A Randomized, Double-blind, Placebo-controlled, Multicenter Study to Evaluate the Efficacy, Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Orally Administered GLPG3970 for 12 Weeks in Adult Subjects With Active Primary Sjögren's Syndrome
Phase: PHASE2
Conditions: Primary Sjögren Syndrome
Sponsor: Galapagos NV

G al a p a g o s  
C O N FI D E N TI A L  
4 3 9 5 2 _ 1 7 1 8 5 _ 5 1 8 4 2  
G L P G 3 9 7 0 - C L-2 0 7  
 
 
C o nfi de nti alit y St ate me nt  
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 be 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.  
 
C LI NI C A L S T U D Y P R O T O C O L  
Pr oj e ct N u m b er:    
G L P G 3 9 7 0  
 
 
St u d y N u m b er:    
G L P G 3 9 7 0 - C L-2 0 7    
 
 
St u d y Titl e    
A r a n d o mi z e d, d o u bl e -bli n d, pl a c e b o -c o ntr oll e d, m ulti c e nt er st u d y t o 
e v al u at e t h e effi c a c y, s af et y, t ol er a bilit y, p h ar m a c o ki n eti c s, a n d 
p h ar m a c o d y n a mi c s  of or all y  a d mi ni st er e d G L P G 3 9 7 0  f or 1 2 w e e k s i n 
a d ult s u bj e ct s wit h a cti v e pri m ar y Sj ö gr e n’ s S y n dr o m e  
S h ort St u d y Titl e    
A st u d y e v al u ati n g t h e eff e ct s of G L P G 3 9 7 0 gi v e n a s a n or al tr e at m e nt f or 
1 2 w e e k s i n a d ult s wit h a cti v e pri m ar y Sj ö gr e n’ s S y n dr o m e  
Cli ni c al St u d y 
P h a s e:  
2 a  
St at u s  
Fi n al  
 
 
Pr ot o c ol  V er si o n:    
7. 0  
D at e:    
1 2 -M a y -2 0 2 1  
A m e n d m e nt    
6  
 
 
E u dr a C T N o:    
2 0 2 0 -0 0 3 2 9 8 -2 2    
C T. g o v N o:    
N C T 0 4 7 0 0 2 8 0  
I N D N o: 
N ot a p pli c a bl e  
S p o n s or:  
G al a p a g o s N V, G e n er a al D e Witt el a a n L 1 1 A 3, 2 8 0 0 M e c h el e n, B el gi u m  
St u d y P h y si ci a n:  
, M D, S e ni or M e di c al Dir e ct or, Tr a n sl ati o n al M e di ci n e 
G e n er al C S P    
 

G al a p a g o s  
C O N FI D E N TI A L  
4 3 9 5 2 _ 1 7 1 8 5 _ 5 1 8 4 2  
G L P G 3 9 7 0 - C L-2 0 7  
-3 - 
 
T A B L E O F C O N T E N T S  
E M E R G E N C Y C O N T A C T I N F O R M A TI O N  ........................................................................... 2  
T A B L E O F C O N T E N T S  ........................................................................................................ 3  
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  ............................................................................ 7  
S U M M A R Y O F C H A N G E S  ................................................................................................... 8  
LI S T O F T A B L E S  .................................................................................................................1 2  
LI S T O F FI G U R E S  ...............................................................................................................1 2  
LI S T O F A P P E N DI C E S  ........................................................................................................1 3  
LI S T O F A B B R E VI A TI O N S A N D D E FI NI TI O N O F T E R M S ..................................................1 4  
1.  
C LI NI C A L S T U D Y P R O T O C O L S Y N O P SI S  .................................................................1 9  
2.  
I N T R O D U C TI O N ...........................................................................................................2 5  
2. 1.   
B a c k gr o u n d - N o n cli ni c al St u di e s  .......................................................................2 6  
2. 1. 1.    
N o n cli ni c al P h ar m a c o ki n eti c s  .............................................................2 6  
2. 1. 2.    
S af et y P h ar m a c ol o g y  ..........................................................................2 6  
2. 1. 3.    
G e n er al T o xi c ol o g y  .............................................................................2 7  
2. 1. 4.    
G e n ot o xi cit y  ........................................................................................2 7  
2. 1. 5.    
E m br y o -F et al D e v el o p m e nt T o xi cit y  ...................................................2 7  
2. 1. 6.    
P h ot ot o xi cit y  .......................................................................................2 7  
2. 2.   
B a c k gr o u n d - Cli ni c al St u di e s  ............................................................................2 7  
3.  
C LI NI C A L S T U D Y O B J E C TI V E S  ..................................................................................3 0  
3. 1.   
Pri m ar y O bj e cti v e s  .............................................................................................3 0  
3. 2.   
S e c o n d ar y O bj e cti v e s  ........................................................................................3 0  
3. 3.   
Ot h er O bj e cti v e s  ................................................................................................3 0  
4.  
E N D P OI N T S  .................................................................................................................3 1  
4. 1.   
Pri m ar y E n d p oi nt s ..............................................................................................3 1  
4. 2.   
S e c o n d ar y E n d p oi nt s  .........................................................................................3 1  
4. 3.   
Ot h er E n d p oi nt s  .................................................................................................3 1  
5.  
I N V E S TI G A TI O N A L P L A N ............................................................................................3 1  
5. 1.   
Cli ni c al St u d y D e si g n  .........................................................................................3 1  
5. 2.   
St art a n d E n d of St u d y D efi niti o n s  .....................................................................3 2  
5. 3.   
Cli ni c al St u d y D e si g n R ati o n al e  .........................................................................3 2  
5. 4.   
D o si n g R ati o n al e  ...............................................................................................3 3  
5. 5.   
P ot e nti al Ri s k s a n d B e n efit s  ..............................................................................3 3  
5. 6.   
E sti m a n d s  ..........................................................................................................3 6  
6.  
C LI NI C A L S T U D Y P O P U L A TI O N  .................................................................................3 7  

G al a p a g o s  
C O N FI D E N TI A L  
4 3 9 5 2 _ 1 7 1 8 5 _ 5 1 8 4 2  
G L P G 3 9 7 0 - C L-2 0 7  
-6 - 
 
1 1. 1. 3.  
U nli st e d ( U n e x p e ct e d) A d v er s e E v e nt s/ R ef er e n c e S af et y 
I nf or m ati o n ..........................................................................................7 4  
1 1. 1. 4.  
A d v er s e E v e nt s of S p e ci al I nt er e st  .....................................................7 4  
1 1. 1. 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 a s A d v er s e E v e nt s or S eri o u s A d v er s e E v e nt s  .............7 4  
1 1. 1. 6.  
S p e ci al Sit u ati o n s  ...............................................................................7 4  
1 1. 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 5  
1 1. 2. 1.  
A cti o n T a k e n R e g ar di n g I n v e sti g ati o n al Pr o d u ct (if A p pli c a bl e) ...........7 5  
1 1. 2. 2.  
A s s e s s m e nt of C a u s alit y  .....................................................................7 5  
1 1 . 2. 3. 
A s s e s s m e nt of S e v erit y  ......................................................................7 6  
1 1. 2. 4.  
O ut c o m e  .............................................................................................7 7  
1 1. 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, 
S eri o u s A d v er s e E v e nt s, Pr e g n a n ci e s, a n d Ot h er S p e ci al Sit u ati o n s t o t h e 
S p o n s or  .............................................................................................................7 7  
1 1. 3. 1.  
A d v er s e E v e nt s  ...................................................................................7 7  
1 1. 3. 2.  
S eri o u s A d v er s e E v e nt s  ......................................................................7 8  
1 1. 3. 3.  
Pr e g n a n c y  ..........................................................................................7 9  
1 1. 3. 4.  
R e p orti n g of S p e ci al Sit u ati o n s ( Ot h er T h a n Pr e g n a n c y) a n d 
A d v er s e E v e nt s  ...................................................................................7 9  
1 1. 4.  S p o n s or R e p orti n g R e q uir e m e nt s  ......................................................................7 9  
1 2.  S P O N S O R’ S A N D I N V E S T I G A T O R’ S R E S P O N SI BI LI TI E S .........................................8 0  
1 2. 1.  S p o n s or’ s R e s p o n si biliti e s  .................................................................................8 0  
1 2. 1. 1.  
R e g ul at or y  A ut h orit y A p pr o v al  ............................................................8 0  
1 2. 1. 2.  
Cli ni c al St u d y Cl o s ur e C o n si d er ati o n s  ................................................8 0  
1 2. 1. 3.  
I n d e m nifi c ati o n ....................................................................................8 1  
1 2. 1. 4.  
I n s ur a n c e ............................................................................................8 1  
1 2. 1. 5.  
Ar c hi vi n g  .............................................................................................8 1  
1 2. 2.  R e p orti n g  ...........................................................................................................8 1  
1 2. 3.  P u bli c ati o n  .........................................................................................................8 2  
1 2. 4.  I n v e sti g at or’ s R e s p o n si biliti e s ............................................................................8 2  
1 2. 4. 1.  
S o ur c e D at a a n d D at a C a pt ur e  ...........................................................8 2  
1 2. 4. 2.  
Ar c hi vi n g  .............................................................................................8 2  
1 2. 4. 3.  
P arti ci p ati o n C ar d s  ..............................................................................8 3  
1 2. 5.  C o nfi d e nti alit y  ....................................................................................................8 3  
1 2. 6.  Et hi c al C o n si d er ati o n s  .......................................................................................8 4  
1 2. 6. 1.  
I n d e p e n d e nt Et hi c s C o m mitt e e / I n stit uti o n al R e vi e w B o ar d ...............8 4  
1 2. 6. 2.  
I nf or m e d C o n s e nt  ...............................................................................8 4  
1 2. 7.  D at a Q u alit y C o ntr ol/ A s s ur a n c e  .........................................................................8 5  
1 2. 7. 1.  
M o nit ori n g  ...........................................................................................8 5  
1 2. 7. 2.  
A u dit a n d I n s p e cti o n  ...........................................................................8 5  
1 3.  R E F E R E N C E S  ..............................................................................................................8 7  
1 4.  A P P E N DI C E S  ...............................................................................................................8 9  
SI G N A T U R E P A G E –  S P O N S O R  ...................................................................................... 1 0 6  
SI G N A T U R E P A G E –  I N V E S TI G A T OR  ............................................................................. 1 0 7  

G al a p a g o s  
C O N FI D E N TI A L  
4 3 9 5 2 _ 1 7 1 8 5 _ 5 1 8 4 2  
G L P G 3 9 7 0 - C L-2 0 7  
-7 - 
 
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 S t u d y P r ot oc ol 
(C S P )/ A me n d me nt # 
D ate  
M ai n R ati o n ale  
Ge ner al/ C o u ntr y -S pecific  
C S P Versi o n 1. 0  
2 1 -Se p -2 0 2 0    
I nitial C S P Versi o n  
Ge neral  
A me n d me nt 1, C S P Versi o n 2. 0  
8 -Dec -2 0 2 0    
U p date d t o i ncl u de m ore details o n t he 
P h ysi ol o gic all y-Base d P har mac o ki netic 
( P B P K) m o deli n g data t o s u p p ort t he ta blet 
f or m ulati o n. 
A me n d me nt 2, C S P Versi o n 3. 0  
6 -Ja n-2 0 2 1  
A pr ot oc ol a me n d me nt create d u p o n 
re q uest of t he 
 u p dati n g t he e xcl usi o n 
criteria, pr o hi bite d me dicati o n s secti o n, 
a n d e xte n di n g t he f oll o w -u p peri o d t o 4 
wee ks . 
A me n d me nt 3 , C S P versi o n 4. 0  
2 1 -Ja n-2 0 2 1    
Pr ot oc ol a me n de d i n res p o nse t o a  f oll o w 
u p  re q uest b y t he   
t o f urt her a da pt 
t he e xcl usi o n criteria. 
A me n d me nt 4, C S P versi o n 5. 0  
8 -Fe b -2 0 2 1    
Pr ot oc ol a me n de d  i n res p o nse t o q uesti o ns 
fr o m t he 
A me n d me nt 5, C S P versi o n 6. 0  
4 -Mar -2 0 2 1    
Pr ot oc ol a me n de d i n ali g n me nt wit h t he 
ne wl y i de ntifie d p ote ntial ris k of Q T 
pr ol o n gati o n  
A me n d me nt 6, C S P versi o n 7. 0  
1 2 -Ma y -2 0 2 1    
Pr ot oc ol a me n de d t o cl oser m o nit or t he 
ne w p ote ntial ris k of Q T pr ol o n gati o n  
C S P =cli nical st u d y pr ot oc ol  
 
 

G al a p a g o s  
C O N FI D E N TI A L  
4 3 9 5 2 _ 1 7 1 8 5 _ 5 1 8 4 2  
G L P G 3 9 7 0 - C L-2 0 7  
-9 - 
 
R ati o n ale:  G ui da nce f or vacci ne  (i ncl u di n g C o vi d-1 9 vacci nes)  use bef ore a n d d uri n g t his st u d y ha ve bee n 
u p date d.  
A p plic a ble secti o ns: 5. 5  a n d 6. 3. 2  
R ati o n ale: Clarificati o n was a d de d t hat S A R S -C o V -2 tests ma y be a nal yze d i n l ocal la b orat ories.  
A p plic a ble secti o n: 8. 9  
R ati o n ale: Mi n or a d mi nistrati ve c ha n ges  a n d ali g n me nts  
A p plic a ble secti o ns: list of a b bre viati o ns ; 1 , 2 , 2. 2 , 6. 2 , 8. 5. 5  a n d 8. 1 1  
 
A me n d me nt 4  (8 -Fe b -2 0 2 1)  
T he o verall reas o n f or t his a me n d me nt:  
T his pr ot oc ol was a me n de d i n res p o nse t o q uesti o ns fr o m t he
T he c ha n ges ma de t o t he C S P G L P 3 9 7 0 -C L -2 0 7 Versi o n  4 . 0, 2 1 -Ja n-2 0 2 0 , are liste d bel o w, reflecti n g a brief 
rati o nale of eac h c ha n ge a n d t he a p plica ble secti o ns.  
R ati o n ale:  T he p h o ne n u m ber of t he s p o ns or me dical lea der has bee n c ha n ge d t o t heir m o bile n u m ber si nce d ue 
t o c urre nt re gi o nal S A R S -C o V -2  restricti o ns, a prese nce at t he office ca n n ot be g uara ntee d. 
A p plic a ble secti o ns:  E mer ge nc y c o ntact i nf or mati o n. 
R ati o n ale:  A f o ot n ote has bee n a d de d t o t he e xcl usi o n criteria t o defi ne t he ter m el derl y.  
A p plic a ble Secti o n : 6. 2  
R ati o n ale: W or di n g of t he e xcl usi o n criteri o n o n vacci nes has bee n clarifie d t o  e xcl u de li ve atte n uate d vacci nes 
(i ncl u di n g li ve atte n uate d c o vi d-1 9  vacci nes ). A ne w s u bsecti o n “ vacci nes”  has bee n s u bse q ue ntl y a d de d t o 6. 3 .2 
Pri or a n d C o nc o mita nt Me dic ati o n.  
A p plic a ble Secti o ns:  6. 2  a n d  6. 3. 2  
R ati o n ale: A ne w e xcl usi o n criteri o n has bee n a d de d t o e xcl u de s u bj ects w h o are i nstit uti o nalize d b y virt ue of a n 
or der iss ue d b y eit her t he j u di cial or t he a d mi nistrati ve a ut h orities or ha ve a de pe n de nc y o n t he s p o ns or or 
i n vesti gat or. 
A p pli c a ble Secti o n : 6. 2  
R ati o n ale:  W or di n g o n s u bj ect disc o nti n uati o n criteria was c ha n ge d fr o m “s h o ul d be disc o nti n ue d” t o “ m ust be 
disc o nti n ue d” f or p ur p oses of clarificati o n.  
A p plic a ble Secti o n : 6. 4  
R ati o n ale:  St u d y st o p pi n g criteria were s pecifie d.  
A p p lic a ble Secti o n: 6. 4  
R ati o n ale:  Clarificati o n has b ee n a d de d t hat t he i n vesti ga t or s h o ul d re p ort S A R S -C o V -2 res ults as re q uire d b y 
l ocal la w.   

G al a p a g o s  
C O N FI D E N TI A L  
4 3 9 5 2 _ 1 7 1 8 5 _ 5 1 8 4 2  
G L P G 3 9 7 0 - C L-2 0 7  
-1 1 - 
 
A p plic a ble Secti o ns : 1  a n d 6. 2  
R ati o n ale : T he e xcl usi o n crit eria re gar di n g a ntic h oli ner gic a ge nts has bee n u p date d t o e xcl u de  a n y me dicati o n 
k n o w n t o ca use dr y m o ut h/ dr y e yes t hat i n t he o pi ni o n of t he i n vesti gat or are a c o ntri b uti n g fact or t o t he s u bj ect’s 
dr y ness.  
A p plic a ble Secti o ns : 1 , 6. 2 , a n d 6. 3. 2  
R ati o n ale : F or s p ora dic use of oc ular me dici nes  i n t he e xcl usi o n criteria, s p ora dic use was defi ne d as a c o urse of 
7 da ys a n d n o m ore t ha n 2 c o urses d uri n g t he st u d y a d mi nist ere d 2 wee ks a part . 
A p plic a ble Secti o ns : 1 , 6. 2 , a n d 6. 3. 2  
R ati o n ale : A n a d diti o nal e xcl usi o n criteri o n was a d de d s pecif yi n g a b n or mal la b orat or y  val ues f or as partate 
a mi n otra n sferase, ala ni ne a mi n otra nsferase , t otal bilir u bi n, pr ot hr o m bi n  ti me or partial t hr o m b o plasti n ti me  t o 
a d dress t he   
c o ncer n.  
A p plic a ble Secti o n : 6. 2  
R ati o n ale : T he f oll o w -u p peri o d of t he st u d y was e xte n de d fr o m 2 t o 4 wee ks 
A p plic a ble Secti o ns : 1 , 5. 1 , 6. 5. 2 , 8. 9 , a n d 8. 1 1  
R ati o n ale : Mi n or a d mi nistrati ve c ha n ges.  
A p plic a ble Secti o ns : 6. 3. 2  a n d 6. 4  
 
A me n d me nt 1  (8 -Dec -2 0 2 0)  
T he o ver all re as o n f or t his a me n d me nt:  
T he o verall reas o n f or t his a me n d me nt is t o i ncl u de m ore details o n t he P h ysi ol o gicall y-B ase d P har mac o ki netic 
( P B P K) m o deli n g data t o s u p p ort t he ta blet f or m ulati o n, u p o n re q uest fr o m t he c o m pete nt a ut h orit y of t he
 
T he c ha n ges ma de t o t he  C S P G L P 3 9 7 0 -C L -2 0 7  Versi o n  1. 0 , 2 1 -Se p -2 0 2 0 , are liste d bel o w, reflecti n g a brief 
rati o nale of eac h c ha n ge a n d t he a p plica ble secti o ns. 
R ati o n ale : A d diti o nal details o n t he P B P K m o deli n g data are i ncl u de d t o s u p p ort t he ta blet f or m ulati o n a n d t o 
c o m pare t he pre vi o us f or m ulati o ns wit h t he ta blet f or m ulati o n. I n a d diti o n, t he list of a b bre viati o ns has bee n 
u p date d.  
A p plic a ble Secti o n : 2. 2  
C S P =cli nical st u d y pr ot oc ol  
 

G al a p a g o s  
C O N FI D E N TI A L  
4 3 9 5 2 _ 1 7 1 8 5 _ 5 1 8 4 2  
G L P G 3 9 7 0 - C L-2 0 7  
-1 2 - 
 
LI S T O F T A B L E S  
T a bl e 1:    
C o m p ari s o n of Pr e di ct e d P K P ar a m et er s f or t h e T a bl et s wit h O b s er v e d P K 
f or S ol uti o n F or m ul ati o n. ..................................................................................3 0  
T a bl e  2:    
Gr a di n g of A E S e v erit y  .....................................................................................7 7  
 
LI S T O F FI G U R E S  
Fi g ur e 1:    
C o m p ari s o n of P K E x p o s ur e f or t h e T a bl et s wit h S ol uti o n f or m ul ati o n  .............2 9  
Fi g ur e  2:    
S c h e m ati c Di a gr a m  ..........................................................................................3 2  

G al a p a g o s  
C O N FI D E N TI A L  
4 3 9 5 2 _ 1 7 1 8 5 _ 5 1 8 4 2  
G L P G 3 9 7 0 - C L-2 0 7  
-1 3 - 
 
LI S T O F A P P E N DI C E S  
A p p e n di x 1:  Pr e d ni s ol o n e C o n v er si o n T a bl e  ........................................................................8 9  
A p p e n di x 7:  E U L A R Sj ö gr e n’ s S y n dr o m e Di s e a s e A cti vit y I n d e x ( E S S D AI) S c or e  ..............9 5  
A p p e n di x 8:  E U L A R Sj ö gr e n’ s S y n dr o m e P ati e nt R e p ort e d I n d e x ( E S S P RI) S c or e  .............9 8  
 
 
 
 
 
A p p e n di x  1 5:    
Al g orit h m f or El e v at e d Li v er F u n cti o n T e st s  ...................................... 1 0 4  
 

G al a p a g o s  
C O N FI D E N TI A L  
4 3 9 5 2 _ 1 7 1 8 5 _ 5 1 8 4 2  
G L P G 3 9 7 0 - C L-2 0 7  
LI S T O F A B B R E VI A TI O N S A N D D E FI NI TI O N O F T E R M S  
A b bre vi ati o ns  
A C R  
A merica n C olle ge of R he u mat ol o g y  
A D L  
Acti vities of Dail y Li vi n g  
A E  
a d verse e ve nt  
A L T  
ala ni ne a mi n otra nsferas e  
A S T  
as partate a mi n otra nsferas e  
A Z A  
azat hi o pri ne 
A U C  
area u n d er t he pl as ma c o nce ntrati o n -ti me c ur ve 
A U C 0 -2 4 h 
Area u n d er t he plas ma c o nce ntrati o n -ti me c ur ve fr o m ti me zer o u ntil 
2 4 h o urs p ost d ose  
A U C ta u 
area u n d er t he pl as ma c o nce ntrati o n -ti me c ur ve fr o m ti me zer o u ntil 
t he e n d of t he d osi n g peri o d 
C A  
citric aci d  
C a v g 
mea n a vera ge c o nce ntrati o n  
CI  
c o nfi de nce i nter val  
C L/ F  
cleara nce  
C ma x  
ma xi m u m o bser ve d plas ma c o nce ntrati o n  
C N S  
ce ntral ner v o us s yste m  
C R F  
case re p ort f or m  
C R O  
c o ntract researc h or ga nizati o n  
C S P  
cli nical st u d y pr ot oc ol  
C S R  
cli nical st u d y re p ort  
C T C A E  
C o m m o n Ter mi n ol o g y Criteria f or A d verse E ve nts  
C tr o u g h 
plas ma tr o u g h c o nce ntrati o n  
C Y P  
c yt o c hr o me P 4 5 0  
D N A  
de o x yri b o n ucleic aci d  
D T P  
direct t o patie nt  
E C 5 0 
half ma xi mal effecti ve c o nce ntrati o n  
E C G  
electr ocar di o gra m  
E D  
earl y disc o nti n uati o n  
E S S D AI  
E U L A R Sj ö gre n’s S y n dr o me Disease Acti vit y I n de x  
E S S P RI  
E U L A R Sj ö gre n’s S y n dr o me Patie nt Re p orte d I n de x  

G al a p a g o s  
C O N FI D E N TI A L  
4 3 9 5 2 _ 1 7 1 8 5 _ 5 1 8 4 2  
G L P G 3 9 7 0 - C L-2 0 7  
-1 5 - 
 
E U  
E ur o pea n U ni o n  
E U L A R  
E ur o pea n Lea g ue  A gai nst R he u matis m  
F A S  
F ull A nal ysis Set  
FI H  
first-i n-h u ma n  
F S H  
f ollicle sti m ulati n g h or m o ne 
F U  
f oll o w-u p  
G C P  
G o o d Cli nical Practice  
G G T  
ga m ma -gl uta m yl tra nsferase  
G L P  
G o o d La b orat or y Practice  
H Bs A g  
he patitis B  vir us s urface a nti ge n  
H B V  
he patitis B vir us  
H C V  
he patitis C vir us  
H D L  
hi g h -de nsit y li p o pr otei n  
HI V  
h u ma n i m m u n o deficie nc y vir us  
H O M A -I R 
h o me ostatic m o del assess me nt of i ns uli n resista nce  
I B 
i n vesti gat or’s br oc h ure 
I C5 0 
half ma xi mal i n hi bit or y c o nce ntrati o ns  
I C F 
i nf or me d c o nse nt f or m 
I C H 
I nter nati o nal C o u ncil f or Har m o nisati o n of Tec h nical Re q uire me nts 
f or P har mace uticals f or H u ma n Use 
I E C 
I n d e pe n de nt Et hics C o m mittee 
I g M 
im m u n o gl o b uli n M  
I L 
i nterle u ki n 
I N R 
i nter nati o nal n or malize d rati o 
I P 
i n vesti gati o nal pr o d uct 
I R 
i m me diate releas e 
I R B 
I nstit uti o nal Re vie w B oar d 
I VI V C 
i n vitr o i n vi v o c orrelati o n 
I WR S  
i nteracti ve we b res p o ns e s yste m  
L D L  
l o w-de nsit y li p o pr otei n  
L F T  
li ver f u ncti o n test 
L P S  
li p o p ol ys acc hari de 
 
 
M M F  
m yc o p h e n olate m ofetil  
M M R M  
mi x e d m o del f or re peate d meas ures  
 
 

G al a p a g o s  
C O N FI D E N TI A L  
4 3 9 5 2 _ 1 7 1 8 5 _ 5 1 8 4 2  
G L P G 3 9 7 0 - C L-2 0 7  
-1 6 - 
 
M T X  
met h otre x ate  
N O A E L  
n o -o bser ve d -a d verse-effect -le vel 
N S AI D  
n o n -ster oi dal a nti-i nfla m mat or y dr u g 
P B B M  
P h ysi ol o gicall y -Base d Bi o p har mace utics M o del  
P B P K  
P h ysi ol o gical l y-Base d P har mac o ki netic  
P C R  
p ol y merase c hai n reacti o n  
 
 
P -g p  
per mea bilit y gl yc o pr otei n  
P K  
p har mac o ki netic (s) 
P o p -P K  
p o p ulati o n p har mac o ki netics  
p S S  
pri mar y Sj ö gre n’s S y n dr o me  
q. d.  
o nce dail y  
Q M P  
Q ualit y Ma n a ge me nt Pla n  
 
 
R A  
r he u mat oi d art hritis 
R B C  
re d bl o o d cell 
R N A  
ri b o n ucleic aci d 
R T -P C R  
real ti me p ol y m eras e c hai n reacti o n 
S A E  
seri o us a d verse e ve nt  
S A P  
statistical a nal ysis pla n 
S A R S -C o V -2    
se vere ac ute res pirat or y s y n dr o me c or o na vir us 2 
S D  
sta n dar d de viati o n 
 
 
S G F  
si m ulate d gastric fl ui d 
SI F  
si m ulate d i ntesti nal fl ui d 
SI K  
salt-i n d uci ble ki nase 
 
 
S o C  
sta n dar d of care 
S jS  
Sj ö gre n’s S y n dr o me  
S U S A R  
s us pecte d u ne x pecte d seri o us a d verse reacti o n 
t1/ 2 
eli mi nati o n half -life 
T B  
t u berc ul osis 
T E A E  
treat me nt-e mer ge nt a d verse e ve nt  

G al a p a g o s  
C O N FI D E N TI A L  
4 3 9 5 2 _ 1 7 1 8 5 _ 5 1 8 4 2  
G L P G 3 9 7 0 - C L-2 0 7  
-1 7 - 
 
tma x  
ti me t o ma xi m u m plas ma c o nce ntrati o n 
T M F  
Trial Master File  
T N F α  
t u m or necr osis fact or al p ha 
U L N  
u p per li mit of n or mal  
 
 
Vss  
v ol u me of distri b uti o n at stea d y st ate  
W O C B P  
w o me n of c hil d beari n g p ote ntial  
 
