Conditions: Primary Sjögren Syndrome
Keywords: Primary Sjögren Syndrome Sjögren Syndrome Autoimmune Diseases Rheumatic Diseases Sicca Syndrome
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 31
Healthy volunteers: no

Brief summary:
This is a first exploration of GLPG3970 in participants with active primary Sjogren's Syndrome (pSS) to evaluate the efficacy, safety and tolerability and to determine its pharmacokinetics (PK) profile compared to placebo.

Detailed description:

Arms:
arm 1: Participants will receive GLPG3970 400 milligrams (mg) (2 \*200 mg tablet), orally, once daily for 12 weeks. arm 2: Participants will receive placebo matched to GLPG3970 tablet, orally, once daily for 12 weeks.

Interventions: intervention 1: GLPG3970 intervention 2: Placebo
Intervention descriptions: intervention 1: GLPG3970 film-coated tablet. intervention 2: Placebo film-coated tablet.

Protocol document:
Prot_000.pdf: 
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 


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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.  


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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 . 


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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 


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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 


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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. 


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− 
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. 


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− 
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 . 


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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, 


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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 


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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  
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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. 


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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.  


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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.  


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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. 


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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 


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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 
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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
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SAP_001.pdf: 
 
-1- 
 
 
 
 
Confidentiality Statement 
The information contained in this document is privileged and confidential. It is the property of Galapagos NV and 
may not be used, disclosed, reproduced or otherwise disseminated within your organization or communicated to any 
third parties without the express written authorization of Galapagos NV. 
 
STATISTICAL ANALYSIS PLAN  
Project Number: 
GLPG3970 
 
Study Number: 
GLPG3970-CL-207 
Study Title: 
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 
Development Phase: 
2a 
Status: 
Final 
Version: 
1.0 
Date: 
17-Sep-2021 
EudraCT: 
2020-003298-22 
IND: 
Not applicable 
Sponsor: 
Galapagos NV, Generaal De 
Wittelaan L11 A3, 2800 
Mechelen, Belgium 
 
Biostatistician: 
 
Medical Leader: 
 




-3- 
 
4.4.4. 
Stratification Factors ...........................................................................32 
4.5. 
Presentation of Results ......................................................................................32 
4.5.1. 
Presentation of Treatment Groups ......................................................32 
4.5.2. 
Calculation of Descriptive Statistics ....................................................32 
4.5.3. 
Calculation of Percentages .................................................................33 
5. 
INTERIM ANALYSES AND INTERNAL DATA SAFETY MONITORING 
COMMITTEE .................................................................................................................33 
6. 
STATISTICAL ANALYSES ............................................................................................34 
6.1. 
Subject Information ............................................................................................34 
6.1.1. 
Demographic and Baseline Disease Characteristics ...........................34 
6.1.2. 
Allocation and Randomization .............................................................35 
6.1.3. 
Disposition Information .......................................................................35 
6.1.4. 
Protocol Deviations and Eligibility .......................................................36 
6.1.5. 
Medical History and Concomitant Diseases ........................................36 
6.1.6. 
Prior and Concomitant Medications ....................................................36 
6.1.6.1. 
Coding of Reported Terms .................................................36 
6.1.6.2. 
Classification of Therapies .................................................36 
6.1.6.3. 
Calculation of Relative Days ..............................................37 
6.1.6.4. 
Presentation of Results ......................................................37 
6.1.7. 
Procedures .........................................................................................37 
6.1.8. 
Exposure to Study Drug and Compliance ...........................................37 
6.1.8.1. 
Derivation Rules ................................................................37 
6.1.8.2. 
Presentation of Results ......................................................38 
6.2. 
Efficacy Analyses ...............................................................................................38 
6.2.1. 
Level of Significance ...........................................................................38 
6.2.2. 
Primary Efficacy Parameter ................................................................38 
6.2.2.1. 
Derivation Rules ................................................................38 
6.2.2.2. 
Analyses Methods .............................................................38 
6.2.2.3. 
Decision Making Methodology ...........................................40 
6.2.2.4. 
Area under the Efficacy Curve (AUEC) ..............................40 
6.2.3. 
Secondary Efficacy Parameters ..........................................................41 
6.2.3.1. 
EULAR Sjögren’s Syndrome Patient Reported Index 
(ESSPRI) Score .................................................................41 
6.2.3.2. 
Derivation Rules ................................................................41 
6.2.3.3. 
Analyses Methods .............................................................41 
6.2.4. 
Other Efficacy Parameters ..................................................................42 
6.2.4.1. 
6.2.4.2. 
6.2.4.2.1 
6.2.4.2.2 
6.2.4.3. 
6.2.4.3.1 
6.2.4.3.2 
6.2.4.4. 
6.2.4.5. 
6.2.4.6. 
6.2.4.7. 
6.2.4.7.1 


-4- 
 
6.2.4.7.2 
6.2.4.8. 
6.2.4.8.1 
6.2.4.8.2 
6.2.4.9. 
6.2.4.9.1 
6.2.4.9.2 
6.2.5. 
Subgroup Analyses .............................................................................46 
6.3. 
Safety Analyses .................................................................................................47 
6.3.1. 
Adverse Events ...................................................................................47 
6.3.1.1. 
Definition of Treatment-Emergent Adverse Events ............47 
6.3.1.2. 
Coding of Reported Terms .................................................47 
6.3.1.3. 
Allocation of Adverse Events to Analysis Periods ..............47 
6.3.1.4. 
Treatment Relatedness .....................................................48 
6.3.1.5. 
Worst-Case Selections ......................................................48 
6.3.1.6. 
Calculation of Relative Days and Duration .........................48 
6.3.1.7. 
Events of Special Interest ..................................................49 
6.3.1.8. 
Presentation of Results ......................................................49 
6.3.1.9. 
EudraCT Adverse Events Reporting ..................................49 
6.3.2. 
Laboratory Safety ...............................................................................50 
6.3.2.1. 
Available Data ...................................................................50 
6.3.2.2. 
Derivation Rules ................................................................50 
6.3.2.3. 
Definition of Toxicity Grades ..............................................50 
6.3.2.4. 
Definition of Non-Graded Abnormalities .............................51 
6.3.2.5. 
Urinalysis Tests with Categorical Results ..........................51 
6.3.2.6. 
Treatment-Emergent Principle ...........................................51 
6.3.2.7. 
Worst-Case Principle .........................................................51 
6.3.2.8. 
Hepatotoxicity ....................................................................52 
6.3.2.9. 
Presentation of Results ......................................................52 
6.3.3. 
Electrocardiogram ...............................................................................53 
6.3.3.1. 
Available Data ...................................................................53 
6.3.3.2. 
Derivation Rules ................................................................53 
6.3.3.3. 
Abnormalities .....................................................................54 
6.3.3.4. 
Presentation of Results ......................................................54 
6.3.4. 
Vital Signs ...........................................................................................55 
6.3.4.1. 
Available Data ...................................................................55 
6.3.4.2. 
Derivation Rules ................................................................55 
6.3.4.3. 
Abnormalities .....................................................................55 
6.3.4.4. 
Treatment-Emergent Principle ...........................................55 
6.3.4.5. 
Worst-Case Abnormality ....................................................55 
6.3.4.6. 
Presentation of Results ......................................................56 
6.3.5. 
Physical Examinations ........................................................................56 
6.3.6. 
SARS-CoV-2 Infection ........................................................................56 
6.3.7. 
Subgroup Analyses .............................................................................56 
6.4. 
Pharmacokinetic Analysis ..................................................................................56 
6.4.1. 
Available Data .....................................................................................56 
6.4.2. 
Presentation of Results .......................................................................57 
6.5. 
 
