
of t he st u d y .

Di d n ot c o m plete bli n de d st u d y  dr u g t hr o u g h Wee k 1 3 wit h reas o ns f or pre mat ure 
disc o nti n uati o n of st u d y  dru g
E xte nsi o n P h ase O pe n -L a bel Fil g oti ni b St u d y Dr u g C o m pleti o n St at us

C o m plete d E xte nsi o n P hase of st u d y  ( o n o pe n -la bel fil g oti ni b)

O n g oi n g i n E xte nsi o n P hase a n d o n o pe n -la bel fil g oti ni b (f or i nteri m a nalysis o nl y, i ncl u des 
s u bjects w h o c o m plete d 1 3 wee ks of d o u ble-bli n d st u d y  dr u g a n d are o n g oi n g o n o pe n-la bel 
fil g oti ni b i n t he e xte nsi o n p hase at t he ti me of i nteri m a nalys is)

Di d n ot c o m plete E xte nsi o n P hase of st u d y  ( o n o pe n-la bel fil g oti ni b) a n d reas o n f or 
pre mat ure disc o nti n uati o n
E xte nsi o n P h ase S t a nd ar d of C are C o m pleti o n St at us

C o m plete d E xte nsi o n P hase of st u d y o n sta n dar d of care

O n g oi n g i n E xte nsi o n P hase of st u d y o n sta n dar d of care (f or i nteri m a nalysis o nl y, i ncl u des 
s u bjects w h o c o m plete d t he D o u ble- bli n d P hase a n d are o n g oi n g o n Sta n dar d of C are i n t he 
e xte nsi o n p hase at t he ti me of i nteri m a nal ys is)

Di d n ot c o m plete E xte nsi o n P hase of st u d y  o n sta n dar d of care a n d reas o n f or pre mat ure 
disc o nti n uati o n (fr o m st u d y c o m pleti o n f or m)
N ote f or pr o gra m mi n g : S u bjects w h o starte d sta n dar d of care i n e xte nsi o n p hase a n d met a s per m 
decrease t hres h ol d at a visit ot her t ha n “ L T Wee k 1 5 6” will be c o nsi dere d t o be pre mat urel y 
disc o nti n ue d fr o m t his p hase f or “ Pre -S pecifie d Decrease i n S per m Para meters ”. F or s u bjects 
w h o starte d sta n dar d of care i n e xte nsi o n p hase, di d n ot g o i nt o t he m o nit ori n g p hase, a n d di d n ot 
c o m plete st u d y, t he reas o n f or pre mat ure disc o nti n uati o n of st u d y  will be use d f or reas o n f or 
earl y ter mi nati o n of e xte nsi o n p hase . S u bjects w h o starte d sta n dar d of care i n e xte nsi o n p hase 
a n d c o m plete d t he st u d y ( wit h o ut g oi n g i nt o m o nit ori n g p hase) will be c o nsi dere d t o ha ve 
c o m plete d t he e xte nsi o n p hase of t he st u d y o n sta n dar d of care .


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M o nit ori n g P h ase C o m pleti o n St at us

C o m plete d M o nit ori n g P hase of st u d y

Met Re versi bilit y  criteria f or all s per m para meters meeti n g pre-s pecifie d s per m decrease 
t hres h ol d[s]

C o m plete d 5 2 -wee ks of off -treat me nt f oll o w-u p

C o nti n ui n g M o nit ori n g P hase of st u d y (f or i nteri m a nalys is o nly, re prese nts t h ose w h o 
re mai n u n der o bser vati o n i n t he M o nit ori n g P hase
at t he ti me of data c ut off date)

Di d n ot c o m plete M o nit ori n g P hase a n d reas o n f or pre mat ure disc o nti n uati o n
N ote f or pr o gra m mi n g : Reas o ns f or Early Ter mi nati o n fr o m M o nit ori n g P hase a n d C o m pleti o n 
of M o nit ori n g P hase will be p ulle d fr o m t he St u d y C o m pleti o n e C R F.
St u d y C o m pleti o n St at us

C o m plete d st u d y

O n g oi n g i n St u d y  (f or i nteri m a nalys is o nl y, i ncl u des s u bjects c urre ntl y partici pati n g i n t he 
st u d y at t he ti me of a n i nteri m a nalys is)

Di d n ot c o m plete st u d y  wit h reas o ns f or pre mat ure disc o nti n uati o n of stu d y
F or t he stat us of st u d y dr u g, st u d y c o m pleti o n a n d reas o ns f or pre mat ure disc o nti n uati o n of st u d y 
dr u g or st u d y , t he n u m ber a n d perce nta ge of s u bjects i n eac h cate g or y will be pr o vi de d. T he 
de n o mi nat or f or t he perce nta ge calc ulati o n will be t he t otal n u m ber of s u bjects i n t he Safet y 
A nal y sis Set w h o e ntere d i nt o t he st u d y p hase f or t he c ol u m n bei n g s u m marize d. 
T he n u m ber of s u bjects scree ne d f or t he st u d y  t hat di d n ot meet eli gi bilit y criteria will be 
s u m marize d o verall a n d b y i ncl usi o n/e xcl usi o n criteria n ot met ( m ulti ple reas o ns ma y be mar ke d 
f or a n i n di vi d ual scree n). S u bjects w h o were rescree ne d will be s u m marize d base d o n t heir last 
c hr o n ol o gic scree ni n g atte m pt. Scree ns t hat di d n ot fail ≥ 1 eli gi bilit y criteria b ut were n ot 
ra n d o mize d will be s u mmarize d b y  t he reas o n t he s u bject was n ot ra n d o mize d. 
T he f oll o wi n g b y- s u bject listi n gs will be pr o vi de d b y s u bject i de ntificati o n (I D) n u m ber i n 
asce n di n g or der t o s u p p ort t he a b o ve s u m mar y  ta bles:

Reas o ns f or pre mat ure st u d y  dr u g or st u d y disc o nti n uati on

Reas o ns f or scree n fail ure ( will be pr o vi de d b y scree ni n g I D n u m ber i n asce n di n g or der)


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Scree n F ail ure f or S per m/ Se me n P ar a meters
T he n u m ber of s u bjects w h o ha d ≥1 s per m/se me n a b n or malit y  f or Incl usi o n Criteria (I C) 
# 7 base d o n t he mea n of 2 e val ua ble se me n sa m ples at t he scree ni n g visit will be dis pla ye d. 
S u bjects w h o were rescree ne d will be i ncl u de d i n a nal ys is base d o n t heir last c hr o n ol o gic 
scree ni n g atte m pt. Incl usi o n criteria # 7 was defi ne d as: se me n v ol u me ≥ 1. 5 m L ; t otal 
s per m/ejac ulate ≥3 9 M/ ejac ulate; s per m c o nce ntrati o n ≥ 1 5 M / 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 % [ W H O 1 9 9 2 criteria]. T he n u m ber a n d perce nta ge of 
s u bjects n ot meeti n g eac h i n di vi d ual s per m/se me n para meter ( de n o mi nat or f or perce nta ge 
calc ulati o n is n u m ber of s u bjects w h o ha d ≥1 s per m/se me n a b n or malit y) will be dis pla y e d. 
M ulti ple s per m/se me n para meters ma y  n ot q ualif y f or a gi ve n scree ni n g atte m pt.
A listi n g of scree ne d s u bjects wit h 2 e val ua ble se me n sa m ples at t he scree ni n g visit w h o scree n 
faile d f or I C # 7 will be pr o vi de d wit h s per m/se me n para meters n ot meeti n g criteria fla g ge d i n 
t he listi n g.
4. 2.
E xte nt of St u d y D r u g E x p os ure a n d A d here nce
E xte nt of e x p os ure t o st u d y  dr u g will be e xa mi ne d b y assessi n g t he t otal d urati o n of e x p os ure t o 
st u d y dr u g a n d t he le vel of a d here nce t o t he st u d y dr u g s pecifie d i n t he pr ot oc ol.
4. 2. 1.
D ur ati o n of E x p os ure t o St u d y Dr u g
T otal d urati o n of e x p os ure t o d o u ble -bli n d st u d y dr u g (i n wee ks) will be defi ne d as: ([last d osi n g 
date of d o u ble -bli n d st u d y  dr u g mi n us first d osi n g date of d o u ble-bli n d st u d y  dr u g pl us 1] 
di vi de d b y  7), re gar dless of a n y 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. Res ults f or 
all calc ulati o ns of d urati o n will be dis pla y e d t o 1 deci mal place (e g, 4. 5 wee ks).
T otal d urati o n of e x p os ure t o o pe n -la bel fil g oti ni b st u d y dr u g (i n wee ks) will be defi ne d as: 
([last d osi n g date of o pe n -la bel fil g oti ni b st u d y dr u g mi n us first d osi n g date of o pe n-la bel 
fil g oti ni b st u d y dr u g pl us 1] di vi de d b y 7), re gar dless of a n y 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. 
T otal d urati o n of e x p os ure t o a n y fil g oti ni b st u d y dr u g (i n wee ks) will be defi ne d as: 
([last d osi n g date of a n y fil g oti ni b st u d y dr u g mi n us first d osi n g date of a n y fil g oti ni b st u d y dr u g 
pl us 1] di vi de d b y  7), re gar dless of a ny t e 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.
F or s u bjects w h o t o o k d o u ble- bli n d place b o a n d t he n s witc he d t o sta n dar d of care i n e xte nsi o n 
p hase ; a n d s u bjects w h o t o o k d o u ble-bli n d fil g oti ni b, were a n o n -res p o n der at Wee k 1 3, a n d 
s witc he d t o sta n dar d of care i n e xte nsi o n p hase, t he d urati o n i n t he e xte nsi o n p hase will be 
calc ulate d as last date i n e xte nsi o n p hase mi n us first date i n e xte nsi o n p hase + 1 di vi de d 
b y 7 ( e g, re p orte d i n wee ks t o 1 deci mal place ).
F or s u bjects wit h a partial last d osi n g date (ie , m on t h a n d year of last d ose are k n o w n), t he latest 
of t he dis pe nsi n g dates of st u d y  dr u g b ottles, st u d y dr u g start dates a n d e n d dates, a n d t he 
i m p ute d last d osi n g date ( da y i m p ute d as 1 5) will be use d as t he fi nal i m p ute d last d osi n g date. If 
t he s u bject die d a n d t he deat h date is c o m plete (ie, n ot partial date) a n d bef ore t he i m p ute d last 
d osi n g date, t he c o m plete deat h date will be use d as t he i m p ute d last d osi n g date.


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If o nl y year is rec or de d (ie, m o nt h a n d da y of last d ose are missi n g), t he latest of t he dis pe nsi n g 
m o nt h of st u d y  dr u g b ottles, st u d y dr u g start m o nt h, a n d st u d y dr u g e n d m o nt h will be use d t o 
i m p ute t he u n k n o w n last d ose m o nt h. If t he s u bject die d a n d t he deat h date has m o nt h a n d year 
a vaila ble a n d bef ore t he i m p ute d last d ose m o nt h, t h e n t he m o nt h of deat h will be use d i nstea d. 
Wit h t he m o nt h i m p ute d, t he af ore me nti o ne d met h o d will be use d t o i m p ute t he last d ose date.
If s u bjects are c o nti n ui n g o n st u d y dr u g at t he ti me of a n i nteri m a nalys is, t he earliest of t he date 
of deat h or data c ut off date f or t he i nteri m a nal y sis will be use d t o i m p ute t he last d osi n g date f or 
t he calc ulati o n of d urati o n of e x p os ure t o st u d y dr u g.
T he t otal d urati o n of e x p os ure t o d o u ble -bli n d st u d y  dr u g will be s u m marize d usi n g descri pti ve 
statistics a n d usi n g t he n u m ber (ie, c u m ulati ve c o u nts) a n d perce nta ge of s u bjects e x p ose d 
t hr o u g h t he f oll o wi n g ti me peri o ds: Da y 1, Wee k 2 ( Da y  1 4), Wee k 4 ( Da y  2 8), Wee k 8 
( Da y 5 6), a n d ≥ Wee k 1 3 ( Da y  9 1).
T he t otal d urati o n of e x p os ure t o o pe n -la bel fil g oti ni b or wee ks i n t he e xte nsi o n p hase f or t h ose 
s witc hi n g t o S O C will be s u m marize d usi n g descri pti ve statistics a n d usi n g t he n u m ber 
(ie, c u m ulati ve c o u nts) a n d perce nta ge of s u bjects e x p ose d t hr o u g h t he f oll o wi n g ti me peri o ds: 
Baseli ne ( Da y 1), Wee k 1 3 ( Da y 9 1), Wee k 2 6 ( Da y  1 8 2), Wee k 3 9 ( D a y  2 7 3) , a n d u p t o 
Wee k
1 4 3 ( Da y 1 00 1 ) at 1 3- wee k i nter vals (as a p pr o priate). T otal d urati o n of e x p os ure t o a n y  
fil g oti ni b will f oll o w t he sa me cate g ories as e xte nsi o n p hase dis pla ys wit h t he a d diti o n of 
Wee k
1 5 6 ( Da y  1 0 9 2).
S u m maries w ill be pr o vi de d b y d o u ble -bli n d treat me nt gr o u p f or d o u ble -bli n d dr u g, o pe n -la bel 
fil g oti ni b a n d “a ny fil g oti ni b” a n d b y d o u ble-bli n d treat me nt gr o u p a n d o verall f or wee ks i n t he 
e xte nsi o n p hase f or t he Safety A nal ys is Set. N o f or mal statistical testi n g is pla n ne d.
4. 2. 2.
A d here nce t o St u d y Dr u g
T he o n -treat me nt ad here nce will be calc ulate d f or d o u ble-bli n d fil g oti ni b 2 0 0 m g/ P T M (ta blets), 
t hr o u g h t he d o u ble-bli n d p hase of t he st u d y f or t he Se me n A nalys is Set.
T he t otal n u m ber of d o u ble -bli n d ta blets a d mi nistere d will be s u m marize d usi n g descri pti ve 
statistics. 
T he pres u me d t otal n u m ber of ta blets a d mi nistere d t o a s u bject d uri n g t he d o u ble -bli n d p hase 
will be deter mi ne d b y t he data c ollecte d o n t he dr u g acc o u nta bilit y eC R F usi n g t he f oll o wi n g 
f or m ula:
T otal N u m ber of Ta blets A d mi nistere d 
=  N o. of Ta blets Dis pe nse d  − N o. of Ta blets Ret ur ne d All o pe n -la bel fil g oti ni b b ottles dis pe nse d will be e xcl u de d fr o m t he calc ulati o ns.


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If a b ottle of d o u ble -bli n d st u d y  dr u g is dis pe nse d a n d t he b ottle is ret ur ne d e m pt y, t he n t he 
n u m ber of ta blets ret ur ne d will be e ntere d as zer o. If a b ottle of d o u ble -bli n d st u d y  dr u g is 
dis pe nse d b ut n ot ret ur ne d ( missi n g), t he n u m ber of ta blets a d mi nistere d will be c o u nte d as 
zer o b y  ass u mi n g t hat a s u bject di d n ot ta ke st u d y dr u g as prescri be d d uri n g t he peri o d f or w hic h 
t he b ottle was dis pe nse d.
4. 2. 2. 1.
O n -Treat me nt A d here nce
T he le vel of o n -treat me nt a d here nce t o st u d y dr u g d uri n g t he d o u ble-bli n d p hase of t he st u d y 
will be deter mi ne d b y t he t otal a m o u nt of s t u d y dr u g a d mi nistere d relati ve t o t he t otal a m o u nt of 
st u d y dr u g e x pecte d t o be a d mi nistere d d uri n g a s u bject’s act ual o n-treat me nt p hase base d o n t he 
st u d y dr u g re gi me n.
T he le vel of o n -treat me nt a d here nce d uri n g t he d o u ble -bli n d p hase of t he st u d y  will be e x presse d 
as a perce nta ge usi n g t he f oll o wi n g f or m ula:
T otal A m o u nt of St u d y  Dr u g A d mi nistere d
O n- Treat m e nt A d here nce ( %) = 
 x 1 0 0
St u d y Dr u g E x pecte d t o  be A d mi nistere d on Treat me nt






N ote: If calc ulate d a d here nce is greater t ha n 1 0 0 %, t he res ult will be set t o 1 0 0 %.
St u d y  dr u g e x pecte d t o be a d mi nistere d f or fil g oti ni b 2 0 0 m g/ P T M (ta blets) = 1 × t otal d urati o n 
of e x p os ure t o d o u ble -bli n d st u d y dr u g ( da ys).
Descri pti ve statistics f or t he le vel of o n -treat me nt a d here nce d uri n g t he d o u ble -bli n d p hase of t he 
st u d y wit h t he n u m ber a n d perce nta ge of s u bjects bel o n gi n g t o a d here nce cate g ories (e g , < 8 0 %, 
≥ 8 0 % t o < 9 0 %, ≥ 9 0 %) will be pr o vi de d b y  treat me nt gr o u p f or t he D o u ble -Bli n d Se me n 
A nal y sis Set. 
N o f or mal statistical testi n g is pla n ne d.
A b y -s u bject listi n g of st u d y dr u g a d mi nistrati o n a n d dr u g acc o u nta bilit y will be pr o vi de d 
se paratel y b y s u bject I D n u m ber (i n asce n di n g or der) a n d visit (i n c hr o n ol o gical or der).
A listi n g of s u bjects w h o ha d i nterr u pti o ns i n st u d y dr u g d osi n g as rec or de d o n t he st u d y  dr u g 
a d mi nistrati o n e C R F will be pr o d uce d .
4. 3. 
Pr ot oc ol De vi ati o ns 
A b y -s u bject listi n g will be pr o vi de d f or t h ose s u bjects w h o di d n ot meet at least 1 eli gi bilit y  
(i ncl usi o n or e xcl usi o n) criteri o n b ut were e nr olle d i nt o t he st u d y f or t he All Ra n d o mize d 
A nal y sis Set. T he listi n g will prese nt t he eli gi bilit y criteri o n ( or criteria if m ore t ha n 1 de viati o n) 
t hat t he s u bject di d n ot meet a n d relate d c o m me nts, if c ollecte d.