 
 

G al a p a g o s  
C O N FI D E N TI A L  
4 3 9 5 2 _ 1 7 1 8 5 _ 5 1 8 4 2  
G L P G 3 9 7 0 - C L-2 0 7  
-1 8 - 
 
Defi niti o n of Ter ms  
B MI  
b o d y mass i n de x  
Wei g ht ( k g) / ( hei g ht [ m])
2 
Q Tc F  
Q T i nter val c orrecte d f or heart rate usi n g Fri derici a’s f or m ula:  
Q Tc F = Q T/ R R 1/ 3  
R R = t he i nter val fr o m t he o nset of o ne Q R S c o m ple x t o t he o nset of 
t he ne xt Q R S c o m ple x   
H O M A -I R   
H o me ostatic m o del assess me nt of i ns uli n resista nce  
H O M A -I R = (fasti n g i ns uli n [ m U/ m L] x fasti n g gl uc ose [ m g/ d L])/ 4 0 5 
] x, y] 
I nter val ra n gi n g fr o m x t o y, wit h x n ot i ncl u de d a n d y i ncl u de d i n t he 
i nter val 

G al a p a g o s  
C O N FI D E N TI A L  
4 3 9 5 2 _ 1 7 1 8 5 _ 5 1 8 4 2  
G L P G 3 9 7 0 - C L-2 0 7  
-1 9 - 
 
1.    
C LI NI C A L S T U D Y P R O T O C O L S Y N O P SI S  
T itle of St u d y 
A ra n d o mize d, d o u ble -bli n d, place b o -c o ntr olle d, m ultice nter st u d y t o e val uate t he efficac y, 
safet y, t olera bilit y, p har mac o ki netics, a n d p har mac o d y na mics of orall y a d mi nistere d 
G L P G 3 9 7 0 f or 1 2 wee ks i n a d ult s u bjects wit h acti ve pri mar y Sj ö gre n’s S y n dr o me  
S h ort Title of St u d y  
A st u d y e v al uati n g t h e effects of G L P G 3 9 7 0 gi ve n as a n oral treat me nt f or 1 2 wee ks i n a d ults 
wit h acti ve pri mar y Sj ö gre n’s S y n dr o me  
P h ase  of De vel o p me nt : P h ase 2 a  
O bjecti ves a n d E n d p oi nts  
O bjecti ves  
E n d p oi nts  
Pri m ary  
 
− T o e val uate t he efficac y of G L P G 3 9 7 0 
c o m pare d t o place b o o n t he si g ns a n d s y m pt o ms 
of pri mar y Sj ö gre n’s S y n dr o me ( p S S).  
− C ha n ge fr o m  baseli ne i n E ur o pea n Lea g u e A gai nst 
R he u matis m ( E U L A R) Sj ö gre n’s S y n dr o me 
Disease Acti vi t y I n de x ( E S S D AI) sc ore at 
Wee k  1 2.  
− T o e val uate t he safet y a n d t olera bilit y of 
G L P G 3 9 7 0 c o m pare d t o place b o.  
− N u m ber, i nci de nce , a n d se verit y of treat me nt -
e mer ge nt a d v erse e ve nts ( T E A Es).  
Sec o n d ary  
 
− T o f urt her c haracterize t he effi cac y of 
G L P G 3 9 7 0 c o m pare d t o place b o o n t he patie nt -
re p orte d si g ns a n d s y m pt o ms of p S S. 
− C ha n ge fr o m baseli ne i n E U L A R Sj ö gre n’s 
S y n dr o me Patie nt Re p orte d I n de x ( E S S P RI) sc ore 
at Wee k 4, 8 , a n d 1 2.  
− C ha n ge fr o m baseli ne i n E S S D AI sc ore o ver ti me 
at Wee k 4, 8 , a n d 1 2. 
− T o c haracterize t he p har mac o ki netics ( P K) of 
G L P G 3 9 7 0.  
− O bser ve d G L P G 3 9 7 0 plas ma tr o u g h c o nce ntrati o ns 
( Ctr o u g h). 
Ot her  
 

G al a p a g o s  
C O N FI D E N TI A L  
4 3 9 5 2 _ 1 7 1 8 5 _ 5 1 8 4 2  
G L P G 3 9 7 0 - C L-2 0 7  
-2 0 - 
 
 
Pl a n ne d N u m ber o f S u bjects  
T he st u d y is pla n ne d t o ra n d o mize 3 0 a d ult s u bjects i n a 2: 1 rati o ( 2 0 s u bjects pla n ne d t o 
recei v e G L P G 3 9 7 0 a n d 1 0 s u bjects pla n ne d t o recei ve place b o). 
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 -co ntr olle d, parallel -gr o u p, m ulti ce nter st u d y.  
T he st u d y will c o nsist of 3 st u d y peri o ds:  
− 
Scree ni n g peri o d: u p t o 4 wee ks wit h 1 st u d y visit.  
− 
Treat me nt peri o d: 1 2 wee ks wit h u p t o 5 st u d y visits ( Da ys 1, 8 , 2 9, 5 7, a n d 8 5).  
− 
F oll o w -u p ( F U) p eri o d: 4  w ee ks wit h 1 st u d y visit .  
A sc he matic dia gra m of cli nical st u d y desi g n a n d peri o ds is pr o vi de d bel o w. 
St u d y D ur ati o n  
T he s u bjects will be i n t he st u d y f or a d urati o n of 2 0  wee ks: u p t o 4  wee ks of scree ni n g, 
1 2  wee ks of treat me nt, a n d 4 wee ks of F U . 
M ai n Criteri a f or I ncl usi o n a n d E xcl usi o n  
M ai n I ncl usi o n Criteri a  
− 
Male or fe m ale s u bject b et wee n 1 8 -7 4 years of a ge (e xtre mes i ncl u de d), o n t he date of 
si g ni n g t he i nf or me d c o nse nt f or m (I C F). 
− 
D oc u me nte d dia g n osis of p S S f or < 1 0 years pri or t o scree ni n g A N D defi ne d b y t he 
classificati o n criteria > = 4 descri be d b y  t he A merica n C olle ge of R he u mat ol o g y - 
E ur o pea n Lea g ue A gai nst  R he u matis m ( A C R -E U L A R).  
− 
S u bject has a n E S S D AI s c ore > = 5 ass esse d o n 7 d o mai ns: c o nstit uti o nal, 
l y m p ha de n o p at h y, gla n d ular, artic ular, c uta ne o us, he mat ol o gical, a n d bi ol o gical.  
− 
S u bject has a n E S S P RI s c ore > = 5.  

G al a p a g o s  
C O N FI D E N TI A L  
4 3 9 5 2 _ 1 7 1 8 5 _ 5 1 8 4 2  
G L P G 3 9 7 0 - C L-2 0 7  
-2 1 - 
 
− 
S u bject has sti m ulate d w h ole sali var y fl o w rate of > = 0. 1  m L/ mi n.  
− 
S u bject has p ositi ve ser u m titers of a nti -S S -A/ R o a n d/ or a nti -S S -B/ La a nti b o dies.  
− 
S u bjects alrea d y o n treat me nt s h o ul d be o n s ta ble sta n dar d of care ( S o C) f or at least 
4  wee ks  pri or t o first I P d osi n g.  
T he f oll o wi n g S o C me di cati o ns are per mitte d:   
•  
C ortic oster oi ds < = 7. 5  m g/ da y ( pre d nis o ne or e q ui vale nt); A N D/ O R  
•  
N o n -ster oi dal a nti-i nfla m mat or y dr u gs (N S AI Ds ); A N D/ O R  
•  
O ne si n gl e a nti malarial at a sta ble d ose ( h y dr o x yc hl or o q ui ne  < = 4 0 0 m g/ da y; 
q ui nacri ne 1 0 0 m g/ k g/ da y, or c hl or o q ui ne < = 2 5 0 m g/ da y); A N D/ O R  
•  
O ne si n gl e i m m u n os u p pressa nt at a sta ble d ose ( met h otre xate [ M T X] < = 1 0  m g/ wee k 
or az at hi o pri ne [ A Z A] < = 2  m g/ k g/ da y); A N D/ O R  
•  
O ne si n gl e c h oli ner gic sti m ula nt at a sta ble d ose (e. g. pil ocar pi ne, ce vi meli ne). 
− 
Fe male s u bject  of c hil d b eari n g p ote ntial m ust ha ve a ne gati ve hi g hl y se nsiti ve (ser u m beta 
h u ma n c h ori o nic g o na d otr o pi n or uri ne di pstic k) pre g na nc y t est.  
− 
Fe male s u bject  of c hil d b eari n g p ote ntial or male s u bject m ust a gree t o use hi g hl y effecti ve 
c o ntrace pti o n/ pre ve nti ve e x p os ure meas ures.  
M ai n Excl usi o n Criteri a  
− 
Sec o n dar y Sj ö gre n's s y n dr o me acc or di n g t o t he A C R -E U L A R  ( 2 0 1 6) classificati o n. 
− 
Hist or y or prese n ce of u nsta ble c o n diti o n n ot relate d t o Sj ö gre n’s S y n dr o me t hat, i n t he 
o pi ni o n of t he i n vesti gat or, c o ul d c o nstit ute a n u nacce pta ble ris k w he n ta ki n g t he I P or 
i nterfere wit h t he i nter pretati o n of data. 
− 
S u bject has a n y acti ve s yste mic i nfecti o n wit hi n 2 wee ks pri or t o first I P d osi n g, or p o orl y 
c o ntr olle d c hr o nic car diac, p ul m o nar y, or re nal disease . 
− 
S u bject has a k n o w n or s us pecte d hist or y of or a c urre nt i m m u n os u p press i ve c o n diti o n, or 
a hist or y of o p p ort u nistic i nfecti o ns (e. g. h u ma n i m m u n o deficie nc y vir us [ HI V] i nfecti o n, 
hist o plas m osis, listeri osis, c occi di o d m yc osis, p ne u m oc yst osis, as per gill osis).  
− 
S u bject has a c hr o nic he p atitis B vir us ( H B V) i nfecti o n, as defi ne d b y persiste nt H B V 
s urface a nti ge n ( H Bs A g) p ositi vit y. S u bject has he patitis C vir us ( H C V) i nfecti o n, as 
defi ne d b y p ositi ve H C V  a nti b o d y at scree ni n g a n d det ecta ble H C V vire mi a. S u bjects 
wit h p ositi ve H C V a nti b o d y  m ust u n der g o refle x H C V ri b o n ucleic aci d (R N A ) testi n g, 
a n d s u bjects wit h H C V R N A p ositi vit y will be e xcl u de d. S u bjects wit h p ositi ve H C V 
a nti b o d y a n d n e gati ve H C V R N A are eli gi ble.  
− 
S u bject testi n g p ositi ve f or se vere ac ut e res pirat or y s y n dr o me c or o na vir us 2 ( S A R S -C o V -
2 ) i nfecti o n as det ecte d at scree ni n g bas e d o n real ti me p ol y m eras e c hai n reacti o n 
( R T-P C R)  or at baseli ne base d o n i m m u n o gl o b uli n M (I g M) i m m u n oassa y, or s u bjects 
w h o ha ve bee n i n c o nt act wit h S A R S -C o V -2 i nfecte d i n di vi d uals i n t he 2 wee ks pri or t o 
first d osi n g of I P. S u bjects prese nti ng a n y si g ns or s y m pt o ms of S A R S -C o V -2 i nfecti o n, 
as detecte d pri or t o first I P d osi n g f oll o wi n g caref ul p h ysical e xa mi nati o n (e. g. c o u g h, 
fe ver, hea d ac hes, fati g ue, d ys p nea, m yal gia, a n os mia, d ys ge usia, a n ore xia, s ore t hr oat , 
etc). I n a d diti o n, a n y ot h er l ocall y a p plica ble sta n dar d dia g n ostic criteria ma y als o a p pl y t o 
r ule o ut S A R S-C o V -2 i nfecti o n.  

G al a p a g o s  
C O N FI D E N TI A L  
4 3 9 5 2 _ 1 7 1 8 5 _ 5 1 8 4 2  
G L P G 3 9 7 0 - C L-2 0 7  
-2 2 - 
 
− 
S u bject has ta ke n a n y dis all o we d t hera pi es:  
•  
M yc o p h e n olate  m ofetil ( M M F) wit hi n a wee k pri or t o scree ni n g . 
•  
C ycl os p ori ne/ T acr oli m us wit hi n a wee k pri or t o scree ni n g . 
•  
C ycl o p h os p ha mi de wit hi n 6  m o nt hs pri or t o scree ni n g . 
•  
O c ular me dici n es (e. g. t o pical c ycl os p ori ne, t o pical N S AI Ds/c ortic oster oi ds) f or at 
least 4 wee ks pri or t o scree ni n g, e xce pt f or a s p ora dic use.  
•  
Bi ol o gics s u c h as , b ut n ot li mite d t o, rit u xi ma b, a batace pt, a n d a n y ot her u na p pr o ve d 
bi ol o gic wit hi n 6 m o nt hs pri or t o scree ni n g . 
•  
Plas ma p heresis wit hi n 1 2 wee ks pri or t o scree ni n g . 
•  
Plas ma e x c ha n ge wit hi n 1 2 wee ks pri or t o scree ni n g . 
•  
I ntra ve n o us i m m u n o gl o b uli n (I VI G) t hera p y wit hi n 2 4 wee ks pri or t o scree ni n g . 
•  
Ot her pr o hi bite d me dicati o ns wit hi n 2 wee ks or 5 half -li ves, w h ic he ver is l o n ger pri or 
t o first I P d osi n g . 
− 
C o nc urre nt use of a ntic h oli ner gic a ge nts or a n y ot her me dicati o n k n o w n t o ca use dr y 
m o ut h/ dr y e yes t h at, i n t he o pi ni o n of t he i n vesti gat or, are  a c o ntri b uti n g fact or t o t he 
s u bject’s dr y ness a n d/ or use of a ntic h oli ner gic a ge nts n ot c o ntri b uti n g t o t his dr y ness , if 
n ot sta ble at least 4 wee ks pri or t o scree ni n g.  
− 
S u bject has a hist or y of t u berc ul osis ( T B) dia g n osis or e vi de nce of acti ve or late nt 
i nfecti o n wit h Myc o b a cteri u m t u berc ul osis . 
− 
S u bject has a hist or y of l y m p h o ma or a n y mali g na nc y wit hi n t he past 5 years pri or t o 
scree ni n g wit h t he e x cepti o n of e xcise d a n d c urati vel y treate d n o n -metastatic basal cell 
carci n o ma or s q ua m o us cell carci n o ma of t he s ki n or carci n o ma i n sit u of cer vi x w hic h is 
c o nsi dere d c ure d wit h mi ni mal ris k of rec urre nce.  
− 
S u bject has s e vere or ga n ma nifestati o n or life -t hreate ni n g c o n diti o n , or has pla n ne d a 
s ur ger y d uri n g t he st u d y. 
Tre at me nt a n d Tre at me nt Sc he d ule  
 
 
St a bl e
Tr e at m e nt
R e gi m e n
4 W
W e e k 1 -1 2
R N D
D 1
F oll o w -u p W 1 6
S cr e e ni n g
W e e k -4
G L P G 3 9 7 0 (4 0 0 m g q. d .) + S o C ( N = 2 0 )
S o C
Pl a c e b o + S o C ( N = 1 0 )
S o C

G al a p a g o s  
C O N FI D E N TI A L  
4 3 9 5 2 _ 1 7 1 8 5 _ 5 1 8 4 2  
G L P G 3 9 7 0 - C L-2 0 7  
-2 3 - 
 
I n vesti g ati o n al Pr o d uct, D os a ge, a n d M o de of A d mi nistr ati o n  
G L P G 3 9 7 0 will be pr o vi de d as a fil m-c oate d ta blet c o ntai ni n g 2 0 0 m g of t he acti ve 
p har mace utical i n gre die nt G 1 5 6 7 9 7 0 ( G 1 5 6 7 9 7 0 is t he c o m p o u n d c o de f or G L P G 3 9 7 0). A 
d ose of 4 0 0 m g ( 2  x 2 0 0 m g ta b lets) q. d. will be ta ke n orall y.  
G L P G 3 9 7 0 will be a d mi nistere d i n a fast e d state at Visit 1  ( Da y 1) a n d i n a fe d state (t o get her 
wit h a meal) at all ot her d osi n g da ys . 
Matc hi n g place b o ta bl ets will als o be pr o vi de d.  
St atistic al A n al ysis   
S afety A n alysis  
All safet y a nal yses will be perf or me d usi n g t he Safet y A nal ysis Set, c o nsisti n g of all 
ra n d o mize d s u bjects w h o recei v e d at least 1 d ose of I P. All safet y data c ollecte d o n or after t he 
first d ose of I P a d mi nistrati o n u p t o t he last c o ntact after t h e last d ose of I P, 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 I P rece i ve d. Cli nical safet y 
will be a d dresse d b y assessi n g a d verse e ve nts ( A Es ), la b orat or y assess me nts, p h ysical 
e x a mi nati o ns, vital si g ns, a n d 1 2 -lea d electr ocar di o gra ms ( E C Gs ). 
Effic acy A n alysis  
All efficac y a n al ys es will be perf or me d usi n g t he F ull A nal ysis Set, c o nsisti n g of all 
ra n d o mize d s u bjects w h o ha ve recei ve d at least 1 d ose of I P.  
T he si g n al detecti o n met h o d ol o g y des cri be d b y Fre wer et al.  will be use d t o pr o vi de f urt her 
i nsi g ht i nt o t he treat me nt effect of G L P G 3 9 7 0 o ver place b o, a n d will s u p p ort sce nari o 
a nal ys es. A mi x e d m o del f or re p eate d meas ures ( M M R M) ( E S S D AI) will be use d t o c o m pare 
treat me nt gr o u ps, wit h a 9 0 % c o nfi de nce i nter val ( CI) of t he treat me nt differe nce at Wee k 1 2 . 
C o nti n u o us efficac y e n d p oi nts, i ncl u di n g t he pri mar y e n d p oi nt: M M R M t o c o m pare treat me nt 
gr o u ps, wit h a 9 0 % CI  of t he treat me nt differe nce at eac h ti me p oi nt.  
Bi nar y efficac y e n d p oi nts will be prese nte d wit h a 9 0 % e xact CI of t he treat me nt differe nce at 
eac h ti me p oi nt.  
P K A n alysis  
Descri pti ve statistics will be d o ne o n C tr o u g h plas ma le vels f or G L P G 3 9 7 0. O bser ve d plas m a 
C tr o u g h f or G L P G 3 9 7 0 will be re p orte d i n t he cli nical st u d y re p ort ( C S R). 
All o bser ve d G L P G 3 9 7 0 plas ma c o nce ntrati o ns will be a nal yze d usi n g a p o p ulati o n P K 
( p o p-P K) a p pr oac h t o c haract erize t he P K pr ofile of G L P G 3 9 7 0. T his a nal ysis will pr o vi de 
si m ulate d p o p -P K para m eters f or G L P G 3 9 7 0, s uc h as cleara nce ( C L/ F) a n d v ol u me of 
distri b u ti o n at stea d y stat e ( Vss), a n d t h eir ass ociate d varia bilit y, as well as i n di vi d ual 
esti mates of area u n der t he plas ma c o nce ntrati o n -ti me c ur ve ( A U C) a n d, if a p pr o priate, 

G al a p a g o s  
C O N FI D E N TI A L  
4 3 9 5 2 _ 1 7 1 8 5 _ 5 1 8 4 2  
G L P G 3 9 7 0 - C L-2 0 7  
-2 5 - 
 
2.    
I N T R O D U C TI O N 
Sj ö gre n’s S y n dr o me ( S jS) is a sl o wl y pr o gressi ve s yste mic c hr o nic a ut oi m m u ne dis or der 
c haracterize d b y l y m p h o c ytic i nfiltrati o n of e x ocri ne gla n ds ca usi n g lacri mal a n d sali var y gla n d 
d ysf u ncti o n. Cli nical prese ntati o n varies fr o m mil d s y m pt o ms s uc h as dr y e yes 
( kerat o c o nj u ncti vitis sicca) a n d dr y m o ut h ( xer ost o mia), art hral gia, a n d c hr o nic fati g ue, t o se vere 
s yste mic s y m pt o ms, i n v ol vi n g m ulti ple or ga n s yst e ms ( 1). I n m ore t ha n 3 0 % of cas es, 
e xtra-gla n d ul ar s yste mic disease ma nifest ati o ns ca n de vel o p, s uc h as art hritis, ne p hritis, 
c yt o p e nia, p ne u m o nitis, vasc ulitis, a n d ne ur ol o gical c o m plicati o ns. F urt her m ore, s u bjects 
s ufferi n g fr o m SjS ha ve a mar ke d i ncrease d ris k of l y m p h o ma ( 2, 3). Disa bli n g fati g ue a n d loss of 
w or ki n g pr o d ucti vit y n e gati vel y affect  t he patie nt’s q ualit y of life ( Q o L). T he disease ma y occ ur 
as a pri mar y f or m ( pri mar y Sj ö gre n’s S y n dr o me [ p S S ]) or as a sec o n dar y f or m ass ociate d wit h 
ot her c o n diti o ns ( m ost c o m m o nl y r he u mat oi d art hritis [ R A] a n d s yst e mic l u p us er yt h e mat os us 
[ S L E]). T he esti mate d pre vale nce is 0. 0 6 % w orl d wi de . It is k n o w n t o affect peri me n o pa usal 
w o me n m ore fre q ue ntl y t ha n me n a n d m ore fre q ue ntl y a n d  m ore s e verel y Ca ucasia ns t ha n ot her 
races ( 1, 3). 
Al t h o u g h diseas e pat h o ge nesis has n ot yet bee n f ull y el uci date d, s u bsta ntial data has 
de m o nstrate d t hat a b n or mal a ut oi m m u ne res p o nses i n v ol ve i n nate a n d a da pti ve i m m u nit y, 
p ossi bl y tri g gere d b y viral i nfecti o ns a n d h or m o n al fact ors i n ge neticall y pre dis p ose d  i n di vi d uals. 
Sali var y gla n d e pit helial cells,  al o n gsi d e cl uster of differe ntiati o n 4 ( C D 4 + )  T -l y m p h oc ytes a n d 
als o B-l y m p h oc ytes, acti vate d a n d/ or sti m ulate d b y i nterfer o ns a n d ot her c yt o ki nes ma y t h us 
tri g ger a n d mai ntai n c hr o nic i m m u ne acti vati o n res ulti n g i n a vici o us c ycle of a ut oi m m u nit y. 
F urt her m ore, a ra n ge of a ut oa nti b o dies ca n be pres e nt i n S jS (a nti -S S A/ R o a n d a nti -S S B/ La 
a nti b o dies, r he u mat oi d fact or, cr y o gl o b uli ns, a nti -n uclear  a ntib o dies), c o m plicati n g t he 
prese ntati o n ( 4, 5). T here is als o a p ote ntial r ole of i m m u ne fact ors t hat i nfl u e nce ce ntral n er v o us 
s yste m (C N S ) be h a vi or wit h a n i mpact u p o n effere nt ne ur o nal pat h wa ys t hat sti m ulate secret or y 
gla n ds ( 6). I n a d diti o n t o i m m u ne mec ha nis ms, se veral n o n-i m m u ne fact ors ma y be i n v ol ve d i n 
t he pat h o ge nesis ( 5).  
C urre ntl y, t here is n o c ure, n or a n efficaci o us s yste mic i m m u n o m o d ulat or y  a ge nt f or t he 
treat me nt of pS S. T he g o als of t hera p y i n patie nts wit h p S S are s y m pt o m palliati o n, pre ve nti o n of 
c o m plicati o ns, ma na ge m e nt of s yst e mic ma nifestati o ns, a n d gla n d ular a n d l y m p h o pr oliferati ve 
disease. T he treat me nt of sicca s y m pt o ms al o ne, wit h o ut gla n d ular e nlar ge me nt or  ot her or ga n 
i n v ol ve me nt, ge n erall y d oes n ot re q uire s yste mic t hera p y ot her t ha n secreta g o g ues ( pil ocar pi ne, 
ci me vili ne). Ster oi ds a n d t y pical disease -m o dif yi n g a ntir he u matic dr u gs ( D M A R Ds ) ha ve ofte n 
li mite d efficac y, a n d t here is n o p har mac ol o gical i nterve nti o n a gai nst t he fati g ue. He nce, t h e 
u n met me dical nee d f or m ore -effecti ve treat me nt o pti o ns is si g nifica nt. N o vel bi ol o gical 
t hera pies ma y directl y i nter ve ne wit h t he pat h o p h ysi ol o g y of t he s y n dr o me a n d t h us i m pr o ve 
gla n d ular a n d e xtra gla n d ular ma nifes tati o ns of p S S ( 7, 8). Oral, s mall-m olec ule i n hi bit ors of 
i ntracell ular ki nases mi g ht bri n g thera pe utic be nefit i n a wi de ra n ge of i nfl a m mat or y dis eases, 
i ncl u di n g p S S ( 9). 
G L P G 3 9 7 0 has a d ual m ec ha ni s m of acti o n wit h t he p ote ntial t o i m pr o ve u p o n t he c urre ntl y 
a vaila ble treat me nts, via t he i n d ucti o n of i m m u n ore g ulat or y mec ha nis ms i n a d diti o n t o its a nti -
i nfla m mat or y pr o perties. G L P G 3 9 7 0 is a n oral, sel ecti ve, s mall-m olec ule seri ne/t hre o ni ne salt -

G al a p a g o s  
C O N FI D E N TI A L  
4 3 9 5 2 _ 1 7 1 8 5 _ 5 1 8 4 2  
G L P G 3 9 7 0 - C L-2 0 7  
-2 8 - 
 
relati ve bi oa vaila bilit y of a n i nitial e x pl orat or y s oli d f or m ulati o n (ca ps ules fille d wit h mi ni-
ta blets) a n d t he effect of f o o d o n t he P K wit h b ot h f or m ulati o ns ha ve bee n c o m plete d, w hile t he 
part i n s u bjects wit h ps oriasis is o n g oi n g. T he si n gle a n d m ulti ple asce n di n g part s of t he st u d y 
were ra n d o mize d, d o u ble-bli n d, a n d place b o -c o ntr olle d t o e val uate t he safet y, t olera bilit y, 
p har mac o ki netics ( P K) 
 of G L P G 3 9 7 0 i n a d ult healt h y male 
s u bjects. T he si n gl e asce n di n g d ose p art e val u ate d G L P G 3 9 7 0 i n t he d ose ra n ge 1 0 m g t o 5 0 0 m g 
a n d i n t he m ulti ple asce n di n g d ose p art d oses of 1 0 0 m g q. d., 2 5 0 m g q. d., a n d 4 0 0 m g q. d were 
e val uate d o v er a p eri o d of 1 4  da ys.  
A d mi nistrati o n of G L P G 3 9 7 0 was well t olerat e d. N o deat hs, seri o us treat me nt-e mer ge nt a d verse 
e ve nts ( T E A Es), or T E A Es lea di n g t o st u d y dr u g disc o nti n uati o n were re p orte d.  N o cli nicall y 
si g nifica nt a b n or malities relate d t o la b orat or y para meters, car di o vasc ular safet y 
(electr ocar di o gra m [ E C G]), vital si g ns, or p h ysical e xami nati o n were re p orte d.  

G al a p a g o s  
C O N FI D E N TI A L  
4 3 9 5 2 _ 1 7 1 8 5 _ 5 1 8 4 2  
G L P G 3 9 7 0 - C L-2 0 7  
-2 9 - 
 

G al a p a g o s  
C O N FI D E N TI A L  
4 3 9 5 2 _ 1 7 1 8 5 _ 5 1 8 4 2  
G L P G 3 9 7 0 - C L-2 0 7  
-3 0 - 
 
A d diti o nal P K a n d safet y data, as well as t h e c o m p ositi o ns of t he f or m ulati o ns are des cri be d i n 
t he latest versi o n of t he I B a n d its rele va nt u p dates/a d de n da. 
3.    
C LI NI C A L S T U D Y O B J E C TI V E S  
3. 1.    
Pri m ar y O bj e cti v e s  
− 
T o e val uate t he effi cac y of G L P G 3 9 7 0 c o m pare d t o place b o o n t he si g ns a n d s y m pt o ms of 
p S S.  
− 
T o e val uate t he safet y a n d t olera bilit y of G L P G 3 9 7 0 c o m pare d t o place b o.  
3. 2.    
S e c o n d ar y O bj e cti v e s  
− 
T o f urt her c haracterize t he effi cac y of G L P G 3 9 7 0 c o m par e d t o place b o o n t he patie nt -
re p orte d si g ns a n d s y m pt o ms of p S S. 
− 
T o c haracterize t he P K  of G L P G 3 9 7 0.  
3. 3.  
 