6.5.1. 
Available Data .....................................................................................57 
6.5.2. 
Presentation of Results .......................................................................57 


-5- 
 
6.6. 
Changes to the Planned Analyses, not Covered by Protocol Amendments ........58 
7. 
REFERENCES ..............................................................................................................59 
APPENDIX ...........................................................................................................................60 
Appendix I: Laboratory: Toxicity Grading .......................................................................60 
Appendix II: Vital Signs and Electrocardiogram grading ................................................68 
Appendix III: EULAR Sjögren’s Syndrome Disease Activity Index (ESSDAI) Score .......69 
Appendix IV: EULAR Sjögren’s Syndrome Patient Reported Index (ESSPRI) Score .....72 
Appendix XI: SAS Code ................................................................................................81 
Appendix XII: Prednisolone Conversion Table ...............................................................84 
 
 
 


-6- 
 
VERSION HISTORY 
SAP Amendment # 
Date 
Description of changes 
SAP Version Final 1.0 
17-Dec-2021 
N/A  
  
 
 
 


-7- 
 
LIST OF ABBREVIATIONS 
AE 
adverse event 
ALT 
alanine aminotransferase 
AST 
aspartate aminotransferase 
ATC 
anatomical therapeutic chemical 
AUC 
area under the plasma concentration-time curve 
BLOQ 
below lower limit of quantification 
BMI 
body mass index 
C3 
complement component 3  
C4 
complement component 4 
CI 
confidence interval 
CL 
clearance 
CLCr 
creatinine clearance 
CRF 
case report form 
CRO 
contract research organization 
CRP 
C-reactive protein 
CSP 
clinical study protocol 
CSR 
clinical study report 
CTCAE 
Common Terminology Criteria for Adverse Events 
Ctau 
trough concentration 
CTx 
serum C terminal telopeptide type I collagen 
ECG 
electrocardiogram 
eCRF 
electronic case report form 
ED 
early discontinuation 
eGFR 
estimated glomerular filtration rate  
ESSDAI 
EULAR Sjögren’s Syndrome Disease Activity Index 
ESSPRI 
EULAR Sjögren’s Syndrome Patient Reported Index 
EULAR 
European League against Rheumatism 
FAS 
full analysis set 
FU 
follow-up 
GLSM 
geometric LS-mean 
GM 
geometric mean  
GSD 
geometric standard deviation  
GSE 
geometric standard error 
H 
high, above the upper limit of the normal range 


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HDL 
high-density lipoprotein 
High 
high specificity test 
HOMA-IR 
homeostatic model assessment of insulin resistance 
HR 
heart rate 
ICF 
informed consent form 
ICH 
International Council for Harmonization of Technical Requirements for 
Pharmaceuticals for Human Use 
IP 
investigational product 
INF 
infinity 
IWRS 
interactive web response system 
L 
low, below the lower limit of the normal range 
LDL 
low-density lipoprotein 
LLN 
lower limit of the normal range 
LLOQ 
lower limit of quantification 
LRV 
lower reference value 
LS 
least squares 
LSM 
least square mean 
MedDRA 
medical dictionary for regulatory activities 
 
  
MMRM 
mixed models for repeated measures 
n 
number of non-missing data points 
N 
normal, with the limits of the normal range 
NCI CTCAE 
National Cancer Institute Common Terminology Criteria for Adverse 
Events 
NRI 
non-responder imputation 
OC 
observed cases 
 
 
PK 
pharmacokinetic(s) 
pop-PK 
population PK 
PR 
pulse rate 
pSS 
primary Sjögren’s Syndrome 
 
 
QTc 
corrected QT interval 
QTcF 
QT interval corrected for the heart rate using Fridericia’s formula 
RR 
respiratory rate 
SAE 
serious adverse event 


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SAP 
statistical analysis plan 
SD 
standard deviation 
SDTM 
study data tabulation model 
SE 
standard error 
 
 
SI 
standard international 
 
 
SMC 
Safety Monitoring Committee 
SoC 
standard-of-care 
TE 
Treatment-emergent 
TEAE 
treatment-emergent adverse event 
 
 
TLF 
tables, listings and figures 
TV 
target value 
ULN 
upper limit of the normal range 
ULOQ 
upper limit of quantification 
 
 
WHO 
World Health Organization 
 


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1. 
INTRODUCTION 
This statistical analysis plan (SAP) describes the final statistical analyses of study 
GLPG3970-CL-207. The results of the analysis will be described in the clinical study 
report (CSR). 
Technical details on derivations and mock tables, listings and figures (TLFs) will be 
presented in a separate document. 
The statistical analysis will process and present the results following the International 
Council for Harmonization (ICH) standards, particularly the ICH-E3, ICH-E6, ICH-E9, 
ICH-R9 (R1) and ICH-E14 guidelines. 
On 26 November 2021, the Safety Monitoring Committee recommended to immediately 
terminate Study GLPG3970-CL-207 due to a safety signal of liver toxicity. Therefore, the 
GLPG3970-CL-207 study was prematurely stopped. In view of this, only the primary 
endpoint and safety analyses will be performed. Results will be presented in an 
abbreviated CSR. Any provisions no longer applicable following premature study 
termination are highlighted in grey. 
2. 
STUDY DESIGN AND OBJECTIVES 
2.1. 
Study Objectives 
2.1.1. 
Primary Objectives 
- 
To evaluate the efficacy of GLPG3970 compared to placebo on the signs and 
symptoms of primary Sjögren’s Syndrome (pSS). 
- 
To evaluate the safety and tolerability of GLPG3970 compared to placebo. 
2.1.2. 
Secondary Objectives 
- 
To further characterize the efficacy of GLPG3970 compared to placebo on the 
patient-reported signs and symptoms of pSS. 
- 
To characterize the pharmacokinetics (PK) of GLPG3970. 
2.1.3. 
Other Objectives 


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2.2. 
Study Endpoints 
2.2.1. 
Primary Endpoints 
- 
Change from baseline in European League against Rheumatism (EULAR) 
Sjögren’s Syndrome Disease Activity Index (ESSDAI) score at Week 12. 
- 
Number, incidence, and severity of treatment-emergent adverse events (TEAEs). 
2.2.2. 
Secondary Endpoints 
- 
Change from baseline in EULAR Sjögren’s Syndrome Patient Reported Index 
(ESSPRI) score at Week 4, 8, and 12. 
- 
Change from baseline in ESSDAI score over time at Week 4, 8, and 12. 
- 
Observed GLPG3970 plasma trough concentration (Ctau). 
2.2.3. 
Other Endpoints 
2.3. 
Study Design 
This is a Phase 2a, randomized, double-blind, placebo-controlled, parallel-group, 
multicenter study to evaluate the efficacy, safety, tolerability, PK, 
 of orally 
administered GLPG3970 for 12 weeks in adult subjects with active pSS. 
One dose level of GLPG3970 will be evaluated in 30 subjects who will be randomized 
2:1 to receive GLPG3970 (400 mg [2 x 200 mg] qd) or matching placebo, respectively. 
The study will consist of 3 study periods: 