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Pr ot oc ol de viati o ns occ urri n g after s u bjects e ntere d t he st u d y  are d oc u me nte d d uri n g r o uti ne 
m o nit ori n g. T he n u m ber a n d perce nta ge of s u bjects wit h ≥ 1 i m p orta nt pr ot oc ol de viati o n (I P D) 
will be s u m marize d b y  treat me nt gr o u p. I n a d diti o n, i m p orta nt pr ot oc ol de viati o ns will be 
s u m marize d b y treat me nt gr o u p a n d I P D cate g or y f or t he All Ra n d o mize d A nal ysis Set. 
A b y -s u bject listi n g will be pr o vi de d f or t h ose s u bjects wit h a n IP D. I n ad diti o n, 2 se parate 
b y -s u bject listi n gs will be pr o vi de d f or s u bjects wit h 1) a n y i m p orta nt pr ot oc ol de viati o ns relate d 
t o C O VID - 1 9, a n d 2) a n y n o n-i m p orta nt pr ot oc ol de viati o ns relate d t o C O VI D- 1 9.  


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5.
B A S E LI N E C H A R A C T E RI S TI C S
5. 1.
De m o gr a p hics
S u bject de m o gra p h ic varia bles (ie, a ge, se x, race, a n d et h nicit y) will be s u m marize d f or t he 
d o u ble -bli n d p hase of t he st u d y  b y  d o u ble -bli n d treat me nt gr o u p a n d o verall usi n g descri pti ve 
statistics f or a ge, a n d usi n g n u m ber a n d perce nta ge of s u bjects f or se x, race a n d et h nicit y f or t he
S afet y/IT T Se me n A nal ysis Set s a n d S e me n A nal ysis S et. Se parate dis pla ys will prese nt data b y  
treat me nt se q ue nce a n d o verall f or t he E xte nsi o n P hase S afet y A n al y sis S et a n d t he at/after 
Wee k 3 9 Se me n A nal ys is Set. Dis pla y s f or t he Wee k 2 6 Se me n A nal y sis Set will be b y 
treat me nt se q ue nce a n d R he u matic Disease Res p o n der/ N o n - Res p o n der stat us at Wee k 1 3.
A ge is calc ulate d i n y ears at t he date of first d o u ble -bli n d st u d y dr u g a d mi nistrati o n. If a s u bject 
d oes n ot recei ve st u d y  dr u g after ra n d o mizati o n, t he s u bject’s a ge will be calc ulate d fr o m t he 
D a y  1/ baseli ne assess me nt. 
A b y -s u bject de m o gra p hic listi n g, i ncl u di n g t he i nf or me d c o nse nt date , will be pr o vi de d by 
s u bject I D n u m ber i n asce n di n g or der.
5. 2.
Ot her B aseli ne C h ar acteristics
Ot her baseli ne c haracteristics i ncl u de :

B o d y wei g ht (i n k g)

Hei g ht (i n c m)

B o d y mass i n de x ( B MI; i n k g/ m 2)

T y pe of r he u mat ol o gic c o n diti o n ( R A, Ps A, A S, nr A x S p A)

D urati o n of i nfla m mat or y c o n diti o n (i n ye ars)

P h y sicia n’s Gl o bal Assess me nt of Disease Acti vity ( P h G A D A) f or all s u bjects

Bat h A n k yl osi n g S p o n d ylitis Disease Acti vit y  In de x ( B A S D AI) f or s u bjects wit h A S or 
nr A x S p A , c o nti n u o us a n d f or cate g ories (˂ 4 , ≥ 4)

Cli nical Disease Acti vit y I n de x ( C D AI) f or s u bject wit h R A, c o nti n u o us a n d f or cate g ories 
(remissi o n, l o w, m o derate, a n d hi g h) as descri be d bel o w

Disease Acti vit y  i n Ps oriatic Art hritis ( D A P S A) f or s u bjects wit h Ps A c o nti n u o us a n d f or 
cate g ories (re missi o n, l o w, m o derate, a n d hi g h) as descri be d bel o w

Hi g h se nsiti vit y C- Reacti ve Pr otei n ( hs C R P, m g/ L)


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
S m o ki n g stat us (f or mer, c urre nt, ne ver) 

Alc o h ol Use ─ fre q ue nc y of dri n ki n g i n past 1 2 m o nt hs ( n o alc o h ol i n m y life, n o alc o h ol i n 
past 1 2 m o nt hs, 1 or 2 ti mes i n past y ear, 3-1 1 ti mes i n t he past y ear, 1 -3 ti mes a m o nt h, 
˂ 4 ti mes a wee k, ≥ 4 ti me s a wee k)

Alc o h olic dri n ks per da y  c o ns u me d o n a dri n ki n g da y ─ past 1 2 m o nt hs ( 1 dri n k, 2 dri n ks, 
3- 4 dri n ks, ≥ 5 dri n ks)

N u m ber of c hil dre n fat here d ( 0, 1 - 2, 3- 4, ≥ 5)

Pri or use of cs D M A R Ds (a n y i ncl u di n g M T X)

C o nc urre nt M T X use stat us ( y es, n o) wit h s u bcate g ories f or M T X d ose (˂ 2 0 m g, ≥ 2 0 m g)

S per m c o nce ntrati o n meas ure d ( 1 5 t o 2 5 M / m L, > 2 5 t o 5 0 M / m L), > 5 0
M / m L)

S per m c o nce ntrati o n ( M / m L)

S per m t otal m otilit y  ( %)

T otal s per m c o u nt ( M/ejac ulate)

Ejac ulate v ol u me ( m L)

S per m m or p h ol o g y  ( % n or mal) ─W H O 1 9 9 2 criteria

L utei nizi n g H or m o ne ( mI U/ m L)

F ollicle -Sti m ulati n g H or m o ne ( mI U/ m L)

I n hi bi n B ( p g/ m L)

T otal Test oster o ne ( n g/ d L)
Cate g ories f or C D AI (f or R A) a n d D A P S A (f or Ps A) t hat will be s u m marize d i ncl u de:
C ate g ories f or Dise ase 
Acti vit y
Cli nic al Dis e ase Acti vit y I n de x ( C D AI f or 
R A)
Dise ase Acti vit y f or Ps ori atic 
Art hritis ( D A P S A f or Ps A)
Re missi o n
0 t o 2. 8
0 t o 4
L o w 
2. 9 t o 1 0
5 t o 1 4
M o derate
1 0. 1 t o 2 2. 0
1 5 t o 2 8
Hi g h
2 2. 1 t o 7 6. 0
> 2 8


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D urati o n of r he u mat ol o gic c o n diti o n is calc ulate d as:
([first d ose date] – [date of i nitial dia g n osis ] + 1 da y ) / 3 6 5. 2 5 
If t he date of i nitial dia g n osis is i nc o m plete, t he n t he f oll o wi n g r ules will be a p plie d:

missi n g da y : use t he first of t he m o nt h

missi n g m o nt h: use Ja n uar y
B aseli ne c haracteristics will be s u m marize d f or t he d o u ble-bli n d p hase of t he st u d y  b y 
d o u ble -bli n d treat me nt gr o u p a n d o verall usi n g descri pti ve statistics f or c o nti n u o us varia bles a n d 
usi n g n u m ber a n d perce nta ge of s u bjects f or cate g orical varia bles f or the S afet y /IT T Se me n 
A nal y sis Sets a n d t he S e me n A nal ys is S et. Se parate dis pla y s will prese nt data b y treat me nt 
se q ue nce i n e xte nsi o n p hase a n d o verall f or t he E xte nsi o n P hase Safet y A nal y sis Set a n d t he 
at/after Wee k 3 9 Se me n A nal y sis Set. Dis pla ys f or t he Wee k 2 6 Se me n A nal y sis Set will be b y 
treat me nt se q ue nce a n d R he u matic Disease Res p o n der/ N o n - Res p o n der stat us at Wee k 1 3.
N o f or mal statistical testi n g is pla n ne d.
A b y -s u bject listi n g of ot her baseli ne c haracteristics will be pr o vi de d b y s u bject I D n u m be r i n 
asce n di n g or der.
5. 3.
Me dic al Hist or y
Disease -s pecific a n d ge neral me dical hist or y data will be c ollecte d at scree ni n g. Me dical hist or y  
will n ot be c o de d.
A b y -s u bject listi n g of me dical hist or y  will be pr o vi de d b y s u bject I D n u m ber i n asce n di n g or der 
a n d a b n or malities i n c hr o n ol o gical or der.


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6.
S E M E N A N D H O R M O N E A N A L Y S E S
6. 1.  
Ge ner al C o nsi der ati o ns
T he defi niti o ns f or t he pri mar y  a n d sec o n dar y e n d p oi nts are liste d i n Ta ble 6- 1 .
T a ble 6- 1.
Defi niti o ns f or t he Pri m ar y a n d Sec o n d ar y E n d p oi nts
T y pe
E ve nt E n d p oi nt
Pri mar y
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
Sec o n dar y
Pr o p orti o n of s u bjects w it 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
Sec o n dar y
C ha n ge fr o m baseli ne i n s per m t otal m otilit y at Wee ks 1 3 a n d 2 6
Sec o n dar y
C ha n ge fr o m baseli ne i n t otal s per m c o u nt at Wee ks 1 3 a n d 2 6
Sec o n dar y
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
Sec o n dar y
C ha n ge fr o m baseli ne i n ejac ulate v ol u me at Wee ks 1 3 a n d 2 6
Sec o n dar y
C ha n ge fr o m baseli ne i n perce nt n or mal s per m m or p h ol o g y at Wee ks 1 3 a n d 2 6
N ote: Val ue at a visit is t he mea n of 2 e val ua ble se me n sa m ple c ollecti o ns at a gi ve n c ollecti o n ti me p oi nt f or pri mar y a nal ysis.
W he n calc ulati n g t he perce nt a ge c ha n ge fr o m baseli ne i n s per m c o nce ntrati o n, n o r o u n di n g will 
be perf or me d i n t he a nal ysis. F or t he p ur p oses of ta bles a n d listi n gs, t he perce nta ge will be 
r o u n de d t o 1 deci mal place.
Eli gi ble s u bjects were re q uire d at scree ni n g t o ha ve t he mea n of 2 e val ua ble se me n c ollecti o ns 
f or eac h of t he 5 s per m/se me n para meters greater t ha n or e q ual t o t he val ue ass ociate d wit h t he 
5 t h perce ntile of t he W H O refere nce set per I ncl usi o n Criteria # 7. S e me n para meters ot her t ha n 
s per m m or p h ol o g y use W H O 2 0 1 0 criteria { W orl d Healt h Or ga nizati o n ( W H O) 2 0 1 0 }; w hile 
s per m m or p h ol o g y used W H O 1 9 9 2 criteria { W orl d Healt h Or ga nizati o n ( W H O) 1 9 9 2 }. Se me n 
para meter eli gi bilit y criteria are pr o vi de d i n Ta ble 6- 2 .
T a ble 6 - 2.
Se me n P ar a meter Eli gi bilit y Criteri a
P a r a m eter
N or m al R a n ge
S per m  c o nce ntrati o n
≥ 1 5 m illi o n per milliliter ( m L)
S p er m  t otal m o tilit y
≥ 4 0 %
T otal s per m per ejac ulate
≥ 3 9 milli o n
Ejac ulate v ol u me
≥ 1. 5 m L
S p er m  mor p h ol o g y
≥ 3 0 % n or mal * 
Liste d se me n para meters use 2 0 1 0 W H O Refere nce val ues { C o o per 2 0 1 0 , W orl d Healt h Or ga nizati o n ( W H O) 2 0 1 0 } f or h u ma n 
se me n c haracteristics e xce pt *( m or p h ol o g y) w hic h utilizes t he 1 9 9 2 W H O s per m m or p h ol o g y criteri o n { W orl d Healt h 
Or ga nizati o n ( W H O) 1 9 9 2 }.


Fil g oti ni b
G L P G 0 6 3 4 -C L -2 2 7
Statistical A nal ysis Pla n
Versi o n 1. 0
C O N FI D E N TI A L
Pa ge 3 8
1 2 Ja n uar y 2 0 2 1
6. 2.
Pri m ar y A n al ysis o f Pri m ar y a n d Sec o n d ar y E n d p oi nt s
T he pri mar y  a nal ys is will be a n o bser ve d cases a nal ysis at Wee k 1 3 w hile s u bjects are o n 
d o u ble -bli n d st u d y dr u g as descri be d i n F D A’s g ui da nce f or i n d ustr y  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 } . 
T he mai n esti mat ors of a W hile o n Treat me nt Strate g y  esti ma n d will be utilize d f or t he pri mar y  
a nal ys is of pri mar y a n d sec o n dar y e n d p oi nts at Wee k 1 3:
BI N A R Y E N D P OI N T
W HI L E O N -T R E A T M E N T S T R A T E G Y
P o p ulati o n
Se me n A nal ysis Set (s u bjects wit h 2 e val ua ble se me n sa m ples c ollecte d at baseli ne a n d at 
t he Wee k 1 3 a nal ysis visit ) as defi ne d i n Secti o n 3. 1. 2 of t his S A P.
Patie nt Le vel O utc o me t o be 
Meas ure d
Bi nar y o utc o me f or a s u bject meeti n g a ≥ 5 0 % decrease fr o m base li ne i n s per m 
c o nce ntrati o n at Wee k 1 3. O utc o me is deter mi ne d base d o n t he mea n of 2 e val ua ble 
se me n sa m ples at a visit.
Meas ure of i nter ve nti o n effect 
a n d ha n dli n g of i nterc urre nt 
e ve nts
Meas ure of treat me nt effect ass u mi n g
t hat t he treat me nt effect pri or t o t he i nterc urre nt 
e ve nt of treat me nt earl y disc o nti n uati o n is of i nterest . Data i ncl u de d t o last d ose date 
d o u ble -bli n d dr u g + 7 da ys will be c o nsi dere d “ w hile o n -treat me nt” f or t h ose w h o 
per ma ne ntl y disc o nti n ue d o u ble -bli n d st u d y dr u g a n d d o n ot c o ntin ue t o E xte nsi o n P hase .
P o p ulati o n le vel s u m mar y 
meas ure
Differe nce i n a bi nar y o utc o me, c o m pari n g t h ose assi g ne d t o fil g oti ni b vers us t h ose 
assi g ne d t o place b o.
Esti mat ors
Mai n esti mat or: A stratifie d Ma ntel -Hae nszel test (stratificati o n fact or: s per m 
c o nce ntrati o n [ 1 5 – 5 0 M/ m L,
> 5 0 M/ m L] , c o nc urre nt M T X use [ yes, n o]) will be use d 
t o esti mate t he differe nce i n pr o p orti o ns (fil g oti ni b – p lace b o) a n d c orres p o n di n g 9 5 % CI
{ K oc h 1 9 8 9 } . Calc ulati o n f or differe nce i n pr o p orti o ns a n d 9 5 % CI pr o vi de d i n 
A p pe n di x 2 . 
N ote: W he n perf or mi n g t he stratifie d Ma ntel -Hae nszel test, t he 1 5 - 2 5  a n d 
> 2 5 – 5 0 M/ m L strata f or s per m c o nce ntrati o n will be c o m bi ne d (e g,
1 5 – 5 0 M/ m L) d ue 
t o t he s mall n u m ber of s u bjects i n t he l o west strat u m; disease t y pe will n ot be i ncl u de d as 
a stratificati o n fact or d ue t o t he s mall n u m ber of s u bjects wit h R A .
C O N TI N U O U S E N D P OI N T S
W HI L E O N T R E A T M E N T S T R A T E G Y
P o p ulati o n
Se me n A nal ysis Set (s u bjects wit h 2 e val ua ble se me n sa m ples c ollecte d at baseli ne a n d at 
t he Wee k 1 3 a nal ysis visit ) as defi ne d i n Secti o n 3. 1. 2 of t his S A P.
Patie nt Le vel O utc o me t o be 
Meas ure d
C ha n ge a n d Perce nta ge C ha n ge fr o m Baseli ne (c o nti n u o us o utc o me) at Wee k 1 3. 
O utc o me is deter mi ne d base d o n t he mea n of 2 e val ua ble se me n sa m ples at a visit, a n d 
a nal ysis visit wi n d o ws are assi g ne d base d o n fir st of 2 e val ua ble se me n sa m ples.
Meas ure of i nter ve nti o n effect 
a n d ha n dli n g of i nterc urre nt 
e ve nts
Meas ure of treat me nt effect ass u mi n g t hat t he treat me nt effect pri or t o t he i nterc urre nt 
e ve nt of treat me nt earl y disc o nti n uati o n is of i nterest . Data i ncl u de d t o last d ose date 
d o u ble -bli n d dr u g + 7 da ys will be c o nsi dere d “ w hile o n -treat me nt” f or t h ose w h o 
per ma ne ntl y disc o nti n ue d o u ble - bli n d st u d y dr u g a n d d o n ot c o nti n ue t o E xte nsi o n P hase.
P o p ulati o n le vel s u m mar y 
meas ure
Me dia n Differe nce bet wee n treat me nt gr o u ps, c o m pari n g t h ose assi g ne d t o fil g oti ni b 
vers us t h ose assi g ne d t o place b o i n t he c ha n ge a n d perce nta ge c ha n ge fr o m baseli ne at 
Wee k 1 3 f or a c o nti n u o us o utc o me.
Esti mat ors
Mai n esti mat or: Q ua ntile re gressi o n m o dels will be use d t o esti mate t he me dia n differe nce 
(fil g oti ni b – place b o) i n c ha n ge a n d perce nta ge c ha n ge fr o m baseli ne at Wee k 1 3, 9 5 % CI 
f or t he s per m/se me n para meter of i nterest. T he CI = R A N K o pti o n will be s pecifie d i n 
P R O C Q U A N T R E G i n S A S.
F or s per m c o nce ntrati o n ( M/ m L), t he m o d el will i ncl u de: baseli ne s per m c o nce ntrati o n 
(c o nti n u o us), M T X use ( yes, n o).
F or s per m t otal m otilit y ( %), perce nt n or mal m or p h ol o g y, t otal s per m c o u nt ( M/ejac ulate) 
a n d ejac ulati o n v ol u me ( m L), t he m o del will i ncl u de:
baseli ne val ue f or para meter (c o nt i n u o us), M T X use ( yes, n o) a n d s per m c o nce ntrati o n 
( 1 5 - 5 0 M/ m L, > 5 0 M/ m L) .