 
 
 
 
 
 
 
 

G al a p a g o s  
C O N FI D E N TI A L  
4 3 9 5 2 _ 1 7 1 8 5 _ 5 1 8 4 2  
G L P G 3 9 7 0 - C L-2 0 7  
-3 6 - 
 
I n case a ra n d o mize d s u bject is n ot a ble t o atte n d a sc he d ule d st u d y visit o n site d ue t o 
S A R S -C o V -2 tra vel restricti o ns, a p h o ne call or a tele visit ma y be c o n d ucte d. It is str o n g l y 
rec o m me n de d t o c o n d uct pla n ne d st u d y assess me nts f or t he a p plica ble visit as per pr ot oc ol as 
m uc h as p ossi ble. If p ossi ble a n d if l ocal re g ulati o ns all o w a n d t he s u bject a grees, trai ne d st u d y 
staff or trai n e d pers o n nel are e n c o ura ge d t o c ollect st u d y assess me nts at t he st u d y s u bject’s h o me 
or a l ocal facilit y if s o cial dista nci n g a n d h y gie ne r ules ca n be a p plie d.  
O nl y staff trai ne d i n c o n d ucti n g t he pr ot o c ol pla n ne d assess me nts are a ut h orize d t o perf or m 
h o me or l ocal facilit y visit assess me nts a n d t he a lter nati ve arra n ge me nts nee d t o be a de q uatel y 
d oc u me nte d. Direct t o Patie nt ( D T P) s hi p me nts are p ossi ble, if nee de d. S u bjects prese nti n g wit h 
si g ns a n d s y m pt o ms of i nfecti o n, i ncl u di n g S A R S-C o V -2 i nfecti o n , s h o ul d i m me diatel y c o ntact 
t he site i n vesti gat or, w h o s h o ul d i nf or m t he s p o ns or’s me dical res p o nsi ble as s o o n as p ossi ble, 
a n d S A R S -C o V -2 testi n g s h o ul d be perf or me d.  
5. 6.    
E sti m a n d s  
I C H draft g ui da nce E 9( R 1) “ St atistic al Pri nci ples f or Cli nic al Tri als: A d de n d u m: Esti m a n ds a n d 
Se nsitivity A n alysis i n Cli nic al Tri als ”  s pecifies t hat a ce ntral q uesti o n f or dr u g de vel o p me nt a n d 
lice nsi n g is t o q ua ntif y treat me nt effects: h o w t he o utc o me of treat me nt c o m pares t o w hat w o ul d 
ha ve ha p p e ne d t o t he sa me s u bjects u n der differe nt treat me nt c o n diti o ns (e. g. ha d t he y n ot 
recei v e d t he treat me nt or ha d t he y recei ve d a differe nt treat me nt). I nt erc urre nt e ve nts nee d t o be 
c o nsi dere d i n t he d escri pti o n of a treat me nt effect o n a varia ble of i nterest b eca use b ot h t he val ue 
of t he varia bl e a n d t he occ urre n ce of t he e ve nt ma y de pe n d o n tre at me nt. T he defi niti o n of a 
treat me nt effect, s pecifie d t hr o u g h a n esti ma n d, s h o ul d c o nsi der w het her val ues of t he varia ble 
after a n i nterc urre nt e ve nt are rele va nt, as well as h o w t o acc o u nt f or t he ( p ossi bl y treat me nt -
relate d) occ urre n ce or n o n-occ urre nc e of t he e ve nt itself. M ore f or mall y, a n esti ma n d defi nes i n 
detail w hat nee ds t o be esti mate d t o a d dress a s pecific scie ntific q uesti o n of i nterest. A 
descri pti o n of a n esti ma n d i ncl u des 4  attri b utes.  
I n dic ate d i n it alic are t he attri b utes i n t he G L P G 3 9 7 0 -C L -2 0 7  st u dy f or t he pri m ary esti m a n d: 
1.  T he p o p ulati o n, t hat is, t he patie nts tar gete d b y t he scie ntific q uesti o n:  
P atie nts wit h active p S S , defi ne d t hr o u g h a p pr o pri ate i ncl usi o n/excl usi o n criteri a t o reflect 
t he t ar gete d patie nt p o p ul ati o n f or a p pr ov al.  F ull A n alysis Set ( F A S), defi ne d as all 
r a n d o mize d s u bjects w h o h ave receive d at le ast 1 d ose of I P. 
2.  T he varia bl e ( or e n d p oi nt), t o be o btai ne d f or eac h patie nt, t hat is re q uire d t o a d dress t he 
scie ntific q uesti o n: 
C h a n ge fr o m b aseli ne i n E S S P RI sc ore at Week 1 2 .  
3.  T he s pecificati o n of h o w t o acc o u nt f or i nterc urre nt e ve nts t o reflect t he scie ntific q uesti o n 
of i nterest:  
E arly tre at me nt disc o nti n u ati o n ( a ny r e as o n) is h a n dle d usi n g t he hy p ot hetic al str ate gy. 
Ot her i nterc urre nt eve nts (e. g. m aj or pr ot oc ol vi ol ati o ns, i nt ake of pr o hi bite d me dic ati o n, 
l ack of c o m pli a nce) are h a n dle d usi n g t he tre at me nt p olicy str ate gy (i.e. t hey are i g n ore d). 
4.  T he p o p ulati o n -le vel s u m mar y f or t he varia ble w hic h pr o vi des, as re q uire d, a basis f or a 
c o m paris o n bet wee n treat me nt c o n diti o ns:  

G al a p a g o s  
C O N FI D E N TI A L  
4 3 9 5 2 _ 1 7 1 8 5 _ 5 1 8 4 2  
G L P G 3 9 7 0 - C L-2 0 7  
-3 7 - 
 
Le ast s q u are me a n o bt ai ne d usi n g mixe d m o del  f or re pe ate d me as ur e me nts ( M M R M). F or 
f urt her det ails, see t he st u dy st atistic al a n alysis pl a n (S A P ). 
T o get h er t hese attri b utes descri be t he pri mar y esti ma n d, defi ni n g t h e treat me nt effect of i nterest.  
T he desi g n of t he G L P G 3 9 7 0 -C L -2 0 7  st u d y tar gets t his esti ma n d as it is a ra n d o mize d parallel-
gr o u p st u d y w here e ver y atte m pt is ma de t o c ollect all meas ure me nts t hr o u g h o ut t he st u d y.  
Details o n se nsiti vit y a nal yses f or t he pri mar y esti ma n d or sec o n dar y esti m a n ds will be i n t he 
S A P.  
6.    
C LI NI C A L S T U D Y P O P U L A TI O N  
6. 1.    
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 partici pati o n i n t his 
st u d y: 
1.  Male or fe m ale s u bject b et wee n 1 8 -7 4  years of a ge (e xtre mes i ncl u de d), o n t he date of 
si g ni n g t he I C F. 
2.  D oc u me nte d dia g n osis of p S S f or < 1 0 years pri or t o scree ni n g A N D defi ne d b y t he 
classificati o n criteria > = 4 descri be d b y t he A merica n C olle ge of R he u mat ol o g y  - E ur o pea n 
Lea g ue A gai nst R he u matis m ( A C R -E U L A R)  ( 1 0). 
3.  S u bject has a n E S S D AI s c ore > = 5  ass esse d o n 7 d o mai ns: c o nstit uti o nal, l y m p ha de n o pat h y, 
gla n d ular, artic ular, c uta ne o us, he mat ol o gi cal, a n d  bi ol o gical . 
4.  S u bject has a n E S S P RI s c ore > = 5.  
5.  S u bject has sti m ulate d w h ole sali var y fl o w rate of > = 0. 1  m L/ mi n.  
6.  S u bject has p ositi ve ser u m titers of a nti -S S -A/ R o a n d/ or a nti -S S -B/ La a nti b o dies.  
7.  S u bjects alrea d y o n treat me nt s h o ul d be o n sta ble  S o C f or at least 4 wee ks pri or t o first I P 
d osi n g.  
T he f oll o wi n g S o C me di cati o ns  are per mitte d : 
•  
C ortic oster oi ds < = 7. 5  m g/ da y  ( pre d nis o ne or e q ui vale nt); A N D/ O R  
•  
N o n -ster oi dal a nti-i nfla m mat or y dr u gs ( N S AI Ds); A N D/ O R  
•  
O ne si n gl e a nti malarial at a sta ble d ose ( h y dr o x yc hl or o q ui ne < = 4 0 0 m g/ da y; q ui nacri ne 
1 0 0 m g/ k g/ da y, or c hl or o q ui ne < = 2 5 0 m g/ da y); A N D/ O R  
•  
O ne si n gl e i m m u n os u p pressa nt at a sta ble d ose ( met h otre xate [ M T X] < = 1 0 m g/ wee k or 
azat hi o pri ne [ A Z A] < = 2  m g/ k g/ da y); A N D/ O R  
•  
O ne si n gl e c h oli ner gic sti m ula nt at a sta ble d ose (e. g. pil ocar pi ne, ce vi meli ne).  
8.  S u bject m ust be a ble a n d willi n g t o c o m pl y wit h t he C S P  re q uire me nts a n d m ust si g n a n d 
date  t he I C F as a p pr o ve d b y t he I n de pe n de nt Et hics C o m mittee (I E C) / I nstit uti o nal Re vie w 
B oar d ( I R B), pri or t o a n y scree ni n g e val uati o ns. 
9.  S u bject m ust be a ble a n d willi n g t o c o m pl y wit h restricti o ns o n pri or a n d c o nc o mita nt 
me dicati o n (as des cri be d i n Secti o n 6. 3. 2 ). 
1 0.  Fe male s u bject of c hil d b eari n g p ote ntial m ust ha ve a ne gati ve hi g hl y se nsiti ve  (ser u m beta 
h u ma n c h ori o nic g o na d otr o pi n or uri ne di pstic k)  pre g na nc y t est.  

G al a p a g o s  
C O N FI D E N TI A L  
4 3 9 5 2 _ 1 7 1 8 5 _ 5 1 8 4 2  
G L P G 3 9 7 0 - C L-2 0 7  
-3 8 - 
 
1 1.  Fe male s u bject of c hil d b eari n g p ot e ntial or male s u bject m ust a gree t o use hi g hl y effecti ve 
c o ntrace pti o n/ pre ve nti ve e x p os ure meas ures (as descri be d i n Secti o n 6. 3. 1 ). 
1 2.  S u bject m ust ha ve a b o d y mass i n de x ( B MI) bet wee n 1 8 -3 2  k g/ m² , i ncl usi ve. 
1 3. 1  S u bject m ust be me dicall y sta ble o n t h e basis of p h ysical e xa mi nati o n, me dical hist or y, vital 
si g ns, 1 2-lea d E C G, a n d cli nical la b orat or y tests p erf or me d pri or t o first I P d osi n g. If t here 
are a b n or malities, t he y s h o ul d be c o nsiste nt wit h t he u n derl yi n g i ll ness i n t he st u d y 
p o p ulati o n or c o nsi dere d n ot t o be cli nicall y si g nifica nt i n t he o pi ni o n of t he i n vesti gat or.  
6. 2.    
E x cl u si o n Crit eri a  
S u bjects meeti n g o ne or m ore of t he f oll o wi n g criteria ca n n ot b e select e d f or t his cli nical st u d y: 
1.  Sec o n dar y Sj ö gre n's s y n d r o me acc or di n g t o t he A C R -E U L A R  ( 2 0 1 6) classificati o n ( 1 0). 
2.  Hist or y or prese n ce of u nsta ble c o n diti o n n ot relate d t o Sj ö gre n’s  S y n dr o me t hat, i n t he 
o pi ni o n of t he i n vesti gat or,  c o ul d c o nstit ute a n u nacce pta ble ris k w he n ta ki n g t he  I P or 
i nterfere wit h t he i nter pretati o n of data.  
3.  S u bject has a n y acti ve s yste mic i nfecti o n wit hi n 2 wee ks pri or t o first I P d osi n g, or p o orl y 
c o ntr olle d c hr o nic car diac, p ul m o nar y, or re nal disease.  
4.  S u bject has a k n o w n or s us pecte d hist or y of or a c urre nt i m m u n os u p pressi ve c o n diti o n , or a 
hist or y of o p p ort u nistic i nfecti o ns (e. g. HI V  i nfecti o n, hist o plas m osis, listeri osis, 
c occi di o d m yc osis, p ne u m oc yst osis, as per gill osis).  
5.  S u bject has a c hr o nic he p atitis B vir us ( H B V) i nfecti o n, as defi ne d b y persiste nt H B V 
s urface a nti ge n ( H Bs A g) p ositi vit y. S u bject has he patitis C vir us ( H C V) i nfecti o n, as defi ne d 
b y p ositi ve H C V  a nti b o d y at scree ni n g a n d detect a ble H C V vire mi a. S u bjects w it h p ositi ve 
H C V a nti b o d y  m ust u n d er g o refle x H C V ri b o n ucleic aci d (R N A ) testi n g, a n d s u bjects wit h 
H C V R N A p ositi vit y will be e x cl u de d. S u bjects wit h p ositi ve H C V a nti b o d y  a n d ne gati ve 
H C V R N A are eli gi ble.  
6. 1  S u bject testi n g p ositi ve f or S A R S -C o V -2 i nfecti o n as detecte d at scree ni n g base d o n real 
ti me p ol y m eras e c h ai n reacti o n ( R T-P C R)  or at baseli ne base d o n  i m m u n o gl o b uli n M (I g M) 
i m m u n oassa y, or s u bjects w h o ha ve bee n i n c o ntact wit h S A R S-C o V -2 i nfecte d i n di vi d uals 
i n t he 2  wee ks pri or t o firs t d osi n g of I P. S u bjects prese nti n g a n y si g ns or s y m pt o ms of 
S A R S -C o V -2 i nfecti o n, as detecte d pri or t o first I P d osi n g f oll o wi n g caref ul p h ysical 
e x a mi nati o n (e. g. c o u g h, fe ver, hea dac hes, fati g ue, d ys p nea, m yal gia, a n os mia, d ys ge usia, 
a n ore xia, s ore t hr o at, etc.) ( 1 1, 1 2). I n a d diti o n, a n y ot her l o call y a p plica bl e sta n dar d 
dia g n ostic criteria ma y als o a p pl y t o r ule o ut S A R S -C o V -2 i nfecti o n.  
S u bject has ta ke n a n y dis all o we d t hera pi es.  
•  
M yc o p h e n olate m ofetil ( M M F) wit hi n a wee k pri or t o scree ni n g. 
•  
C ycl os p ori ne/ T acr oli m us wit hi n a wee k pri or t o scree ni n g . 
•  
C ycl o p h os p ha mi de wit hi n 6  m o nt hs pri or t o scree ni n g . 
•  
O c ular me dici n es (e. g. t o pical c ycl os p ori ne , t o pical N S AI Ds/c ortic oster oi ds) f or at least 
4 wee ks pri or t o scree ni n g, e x ce pt f or a s p ora dic use. 
•  
Bi ol o gics s u c h as , b ut n ot li mite d t o, rit u xi ma b, a batace pt, a nd a n y ot her u na p pr o ve d 
bi ol o gic  wit hi n 6 m o nt hs pri or t o scree ni n g . 
•  
Plas ma p heresis wit hi n 1 2 wee ks pri or t o scree ni n g . 
7. 3  

G al a p a g o s  
C O N FI D E N TI A L  
4 3 9 5 2 _ 1 7 1 8 5 _ 5 1 8 4 2  
G L P G 3 9 7 0 - C L-2 0 7  
-3 9 - 
 
•  
Plas ma e x c ha n ge wit hi n 1 2 wee ks pri or t o scree ni n g . 
•  
I ntra ve n o us i m m u n o gl o b uli n (I VI G) t hera p y wit hi n 2 4 wee ks pri or t o scree ni n g . 
•  
Ot her pr o hi bite d me dicati o ns wit hi n 2 wee ks or 5 half -li ves, w h ic he ver is l o n ger , pri or 
t o first I P d osi n g, as liste d i n Secti o n 6. 3. 2 .  
8 . 1  C o nc urre nt use of a ntic h oli ner gic a ge nts  or a n y ot her m e dicati o n k n o w n t o ca use dr y 
m o ut h/ dr y e yes  t h at, i n t he o pi ni o n of t he i n vesti gat or, are  a c o ntri b uti n g fact or t o t he 
s u bject’s dr y ness  a n d/ or use of a ntic h oli ner gic a ge nts n ot c o ntri b uti n g t o t his dr y ness, i f n ot 
sta ble f or at least 4 wee ks pri or t o scree ni n g (see Secti o n 6. 3. 2 ). 
9.  S u bject has a hist or y of T B dia g n osis or e vi de nce of acti ve or late nt i nfecti o n wit h 
Myc o b act eri u m t u berc ul osis.  
•  
P ositi ve Q ua nti F E R O N -T B G ol d test res ult at scree ni n g, A N D/ O R  
•  
C hest ra di o gra p h ( p osteri or a nteri or vie w) ta ke n wit hi n 1 2 wee ks pri or t o scree ni n g, rea d 
b y a q u alifie d ra di ol o gist or p ul m o n ol o gist, wit h e vi de nce of c urre nt acti ve T B or 
i nacti ve T B. 
1 0.  I n v esti gat or or ot her st u d y staff or relati ve t here of w h o is directl y i n v ol ve d i n t he c o n d uct of 
t he st u d y. 
1 1.  S u bject has a n y c o n diti o n or circ u msta nces t hat , i n t he o pi ni o n of t he i n vesti gat or, ma y ma ke 
a s u bject u nli kel y or u na ble t o c o m plete t he st u d y or c o m pl y wit h st u d y pr oce d ures a n d 
re q uire me nts (e. g. acti ve alc o h ol or dr u g a b us e) . 
1 2.  S u bject has a k n o w n h y p erse nsiti vit y t o I P i n gre di e nts or hist or y of a si g nifica nt aller gic 
reacti o n t o IP i n gre die nts as deter mi ne d b y t he i n vesti gat or.  
1 3.  S u bject has a n y c o n diti o n f or w hic h, i n t he o pi ni o n of t he i n vesti gat or, partici pati o n w o ul d 
n ot be i n t he best i nterest of t he s u bject (e .g . c o m pr o mise t he well -bei n g) or t hat c o ul d 
pre ve nt, li mit, or c o nf o u n d t he pr ot oc ol -s pecifie d assess me nts. 
S u bject has prese n ce or se q uelae of gastr oi ntesti nal, li ver , ki d ne y (creati ni ne cleara nce 
< 6 0  m L / mi nute , usi n g t he C oc kcr oft-Ga ult f o r m ul a: if calc ulat e d res ult is <6 0  m L/ mi n ute , a 
2 4 -h o ur uri ne c ollecti o n ca n be d o ne) , or ot her c o n diti o ns k n o w n t o i nterfere wit h t he 
a bs or pti o n, distri b uti o n, meta b olis m, or e xcreti o n of dr u gs.   
1 5.  S u bject has a hist or y of l y m p h o ma or a n y mali g na nc y wit hi n t he past 5  years pri or t o 
scree ni n g wit h t he e x ce pti o n of e x cise d a n d c urati vel y treate d n o n -metastatic basal cell 
carci n o ma or s q ua m o us cell carci n o ma of t he s ki n or carci n o ma i n sit u of cer vi x w hic h is 
c o nsi dere d c ured wit h mi ni mal ris k of rec urre nce . 
1 6.  S u bject c o nc urre nt l y p artici pates or partici p ate d i n a dr u g, dr u g/ de vice, or bi ol o gic 
i n vesti gati o nal researc h st u d y wit hi n 3 m o nt hs or 5  half -li ves of t he IP, w hic he ver is l o n ger, 
pri or t o t he first d ose. 
S u bject has a h ist or y or prese nce  of car di o pat h y,  or  cli nicall y si g nifica nt a b n or malities 
detecte d o n 1 2 -l ea d E C G of eit her r h yt h m or c o n d ucti o n e. g. re peate d de m o nstrati o n of a 
Q Tc F > 4 5 0  ms detect e d o n t he 1 2 -lea d E C G or a hist or y of a d diti o nal ris k fact o rs f or T d P 
(e. g. heart fail ure, fa mil y hist or y of l o n g Q T sy n dr o me, h y p o kale mia a n d ot her electr ol yt e 
dis or ders) . A first-de gree atri o ve ntric ular bl o c k will n ot be c o nsi dere d as a si g nifica nt 
a b n or malit y.  
1 8.  Hist or y of or ga n or b o n e marr o w tra ns pl a nt.  
1 9.  Fe male s u bject is pre g na nt or breast fee di n g or i nt e n di n g t o bec o me pre g na nt or breastfee d 
d uri n g t he st u d y . 
1 4. 2  
1 7. 2  

G al a p a g o s  
C O N FI D E N TI A L  
4 3 9 5 2 _ 1 7 1 8 5 _ 5 1 8 4 2  
G L P G 3 9 7 0 - C L-2 0 7  
-4 0 - 
 
2 0. 1 S u bject was vacci nate d wit h a li ve atte n uate d vacci ne wit hi n 6 0 da ys pri or t o scree ni n g.  
2 1. 1 S u bject has se vere or ga n ma nifestati o n or life-t hreate ni n g c o n diti o n, or has pla n ne d a 
s ur ger y d uri n g t he st u d y. 
2 2. 2 S u bject  has a n y of t he f oll o wi n g la b orat or y a b n or malities:  
•  
as partate a mi n otra nsferas e ( A S T)  > 2 ti mes t he u p per li mit of n or mal ( U L N)  
•  
ala ni ne a mi n otra nsferas e ( A L T) > 2 ti mes t he U L N  
•  
t otal bilir u bi n > 2 ti mes t he U L N  
•  
pr ot hr o m bi n ti me or partial t hr o m b o plasti n ti me >  U L N.  
•  
ser u m p otassi u m c o nce ntrati o n < 3. 5 m m ol/ L  
2 3.  S u bject is i nstit uti o nalize d b y virt ue of a n or der iss ue d b y eit her t he j u dicial or t he 
a d mi nistrati ve a ut h orities or has a de pe n de nc y o n t he s p o ns or or i n vesti gat or. 
6. 3.    
Pr o hi biti o n a n d R e stri cti o n s  
6. 3. 1.    
Pr e c a uti o n s f or S e x u al Int er c o ur s e  
Hi g hl y effecti ve c o ntrace pti ve meas ures f or b ot h males a n d fe m ales of c hil d beari n g p ote ntial 
m ust be d oc u me nte d i n t he s o urce d o c u me nts.  
6. 3. 1. 1.    
F e m al e S u bj e ct s  
F e male s u bjects are c o nsi dere d of n o n -c hil d beari n g p ote ntial if t he y meet o ne of t he f oll o wi n g 
criteria:  
− 
N o me nses f or 1 2 or m ore m o nt hs wit h o ut a n alter nati ve me dical ca use. A hi g h f ollicle 
sti m ulati n g h or m o ne ( F S H) le vel i n t he p ostme n o pa usal  ra n ge ma y be use d t o c o nfir m a 
p ost me n o pa usal state i n w o me n n ot usi n g h or m o nal c o ntrace pti o n or h or m o nal re place me nt 
t hera p y. H o we ver, i n t he a bse nce of 1 2 m o nt hs of a me n orr hea, a si n gle F S H meas ure m e nt is 
i ns ufficie nt. 
− 
Per ma ne ntl y s ur gicall y st erile ( bilater al o o p h orect o m y, i.e. s ur gical re m o val of o varies, 
bilateral sal pi n gect o m y , or h ysterect o m y, i.e. s ur gical re m o val of ut er us). 
 
All ot her fe male s u bjects are c o nsi d ere d t o be of c hil d beari n g p ot e ntial ( W O C B P) a n d m ust use 
o ne of t he f oll o wi n g hi g hl y effecti ve met h o ds of birt h c o ntr ol pri or t o t he first d ose of I P, d uri n g 
t he cli nical st u d y a n d f or at least 3 5 da ys  after t he l ast d ose of I P : 
− 
C o m bi ne d (estr o ge n a n d pr o gester o ne c o ntai ni n g) ( oral, i ntra va gi n al, tra ns d er mal) h or m o nal 
c o ntrace pti o n ass ocia te d wit h i n hi biti o n of o v ulati o n pl us a barrier met h o d.  
− 
Pr o gester o ne -o nl y h or m o nal ( oral, i njecta ble, i m pla nta ble) c o ntrace pti o n ass ociate d wit h 
i n hi biti o n of o v ulati o n pl us a barrier met h o d.  
− 
I ntra uteri ne de vice. 
− 
I ntra uteri ne h or m o ne-rel easi n g s yst e m. 
− 
Bila teral t u bal occl usi o n. 

G al a p a g o s  
C O N FI D E N TI A L  
4 3 9 5 2 _ 1 7 1 8 5 _ 5 1 8 4 2  
G L P G 3 9 7 0 - C L-2 0 7  
-4 1 - 
 
− 
Se x ual a bsti ne nce defi ne d as refrai ni n g fr o m heter ose x ual i nterc o urse d uri n g t he e ntire 
peri o d of ris k ass oci ate d wit h t he st u d y treat me nts. T he relia bilit y of se x ual a bsti ne nce nee ds 
t o be e val uate d i n relati o n t o t he d urati o n of t he cli nical st u d y a n d t he preferre d a n d us u al 
lifest yle of t h e s u bject. 
 
Peri o dic a bsti ne nce ( e. g. cale n dar, s y m pt ot her mal, p ost -o v ulati o n met h o ds), declarati o n of 
a bsti ne nce f or t he d urati o n of a cli nical st u d y, wit h dra wal, s per mici des o nl y , a n d lactati o nal 
a me n orr hea met h o d are n ot acce pt a ble as met h o ds of c o ntrace pti o n.  
I n case a W O C B P has a vasect o mize d part ner, pr o vi de d t hat part ner is t he s ole se x ual part ner of 
t he W O C B P cli nical st u d y partici pa nt a n d t hat t he vasect o mize d part ner has recei v e d me dical 
assess me nt of t he s ur gical s uccess, t he n s he is n ot re q uire d t o use a n a d diti o nal f or m of 
c o ntrace pti o n.  
Wit hi n t hese li mits, t he s pecific f or ms of c o ntrace pti o n e m pl o ye d are left t o t he discreti o n of t he 
s u bject, t he i n vesti gat or, a n d/ or t he s u bject’s p h ysicia n.  
T he safet y of G L P G 3 9 7 0  d uri n g breastfee di n g is u n k n o w n. N ursi n g w o me n  are n ot all o we d t o 
ta ke part i n t his cli nical st u d y. 
6. 3. 1. 2.    
M al e S u bj e ct s  
N o n -vasect o mize d male s u bjects wit h fe male part ners of c hil d beari n g p ote ntial m ust be willi n g 
t o use a c o n d o m fr o m t he ti me of t he first d ose of I P, d uri n g t he cli nical st u d y, a n d f or at least 
7  da ys after t he last d ose of I P, i n a d diti o n t o ha vi n g t heir fe male part ner use o ne  of t he f oll o wi n g 
f or ms of c o ntrace pti o n: 
− 
I ntra uteri ne de vice. 
− 
I ntra uteri ne h or m o ne -rel easi n g s yst e m. 
− 
C o m bi ne d (estr o ge n a n d pr o gester o ne c o ntai ni n g) h or m o nal c o ntrace pti o n ass ociate d wit h 
i n hi biti o n of o v ulati o n ( oral, i ntra va gi nal, tra ns der mal). 
− 
Pr o gester o ne -o nl y h or m o nal c o ntrace pti o n ass ociate d wit h i n hi biti o n of o v ulati o n  ( oral, 
i njecta ble, i m pla nta ble). 
 