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− 
Screening period: up to 4 weeks with 1 study visit. During the Screening visit, 
subjects will be selected based on the eligibility criteria. Subjects already on 
treatment will remain on a stable standard of care (SoC) treatment during the study. 
− 
Treatment period: 12 weeks with up to 5 study visits (Days 1, 8, 29, 57, and 85). At 
any time during the course of the study, phone calls or unscheduled visits can be 
added if deemed necessary by the investigator. Subjects will receive GLPG3970 or 
placebo qd.  
− 
Follow-up (FU) period: 4 weeks with 1 study visit. Subjects remain on stable SoC 
treatment, if applicable. 
The subjects will be in the study for a duration of 20 weeks: up to 4 weeks of screening, 
12 weeks of treatment, and 4 weeks of FU. 
Refer to the Schedule of Assessments (Section 2.5) for further details.  
A schematic diagram of clinical study design and periods is provided in Figure 1. 
Figure 1 
Schematic Diagram 
 
2.4. 
Clinical Study Protocol (CSP) and CSP Amendments 
This SAP was based on the protocol version 7.0, dated 12-May-2021. 
2.5. 
Scheduled of Assessments 
The study assessments will be undertaken at time points as specified in the Schedule of 
Assessments (Table 1). For detailed instructions on the clinical study procedures, please 
see the relevant CSP sections and CSP Section 8.1, “Timing of Assessments”. 
Stable
Treatment
Regimen
4W
Week 1-12
RND
D1
Follow-up W16
Screening
Week -4
GLPG3970 (400 mg q.d.) + SoC (N=20)
SoC
Placebo + SoC (N=10)
SoC


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Table 1 Schedule of Assessments 
 
EVENT 
SCREENING 
PERIOD 
TREATMENT PERIOD1 
FOLLOW-UP 
PERIOD 
Study Visit 
S 
1 
2 
3 
4 
5 
ED2 
Follow-up 
Visit 
Study Week 
-4 to -1 
Baseline 
1 
4 
8 
12 
 
 
Study Day (D) ± Days  
-28 to -1 
1 
8±1 
29±2 
57±2 
85±2 
Early treatment 
discontinuation 
28 ± 3 after 
last IP dosing 
Informed consent  
✓ 
 
 
 
 
 
 
 
Inclusion/exclusion criteria  
✓ 
✓ 
 
 
 
 
 
 
Demographics  
✓ 
 
 
 
 
 
 
 
Medical history  
✓ 
 
 
 
 
 
 
 
Physical examination 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
Vital signs  
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
Body weight and height3 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
12-lead ECG4  
✓ 
Predose, 
1.5h, 3h, 
4.5h 
postdose4 
Predose 
Predose  
Predose  
Predose  
✓ 
✓ 
                                                 
1 On dosing days, all assessments are to be performed predose, unless otherwise specified. 
2 Subjects who discontinue treatment early will be requested to return for an ED visit and to return for a FU visit 28 ± 3 days after last IP administration. 
3 Height only to be measured at screening. 
4 At Visit 1 (Day 1), triplicate ECGs will be recorded predose and at 4.5 hours postdose. At all other timepoints, single ECGs will be taken. 


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EVENT 
SCREENING 
PERIOD 
TREATMENT PERIOD1 
FOLLOW-UP 
PERIOD 
Study Visit 
S 
1 
2 
3 
4 
5 
ED2 
Follow-up 
Visit 
Study Week 
-4 to -1 
Baseline 
1 
4 
8 
12 
 
 
Study Day (D) ± Days  
-28 to -1 
1 
8±1 
29±2 
57±2 
85±2 
Early treatment 
discontinuation 
28 ± 3 after 
last IP dosing 
QuantiFERON-TB Gold test 
✓ 
 
 
 
 
 
 
 
SARS-CoV-2 RT-PCR test5,6 
✓ 
✓ 
As needed 
SARS-CoV-2 serology test5,6 
 
✓ 
As needed 
Randomization 
 
✓ 
 
 
 
 
 
 
Blood collection  
 
− Safety (hematology, coagulation, 
chemistry) 
✓ 
✓7 
✓ 
✓ 
✓7 
✓7 
✓ 
✓ 
− Safety (HBV, HCV, HIV serology) 
✓ 
 
 
 
 
 
 
 
− Pregnancy test serum (all females)  
✓ 
 
 
 
 
 
 
 
− FSH test (WOnonCBP, non-surgical 
postmenopausal women) 
✓ 
 
 
 
 
 
 
 
                                                 
5 RT-PCR from a nasal swab sample at screening and RT-PCR from a nasal swab sample and serology testing at Visit 1 (Day 1), and as needed when subject presents signs 
and symptoms of SARS-CoV-2 infection. 
6 SARS-CoV-2 RT-PCR and serology tests can (optionally) be sampled by a nurse at the subject’s home 2-3 days before Visit 1 (Day 1). 
7 Fasted glucose, fasted insulin, and HOMA-IR only at Visit 1, 4, and 5. 




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EVENT 
SCREENING 
PERIOD 
TREATMENT PERIOD1 
FOLLOW-UP 
PERIOD 
Study Visit 
S 
1 
2 
3 
4 
5 
ED2 
Follow-up 
Visit 
Study Week 
-4 to -1 
Baseline 
1 
4 
8 
12 
 
 
Study Day (D) ± Days  
-28 to -1 
1 
8±1 
29±2 
57±2 
85±2 
Early treatment 
discontinuation 
28 ± 3 after 
last IP dosing 
− Pregnancy testing (UPT, dipstick) 
(WOCBP only) 
 
Predose 
Predose 
Predose 
Predose 
Predose 
 
 
Subject diary evaluation 
 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
✓ 
ESSDAI 
✓ 
✓ 
 
✓ 
✓ 
✓ 
✓ 
 
ESSPRI 
✓ 
✓ 
 
✓ 
✓ 
✓ 
✓ 
 
                                                 




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2.6. 
Sample Size Justification 
Up to 30 subjects are planned to be randomized 2:1, i.e. 20 subjects will receive GLPG3970 
(400 mg qd) and 10 subjects will receive placebo. In case of drop-outs due to SARS-CoV-2 
infection, additional subjects may be randomized on top of the planned sample size. The number 
of additional subjects randomized will not exceed the number of subjects dropping out of the 
study in relation to SARS-CoV-2. Randomization of additional subjects will be decided by the 
sponsor before study lock or related unblinding has occurred. 
This sample size provides favorable operating characteristics for the primary efficacy endpoint 
(i.e. ESSDAI change from baseline at Week 12) in terms of the modified signal detection 
methodology r. This methodology will be used to provide further insight into the treatment effect 
of GLPG3970 over placebo, and will support scenario analyses. The posterior distribution of this 
treatment effect will be estimated, and from this distribution probabilities of reaching at least a 
certain effect (delta) will be derived, e.g. a range of plausible effect size values going from as 
high as P (delta <=-5) to as low as P (delta <=-2). A common standard deviation (SD) of 4 was 
assumed for both active and placebo arm. 
Probability 
Reference value 
Outcome 
0.852 
-5 
Signal detected 
0.041 
No conclusion 
0.107 
Signal not detected 
0.427 
-3 
Signal detected 
0.088 
No conclusion 
0.485 
Signal not detected 
0.205 
-2 
Signal detected 
0.050 
No conclusion 
0.745 
Signal not detected 
 


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2.7. 
Randomization and Blinding 
2.7.1. 
Randomization 
At screening, subjects will be assigned a subject identification number. When a subject is 
confirmed to be eligible for the clinical study, the subject will be randomized. Allocation of each 
subject to a given treatment will be done using a centralized electronic system (interactive web 
response system [IWRS]). Subjects will be randomized in a 2:1 ratio to GLPG3970 or placebo. 
2.7.2. 
Blinding and Unblinding 
This is a randomized, double-blind clinical study. The subjects and the entire clinical study team, 
including the investigators, clinical study coordinators, and sponsor personnel, except for the 
Safety Monitoring Committee, are blinded to treatment assignment. 
Blinded and packaged medication will be provided to the site. All IP formulations will be 
identical in appearance, shape, smell and taste, and will be packaged in the proper proportion to 
assure desired dosages and maintenance of the blinding. 
The blind can be broken only if the investigator deems it necessary for the safety of a subject. 
The investigator is encouraged to discuss considerations to break the blind with the medical 
leader of the study, whenever possible and where the situation allows. However, the 
responsibility to break the treatment code in emergency situations resides solely with the 
investigator. The investigator is not required to discuss unblinding beforehand if he or she feels 
rapid emergency unblinding is necessary but is required to inform the sponsor in within 24 hours 
after unblinding has occurred. 
The blind can be broken by the investigator via IWRS. 