Fil g oti ni b
G L P G 0 6 3 4 -C L -2 2 7
Statistical A nal ysis Pla n
Versi o n 1. 0
C O N FI D E N TI A L
Pa ge 3 9
1 2 Ja n uar y 2 0 2 1
Ei g ht -p oi nt s u m mar y  statistics ( 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 
d o u ble - bli n d treat me nt gr o u p will be prese nte d f or baseli ne val ue, a bs ol ute val ue at t he visit, a n d 
c ha n ge a n d perce nta ge c ha n ge fr o m baseli ne f or eac h s e me n  para meter at Wee k 1 3. A 9 5 % 
distri b uti o n -free CI o n t he me dia n c ha n ge a n d perce nta ge c ha n ge fr o m baseli ne f or eac h se me n 
para meter will be c o nstr ucte d b y treat me nt gr o u p at Wee k 1 3 usi n g t he CIP C T L D F o pti o n i n 
P R O C U NI V A RI A T E i n S A S. 
Base d o n F D A’s g ui da nce f or i n d ustr y  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 } a n d c o m m u nicati o n wit h t he F D A, a c u m ulati ve 
distri b uti o n pl ot f or perce nta ge 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 will be 
c o nstr ucte d b y d o u ble -bli n d treat me nt gr o u p. C u m ulati ve distri b uti o n pl ots f or perce nta ge 
c ha n ge fr o m baseli ne at d o u ble- bli n d Wee k 1 3 f or t otal s per m m otilit y  ( %) a n d s per m 
m or p h ol o g y  ( % n or mal) will als o be prese nte d b y d o u ble -bli n d treat me nt gr o u p.
A waterfall pl ot will be c o nst r ucte d t o prese nt t he distri b uti o n of perce nta ge 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. Eac h li ne o n t he x-a xis of t he waterfall pl ot will 
re prese nt t he perce nta ge c ha n ge fr o m baseli ne i n s per m c o nce ntrati o n f or a n i n di vi d ual s u bject 
wit h t heir treat me nt assi g n me nt dis pla ye d base d o n t he c ol or/s ym b ol dis pla y e d f or t he li ne.
6. 3.
S u b gr o u p A n al ysis f or S per m C o nce ntr ati o n P ar a meter at Wee k 1 3
T he f oll o wi n g s u b gr o u p a nal ys es will be perf or me d b y  treat me nt gr o u p f or t he e n d p oi nts 
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, 
a n d c ha n ge a n d perce nta ge 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 :

T y pe of R he u matic Disease dis or der ( R A , S p o n d y l oart hritis [ A S, Ps A, nr A x S p A] )

S per m c o nce ntra ti o n ( mea n of 2 e val ua ble sa m ples) meas ure d at Scree ni n g visit: 
( 1 5 - 5 0
M/ m L, > 5 0 M/ m L)

C o nc urre nt M T X use ( y es, n o)
6. 4. 
S u p p orti ve A n al ysis f or Pri m ar y a n d Sec o n d ar y E n d p oi nts at Wee k 1 3
I n a d diti o n t o t he pri mar y a n al ysis, t he mai n esti mat ors of a h yp ot hetical strate g y esti ma n d will 
pr o vi de s u p p ort t o t he pri mar y  a nalys is of pri mar y a n d sec o n dar y e n d p oi nts at t he Wee k 1 3 
ti me p oi nt. T he esti ma n ds f or bi nar y a n d c o nti n u o us e n d p oi nts are descri be d bel o w.


Fil g oti ni b
G L P G 0 6 3 4 -C L -2 2 7
Statistical A nal ysis Pla n
Versi o n 1. 0
C O N FI D E N TI A L
Pa ge 4 0
1 2 Ja n uar y 2 0 2 1
Esti m a n d f or Bi n ar y E n d p oi nt
BI N A R Y E N D P OI N T S
H Y P O T H E TI C A L S T R A T E G Y
P o p ulati o n
I T T Se me n A nal ysis Set (s u bjects wit h 2 e val ua ble se me n sa m ples c ollecte d at baseli ne) 
as defi ne d i n Secti o n 3. 1. 2 of t his S A P .
Patie nt Le vel O utc o me t o be 
Meas ure d
Bi nar y o utc o me f or a s u bject meeti n g 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. O utc o me is deter mi ne d base d o n t he me a n of 2 e val ua ble 
se me n sa m ples at a visit. A s u bject wit h o nl y 1 of t he 2 e val ua ble se me n sa m ples at Wee k 
1 3 will be i ncl u de d wit h t heir 1 sa m ple. If a meas ure me nt f or a s pecific se me n para meter 
[ S u bject I D 1 5 8 5 8- 6 0 6 4 0, m otilit y] is dee me d i neli gi ble at
Wee k 1 3, t he 1 e val ua ble 
res ult will be use d.
Meas ure of i nter ve nti o n effect 
a n d ha n dli n g of i nterc urre nt 
e ve nts
Meas ure of treat me nt effect ass u mi n g t hat t he i nterc urre nt e ve nt of earl y ter mi nati o n pri or 
t o Wee k 1 3 d oes n ot occ ur. S u bjects w h o ha d missin g data at Wee k 1 3 d ue t o earl y 
ter mi nati o n will be ass u me d t o be missi n g at ra n d o m ( M A R) a n d data will be i m p ute d 
usi n g P R O C MI i n S A S a n d a l o gistic re gressi o n m o del wit h treat me nt gr o u p, baseli ne 
s per m c o nce ntrati o n cate g or y ( 1 5 - 5 0 M/ m L , > 5 0 M/ m L ), an d c o nc urre nt M T X use 
( yes, n o) as i n de pe n de nt varia bles i n t he m o del.
P o p ulati o n le vel s u m mar y 
meas ure
Differe nce i n a bi nar y o utc o me, c o m pari n g t h ose assi g ne d t o fil g oti ni b vers us t h ose 
assi g ne d t o place b o.
Esti mat ors
Mai n esti mat or: I m p ute d datasets w ill be a nal yze d usi n g t he stratifie d Ma ntel-Hae nszel 
met h o d (stratificati o n fact ors: s per m c o nce ntrati o n [ 1 5 - 5 0 M/ m L,
> 5 0 M/ m L], a n d 
c o nc urre nt M T X use [ yes, n o]). Res ults will be c o m bi ne d usi n g R u bi n’s r ule 
{ R u bi n 1 9 8 7 } t o esti mate t he differe nce i n pr o p orti o ns (fil g oti ni b – p lace b o) a n d 
c orres p o n di n g 9 5 % CI.
Esti m a n d f or C o nti n u o us E n d p oi nts
C O N TI N U O U S E N D P OI N T S
H Y P O T H E TI C A L S T R A T E G Y
P o p ulati o n
I T T Se me n A nal ysis Set (s u bjects wit h 2 e val ua ble se me n sa m ples c ollecte d at baseli ne) 
as defi ne d i n Secti o n 3. 1. 2 of t his S A P .
Patie nt Le vel O utc o me t o be 
Meas ure d
C ha n ge a n d Perce nta ge C ha n ge fr o m Baseli ne (c o nti n u o us o utc o me) at Wee k 1 3. 
O utc o me is deter mi ne d base d o n t he mea n of 2 e val ua ble se me n sa m p les at a visit. A 
s u bject wit h o nl y 1 of t he 2 e val ua ble se me n sa m ples at Wee k 1 3 will be i ncl u de d wit h 
t heir 1 sa m ple. If a meas ure me nt f or a s pecific se me n para meter 
[ S u bject I D 1 5 8 5 8- 6 0 6 4 0, m otilit y] is dee me d i neli gi ble at Wee k 1 3, t he 1 e val ua ble 
res ult will be use d.
Meas ure of i nter ve nti o n effect 
a n d ha n dli n g of i nterc urre nt 
e ve nts
Meas ure of treat me nt effect ass u mi n g t hat i nterc urre nt e ve nt of earl y ter mi nati o n pri or t o 
Wee k 1 3 d oes n ot occ ur. S u bjects w h o ha d missi n g data at Wee k 1 3 d ue t o earl y 
ter mi nati o n will be ass u me d t o be M A R a n d data will be i m p ute d b y c o n diti o nal q ua ntile 
esti mati o n usi n g t he q ua ntile re gressi o n m o del s pecifie d f or t he pri mar y a nal ysis usi n g 
t he met h o ds of { B ottai 2 0 1 3 }.
P o p ulati o n le vel s u m mar y 
meas ure
Me dia n Differe nce bet wee n treat me nt gr o u ps, c o m pari n g t h ose assi g ne d t o fil g oti ni b
vers us t h ose assi g ne d t o place b o i n t he c ha n ge a n d perce nta ge c ha n ge fr o m baseli ne at 
Wee k 1 3 f or a c o nti n u o us o utc o me.
Esti mat ors
Mai n esti mat or: I m p ute d datasets will be a nal yze d usi n g q ua ntile re gressi o n m o dels use d 
f or pri mar y a nal ysis t o o btai n esti mates a n d sta n dar d err ors (sta n dar d err ors o btai ne d 
t hr o u g h b o otstra p met h o ds). Res ults of t he esti mates a n d sta n dar d err ors will be 
c o m bi ne d usi n g R u bi n’s r ule t o esti mate t he me dia n differe nce ( fil g oti ni b – p lace b o) i n 
c ha n ge or perce nta ge c ha n ge fr o m baseli ne, 9 5 % CI f or t he s per m/se me n para meter of 
i nterest.


Fil g oti ni b
G L P G 0 6 3 4 -C L -2 2 7
Statistical A nal ysis Pla n
Versi o n 1. 0
C O N FI D E N TI A L
Pa ge 4 1
1 2 Ja n uar y 2 0 2 1
6. 5.
Ot her Dis pl a ys of S per m/ Se me n D at a
6. 5. 1.  
Wee k 2 6 b y Tre at me nt Se q ue nce a n d Res p o n der/ N o n - Res p o n der at Wee k 1 3 
Dis pl a ys
Dis pla y s will be prese nte d at t he Wee k 2 6 visit f or t he f oll o wi n g 4 gr o u ps:

filg oti ni b res p o n der at Wee k 1 3 s witc he d t o o pe n -la bel fil g oti ni b

fil g oti ni b no n -res p o n der at Wee k 1 3 s witc he d t o sta n dar d of care

p lace b o res p o n der at Wee k 1 3 s witc he d t o sta n dar d of care

p lace b o n o n-r es p o n der at Wee k 1 3 s witc he d t o sta n dar d of care
T he n u m ber a n d 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 t he Wee k 2 6 visit will be prese nte d. A n e xact 9 5 % CI f or 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 wit hi n
treat me nt se q ue nce a n d res p o n der/ n o n -res p o n der stat us gr o u p will be prese nte d base d o n t he 
Cl o p per -Pears o n met h o d. 
F or all sec o n dar y  c o nti n u o us e n d p oi nts, 8-p oi nt s u m mar y  statistics ( 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 se q ue nce a n d res p o n der/ n o n -res p o n der stat us at 
Wee k 1 3
will be pr o vi de d f or t he val ue at t he visit, c ha n ge fr o m baseli ne, a n d perce nta ge c ha n ge 
fr o m baseli ne i n s per m/se me n para meters at Wee k 2 6. A 9 5 % distri b uti o n-free CI o n t he me dia n 
c ha n ge a n d perce nta ge c ha n ge fr o m baseli ne at Wee k 2 6 i n all s per m/se me n para meters will be 
c o nstr ucte d b y treat me nt se q ue nce a n d res p o n der/ n o n -res p o n der stat us at Wee k 1 3 usi n g t he 
CI P C T L D F o pti o n i n P R O C U NI V A RI A T E i n S A S.
A c u m ulati ve distri b uti o n pl ot f or perce nt a ge c ha n ge fr o m baseli ne i n s per m c o nce ntrati o n at 
Wee k 2 6 will be c o nstr ucte d b y  treat me nt se q ue nce a n d res p o n der/ n o n -res p o n der stat us at 
Wee k
1 3 f or t h ose w h o re mai n o n st u d y dr u g at t he Wee k 2 6 visit. 
6. 5. 2.
Tre at me nt Se q ue nce Dis pl a ys at/ after Wee k 3 9
Dis pla y s will be prese nte d b y a nalys is visit at Wee k 3 9 a n d t hereafter i n t he E xte nsi o n P hase f or 
t he f oll o wi n g 3 treat me nt se q ue nces:

fil g oti ni b t o o pe n -la bel fil g oti ni b

fil g oti ni b t o sta n dar d of c are

p lace b o t o sta n dar d of c are
T he n u m ber a n d 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 will be prese nte d b y  a nalys is visit. 