Se x ual a bsti ne nce defi ne d as refrai ni n g fr o m heter ose x ual i nterc o urse is c o nsi dere d a hi g hl y 
effecti ve c o ntrace pti ve m eas ure  o nl y if it is t he preferre d a n d us ual lifest yle of t he s u bject. T he 
relia bilit y of se x ual a bsti ne nce n ee ds t o be e val uate d i n relati o n t o t he d urati o n of t he cli nical 
st u d y. 
Peri o dic a bsti ne nce ( e. g. cale n dar, s y m pt ot her mal , p ost -o v ulati o n met h o ds), declarati o n of 
a bsti ne nce f or t he d urati o n of a cli nical st u d y, wit h dra wal, s per mici des o nl y , a n d lactati o nal 
a me n orr hea met h o d are n ot acce pt a ble met h o ds of c o ntrace pti o n.  
I n a cas e w here t he fe mal e part ner of a male s u bject has u n der g o ne d oc u me nte d s ur gi cal 
sterilizati o n t hat was perf or me d m ore t ha n 1 year bef ore s cree ni n g, t he n t he s u bject is n ot 
re q uire d t o use a n a d diti o nal f or m of c o ntrace pti o n. 

G al a p a g o s  
C O N FI D E N TI A L  
4 3 9 5 2 _ 1 7 1 8 5 _ 5 1 8 4 2  
G L P G 3 9 7 0 - C L-2 0 7  
-4 2 - 
 
Vasect o mize d male s u bjects wit h fe male part ners of c hil d beari n g p ote ntial are n ot re q uire d t o use 
a n a d diti o nal f or m of c o ntrace pti o n pr o vi di n g t hat s ur gical sterilizati o n has  bee n s uccessf ul 
( d oc u me nte d az o os per mi a b y s e me n a nal ysis). 
N o s per m d o nati o n is all o we d fr o m t he first d ose of I P d uri n g t h e cli nical st u d y u ntil 7 da ys  after 
t he last d ose of I P. 
6. 3. 2.    
Pri or a n d C o n c o mit a nt M e di c ati o n s  
Pri or a n d c o nc o mita nt t h era pies ta k e n f or l o n g-t er m treat me nt of pre-e xisti n g c o n diti o ns are 
all o we d, pr o vi de d t he y are i n acc or da nce wit h t he i ncl usi o n a n d e xcl usi o n criteria (see 
Secti o n  6. 1  a n d Secti o n  6. 2 , res pecti vel y) a n d wit h t he pr o hi biti o ns a n d restricti o ns liste d bel o w.  
I n case a d diti o nal c o nc o mita nt me dicati o ns nee d t o be a d mi nistere d or d os e a dj ust me nts f or pre-
e xisti n g c o n diti o ns (e x c e pt f or acti ve p S S) are nee de d d uri n g t he st u d y, t h e ris k/ be nefit t o t he 
s u bject s h o ul d be caref ull y assess e d b y t he s p o ns or’s me dical lea der a n d c o nsi derati o n gi v e n t o 
t he ti mi n g of a n y necessar y i ntr o d ucti o n of ne w me dicati o ns. 
If d uri n g t he st u d y, t he su bject’s c o n diti o n necessitates t he use of pr o hi bite d me dicati o n, t he use 
of I P ma y b e i nterr u pt e d, prefera bl y after c o ns ultati o n wit h t he s p o ns or’s me dical lea der. 
Re -i ntr o d ucti o n of I P ca n be c o nsi dere d after t he treat me nt c o urs e wit h t he pr o hi bite d me dicati o n 
has bee n st o p pe d, a n d after c o ns ultati o n wit h t he s p o ns or’s me dical lea der.  
D uri n g t h e st u d y, s u bjects will be i nstr ucte d t o rec or d a n y c ha n ge i n c o nc o mita nt me dicati o n i n a 
diar y (see Secti o n  8. 8. 6 ). 
Per mitte d Me dic ati o ns  
Per mitte d me dicati o ns at scree ni n g a n d d uri n g t he st u d y i ncl u de:  
− 
S u bjects alrea d y o n treat me nt s h o ul d be o n sta ble S o C  f or at least 4 wee ks pri or t o first I P 
d osi n g.  
T h e f oll o wi n g m e dicati o ns are per mitte d:  
•  
C ortic oster oi ds, at a d ose of < = 7. 5  m g/ da y pre d nis o ne or e q ui vale nt (see A p pe n di x 1  f or 
pre d nis o ne  c o n v ersi o n ta ble); A N D/ O R  
•  
N S AI Ds; A N D/ O R  
•  
O ne si n gl e a nti malarial at a sta ble d ose ( h y dr o x yc hl or o q ui ne < = 4 0 0 m g/ da y, q ui nacri ne 
1 0 0 m g/ k g/ da y, or c hl or o q ui ne < = 2 5 0  m g/ da y); A N D/ O R  
•  
O ne si n gl e i m m u n os u p pressa nt at a sta ble d ose ( M T X < = 1 0  m g/ wee k  or A Z A 
< = 2 m g/ k g / d a y); A N D/ O R 
•  
O ne si n gl e c h oli ner gic sti m ula nt at a sta ble d ose (e. g. pil ocar pi ne, ce vi meli ne).  
− 
A nal gesics, ot her t ha n N S AI Ds, u p t o t he ma xi m u m rec o m me n de d d os es ma y be use d  f or 
pai n if re q uire d.  
− 
Me dicati o ns prescri be d f or t he treat me nt of c o m or bi dities a n d w hic h are n ot descri be d as 
pr o hi bite d me dicati o ns.  

G al a p a g o s  
C O N FI D E N TI A L  
4 3 9 5 2 _ 1 7 1 8 5 _ 5 1 8 4 2  
G L P G 3 9 7 0 - C L-2 0 7  
-4 6 - 
 
partici pati o n. I n s uc h cas e, t he reas o n f or wit h dra wal will be d oc u me nte d i n t he s o urce 
d oc u me nts, a n d t he s u bject will be as ke d t o c o m pl ete t he earl y disc o nti n uati o n ( E D) v isit, a n d F U 
v isit(s) f or safet y assess me nts. 
Treat me nt wit h I P m ust  be disc o nti n ue d b y t h e i n vesti gat or ( w h o ma y  c o ns ult t he s p o ns or’s 
me dical  lea der) f or a n y of t he f oll o wi n g c o n diti o ns: 
− 
Life -t hreate ni n g a d verse e ve nt ( A E) or a seri o us a d verse e ve nt ( S A E ) t hat places t he s u bject 
at i m me diate ris k.  
− 
Seri o us i nfecti o ns dee me d relate d t o st u d y treat me nt b y t he i n vesti gat or, a n d re q uiri n g 
pare nteral a nti micr o bial t hera p y a n d/ or h os pitalizati o n.  
− 
C o nfir me d pre g na n c y or lactati o n.  
− 
S u bjects n ot meeti n g all i ncl usi o n criteria (e. g. E S S D AI s c ore > = 5 ; see als o Secti o n  6. 1 ) 
a n d/ or s u bjects meeti ng 1  of t he e xcl usi o n criteria  (e. g. creati ni ne cleara nce < 6 0  m L/ mi n ute 
usi n g C oc kcr oft -Ga ult f or m ula ; see als o Secti o n 6. 2 ), as deter mi ne d b y t h e ce ntral la b orat or y  
res ults of Visit 1 ( Da y 1). Bef ore disc o nti n ui n g treat me nt wit h I P bas e d o n t he Visit 1 
( Da y 1) ce ntral la b orat or y res ult s, t he s p o ns or’s me dical lea der s h o ul d be c o ns ulte d. 
− 
S u bjects prese nti n g wit h si g ns a n d s y m pt o ms of S A R S -C o V -2 i nfecti o n s h o ul d i m me diatel y 
c o ntact t he site i n vest i gat or, w h o s h o ul d i nf or m t he s p o ns or’s me dical res p o nsi ble as s o o n as 
p ossi ble, a n d re p ort a n A E/ S A E as a p plica ble. I n case of s us pecte d S A R S -C o V -2 i nfecti o n 
R T -P C R a n d ser ol o g y tests s h o ul d be perf or me d t o c o nfir m t he i nfecti o n. T he i n vesti gat or, 
prefera bl y after c o ns ultati o n wit h t he s p o ns or’s me dical res p o nsi ble, m ust disc o nti n ue t he 
s u bject fr o m t he st u d y. T he s u bject c o ul d be test e d f or S A R S-C o V -2 i n facilities o utsi de t he 
st u d y site a n d if s o, t he s u bject s h o ul d be i nstr ucte d t o i m me diatel y i nf or m t he st u d y 
i n vesti gat or if t he t est is p ositi ve a n d test res ults s h o ul d be s hare d wit h t he i n vesti gat or as 
s o o n as p ossi ble. 
− 
Arr h yt h mia or c o n d u cti o n a b n or malit y, i ncl u di n g b ut n ot li mite d t o pr ol o n ge d Q Tc F,  w here 
t he se verit y is cate g orize d as 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 de 3 or hi g h er ( Q Tc > 5 0 0 ms  a n d/ or 6 0 ms o ver baseli ne  o n at least 2  s e parat e E C Gs 
5  mi n utes a part ) or cli nicall y si g nifica nt arr h yt h mia of a n y gra de. 
− 
Li ver e nz y m e i ncrease  (see als o A p pe n di x  1 5 ) 
•  
A S T a n d/ or A L T > = 8 x t he U L N . 
•  
A S T a n d/ or A L T ele vati o ns > = 3 x U L N wit h si g ns of li ver da ma ge  (i.e. wit h t he 
a p peara nce of fati g u e, na usea, v o miti n g, ri g ht u p p er q ua dra nt pai n or te n der ness , fe ver, 
ras h a n d/ or e osi n o p hilia [ > 5 %], a n d/ or t otal bilir u bi n > = 2. 0 x U L N or i nter nati o nal 
n or malize d rati o [ I N R] > 1. 5) . 
•  
I n a d diti o n, a d ose i nterr u pti o n or re d ucti on (if a p plica ble) s h o ul d be c o nsi dere d if A S T 
a n d/ or A L T > = 3 x U L N a n d < 5 x U L N a n d d osi n g wit h I P s h o ul d be i nterr u pte d if A S T 
a n d/ or A L T > = 5 a n d < 8 x U L N.  
 
F or s u bjects h a vi n g:  
•  
A S T or A L T > = 8 x U L N . 
•  
A S T or A L T > = 3 x U L N wit h si g ns of li ver da m a ge (i.e. wit h t he  a p peara nce of fati g ue, 
na usea, v o miti n g, ri g ht u p per q ua dra nt pai n or te n der ness, fe ver, ras h , a n d/ or 

G al a p a g o s  
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-4 7 - 
 
e osi n o p hilia [ > 5 %], a n d/ or t otal bilir u bi n > = 1. 5 x U L N or I N R > 1. 5) . T hes e cases s h o ul d 
be re p orte d as S A Es.  
 
t he f oll o wi n g ste ps will n ee d t o be perf or me d b y t he i n vesti gat or:  
 
•  
T he site s h o ul d i m me diatel y c o ntact t he s u bject a n d re q uire t he s u bject t o disc o nti n ue I P 
i m me diatel y. T he s u bject s h o ul d be as ke d t o ret ur n t o t he site wit hi n a 4 8-h o ur wi n d o w 
fr o m a ware ness of t he res ult.  
•  
A f ull e val uati o n of vari o us ca uses of he pa titis s h o ul d be c o n d ucte d (i. e. i nfecti o us, 
alc o h ol, me dicati o ns, a nat o mical).  
•  
A n assess me nt of ot her c o nc o mita nt me dicati o ns a n d S o C s h o ul d be ma de. T he 
i n vesti gat or s h o ul d c o nsi der t o w het her it is i n t he best i nterest of t he s u bject to 
st o p/i nterr u pt c o nc o mita nt me dicati o ns a n d S o C treat me nt.  
•  
A detaile d hist or y i nc l u di n g rele va nt i nf or m ati o n o n alc o h ol use, recreati o nal dr u g use, 
s u p ple me nt c o ns u m pti o n, a n y her bal re me dies, fa mil y hist or y, se x ual hist or y, tra vel 
hist or y, hist or y of c o ntact wit h a ja u n dice d s u bject, s ur ger y, occ u pati o nal hist or y, bl o o d 
tra nsf usi o n, hist or y of li ver or aller gic diseas e, a n d a n y ot h er p ote ntial ca uses 
attri b uta ble t o a li ver i ns ult s h o ul d be c ollecte d.  
•  
A detaile d assess me nt of t he s u bject’s cli nical c o n d iti o n a n d re peat la b orat or y tests f or 
li ver f u ncti o n test (L F T ), i ncl u di n g al b u mi n, creati ne ki nase, t otal bilir u bi n ( direct a n d 
i n direct), ga m ma -gl uta m yl tra nsferase ( G G T ), I N R, a n d al kali ne p h os p hat ase s h o ul d be 
d o ne .  
•  
F urt her testi n g f or he patitis A, B,  a n d C, a n d f or a ut oi m m u ne he patitis s h o ul d be d o ne. 
Ot h er ca us es of viral he patitis ( c yt o me gal o vir us  or E pstei n -Barr vir us , etc) s h o ul d be 
e x cl u de d. Li ver i ma gi n g s h o ul d be c o nsi dere d.  
•  
Referral t o a he p at ol o gist or gastr oe nter ol o gist s h o ul d be re q ueste d. 
 
E ver y eff ort s h o ul d be m a de t o kee p s u bjects i n t he st u d y a n d o n treat me nt. H o we ver, t he 
i n vesti gat or, w h o m a y c o ns ult t he s p o ns or’s me dical  lea der, ca n c o nsi der st o p pi n g t he st u d y 
treat me nt i n case of c o n cer ns a b o ut t he s u bject’s safet y, seri o us or se vere A Es or w orse ni n g of 
t he disease c o n diti o n, w hic h i n t he i n vesti gat or’s o pi ni o n nee ds a n alter nati ve treat me nt a p pr oac h 
n ot bei n g c o v ere d i n t he cli nical st u d y ( e. g. res c ue me dicati o n). 
W he n st u d y treat me nt is disc o nti n ue d, t he s u bject will be re q ues te d t o c o m plete t he assess me nts 
of t he E D v isit a n d t o ret ur n f or t he F U visit. Reas o n f or disc o nti n uati o n m ust be d oc u me nte d i n 
t he case re p ort f or m ( C R F). 
S u bjects will be i nf or me d pri or t o cli nical st u d y e ntr y t hat t he y are all o we d t o wit h dra w fr o m t he 
cli nical st u d y. At a n y ti m e a n d f or a n y reas o n, a s u bject’s partici pati o n i n t h e cli nical st u d y m a y 
ter mi nate at t heir re q uest, wit h o ut prej u dice t o t heir f ut ure me dical care. T he s u bject will be 
e nc o ura ge d t o s hare t he reas o n(s) f or wit h dra wal s o t his ca n  be d oc u me nte d i n t he s o urce 
d oc u me nts, a n d t o c o m plete t he E D visit a n d F U  v isit f or safet y assess me nts, b ut will n ot be 
o bli ge d t o d o s o.  

G al a p a g o s  
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-4 8 - 
 
S u bjects w h o wit h dra w fr o m t he cli nical st u d y wit h o ut c o ntact wit h t he site (l ost -t o-F U ) s h o ul d 
be c o ntact e d b y t he site s o t hat t heir healt h stat us ca n be assesse d a n d d oc u me nte d i n t he s o urce 
d oc u me nts. T he site s h o ul d ma ke e ver y eff ort t o u n dersta n d w het h er t he s u bject is ali ve, 
i ncl u di n g c h ec ki n g t he m e dical rec or ds a n d c o ntacti n g ge neral practiti o ner or relati ves, if 
necessar y. All atte m pts m ust be d oc u me nte d i n t he s o urce d oc u me nts.  
T he s p o ns or has t he ri g ht t o ter mi nate t he cli nical st u d y at a n y ti me  a n d f or a n y reas o n .  
T he s p o ns or a n d/ or i n vesti gat or will disc o nti n ue t he st u d y if:  
- 
J u d ge d necess ar y f or me dical, safet y, re g ulat or y, or ot her reas o ns c o nsiste nt wit h 
a p plica ble la ws, re g ulati o ns, a n d I C H-G C P . 
- 
I E C/I R B a n d/ or R A a p pr o val or fa v ora ble o pi ni o n is wit h dra w n , re v o ke d, or s us pe n de d.  
I n t he e ve nt of st u d y ter mi nati o n , t he i n vesti gat ors 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 cli nical st u d y ter mi nati o n. Pleas e als o see f or refere nce Secti o n 1 2. 1. 2  “ Cli nical 
St u d y Cl os ur e C o nsi derati o ns”.  
6. 5.    
M e a s ur e s t o Mi ni mi z e Bi a s  
6. 5. 1.    
R a n d o mi z ati o n  
At scree ni n g, s u bjects will be assi g ne d a s u bject i de ntificati o n  n u m ber . W he n a s u bject is 
c o nfir me d t o be eli gi ble f or t he cli nical st u d y, t he s u bject will be ra n d o mize d. All ocati o n of eac h 
s u bject t o a gi v e n treat me nt will be d o ne usi n g a ce ntralize d el ectr o nic s yst e m (i nteracti ve we b 
res p o nse s yste m [I WR S]) . S u bjects will be ra n d o mize d i n a  2: 1 rati o  t o G L P G 3 9 7 0  or place b o.  
6. 5. 2.    
Bli n di n g a n d U n bli n di n g  
T his is a ra n d o mize d, d o u ble -bli n d cli nical st u d y. T he s u bjects a n d t he e ntire cli nical st u d y tea m, 
i ncl u di n g t he i n vesti gat ors, cli nical st u d y c o or di nat ors, a n d s p o ns or pers o n nel , e xce pt f or t he 
Safet y M o nit ori n g C o m mi ttee, are bli n de d t o treat me nt assi g n me nt . 
Bli n de d a n d pac ka ge d me dicati o n will be pr o vi de d t o t he site. All I P f or m ulati o ns will be 
i de ntical i n a p peara nce, s ha pe, s mell a n d taste, a n d will be pac ka ge d i n t he pr o per pr o p orti o n t o 
ass ure desir e d d osa ges a n d mai nte na nce of t he bli n di n g.  
T he bli n d ca n be br o ke n o nl y if t he i n vesti gat or dee ms it necessar y f or t h e safet y of a s u bj ect. 
T he i n vesti gat or is e nc o ura ge d t o disc uss c o nsi derati o ns t o brea k t he bli n d wit h t he me dical 
lea der of t he st u d y , w he n e ver p ossi ble a n d w here t he sit uati o n all o ws. H o we ver, t he 
res p o nsi bilit y t o brea k t h e treat me nt c o de i n e mer ge nc y sit uati o ns resi des s olel y wit h t he 
i n vesti gat or. T he i n vesti gat or is n ot re q uire d t o dis c uss u n bli n di n g bef ore ha n d if he or s he feels 
ra pi d e mer ge nc y u n bli n di n g is necessar y, b ut is re q uire d t o i nf or m t he s p o ns or i n wit hi n 2 4 h o urs 
after u n bli n di n g has occ urre d . 
T he bli n d ca n be b r o ke n b y t he i n vesti gat or vi a I WR S . 

G al a p a g o s  
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If t he bli n d is br o ke n f or a n y reas o n d uri n g t he c o urse of t he cli nical st u d y, t he m o me nt o n w hic h 
t he bli n d was br o ke n,  a n d all ot her rele va nt i nf or mati o n will be d oc u me nte d b y t h e site. T he 
reas o n f or brea ki n g t he bli n d will be i n dicate d a n d j ustifie d i n t he s o urce d oc u me ntati o n. 
If a n A E lea ds t o u n bli n di n g, t he A E will be gi ve n as t he reas o n f or u n bli n di n g. All s u bjects w h o 
are u n bli n de d s h o ul d, w here p ossi ble, c o m plete t he F U  visit  assess me nts 2 8 ± 3 da ys after last I P 
d osi n g . A n y A Es will be f oll o we d u ntil res ol uti o n. 
T he c o de -brea k i nf or mati o n ( via I W R S ve n d or) will be pr o vi de d t o t he bi o a nal ytical la b orat or y  
res p o nsi ble f or P K sa m pl e a nal ysis , t he sp o ns or  pers o n res p o nsi ble f or pr o vi di n g u n bli n de d data 
t o t he Safet y M o nit ori n g C o m mittee, t he C R O res p o nsi ble f or t he p o p ulati o n P K ( p o p-P K)  
 
, a n d t o t he p har ma c ovi gila nce  ve n d o r f or S A E re p orti n g p ur p oses. 
7.    
I N V E S TI G A TI O N A L P R O DU C T S  
7. 1.    
I d e ntit y of t h e I nv e sti g ati o n al Pr o d u ct s  
G L P G 3 9 7 0 will be s u p plie d t o t he p har macist of t he st u d y site or t o t he h os pital p har mac y, b y 
a n d u n der t he res p o nsi bilit y of t he s p o ns or, w h o will als o pr o vi de  t he i n vesti gat or a n d p har macist 
( or a p pr o priate q ualifie d me m ber of t he cli nical st u d y staff) wit h a p pr o priate certificates of 
a nal yti cal c o nf or mit y a n d E ur o pea n U ni o n ( E U) Q ualifie d Pers o n release d oc u me nts.  
Matc hi n g place b o ta bl ets will als o be pr o vi de d . 
F or m ore d etails o n t he c o m p ositi o n of t he I P refer t o t he latest versi o n of t he I B a n d its rele va nt 
u p dates/a d de n da . 
7. 2.    
D o s a g e a n d A d mi ni str ati o n  
G L P G 3 9 7 0 will be pr o vi de d as a fil m-c oate d ta blet c o ntai ni n g 2 0 0 m g of t he acti ve 
p har mace utical i n gre die nt G 1 5 6 7 9 7 0 ( G 1 5 6 7 9 7 0 is t he c o m p o u n d c o de f or G L P G 3 9 7 0). A d ose 
of 4 0 0 m g ( 2 x 2 0 0 m g ta blets) q. d. will be ta ke n orall y. 
At all d osi n g da ys, t he I P nee ds t o be ta ke n  q. d.  at a p pr o xi matel y t he sa me ti me e ver y m or ni n g  i n 
a fe d state (t o get her wit h  a meal), e x ce pt at Visit 1 ( Da y 1) w he n t he I P will be ta ke n i n a faste d 
state. At Visit 1 ( Da y 1), brea kfast will be pr o vi de d t o t he s u bject 0. 5 -1 h o ur after t he I P i nta ke  
a n d lu nc h s h o ul d be eat e n 1 h o ur bef ore or after t he E C G me as ure me nt at 4. 5 h o urs p ost d os e. 
S u bjects will be i nstr ucte d t o s wall o w t he ta blets of G L P G 3 9 7 0 or place b o as a w h ole wit h a 
glass of water a n d t o n ot c he w t he dr u g pri or t o s wall o wi n g. At Visit 1  ( Da y 1), I P will be 
a d mi nistere d o n site after pre d ose ass ess me nts ha ve bee n c o m plete d. A t Visit  2, 3 , 4 , a n d 5, 
s u bjects als o nee d t o ta ke t heir I P o n site.   
S u bjects wi ll recei ve ta bl ets t o ta ke h o me. I nstr ucti o ns f or d osi n g a n d st ora ge are i n c or p orate d i n 
t he I P la bels. 
If a s u bject misses a d os e (e. g. beca use he/s he f or g ot t o ta ke t he me di cati o n), he/s he s h o ul d ta ke 
t he misse d d ose wit hi n 1 2  h o ur s after t he pla n ne d i nta ke ti me. If I P is n ot ta ke n wit hi n 1 2  h o urs  

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after t he pl a n ne d ti me, t he misse d d ose s h o ul d be s ki p pe d. F or eac h d os e ta ke n  at h o me, t he ti me, 
date , a n d n u m ber of ta blets ta ke n s h o ul d be rec or de d i n t he s u bject’s diar y car d. 
7. 3.    
P a c k a gi n g, L a b eli n g a n d Di stri b uti o n  
I P pac ka ges will be la bel e d wit h cli nical st u d y -s p ecific det ails, i ncl u di n g st ora ge c o n diti o ns. 
All ma n ufact uri n g, pac ka gi n g , a n d la beli n g o perati o ns will be perf or m e d acc or di n g t o G o o d 
Ma n ufact uri n g Practice f or Me dici nal Pr o d ucts a n d t he rele va nt re g ulat or y re q uire me nts.  
Eac h me dicati o n kit will be i de ntifie d wit h a u ni q ue kit n u m ber. M ulti ple kits ca n be pr o vi de d t o 
a s u bject at eac h visit, pr o vi di n g t he s u bject wi t h s ufficie nt I P t o c o ver t he peri o d u ntil t he ne xt 
sc he d ule d visit. 
T he distri b uti o n  of I P t o t he site will o nl y occ ur after t he re q uire d l ocal d oc u me ntati o n is 
o btai ne d , i ncl u di n g cli nical st u d y a p pr o val b y re g ulat or y a ut h orities a n d t he I E Cs/I R Bs, 
d oc u m e ntati o n o n w hic h t he assess me nt of t he i n vesti gat or’s q ualificati o ns was base d (e. g. 
c urric ul u m vitae) , a n d t h e si g ne d a n d date d st u d y a gree m e nt a n d fi na ncial a gree m e nt.  
I n case of S A R S-C o V -2 tra vel restricti o ns, t o e ns ure st u d y s u bj ects mai ntai n d osi n g p er pr ot oc ol 
re q uire me nts d uri n g t his st u d y, s peci al deli ver y ser vices t hr o u g h D T P s hi p me nts of I P t o t he 
s u bject ca n be i m ple me nt e d. D T P s h o ul d o nl y be use d i n case of e mer ge nc y w here o n  site I P 
dis pe nsati o n is n ot p ossi ble, a n d if all o we d per l ocal re g ula ti o ns. L ocal g ui deli nes m ust be 
f oll o we d a n d re g ulat or y a p pr o val or n otificati o n t o a ut h orities ma y be re q uire d. A gree me nt of t he 
s u bject t o recei ve I P at h o me is re q uire d pri or t o t he s hi p me nt of I P t o t he s u bject’s h o me. T he 
D T P pr ocess use d will be re vi e we d a n d a p pr o ve d b y t he s p o ns or. I n cas e t h e D T P s hi p me nts 
ori gi nates fr o m t he i n vesti gati o nal site, t he y will be c o or di nate d b y t h e i n vesti gati o nal site(s) i n 
c olla b orati o n wit h t he l ocal C R O wit h o ut t he i n v ol ve me nt of t he s p o ns or, t o e ns ure cli nical st u d y 
i nte grit y. 
7. 4.    
St or a g e  
Sites are t o st ore I P s u p plies i n a sec ure area u ntil dis pe nse d. G L P G 3 9 7 0 2 0 0 m g ta blets a n d 
matc hi n g place b o ta blets s h o ul d be st ore d at r o o m te m perat ure ( bel o w 3 0 ° C), s h o ul d n ot be 
refri gerate d or fr oze n a n d s h o ul d be pr otecte d fr o m li g ht a n d st ore d i n t he ori gi nal pac ka gi n g.  
Sites will be re q uire d t o m o nit or t he st ora ge te m perat ure b y usi n g at least a mi n -ma x 
te m perat ure-rec or di n g de vice a n d t o kee p a mi ni m u m t o ma xi m u m te m perat ure l o g, w hic h m ust 
be c o m plete d eac h w or ki n g da y i n o r der t o esta blis h a rec or d of c o m plia nce wit h t hese st ora ge 
c o n diti o ns. T he i n vesti gat or will i nstr uct s u bjects o n h o w t he I P s h o ul d be st ore d at h o me. 
St ora ge c o n diti o ns t o be ta ke n i nt o acc o u nt b y t h e s u bject w he n ta ki n g I P h o me, are descri be d i n 
t he patie nt leaflet. 
7. 5.    
Tr e at m e nt C o m pli a n c e a n d Dr u g A c c o u nt a bilit y  
T he i n vesti gat or s h o ul d disc uss treat me nt c o m plia nce wit h t he s u bject pri or t o t he start of t he 
st u d y. Misse d d oses s h o ul d be disc usse d t o tr y t o ascertai n t he reas o n(s). E ver y eff ort s h o ul d be 