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If the blind is broken for any reason during the course of the clinical study, the moment on which 
the blind was broken, and all other relevant information will be documented by the site. The 
reason for breaking the blind will be indicated and justified in the source documentation. 
If an adverse event (AE) leads to unblinding, the AE will be given as the reason for unblinding. 
All subjects who are unblinded should, where possible, complete the FU visit assessments 28±3 
days after last IP dosing. Any AEs will be followed until resolution. 
The code-break information (via IWRS vendor) will be provided to the bioanalytical laboratory 
responsible for PK sample analysis, the sponsor person responsible for providing unblinded data 
to the Safety Monitoring Committee, the contract research organization (CRO) responsible for 
the population PK (pop-PK) 
, and to the pharmacovigilance vendor for serious 
adverse event (SAE) reporting purposes. 
3. 
STUDY ESTIMANDS 
Estimand for the primary endpoints: 
Attribute 
Details 
Treatments 
GLPG3970 (400 mg qd) vs. Placebo 
Population 
• Population target defined through the 
inclusion/exclusion criteria (see CSP 
section 6).  
• Analysis Set: Full Analysis Set (FAS), 
defined as all randomized subjects 
who have received at least one dose of 
IP. 
Endpoint 
Change from baseline in ESSDAI score at 
Week 12. 
Population-level summary 
Difference (GLPG3970-Placebo) in least 
square mean (LSM). For further details see 
study SAP section 6.2.2.2. 
Intercurrent events and strategies to handle 
those 
• Early treatment discontinuation (for 
any reason) is handled using the 
hypothetical strategy 
• Other intercurrent events (e.g. major 
protocol violations, intake of 
prohibited medication, lack of 
compliance) are handled using the 


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treatment policy strategy (i.e. they are 
ignored) 
 
Estimand for the safety endpoint 
Attribute 
Details 
Treatments 
GLPG3970 (400 mg qd) vs. Placebo 
Population 
• Population target defined through the inclusion/exclusion 
criteria (see CSP).  
• Analysis Set: Safety Analysis Set, defined as all randomized 
subjects who have received at least one dose of IP. 
Endpoint 
Presence of TEAE 
Population-level 
summary 
Percentage of subjects with TEAEs. 
Intercurrent events and 
strategies to handle 
these 
Intercurrent event:  
• Early treatment discontinuation (for any reason): handled 
using the while-on-treatment strategy. All collected data up 
to (and including) the last contact visit is regarded as 
possibly influenced by the drug exposure and thus will be 
used in the analysis. 
• Intercurrent event: major protocol deviations, intake of 
prohibited/rescue medication, lack of compliance): handled 
using the treatment policy strategy. All collected data will be 
used in the analysis. 
 
4. 
GENERAL METHODOLOGY 
4.1. 
Analysis Sets 
The analysis set will always be indicated in a subtitle in the table, listing or figure. 
4.1.1. 
All Screened Analysis Set 
All subjects who signed and dated an informed consent form (ICF). 




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4.3. 
Analysis Periods and Analysis Time Points 
4.3.1. 
Relative Day 
The timing of an assessment or an event relative to a reference date will be calculated as follows: 
When the concerned date is before the reference date: 
Relative day (days) = concerned date-reference date 
When the concerned date is the equal or later than the reference date: 
Relative day (days) = concerned date-reference date +1 day 
Where: 
− 
The concerned date could be the measurement date of the assessment, or the start or end date 
of the event. 
− 
The reference date default is the date of the first dose of study drug administration, unless 
specified otherwise. 
− 
Date implies a complete date having day, month and year available. Unless otherwise 
specified, the relative day will remain missing when it cannot be calculated due to absence or 
incompleteness of the concerned and/or reference dates. 
The general terms of this formula also apply when similar relative timings are required in other 
time units, for example in minutes. 
4.3.2. 
Analysis Periods 
For treated subjects, AEs and assessments will be allocated to analysis periods according to Table 
2. 
Table 2 
Analysis Periods 
Analysis Period 
Start Analysis Period 
End Analysis Period 
Screening 
Date of signing the ICF, with 
00:00 added as time part 
Date (time) of first IP 
administration - 1 minute 
Treatment 
Date (time) of first IP 
administration.  
Study termination date (i.e. 
date of last contact), with 
23:59 added as time part  
  
The last analysis period will always end on the date of last contact. 
For every subject, all assessments performed and all events occurring during the study are 
expected to have a (start) date (/time) between the date of informed consent (IC) signature and 
the last contact date. Obvious exemptions are historical records like medical history or 
concomitant therapies having started before the study. 


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Assessments and events will be allocated to one of these analysis periods by incidence, meaning 
placing the record (start) date and time between the matching start and end dates and times of the 
subject’s own analysis periods, assuming completeness of all dates and times, or further 
determined by the presence of timing indicators such as tick boxes flagging AEs starting 
before/after first IP administration, or by worst-case considerations for AEs if needed. For the 
parameters for which the time of assessment was not planned to be collected, their assessment on 
the day of first IP administration will be considered as baseline and will be reported under the 
‘Screening’ analysis period with the exception of AEs.


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4.3.3. 
Analysis Windows 
For the efficacy, PK, 
 and safety assessments, all data (including data obtained at unscheduled 
visits) will be placed into time windows based on the relative day (ADY) of the assessment 
(relative to the first dose of IP), according to the following allocation tables: 
For endpoints with multiple components, analysis windows will be derived separately for each 
component/parameter. 
All assessments, including data collected on unscheduled visits, will be allocated to analysis 
windows based on the relative day of the assessment (see Section 4.3.1) and according to the 
algorithm in Table 3-6. TFLs will present the analysis windows. 
 


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Table 3: Analysis Visit Window for 12-Lead ECG Data 
 
Visit date and 
time 
Relative day 
(ADY) 
Time window 
(in ADY) 
Target 
day 
Analysis 
visit 
(AVISIT) 
Analysis time 
point (ATPT) 
Before first 
study drug 
administration 
<1 or predose 
at ADY=1 
<1 or predose 
at ADY=1 
1 
Baseline 
 
Same as or 
after first 
study drug 
administration  
≥ 1 
1 
1 
Day 1 
As indicated in the 
database: 
1.5, 3, 4.5 hours 
postdose 
2 to 19 
8 
Week 1 
Predose 
20 to 43 
29 
Week 4 
Predose 
44 to 71 
57 
Week 8 
Predose 
72 to 92 
85 
Week 12 
Predose 
>7 days after 
last dose of IP 
Last dose 
of IP + 
28 days 
Follow-up *  
* The Follow-up window has precendence over all other time windows. 
Note: At baseline and Day 1 predose and 4.5 hours postdose, triplicate ECGs will be recorded. At all other timepoints, single ECGs 
will be taken.  
 