Fil g oti ni b
G L P G 0 6 3 4 -C L -2 2 7
Statistical A nal ysis Pla n
Versi o n 1. 0
C O N FI D E N TI A L
Pa ge 4 2
1 2 Ja n uar y 2 0 2 1
F or all sec o n dar y  c o nti n u o us e n d p oi nts, 8-p oi nt s u m mar y  statistics ( 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 se q ue nce will be pr o vi de d f or t he val ue at t he visit, 
c ha n ge fr o m baseli ne, a n d perce nta ge c ha n ge fr o m baseli ne i n s per m/se me n para meters .
6. 5. 3.
Pre -S pecifie d S per m Decre ase T hres h ol d Criteri a a n d C o nfir me d Se me n 
A b n or m alities
S u bjects w h o met a pre -specifie d s per m decrease t hres h ol d (a ≥ 5 0 % decrease fr o m baseli 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) were t o st o p st u d y dr u g a n d be gi n a 
sta n dar d of care re gi me n selecte d by t he i n vesti gat or i n acc or da nce wit h t he pr ot oc ol a n d be 
f oll o we d off st u dy dr u g t o e val uate f or re versi bilit y criteria.
A “c o nfir me d se me n a b n or malit y ” as defi ne d b y J ar vi a n d c ollea g ues { Jar vi 2 0 0 8} reflects t he 
prese nce of a b n or mal s per m para meters p ote ntiall y ass ociate d wit h decrease d male fertilit y ; t he 
criteri o n is met w he n o ne or m ore of t he f oll o wi n g are o bser ve d: a s per m c o nce ntrati o n 
˂ 5 M / m L, or s per m m otilit y ˂ 2 0 %, or a perce nt n or mal s per m m or p h ol o g y of ˂ 1 0 %.
T he n u m ber a n d pr o p orti o n of s u bjects meeti n g a n y  of t he s per m decrease t hres h ol ds (fr o m t he 
baseli ne val ue [ mea n of 2 e val ua ble se me n c ollecti o ns at scree ni n g]) or a n y of t he c om p o ne nts of 
a c o nfir me d se me n a b n or malit y ( mea n of 2 e val ua ble sa m ples at a st u d y visit) at Wee k 13 will 
be dis pla y e d b y d o u ble -bli n d treat me nt gr o u p f or t he Se me n A nal ys is Set.
S per m Decrease Criteria

≥5 0 % decrease i n s per m c o nce ntrati o n

≥5 0 % decrease i n s per m t otal m otilit y

≥5 0 % decrease i n s per m m or p h ol o g y [ % n or mal] ( W H O 1 9 9 2 criteria)

≥5 0 % decrease i n s per m c o nce ntrati o n a n d ( ≥5 0 % decrease i n t otal m otilit y  a n d/or
m or p h ol o g y [ % n or mal]) at t he sa me visit)
C o nfir me d Se me n A b n or malit y Criteria (as defi ne d b y Jar vi et al) 

S per m c o nce ntrati o n < 5 M/ m L

S per m t otal m otilit y  < 2 0 %

S per m m or p h ol o g y  ( % n or mal) < 1 0 %

C o nfir me d Se me n A b n or malit y  (S per m c o nce ntrati o n < 5 M / m L or s per m t otal m otilit y  
< 2 0 % or s per m m or p h ol o g y [% n or mal ] < 1 0 % at t he sa me visit)


Fil g oti ni b
G L P G 0 6 3 4 -C L -2 2 7
Statistical A nal ysis Pla n
Versi o n 1. 0
C O N FI D E N TI A L
Pa ge 4 3
1 2 Ja n uar y 2 0 2 1
T he n u m ber a n d pr o p orti o n of s u bjects meeti n g a n y  of t he pre-s pecifie d s per m decrease 
t hres h ol ds or c o m p o ne nts of a c o nfir me d se me n a b n or malit y will be dis pla y e d at Wee k 2 6 f or 
t he Wee k 2 6 Se me n A nal ysis Set; a n d at or after t he Wee k 3 9 visit f or t he At/ After Wee k 3 9 
Se me n A nal ys is Set. Prese ntati o ns will be dis pla y e d b y treat me nt se q ue nce a n d 
res p o n der/ n o n-res p o n der at Wee k 1 3 a n d treat me nt se q ue nce, res pecti vel y.
A listi n g of s u bjects w h o met a n y  of t he c o m p o ne nts of a c o nfir me d se me n a b n or malit y will be 
pr o vi de d.
6. 6.
E x pl or at or y E n d p oi nts
6. 6. 1.
Defi niti o n of t he 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 re versi bilit y  a m o n g s u bjects w h o e x perie nce a ≥ 5 0 % decrease i n s per m 
c o nce ntrati o n, a n d/ or m otilit y, a nd/ or m or p h ol o g y

C ha n ge fr o m baseli ne i n 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 
Wee ks 1 3 a n d 2 6
6. 6. 2.
Re versi bilit y A n al ysis
R e versi bilit y will be s u m marize d se parately f or eac h s per m para meter t hat met a pre -s pecifie d 
s per m para meter decrease. T he n um ber ( perce nt) w h o met re versi bilit y  criteria a n d t he 
c u m ulati ve n u m ber ( perce nt) w h o met re versi bilit y criteria at eac h M o nit ori n g P hase visit will be 
prese nte d. 
Re versi bilit y  f or s u bjects meeti n g pre-s pecifie d s per m para meter decrease t hres h ol d[s] at 
Wee k
1 3 will be dis pla y e d b y d o u ble-bli n d treat me nt gr o u p; at Wee k 2 6 b y treat me nt se q ue nce 
a n d res p o n der/ n o n -res p o n der at Wee k 1 3; a n d at/after Wee k 3 9 b y  act ual treat me nt se q ue nce.
F or t he Wee k 2 6 interi m anal ys is, a n a d diti o nal re versi bilit y  ta ble f or “c o m pleters” (ie, s u bjects 
w h o ha ve c o m plete d t he f ull 5 2 wee ks of off -st u d y dr u g f oll o w- u p, met re versi bilit y criteria, or 
pre mat urel y disc o nti n ue d fr o m st u d y w hile bei n g f oll o we d i n t he m o nit ori n g p hase) will be 
pr o d uce d if at least 1 s u bject has a n e val ua ble m o nit ori n g p hase visit a n d is o n g oi n g i n t he 
m o nit ori n g p hase at t he ti me of data c ut off.
N o f or mal testi n g or CI is pla n ne d. A b y- s u bject data listi n g of se me n data ( wit h meas ure me nt 
w here re versi bilit y  criteria was met fla g ge d) will be pr o vi de d f or s u bjects w h o e ntere d t he 
M o n it ori n g P hase.
Ta ble 6- 3 s h o ws a n e xa m ple f or h y p ot hetical pr o p orti o n s of s u bjects (at fi nal a nalys is) wit h 
re verse d s per m c o nce ntrati o n b y  m o nit ori n g visit n um ber a n d d o u ble -bli n d treat me nt gr o u p f or 
s u bjects wit h a ≥5 0 % decrease at/ pri or t o Wee k 1 3.


Fil g oti ni b
G L P G 0 6 3 4 -C L -2 2 7
Statistical A nal ysis Pla n
Versi o n 1. 0
C O N FI D E N TI A L
Pa ge 4 4
1 2 Ja n uar y 2 0 2 1
T a ble 6- 3.
H y p ot hetic al Pr o p orti o n of S u bjects W h o Met Re v ersi bilit y Criteri a 
f or S per m C o nce ntr ati o n b y Tre at me nt Gr o u p a n d M o nit ori n g P h ase 
Visit ( S u bjects wit h a ≥5 0 % Decre ase i n S per m C o nce ntr ati o n 
at/ pri or t o Wee k 1 3)
Tre at m e nt bef ore 
M o nit ori n g
M o nit ori n g 
Visit 1
M o nit ori n g 
Visit 2
M o nit ori n g 
Visit 3
M o nit ori n g 
Visit 4
Re versi bilit y i n 
M o nit ori n g 
P h ase
F il g oti ni b
3 / 5
1 / 2
1 / 1
0 / 0
5 / 5
C u m ulati ve Rate
3 / 5 = 6 0. 0 % 
4 / 5 = 8 0. 0 %
5 / 5 = 1 0 0. 0 % 
5 / 5 = 1 0 0. 0 % 
5 / 5 = 1 0 0. 0 %
P lace b o
3 / 6
1 / 3
1 / 2
0 / 1
5 / 6
C u m ulati ve Rate
3 / 6 = 5 0 %
4 / 6 = 6 8 %
5 / 6 = 8 3. 3 % 
5 / 6 = 8 3. 3 % 
5 / 6 = 8 3. 3 %
6. 6. 3.
H or m o nes
Si milar a nal y sis met h o ds use d t o s u m marize c o nti n u o us sec o n dar y se me n para meters will be 
use d t o a nal yz e h or m o nes LH, F S H, i n hi bi n B, a n d t otal test oster o ne. Baseli ne will be t he last 
val ue pri or t o a d mi nistrati o n of a n y st u d y dr u g.
F or all c o nti n u o us h or m o ne para meters, 8 -p oi nt s u m mar y  statistics ( 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 ( d o u ble-bli n d treat me nt gr o u p f or Baseli ne, Wee k 4 
a n d Wee k 1 3 ; b y  treat me nt se q ue nce a n d res p o n der/ n o n-res p o n der stat us at Wee k
1 3 f or 
Baseli ne a n d Wee k 2 6 ) will be pr o vi de d f or t he val ue at t he visit, c ha n ge fr o m baseli ne, a n d 
perce nt a ge c ha n ge fr o m baseli ne i n h or m o ne para meter s f or t he Se me n A nal y sis Set a n d 
Wee k
2 6 Se me n A nal ys is Set, res pecti vel y . A 9 5 % distri b uti o n-free CI o n t he me dia n c ha n ge 
a n d perce nta ge c ha n ge fr o m baseli ne i n all h or m o ne para meters will be c o nstr ucte d by 
d o u ble -bli n d treat me nt gr o u p at Wee ks 4 a n d 1 3; a n d b y  d o u ble -bli n d treat me nt a n d 
res p o n der/ n o n-res p o n der stat us at Wee k 1 3 f or t he Wee k 2 6 visit usi n g t he CI P C T L D F o pti o n i n 
P R O C U NI V A RI A T E i n S A S. 
Q ua ntile re gressi o n will be use d t o esti mate t he differe nce (fil g oti ni b mi n us place b o) i n me dia n 
c ha n ge a n d perce nta ge c ha n ge fr o m baseli ne i n h or m o nes at d o u ble -bli n d W ee ks 4 a n d 1 3 a n d t o 
c o nstr uct a 9 5 % CI . M o dels will a dj ust f or t he baseli ne h or m o ne val ue , c o nc urre nt M T X use 
( yes, n o), a n d s per m c o nce ntrati o n strata ( 1 5 - 5 0 M/ m L , > 5 0 M/ m L). T he CI = R A N K o pti o n
will be s pecifie d i n P R O C Q U A N T R E G i n S A S . 
F or Wee k 2 6 , t he c ha n ge a n d perce nta ge c ha n ge fr o m baseli ne i n h or m o ne para meters will be 
dis pla y e d b y treat me nt se q ue nce, res p o n der/ n o n-res p o n der stat us at Wee k 1 3 , an d visit f or 
s u bjects i n t he Wee k 2 6 Se me n A nalys is Set.
F or visits at/after Wee k 3 9 , t he c ha n ge a n d perce nta ge c ha n ge fr o m baseli ne i n h or m o ne 
para meters will be dis pla y e d b y treat me nt se q ue nce a n d visit f or s u bjects i n t he At/ After 
Wee k
3 9 Se me n A nal ys is Set.


Fil g oti ni b
G L P G 0 6 3 4 -C L -2 2 7
Statistical A nal ysis Pla n
Versi o n 1. 0
C O N FI D E N TI A L
Pa ge 4 5
1 2 Ja n uar y 2 0 2 1
S hift ta bles fr o m baseli ne t o Wee k 4 a n d Wee k 1 3
f or L H, F S H, i n hi bi n B, a n d t otal test oster o ne 
will be s u m marize d b y  d o u ble-bli n d treat me nt gr o u p f or t he Se me n A nal y sis Set. S hift ta bles 
fr o m baseli ne t o Wee k 2 6 f or L H, F S H, i n hi bi n B, a n d t otal test oster o ne will be s u m marize d b y 
treat me nt se q ue nce a n d res p o n der/ n o n-res p o n der stat us at Wee k 1 3 f or t he Wee k 2 6 a nal ys is 
visit ( usi n g t he cl osest val ue t o tar get da y s) a n d t he Wee k 2 6 Se me n A nal ysis Set. T he s hift 
ta bles i ncl u de s hift a nalysis f or h or m o ne para meters bel o w, wit hi n, a n d a b o ve t he ce ntral 
la b orat or y defi ne d n or mal ra n ge at baseli ne t o bel o w, wit hi n a n d a b o ve t he n or mal ra n ge at 
Wee k 4, Wee k 1 3 a n d Wee k
2 6.
N o se nsiti vit y  a nalys is will be perf or me d. N o f or mal testi n g is pla n ne d. 
A b y -s u bject listi n g will be pr o vi de d f or h or m o nes. A se parate list i n g of t he h or m o ne data f or 
s u bjects w h o e ntere d t he M o nit ori n g P hase of t he st u d y will be pr o vi de d.
6. 7.
C h a n ges t o Pr ot oc ol -S pecifie d A n al yses of Se me n a n d H or m o ne D at a
T he pr ot oc ol s pecifie d a n a nal ys is of c o varia nce ( A N C O V A) m o del a dj usti n g f or baseli ne val ue 
a n d stratificati o n fact ors t o esti mate treat me nt differe nces ( 9 5 % CI) f or t he c o nti n u o us e n d p oi nts 
at ti me p oi nts w here a nal ysis was t o be c o n d ucte d f or c o nti n u o us se me n para meter a n d h or m o ne 
data. Q ua ntile re gressi o n was use d i n place of a n A N C O V A m o del as me dia ns were t h o u g ht t o 
be a m ore a p pr o priate esti mate t ha n mea ns f or t his data w hic h is p ote ntiall y s ke we d wit h 
o utliers.
Disease t y pe was n ot i ncl u de d as a stratificati o n fact or f or t he stratifie d Ma ntel -Hae nszel test f or 
t he pri mar y e n d p oi nt or as a de pe n de nt varia ble i n q ua ntile re gressi o n m o dels f or s per m/se me n 
para meters (sec o n dar y  e n d p oi nts) or h or m o nes (e x pl orat or y e n d p oi nts) si nce o nl y a fe w R A 
s u bjects were e nr olle d. T he l o west 2 le vels ( 1 5 - 2 5 M/ m L  a n d > 2 5 - 5 0 M/ m L ) f or s per m 
c o nce ntrati o n strata were c o m bi ne d i n t hese a nal yses d ue t o t he s mall n u m ber of s u bjects i n t he 
l o west s per m c o nce ntrati o n strat u m.


Fil g oti ni b
G L P G 0 6 3 4 -C L -2 2 7
Statistical A nal ysis Pla n
Versi o n 1. 0
C O N FI D E N TI A L
Pa ge 4 6
1 2 Ja n uar y 2 0 2 1
7.
A S S E S S M E N T O F  R E S P O ND E R/ N O N -R E S P O N D E R A N D 
DI S E A S E W O R S E NI N G
P h y sicia n Gl o bal Assess me nt of Disease Acti vit y ( P h G A D A) was use d t o deter mi ne w het her a 
s u bject was a n “Art hritis Res p o n der ” ( defi ne d as a n i m pr o ve me nt i n P h G A D A of at least 
2 0 % c o m pare d t o baseli ne at t he s pecifie d assess me nt ti me p oi nt) or “ Art hritis N o n -res p o n der” 
( defi ne d as a s u bject 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 p oi nt). T he p h y sicia n ( w h o ha d access t o disease assess me nts descri be d i n Pr ot oc ol Secti o ns
6. 1 8 t hr o u g h 6. 2 3 [ as a p pr o priate]) drew a per pe n dic ular li ne o n a 1 0 0 -milli meter ( m m) vis ual 
a nal o g ue scale ( V A S) re prese nti n g t he s u bject’s disease se verit y  a n d meas ured t he dista nce 
(i n m m) bet wee n t he “ n o disease acti vit y ” a nc h or (at 0) a n d t he mar k o n t he 1 0 0- m m li ne. T he 
P h G A D A ra n g e d fr o m 0- 1 0 0.
A listi n g of all o bser ve d data base d o n t he All Ra n d o mize d A nal y sis Set will dis pla y t he 
P h G A D A at Scree ni n g, Da y  1, a n d Wee k 1 3; a n d t he perce nt c ha n ge fr o m baseli ne i n P h G A D A 
a n d ass ociate d art hritis res p o n der/ n o n -res p o n der stat us at Wee k
1 3.


Fil g oti ni b
G L P G 0 6 3 4 -C L -2 2 7
Statistical A nal ysis Pla n
Versi o n 1. 0
C O N FI D E N TI A L
Pa ge 4 7
1 2 Ja n uar y 2 0 2 1
8.
S A F E T Y  AN A L Y S E S
S afet y a nalys es will be c o n d ucte d o n t he Safet y A nal ysis Set a n d E xte nsi o n P hase Safet y 
A nal y sis Set, defi ne d i n Secti o n 3. 1. 3 . 
S afet y data d uri n g t he d o u ble -bli n d p hase will be s u m marize d base d o n act ual treat me nt w hile 
t he s u bject is o n d o u ble-bli n d st u d y  dr u g. S u bjects will be i ncl u de d i n a nal ysis after first d ose 
date of d o u ble -bli n d st u d y  dr u g u p t o:

First d ose date of o pe n -la bel fil g oti ni b or first date i n e xte nsi o n p hase (mi n us 1 da y  f or 
a d verse e ve nts) f or s u bjects w h o recei ve o pe n la bel fil g oti ni b or sta n dar d of care i n e xte nsi o n 
p hase

L ast d ose date of d o u ble -bli n d st u d y dr u g + 3 0 da ys (s u bjects meeti n g pre -s pecifie d s per m 
decrease t hres h ol ds at/ pri or t o Wee k 1 3 w h o were s witc he d t o M o nit ori n g P hase t o assess 
re versi bilit y of all s per m para meters meeti n g decrease t hres h ol ds; s u bjects per ma ne ntl y
disc o nti n ue d fr o m st u d y  dr u g at/ pri or t o Wee k 1 3)
S afet y data d uri n g t he e xte nsi o n p hase will be s u m marize d b ase d o n act ual treat me nt se q ue nce as 
descri be d i n Secti o n 3. 2 of t his S A P. Safet y  data c ollecte d o n ( A Es o nl y ) or after first d ose date 
of o pe n -la bel fil g oti ni b/first date i n e xte nsi o n p hase t o:

L ast d ose date of o pe n -la bel fil g oti ni b/sta n dar d of care i n e xte nsi o n p hase + 3 0 da ys will be 
i ncl u de d f or s u bjects w h o ha ve st o p pe d or c o m plete d all stu d y  dr u g/ S O C i n t he e xte nsi o n 
p hase

All a vaila ble data (after start of e xte nsi o n p hase) at ti me of data c ut f or su bjects w h o are 
o n g oi n g o n o pe n -la bel fil g oti ni b/sta n dar d of care i n t he e xte nsi o n p hase at t he ti me of a n 
i nteri m a nal ysis
8. 1.  
A d verse E ve nts a n d De at hs
8. 1. 1.
A d verse E ve nt Dicti o n ar y
Cli nical a n d la b orat or y  a d verse e ve nts ( A Es) will be c o de d usi n g t he c urre nt versi o n of 
Me d D R A. S y ste m or ga n class ( S O C), 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 pr o vi de d i n t he A E dataset.
8. 1. 2.
A d verse E ve nt Se verit y
A d verse e ve nts are gra de d b y  t he i n vesti gat or as Gra de 1, 2, 3, 4, or 5 acc or di n g t o C o m m o n 
Ter mi n ol o g y  Criteria f or A d verse E ve nts ( C T C A E) Gra di n g Scale . If C T C A E criteria d o n ot 
e xist f or a s pecific e ve nt, Ta ble 7 -1 of t he st u d y pr ot oc ol pr o vi des g ui da nce f or t he i n vesti gat or 
t o gra de t he e ve nt. T he se verity gra de of e ve nts f or w hic h t he i n vesti gat or di d n ot rec or d se verit y 
will be cate g orize d as “ missi n g” f or ta b ular s u m maries a n d data listi n gs . T he missi n g cate g or y
will be liste d last i n s u m mar y prese ntati o n.