G al a p a g o s  
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G L P G 3 9 7 0 - C L-2 0 7  
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ma de t o e ns ure t h e pr o per s u bject d ose. S u bjects wit h p o or c o m plia nce will be retrai ne d b y t h e 
site. I P a d mi nistrati o n as i n dicate d b y t he s u bject (a m o u nts as well as peri o ds) will be rec or de d 
o n t he C R F.  
T he p har macist or desi g n ate d cli nical st u d y staff w ill mai ntai n d oc u me ntati o n of t he t otal a m o u nt 
of I P recei ve d at t he site, a m o u nt dis pe nse d t o t he s u bject, a n d t he a m o u nt of I P ret ur ne d b y t h e 
s u bject t o t he site. I P s u p plies f or eac h s u bject will be i n ve nt orie d a n d acc o u nte d f or t hr o u g h o ut 
t he cli nical st u d y. At t he e n d of t he treat me nt peri o d, t hese rec or ds will be c hec ke d a gai nst t he 
i n ve nt or y b y t he st u d y m o nit or. All cli nical s u p plies will be st ore d i n l oc ke d a n d access 
c o ntr olle d facilities. S u bjects will rec or d I P a d mi nistrati o n at h o me i n a s u bje ct diar y.  
S u bjects will ret ur n a n y u n use d I P a n d e m pt y I P pac ka ges at eac h st u d y visit  a n d/ or E D v isit. 
U p o n s p o ns or a p pr o val, all u n use d I P a n d use d a n d/ or e m pt y I P pac ka ges  are t o be ret ur ne d fr o m 
t he sites a n d/ or a n y ve n d or i n v ol ve d i n t he cli nical st u dy s u p plies ma na ge me nt acti vities t o t he 
a gree d l o cati o n ( de p ot) , if p ossi ble. All ret ur ns a n d destr ucti o ns  m ust be pr o perl y d oc u me nte d.  
8.    
C LI NI C A L S T U D Y A S S E S S M E N T S  
E ver y eff ort s h o ul d be m a de t o e ns ure t hat C S P -re q uire d tests a n d pr oce d ures are c o m plete d as 
descri be d i n t he Sc h e d ule of Acti vities (see Secti o n  8. 1 1 ). T o a v oi d i nter-o bser ver varia bilit y, 
e ver y eff ort s h o ul d be m a de t o e ns ure t hat all safet y a n d efficac y e val uati o ns are c o m plet e d b y 
t he sa me i n di vi d ual w h o ma de t he i nitial baseli ne deter mi nati o ns. I n cas e st u d y ass ess me nts are 
n ot perf or me d f or reas o ns relate d t o S A R S -C o V -2 pa n de mic restri cti o ns, t his s h o ul d be 
d oc u me n te d i n t he me dical rec or ds a n d C R F.  
I n case a ra n d o mize d s u bject is n ot a ble t o atte n d a sc he d ule d st u d y visit o n site beca use of 
S A R S -C o V -2 tra vel restricti o ns, a p h o ne call or a tele visit ma y be c o n d ucte d. It is str o n gl y 
rec o m me n de d t o c o n d uct pla n ne d st u d y assess me nts f or t he a p plica ble visit as per pr ot oc ol as 
m uc h as p ossi ble. If p ossi ble a n d if l ocal re g ulati o ns all o w a n d t he s u bject a grees, trai ne d st u d y 
staff or trai n e d pers o n nel are e n c o ura ge d t o c ollect st u d y assess me nts at t he st u d y s u bject’s h o me 
or a l ocal facilit y if s o cial dista nci n g a n d h y gie ne r ules ca n be a p plie d.  
O nl y staff trai ne d i n c o n d ucti n g t he pr ot o c o l pla n ne d assess me nts are a ut h orize d t o perf or m 
h o me or l ocal facilit y visit assess me nts a n d t he alter nati ve arra n ge me nts nee d t o be a de q uatel y 
d oc u me nte d. S u bjects pr ese nti n g wit h si g ns a n d s y m pt o ms of i nfecti o n, i n cl u di n g S A R S -C o V -2 
i nfecti o n s h o ul d i m mediatel y c o nt act t he site i n vesti gat or, w h o s h o ul d i nf or m t he s p o ns or’s 
me dical res p o nsi ble as s o o n as p ossi ble, a n d S A R S -C o V -2 testi n g s h o ul d be perf or me d.  
8. 1.    
Ti mi n g of A s s e s s m e nt s  
T he st u d y assess me nts d escri be d b el o w will be perf or me d at ti me p oi nts as s pec ifie d i n t he 
Sc he d ule of Acti vities i n Secti o n  8. 1 1 . At Visit 1, 4 , a n d 5, s u bjects nee d t o c o me f or t he st u d y 
visits i n a fasti n g state ( n o f o o d i nta ke f or at least 8 h o urs).  
I C F nee ds t o b e si g n e d b ef ore a n y st u d y pr oce d ure, i ncl u di n g scree ni n g pr oce d ure, is carrie d o ut. 

G al a p a g o s  
C O N FI D E N TI A L  
4 3 9 5 2 _ 1 7 1 8 5 _ 5 1 8 4 2  
G L P G 3 9 7 0 - C L-2 0 7  
-5 4 - 
 
8. 3.    
S u bj e ct a n d Di s e a s e C h ar a ct eri sti c s  
S u bjects will be as ke d t o atte n d t he site f or a s cree ni n g assess me nt. After givi n g writte n i nf or me d 
c o nse nt, de m o gra p hi c data ( year of birt h, a ge, se x , et h nicit y, a n d race) will be c ollecte d  a n d a 
me dical hist or y will be ta ke n, i ncl u di n g p S S disease hist or y. p S S disease hist or y will ca pt ure at 
least t he d urati o n of disease, cli nical s y m pt o ms, a n d me dicati o n use d t o treat t he disease. A 
p h ysical e x a mi nati o n will be perf or me d, i ncl u di n g meas ure me nt of wei g ht a n d hei g ht.  T he 
s u bject’s dia g n osis of acti ve p S S will be c o nfir me d base d o n t he p S S classificati o n criteria 
descri be d b y t he A C R -E U L A R ( 1 0). 
Vital si g ns (s yst olic a n d diast olic bl o o d press ure, heart rate, oral/t y m pa nic  b o d y te m perat ure , t he 
sa me met h o d of meas uri n g b o d y te m perat ure t o be use d t hr o u g h o ut t he st u d y) will be meas ure d 
a n d a 1 2-lea d E C G will be rec or de d. S u bjects s h o ul d rest f or at least 5 mi n utes i n t he s u pi ne 
p ositi o n bef ore t he E C G rec or di n g, bl o o d press ure , a n d heart rat e meas ure me nt.  
T he i ncl usi o n a n d e x cl usi o n criteria will be c hec ke d t o assess eli gi bilit y f or t he st u d y  bas e d o n 
t he scree ni n g assess me nts. At Visit 1 ( Da y 1 ), it is t he res p o nsi bilit y of t he i n vesti gat or t o 
c o nfir m t hat eac h s u bject re mai ns eli gi ble f or t he st u d y, bas e d o n t he a vaila ble data (i ncl u di n g 
data fr o m Visit 1 [ Da y 1 ]), bef ore ra n d o mizati o n a n d first I P d osi n g .  
8. 4.    
Effi c a c y A s s e s s m e nt s  
8. 4. 1.    
E U L A R Sj ö gr e n’ s S y n dr o m e Di s e a s e A cti vit y I n d e x ( E S S D AI) S c or e  
T he E S S D AI is a s yst e mic disease acti vit y i n de x t o a ssess 1 2 d o mai ns (i.e. or ga n s yste ms: 
c o nstit uti o nal, l y m p ha de n o pat h y, gla n d ular, artic ular, c uta ne o us, p ul m o nar y, re nal, m usc ular, 
peri p heral ner v o us s yste m, C N S , he mat ol o gical, bi ol o gical) i n patie nts wit h p S S, w here eac h of 
t he d o mai ns is di vi de d i nt o 3-4 le vels of acti vit y. T hese sc ores are s u m me d acr oss t he 1 2 
d o mai ns i n a wei g ht e d ma n ner t o pr o vi de t he t otal sc ore (ra n ge 0 -1 2 3). A cli nicall y mea ni n gf ul 
re d ucti o n fr o m baseli ne ( > = 3 p oi nts) i n dicates t he i m pr o ve me nt of s y m pt o ms. (A p pe n di x 7 ) ( 1 3).  
8. 4. 2.    
E U L A R Sj ö gr e n’ s S y n dr o m e P ati e nt R e p ort e d I n d e x ( E S S P RI) S c or e  
T he E S S P RI is a patie nt self -re p orte d o utc o me m eas ure t o assess dr y ness, li m b pai n, fati g ue, a n d 
me ntal fati g u e, w here eac h of t he d o mai ns n or mall y re p orte d as 0 ( n ot at all) t o 1 0 (e xtre mel y 
se vere). T he fi nal E S S PRI s c ore is t he a vera ge of 3 : dr y ness, p ai n, a n d fati g ue. A cli nicall y 
si g nifica nt re d uctio n fr o m baseli ne (at least 1 p oi nt or 1 5 % of t he bas eli ne val ue) i n dicates t h e 
i m pr o ve me nt of s y m pt o ms. (A p pe n di x 8 ) ( 1 3).  

G al a p a g o s  
C O N FI D E N TI A L  
4 3 9 5 2 _ 1 7 1 8 5 _ 5 1 8 4 2  
G L P G 3 9 7 0 - C L-2 0 7  
-5 6 - 
 
t he s u bject’s p ost-treat me nt F U visit a n d t he e ve nt is dee me d relate d t o t he use of I P, t he y 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 b y usi n g t he S A E f or m.  
Detaile d defi niti o ns,  re p orti n g peri o d, rati n gs a n d re p orti n g re q uire m e nts f or A Es a n d S A Es are 
f o u n d i n Secti o n 1 1 . 
8. 5. 2.    
Cli ni c al L a b or at or y E v al u ati o n s  
T he f oll o wi n g cli nical la b orat or y safet y tests will be perf or me d:  
− 
He m at ol o g y :  
H e mat ocrit, mea n c or p usc ular v ol u me , mea n c or p usc ular he m o gl o bi n , mea n c or p usc ular 
he m o gl o bi n c o n ce ntrati o n , he m o gl o bi n, re d bl o o d cell ( R B C) c o u nt, w hite bl o o d cell c o u nt, 
w hite bl o o d cell differe ntial c o u nt (a bs ol ute a n d relati ve), R B C  differe ntial c o u nt/ 
m or p h ol o g y (if i n dicate d), a n d platelets.  
− 
C o a g ul ati o n:  
IN R , acti vate d partial t hr o m b o plasti n ti me, a n d pr ot hr o m bi n ti me. 
− 
Cli nic al c he mistr y:  
G l uc ose, faste d gl uc ose, faste d i ns uli n, he m o gl o bi n A 1c, urea, creati ni ne, bicar b o nate, uric 
aci d, s o di u m, p otassi u m, calci u m  (t otal), refle x cal ci u m (free/i o nize d o nl y if ser u m cal ci u m 
t otal is ele vate d), c hl ori d e, p h os p h or us / p h os p hate, A S T, A L T, G G T, t otal bilir u bi n, al kali ne 
p h os p hatase, al kali ne p h os p h atase b o ne fracti o n (if t otal al kali ne p h os p hatase  ele vate d), 
creati ni ne p h os p h o ki nas e , t otal i m m u n o gl o b uli n (I g) le vels, lactate de h y dr o ge nase, al b u mi n, 
t otal pr otei ns, tri gl yceri des, t otal c h olester ol, hi g h -de nsit y li p o pr otei n  ( H D L), l o w-de nsit y 
li p o pr otei n ( L D L), H D L/ L D L rati o, hi g h s e nsiti vit y C -reacti ve pr otei n ( hs C R P), li pase, a n d 
a m ylase. 
H o me ostatic m o del assess me nt of  i ns uli n resista nce ( H O M A-I R) a n d H D L/ L D L rati o will be 
deri ve d fr o m cli nical c he mistr y par a meters. A n esti mate of t he creati ni ne C L  bas e d o n t he 
ser u m creati ni ne le vel will be calc ulate d. 
− 
Uri n al ysis:  
Di pstic k: p H, gl uc ose, pr otei ns, bl o o d, le u k oc ytes , ket o nes , calci u m, p h os p hate, a n d 
creati ni ne. 
M icr osc o pic e x a mi nati o n of t he se di me nt f or cell ular ele me nts (c yli n ders, er yt hr oc ytes, 
le u k oc yt es), if i n dicat e d. 
− 
Ser ol o g y / bl o o d:  
H Bs A g  (if p ositi ve, c o nfir me d b y H B V de o x yri b o n ucleic aci d [ D N A ] p ol y merase c hai n 
reacti o n [P C R ]), H C V a nti b o d y (if p ositi ve, c o nfir me d b y refle x H C V R N A) , a n d HI V  1 a n d 
2  a nti b o dies at scree ni n g . P ositi ve he patitis a n d HI V res ults s h o ul d be re p orte d b y t he 
i n vesti gat or as re q uire d b y l ocal la w. 
F S H test f or fe males at s cree ni n g t o c o nfir m me n o pa use , if a p plica ble. 
− 
Pre g n a nc y test f or fe m ales:  
Ser u m beta h u ma n c h ori o nic g o n a d otr o pi n at scree ni n g (all fe males), uri ne pre g na nc y t est 
( U P T) a n d uri ne di pstic k ( W O C B P o nl y) at Visit 1 ( Da y 1 pre d ose), at Visit 2 ( Da y 8 
pre d ose), at Visit 3  ( Da y 2 9 pre d ose), Visit 4  ( Da y 5 7 pre d ose), a n d at Visit 5 ( Da y 8 5 
pre d ose).  

G al a p a g o s  
C O N FI D E N TI A L  
4 3 9 5 2 _ 1 7 1 8 5 _ 5 1 8 4 2  
G L P G 3 9 7 0 - C L-2 0 7  
-5 7 - 
 
− 
Q u a nti F E R O N -T B G ol d test  t o c hec k f or late nt or acti ve T B (at scree ni n g). T B res ults 
s h o ul d be re p orte d b y t he i n vesti gat or as re q uire d b y l ocal la w. 
− 
S A R S -C o V -2:  
I g M I m m u n o assay . 
R T -P C R  fr o m a nasal s w a b sa m ple t o c hec k f or S A R S-C o V -2 i nfecti o n at scree ni n g a n d 
R T -P C R fr o m a nasal s w a b sa m ple a n d ser ol o g y t esti n g at baseli ne, a n d t hr o u g h o ut t he st u d y 
as nee de d ( w he n S A R S -C o V -2 s y m pt o ms prese nt).  T he re peat R T -P C R ma y be perf or me d 
2 -3 da ys pri or t o t he bas eli ne visit t o all o w f or res ults a vaila bilit y pri or t o ra n d o mizati o n.  
P ositi ve S A R S -C o V -2 res ults s h o ul d be re p orte d b y t he i n vesti gat or as re q uire d b y l o cal la w. 
 
T he cli nical la b orat or y e val uati o ns will be perf or me d at  visits s pecifie d i n t he Sc he d ule of 
A cti vities i n Secti o n  8. 1 1  (see als o Secti o n 8. 1 , “Ti mi n g of Assess me nts ”). Refere nce ra n ges will 
be s u p plie d b y t he ce ntral la b orat ory. Cli nical la b orat or y val ues o utsi de t h e n or mal ra n ge will be 
fla g ge d a n d cli nical rele va nce will be assesse d b y t he i n vesti gat or. O nl y l a b orat or y test 
a b n or malities j u d ge d as cli nicall y si g nifica nt b y t h e pri nci pal i n vesti gat or s h o ul d be rec or de d as 
A Es . At t he dis creti o n of t he i n vesti gat or, w he n f oll o wi n g u p A Es, a d diti o nal la b orat or y  
para meters ma y be test e d, a n d a d diti o nal sa m ples ta ke n.   
B l o o d a n d uri ne sa m ple ha 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 ual. 
8. 5. 3.    
P h y si c al E x a mi n ati o n  
P h ysical e xa mi nati o ns , i ncl u di n g wei g ht a n d hei g ht (at scree ni n g), will be c o n d ucte d b y a 
p h ysicia n, trai ne d p h ysicia n’s assista nt, or n urse practiti o ner as acce pta ble acc or di n g t o l ocal 
re g ulati o n at visits s pecifie d i n t he Sc he d ule of Acti vities i n Secti o n 8. 1 1  (see als o Secti o n 8. 1 , 
“Ti mi n g of Ass ess me nts ”). T he p ers o n c o n d ucti n g t he p h ysical e xa mi nati o n will d oc u me nt t his 
i n t he s u bject’s me dical s o urce rec or ds. Cli nicall y si g nifica nt a b n or mal fi n di n gs s h o ul d be 
rec or de d as A Es. 
P artic ular atte nti o n s h o ul d g o t o p h ysical e xa mi nati o n at all visits, t o i de ntif y a n y p ote ntial 
S A R S -C o V -2 relate d si g ns a n d s y m pt o ms, i n dicati n g p ote ntial i nfecti o n (e. g. c o u g h, fe ver, 
hea dac hes, fati g u e, d ys p nea, m yal gia, a n os mia, d ys ge usia, a n ore xia, s or e t hr oat, etc). S u bjects 
prese nti n g s uc h s y m pt o ms at scree ni n g/ baseli ne s h o ul d n ot be i ncl u de d/ra n d o mize d i n t he st u d y 
(see Secti o n 6. 2 ). De vel o pi ng s uc h s y m pt o ms d uri n g t he st u d y, s h o ul d be ma na ge d as p er 
Secti o n  8. 5. 6 . 
8. 5. 4.    
Vit al Si g n s  
Vital si g ns (s yst olic a n d diast olic bl o o d press ure, heart rate , a n d oral/t y m p a nic b o d y te m perat ure, 
t he sa me met h o d of meas uri n g b o d y te m perat ure t o be use d t hr o u g h o ut t he st u d y) will be 
rec or de d i n a sta n dar dize d ma n ner (i.e. after t he s u bject has reste d i n a s u pi ne p ositi o n f or at least 
5  mi n utes) at visits s pecifie d i n t he S c he d ule of A cti vities i n Secti o n  8. 1 1  (see als o Secti o n 8. 1 , 
“Ti mi n g of Ass ess me nts ”). Cli nicall y si g nifica nt a b n or mal val ues s h o ul d be rec or de d as A Es.  

G al a p a g o s  
C O N FI D E N TI A L  
4 3 9 5 2 _ 1 7 1 8 5 _ 5 1 8 4 2  
G L P G 3 9 7 0 - C L-2 0 7  
-5 8 - 
 
8. 5. 5.    
1 2 -l e a d El e ctr o c ar di o gr a m 
At t he ti me p oi nts s pecifie d i n t he Sc he d ule of Acti vities (see Secti o n 8. 1 1  a n d als o Secti o n  8. 1 , 
“Ti mi n g of Ass ess me nts ”), a 1 2-l ea d E C G will be rec or de d a n d res ults will be se nt f or ce ntral 
rea di n g.  
1 2 -lea d E C G rec or di n gs will be perf or me d bef ore bl o o d sa m pli n g a n d after s u bjects reste d f or at 
least 5  mi n utes i n s u pi ne p ositi o n. I n cas e a n i n d welli n g cat heter is use d, E C Gs ma y be rec or de d 
after bl o o d sa m pli n g, pr o vi de d t hat t here i s at least 3 0 mi n utes bet wee n cat heter i nserti o n a n d t he 
E C G rec or di n g. W he n cat heter i nserti o n w o ul d fail, t he 1 2 -lea d E C G nee ds t o be ta ke n bef ore t he 
ve ni p u nct ure a n d at least 3 0 mi n utes after t he faile d atte m pt. Tri plicate E C Gs (i.e. 3 E C Gs) will 
be pe rf or me d at Visit 1 ( Da y 1) pre d ose a n d at 4. 5  h o urs  p ost d ose, wit hi n a ti me s pa n of 
6  mi n utes, wit h a n a p pr o xi mate 3 -mi n ute i nter val bet wee n E C Gs.  At all ot her ti me p oi nts, si n gle 
E C Gs will be ta ke n.  
T he f oll o wi n g p ara m eters nee d t o be rec or de d : heart rate, P R i nter val, R R i nter val, Q R S i nter val, 
u nc orrecte d Q T i nter val, m or p h ol o g y , a n d r h yt h m a nal ysis . Q Tc F  will be deri ve d. Q Tc F  will be  
c o nsi dere d as n or mal if < = 4 5 0 ms , w hile a pr ol o n gati o n of Q TcF  t o > 5 0 0 ms a n d/or a n i ncrease 
fr o m baseli ne > 60 ms will be c o nsi dere d a t hres h ol d of c o ncer n.  
I m me diat el y after rec or di n g, the E C G s will be re vi e we d b y t he i n vesti gat or  t o detect cli nicall y 
si g nifica nt a b n or malities. T his i m me diate re vie w d uri n g t he visit nee ds t o be d oc u me nte d i n t he 
s u bject’s s o urce. After recei pt of t he ce ntral re p ort, als o all fla g ge d E C G a b n or malities nee d t o be 
assesse d b y t he i n ve sti gat or o n cli nical rele va nce. Cli nicall y si g nifica nt a b n or mal fi n di n gs s h o ul d 
be rec or de d as A Es.  
8. 5. 6.    
Ot h er S af et y A s s e s s m e nt s  
S A R S -C o V -2 i nfecti o n will  be assesse d at scree ni n g b y R T -P C R a n d at baseli ne t hr o u g h caref ul 
p h ysical e x a mi nati o n t o e x cl u de a n y p ot e ntial si g ns a n d s y m pt o ms of i nfecti o n, e. g. c o u g h, fe ver, 
hea dac hes, fati g u e, d ys p nea, m yal gia, a n os mia, d ys ge usia, a n ore xia, s ore t hr oat, etc.  
A d di ti o nal R T-P C R a n d ser ol o g y t esti n g will be re peate d at baseli ne a n d t hr o u g h o ut t he st u d y as 
nee de d. T he re p eat R T -P C R ma y be perf or me d 2 -3 da ys pri or t o t he baseli ne visit t o all o w f or 
res ults a vaila bilit y pri or t o ra n d o mizati o n. T he s u bject c o ul d be teste d f or S A R S -C o V -2 i n 
facilities o utsi de t he st u d y site a n d if s o, t he s u bj ect s h o ul d be i nstr ucte d t o i m me diatel y i nf or m 
t he st u d y i n vesti gat or if t he test is p ositi ve a n d test res ults s h o ul d be s hare d wit h t he i n vesti gat or 
as s o o n as p ossi ble.  
8. 6.    
P h ar m a c o ki n e ti c A s s e s s m e nt s 
Bl o o d sa m ples ( 2 m L) f or t he P K assess me nt s h o ul d be c ollecte d o n t he visits s pecifie d i n t he 
S c he d ule of A cti vities i n Secti o n 8. 1 1  (see als o Secti o n 8. 1 , “Ti mi n g of Ass ess me nts ”). Sa m ples 
will be o btai ne d b y v e ni p u nct ure ( or i n d welli n g ca n n ula) , prefera bl y i n t he f orear m  i nt o t u bes 
c o ntai ni n g K 2 E D T A a n d will be i m me diatel y c hille d (ice bat h). Wit hi n 3 0  mi n utes  after bl o o d 
c ollecti o n, t he plas ma will be se parat e d i n a refri ge rate d ce ntrif u ge at 4 ° C f or 1 0 mi n utes  at circa 
1 5 0 0 g a n d tra nsferre d i nt o t u bes as descri be d i n t he la b orat or y  m a n ual. T h e plas ma sa m ples will 

G al a p a g o s  
 
C O N FI D E N TI A L  
4 3 9 5 2 _ 1 7 1 8 5 _ 5 1 8 4 2  
G L P G 3 9 7 0 - C L-2 0 7  
 
-6 3 - 
 
8. 1 1.    
S c h e d ul e of A cti viti e s  
F or detaile d i nstr ucti o ns o n t he cli nical st u d y pr oce d ures, please see referre d secti o ns a n d Secti o n 8. 1 , “Ti mi n g of Ass ess me nts ”. 
E V E N T  
S C R E E NI N G 
P E RI O D  
T R E A T M E N T P E RI O D 1 
F O L L O W -U P 
P E RI O D  
St u d y V isit 
S  
1    
2    
3    
4    
5  
E D 2 
F oll o w -u p 
Visit  
St u d y W ee k 
-4 t o -1    
B aseli ne    
1    
4    
8    
1 2  
 
 
St u d y D a y ( D) ± D a ys  
-2 8 t o -1    
1    
8 ± 1    
2 9 ± 2    
5 7 ± 2    
8 5 ± 2  
E arl y tre at me nt 
disc o nti n u ati o n  
2 8  ± 3 after 
l ast I P d osi n g 
I nf or me d c o nse nt  
✓ 
 
 
 
 
 
 
 
I ncl usi o n/e xcl usi o n criteria  
✓ 
✓ 
 
 
 
 
 
 
De m o gra p hics  
✓ 
 
 
 
 
 
 
 
Me dical hist or y  
✓ 
 
 
 
 
 
 
 
P h ysical e xa mi nati o n  
✓ 
✓   
✓   
✓   
✓   
✓ 
✓ 
✓ 
Vital si g ns  
✓ 
✓   
✓   
✓   
✓   
✓ 
✓ 
✓ 
B o d y wei g ht a n d hei g ht 3 
✓ 
✓   
✓   
✓   
✓   
✓ 
✓ 
✓ 
                                                 
1 O n d osi n g da ys, all assess me nts are t o be perf or me d pre d ose, u nless ot her wise s pecifie d . 
2 S u bj ects w h o disc o nti n ue treat me nt earl y will be re q ueste d t o ret ur n f or a n E D visit  a n d  t o ret ur n f or a F U visit 2 8  ±  3 da ys after last I P a d mi nistrati o n.  
3 Hei g ht o nl y t o be meas ure d at scree ni n g.  
 

G al a p a g o s  
 
C O N FI D E N TI A L  
4 3 9 5 2 _ 1 7 1 8 5 _ 5 1 8 4 2  
G L P G 3 9 7 0 - C L-2 0 7  
 
-6 4 - 
 
E V E N T  
S C R E E NI N G 
P E RI O D  
T R E A T M E N T P E RI O D 1 
F O L L O W -U P 
P E RI O D  
St u d y V isit 
S  
1    
2    
3    
4    
5  
E D 2 
F oll o w -u p 
Visit  
St u d y W ee k 
-4 t o -1    
B aseli ne    
1    
4    
8    
1 2  
 
 
St u d y D a y ( D) ± D a ys  
-2 8 t o -1    
1    
8 ± 1    
2 9 ± 2    
5 7 ± 2    
8 5 ± 2  
E arl y tre at me nt 
disc o nti n u ati o n  
2 8  ± 3 after 
l ast I P d osi n g 
1 2 -lea d E C G4   
✓ 
Pre d ose, 
1. 5 h, 3 h, 
4 . 5h  
p ost d ose 4 
Pre d ose  
Pre d ose   
Pre d ose   
Pre d ose   
✓ 
✓ 
Q ua nti F E R O N -T B G ol d test  
✓ 
 
 
 
 
 
 
 
S A R S -C o V -2 R T -P C R test 5 ,6 
✓ 
✓ 
As nee de d  
S A R S -C o V -2 ser ol o g y test 5, 6 
 
✓ 
As nee de d  
Ra n d o mizati o n  
 
✓   
 
 
 
 
 
 
Bl o o d c ollecti o n  
 
− Safet y ( he mat ol o g y, c oa g ulati o n, 
c he mistr y)  
✓ 
✓7    
✓   
✓   
✓7   
✓7 
✓ 
✓ 
− Safet y ( H B V, H C V, HI V ser ol o g y)  
✓ 
 
 
 
 
 
 
 
                                                 
4 At Visit 1 ( Da y 1), tri plicate E C Gs will be rec or de d pre d ose a n d at 4. 5 h o urs p ost d ose. At all ot her ti me p oi nts, si n gle E C Gs will be ta ke n.  
5 R T -P C R fr o m a nasal s wa b sa m ple at scree ni n g a n d R T -P C R fr o m a nasal s wa b sa m ple a n d ser ol o g y testi n g at Visit 1  ( Da y 1), a n d as nee de d w he n s u bj ect prese nts si g ns 
a n d s y m pt o ms of S A R S -C o V -2 i nfecti o n.  
6 S A R S -C o V -2 R T -P C R a n d ser ol o g y tests ca n  ( o pti o nall y) be sa m ple d b y a n urse at t he s u bj ect’s h o me 2-3 da ys bef ore Visit 1  ( Da y 1). 
7 Faste d gl uc ose, faste d i ns uli n, a n d H O M A -I R o nl y at Visit 1, 4, a n d 5. 
 