 
 
 


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Table 4: Analysis Visit Window for PK Data 
 
Visit date and 
time 
Relative day 
(ADY) 
Time 
window (in 
ADY) 
Target 
day 
Analysis visit 
(AVISIT) 
Analysis time point 
(ATPT) 
Before first 
study drug 
administration 
<1 or predose 
at ADY=1 
<1 or predose 
at ADY=1 
1 
Baseline 
Predose (within 30 
minutes prior to 
dosing) 
Same as or 
after first 
study drug 
administration  
≥ 1 
1 
1 
Day 1 
As indicated in the 
database: 
0.5-1.5, 2-2.5, 4.5 
hours postdose 
2 to 19 
8 
Week 1 
As indicated in the 
database: 
Predose 
20 to 43 
29 
Week 4 
As indicated in the 
database: 
Predose 
44 to 71 
57 
Week 8* 
As indicated in the 
database: 
Predose, 0.5-1.5, 2-2.5 
hours postdose 
72 to 92 
85 
Week 12 
As indicated in the 
database: 
Predose 
>2 days after 
last dose of 
IP 
Last dose 
of IP+28 
days 
 Follow-up** 
 
*If postdose week 8 is missing and postdose week 12 are available, it means these postdose week 12 will be considered as 
postdose week 8, that records will be presented in week 8 in tables (with footnote) and with flagged in listings 
**The Follow-up window has precendence over all other time windows. 
 
 


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4.3.4. 
Definition of Baseline 
Baseline is defined as the last available assessment prior to the first intake of IP. For the 
parameters for which the time of assessment was planned to be collected, if for their assessment 
on the day of first intake the time is missing, their assessment at time point “PREDOSE” (when 
applicable) will be considered as baseline, otherwise, previous days last available assessment will 
be selected. For the parameters for which the time of assessment was not planned to be collected, 
their assessment on the day of first intake of IP will be considered as baseline. For efficacy 
endpoints, the baseline visit will be defined as Table 6.  If multiple values on the same day 
qualify as last available assessment, the average of these values will be used in the analysis. 
For ECG data assessed in triplicate, baseline is defined as the average (stored without rounding) 
of the combination of the most complete replicated ECG parameter before first intake of IP and at 
the same time the closest to it, selecting in the following order: 


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First consider Day 1, predose: 
- 
Select the average of the last available triplicate ECG parameter on that day; 
- 
If there is no triplicate, select the average of the last available duplicate ECG parameter; 
- 
In the absence of triplicates and duplicates the last available single ECG parameter will 
become baseline. 
 
If baseline is not yet determined, consider the previous day and repeat the above selection 
(average of last triplicate, average of last duplicate, last single ECG on that day). Repeat the 
whole process successively for each previous day(s) as needed until baseline is determined. 
4.3.5. 
Selection and Use of Analysis Visit 
Before first administration of IP, only Baseline will be used for the entire statistical analysis. Pre-
baseline assessments will only be listed. After first administration of IP, if multiple valid, non-
missing assessments exist in an analysis window, records will be chosen based on the following 
rules if a single value is needed: 
• The record closest to the target day for that visit will be selected, or 
• If there are 2 records that are equidistant from the nominal day, or more than 1 record (with 
time known) on the selected day, the latest record will be taken 
• If chronological order cannot be determined (e.g., more than 1 record on the same day with 
time missing), the average of the records will be computed and reported in the analysis 
4.4. 
Handling of Data 
4.4.1. 
Handling of Missing Data 
4.4.1.1. 
Handling of Missing Date-Time Data 
No imputations will be done in case of missing date (time) fields, nor for the missing parts of 
partially known date (time) fields. 
Assessments with missing date (time) will be omitted from the analysis. 
Event-type data (e.g. adverse events, concomitant medications) with missing date (time) will be 
allocated to analysis periods using a worst-case approach as explained in the respective sections. 
For the date of diagnosis of Sjogren's Syndrome disease to allow the computation of the disease 
duration, if missing month, impute as January (01), if missing day, impute as the first day of the 
month (01). 
4.4.1.2. 
Handling of Missing Result Data 
No imputation will be done of missing result data unless otherwise specified. That is, an observed 
case (OC) analysis will be performed. Endpoints analyzed via mixed model for repeated 


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measures (MMRM) handle missing data via the maximum-likelihood function. The MMRM will 
be applied only when the number of subjects with non-missing values is more than 30% of the 
sample size Following a hypothetical strategy estimand, non-PK data observed more than 7 days 
after the last dose of IP will not be used for the on-treatment related analysis visits. PK data 
observed more than 2 days after the last dose of IP will not be used for the on-treatment related 
analysis visits. 
For analyses of binary endpoints, the non-responder imputation (NRI) method will be used for 
missing value imputation in addition to the observed case (OC) analysis.  
4.4.1.3. 
Censoring of Time-to-Event Data 
Not applicable.  
4.4.2. 
Handling of Values Below or Above a Threshold 
Results of continuous parameters, as well as normal limits of these reported as below (or above) 
the detection limit will be imputed by the value one precision unit smaller (or larger) than the 
detection limit itself. In listings, the original value will be presented. 
Example: if the database contains the value “<0.04”, then for the descriptive statistics the value 
“0.03” will be used. The value “>1000” will be imputed by “1001”. 
For PK data, values below the limit of quantification will be imputed by 0 for the calculation of 
descriptive statistics presentation; except for the geometric mean and the geometric coefficient of 
variation (CV%), where it will be imputed as lower limit of quantification (LLOQ)/2. These 
values will be listed as “below lower limit of quantification (BLOQ)”. 
:  
- 
- 
- 




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For PK data, descriptive statistics will include: 
 
− 
the number of non-missing observations (n); 
− 
the number of data points above the LLOQ; 
− 
the arithmetic mean; 
− 
SE and SD; 
− 
the median, minimum and maximum; 
− 
the CV%; 
− 
the geometric mean and geometric CV%. 
 
If less than 50% of the subjects have quantifiable values, only the number of subjects with data, 
number of data points above the LLOQ, the arithmetic mean, median, minimum, and maximum 
will be presented with the original calculated value. The other descriptive statistics will be listed 
as “NC” (not calculated). 
If the calculated descriptive statistic is BLOQ, then it will be presented as “BLOQ”. 
Individual values and descriptive statistics of concentrations and PK parameters will be presented 
with 3 significant digits. 
4.5.3. 
Calculation of Percentages 
Frequencies and percentages will be generated for categorical parameters. 
For event-type data (e.g. adverse events), the denominator will be all subjects in the analysis set 
and analysis period. For other data (e.g. worst-case analysis of assessments), the denominator 
will be all subjects with (post-baseline) data for the parameter, in the analysis set and analysis 
window/period. 
 
5. 
INTERIM ANALYSES AND INTERNAL DATA SAFETY 
MONITORING COMMITTEE 
No formal interim analysis is planned for this clinical study.  
A Safety Monitoring Committee independent from the study will review unblinded data during 
the course of the study. This Committee will include a physician with experience in drug 
development, a biostatistician, and a safety physician. External medical experts (such as an expert 
in the field of pSS and an infectious diseases expert) may be included to support data 
interpretation. The Committee will review unblinded safety data and assess any potential safety 
issues arising during the conduct of the clinical study, including (but not limited to) any potential 
issues in the context of the SARS-CoV-2 pandemic. The process is described in a separate 
‘Safety Monitoring Committee Charter’. 