Fil g oti ni b
G L P G 0 6 3 4 -C L -2 2 7
Statistical A nal ysis Pla n
Versi o n 1. 0
C O N FI D E N TI A L
Pa ge 4 8
1 2 Ja n uar y 2 0 2 1
8. 1. 3.  
Rel ati o ns hi p of A d verse E ve nts t o St u d y Dr u g
Relate d A Es are t h ose f or w hic h t he i n vesti gat or selecte d “ Relate d” o n t he A E e C R F t o t he 
q uesti o n of “ Relate d t o St u d y  Treat me nt.” F or t he e xte nsi o n p hase, A Es mar ke d as “ Relate d t o 
S O C” will be c o nsi dere d as relate d f or s u bjects w h o s witc h t o S O C i n t he e xte nsi o n p hase. 
Relate d ness will al wa y s defa ult t o t he i n vesti gat or’s c h oice, n ot t hat of t he me dical m o nit or. 
E ve nts f or w hic h t he i n vesti gat or di d n ot rec or d relati o ns hi p t o st u d y dr u g will be c o nsi dere d 
relate d t o st u dy dr u g f or s u m mar y p ur p oses. H o we ver, b y- s u bject data listi n gs will s h o w t he 
relati o ns hi p as missi n g.
8. 1. 4.
Seri o us A d verse E ve nts
Seri o us a d verse e ve nts ( S A Es) will be i de ntifie d a n d ca pt ure d as S A Es if t he A Es met t he 
defi niti o ns of S A E s t hat were s pecifie d i n t he st u d y pr ot oc ol. S A Es ca pt ure d a n d st ore d i n t he 
cli nical data base will be rec o ncile d wit h t he S A E data base fr o m t he Gilea d Gl o bal Patie nt Safet y  
(f or merly Gilea d P har mac o vi gil ance a n d E pi de mi ol o g y ) De part me nt bef ore data base
fi nalizati o n.
8. 1. 5.
Tre at me nt -E m er ge nt A d verse E ve nts
8. 1. 5. 1.
Defi niti o n of Treat me nt -E mer ge nt A d verse E ve nts
Treat me nt -e mer ge nt a d verse e ve nts ( T E A Es) d uri n g t he d o u ble- bli n d p hase are defi ne d as 1 or 
b ot h of t he f oll o wi n g:

A n y  A Es wit h a n o nset date o n or after t he d o u ble -bli n d st u d y dr u g start date t hr o u g h 
first d ose date of o pe n -la bel fil g oti ni b/start date i n e xte nsi o n p hase mi n us 1 da y (if s u bject 
e nr olle d i n e xte nsi o n p hase) or t o last d ose date of d o u ble- bli n d st u d y  dr u g + 3 0 d a y s f or 
s u bjects w h o per ma ne nt l y disc o nti n ue d o u ble-bli n d dr u g a n d d o n ot e nr oll i nt o e xte nsi o n 
p hase (i ncl u di n g s u bjects w h o mee t a s per m decrease t hres h ol d w h o st o p st u d y dr u g a n d 
c o nti n ue t o be f oll o we d i n t he m o nit ori n g p hase f or re versi bilit y)

A n y  A Es lea di n g t o pre mat ure disc o nti n uati o n of d o u ble -bli n d st u d y dr u g
Treat me nt - e mer ge nt a d verse e ve nts ( T E A Es) d uri n g t he e xte nsi o n p hase are defi ne d as 1 or b ot h 
of t he f oll o wi n g:

A n y  A Es wit h a n o nset date o n or after first d ose date of o pe n-la bel fil g oti ni b/first d ose date 
i n e xte nsi o n p hase t o last d ose date of o pe n-la bel fil g oti ni b + 3 0 da y s f or s u bjects w h o 
per ma ne ntl y disc o nti n ue o pe n -la bel fil g oti ni b (i ncl u di n g s u bjects w h o meet a s per m decrease 
t hres h ol d w h o st o p st u d y dr u g a n d c o nti n ue t o be f oll o we d i n t he m o nit ori n g p hase f or 
re versi bilit y) or all A Es f or s u bjects w h o are o n g oi n g o n o pe n -la bel fil g oti ni b/sta n dar d of 
care i n exte nsi o n p hase at t he ti me of a n  i nteri m a nal y sis

A n y  A Es lea di n g t o pre mat ure disc o nti n uati o n of o pe n-la bel fil g oti ni b st u d y dr u g


Fil g oti ni b
G L P G 0 6 3 4 -C L -2 2 7
Statistical A nal ysis Pla n
Versi o n 1. 0
C O N FI D E N TI A L
Pa ge 4 9
1 2 Ja n uar y 2 0 2 1
F or e xa m ple, f or a s u bject w h o t o o k d o u ble-bli n d place b o a n d s witc he d t o sta n dar d of care i n t he 
e xte nsi o n p hase , T E A Es wit h a n o nset date o n/after first d ose date of d o u ble -bli n d fil g oti ni b a n d 
pri or t o first d ate i n exte nsi o n p hase will be T E f or d o u ble -bli n d fil g oti ni b (s u m marize d wit h 
d o u ble -bli n d p hase) ; fr o m first date i n e xte nsi o n p hase u p t o last d ose date o f sta n dar d of care i n 
e xte nsi o n p hase + 3 0 da ys will be T E f or sta n dar d of care (s u m marize d b y treat me nt se q ue nce 
[d o u ble -bli n d fil g oti ni b t o sta n dar d of care] f or t he e xte nsi o n p hase). 
8. 1. 5. 2.
I nc o m plete Dates
If t he o nset date of t he A E is i nc o m plete a n d t he A E st o p date is n ot pri or t o t he first d osi n g date 
of st u d y  dr u g, t he n t he m o nt h a n d year ( or year al o ne if m o nt h is n ot rec or de d) of o nset 
deter mi ne w het her a n A E is treat me nt e mer ge nt . F or t he d o u ble -bli n d p hase , the e ve nt is
c o nsi dere d treat me nt e mer ge nt if b ot h of t he f oll o wi n g 2 criteria are met:

T he A E o nset is t he sa me as or after t he m o nt h a n d year ( or year) of t he first d osi n g date of 
d o u ble -bli n d st u d y dr u g, a n d

T he A E o nset date is t he sa me as or bef ore t he m o nt h a n d year ( or ye ar) of t he e xte nsi o n 
p hase o pe n -la bel fil g oti ni b or e xte nsi o n p hase start date (if n o n-missi n g) or bef ore t he date 
c orres p o n di n g t o 3 0 da ys after t he date of t he last d ose of d o u ble -bli n d st u d y dr u g 
(if per ma ne ntl y  disc o nti n ue d fr o m d o u ble-bli n d st u d y  dr u g)
F or t he exte nsi o n p hase , t he e ve nt is c o nsi dere d treat me nt e mer ge nt if b ot h of t he f oll o wi n g 
2 criteria are met:

T he A E o nset is t he sa me as or after t he m o nt h a n d y ear ( or year) of t he first d osi n g date of 
o pe n -la bel fil g oti ni b/start date i n t he e xte nsi o n p hase, a n d

T he A E o nset date is t he sa me as or bef ore t he m o nt h a n d year ( or ye ar) c orres p o n di n g t o 
3 0 da y s after t he date of t he last d ose of o pe n-la bel fil g oti ni b/last date i n e xte nsi o n p hase 
(if per ma ne ntl y  disc o nti n ue d fr o m e xte nsi o n p hase dr u g or e ntere d m o ni t ori n g p hase f or 
meeti n g a pre -s pecifie d s per m decrease t hres h ol d) or all e ve nts after first d ose date of dr u g 
f or e xte nsi o n p hase if s u bject is o n g oi n g i n e xte nsi o n p hase at ti me of i nteri m a nal ysis
A n A E wit h c o m pletel y missi n g o nset a n d st o p dates, or w it h t he o nset date missi n g a n d a st o p 
date later t ha n t he first d osi n g date of d o u ble -bli n d st u d y dr u g, will be c o nsi dere d t o be treat me nt 
e mer ge nt f or t he d o u ble-bli n d p hase . I n a d diti o n, a n A E wit h t he o nset date missi n g a n d 
i nc o m plete st o p date wit h t he sa me or later m o nt h a n d year ( or year al o ne if m o nt h is n ot 
rec or de d) as t he first d osi n g date of o pe n -la bel fil g oti ni b/first date i n e xte nsi o n p hase will be 
c o nsi dere d treat me nt e mer ge nt f or e xte nsi o n p hase.


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8. 1. 5. 3.
A nal y sis of E x p os ure-A dj uste d I nci de nce Rate
T he E x p os ure -A dj uste d I nci de nce Rate ( E AI R) f or a T E A E is defi ne d as:
T he t otal patie nt -years of e x p os ure ( P Y E) t o a treat me nt is t he s u m of t he i n di vi d ual s u bject’s 
P Y E a n d is defi ne d as:
F or s u bjects wit h a n e ve nt:
P Y E = ( Eve nt st art d ate – first d ate i n D B p h ase + 1) / 3 6 5. 2 5
F or s u bjects wit h n o e ve nt:
P Y E = ( C alc ul ati o n e n d d ate – first d ate i n D B p h ase + 1) / 3 6 5. 2 5
w here calc ulati o n e n d date f or t he d o u ble bli n d p hase = t he earliest date a m o n g 
(last d osi n g date of d o u ble bli n d p hase + 3 0, first date i n e xte nsi o n p hase of t he st u d y -1 
da y , deat h date, c ut off date). If t he last st u dy dr u g d osi n g date is missi n g a n d t he s u bject 
has st o p pe d dr u g , t he latest date a m o n g st u dy dr u g e n d date, cli nical visit date, a n d 
la b orat or y sa m ple c ollecti o n date t hat occ urre d d uri n g t he d o u ble-bli n d p hase will be 
use d.
w here calc ulati o n e n d date f or t he e ntire st u d y dis pla y  = t he earliest date a m o n g
(last d osi n g date of O L fil g oti ni b+ 3 0 da y s [s u bjects i n t he fil g oti ni b t o O L fil g oti ni b 
se q ue nce w h o per ma ne ntl y  disc o nti n ue d O L fi lg oti ni b); last d osi n g date of d o u ble -bli n d 
fil g oti ni b [s u bjects i n t he fil g oti ni b t o sta n dar d of care gr o u p], last date o n sta n dar d of 
care i n e xte nsi o n p hase [s u bjects i n place b o t o sta n dar d of care se q ue nce w h o s witc he d t o 
m o nit ori n g p hase or earl y ter mi nate d fr o m st u d y after starti n g e xte nsi o n p hase], last 
d osi n g date of d o u ble -bli n d st u d y  dr u g + 3 0 f or s u bjects w h o di d n ot start e xte nsi o n 
p hase , data c ut off date, deat h date).
If e ve nt start date d uri n g t he d o u ble-bli n d p hase is partia ll y missi n g a n d t he n o n-missi n g p orti o n 
matc hes t he first d osi n g date ( m o nt h a n d/ or year) of d o u ble -bli n d st u d y  dr u g; or if t he date is 
c o m pletel y missi n g, A E o nset is i m p ute d as t he date of first d ose of d o u ble-bli n d st u d y  dr u g. 
Ot her wise it is i m p ute d as t he first da y of t he m o nt h (if o nl y da y is missi n g) or Ja n uar y 1st of t he 
ye ar (if da y a n d m o nt h are missi n g).


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T he e xact 9 5 % CI base d o n t he P oiss o n distri b uti o n { Ul m 1 9 9 0 } f or E AI R is defi ne d as:
T o esti mate t he 9 5 % CI f or t he E AI R differe nce bet wee n t w o treat me nt gr o u ps f or e ve nts d uri n g 
t he d o u ble-bli n d p hase , t he Met h o d of Varia nce Esti mates Rec o ver y ( M O V E R)-t ype c o nfi de nce 
i nter val descri be d i n { Li  2 0 1 1} will be use d:
W here n a is t he t otal n u m ber of s u bjects wit h t he e ve nt, T a is t he t otal P Y E, la is t he l o wer 
b o u n d a n d u a is t he u p per b o u n d of t he e xact 9 5 % CI base d o n t he P oiss o n distri b uti o n f or gr o u p 
a, Si milarl y f or gr o u p b.
8. 1. 6.
S u m m aries of A d verse E ve nts a n d De at hs
A brief, hi g h -le vel s u m mar y of t he n u m ber a n d perce nta ge of s u bjects w h o e x perie nce d at 
least 1 T E A E i n t he cate g ories descri be d bel o w will be pr o vi de d b y treat me nt ( b y d o u ble-bli n d 
treat me nt f or d o u ble-bli n d p hase; b y treat me nt se q ue nce f or e xte nsi o n p hase):

T E A E

T E A Es wit h Gra de 3 or hi g her (f urt her br o ke n d o w n t o Gra de 3, Gra de 4, a n d Gra de 5)

T E A Es wit h Gra de 2 or hi g her

T E treat me nt- relate d A E

T E treat me nt- relate d A Es wit h Gra de 3 or hi g her (f urt her br o ke n d o w n t o Gra de 3, Gra de 4,
a n d Gra de 5)

T E treat me nt- relate d A Es wit h Gra de 2 or hi g her

T E S A E

T E treat me nt-relate d S A E 

T E A E t hat le d t o pre mat ure disc o nti n uati o n of d o u ble -bli n d st u d y dr u g ( N O T E: cate g or y 
a p plica ble o nl y f or d o u ble -bli n d p hase)


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
T E A E t hat le d t o pre mat ure disc o nti n uati o n of o pe n -la bel fil g oti ni b st u d y dr u g
( N O T E: cate g or y a p plica ble o nl y f or e xte nsi o n p hase)

T E A E t hat le d t o te m p orar y  i nterr u pti o n of d o u ble-bli n d st u d y dr u g ( N O T E: cate g or y 
a p plica ble o nl y f or d o u ble -bli n d p hase)

T E A E t hat le d t o te m p orar y  i nterr u pti o n of o pe n-la bel fil g oti ni b ( N O T E: cate g or y a p plica ble 
o nl y  f or e xte nsi o n p hase)

T E A E t hat le d t o pre mat ure disc o nti n uati o n of st u d y

All deat hs o bser ve d i n t he st u d y (if a s u bject recei ve d ≥1 d ose of o pe n -la bel fil g otini b or 
sta n dar d of care i n e xte nsi o n p hase, t he deat h will be s u m marize d i n e xte nsi o n p hase; if t he 
last st u d y dr u g recei ve d was d o u ble-bli n d dr u g , t he deat h will be s u m marized wit h t he
d o u ble bli n d p hase)
T he n u m ber a n d perce nta ge of s u bjects w h o e x perie nce d at least 1 T E A E will be pr o vi de d a n d 
s u m marize d b y S O C, H L T, P T, a n d treat me nt ( d o u ble-bli n d treat me nt f or d o u ble - bli n d p hase; 
treat me nt se q ue nce f or e xte nsi o n p hase). 
F or ot her A Es descri be d bel o w, s u m maries will be pr o vi de d b y  S O C, P T, a n d treat me nt
( d o u ble-bli n d treat me nt f or d o u ble -bli n d p hase; treat me nt se q ue nce f or e xte nsi o n p hase):

All T E A E s

All T E A Es b y  C o nc o mita nt Me dicati o n Use (I m m u n o m o d ulat or a n d C ortic oster oi d Use)