G al a p a g o s  
 
C O N FI D E N TI A L  
4 3 9 5 2 _ 1 7 1 8 5 _ 5 1 8 4 2  
G L P G 3 9 7 0 - C L-2 0 7  
 
-6 6 - 
 
E V E N T  
S C R E E NI N G 
P E RI O D  
T R E A T M E N T P E RI O D 1 
F O L L O W -U P 
P E RI O D  
St u d y V isit 
S  
1    
2    
3    
4    
5  
E D 2 
F oll o w -u p 
Visit  
St u d y W ee k 
-4 t o -1    
B aseli ne    
1    
4    
8    
1 2  
 
 
St u d y D a y ( D) ± D a ys  
-2 8 t o -1    
1    
8 ± 1    
2 9 ± 2    
5 7 ± 2    
8 5 ± 2  
E arl y tre at me nt 
disc o nti n u ati o n  
2 8  ± 3 after 
l ast I P d osi n g 
− 
 
Uri ne sa m ple 
 
− Safet y ( uri ne)  
✓ 
Pre d ose  
Pre d ose  
Pre d ose  
Pre d ose  
Pre d ose  
✓ 
✓ 
− Pre g na nc y testi n g ( U P T, di pstic k) 
( W O C B P o nl y) 
 
Pre d ose    
Pre d ose    
Pre d ose    
Pre d ose    
Pre d ose  
 
 
S u bj ect diar y e val uati o n  
 
✓   
✓   
✓   
✓   
✓ 
✓ 
✓ 
E S S D AI  
✓ 
✓   
   
✓   
✓   
✓ 
✓ 
 
E S S P RI  
✓ 
✓   
   
✓   
✓   
✓ 
✓ 
 
                                                 
1 2

G al a p a g o s  
C O N FI D E N TI A L  
4 3 9 5 2 _ 1 7 1 8 5 _ 5 1 8 4 2  
G L P G 3 9 7 0 - C L-2 0 7  
-6 8 - 
 
9.    
S T A TI S TI C A L M E T H O D S  
All statistical met h o ds s hall be detaile d i n a S A P  t hat will be fi nalize d pri or t o t he data base l oc k 
a n d u n bli n di n g. All rele va nt data c ollect e d i n t his cli nical st u d y will be d oc u me nte d usi n g 
s u m mar y ta bl es, fi g ures, a n d s u bject data listi n gs. 
A n y d e viati o ns fr o m t he C S P are t o be j ustifie d i n t he S A P.  
9. 1.    
D et er mi n ati o n of S a m pl e Si z e  
U p t o 3 0 s u bjects are pla n ne d t o be ra n d o mize d 2: 1, i.e. 2 0  s u bjects will recei ve G L P G 3 9 7 0 
( 4 0 0 m g q. d.) a n d 1 0 s u bjects will recei ve place b o. I n case of dr o p -o uts d ue  t o S A R S-C o V -2 
i nfecti o n, a d diti o nal s u bjects ma y be ra n d o mize d o n t o p of t he pla n ne d sa m ple size. T he n u m ber 
of a d diti o nal s u bjects ra n d o mize d will n ot e xcee d t he n u m ber of s u bjects dr o p pi n g o ut of t he 
st u d y i n relati o n t o S A R S-C o V -2. Ra n d o mizati o n of a d d iti o nal s u bjects will be deci de d b y t he 
s p o ns or bef ore st u d y l oc k or relate d u n bli n di n g has occ urre d.  
T his sa m ple size pr o vi des fa v ora ble o perati n g c haracteristics f or t he pri mar y efficac y e n d p oi nt 
(i.e. E S S D AI c ha n ge fr o m baseli ne at Wee k 1 2) i n ter ms of t he m o difie d si g nal detecti o n 
met h o d ol o g y ( 2 1). T his met h o d ol o g y will be use d t o pr o vi de f urt her i nsi g ht i nt o t he treat me nt 
effect of G L P G 3 9 7 0 o ver place b o, a n d will s u p p ort sce nari o a nal yses. T he p osteri or distri b uti o n 
of t his treat me nt effect will be esti mate d, a n d fr o m t his distri b uti o n pr o ba bilities of reac hi n g at 
least a certai n effect ( delt a) will be deri ve d, e. g. a ra n ge of pla usi ble effect size val ues g oi n g fr o m 
as hi g h as P ( delta < = -5) t o as l o w as P ( delta < =-2). A c o m m o n S D of 4 was ass u me d f or b ot h 
acti ve a n d place b o ar m.  
Pr o b a bilit y    
Refere nce v al ue    
O utc o me  
0. 8 5 2  
-5  
Si g nal detecte d  
0. 0 4 1  
N o c o ncl usi o n  
0. 1 0 7  
Si g nal n ot detecte d  
0. 4 2 7  
-3  
Si g nal detecte d  
0. 0 8 8  
N o c o ncl usi o n  
0. 4 8 5  
Si g nal n ot detecte d  
0. 2 0 5  
-2  
Si g nal detecte d  
0. 0 5 0  
N o c o ncl usi o n  
0. 7 4 5  
Si g nal n ot detecte d  

G al a p a g o s  
C O N FI D E N TI A L  
4 3 9 5 2 _ 1 7 1 8 5 _ 5 1 8 4 2  
G L P G 3 9 7 0 - C L-2 0 7  
-6 9 - 
 
 
9. 2.    
P o p ul ati o n f or A n al y s e s  
9. 2. 1.    
All S cr e e n e d S u bj e ct s  
All s u bjects w h o si g ne d a n d date d a n I C F.  
9. 2. 2.    
All R a n d o mi z e d S u bj e ct s  
All scree n e d s u bjects w h o were ra n d o mize d i nt o t he cli nical st u d y.  
9. 2. 3.    
F ull A n al y si s S et  
All ra n d o mize d s u bjects w h o ha ve recei v e d  at least 1  d ose of I P 
9. 2. 4.    
S af et y A n al y si s S et  
All ra n d o mize d s u bjects w h o ha ve recei v e d at least 1  d ose of I P. 
9. 2. 5.    
P h ar m a c o ki n eti c  A n al y si s S et  
S u bset of t he Safet y A nal ysis Set f or w hic h pl as ma c o nce ntrati o n data are a vai la ble t o facilitate 
de vel o p me nt  of t he p o p ulati o n P K m o del as descri be d i n t he p har mac o m etric a nal ysis pla n a n d 
e x cl u di n g C S P de viati o ns w hic h ha ve a n i m pact o n t he P K a nal yses.   
9. 2. 6.  
 

G al a p a g o s  
C O N FI D E N TI A L  
4 3 9 5 2 _ 1 7 1 8 5 _ 5 1 8 4 2  
G L P G 3 9 7 0 - C L-2 0 7  
-7 0 - 
 
9. 2. 7.    
P h ar m a c o ki n eti c/
 A n al y si s S et 
I ntersecti o n of t he P K    
 A nal ysis Sets.  
9. 3.    
St ati sti c al A n al y s e s  
9. 3. 1.    
G e n er al St ati sti c al C o n si d er ati o n s  
S u m mar y ta b ulati o ns will be prese nte d a n d will dis pla y t he n u m ber of o bser vati o ns, mea n, 
sta n dar d deviati o ns ( S Ds) a n d/ or sta n dar d err or ( as a p pr o priate ), me dia n, mi ni m u m a n d 
ma xi m u m (for c o nti n u o us varia bles ), a n d t he n u m ber a n d perce nta ge per cate g or y (f or 
cate g orical data ). I n a d diti o n t o ta b ulate d descri pti ve statistics, gra p hical data dis pla ys ma y be 
use d t o s u m marize t he data.  
Baseli ne is defi ne d as t he last a vaila ble assess me nt p ri or t o t he first i nta ke of I P. F or E C G, t he 
baseli ne E C G res ult is t he mea n of t he l ast a vaila ble tri plicate pri or t o t he first i nta ke of I P. 
U nless ot her wise n ote d, i nfere ntial statistics wil l be i nter pret e d at t he 2-si de d 1 0 % si g nifica nce 
le vel. 
9. 3. 2.    
I nt eri m A n al y si s  
N o f or mal i nteri m a nal ysis is pla n ne d f or t his cli nical st u d y.  
9. 3. 3.    
A n al y s e s of D e m o gr a p hi c s a n d B a s eli n e C h ar a ct eri sti c s  
S u bject dis p ositi o n (i ncl u di n g reas o ns f or E D ), C S P de viati o ns, de m o gra p hics, baseli ne 
c haracteristics, me dical hist or y, a n d c o n c o mita nt t hera pies will be a nal yz e d descri pti vel y . 
9. 3. 4.    
A n al y s e s of Effi c a c y P ar a m et er s  
Efficac y a nal ysis will be perf or me d o n t h e F A S . 
9. 3. 4. 1.    
A n al y si s f or Pri m ar y Effi c a c y E n d p oi nt  
T he si g n al detecti o n met h o d ol o g y des cri be d b y Fre wer et al ( 2 1) will be use d t o pr o vi de f urt her 
i nsi g ht i nt o t he treat me nt effect of G L P G 3 9 7 0 o ver place b o, a n d will s u p p ort sce nari o a nal yses. 
See als o Secti o n 9. 1 . 
A M M R M  ( E S S D AI) will be use d t o c o m pare treat me nt gr o u ps, wit h a 9 0 % c o nfi de nce i nter val 
( CI) of t he treat me nt differe nce at Wee k 1 2 . 
9. 3. 4. 2.    
A n al y s e s f or S e c o n d ar y a n d Ot h er Effi c a c y E n d p oi nt s  
C o nti n u o us efficac y e n d p oi nts, i ncl u di n g t he pri mar y e n d p oi nt: M M R M t o c o m pare treat me nt 
gr o u ps, wit h a 9 0 % CI of t he treat me nt differe nce at eac h ti me p oi nt.  

G al a p a g o s  
C O N FI D E N TI A L  
4 3 9 5 2 _ 1 7 1 8 5 _ 5 1 8 4 2  
G L P G 3 9 7 0 - C L-2 0 7  
-7 1 - 
 
Bi nar y efficac y e n d p oi nts: Prese nte d wit h a 9 0 % e xact CI of t he treat me nt differe nce at eac h ti me 
p oi nt.  
9. 3. 5.    
A n al y s e s of S af et y D at a  
All safet y a nal yses will be perf or me d usi n g t he Safet y A nal ysis Set ( Secti o n 9. 2. 4 ). All safet y 
data c ollecte d o n or after t he  first d ose of I P a d mi nistrati o n u p t o t he last c o ntact after t he last 
d ose of I P, u nless s pecifi e 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 I P 
recei v e d. Cli nical safet y will be a d dresse d b y assessi n g A Es, la b orat or y ass ess me nts, ph ysical 
e x a mi nati o ns , vital si g ns, a n d 1 2-lea d E C Gs. 
9. 3. 5. 1.    
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 t he I P will be ge nerate d fr o m t he I P a d mi nistrati o n pa ge of t he 
C R F. E x p os ure data will be s u m marize d b y treat m e nt gr o u p. D urati o n of e x p os ure t o t he I P will 
be e x presse d as t he n u m b er of da ys  b et wee n t he first a n d last d ose of I P, i ncl usi ve, re gar dless of 
te m p orar y i nterr u pti o ns i n I P a d mi nistrati o n a n d s u m marize d b y treat me nt gr o u p.  
9. 3. 5. 2.    
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 la test versi o n of t he Me dical Dicti o nar y f or 
Re g ulat or y Acti vities. S yste m Or ga n Class , Hi g h-Le vel Gr o u p Ter m, Hi g h -Le vel Ter m, 
Preferre d Ter m, a n d L o wer -Le v el Ter m will be attac he d t o t he cli nical data base.  
T he f oll o wi n g A Es will be c o nsi dere d as treat me nt-e mer ge nt  a d verse e ve nts ( T E A Es):  
A n y A E wit h a n o nset date o n or after t he I P start date a n d n o later t ha n 3 0 da ys after last d ose of 
I P, or a n y w orse ni n g of a n y A E o n or after t he I P start date. 
S u m maries ( n u m ber a n d perce nt a ge of s u bje cts) of T E A Es per s u bj ect b y S yste m Or ga n Class  
a n d Preferre d Ter m 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 
ca usal relati o ns hi p t o t he I P a n d s e verit y. I n a d diti o n, T E A Es lea di n g t o E D  of t he I P will be 
s u m marize d a n d liste d. Als o, all S A Es, i nclu di n g t he n o n -treat me nt-e mer ge nt S A Es, will be 
liste d. 
9. 3. 5. 3.    
Cli ni c al L a b or at or y E v al u ati o n s  
La b orat or y assess me nts will be a nal yze d descri pti vel y. C ha n ges fr o m baseli ne a n d treat me nt-
e mer ge nt s hifts acc or di n g t o n or mal ra n ges a n d C T C A E gra des will be prese nte d as well. 
A nal ys es will be d o ne per treat me nt gr o u p.  
9. 3. 5. 4.    
P h y si c al E x a mi n ati o n s  
O nl y a b n or mal p ost -baseli ne p h ysical e xa mi nati o n res ults will be liste d, w he n a vaila ble . 

G al a p a g o s  
C O N FI D E N TI A L  
4 3 9 5 2 _ 1 7 1 8 5 _ 5 1 8 4 2  
G L P G 3 9 7 0 - C L-2 0 7  
-7 3 - 
 
1 0.    
D A T A M O NI T O RI N G  
1 0. 1.    
S af et y M o nit ori n g C o m mitt e e  
A  Safet y M o nit ori n g C o m mittee i n de pe n de nt fr o m t he st u d y will re vie w u n bli n de d data d uri n g 
t he c o urse of t he st u d y. T his C o m mittee will i ncl u de a p h ysicia n  wit h e x perie nce i n dr u g 
de vel o p me nt , a bi ostatisticia n, a n d a safet y p h ysicia n . E xter nal me dical e x perts (s uc h as a n e x pert 
i n t he fiel d of p S S a n d a n i nfecti o us diseases e x pert) ma y be i ncl u de d  t o s u p p ort data 
i nter pretati o n. T he C o m mittee will re vie w u nbli n de d safet y data a n d assess a n y p ot e ntial safet y 
iss ues arisi n g d uri n g t he c o n d uct of t he cli nical st u d y, i ncl u di n g ( b ut n ot li mite d t o) a n y p ote ntial 
iss ues i n t he c o nte xt of t he S A R S-C o V -2 pa n de mic. T he pr ocess is descri be d i n a se parate 
‘ Safet y M o nitori n g C o m mittee C harter’.  
1 1.    
S A F E T Y R E P O R TI N G  
1 1. 1.    
D efi niti o n s of A d v er s e E v e nt s,  S eri o u s A d v er s e E v e nt s , a n d 
S p e ci al S it u ati o n s 
1 1. 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 nce, ne w or w orse ni n g of a n y pre -e xisti n g c o n diti o n, 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 a n d w hic h d oes n ot necessaril y ha ve t o 
ha ve a ca usal relati o ns hi p wit h t his treat me nt.  
A n A E ca n t h eref ore b e a n y u nfa v ora bl e a n d u ni nt e n de d si g n ( e. g. a n a b n or mal la b orat or y 
fi n di n g), s y m pt o m, or dis ease te m p orall y ass ociate d wit h t he use of a me dici nal pr o d uct, w het her 
or n ot c o nsi dere d relate d. 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 C S P -s pecifi e d pr oce d ures, w orse ni n g of t he t ar get e d disease, o ver d ose, dr u g 
a b use/ mis use re p orts, or occ u pati o nal e x p os ure. Pre -e xisti n g c o n diti o ns t hat i ncrease i n se verit y 
or c ha n ge i n n at ure d uri n g or as a c o ns e 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.  
1 1. 1. 2.   
S eri o u s A d v er s e E v e nt s  
A n S A E is defi ne d as a n A E t hat:  
− 
Res ults i n deat h . 
− 
Is life-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  deat h if it were m ore s e vere) . 
− 
Re q uires i n -patie nt h os pitalizati o n or pr ol o n gati o n of e xisti n g h os pitalizati o n . 
− 
Res ults i n persiste nt or si g nifica nt disa bilit y/i nca pacit y . 
− 
Is a c o n ge nital a n o mal y / birt h defect . 
− 
Is me di call y si g nifi ca nt ( me dical a n d scie ntific j u d g me nt s h o ul d be e xercise d i n deci di n g 
w het her ot her sit uati o ns s h o ul d be c o nsi dere d s eri o us s uc h as i m p orta nt me dical e ve nts t hat 
mi g ht n ot be i m me diatel y life -t hreat e ni n g or res ult i n deat h or h os pitalizati o n b ut mi g ht 

G al a p a g o s  
C O N FI D E N TI A L  
4 3 9 5 2 _ 1 7 1 8 5 _ 5 1 8 4 2  
G L P G 3 9 7 0 - C L-2 0 7  
-7 4 - 
 
je o par dize t he s u bject or mi g ht re q uire i nter ve nti o n t o pre ve nt o ne of t h e ot her o utc o mes 
liste d i n t he defi niti o n a b o ve). 
1 1. 1. 3.   
U nli st e d ( U n e x p e ct e d) A d v er s e E v e nt s / R ef er e n c e S af et y I nf or m ati o n  
A n A E is c o nsi dere d u nliste d if t he nat ure or i nte nsit y is n ot c o nsiste nt wit h t he a p plica ble 
pr o d uct refere nce s afet y i nf or mati o n. F or a n I P, t he e x pecte d ness of a n A E will be deter mi ne d b y 
w het her or n ot it is liste d i n t he refere nce safet y i nf or mati o n p art of t he I B.  
1 1. 1. 4.   
A d v er s e E v e nt s of S p e ci al Int er e st  
N ot a p plica ble.  
1 1. 1. 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 a s 
A d v er s e E v e nt s  or S eri o u s A d v er s e E v e nt s  
La b orat or y a b n or malities wit h o ut cli nical si g nifica nce base d o n t h e i n vesti gat or’s j u d gme nt  are 
n ot c o nsi dere d A Es or S A Es. H o we ver, la b orat or y a b n or malities (e. g. cli nical c he mistr y, 
he mat ol o g y , a n d uri nal ysis) or ot her a b n or mal (cli nical st u d y -s p ecific) assess me nts (e. g. E C G, 
ra di o gra p h y, vital si g ns) t hat re q uire me dical or s ur gical i nter ve nti o n, are ass ociate d wit h si g ns 
a n d/ or s y m pt o ms, a n d/ or lea d t o I P i nterr u pti o n, m o dificati o n or disc o nti n uati o n m ust be 
rec or de d as a n A E or S A E if t he y m eet t he defi niti o n as descri be d i n Secti o ns 1 1. 1. 1  a n d 1 1. 1. 2 , 
res pecti vel y. If t he la b orat or y a b n or malit y is part of a s y n dr o me, t he s y n dr o me or dia g n osis is t o 
be re p orte d (e. g. a ne mia i nstea d of decrease d he m o gl o bi n).  
T he f oll o wi n g li ver e nz y me ele vati o ns m ust  be re p orte d as S A Es:  
− 
A S T or A L T > = 3 x U L N wit h si g ns of li ver da m a ge (t otal bilir u bi n > 2 x U L N O R I N R > 1. 5, 
a n d/ or wit h t he a p pea ra n ce of fati g ue, na usea, v o miti n g, ri g ht u p per q ua dra nt pai n or 
te n der ness, fe ver, ras h a n d/ or e osi n o p hilia [ > 5 %]). 
1 1. 1. 6.   
S p e ci al Sit u ati o n s  
S pecial sit uati o ns are sit uati o ns t hat ha ve a p ossi ble i m pact o n t he safe use of t he I P. T hese 
sit uati o ns mi g ht be or mig ht n ot be ass o ciate d wit h A Es . 
− 
Pre g n a nc y . 
− 
O ver d ose wit h I P. 
A n o ver d ose of I P is d efi ne d as t he a dmi nistrati o n  of a q ua ntit y of t he I P gi ve 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 d ose of I P gi ve n d uri n g t his st u d y. 
− 
Me dicati o n err or wit h I P. 
A me dicati o n err or wit h I P is defi ne d as a n u ni nte n de d fail ure i n t he dr u g treat me nt pr ocess 
t hat lea ds t o, or has t he p ote ntial t o lea d t o, har m t o t he s u bject. 
− 
Pr o d uct c o m plai nt or q ualit y d efect of I P. 
Pr o d uct c o m plai nt or q ualit y d efect of I P is defi ne d as c o m plai nts or defects of t he I P arisi n g 
fr o m p ote ntial de viati o ns i n t he ma n ufact ure, pac ka gi n g, or distri b uti o n of t he I P. 

G al a p a g o s  
C O N FI D E N TI A L  
4 3 9 5 2 _ 1 7 1 8 5 _ 5 1 8 4 2  
G L P G 3 9 7 0 - C L-2 0 7  
-7 5 - 
 
− 
A b use or mis use of I P. 
A b use of I P is defi ne d as t he persiste nt or s p ora di c, i nte nti o nal e xcessi ve use of t he I P, w hic h 
is acc o m pa nie d b y h ar mf ul p h ysical or ps yc h ol o gi cal effects.  
Mis use of I P is defi ne d as a sit uati o n w here t he I P is i nte nti o nall y a n d i na p pr o priatel y use d 
n ot i n acc or da n ce wit h t h e pr o d uct  i nf or mati o n. 
− 
Dr u g i nteracti o n or f o o d i nteracti o n wit h I P. 
A dr u g i nt eracti o n wit h I P is defi ne d as a sit uati o n i n w hic h t here is e vi de nce or a s us pici o n 
t hat t he I P i nteracts wit h a n ot her dr u g w he n b ot h are a d mi nistere d t o get h er. 
A f o o d i nteracti o n wit h I P is defi ne d as a sit uati o n i n w hic h t here is e vi de nce or a s us pici o n 
t hat t he I P i nteracts wit h a f o o d w he n t a ke n t o get h er. 
− 
Occ u pati o nal e x p os ure t o I P. 
Occ u pati o nal e x p os ure t o I P is defi n e d as a n e x p os ure t o t he I P 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.  
1 1. 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 is res 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 verit y. T his is t he 
basis f or t he s p o ns or’s fi nal re vie w a n d c o nfir m ati o n of acc urac y a n d c o m plete ness of e ve nt 
i nf or mati o n a n d ca us alit y assess me nts. 
1 1. 2. 1.   
A cti o n T a k e n R e g ar di n g I n v e sti g ati o n al Pr o d u ct (if A p pli c a bl e)  
T he acti o n ta ke n m ust be descri be d b y c h o osi n g fr o m: 
− 
D ose n ot c ha n ge d:  I n cas e n o acti o n is ta ke n re gar di n g t he I P. 
− 
I P per ma ne ntl y disc o nti n ue d : I n cas e a s u bject is p er ma ne ntl y disc o nti n ue d fr o m treat me nt 
or wit h dra w n fr o m t he st u d y  b y t he i n vesti gat or ( w h o ma y c o ns ult t he s p o ns or’s  me dical 
lea der). 
− 
I P te m p oraril y dis c o nti n ue d : I n cas e t he I P is te m p oraril y disc o nti n ue d b y t he i n vesti gat or 
(w h o ma y c o ns ult t he s p o ns or’s  me dical lea der ). 
− 
N ot a p plica ble: Ot her sit uati o ns ( e. g. i n case a n A E starte d after t he last I P a d mi nistrati o n) . 
1 1. 2. 2.   
A s s e s s m e nt of C a u s alit y  
T he i n vesti gat or is res p o nsi ble f or assessi n g t he ca usal relati o ns hi p t o I P(s) a d mi nistrati o n or 
st u d y pr oce d ures (e. g. i n vasi ve p r oce d ures s u c h as ve ni p u nct ure) base d o n her/ his cli nical 
j u d g me nt. T he f oll o wi n g decisi o n c h oice will be use d b y t h e i n vesti gat or t o descri be t he ca usalit y 
assess me nt bet wee n t he re p orte d e v e nt or la b orat or y test a b n or malit y a n d t he I P. 

G al a p a g o s  
C O N FI D E N TI A L  
4 3 9 5 2 _ 1 7 1 8 5 _ 5 1 8 4 2  
G L P G 3 9 7 0 - C L-2 0 7  
-7 6 - 
 
− 
U nrel ate d:  
Ti me relati o ns hi p t o I P i nta ke is i m pr o ba ble. Relate d t o ot her eti ol o gies s uc h as c o nc o mita nt 
me dicati o ns or s u bject's cli nical state.  
− 
U nli kel y:  
Ti me relati o ns hi p t o I P i nta ke is i m pr o ba ble ( b ut n ot i m p ossi ble). C o nc o mita nt disease or 
ot her dr u gs pr o vi de pla usi ble e x pla nati o ns.  
− 
P ossi ble:  
Ti me relati o ns hi p t o I P i nta ke is reas o n a ble. E ve nt or la b orat or y test a b n or malit y c o ul d als o 
be e x plai ne d b y disease or ot her dr u gs. I nf or mati o n o n I P wit h dra wal ma y be lac ki n g or 
u nclear.  
− 
Pr o b a ble:  
Ti me relati o ns hi p t o I P i ntake is reas o n a ble. U nli kel y t o be attri b ute d t o c o nc urre nt disease 
or ot her dr u gs. Res p o nse t o wit h dra wal is cli nicall y reas o na bl e a n d rec halle n ge n ot re q uire d.  
− 
Cert ai n:  
Ti me relati o ns hi p t o I P i nta ke is pla usi ble. Ca n n ot be e x plai ne d b y c o nc o mita nt disease or 
ot her dr u gs. Res p o nse t o wit h dra wal is pla usi ble ( p har mac ol o gicall y, pat h ol o gicall y). E ve nt 
defi niti ve p har mac ol o gicall y or p he n o me n ol o gicall y ( i.e. a n o bjecti ve a n d s pecific me dical 
dis or der or a rec o g nize d p har mac ol o gical p he n o me n o n). Rec halle n ge sat isfact or y, if et hical 
a n d necessar y. 
 
It s h o ul d be e m p hasize d t hat i neffecti ve treat me nt ( w orse ni n g of t he dis ease) s h o ul d n ot be 
c o nsi dere d as ca us all y relate d i n t he c o nte xt of A E re p orti n g.  
1 1. 2. 3.   
A s s e s s m e nt of S e v erit y  
T he se verit y of A Es s h o ul d be gra de d usi n g t he C T C A E  versi o n c urre nt at t he ti me of 
assess me nt . 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 de or 
a djecti ves: Gra de  1 ( mil d), Gra d e 2 ( m o derate), Gra de 3 (se vere), Gra de 4 (life -t hreate ni n g), or 
Gra de 5 (fatal) t o descri be t he ma xi m u m i nte nsit y of t he A E. 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 d es are defi ne d i n Ta ble  2 . 

G al a p a g o s  
C O N FI D E N TI A L  
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G L P G 3 9 7 0 - C L-2 0 7  
-7 7 - 
 
T a ble  2 :  
Gr a di n g of A E  Se verit y  
Gr a de    
A djecti ve    
Descri pti o n  
Gra de 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 de 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 de 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 de 4    
Life -t hreate ni n g   
Ur ge nt i nter ve nti o n i n dicate d  
Gra de 5    
Deat h  
Deat h -relate d A E  
* I nstr u me ntal A cti vities of Dail y Li vi n g ( A D L) refer t o pre pari n g meals, s h o p pi n g f or gr oceries or cl ot hes, usi n g t he tele p h o ne, ma na gi n g 
m o ne y, etc.  
* * Self -care 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 he t oil et, ta ki n g me dicati o ns, a n d n ot be dri d de n.  
 