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6.  
S T A TI S TI C A L A N A L Y S E S  
6. 1.  
S u bj e ct I nf or m ati o n  
S u bject i nf or mati o n will be ta b ulate d usi n g t he Safet y A nal ysis Set, u nless s pecifie d ot her wise. 
N o i nfere ntial testi n g will be perf or m e d, n or will p -val ues be pr o vi de d.  
S u bject i nf or mati o n will be ta b ulate d wit h descri pti ve statistics per pla n ne d  treat me nt gr o u p, as 
well as o verall.  
6. 1. 1.  
D e m o gr a p hi c a n d B a s eli n e Di s e a s e C h ar a ct eri sti c s  
T he f oll o wi n g p ara m eters will be s u m marize d:  
− 
d ate of I C F si g n at ure (liste d) ; 
− 
se x ; 
− 
age at si g ni n g t h e I C F ( years) ; 
− 
age,  cate g orize d ( years):  1 8 ≤a ge< 6 5 ; 6 5 ≤a ge≤7 4 ; 
− 
race a n d et h nicit y; 
− 
h ei g ht at b aseli ne (c m) ; 
− 
w ei g ht at baseli ne ( k g) ; 
− 
b o d y mass i n de x ( B MI) at baseli ne ( k g/ m²) =  
 (
)
 (
) ; 
( B MI will n ot be recal c ulate d if alr ea d y a v aila ble i n t he data base) 
− 
d urati o n of Sj o gre n's S y n dr o me disease ( years)  
 =
(
 
 
 
 
 
)
(
 
 
)
 
.
 
F or t he  d ate of dia g n osis, i f missi ng m o nt h, i m p ute as J a n uar y ( 0 1),  if missi n g da y, i m p ute as 
t he first da y  of t he m o nt h ( 0 1) . 
− 
d urati o n of Sj o gre n's S y n dr o me disease , cate g orize d ( years): < 1; 1 ≤ d urati o n < 5 ; 5  ≤ 
d urati o n < 1 0 ; 
− 
E S S D AI  at b aseli ne;  
− 
E S S P RI  at b aseli ne; 
De m o gra p hic a n d baseli n e disease c haracteristics will be liste d.  


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6.1.2. 
Allocation and Randomization 
The number of subjects (and percent) per treatment group and overall will be tabulated per 
country and site. 
The following listings will be provided: 
− 
Listing per subject of the IP kit numbers, IP lot numbers dispensed/returned.  
− 
Randomization schemes and codes, with the treatment assigned to each subject. This listing 
includes a flag in case of discrepancies or errors between the assigned and the actual 
treatment taken, and should also include flags declaring any (potential) unblinding. 
6.1.3. 
Disposition Information 
The following tabulations will be provided, by treatment group and overall: 
− 
The number of subjects screened, not-randomized (including reasons), randomized (treated 
and not treated), and treated with GLPG3970 and Placebo. 
− 
Number (percent) of subjects randomized per country and site. 
− 
The number (percent) of subjects in each analysis set as defined in Section 4.1. 
− 
The number (percent) of subjects per analysis window as defined in Section 4.3.3. 
− 
The number (percent) of subjects who completed/discontinued the IP administration 
schedule and the reasons for discontinuation. 
− 
The number (percent) of subjects who completed/discontinued the study and the reasons for 
discontinuation.  
 
Subjects who discontinued early from study or treatment will be listed. Discontinuation related to 
SARS-CoV-2 will be flagged in the listing. 
 
Additionally, the following information will be provided in listings: 
 
− 
Subject identification and randomization (country, site number, investigator, subject 
number). 
− 
Randomization number and date planned and actual randomization group, with flags for any 
discrepancies. 
− 
Subjects excluded from the safety and full analysis sets. 
− 
First and Last Key Dates in the Study will be listed. 
 


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6.1.4. 
Protocol Deviations and Eligibility 
Major protocol deviations are determined and recorded while the study is ongoing, and the list is 
finalized prior to database lock (and unblinding). For more details, please refer to the Protocol 
Deviations Plan. 
The number (percent) of subjects with major protocol deviations will be tabulated, overall and 
per class of deviation, by treatment group and overall. 
All available information concerning major protocol deviations, including COVID-19 related 
verbatim, violations on eligibility criteria and subjects not treated will be listed. Protocol 
deviations leading to the exclusion of subjects from any analysis set, as applicable, will be 
flagged. 
Minor protocol deviations will not be tabulated and will be listed. 
6.1.5. 
Medical History and Concomitant Diseases 
Frequency tabulations, per treatment group and overall, per system organ class and preferred term 
will be provided for the medical history findings (i.e., conditions no longer present at the start of 
the study) as well as for the concomitant diseases (i.e. conditions present at the start of the study) 
using Medical Dictionary for Regulatory Activities (MedDRA) coding dictionary. 
All medical history findings and concurrent diseases will be listed separately. 
6.1.6. 
Prior and Concomitant Medications 
6.1.6.1. 
Coding of Reported Terms 
All prior and concomitant therapy terms will be coded in the database using the World Health 
Organization (WHO) drug coding dictionary. 
6.1.6.2. 
Classification of Therapies 
All prior and concomitant medication records will be categorized as follows, considering their 
date and flags indicating the relative timing versus study (drug) start or end (before, after, 
ongoing): 
− 
Prior only: when the record ended before the first IP administration date. 
− 
Concomitant only: when the record started on or after the first IP administration date. 
− 
Prior and concomitant: when the record started before the date of first IP administration, and 
ended on or after this point, or continued. 
When the start or end date of the prior and concomitant medication records are incomplete (and 
no flags indicating relative timing are available), the date of first IP administration will be 
considered to the same level of information provided by these incomplete dates to categorize the 
timing of these records. This means that a record only having month and year will be categorized 


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c o m pari n g o nl y t o t he m o nt h a n d t he ye ar of t he d ate of first I P a d mi nistrati o n.  T he rec or d o nl y 
ha vi n g year will be cate g orize d c o m pari n g o nl y t o t he year of t he date of first I P a d mi nistrati o n.  
6. 1. 6. 3.  
C al c ul ati o n of R el ati v e D a y s  
If b ot h t he start a n d t he e n d dates of t he c o n c o mita nt me dicati o n recor ds  are c o m plete d , t heir d a y 
relati ve t o t he da y of first I P a d mi nistrati o n will  be calc ulate d as descri be d i n Secti o n 4. 3. 1 . 
6. 1. 6. 4.  
Pr e s e nt ati o n of R e s ult s  
A fre q u e nc y ta b ulati o n p er pla n ne d  tr eat me nt gr o u p a n d o verall of t h e A nat o mical T hera pe utic 
C he mical  ( A T C) classifi cati o n classes le v el 4 b y t hera pe utic s u b gr o u p ( A T C le vel 2) a n d ge n eric 
ter m of t he pri or me di cati o n ( defi ne d as ‘ prior o nl y’ a n d ‘ pri or a n d c o n c o mita nt’) will be 
pr o vi de d as well as of t he c o nc o mita nt me dicati o n ( defi ne d as ‘c o n c o mita nt o nl y’ a n d ‘ pri or a n d 
c o nc o mita nt’).  
A listi n g of pri or a n d c o nc o mita nt me dicati o ns  will be pr o vi de d.  Als o, pri or a n d c o nc o mita nt 
c ortic osteri oi d listi n g will be pr o vi de d se paratel y (t he list of t he A T C c o des t o be selecte d i n t his 
listi n g will be pr o vi de d b y t he G ala pa g os  me di cal ser vices).  
6. 1. 7.  
Pr o c e d ur e s  
Pr oce d ures  res ults will o nl y be liste d . 
6. 1. 8.  
E x p o s ur e t o S t u d y D r u g a n d C o m pli a n c e 
6. 1. 8. 1.  
D eri v ati o n R ul e s  
Deri ve d P ar a meters: E xte nt of E x p os ure t o I P  
− 
T ot al tre at me nt d ur ati o n  ( da ys) = l ast I P a d mi nistrati o n date –  first I P a d mi nistrati o n date 
+ 1 da y , 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. 
− 
T ot al tre at me nt d ur ati o n, excl u di n g d ays off I P: S u m of t he n u m ber of da ys wit h a n y I P 
a d mi nistrati o n.  
− 
T ot al tre at me nt d ur ati o n, f ull c o m pli a n ce ( da ys): N u m ber of da ys w here   I P has bee n 
ta ke n. 
 