T E A Es of Gra de 3 or hi g he r ( by ma xi m u m se verit y)

T E A Es of Gra de 2 or hi g her

All T E treat me nt-relate d A Es

T E Treat me nt -relate d A Es of Gra de 3 or hi g her ( b y ma xi m u m se verit y)

T E S A Es

T E S A Es b y  C o nc o mita nt Me dicati o n Use (I m m u n o m o d ulat or a n d C ortic oster oi d Use)

T E treat me nt-relate d S A Es

T E A Es lea di n g t o te m p orar y  i nterr u pti o n of d o u ble -bli n d st u d y dr u g
( N O T E: ta ble a p plica ble o nl y f or d o u ble-bli n d p hase)

T E A Es lea di n g t o te m p orar y  i nterr u pti o n of o pe n-la bel fil g oti ni b st u d y dr u g
( N O T E: ta ble a p plica ble o nl y f or e xte nsi o n p hase)


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
T E A Es lea di n g t o pre mat ure disc o nti n uati o n of d o u ble -bli n d st u d y dr u g
( N O T E: ta ble a p plica ble o nl y f or d o u ble-bli n d p hase)

T E A Es lea di n g t o pre mat ure disc o nti n uati o n of o pe n- la bel fil g oti ni b st u d y dr u g
( N O T E: ta ble a p plica ble o nl y f or e xte nsi o n p hase)

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

T E A Es lea di n g t o deat h
M ulti ple e ve nts will be c o u nte d o nl y  o nce per s u bject i n eac h s u m mar y . A d verse e ve nts will be 
s u m marize d a n d liste d first i n al p ha betic or der of S O C a n d H L T wit hi n eac h S O C (if a p plica ble ), 
a n d t he n b y P T i n desce n di n g or der of t otal fre q ue nc y wit hi n eac h S O C. F or s u m maries by 
se verity gra de, t he m ost se vere gra de will be use d f or t h ose A Es t hat occ urre d m ore t ha n o nce i n 
an i n di vi d ual s u bject d uri n g t he st u d y. 
I n a d diti o n t o t he a b o ve s um mar y  ta bles, all T E A Es , S A Es, a n d T E treat me nt-relate d A Es will be 
s u m marize d b y P T o nl y a n d treat me nt ( d o u ble-bli n d treat me nt f or d o u ble -bli n d p hase; treat me nt 
se q ue nce f or e xte nsi o n p hase), i n desce n di n g or der of t otal fre q ue nc y f or P T.
D ata listi n gs will be pr o vi de d f or t he f oll o wi n g:

All A Es , i n dicati n g w het her t he e ve nt is treat me nt e mer ge nt

All A Es of Gra de 3 or hi g her

S A Es

Deat hs

C O VI D -1 9 A Es

All A Es lea di n g t o te m p orar y i nterr u pti o n of d o u ble -bli n d st u d y dr u g

All A Es lea di n g t o te m p orar y  i nterr u pti o n of o pe n-la bel fil g oti ni b st u d y dr u g 

A Es lea di n g t o pre mat ure disc o nti n uati o n of d o u ble -bli n d st u d y dr u g

A Es lea di n g t o pre mat ure disc o nti n uati o n of o pe n -la bel fil g oti ni b
8. 1. 7.  
A d verse E ve nts of I nterest
A d verse e ve nts o f i nterest ( A EIs) i ncl u de i nfecti o ns, gastr oi ntesti nal perf orati o ns, her pes z oster, 
mali g na ncies (e xcl u di n g n o n -mela n o ma s ki n ca ncers), n o n - mela n o ma s ki n ca ncers, a n d 
t hr o m b oe m b olic e ve nts. S u m maries of t he f oll o wi n g treat me nt-e mer ge nt A EIs will be pr o d uce d 
t o e n ha nce t he a nalys is of safety data. 


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
E ve nts of i nfecti o n prese nte d i n t he f oll o wi n g s u bcate g ories:

A Es of i nfecti o ns, utilizi n g all A Es i n t he Me d D R A I nfecti o ns a n d I nfestati o ns S O C

A Es of seri o us i nfecti o ns, usi n g all A Es i n t he Me d D R A I nfecti o ns a n d I nfestati o ns S O C 
t hat are classifie d as S A Es

A Es of her pes z oster, utilizi n g a Me d D R A searc h ter m ( M S T) list de vel o pe d b y  Gilea d 

A Es of o p p ort u nistic i nfecti o ns ( OIs), usi n g a Sta n dar dize d Me d D R A Q uer y  
( S M Q)--narr o w sc o pe

Acti ve t u berc ul osis , usi n g a M S T list de vel o pe d b y Gilea d

He patitis B or C i nfecti o ns , usi n g a M S T list de vel o pe d b y Gilea d

A Es of mali g na ncies, e xcl u di n g n o n -mela n o ma s ki n ca ncers, utilizi n g a M S T list de vel o pe d 
b y  Gilea d 

A Es of n o n -mela n o ma s ki n ca ncers, utilizi n g a M S T list de vel o pe d b y  Gilea d

A Es of gastr oi ntesti nal perf orati o n, utilizi n g a M S T list  de vel o pe d b y  Gilea d 

A Es of arterial or ve n o us t hr o m b osis a n d/ or t hr o m b oe m b olis m, prese nte d i n t he f oll o wi n g 
s u bcate gories:

A Es of ve n o us t hr o m b osis, utilizi n g a M S T list de vel o pe d b y Gilea d 

A Es of p ul m o nar y  e m b olis m, utilizi n g a M S T list de vel o pe d b y Gilea d

A Es of arterial t hr o m b osis, utilizi n g t he e m b olic a n d t hr o m b otic e ve nts, arterial S M Q

A Es of cere br o vasc ular e ve nts, utilizi n g t he isc hae mic ce ntral ner v o us sys te m vasc ular 
c o n diti o ns S M Q
F or t he d o u ble -bli n d p hase, t he n u m ber of s u bjects wit h T E A EI s a n d S A E s, t he c orres p o n di n g 
P Y E, t he calc ulate d E AI R, a n d t he e xact 9 5 % CI s ( defi ne d i n Secti o n 8. 1. 5. 3 ) will be 
s u m marize d f or eac h treat me nt gr o u p b y P T. T he E AIR differe nce ( F il g oti ni b 2 0 0 m g – Place b o) 
a n d c orres p o n di n g 9 5 % CIs f or t he differe nce bet wee n treat ment gr o u ps (s pecifie d i n 
secti o n 8. 1. 5. 3 ) will als o be prese nte d f or t he d o u ble-bli n d p hase of t he st u d y . 


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F or t he o verall st u d y , t he n u m ber of s u bjects wit h T E A EIs a n d S A E s, t he c orres p o n di n g P Y E, 
t he calc ulate d E AI R, a n d t he e xact 9 5 % CIs ( defi ne d i n Secti o n 8. 1. 5. 3 ) will be s u m marize d f or 
eac h treat me nt (fil g oti ni b a n d place b o) b y  P T f or eac h A EI cate g or y a n d se parately f or S A Es. 
Fil g oti ni b gr o u p will i ncl u de fil g oti ni b t o o pe n -la bel fil g oti ni b treat me nt se q ue nce pl us t he 
fil g oti ni b e x p os ure f or fil g oti ni b t o S O C treat me nt se q ue nce a n d t h ose ra n d o mize d t o fil g oti ni b 
w h o di d n ot c o nti n ue t o e xte nsi o n p hase . Place b o will i ncl u de t he p lace b o t o S O C treat me nt 
se q ue nce a n d t h ose ra n d o mize d t o place b o w h o di d n ot c o nti n ue t o e xte nsi o n p hase.
Data listi n gs f or eac h A EI will als o be pr o vi de d.
8. 1. 7. 1.
Car di o vasc ular E ve nt A dj u dicati o n C o m mittee
A n i n de pe n de nt car di o vasc ular e ve nt a dj u dicati o n c o m mittee ( C V E A C) re vie w s a n d a dj u dicates
all p ote ntial 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 o i de ntif y  p ote ntial 
M A C E a n d t hr o m b oe m b olic e ve nts, t he f oll o wi n g A Es will be se nt f or a dj u dicati o n. Please refer 
t o t he Car di o vasc ular E ve nt A dj u dicati o n C o m mittee C harter f or m ore details.

All A Es lea di n g t o deat h

C V e ve nts ( meeti n g seri o us criteria), utilizi n g a M S T list de vel o pe d b y  Gilea d

MI , utilizi n g a narr o w sc o pe Sta n dar dize d Me d D R A Q uer y ( S M Q) 

U nsta ble a n gi na ( meeti n g h os pitalizati o n criteria), utilizi n g a M S T list de vel o pe d b y  Gilea d

Tra nsie nt isc he mic attac k, utilizi n g a M S T list de vel o pe d b y Gilea d

Str o ke, utilizi n g a M S T list de vel o pe d b y  Gilea d

Ca r diac fail ure ( meeti n g h os pitalizati o n criteria), utilizi n g a M S T list de vel o pe d b y Gilea d

Perc uta ne o us c or o nar y  i nter ve nti o n, utilizi n g a M S T list de vel o pe d b y Gilea d

E m b olic a n d t hr o m b otic e ve nts, utilizi n g a narr o w sc o pe S M Q  
T he C V E A C will re vie w t he a b o ve A Es, a n d relate d cli nical data t o a dj u dicate w het her t he 
criteria f or M A C E ( C V deat h, MI, a n d/ or str o ke), A S T E, a n d V T E ha ve bee n met f or eac h A E. 
T he n u m ber a n d perce nta ge of s u bjects wit h p ositi vel y  a dj u dicate d T E M A C E, T E A S T E, a n d 
T E V T E will be s u m marize d b y treat me nt gr o u p usi n g t he a dj u dicate d cate g or y if a p plica ble f or 
t he fi nal a nalys is of t he st u d y o nl y.
A b y -s u bject listi n g f or s u bjects wit h p ote ntial e ve nts f or a dj u dicati o n ( M A C E, A S T E, a n d V T E) 
a n d w het her t he e ve nt was p ositi vel y  a dj u dicate d b y C V E A C will be pr o vi de d f or eac h i nteri m 
a nal ys is a n d f or t he fi nal a nalys is of t he st u d y.
A b y -s u bject listi n g of t hr o m b oe m b olic hist or y a n d ris k fact ors will be pr o vi de d f or s u bjects wit h 
p ote ntial e ve nts f or a dj u dicati o n ( M A C E, A S T E, a n d V T E), if a p plica ble.


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8. 2.
L a b or at or y E v al u ati o ns
La b orat or y  data c ollecte d d uri n g t he st u d y will be a nalyz e d a n d s u m marize d usi n g b ot h 
q ua ntitati ve a n d q ualitati ve met h o ds. S u m maries of la b orat or y  data d uri n g t he d o u ble -bli n d 
p hase of t he st u d y will be pr o vi de d b y  d ou ble -bli n d treat me nt gr o u p f or t he Safet y A nal ys is Set. 
S u m maries of la b orat or y  data d uri n g t he e xte nsi o n p hase of t he st u d y will be pr o vi de d by 
treat me nt se q ue nce f or t he E xte nsi o n P hase Safet y A nal ysis Set.
A nal y sis will be base d o n val ues re p orte d i n c on ve nti o nal u nits. W he n val ues are bel o w t he 
L O Q, t he y  will be liste d as s uc h, a n d t he cl osest i m p ute d val ue will be use d f or t he p ur p ose of 
calc ulati n g s u m mar y statistics as s pecifie d i n Secti o n 3. 7 . He m olize d test res ults will n ot be 
i ncl u de d i n t he a nalys is, b ut t he y will be liste d i n b y-s u bject la b orat or y listi n gs.  
A b y -s u bject listi n g f or la b orat or y test res ults will be pr o vi de d b y s u bject I D n u m ber a n d ti me 
p oi nt i n c hr o n ol o gical or der f or he mat ol o g y , ser u m c he mistr y, a n d uri nalysis se paratel y. Val ues 
falli n g o utsi de of t he rele va nt refere nce ra n ge a n d/ or ha vi n g a se verit y gra de of 1 or hi g her base d 
o n C T C A E criteria will be fla g ge d i n t he data listi n gs, as a p pr o priate.
N o f or mal statistical testi n g is pla n ne d.
8. 2. 1. 
S u m m aries of N u meric L a b or at or y Res ults
Descri pti ve statistics will be pr o vi de d b y treat me nt ( d o u ble- bli n d treat me nt gr o u p f or 
d o u ble -bli n d p hase a n d b y  treat me nt se q ue nce of e xte nsi o n p hase) f or selecte d la b orat or y tests as 
f oll o ws:

Baseli ne val ues 

Val ues at eac h p ost baseli ne ti me p oi nt

C ha n ge fr o m baseli ne at eac h p ost baseli ne ti me p oi nt
A baseli ne la b orat or y  val ue will be defi ne d as t he last meas ure me nt o btai ne d o n or pri or t o t he 
date of first d ose of d o u ble -bli n d st u d y dr u g. C ha n ge fr o m baseli ne t o a p ost baseli ne visit will be 
defi ne d as t he visit val ue mi n us t he baseli ne val ue. T he mea n, me dia n, Q 1, Q 3, mi ni m u m, a n d 
ma xi m u m val ues will be dis pla y e d t o t he re p orte d n u m ber of di gits; S D val ues will be d is pla ye d 
t o t he re p orte d n u m ber of di gits pl us 1.
Me dia n ( Q 1, Q 3)
c ha n ge fr o m baseli ne at eac h ti me p oi nt f or selecte d la b orat or y tests w ill be 
pl otte d usi n g a li ne pl ot b y treat me nt ( d o u ble-bli n d treat me nt f or d o u ble -bli n d p hase a n d 
treat me nt se q ue nce f or e xte nsi o n p hase) a n d ti me p oi nt.
I n t he case of m ulti ple val ues i n a n a nalys is wi n d o w, data will be selecte d f or a nalys is as 
descri be d i n Secti o n 3. 7. 3 .


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8. 2. 2.  
Gr a de d L a b or at or y V al ues
T he C T C A E versi o n 4. 0 3 will be use d t o assi g n t o xicit y gra des ( 0 t o 4) t o la b orat or y res ults f or 
a nal ys is. Gra de 0 i ncl u des all val ues t hat d o n ot meet t he criteria f or a n a b n or malit y of at least 
Gra de 1. F or la b orat or y tests wit h criteria f or b ot h i ncrease d a n d decrease d le vels , a nal ys es f or 
eac h directi o n (ie, i ncrease d, decrease d) will be prese nte d se paratel y. 
8. 2. 2. 1.
Treat me nt -E mer ge nt La b orat or y  A b n or malities
Treat me nt -e mer ge nt la b orat or y a b n or malities d uri n g t h e d o u ble -bli n d p hase are defi ne d as 
val ues t hat i ncrease at least 1 t o xicit y gra de fr o m baseli ne at a n y p ost baseli ne ti me p oi nt, u p t o 
t he first d ose date of o pe n-la bel fil g oti ni b/first date i n e xte nsi o n p hase (if n o n-missi n g) or t o t he 
date of last d ose o f d o u ble -bli n d st u d y dr u g pl us 3 0 da ys f or s u bjects w h o per ma ne ntly 
disc o nti n ue d d o u ble -bli n d st u d y dr u g (a n d di d n ot c o nti n ue t o e xte nsi o n p hase).
Treat me nt -e mer ge nt la b orat or y a b n or malities d uri n g t he e xte nsi o n p hase are defi ne d as val ues 
t hat i ncrease at least 1 t o xicit y gra de fr o m baseli ne at a n y p ost baseli ne ti me p oi nt after first d ose 
date of o pe n -la bel fil g oti ni b/first date i n e xte nsi o n p hase t o last d ose date of o pe n-la bel 
fil g oti ni b/sta n dar d of care i n e xte nsi o n pl us 3 0 da ys or t o t he last a vaila ble date i n t he data base 
s na ps h ot f or s u bjects w h o were o n e xte nsi o n p hase treat me nt at t he ti me of a n i nteri m a nalys is. 
If t he rele va nt baseli ne la b orat or y val ue is missi n g, a n y a b n or mality of at least Gra de 1 o bser ve d 
wit hi n t he ti me fra me s pecifie d a b o ve will be c o nsi dere d treat me nt e mer ge nt.
8. 2. 2. 2.
Treat me nt -E mer ge nt Mar ke d La b orat or y  A b n or malities
Treat me nt -e mer ge nt mar ke d la b orat or y  a b n or malities d uri n g t he d o u ble -bli n d p hase are defi ne d 
as val ues t hat i ncrease fr o m baseli ne b y  at least 3 t o xicit y gra des at an y  p ost baseli ne ti me p oi nt, 
d uri n g d o u ble -bli n d p hase . Treat me nt -e mer ge nt mar ke d la b orat or y  a b n or malities d uri n g t he 
e xte nsi o n p hase are defi ne d as val ues t hat i ncrease fr o m baseli ne b y at least 3 t o xicit y  gra des at 
a n y p ost baseli ne ti me p oi nt d uri n g e xte nsi o n p hase.
If t he rele va nt baseli ne la b orat or y val ue is missi n g, a n y Gra de 3 or 4 val ues o bser ve d wit hi n t he 
ti mefra me s pecifie d a b o ve will be c o nsi dere d treat me nt-e mer ge nt mar ke d a b n or malities.
8. 2. 2. 3.
S u m maries of La b orat or y  A b n or malities
T he f oll o wi n g s u m maries ( n u m ber a n d perce nta ge of s u bjects) f or treat me nt -e mer ge nt la b orat or y 
a b n or malities will be pr o vi de d b y  la b test a n d treat me nt ( d o u ble-bli n d treat me nt f or d o u ble -bli n d 
p hase; treat me nt se q ue nce f or e xte nsi o n p hase) . Su bjects will be cate g orize d acc o r di n g t o t he 
m ost se vere p ost baseli ne a b n or malit y  gra de f or a gi ve n la b test:

Gra de d la b orat or y a b n or malities (f or t he fi nal a nal ysis of t he st u d y o nl y)

Gra de 3 or 4 la b orat or y a b n or malities

Mar ke d la b orat or y  a b n or malities


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F or all d o u ble -bli n d p hase s u m maries of la b orat or y a b n or malities, t he de n o mi nat or is t he n u m ber 
of s u bjects wit h ≥1 n o n missi n g p ost baseli ne val ue d uri n g t he d o u ble- bli n d p hase . F or t he 
e xte nsi o n p hase t he de n o mi nat or is t he n u m ber of s u bjects wit h ≥1 n o n missi n g p ost baseli ne 
val ue d uri n g t he e xte nsi o n p hase.
A b y -s u bject listi n g of treat me nt-e mer ge nt Gra de 3 or 4 la b orat or y a b n or malities will be 
pr o vi de d b y s u bject I D n u m ber a n d ti me p oi nt i n c hr o n ol o gical or der. T his listi n g will i ncl u de all 
test res ults t hat were c ollecte d t hr o u g h o ut t he st u d y f or t he la b test of i nterest, wit h all a p plica ble 
se verity gra de s dis pla y e d .
8. 2. 3.
Li ver -rel ate d L a b or at or y E v al u ati o ns
Li ver -relate d a b n or malities will be e xa mi ne d a n d s u m marize d ( b y d o u ble- bli n d treat ment d uri n g 
d o u ble -bli n d p hase; b y  treat me nt se q ue nce d uri n g e xte nsi o n p hase) usi n g t he n u m ber a n d 
perce nta ge of s u bjects wit h ≥1 val ue i n t he re p orti n g peri o d f or t he f oll o wi n g:

A S T: (a) > 3 ti mes t he u p per li mit of n or mal ra n ge ( U L N); ( b) > 5 x U LN; (c) > 1 0 x U L N; 
( d) > 2 0 x U L N

A L T: (a) > 3 x U L N; ( b) > 5 x U L N; (c) > 1 0 x U L N; ( d) > 2 0 x U L N

(A S T or A L T > 3 x U L N ) a n d (t otal bilir u bi n > 2 x U L N)
F or i n di vi d ual la b orat or y tests, s u bjects will be c o u nte d o nce base d o n t he ir m ost se vere
p ost baseli ne val ue d uri n g t he d o u ble -bli n d p hase f or d o u ble -bli n d p hase s u m maries a n d m ost 
se vere p ost baseli ne val ue d uri n g t he e xte nsi o n p hase f or e xte nsi o n p hase s u m maries. F or t he
c o m p osite e n d p oi nt of A S T or A L T a n d t otal bilir u bi n, s u bjects will be c o u nte d o nce w he n t h e 
criteria are met at t he sa me p ost baseli ne visit date. T he de n o mi nat or is t he n u m ber of s u bjects i n 
t he Safety A nal ys is Set w h o ha ve ≥1 n o n missi n g p ost baseli ne val ue of all rele va nt tests at t he 
sa me p ost baseli ne visit date f or visits d uri n g d o u ble-bli n d p hase; a n d t he n u m ber of s u bjects wit h 
≥ 1 n o n missi n g p ost baseli ne val ue of all rele va nt tests at t he sa me p ost baseli ne visit date f or 
visits d uri n g t he e xte nsi o n p hase f or t he E xte nsi o n P hase Safet y A nal ys is Set.
A listi n g of s u bjects w h o met at least 1 of t he a b o ve criteria will be pr o vi de d.
8. 3.
B o d y Wei g ht a n d Vit al Si g ns
Descri pti ve statistics will be pr o vi de d b y treat me nt ( d o u ble-bli n d treat me nt f or d o u ble -bli n d 
p hase; treat me nt se q ue nce f or e xte nsi o n p hase) f or b o d y wei g ht, B MI a n d vital si g ns
( p ulse, sys t olic a n d diast olic bl o o d press ure, res pirati o n rate, a n d te m perat ure) as f oll o ws:

Baseli ne val ue

Val ues at eac h p ost baseli ne ti me p oi nt

C ha n ge fr o m baseli ne at eac h p ost baseli ne ti me p oi nt


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A baseli ne val ue will be defi ne d as t he last a vaila ble val ue c ol lecte d o n or pri or t o t he date of 
first d ose of st u d y dr u g. C ha n ge fr o m baseli ne t o a p ost baseli ne visit will be defi ne d as t he 
p ost baseli ne val ue mi n us t he baseli ne val ue.
I n t he case of m ulti ple val ues i n a n a nalys is wi n d o w, data will be selecte d f or a nal ysis as 
descri be d i n Secti o n 3. 7. 3 . N o f or mal statistical testi n g is pla n ne d.
A b y -s u bject listi n g of vital si g ns will be pr o vi de d b y s u bject I D n u m ber a n d ti me p oi nt i n 
c hr o n ol o gical or der. B o d y  wei g ht , hei g ht, a n d B MI will b e i ncl u de d i n t he vital si g ns listi n g, if 
s pace per mits. If n ot, t he y will be pr o vi de d se paratel y .
8. 4.
Pri or a n d C o nc o mit a nt Me dic ati o ns
Me dicati o ns c ollecte d at s cree ni n g a n d d uri n g t he st u d y  will be c o de d usi n g t he c urre nt versi o n 
of t he W H O Dr u g dicti o nar y .
8. 4. 1. 
Pri or Me dic ati o ns
Pri or me dicati o ns are defi ne d as a n y me dicati o n s ta ke n bef ore a s u bject t o o k t heir first d ose of 
st u d y dr u g.
If a partial start date is e ntere d, t he me dicati o n will be c o nsi dere d pri or u nless t he m o nt h a n d 
ye ar (if da y is missi n g) or year (if da y a n d m o nt h are missi n g) of t he start date are after t he 
first d osi n g/start date i n t he rele va nt p hase of t he st u d y. Me dicati o ns wit h a c o m pletel y missi n g 
start date will be ass u me d t o be a pri or me dica ti o n, u nless ot her wise s pecifie d.
Pri or me dicati o ns will be liste d as part of t he Pri or a n d C o nc o mita nt Me dicati o ns listi n g.
8. 4. 2.
C o nc o mit a nt Me dic ati o ns
C o nc o mita nt me dicati o ns are defi ne d as me dicati o ns ta ke n w hile a s u bject is als o ta ki n g st u d y 
dr u g. Use of c o nc o mita nt medicati o ns will be s u m marize d b y  A T C preferre d na me usi n g t he 
n u m ber a n d perce nta ge of s u bjects f or eac h treat me nt gr o u p. A s u bject re p orti n g t he sa me 
me dicati o n m ore t ha n o nce will be c o u nte d o nl y o nce w he n calc ulati n g t he n u m ber a n d 
perce nta ge of s u bjects w h o recei ve d t hat me dicati o n. T he s u m mar y will be pr o vi de d b y preferre d 
ter m i n desce n di n g o verall fre q ue nc y. F or dr u gs wit h t he sa me fre q ue nc y, s orti n g will be d o ne 
al p ha beticall y.
F or t he p ur p oses of a nal ysis, a n y me dicati o n s wit h a start date pri or t o or o n t he first d osi n g date 
of st u d y dr u g t hat are c o nti n ue d after t he first d osi n g date or starte d after t he first d osi n g date b ut 
pri or t o or o n t he last d osi n g date of st u d y dr u g will be c o nsi dere d c o nc o mita nt me dicati o ns. 
Me dicati o ns starte d a n d st o p pe d o n t he sa me da y  as t he first d osin g date or t he last d osi n g date of 
st u d y dr u g will als o be c o nsi dere d c o nc o mita nt. Me dicati o ns wit h a st o p date pri or t o t he date of 
first d osi n g date of st u d y dr u g or a start date after t he last d osi n g date of st u d y dr u g will be 
e xcl u de d fr o m t he c o nc o mit a nt me dicati o n s u m mar y. If a partial st o p date is e ntere d, a ny 
me dicati o n wit h t he m o nt h a n d y ear (if da y is missi n g) or ye ar (if da y a n d m o nt h are missi n g) 


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pri or t o t he date of first st u d y  dr u g a d mi nistrati o n will be e xcl u de d fr o m t he c o nc o mita nt 
me dicati o n s u m mar y . If a partial start date is e ntere d, a ny me dicati o n wit h t he m o nt h a n d year 
(if d a y  is missi n g) or ye ar (if da y a n d m o nt h are missi n g) after t he st u d y dr u g st o p date will be 
e xcl u de d fr o m t he c o nc o mita nt me dicati o n s u m mar y . Me dicati o ns wit h c o m pletel y missi n g start 
a n d st o p dates will be i ncl u de d i n t he c o nc o mita nt me dicati o n s u m mar y , u nless ot her wise 
s pecifie d (ie, t he me dicati o n is s pecificall y mar ke d as a pri or me dicati o n o n t he e C R F).
S u m maries d uri n g t he d o u ble- bli n d p hase will be b y  d o u ble- bli n d treat me nt gr o u p f or s u bjects i n 
t he Safet y A nal ys is Set. S u m maries d uri n g t he e xte nsi o n p hase will be b y treat me nt se q ue nce f or 
s u bjects i n t he E xte nsi o n P hase Safet y A nal ys is Set. 
N o f or mal statistical testi n g is pla n ne d.
All pri or a n d c o nc o mita nt me dicati o ns ( ot her t ha n per -pr ot oc ol st u d y  dr u gs) will be pr o vi de d i n a 
b y -s u bject listi n g s orte d b y  s u bject I D n u m ber a n d a d mi nistrati o n date i n c hr o n ol o gical or der.
8. 5.
Electr oc ar di o gr a m ( E C G) Res ults
A s hift ta ble of t he i n vesti gat or’s assess me nt of E C G res ults at baseli ne vers us Wee k 1 3 or 
E arl y T er mi nati o n fr o m d o u ble-bli n d p hase will be prese nte d b y d o u ble -bli n d treat me nt gr o u p 
f or t he Safety A nal ys is Set. T he s hift ta bles of E C G res ults f or baseli ne vs. E xte nsi o n Wee k 1 5 6
or Earl y Ter mi nati o n will be prese nte d f or s u bjects i n t he fil g oti ni b 2 0 0 m g t o o pe n-la bel 
fil g oti ni b 2 0 0 m g gr o u p f or t he E xte nsi o n P hase Safety A nal ys is Set.
T he i n vesti gat or will rate t he E C G base d o n t he f oll o wi n g cate g ories: n or mal; a b n or mal 
( n ot cli nicall y si g nifica nt); a b n or mal (cli nicall y si g nifica nt); or missi n g. Baseli ne val ues will be 
E C Gs c ollecte d wit h a n o mi nal visit of “ Scree ni n g”; Wee k 1 3 will i ncl u de n o mi nal visits of 
“ Wee k 1 3” or “ E arl y Ter mi nati o n ” if earl y ter me d fr o m d o u ble-bli n d p hase ; a n d Wee k 1 5 6/early 
ter mi nati o n will ha ve n o mi nal visits of “ E xte nsi o n Wee k 1 5 6” or “ Earl y Ter mi nati o n ” if early 
ter mi nate d fr o m e xte nsi o n p hase a n d ta ki n g o pe n -la bel fil g oti ni b.
T he n u m ber a n d perce nta ge of s u bjects i n eac h cr oss -classificati o n gr o u p of t he s hift ta ble will 
be prese nte d. S u bjects wit h a missi n g val ue at baseli ne or p ost baseli ne will n ot be i ncl u de d i n t he 
de n o mi nat or f or t he perce nta ge calc ulati o n. N o f or mal statistical testi n g is pla n ne d.
A b y -s u bject listi n g f or E C G assess me nt res ults will be pr o vi de d b y  s u bject I D n u m ber a n d visit 
i n c hr o n ol o gical or der.


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9.
P H A R M A C O KI N E TI C A N A L Y S E S
C o nce ntrati o ns of fil g oti ni b a n d G S -8 2 9 8 4 5 i n plas ma will be deter mi ne d usi n g vali date d 
bi oa nal y tical met h o ds. T he P K a nalys is will be co n d ucte d o n t he P K A nal ysis Set, defi ne d i n 
Secti o n 3. 1. 4 .
I n di vi d ual s u bject c o nce ntrati o n data f or fil g oti ni b a n d G S-8 2 9 8 4 5 will be liste d (i ncl u di n g date 
a n d ti me of last fil g oti ni b st u d y  dr u g a d mi nistrati o n; P K c ollecti o n date a n d ti me; a n d ti me 
p ost -d ose t hat t he P K sa m ple was c ollecte d).


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1 0.
R E F E R E N C E S
B ottai M, Z he n H. M ulti ple i m p utati o n base d o n c o n diti o nal q ua ntile esti mati o n. E pi de mi ol o g y  
Bi ostatistics a n d P u blic Healt h 2 0 1 3; 1 0 ( 1).
C o o per T G, N o o na n E, v o n Ec kar dstei n S, A u ger J, Ba ker H W, Be hre H M, et al. W orl d Healt h 
Or ga nizati o n refere nce val ues f or h u ma n se me n c haracteristics. H u ma n 
re pr o d ucti o n u p date 2 0 1 0; 1 6 ( 3): 2 3 1- 4 5.
Jar vi K, D ula E, Dre h o bl M, Pr yor J, S ha pir o J, Se ger M. Dail y  var de nafil 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 vels. J Ur ol 2 0 0 8; 1 7 9 ( 3): 1 0 6 0 - 5.
K oc h G G, Carr GJ, A m ara I A, St o kes M E, Ur ynia k TJ. Cate g orical Data A nal y sis. C ha pter 1 3 i n 
Berr y , D. A. (e d.).  Statistical Met h o d ol o g y i n t he P har mace utical Scie nces. Ne w 
Y or k: Marcel De k ker, I nc., 1 9 8 9: p p. 4 1 4 - 2 1. 
Li H Q, Ta n g M L, P o o n W Y, Ta n g N S. C o nfi de nce I nter vals f or Differe nce Bet wee n T w o 
P oiss o n Rates. C o m m u nicati o ns i n Statistics - Si m ulati o n a n d C o m p utati o n 
2 0 1 1; 4 0 ( 9): 1 4 7 8 - 9 3.
R u bi n D B. M ulti ple I m p utati o n f or N o nres p o nse i n S ur ve y s. Ne w Y or k, N Y: J o h n Wile y & 
S o ns, I nc; 1 9 8 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 nistrati 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.
Ul m K. A si m ple met h o d t o calc ulate t he c o nfi de nce i nter val of a sta n dar dize d m ortalit y  rati o 
( S M R). A m J E pi de mi ol 1 9 9 0; 1 3 1 ( 2): 3 7 3- 5.
W orl d Healt h Or ga nizati o n ( W H O). W H O La b orat or y  ma n ual f or t he e xa mi nati o n of h u ma n 
se me n a n d s per m-cer vical m uc us i nteracti o n. T hir d E diti o n.  1 9 9 2.
W orl d Healt h Or ga nizati o n ( W H O). W H O L a b orat or y ma n ual f or t he E xa mi nati o n a n d 
pr ocessi n g of h u ma n se me n. Fift h E diti o n.  2 0 1 0.


Fil g oti ni b
G L P G 0 6 3 4 -C L -2 2 7
Statistical A nal ysis Pla n
Versi o n 1. 0
C O N FI D E N TI A L
Pa ge 6 3
1 2 Ja n uar y 2 0 2 1
1 1.
S O F T WA R E
S A S ® S oft ware Versi o n 9. 4 . S A S Instit ute I nc., Car y , N C, U S A.
n Q uer y  A d vis or( R) Versi o n 4 . 0. Statistical S ol uti o ns, C or k, Irela n d.