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 de d o n t he basis of t he 
cli nical se verit y i n t he c o nte xt of t he u n derl yi n g c o n diti o ns; t his ma y or ma y n ot be i n a gree m e nt 
wit h t he gra di n g of t he la b orat or y a b n or malit y. T his is u p o n t he i n vesti gat or’s assess me nt.  
If t here is a c ha n ge i n i nte nsit y ( w orse ni n g or i m pr o ve me nt) of a n A E, it m ust be rec or de d.  
1 1. 2. 4.   
O ut c o m e  
Eac h A E m ust be rate d b y c h o osi n g a m o n g:  
− 
Rec o vere d/res ol ve d;  
− 
Rec o vere d/res ol ve d wit h se q uelae;  
− 
Rec o veri n g/res ol vi n g;  
− 
N ot rec o vere d/ n ot res ol v e d;  
− 
Fatal;  
− 
U n k n o w n.  
1 1. 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 Ad v er s e 
E v e nt s , S eri o u s A d v er s e E v e nt s , Pr e g n a n ci e s, a n d O t h er S p e ci al 
S it u ati o n s t o t h e S p o n s or 
1 1. 3. 1.   
A d v er s e E v e nt s  
T he A E re p orti n g p eri o d f or safet y s ur veilla nce be gi ns w he n t h e s u bject si g ns t he I C F a n d e n ds at 
t he s u bject’s last F U  visit (t he last F U  visit after t h e last d ose of I P). I n t his peri o d, all ne w A Es, 

G al a p a g o s  
C O N FI D E N TI A L  
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G L P G 3 9 7 0 - C L-2 0 7  
-7 8 - 
 
re gar dless of ca us e or rel ati o ns hi p, deri ve d b y s p o nta ne o us, u ns olicite d re p orts of s u bjects, b y 
o bser vati o n a n d b y r o uti ne o pe n q uesti o ni n g (s uc h as “ H o w d o y o u feel? ”) nee d t o be rec or de d i n 
t he s o urce a n d i n t he C R F. 
I n case a n A E is o n g oi n g at t he ti me of t he last F U  visit, t he i n vesti gat or nee ds t o f oll o w  u p  o n 
t he s u bject u ntil A E res ol uti o n or reas o na ble st a bilizati o n a n d t o d oc u me nt i n t he s u bject’s s o urce 
d oc u me ntati o n. N o relat e d u p dates or a d diti o n al d ata o n t he A E s h o ul d be re p orte d i n t he C R F.  
If a s u bject is d oc u m e nte d as l ost -t o-F U , o n g oi n g/ u n k n o w n outc o me A Es will n ot be f oll o we d -
u p.  
If t he A E meets t he criteria f or seri o us ness, t he S A E f or m m ust be c o m plete d a n d se nt t o t he 
s p o ns or wit hi n 2 4 ho urs (see Secti o n 1 1. 3 . 2). 
1 1. 3. 2.   
S eri o u s A d v er s e E v e nt s  
S u bjects e x perie nci n g a n S A E or a n e mer ge nc y sit uati o n will be e xa mi ne d b y a p h ysi cia n as s o o n 
as p ossi ble. T he s u bject will re mai n u n der o bser vati o n as l o n g as m e dicall y i n dicat e d. 
A p pr o priate la b orat or y tests will be perf or me d u ntil all para meters ret ur n t o n or mal or are 
ot her wise e x plai ne d or st a ble.  
All S A Es, w het her or n ot dee me d I P-relate d, m ust be rec or de d o n t he S A E f or m a n d i n t he C R F. 
T he i n vesti gat or m ust re p ort eac h S A E i m me diat el y, a n d u n der n o circ u msta nces s h o ul d t his 
e x cee d 2 4 h o urs f oll o wi n g t he k n o wl e d ge of t he S A E, as is i n dicate d o n p a ge 2  u n der 
“ E mer ge n c y C o ntact I nf or mati o n”.  
T he S A E f or m s h o ul d at least c o ntai n i de ntifiers of t he s u bject a n d t he re p orter, S A E ter m a n d 
state me nt of relat e d ness t o t he I P, a n d at a later sta ge if n ot yet a vaila ble wit hi n 2 4 h o urs, t he 
f or m nee ds t o be c o m plete d wit h a clearl y writte n narrati ve descri bi n g si g ns, s y m pt o ms, a n d 
treat me nt of t he e ve nt, dia g n ostic pr oce d ures, as well as a n y rele va nt la b orat or y data a n d a n y 
se q uelae. 
F U  a n d o utc o m es s h o ul d be re p orte d a n d d oc u m e nte d i n t he s o urce d oc u me nts f or all s u bjects 
t hat e x perie nce a n S A E. It is i m p orta nt t hat t he i nf or mati o n pr o vi de d o n t h e S A E f or m matc hes 
t he i nf or mati o n rec or de d o n t he C R F f or t he sa me e ve nt. 
C o pies of a d diti o nal la b orat or y tests, c o ns ultati o n re p orts, p ost -m orte m re p orts, 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 s h o ul d be se nt w he n re q uest e d a n d a vaila ble. O nl y 
s u bject i de ntifiers (s u bject n u m ber) s h o ul d a p pear o n t he c o pies, a n d all na mes a n d i nitials s h o ul d 
be blac ke n e d a n d re n dere d ille gi ble. F oll o w -u p ( F U) re p orts relati ve t o t he s u bject’s s u bse q ue nt 
c o urse m ust be s u b mitte d u ntil t he e ve nt has s u bsi de d or, i n cas e of per ma ne nt i m pair me nt, u ntil 
t he c o n diti o n sta bilizes. 
A n y S A Es t hat occ ur after t he p ost -treat me nt F U  visit b ut wit hi n 3 0 da ys of t he last d ose of I P(s), 
re gar dless of ca us alit y, s h o ul d als o be re p orte d ( E mer ge nc y C o ntact I nf or mati o n o n P a ge 2 ) b ut 
n ot e ntere d i n t he C R F . I n vesti gat ors are n ot o bli gate d t o acti vel y see k S A Es after t he C S P-
defi ne d  F U  peri o d. H o we ver, if t he i n vesti gat or is i nf or me d a b o ut a n S A E t hat occ urs at a n y ti me 

G al a p a g o s  
C O N FI D E N TI A L  
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G L P G 3 9 7 0 - C L-2 0 7  
-7 9 - 
 
after t he s u bjects’ p ost-treat me nt F U  visit a n d t he e ve nt is dee me d rele va nt t o t he use of I P(s), 
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 b y usi n g t he S A E f or m.  
1 1. 3. 3.   
Pr e g n a n c y  
All i nitial re p orts of pre g na nc y i n fe male s u bjects a n d pre g na ncies  i n part n ers of male s u bjects 
i ncl u de d i n t he cli nical st u d y m ust be rec or de d a n d d oc u me nte d i n t he s o urce d oc u me nts a n d o n 
t he pre g na n c y f or m. T h e i n vesti gat or m ust re p ort eac h pre g na nc y i m me diatel y, a n d u n der n o 
circ u msta nces s h o ul d t his e x cee d 2 4 h o urs f oll o wi n g t he k n o wle d ge of t he pre g na nc y, as is 
i n dicate d o n p a ge 2  u n d er “ E mer ge nc y C o ntact I nf or mati o n”.   
All  pre g n a ncies s h o ul d b e f oll o we d -u p u ntil deli v er y or pre g na nc y i nterr u pti o n. T he i n vesti gat or 
will c o ntact t he s u bject or part ner of t he s u bject after gi vi n g  c o ns e nt, at t he e x pecte d ti me of 
deli ver y f or F U  a n d f or i nf or mati o n re gar di n g t he o utc o me of t he ne w b or n. A b n or mal pre g na nc y 
a n d/or a b n or mal n e w b or n o utc o mes are c o nsi dere d S A Es a n d m ust be re p orte d usi n g t he S A E 
f or m. 
1 1. 3. 4.   
R e p orti n g of S p e ci al Sit u ati o n s ( O t h er T h a n Pr e g n a n c y) a n d A d v er s e 
E v e nt s  
I n case a s peci al sit uati o n is n ot ass ociate d wit h a n A E, t he s pecial sit uati o n s h o ul d be rep orte d 
wit hi n 2 4 h o urs b y usi n g t he S pecial Sit uati o ns f or m as i s i n dicate d o n pa ge 2  u n der “ E mer ge nc y 
C o ntact I nf or mati o n” . 
I n case a s peci al sit uati o n is ass ociate d wit h a n A E, t he s pecial sit uati o n s h o ul d be re p orte d 
wit hi n 2 4 h o urs b y usi n g t he S pecial  Sit uati o ns f or m a n d t he ass ociate d A E s h o ul d be re p orte d as 
s pecifie d i n Secti o n  1 1. 3. 1 . 
I n case a s peci al sit uati o n is ass ociate d wit h a n S A E, t he s pecial sit uati o n s h o ul d be re p orte d 
wit hi n 2 4 h o urs b y usi n g t he S A E f or m (a n d n ot t he S pecial Sit uati o ns f or m) a n d t he ass o ciate d  
S A E s h o ul d be re p orte d as s pecifie d i n S ecti o n 1 1. 3. 2 . 
1 1. 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 nite d States 
Fe deral Dr u g A d mi nistrati o n C o de 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 rele va nt u p dates, a n d ot her c o u ntr y-s p ecific l e gislati o n or re g ulati o ns, t he 
s p o ns or ma y b e re q uire d t o e x pe dite rep orts of S A Es a n d seri o us a d verse dr u g reacti o ns or 
s us pecte d u ne x pecte d seri o us a d verse reacti o ns ( S U S A Rs) t o w orl d wi de re g ulat or y aut h orities . 
T he s p o ns or or a s p ecifie d desi g nee will n otif y w orl d wi de re g ulat or y aut h orities a n d t he rele va nt 
I E C/I R B i n c o ncer ne d M e m ber States of a p plica bl e S U S A Rs as o utli ne d i n c urre nt re g ulati o ns.  
Assess me nt of e x pecte d ness f or S A Es will be deter mi ne d usi n g t he refere nce safet y inf or mati o n 
secti o n i n t he I B or rele va nt l ocal la bel as a p plica ble. 
All c o ncer ne d i n vesti gat ors will recei ve a safet y letter n otif yi n g t h e m of rele va nt S U S A R re p orts 
ass ociate d wit h a n y I P(s). T he i n vesti gat or s h o ul d n otif y t he I E C/I R B of S U S A R re p orts as s o o n 

G al a p a g o s  
C O N FI D E N TI A L  
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G L P G 3 9 7 0 - C L-2 0 7  
-8 0 - 
 
as is practical, w h ere t his is re q uire d b y l ocal re g ulat or y aut h orities , a n d i n acc or dance wit h t he 
l ocal i nstit uti o nal p olic y. 
1 2.    
S P O N S O R’ S A N D I N V E S T I G A T O R’ S R E S P O N SI BI LI TI E S 
T his cli nical st u d y will be c o n d ucte d i n c o m plia nce wit h t his C S P, t he c urre nt I C H-G C P 
G ui deli ne E 6 , a n d a p plica ble l ocal et hical a n d le gal re q uire m e nts. 
G o o d Cli nical P ractice is a n i nter nati o nal et hical a n d scie ntific q ualit y sta n dar d f or desi g ni n g, 
c o n d ucti n g, rec or di n g , a n d re p orti n g st u dies t hat i n v ol ve t he partici pati o n of h u ma n s u bjects. 
C o m plia nce wit h t his sta n dar d pr o vi des p u blic ass ura nce t h at t he ri g hts, safet y a n d well -bei n g of 
cli nical st u d y s u bjects are pr otecte d, c o nsiste nt wit h t he pri nci ples t hat ha ve t heir ori gi n i n t he 
Declarati o n of Helsi n ki  ( 1 9 9 6 a n d s uccessi ve a me n d me nts), a n d t hat t he cli nical st u d y dat a are 
cre di ble.  
T he na me a n d a d dress of eac h t h ir d part y ve n d or (e. g. C R O) us e d i n t his st u d y a n d t h e s p o ns or’s 
st u d y tea m me m bers will be mai ntai ne d i n t he i n vesti gat or’s a n d s p o ns or’s files as a p pr o priate.  
1 2. 1.    
S p o n s or’ s R e s p o n si biliti e s  
1 2. 1. 1.   
R e g ul at or y A ut h or it y A p pr o v al  
Pri or t o cli nical st u d y start, t his C S P t o get her wit h all rele va nt d oc u me ntati o n nee ds  t o be 
s u b mitte d t o t he res pecti ve re g ulat or y a ut h orities f or re vie w a n d a p pr o val i n c o m plia nce wit h 
c urre nt re g ulati o ns bef ore t he st u d y ca n start . 
1 2. 1. 2.   
Cli ni c al St u d y Cl o s ur e C o n si d er ati o n s  
T he s p o ns or res er ves t he ri g ht t o cl ose t he site or e n d t he cli nical st u d y at a n y ti me f or a n y 
reas o n. I n case of a n earl y ter mi nati o n of t h e cli nical st u d y or te m p orar y halt b y t he s p o ns or, t he 
I E C/I R B s h o ul d be n otifie d acc or di n g t o l ocal re q uire me nts , u nless ot her wise s pecifie d b y t he 
s p o ns or, t he I E C/I R B, a n d/ or t he re g ulat or y aut h orities  i ncl u di n g a detaile d writte n e x pla nati o n 
of t he reas o ns f or t he ter mi nati o n/ halt.  
Reas o ns f or t he cl os ure of a site ma y i ncl u de, b ut are n ot li mite d t o:  
− 
S uccessf ul c o m pleti o n of t he cli nical st u d y at t he ce nter.  
− 
T he o verall re q uire d n u m ber of s u bjects f or t he cli nical st u d y has b ee n recr uite d.  
− 
Fail ure of t he i n vesti gat or t o c o m pl y wit h t he C S P, I C H -G C P g ui deli nes , or l ocal 
re q uire me nts. 
− 
I n a de q uat e recr uit me nt of s u bjects b y t he i n vesti gat or. 

G al a p a g o s  
C O N FI D E N TI A L  
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-8 1 - 
 
Reas o ns f or earl y ter mi n ati o n of a cli nical st u d y b y t he s p o ns or m a y i ncl u de , b ut are n ot li mite d 
t o: 
− 
Safet y c o ncer ns.  
− 
S ufficie nt data s u g gesti n g lac k of efficac y.  
T he e n d of cli nical st u d y declarati o n will be s u b mitte d t o t he re g ulat or y aut h orities a n d I E C/I R B 
after t he c o m plete cli nical st u d y has e n de d i n all partici pati n g ce nters, i n all c o u ntries. T his 
n otificati o n will als o be s u b mitte d acc or di n g t o l ocal re q uire me nts of t he e n d of t he cli nical st u d y 
i n a gi ve n c o u ntr y/ me m b er state. 
1 2. 1. 3.   
I n d e m nifi c ati o n 
U n der t he c o n diti o ns of a c o ntract c o ncl u de d bet wee n i n vesti gat or, site , a n d s p o ns or or desi g nee, 
w hic h s hall pre vail, t he s p o ns or s hall, e xce pt i n case of gr oss ne gli ge nce or willf ul misc o n d uct, 
i n de m nif y a n d h ol d h ar mless t he i n vesti gat or a n d his/ her me dical staff fr o m a n y clai m arisi n g 
fr o m t he cli nical st u d y acti vities carrie d o ut i n c o m plia nce wit h t he C S P, s p o ns or’s i nstr ucti o ns, 
a n d a p plica ble l ocal re g ulati o ns.  
T he i n vesti gat or m ust n otif y t he s p o ns or i m me diatel y u p o n n otice  of a n y cl ai ms or la ws uits.  
1 2. 1. 4.   
I n s ur a n c e 
T he s p o ns or s hall mai ntai n i ns ura nce c o vera ge t hat is s ufficie nt t o c o ver its o bli gati o ns a n d t hat 
is c o nsiste nt wit h h u ma n cli nical st u d y l ocal re g ul ati o ns. Pr o vi de d t hat t he s u bject has bee n 
treate d acc or di n g t o t he C S P a n d s p o ns or’s i nstr ucti o ns, a n y i nj ur y ca use d t o a s u bject w hic h is 
t he direct res ult of his/ her partici pati o n t o t he cli nical st u d y s h all be c o vere d b y t he s p o ns or’s 
i ns ura nce, e x ce pt i n case of gr oss ne gli ge nce or willf ul misc o n d uct b y t he i n vesti gator . 
1 2. 1. 5.   
Ar c hi vi n g  
T he s p o ns or will arc hi ve t he c o nte nt of t he Tri al  Master File ( T M F ) f or at least 2 5 years after t he 
e n d of t he cli nical st u d y.  
1 2. 2.    
R e p orti n g  
W here re q uire d b y I E C/I R B per l ocal re q uire me nts, at least o nce a year t he i n vesti gat or will 
pr o vi de t he I E C/I R B wit h a pr o gress re p ort t o all o w re vie w of t he cli nical st u d y (see 
Secti o n  1 2. 6. 1 ).  
At t he e n d of t he cli nical st u d y, t he res ults of t he cli nical st u d y will be re p orte d i n a C S R b y t he 
s p o ns or. T he p o p -P K a n al ysis data    
 data ma y be re p orte d se paratel y fr o m t he mai n 
C S R. A s u m mar y or f ull re p ort, de p e n di n g o n t h e re q uire me nts, will be pr o vi de d b y t he s p o ns or 
t o t he i n vesti gat ors, t o t h e rele va nt re g ulat or y a ut h orities, a n d I E Cs/I R Bs (if re q uire d b y t he 
a p plica ble re gulat or y re q uire me nts) wit hi n 1  year, or 6 m o nt hs f or pe diatric st u dies, after t he e n d 
of t he cli nical st u d y.  

G al a p a g o s  
C O N FI D E N TI A L  
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G L P G 3 9 7 0 - C L-2 0 7  
-8 2 - 
 
1 2. 3.    
P u bli c ati o n  
It is u n derst o o d b y t he i n vesti gat or t h at t he s p o ns or s hall be free t o use t he c o m p o u n d-relate d 
i nf or mati o n, w hic h is ge nerate d d uri n g t h e cli nical st u d y a n d ma y discl ose it t o ot her cli nical 
i n vesti gat ors a n d t o re g ul at or y a ge n cies. As a c o ns e q ue nce, t he i n vesti gat or a grees t o pr o vi de all 
cli nical st u d y res ults a n d data ge nerate d d uri n g t his cli nical st u d y t o t he s p o ns or.  
T he i n vesti gat or s hall n ot be a ut h orize d t o s u b mit t he res ults of t his cli nical st u d y a n d a n y data 
f or p u blic discl os ure (e. g. p u blicati o n or prese ntati o n) wit h o ut t he pri or writte n a p pr o val of t h e 
s p o ns or, w hic h s hall n ot be u nreas o n a bl y wit h hel d. 
H o we ver, it is u n derst o o d a n d a gree d b y t he i n vesti gat ors t hat t heir res ults a n d/ or fi n di n gs s h all 
n ot be a ut h orize d f or p u blicati o n pri or t o s p o ns or’s p u blicati o n of t he o verall cli nical st u d y 
res ults. T he i n vesti gat or a grees t h at pri or t o t he p u blicati o n of a n y res ults, he/s he s hall pr o vi de 
t he s p o ns or wit h a draft c o p y of t he i nte n de d p u blicati o n. T he s p o ns or s hall ha ve t he ri g ht t o 
re vie w it a n d t o ma ke a n y c o m me nts. I n acc or da nce wit h ge nerally acce pte d scie ntific 
c olla b orati o n pri nci ples, c o -a ut h ors hi p wit h a n y st aff me m ber s p o ns or i n v ol ve d i n t he cli nical 
st u d y, will be disc usse d a n d m ut uall y a gree d u p o n bef ore s u b missi o n of a n y ma n uscri pt t o a 
p u blis her.  
1 2. 4.    
I n v e sti g at or’ s R e s p o n si biliti e s 
1 2. 4. 1.   
S o ur c e D at a a n d D at a C a pt ur e  
T he nat ure a n d l ocati o n of all s o urce d oc u me nts nee d t o be i de ntifie d a n d d oc u me nte d t o e ns ure 
t hat all s o urces of ori gi nal data re q uire d t o c o m plete t he C R F are k n o w n a n d are accessi ble f or 
verificati o n b y t he m o nit or.  
S o urce data ma y b e directl y ca pt ure d fr o m d e vices tra nsferre d fr o m t hir d part ners ( e. g. l a b orat or y 
data) or e ntere d m a n uall y i nt o t he C R F. T he C R F c o m pleti o n g ui deli nes will be pr o vi de d t o eac h 
site. 
It is rec o m me n de d t hat t h e a ut h or of a n e ntr y i n t he s o urce d oc u me nts s h o ul d be i de ntifia ble. 
F oll o wi n g I C H -G C P g ui deli nes, direct access t o s p o ns or’s re prese ntati ves t o s o urce d oc u m e nts 
m ust be gra nte d f or t he p ur p ose of verif yi n g t hat t he data rec or de d o n t he C R F are c o nsiste nt 
wit h t he ori gi nal s o urce d ata.  
1 2. 4. 2.   
Ar c h i vi n g 
U nless l ocal le gislati o n re q uires arc hi vi n g f or a l o n ger peri o d, t he i n vesti gat or s hall arc hi ve t he 
c o nte nt of t he cli nical i n v esti gat or site file f or at least 2 5 years after t he e n d of t he cli nical st u d y. 
H o we ver, t he me dical files of s u bjects s hall be arc hi ve d i n acc or da nce wit h nati o nal la w.  
T he i n vesti gat or s h o ul d ta ke meas ures t o pre ve nt acci de ntal or pre mat ure destr ucti o n of t hese 
d oc u me nts.  

G al a p a g o s  
C O N FI D E N TI A L  
4 3 9 5 2 _ 1 7 1 8 5 _ 5 1 8 4 2  
G L P G 3 9 7 0 - C L-2 0 7  
-8 3 - 
 
U n der n o circ u msta nce s hall t he i n vesti gat or rel ocate or dis p ose a n y cli nical st u d y d oc u me nts 
bef ore h a vi n g o btai ne d a writte n a p pr o val of t h e s p o ns or.  
If it bec o mes necessar y f or t he s p o ns or or t he a p pr o priate Re g ulat or y A ut h or it y t o re vi e w a n y 
d oc u me ntati o n relati n g t o t his cli nical st u d y, t he i n vesti gat or m ust per mit access t o s uc h re p orts. 
T he s u bject is gra nti n g access t o his/ her s o urce data b y si g ni n g t he I C F.  
A n y diffic ult y i n st ori n g ori gi nal d oc u m e nts m ust be disc usse d wit h t he m o nit or pri or t o t he 
i nitiati o n of t he cli nical st u d y. 
After st u d y c o m pleti o n , t he site m ust n otif y t he s p o ns or (P ost St u d y S u p p ort @ gl p g.c o m ) o n 
pla n ne d a u dits, arc hi ves, etc . 
1 2. 4. 3.   
P arti ci p ati o n C ar d s  
If t he s u bjects are n ot u n der 2 4-h o ur s u p er visi o n of t he i n vesti gat or or site staff, t he y m ust be 
pr o vi de d wit h a s u bject p artici pati o n car d i n dicati n g t he na me of t he I P, t h e cli nical st u d y 
n u m ber, t he i n vesti gat or's na me , a n d t he site’s 2 4 -h o ur e mer ge nc y c o nt act n u m ber. T he s u bject 
s h o ul d be a d vise d t o kee p t he partici pati o n car d i n his/ her wallet at all ti mes. 
1 2. 5.    
C o nfi d e nti alit y  
T he s u bject will recei ve all i nf or mati o n as re q uire d b y t he E U Ge neral Data Pr otecti o n 
Re g ulati o n, na mel y t he i de ntit y a n d c o ntact details of t he c o ntr oller, t he c o ntact details of t he data 
pr otecti o n officer, t he cli nical researc h p ur p oses, t he le gal basis f or t h e pr ocessi n g, t h e reci pie nts 
of t he pers o nal d ata, t he tra nsfer of t he pers o nal data t o t hir d c o u ntries  a n d res pecti ve safe g uar ds, 
t he rete nti o n peri o ds, t he fair pr ocessi n g of his dat a, a n d all his/ her dat a s u bject’s ri g hts. All 
details are liste d i n t he I C F.  
All i nf or mati o n c o ncer ni n g t he pr o d uct a n d t he s p o ns or’s o perati o ns (s uc h as pate nt a p plicati o ns, 
f or m ulas, ma n ufact uri n g pr ocesses, basic scie ntifi c data, or f or m ulati o n i nf or mati o n s u p plie d t o 
t he i n vesti gat or b y t h e s p o ns or a n d n ot pre vi o usl y p u blis he d) is c o nsi dere d c o nfi de ntial a n d 
s h o ul d n ot be discl ose d b y t he i n vesti gat or t o a n y t hir d part y with o ut t he s p o ns or’s pri or writte n 
a p pr o val. T he i n v esti gat or a grees t o use t his i nf or mati o n o nl y i n acc o m plis hi n g t he cli nical st u d y 
a n d will n ot use it f or ot her p ur p oses.  
I n or der t o per mit eas y i d e ntificati o n of t he i n di vi d ual s u bject d uri n g a n d after t he cli nical st u d y, 
t he i n vesti gat or is res p o nsi ble f or kee pi n g a n u p date d S u bject I de ntificati o n C o de List. T he 
m o nit or will re vie w t his d oc u me nt f or c o m plet e ness. H o we ver, t he i n vesti gat or m ust g uara ntee 
t he s u bject’s a n o n y mit y will be mai ntai ne d. T heref ore, i n or der t o e ns ure s u bject c o nfi de ntialit y, 
t he S u bject I d e ntificati o n C o de List m ust re mai n at t he ce nter a n d n o c o p y will be ma de. 