Deri ve d P ar a meters: C o m pli a nce  
− 
O verall c o m plia nce ( %) = 1 0 0   ×  
 
 
 
 
 
 
 
 
 
 
 
 
 
− 
Perce nt da ys wit h a n y i nt a ke ( %) = 1 0 0  ×  
 
 
,   
 
 
 
 
 
 
 
− 
Perce nt da ys f ull c o m plia nce ( %) = 1 0 0  ×  
 
 
,
 
 
 
 
 


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6.1.8.2. 
Presentation of Results 
Summary statistics per planned treatment group and overall will be provided for each compliance 
and extent of exposure parameter for IP administration. Frequency tables will be provided for the 
compliance parameters, using the following categories: <80%; 80% ≤ x < 100%; 100%; 100% < 
x ≤ 120%; > 120%. 
All original IP administration records will be listed per subject. The listing will include all 
deviations from IP schedules such as missed or reduced doses and GLPG3970/placebo switches. 
IP exposure and compliance data will be listed. 
6.2. 
Efficacy Analyses 
Efficacy analyses will be performed on the FAS.  
Tabulations will be shown per planned treatment group. 
6.2.1. 
Level of Significance 
Statistical tests for efficacy analysis will be done at a 2-sided significance level of 10%. 
6.2.2. 
Primary Efficacy Parameter 
The primary efficacy endpoints for this study is the change from baseline in ESSDAI score at 
Week 12. 
The ESSDAI is a systemic disease activity index to assess 12 domains (i.e. organ systems: 
constitutional, lymphadenopathy, glandular, articular, cutaneous, pulmonary, renal, muscular, 
peripheral nervous system, CNS, hematological, biological) in patients with pSS, where each of 
the domains is divided into 3-4 levels of activity. These scores are summed across the 12 
domains in a weighted manner to provide the total score (range 0-123). A clinically meaningful 
reduction from baseline (>=3 points) indicates the improvement of symptoms.  
The ESSDAI will be assessed at baseline, week 4, week 8 and week 12.  
6.2.2.1. 
Derivation Rules 
The binary categorizations of the ESSDAI actual values calculated per visit is defined as follows:  
 
• ESSDAI Responder: Subjects having reduction from baseline ≥ 3 points by 
analysis window 
6.2.2.2. 
Analyses Methods 
Analysis will be performed on total score as well as the 12 domain scores for each treatment group 
and analysis visit. Observed and change from baseline will be summarized using descriptive 
statistics by treatment group and visit.  


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An MMRM will be used on the change from baseline to week 12 to compare treatment groups, 
with a 90% CI of the treatment difference.  
The following covariates will be used: treatment-by-visit interaction and baseline-by-visit 
interaction. An unstructured variance-covariance matrix will be used to model the residuals. If the 
default Newton–Raphson algorithm used by SAS PROC MIXED fails to converge, the following 
will be tried to avoid lack of convergence while maintaining an unstructured variance: 
A. The Fisher scoring algorithm (via the SCORING option of the PROC MIXED 
statement) will be used to obtain the initial values of covariance parameters.  
B. If the above fails, the no-diagonal factor analytic structure will be used which 
effectively performs the Cholesky decomposition via the TYPE=FA0(V) option of 
the REPEATED statement, where V is the total number of visits in the response 
vector (V = 3). 
C. If all the above fails, the variance-and-correlations parameterization will be 
attempted using TYPE =UNR 
In the rare case where all the above fails, the Toeplitz structure with the sandwich variance 
estimator (EMPIRICAL option) will be used. If this option also fails, the AR(1) + random 
intercept model will be tried with the sandwich variance estimator. 
The LSM, LSM difference between GLPG3970 and the placebo group (reference category), 
standard error, two-sided 90% CIs for the LSM and difference between treatment groups and p-
value for treatment differences will be presented. The number of subjects in the analysis population 
and number of subjects in the analysis will be provided by treatment group. 
Graphs of the mean (+- SE) actual values over time and of the mean (+- SE) change from baseline 
will be presented. Also, graph of the LSM (+-SE) change from baseline will be provided. In 
addition, profile plot of the actual values and change from baseline will be provided by treatment 
group. All values, including unscheduled visits will be presented in profile plot of the actual values. 
If there are more than one visits on the same day, time will be considered to order them. 
Analysis of Binary Endpoint 
The ESSDAI response will be summarized for the OC and NRI using number and percentages by 
treatment group. Fisher’s exact method will be used to compare the GLPG3970 and placebo 
based on NRI rates. Fisher’s exact p-value and 90% modified Santner-Snell confidence interval 
of the difference in response rates will be presented (In particular, the modification of Santner-
Snell methodology proposed by Chang and Zhang in 1999 will be used (score option)). In 
addition, 90% Clopper-Pearson confidence interval based on NRI rates for each treatment group 
will be provided. 
 
A frequency plot over time will be provided for the subjects having reduction ESSDAI ≥ 3 
points.  


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6.2.2.3. 
Decision Making Methodology 
The decision making methodology described by Frewer et al (Frewer, Mitchell, Watkins, & 
Matcham, 2016) will be used to provide further insight into the treatment effect of GLPG3970 
over placebo, and will support scenario analyses.  
The posterior distribution of this treatment effect will be estimated, and from this distribution 
probabilities of reaching at least a certain effect (delta) will be derived, e.g., a range of plausible 
effect size values going from as high as P (delta <=-5) to as low as P (delta <=-2). A common SD 
of 4 was assumed for both active and placebo arm. 
More details about this analysis will be provided in a separate document. This output will be 
generated for decision making purposes and will not be part of the CSR. 
6.2.2.4. 
Area under the Efficacy Curve (AUEC)  
To further explore the data in a slightly different fashion, the area under the efficacy curve (AUEC) 
based on the MMRM-derived LS-means will be derived for GLPG3970 and placebo. The AUEC 
will be calculated using the trapezoidal rule as illustrated in Figure 2.  A 90% confidence interval 
and between-group p-value will be derived as well. All will be based on the MMRM model for 
change from baseline in total and 12 domain scores. 
Figure 2. Graphical illustration, calculation of AUEC. 
 