Fil g oti ni b
G L P G 0 6 3 4 -C L -2 2 7
Statistical A nal ysis Pla n
Versi o n 1. 0
C O N FI D E N TI A L
Pa ge 6 4
1 2 Ja n uar y 2 0 2 1
1 2.
S A P  R E VI SI O N
Re visi o n D ate
(D D M M M Y Y Y Y )
Secti o n
S u m m ar y of Re visi o n
Re as o n f or Re visi o n


Fil g oti ni b
G L P G 0 6 3 4 -C L -2 2 7
Statistical A nal ysis Pla n
Versi o n 1. 0
C O N FI D E N TI A L
Pa ge 6 5
1 2 Ja n uar y 2 0 2 1
1 3.
A P P E N DI C E S
A p pe n di x 1.
St u d y Pr oce d ures Ta ble – D o u ble -bli n d Treat me nt P hase
A p pe n di x 2.
Calc ulati o n o f t he Differe nce i n Pr o p orti o ns a n d 9 5 % CI ( Strat u m-A dj uste d Ma ntel -
Hae nszel Pr o p orti o ns)


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


Fil g oti ni b
G L P G 0 6 3 4 -C L -2 2 7
Statistical A nal ysis Pla n 
Versi o n 1. 0
C O N FI D E N TI A L
Pa ge 6 7
1 2 Ja n uar y 2 0 2 1
E V E N T
Scree ni n g
E T b
S afet y f oll o w -u p c
St u d y d a ys ( D)/ wee ks ( W) a
D a y 1
W 2
( ± 5 d a ys)
W 4
( ± 5 d a ys)
W 8
( ± 5 d a ys)
W 1 3 * *
( + 5 d a ys)
3 0 D a ys after l ast 
d ose of st u d y dr u g 
( ± 5 d a ys)
S w olle n J oi nt C o u nt 6 6 ( SJ C 6 6) 
(f or Ps A s u bjects o nl y)
X
Patie nt Gl o bal Assess me nt of 
Disease Acti vit y ( Pt G A D A)
(f or R A a n d Ps A s u bjects o nl y)
X
P h y sicia n’s Gl o bal Assess me nt 
of Disease Acti vit y ( P h G A D A) d
(f or all s u bjects)
X
X
X
Patie nt’s Gl o bal Assess me nt of 
Pai n I nte nsit y ( P Pai n) (f or Ps A 
s u bjects o nl y)
X
Bat h A n k yl osi n g 
S p o n d yl oart hritis Disease 
Acti vit y I n de x ( B A S D AI) 
(f or A S/ nr A x S p A s u bjects o nl y)
X
T B ( Q ua ntifer o n ® ) Teste
X
C hest X -r a yf
X
Uri nal ysis g
X
X
X  
X
X
Uri ne dr u g scree n g
X
H e m at ol o g y a n d Ser u m 
C he mistr y g
X
X
X
X
X
X  
X
X
Li pi d pr ofile (fasti n g) ( T otal 
c h olester ol a n d s u bfracti o ns) g
X
X
Ser u m hs C R P
X
X
X
X
X
X
E n d ocri ne: T S H, H b A 1c g
X


Fil g oti ni b
G L P G 0 6 3 4 -C L -2 2 7
Statistical A nal ysis Pla n 
Versi o n 1. 0
C O N FI D E N TI A L
Pa ge 6 8
1 2 Ja n uar y 2 0 2 1
E V E N T
Scree ni n g
E T b
S afet y f oll o w -u p c
St u d y d a ys ( D)/ wee ks ( W) a
D a y 1
W 2
( ± 5 d a ys)
W 4
( ± 5 d a ys)
W 8
( ± 5 d a ys)
W 1 3 * *
( + 5 d a ys)
3 0 D a ys after l ast 
d ose of st u d y dr u g 
( ± 5 d a ys)
L H, F S H, i n hi bi n B, t otal 
Test oster o ne c ollecti o n ti me 
bet w ee n 0 7: 0 0 -1 1: 0 0 i n t he 
m o r ni n gg
X
X
X
X  
X
X
P K c ollecti o n (s parse) h
X
X
X
C o nc o mita nt Me dicati o ns
X
X
X
X
X
X  
X
X
Assess me nt of A d verse E ve nts
X
X
X
X
X
X  
X
X
Se m e n C ollecti o n 
( 2 sa m ples as per c ollecti o n 
i nstr ucti o ns i n Pr ot oc ol Secti o n 
6. 1 1) i
X
X  
X j
Date a n d ti me of m ost rece nt 
ejac ulati o n k
X
X  
X
HI V, He patitis B, a n d 
He patitis C l
X
H B V D N A l, m
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
St u d y Dr u g Dis pe nsati o n n
X
X
X
X o
I n-cli nic D osi n g n
X
X
X


Fil g oti ni b
G L P G 0 6 3 4 -C L -2 2 7
Statistical A nal ysis Pla n 
Versi o n 1. 0
C O N FI D E N TI A L
Pa ge 6 9
1 2 Ja n uar y 2 0 2 1
a
Visits c orrelate wit h t he n u m ber of da ys/ wee ks o n dr u g.
b
A n y ti me a s u bject disc o nti n ues partici pati o n i n t he st u d y pri or t o Wee k 1 3 a n Earl y Ter mi nati o n ( E T) Visit is re q uire d. S u bjects w h o are Res p o n ders at Wee k 1 3 a n d c h o ose 
n ot t o c o nti n ue i n t he E xte nsi o n P hase are als o re q uire d t o c o m plete E T visit assess me nts.
c
All s u bjects will ha ve a 3 0 -da y safet y f oll o w -u p visit after disc o nti n ui n g bli n de d st u d y dr u g, e xce pt Art hritis Res p o n ders at Wee k 1 3 w h o are c o nti n ui n g i n t he E xte nsi o n 
P hase of t he st u d y.
c  
As detaile d i n Pr ot oc ol A p pe n di x 1 1
d 
F or defi niti o ns of Art hritis Res p o n der/ N o n- res p o n der stat us please refer t o pr ot oc ol Defi niti o n of Ter ms.
e
Pr o of of n o acti ve or u ntreate d late nt t u berc ul osis ( T B) at Scree ni n g. S u bjects w h o are dia g n ose d wit h late nt T B at Scree ni n g m ust i nitiate a n a de q uate c o urse of pr o p h yla xis 
as per l ocal sta n dar d of care 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 ultati o n wit h t he S p o ns or Me dical 
Lea der or desi g nee.
f
C hest x -ra y ( 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 ort or fil ms a vaila ble f or i n vesti gat or re vie w) wit h o ut 
e vi de nce of acti ve or late nt T B i nfecti o n.
g
As detaile d i n Pr ot oc ol A p pe n di x 1 1. F or visits t hat r e 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 he visit.
h
S parse plas ma p har mac o ki netic ( P K) sa m ples at Wee k 2 are c ollecte d at 3 0 mi n utes p ost d ose. T he P K sa m ple at Wee k 4 ca n be c ollecte d at a n y t i me wit h o ut re gar d t o 
d osi n g. T he P K sa m ple at Wee k 1 3 is c ollecte d pri or t o st u d y dr u g a d mi nistrati o n. Please refer t o pr ot oc ol Secti o n 6. 1 4 f or d etails o n st u d y dr u g a d mi nistrati o n. 
i 
T he Scree ni n g se me n sa m ple c ollecti o n s h o ul d c oi nci de wit h t he Da y 1 ( Baseli ne) visit as m uc h as p ossi ble. Se me n sa m ples will be c ollecte d o n t he visit da y a n d/ or as s o o n 
as p ossi ble after t he visit da y. 
j
Se me n c ollecti o n will be c o m plete d at E T visit o nl y if pre vi o us se me n sa m ples were n ot c ollecte d wit hi n 2 wee ks of E T.
k
T his q uesti o n will be as ke d pri or t o eac h se me n c ollecti o n.
l
A n HI V -1/ HI V -2 a nti ge n/a nti b o d y test, a He patitis C vir us a nti b o d y test, a He patitis B s urface a nti ge n, a He patitis B s urface a nti b o d y a n d a He patitis c ore a nti b o d y test will 
be c o n d ucte d o n all s u 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 he st u dy . S u bjects wit h p ositi ve H B V c ore A b a n d 
ne gati ve H Bs A g, re q uire refle x testi n g f or H B V D N A. S u bjects wit h p ositi ve H B V D N A at Scree ni n g will b e 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 per i n vesti gat or j u d g me nt b ut ma y re q uire pr o p h ylactic treat me nt i n acc or da nce wit h H B V treat me nt g ui deli 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 t ests 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 ve 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 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. 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 gat or j u d g me nt.
m 
S u bjects wit h p ositi ve H B V c ore A b a n d ne gati ve H B V D N A at Scree ni n g re q 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.
n
T he s u bject will ta ke t he first d ose ( Da y 1) i n t he cli nical st u d y ce nter. F or P K c ollecti o n p ur p oses, at Wee ks 2 a n d 1 3, s u bjects s h o ul d be i nstr ucte d n ot t o ta ke t he ir 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 he cli nic. S u bjects will be i nstr ucte d t o ta ke t heir d ose d uri n g t heir sc he d ule d visit, as detaile d i n pr ot oc ol Secti o n 6. 1 4.
o  
O nl y f or s u bjects c o nti n ui n g o n o pe n- la bel fil g oti ni b i n t he E xte nsi o n P hase.
* * Wee k 1 3 visit m ust occ ur after 1 3 wee ks of dr u g e x p os ure. T heref ore, visit wi n d o w f or t his visit is + 5 da ys. T he e n d of t he D o u ble - Bli n d Treat me nt P hase is w he n t he Wee k 1 3 
se me n res ults are a vaila ble t o t he i n vesti gat or a n d ha ve bee n e val uate d. Base d o n t his e valuati o n, s u bjects are assi g ne d t o e nter t he M o nit ori n g P hase or t he E xte nsi o n P hase.


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


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


Fil g oti ni b
G L P G 0 6 3 4 -C L -2 2 7
Statistical A nal ysis Pla n 
Versi o n 1. 0
C O N FI D E N TI A L
Pa ge 7 2
1 2 Ja n uar y 2 0 2 1
a 
S u bjects i n t he E xte nsi o n P hase ( E P) will c o m plete E P Wee k 2 6 visit a n d e ver y 1 3 wee ks t hereafter u p t o 1 5 6 wee ks.
b
A n y ti me a s u bject disc o nti n ues partici pati o n i n t he st u d y pri or t o Wee k 1 5 6 i n t he E xte nsi o n P hase, a n Earl y Ter mi nati o n ( E T ) Visit is re q uire d.
c
I n t he E P s u bjects m ust ha ve yearl 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 he scree ni n g T B test date. If yearl y T B testi n g falls bet wee n st u d y visits, t he 
yearl y T B testi n g s h o ul d be perf or me d at t he visit pri or t o 1 year fr o m t he scree ni n g T B test date. S u bjects wit h ne wl y p osit i ve (c o n verte d) Q ua nti F ER 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 uate c o urse of t hera p y as 
per l ocal Sta n dar d of Care a n d as verifie d b y t he i n vesti gat or d o n o t nee d t o ha ve yearl y Q ua nti F E R O N ® tests. S u bjects pre vi o usl y treate d f or T B s h o ul d be scree ne d at least 
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. 
d
As detaile d i n pr ot o c ol A p pe n di x 1 2. 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 he visit.
e
Li pi d pr ofile s h o ul d be perf or me d at Wee ks 2 6, 3 9, 6 5, 9 1, 1 1 7 a n d 1 4 3.
f
T his q uesti o n will be as ke d pri or t o se me n c ollecti o n n ot at t he site visit.
g
O nl y a p plica ble f or s u bjects o n fil g oti ni b. 
h 
E C G will be perf or me d at Wee k 1 5 6 or E T (f or s u bjects o n o pe n- la bel fil g oti ni b o nl y). 
i
A s parse plas ma P K sa m ple is c ollecte d at Wee k 2 6 pri or t o st u d y dr u g a d mi nistrati o n (f or s u bjects o n o pe n la bel fil g oti ni b o nl y). Please refer t o pr ot oc ol Secti o n 6. 1 4 f or 
details o n st u d y dr u g a d mi nistrati o n. 
j
A n HI V -1/ HI V -2 a nti ge n/a nti b o d y test, a He patitis C vir us a nti b o d y test, a He patitis B s urface a nti ge n, a He patitis B s urface a nti b o d y a n d a He patitis c ore a nti b o d y test will 
be c o n d ucte d o n all s u bjects; S u bjects wit h e vi de nce of acti ve 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 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. 
k 
S u bjects wit h p ositi ve H B V c ore A b a n d ne gati ve H B V D N A at Scree ni n g re q uire o n g oi n g m o nit ori n g wit h bl o o d tests f or H B V D N A e ver y 3 m o nt hs.
l
Se me n c ollecti o n will be c o m plete d at E T visit o nl y if pre vi o us se me n sa m ples were n ot c ollecte d wit hi n 2 wee ks of E T.


Fil g oti ni b
G L P G 0 6 3 4 -C L -2 2 7
Statistical A nal ysis Pla n 
Versi o n 1. 0
C O N FI D E N TI A L
Pa ge 7 3
1 2 Ja n uar y 2 0 2 1
A p pe n di x 2.
C alc ul ati o n of t he Differe nce i n Pr o p orti o ns a n d 9 5 % CI ( Str at u m-
A dj uste d M a ntel -H ae nszel Pr o p orti o ns)
T he 9 5 % c o nfi de nce i nter val o n t he differe nce i n pr o p orti o ns ( 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) bet wee n Treat me nt A (fil g oti ni b) a n d 
Treat me nt B ( place b o) will be c o nstr ucte d base d o n strat u m -a dj uste d M H pr o p orti o ns 
{ K oc h 1 9 8 9 } :
w here

( PA – P B ) = 

h
h
h
w
d
w
, is t he strat u m-a dj uste d M H pr o p orti o n differe nce, w here 
hd
=
B h
A h
p
p

is t he differe nce i n 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 bet wee n fil g oti ni b a n d place b o i n strat u m h ( h = 1 t o 4). Strata 
are ( 1) M T X use = yes, s per m c o nce ntrati o n 1 5 -5 0 M/ m L ; ( 2) M T X use = n o, s per m 
c o nce ntrati o n 1 5-5 0 M/ m L; ( 3) M T X use = y es, s per m c o nce ntrati o n > 5 0 M/ m L; ( 4) M T X 
use = n o, s per m c o nce ntrati o n > 5 0 M/ m L

h
w
=
B h
A h
B h
A h
n
n
n
n

, is t he wei g ht base d o n t he har m o nic mea n of sa m ple size per treat me nt gr o u p 
f or eac h strat u m w here 
A h
n
a n d 
B h
n
are t he sa m ple sizes of t he Treat me nt Gr o u ps A 
(fil g oti ni b) a n d B ( place b o) i n strat u m h. 

S E( P A – P B ) = 
2
*
*
*
*
2
)
(
1
)
1(
1
)
1(













h
B h
B h
B h
A h
A h
A h
h
w
n
p
p
n
p
p
w
, w here 
1
5.0
*



A h
A h
A h
n
m
p
a n d 
1
5.0
*



B h
B h
B h
n
m
p
a n d 
A h
m
a n d 
B h
m
are t he n u m ber of s u bjects wit h a ≥ 5 0 % decrease i n s per m 
c o nce ntrati o n i n t he Treat me nt Gr o u ps A (fil g oti ni b) a n d B ( place b o) i n strat u m h.  

α = 0. 0 5 f or t his st u dy 

Z ( 1-α/ 2 ) = Z 0. 9 7 5 = 1. 9 6 is t he 9 7. 5t h perce ntile of t he n or mal distri b uti o n
If t he c o m p ute d l o wer c o nfi de nce b o u n d is less t ha n – 1, t he l o wer b o u n d is defi ne d as – 1. If t he 
c o m p ute d u p per c o nfi de nce b o u n d is greater t ha n 1, t he n t he u p per b o u n d is defi ne d as 1. If t he
r o w or c ol u m n mar gi nal t otals are zer o i n a ny strata, t he n s o me re gr o u pi n g of strata ma y be 
perf or me d.


S A P G L P G 0 6 3 4- C L- 2 2 7 _ v 1. 0
E L E C T R O NI C SI G N A T U R E S
Si g n e d b y
M e a ni n g of Si g n at ur e
S er v er D at e
( d d- M M M-
y y y y h h: m m: s s)
R e g ul at or y Aff air s e Si g n e d
1 8- J a n- 2 0 2 1
0 4: 4 9: 4 9
Cli ni c al R e s e ar c h e Si g n e d
1 9- J a n- 2 0 2 1
1 6: 0 4: 4 2
Bi o st ati sti c s e Si g n e d
1 9- J a n- 2 0 2 1
1 6: 0 9: 1 9
P P D
P P D
P P D


Si g nat ure Pa ge f or gl p g 0 6 3 4-cl- 2 2 7-sa p 1 5 5 4 8
Si g nat ure Pa ge f or gl p g 0 6 3 4-cl- 2 2 7-sa p 4 3 9 5 2 _ 1 6 5 7 7 _ 3 6 9 3 0
A p pr o val
ia n
Bi o metrics
2 0-Ja n- 2 0 2 1 1 7: 5 5: 5 9 G M T + 0 0 0 0
A p pr o val
ect or
Cli nical De vel o p me nt
2 0-Ja n- 2 0 2 1 1 8: 0 0: 5 7 G M T + 0 0 0 0
P P D
P P D