G al a p a g o s  
C O N FI D E N TI A L  
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G L P G 3 9 7 0 - C L-2 0 7  
-8 4 - 
 
1 2. 6.    
Et hi c al C o n si d er ati o n s  
1 2. 6. 1.   
I n d e p e n d e nt Et hi c s C o m mitt e e / I n stit uti o n al R e vi e w B o ar d  
T his cli nical st u d y ca n o nl y be u n d erta ke n after IE C/I R B a p pr o val of t his C S P t o get her wit h all 
rele va nt d oc u m e ntati o n. T his a p pr o val d oc u me nt m ust be date d a n d clearl y i de ntif y t he cli nical 
st u d y a n d t he relate d cli nical st u d y d oc u m e nts bei n g a p pr o ve d, i ncl u di n g t he s u bject 
c o m pe nsati o n pr o gra ms, if a p plica ble.  
D uri n g t h e c o urse of t he cli nical st u d y, at least t he f oll o wi n g d oc u me nts ha ve t o  be s u b mitte d t o 
t he I E C/I R B, per l ocal re q uire me nts:  
− 
C ha n ges t o t he I B  
− 
Re p orts of A Es t hat are s eri o us, u nliste d , a nd ass o ciate d wit h t he I P (i n c o m plia nce wit h 
I E C/I R B, per l ocal re q uire me nts) 
− 
C S P a me n d me nts  
− 
I C F a me n d me nts 
 
T he I E C/I R B is res p o nsi ble f or c o nti n u o us re vi e w of t he cli nical st u d y. W here re q uire d b y 
I E C/I R B, per l ocal re q uire me nts, at least o nce a year t he  i n vesti gat or will pr o vi de t he I E C/I R B 
wit h a pr o gress re p ort t o all o w re vie w of t he cli nical st u d y. A d diti o nal pr o gress re p orts s h o ul d be 
pr o vi de d acc or di n g t o l ocal le gal re q uire me nts. T hese re q uests a n d (re -)a p pr o vals, if a p plica ble, 
s h o ul d be d oc u me nted i n writi n g.  
1 2. 6. 2.   
I nf or m e d C o n s e nt 
T he i n vesti gat or or desi g nate d pers o n nel m ust e x plai n t he cli nical st u d y a n d t he i m plicati o ns of 
partici pati o n ( e. g. o bjecti ves, met h o ds, a ntici pate d be nefits, p ossi ble ris ks) t o p ote ntial s u bjects 
acc or di n g t o a p plica ble re g ul ati o ns pri or t o a n y cli nical st u d y -relate d acti vit y. S u bjects will be 
i nf or me d t hat t heir partici pati o n is v ol u ntar y a n d t hat t he y m a y wit h dra w fr o m t he cli nical st u d y 
at a n y ti me. T he y will be i nf or me d t hat c h o osi n g n ot t o partici pate or t o wit h dra w fr o m t he 
cli nical st u d y will n ot ha ve a n i m pact o n t he care t he s u bject will recei ve f or t he treat me nt of 
his/ her disease.  
T he s u bject will be gi ve n s ufficie nt ti me t o rea d t h e I C F a n d t o as k a d diti o nal q uesti o ns. After 
t his e x pla nati o n a n d bef ore e ntr y i n t he cli nical st u d y, t he s u bject’s c o nse nt s h o ul d be 
a p pr o priatel y rec or de d b y mea ns of t he s u bject's pers o nall y date d si g nat ure a n d b y t he 
i n vesti gator’s d ate d si g nat ure. I n case t he s u bject is u na ble t o rea d a n d / or write,  oral c o nse nt  i n 
t he prese n ce of at least 1 i m partial wit ness w h o was als o i ncl u de d w he n t h e affecte d pers o n was 
bei n g i nf or me d , ma y be gi ve n. T h e wit ness ma y n ot be a n y o ne w or ki n g at  t he site n or a me m ber 
of t he i n vesti gati n g tea m. T he orall y gi ve n c o ns e nt s hall be d oc u me nte d i n writi n g, date d a n d 
si g ne d b y t he wit ness. After ha vi n g o btai ne d t he c o nse nt, a c o p y of t he si g ne d a n d date d I C F 
m ust be gi ve n t o t he s u bj ect.  
If ne w i nf or matio n bec o mes a vaila ble rele va nt t o t he s u bject’s willi n g ness t o partici pate i n t he 
cli nical st u d y, t he s u bject will be i nf or me d i n a ti mel y ma n ner b y mea ns of a n a me n de d I C F. T his 

G al a p a g o s  
C O N FI D E N TI A L  
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G L P G 3 9 7 0 - C L-2 0 7  
-8 5 - 
 
a me n de d I C F will be si g ne d a n d date d b y t h e s u bject ( or, if a p plica ble, b y a n i n de pe n de nt 
wit ness) a n d t he i n vesti gat or t o d oc u me nt t he willi n g ness of t h e s u bject t o c o nti n ue wit h t he 
cli nical st u d y.  
T his si g ne d a n d d ate d a m e n de d versi o n will be file d t o get her wit h t he i nitial si g ne d a n d date d 
I C F. 
A pre g na nt part ner , w h o a grees t h a t i nf or mati o n will be gat h ere d a b o ut her pre g na nc y a n d t he 
birt h , will be as ke d t o si g n a s pecific I C F t o partici pate i n t he data c ollecti o n. Data a b o ut t he 
healt h of t he ba b y will be c ollecte d if t he pare nt (s)/le gal g uar dia n(s) a gree wit h t he data 
c ollecti o n a n d si g n a s pecific I C F.  
S u bjects w h o a gree t o partici pate i n t he st u d y a n d w h o ha ve si g ne d i nf or me d c o nse nt, will be 
gi ve n t he o pti o n t o pr o vi de a d diti o nal (a n d o pti o nal) i nf or me d c o ns e nt f or t he l o n g -t er m st ora ge 
of a d diti o nal c ollecti o n of sa m ple(s) a n d/ or of left o ver sa m ples a n d ass ociate d data , c ollect e d 
d uri n g t he st u d y, f or f ut ure scie ntific researc h.  
1 2. 7.    
D at a Q u alit y C o ntr ol/ A s s ur a n c e  
1 2. 7. 1.   
M o nit ori n g  
Data q ualit y will be ass ure d t hr o u g h Ris k -Bas e d M o nit ori n g, me dical m o nit ori n g, a n d ot her 
rele va nt acti vities as descri be d i n t he Data Ma na ge me nt Pla n or Me dical Re vie w Pla n a n d 
m o nit ori n g pla ns a vaila bl e i n t he T M F. T his cli nical st u d y will be m o nit ore d b y s p o ns or 
re pres e ntati ves acc or di n g t o t heir c urre nt sta n dar d o perati n g p r oce d ures.  
T o g uara ntee a d e q uate pr otecti o n of t h e s u bjects a n d t o g uara ntee t h e q ualit y of t he data, t he 
s p o ns or will e ns ure o versi g ht of a n y cli nical st u d y-relate d d uties a n d f u ncti o ns carrie d o ut o n its 
be half, i ncl u di n g cli nical st u d y -relate d d uties a n d f u ncti o ns t hat are s u bc o ntracte d t o a n ot h er 
par t y b y t h e s p o ns or’s c o ntracte d C R O(s).  
A ris k -base d Q ualit y M a na ge me nt Pla n  ( Q M P) is pre pare d f or t h e st u d y t h at e val uates p ote ntial 
ris ks i n relati o n t o ri g hts, safet y, a n d well-bei n g of t he st u d y s u bjects as well as t he data i nte grit y. 
T he Q M P descri bes  a n d e val uates all i n v ol ve d sta ke h ol der i nterfaces ha vi n g p ote ntial critical 
i m pact o n t he a b o ve. Ris ks are c o nsi dere d at b ot h t he s yste m le vel (e. g. sta n dar d o perati n g 
pr oce d ures, c o m p uterize d s yste ms, pers o n n el, a n d ve n d ors) a n d st u d y le vel (e. g. I P, st ud y desi g n, 
data c ollecti o n, i nf or me d c o nse nt pr ocess , a n d rec or di n g).  
1 2. 7. 2.   
A u dit a n d I n s p e cti o n  
T o e ns ure c o m plia nce wit h rele va nt re g ulati o ns, a n i n de pe n de nt q ualit y ass ura nce re prese ntati ve, 
re g ulat or y aut h or ities a n d/ or I E Cs/I R Bs ma y re vi e w t his cli nical st ud y. T his i m plies t hat 
a u dit ors/i ns pect ors will ha ve t he ri g ht t o i ns pect t he cli nical st u d y ce nter(s) at a n y ti me d uri n g 

G al a p a g o s  
C O N FI D E N TI A L  
4 3 9 5 2 _ 1 7 1 8 5 _ 5 1 8 4 2  
G L P G 3 9 7 0 - C L-2 0 7  
-8 6 - 
 
a n d/ or after c o m pleti o n of t he cli nical st u d y a n d will ha ve access t o t he data ge nerat e d d uri n g t he 
cli nical st u d y, s o urce d oc u me nts, a n d s u bject's files. B y partici pati n g i n t his cli nical st u d y, 
i n vesti gat ors a gree t o t his re q uire me nt. 
 

G al a p a g o s  
C O N FI D E N TI A L  
4 3 9 5 2 _ 1 7 1 8 5 _ 5 1 8 4 2  
G L P G 3 9 7 0 - C L-2 0 7  
-8 7 - 
 
1 3.    
R E F E R E N C E S  
1.    
Patel R, S ha ha ne A. T he e pi de mi ol o g y of Sj ö gre n’s s y n dr o me. Cli n E pi de mi ol. 2 0 1 4 J ul 
3 0; 6: 2 4 7 – 5 5.  
2.    
Fra n cesc hi ni F, Ca vazza na I, A n dre oli L, Ti n ca ni A. T he 2 0 1 6 classificati o n criteria f or 
pri mar y Sj o gre n’s s y n dr o me: w hat’s ne w? B M C Me d. 2 0 1 7 Mar 3 1; 1 5( 1): 6 9.  
3.    
Qi n B, Wa n g J, Ya n g Z, Ya n g M, Ma N, H ua n g F, et al. E pi de mi ol o g y of pri mar y 
Sj ö gre n’s s y n dr o me: a s yste matic re vie w a n d meta -a nal ysis. A n n R he u m Dis. 2 0 1 5 
N o v; 7 4( 1 1): 1 9 8 3 – 9.  
4.    
H ua n g Y, C he n g Q, Jia n g C, A n S, Xia o L, G o u Y, et al. T he I m m u n e Fact ors I n v ol ve d i n 
t he Pat h o ge n esis, Dia g n osis, a n d Treat me nt of Sj o gre n’s S y n dr o me [I nter net]. V ol. 2 0 1 3, 
Cli nical a n d De vel o p me ntal I m m u n ol o g y. Hi n da wi; 2 0 1 3 [cite d 2 0 2 0 A pr 2 2]. p. e 1 6 0 4 9 1. 
A vaila ble fr o m: htt ps:// w w w. hi n da wi.c o m/j o ur nals/jir/ 2 0 1 3/ 1 6 0 4 9 1/  
5.    
Sa n d h ya P, K urie n B T, Da n da D, Sc ofiel d R H. U p date o n Pat h o ge nesis of Sj o gre n’s 
S y n dr o me. C urr R h e u mat ol Re v. 2 0 1 7; 1 3( 1): 5 – 2 2.  
6.    
F o x RI, F o x C M. Sj ö gre n S y n dr o me: W h y D o Cli nical Trials Fail? R he u m Dis Cli n N ort h 
A m. 2 0 1 6; 4 2( 3): 5 1 9 – 3 0.  
7.    
Ve rsta p pe n G M, va n Ni m we ge n J F, Vissi n k A, Kr oese F G M, B o ots ma H. T he val ue of 
rit u xi ma b treat me nt i n pri mar y Sj ö gre n’s s y n dr o me. Cli n I m m u n ol Orla n d o Fla. 2 0 1 7; 1 8 2: 6 2 – 7 1.  
8.    
Vi vi n o F B, Cars o ns S E, F o ul ks G, Da niels T E, Par ke A, Bre n na n M T, et al. Ne w 
Trea t me nt G ui deli nes f or Sj ö gre n’s Disease. R he u m Dis Cli n N ort h A m. 2 0 1 6; 4 2( 3): 5 3 1– 5 1.  
1 0.  
S hi b os ki C H, S hi b os ki S C, Ser or R, Cris well L A, La bet o ulle M, Li et ma n T M, et al. 2 0 1 6 
A C R -E U L A R Classificati o n Criteria f or pri mar y Sj ö gre n’s S y n dr o me: A C o nse ns us a n d Data -
Dri ve n Met h o d ol o g y I n v ol vi n g T hree I nter nati o nal Patie nt C o h orts. Art hritis R he u mat ol 
H o b o ke n NJ. 2 0 1 7 J a n; 6 9( 1): 3 5 – 4 5.  
1 1.  
B MJ, B. M. ( 2 0 2 0, Ma y 1 3). Britis h Me dical J o ur nal Best Practice. Retrie ve d fr o m 
C or o na vir us disease 2 0 1 9 ( C O VI D -1 9) Dia g n ostic g ui d eli nes. [I nter net]. A vaila ble fr o m: 
htt ps:// best practice. b mj.c o m/t o pics/e n -g b/ 3 0 0 0 1 6 8/ g ui deli nes  
1 2.  
B MJ, B. M. ( 2 0 2 0, Ma y 1 3). Britis h Me dical J o ur nal Best Practice. Retrie ve d fr o m 
C or o na vir us disease 2 0 1 9 ( C O VI D -1 9) Hist or y a n d e xa m: [I nter net]. A vaila ble fr o m: 
htt ps:// best practice. b mj.c o m/t o pics/e n -g b/ 3 0 0 0 1 6 8/ hist or y -e xa m 
1 3.  
Ser or R, B o ots ma H, Sara u x A, B o w ma n SJ, T hea n der E, Br u n J G, et al. Defi ni n g disease 
acti vit y states a n d cli nicall y mea ni n gf ul i m pr o ve m e nt i n pri mar y Sj ö gre n’s s y n dr o me wit h 

G al a p a g o s  
C O N FI D E N TI A L  
4 3 9 5 2 _ 1 7 1 8 5 _ 5 1 8 4 2  
G L P G 3 9 7 0 - C L-2 0 7  
-8 8 - 
 
E U L A R pri mar y Sj ö gre n’s s y n dr o me disease  acti vit y ( E S S D AI) a n d patie nt -re p orte d i n de xes 
( E S S P RI). A n n R he u m Dis. 2 0 1 6 Fe b; 7 5( 2): 3 8 2– 9.  
1 7.  
Se nc h y n a M, Wa x M B. Q ua ntitati ve assess me nt of tear pr o d ucti o n: A re vi e w of met h o ds 
a n d utilit y i n dr y e ye dr u g disc o ver y. J Oc ul Bi ol Dis I nf or. 2 0 0 8 Mar; 1( 1): 1 – 6.  
1 9.  
S ha hi d A, Wil ki ns o n K, Marc u S, S ha pir o C M, e dit ors. S T O P, T H A T a n d O ne H u n dre d  
Ot her Slee p Scales [I nter net]. Ne w Y or k: S pri n ger -Verla g; 2 0 1 2 [cite d 2 0 2 0 A u g 6]. A vaila ble 
fr o m: htt ps:// w w w.s pri n ger.c o m/ g p/ b o o k/ 9 7 8 1 4 4 1 9 9 8 9 2 7 
2 1.  
Fre wer P, Mitc hell P, Wat ki ns C, Matc ha m J. Decisi o n -ma ki n g i n earl y cli nical dr u g 
de vel o p me nt. P har m Stat. 2 0 1 6; 1 5( 3): 2 5 5 – 6 3.  
 
 

G al a p a g o s  
C O N FI D E N TI A L  
4 3 9 5 2 _ 1 7 1 8 5 _ 5 1 8 4 2  
G L P G 3 9 7 0 - C L-2 0 7  
-8 9 - 
 
1 4.    
A P P E N DI C E S  
A p pe n di x 1 : Pre d nis ol o ne C o n versi o n T a ble  
Gl uc oc ortic oi d N a me  
D ose E q ui v ale nt t o 5 m g Pre d nis ol o ne  
Pre d nis o ne  
5 m g  
Beta met has o ne  
0. 6 m g  
C ortis ol ( h y dr oc ortis o ne)  
2 0 m g  
C ortis o ne  
2 5 m g  
Deflazac ort  
7. 5 m g  
De xa met has o ne  
0. 7 5 m g  
Met h yl pre d nis ol o ne  
4 m g  
Met h yl pre d nis ol o ne Acetate  
4 m g  
Met h yl pre d nis ol o ne S o di u m S ucci nate  
4 m g  
P ara met has o ne  
2 m g  
Pre d nis ol o ne  
5 m g  
Tria mci n ol o ne  
4 m g  
Becl o metas o ne Di pr o pi o nate  
1. 2 5 m g  
B u des o ni de  
1. 5 m g  
H y dr oc ortis o ne S o di u m S ucci nate  
2 0 m g  
( Ster oi d C o n versi o n Calc ulat or) 
 

G al a p a g o s  
C O N FI D E N TI A L  
4 3 9 5 2 _ 1 7 1 8 5 _ 5 1 8 4 2  
G L P G 3 9 7 0 - C L-2 0 7  
-9 0 - 
 

G al a p a g o s  
C O N FI D E N TI A L  
4 3 9 5 2 _ 1 7 1 8 5 _ 5 1 8 4 2  
G L P G 3 9 7 0 - C L-2 0 7  
-9 1 - 
 

G al a p a g o s  
C O N FI D E N TI A L  
4 3 9 5 2 _ 1 7 1 8 5 _ 5 1 8 4 2  
G L P G 3 9 7 0 - C L-2 0 7  
-9 2 - 
 

G al a p a g o s  
C O N FI D E N TI A L  
4 3 9 5 2 _ 1 7 1 8 5 _ 5 1 8 4 2  
G L P G 3 9 7 0 - C L-2 0 7  
-9 3 - 
 

G al a p a g o s  
C O N FI D E N TI A L  
4 3 9 5 2 _ 1 7 1 8 5 _ 5 1 8 4 2  
G L P G 3 9 7 0 - C L-2 0 7  
-9 4 - 
 

G al a p a g o s  
C O N FI D E N TI A L  
4 3 9 5 2 _ 1 7 1 8 5 _ 5 1 8 4 2  
G L P G 3 9 7 0 - C L-2 0 7  
-9 5 - 
 
A p pe n di x 7 : E U L A R Sj ö gre n’s S y n dr o me Dise as e Acti vit y I n de x ( E S S D AI) Sc ore  
 
 
 
 
 
 

G al a p a g o s  
C O N FI D E N TI A L  
4 3 9 5 2 _ 1 7 1 8 5 _ 5 1 8 4 2  
G L P G 3 9 7 0 - C L-2 0 7  
-9 6 - 
 
 
 
 
 
 

G al a p a g o s  
C O N FI D E N TI A L  
4 3 9 5 2 _ 1 7 1 8 5 _ 5 1 8 4 2  
G L P G 3 9 7 0 - C L-2 0 7  
-9 7 - 
 
 
 
 

G al a p a g o s  
C O N FI D E N TI A L  
4 3 9 5 2 _ 1 7 1 8 5 _ 5 1 8 4 2  
G L P G 3 9 7 0 - C L-2 0 7  
-9 8 - 
 
A p pe n di x 8 : E U L A R Sj ö gre n’s S y n dr o me P atie nt Re p orte d I n de x ( E S S P RI) Sc ore  
 

G al a p a g o s  
C O N FI D E N TI A L  
4 3 9 5 2 _ 1 7 1 8 5 _ 5 1 8 4 2  
G L P G 3 9 7 0 - C L-2 0 7  
-9 9 - 
 

G al a p a g o s  
C O N FI D E N TI A L  
4 3 9 5 2 _ 1 7 1 8 5 _ 5 1 8 4 2  
G L P G 3 9 7 0 - C L-2 0 7  
-1 0 0 - 
 

G al a p a g o s  
C O N FI D E N TI A L  
4 3 9 5 2 _ 1 7 1 8 5 _ 5 1 8 4 2  
G L P G 3 9 7 0 - C L-2 0 7  
-1 0 1 - 
 

G al a p a g o s  
C O N FI D E N TI A L  
4 3 9 5 2 _ 1 7 1 8 5 _ 5 1 8 4 2  
G L P G 3 9 7 0 - C L-2 0 7  
-1 0 2 - 
 

G al a p a g o s  
C O N FI D E N TI A L  
4 3 9 5 2 _ 1 7 1 8 5 _ 5 1 8 4 2  
G L P G 3 9 7 0 - C L-2 0 7  
-1 0 3 - 
 

G al a p a g o s  
C O N FI D E N TI A L  
4 3 9 5 2 _ 1 7 1 8 5 _ 5 1 8 4 2  
G L P G 3 9 7 0 - C L-2 0 7  
-1 0 4 - 
 
A p pe n di x  1 5 : Al g orit h m f or Ele v ate d Li ver F u ncti o n Tests  
 
A S T or A L T i ncre ase t o  
V al ue R a n ge    
> = 1. 5 x t o 
3 x U L N  
> = 3 x t o 
< 5 x U L N  
> = 5 x t o 
< 8 x U L N  
> = 3 x U L N wit h si g ns 
of li ver da ma ge 1 
> = 8 x U L N  
I P Acti o n 
C o nti n ue as 
pla n ne d  
Re d uce or 
i nterr u pt I P f or 
at least 2  wee ks  
Cl ose 
o bser vati o n 2  
Interr u pt I P f or 
at least 2  wee ks  
Cl ose 
o bser vati o n 2 
Disc o nti n ue I P 2   
Disc o nti n ue I P 2 
 
 
 
 
↙ ↘ 
 
After at least 
2  wee ks  
A S T a n d A L T < 3 x U L N  
 
A S T or A L T > = 3 x U L N  
  
Wee kl y L F Ts f or t he first 2 wee ks 
( bi wee kl y f or t he f oll o wi n g 
wee ks, or m ore fre q ue ntl y at 
i n vesti gat or’s discreti o n) 
 
Disc o nti n ue I P  
Re p ort S A E a n d c o m plete li ver e ve nt pa ge f or a n y of 
a b n or malities liste d bel o w 3: 
-  
A S T/ A L T i ncrease > = 3 x U L N wit h si g ns of li ver 
da ma ge 1  
 
1  Si g ns of li ver da ma ge:  
- t otal bilir u bi n > =2. 0 x U L N O R I N R > 1. 5, a n d/ or  
- s y m pt o ms: a p peara nce of fati g ue, na usea, v o miti n g, ri g ht u p per a b d o mi nal q ua dra nt pai n or te n der ness, fe ver, ras h a n d/ or e osi n o p hilia ( > 5 %)  
2 Cl ose o bser vati o n rec o m me n dati o ns:  
- M o nit or 2  t o 3  ti mes per wee k all of t he f oll o wi n g para meters: A L T, A S T, al kali ne p h os p hatase, t otal bilir u bi n, e osi n o p hils, I N R. If l ocal 
re g ulati o ns all o w, h o me visits ca n be perf or me d if s u bjects ca n n ot c o me t o t he cli nical st u d y ce nter. 
- Fr e q ue nc y of r etesti n g ca n be re d uce d t o o nce a wee k or less if a b n or malities sta bilize or t he I P has bee n disc o nti n ue d; h o we ver, m o nit ori n g 
mi g ht still be nee de d m ore fre q ue ntl y ta ki n g i nt o c o nsi derati o n t he S o C a n d/ or c ha n ges t o t his. 
- Base d u p o n i n vesti gat or’s discr eti o n gastr oe nter ol o g y or he pat ol o g y c o ns ultati o ns, a d diti o nal ser ol o g y testi n g, i ma gi n g , a n d pat h ol o g y 
assess me nts ma y be re q uire d . 
- Re -q uer y hist or y of s y m pt o ms, pri or a n d c o nc urre nt diseases, c o nc o mita nt me dicati o n a n d n o n -prescri pti o n me dici nes, her ba l, dietar y 
s u p ple me nts, alc o h ol use, recreati o nal dr u g use, s pecial diets. 
- R ule o ut all of t he f oll o wi n g: ac ute viral he patitis, a ut o i m m u ne he patitis, alc o h olic he patitis, n o n -alc o h olic fatt y he patitis, h y p o xic/isc he mic 
he patitis, biliar y tract disease, a n d c h olestasis. 
- Re -q uer y e x p os ure t o e n vir o n me ntal c he mical a ge nts.  
3 T he f oll o wi n g ste ps s h o ul d be f oll o we d:  
- T he site s h o ul d i m me diatel y c o ntact t he s u bject a n d re q uire t he s u bject t o disc o nti n ue I P i m me diatel y. T he s u bject s h o ul d be as ke d t o ret ur n t o 
t he site wit hi n a 4 8-h o ur wi n d o w fr o m a ware ness of t he res ult.  
- A f ull e val uati o n of vari o us ca uses of he patitis s h o ul d be  c o n d ucte d (i.e. i nfecti o us, alc o h ol, me dicati o ns, a nat o mical).  
- A n assess me nt of ot her c o nc o mita nt me dicati o ns a n d S o C s h o ul d be ma de. T he i n vesti gat or s h o ul d c o nsi der t o w het her is i n t he best i nterest of 
t he s u bject t o st o p/i nterr u pt c o nc o mita nt me dicati o ns a n d S oC treat me nt.  
- A detaile d hist or y i nc l u di n g rele va nt i nf or mati o n o n alc o h ol use, recreati o nal dr u g use, s u p ple me nt c o ns u m pti o n, a n y her bal re me dies, fa mil y 
hist or y, se x ual hist or y, tra vel hist or y, hist or y of c o ntact wit h a ja u n dice d s u bject, s ur ger y, occ u pati o nal hist or y, bl o o d tr a nsf usi o n, hist or y of li ver 
or aller gic disease, a n d  a n y ot her p ote ntial ca uses of attri b u ta ble t o a li ver i ns ult s h o ul d be c ollecte d.  

G al a p a g o s  
C O N FI D E N TI A L  
4 3 9 5 2 _ 1 7 1 8 5 _ 5 1 8 4 2  
G L P G 3 9 7 0 - C L-2 0 7  
-1 0 5 - 
 
- A detaile d assess me nt of t he s u bject’s cli nical c o n diti o n a n d re peat la b orat or y tests f or L F T, i ncl u di n g al b u mi n, creati ne ki nase, t otal bilir u bi n 
( direct a n d i n direct), G G T, I N R, a n d al kali ne p h os p hatase s h o ul d be d o ne.  
- F urt her testi n g f or He patitis A, B, a n d C, a n d f or a ut oi m m u ne he patitis s h o ul d be d o ne. Ot her ca uses of viral he patitis ( c yt o me gal o vir us or 
E pstei n -Barr vir us etc) s h o ul d be e xcl u de d.  Li ver i ma gi n g s h o ul d be c o nsi dere d.  
- Referral t o a he pat ol o gist or gastr oe nter ol o gist s h o ul d be re q ueste d. 
- T hese cases s h o ul d be re p orte d as S A Es . 
 
 
 

G al a p a g o s  
C O N FI D E N TI A L  
4 3 9 5 2 _ 1 7 1 8 5 _ 5 1 8 4 2  
G L P G 3 9 7 0 - C L-2 0 7  
-1 0 6 - 
 
SI G N A T U R E P A G E –  S P O N S O R  
St u d y Title:  
A r a n d o mi z e d, d o u bl e -b li n d, pl a c e b o-c o ntr oll e d, m ulti c e nt er st u d y t o 
e v al u at e t h e effi c a c y, s af et y, t ol er a bilit y, p h ar m a c o ki n eti c s, a n d 
p h ar m a c o d y n a mi c s of or all y a d mi ni st er e d G L P G 3 9 7 0 f or 1 2 w e e k s i n a d ult 
s u bj e ct s wit h a cti v e pri m ar y Sj ö gr e n’ s S y n dr o m e  
C S P Versi o n:  
7. 0  
Date:    
1 2 -Ma y -2 0 2 1  
A me n d me nt  
6  
 
 
 
T his C S P  has bee n re vie we d a n d a p pr o ve d b y t he s p o ns or t o e ns ure c o m plia nce wit h t his C S P, 
t he c urre nt I C H-G C P G ui deli ne E 6, a n d a p plica bl e l ocal et hical a n d le gal re q uire me nts . 
 
 
M D,  
 A n electr o nic si g nat ure f or t he s p o ns or is pr o vi de d 
at t he en d of t he d oc u me nt  
Me dical Lea der  
 Si g nat ure  
 Date  
 
 
 

G al a p a g o s  
C O N FI D E N TI A L  
4 3 9 5 2 _ 1 7 1 8 5 _ 5 1 8 4 2  
G L P G 3 9 7 0 - C L-2 0 7  
-1 0 7 - 
 
SI G N A T U R E P A G E –  I N VE S TI G A T O R  
St u d y Title:  
A r a n d o mi z e d, d o u bl e -b li n d, pl a c e b o-c o ntr oll e d, m ulti c e nt er st u d y t o 
e v al u at e t h e effi c a c y, s af et y, t ol er a bilit y, p h ar m a c o ki n eti c s , a n d 
p h ar m a c o d y n a mi c s of or all y a d mi ni st er e d G L P G 3 9 7 0 f or 1 2 w e e k s i n a d ult 
s u bj e ct s wit h a cti v e pri m ar y Sj ö gr e n’ s S y n dr o m e  
C S P Versi o n:  
7. 0  
Date:    
1 2 -Ma y -2 0 2 1  
A me n d me nt  
6  
 
 
 
I, t he u n dersi g ne d, h a ve rea d t his C S P  a n d will c o n d uct t he st u d y as d escri be d i n c o m plia nce wit h 
t his C S P, t he c urre nt I C H-G C P G ui deli ne E 6, a n d a p plica ble l ocal et hical a n d le gal re q uire me nts . 
 
 
 
  
  
I n v esti gat or Na me 
 Si g nat ure  
 Date  
 

Si g nat ure Pa ge f or gl p g 3 9 7 0-cl- 2 0 7- pr ot oc ol 1 5 9 8 5
Si g nat ure Pa ge f or gl p g 3 9 7 0-cl- 2 0 7- pr ot oc ol 4 3 9 5 2 _ 1 7 1 8 5 _ 5 1 8 4 2
A p pr o val
Se ni or Me dical Direct or
Cli nical De vel o p me nt
1 2- Ma y- 2 0 2 1 1 2: 5 9: 5 0 G M T + 0 0 0 0