 
 


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6.2.3. 
Secondary Efficacy Parameters 
6.2.3.1. 
EULAR Sjögren’s Syndrome Patient Reported Index (ESSPRI) Score 
The ESSPRI is a patient self-reported outcome measure to assess dryness, limb pain, fatigue, and 
mental fatigue, where each of the domains normally reported as 0 (not at all) to 10 (extremely 
severe). The final ESSPRI score is the average of 3: dryness, pain, and fatigue. A clinically 
significant reduction from baseline of the ESSPRI score (at least one point or 15% of the baseline 
value) indicates the improvement of symptoms.   
The ESSPRI will be assessed at baseline, week 4, week 8 and week 12.  
6.2.3.2. 
Derivation Rules 
The binary categorizations of the ESSPRI actual values calculated at week 12 is defined as 
follows:  
 
• ESSPRI Responder: Subjects having reduction ≥ 1 point from baseline or 15% 
change (i.e., decrease) from baseline 
6.2.3.3. 
Analyses Methods 
Analysis will be performed on average score as well as the 3 domain scores for each treatment 
group and analysis visit. Observed and change from baseline over time will be summarized using 
descriptive statistics by treatment group and visit. 
The analysis of change from baseline up to week 12 in average and domain scores will use the 
same method as for analysis of the primary efficacy endpoint as detailed in section 6.2.2.2. 
Graphs of the mean (+- SE) actual values over time, mean (+- SE) change from baseline and LSM 
(+-SE) change from baseline will be presented. In addition, profile plot of the actual values will be 
provided by treatment group. A frequency plot over time will be provided for the subjects having 
reduction ≥ 1 point from baseline or 15% change (i.e., decrease) from baseline 
The analysis of the binary categorizations of ESSPRI at each time point will use same method as 
for the analysis of ESSDAI binary categorization as detailed in section 6.2.2.2. 
To further explore the data in a slightly different fashion, an AUEC based on the MMRM-derived 
LS-means will be derived for GLPG3970 and placebo as detailed in section 6.2.2.4. 
A listing will be provided for the ESSPRI domain scores and the total score along with actual 
values and change from baseline. 




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6.2.4.3.2 
 
6.2.4.4. 
6.2.4.4.1 
 
 
6.2.4.4.2 
 
6.2.4.5. 




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6.2.4.7.2 
 
6.2.4.8. 
 
6.2.4.8.1 
 


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6.2.4.9. 
 
6.2.4.9.1 
 
 
6.2.4.9.2 
 
6.2.5. 
Subgroup Analyses 
No subgroup analysis is planned for this clinical study as the study sample size is too small. 
Thus, any subgroup of this would have small sample size to be relevant or even uninterpretable.  


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6.3. 
Safety Analyses 
Safety analyses will be performed on the Safety Analysis Set. 
Safety tables will be presented by treatment group. 
Safety parameters will be analyzed descriptively (see Section 4.5.2 and Section 4.5.3). No formal 
testing will be performed to compare the treatment groups. 
6.3.1. 
Adverse Events 
All adverse events (AEs) and changes in attributes (worsening and improvement) of AEs are 
reported in the database. An identification number serves to link the records considered by the 
investigator as describing the evolution of one and the same event. 
6.3.1.1. 
Definition of Treatment-Emergent Adverse Events 
The analysis of AEs will be based on treatment-emergent events (TEAE).  
TEAEs are defined as 
− 
Any AE with an onset date on or after the IP start date and no later than 30 days after last 
dose of IP, or any worsening of any AE on or after the IP start date. 
− 
Improvement or no change of any ongoing AEs on or after the IP start date are not 
considered treatment-emergent. If an AE is ongoing at the time of first IP intake, if there is 
no change or an improvement in its toxicity grade or its seriousness status (reported in the 
‘Change in Adverse event details Entry’ CRF page), this AE will not be considered as 
treatment-emergent. 
6.3.1.2. 
Coding of Reported Terms 
All AE terms will be coded in the database using the latest version of MedDRA coding 
dictionary. AEs will be graded using the latest version of the National Cancer Institute Common 
Terminology Criteria for Adverse Events (NCI CTCAE). 
All tables will show the AE preferred terms grouped into system organ class. Subject listings will 
also show the reported terms (verbatim). Any other coding levels will only be shown in a listing 
summarizing coding unless explicitly mentioned otherwise. 
6.3.1.3. 
Allocation of Adverse Events to Analysis Periods 
All AEs will be placed into analysis periods considering their start date, aiming to report the 
incidence of these events only in the analysis period during which they started. 
The general rule for allocation of AEs to analysis periods follows: 
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If the start date of an AE is missing or incomplete to a level preventing a clear allocation of the 
AE to one single analysis period and no flag indicating timing relative to study medication is 
available, a worst-case consideration (see below) will be done aiming to allocate the AE to one 
single analysis period, if possible. When a worst-case consideration is needed, the end date of the 
AE, if and as available, should also be considered; if such AEs clearly end on a given point, this 
will exclude the possibility to allocate the AE to an analysis period after that point. 
− 
An AE which according to the available information of its start date could belong to the 
screening as well as to the treatment analysis period will only be placed in the treatment 
period. 
− 
An AE with a missing start date will be allocated to the treatment period unless the “Prior to 
First GLPG3970/Placebo Treatment” = “Yes”. 
6.3.1.4. 
Treatment Relatedness 
Following the guideline ICH-E3 Structure and Content of Clinical Study Reports (Step 4 
Version), the originally reported relatedness to IP of an AE will be dichotomized as follows: 
− 
Not IP related: all non-missing weaker levels of relatedness than ‘possibly drug related’. 
− 
IP related: ‘possibly drug related’ and all stronger levels of relatedness (this class also 
includes any missing drug relatedness, as a worst-case consideration). 
 
Only this dichotomized relatedness will be used in tables and can apply to different IPs when 
relatedness has been collected separately per IP; relatedness as originally reported will only be 
listed. 
6.3.1.5. 
Worst-Case Selections 
When cross-tabulating AE preferred terms versus an AE attribute (like intensity), only the worst-
case within each same preferred term, same subject and same analysis period will be considered, 
i.e. when the same subject has more than once the same AE preferred term reported in the same 
treatment group, the subject will be counted only once and will be shown under the worst 
outcome (like the worst intensity for that AE in the concerned treatment period). 
The severity grade of events for which the investigator did not record severity will be categorized 
as “missing” for tabular summaries and data listings. The missing category will be presented last 
in summary presentation. 
6.3.1.6. 
Calculation of Relative Days and Duration 
For each newly reported event, and reported worsening or improvement of an existing event, the 
start day in the study (the day of the AE start date relative to the date of first IP administration), 
the start day in the analysis period, and the duration (in days) will be calculated. In addition, the 
relative day and duration will be derived for the entire event; that is, the full evolution of the 
event, including the initial reporting and all subsequent worsening and/or improvement. 


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Relative days and durations will only be listed. 
See Section 4.3.1 for the calculation of relative days. 
6.3.1.7. 
Events of Special Interest 
Not applicable. 
6.3.1.8. 
Presentation of Results 
The analysis will focus on AEs reported during the treatment period. AEs reported during the 
screening period will only be listed. 
All AEs tables will show the number of subjects with TEAEs. 
AEs which are not treatment-emergent will only be listed. 
A summary table will be provided, showing the number (percent) of subjects with at least one: 
− 
TEAE, 
− 
IP-related TEAE, 
− 
Serious TEAE, 
− 
TEAE leading to death, 
− 
TEAEs by worst intensity (CTCAE Toxicity Grade), 
− 
TEAE leading to IP interruption, 
− 
TEAE leading to IP discontinuation. 
 
The AE terms will be presented sorted in descending order of frequency, prioritizing the 
GLPG3970 treatment group and then for placebo, first by system organ class, then by preferred 
term, and then alphabetically. 
Frequency tabulations, by system organ class and preferred term, of the number (percent) of 
subjects with a TEAE will be presented. Similar tables will be provided by worst intensity, and 
for IP-related TEAEs, grade 3-4-5 TEAEs, serious TEAEs and TEAEs leading to IP 
discontinuation of IP. 
All AE data will also be listed, including separate lists for SAEs, AEs leading to death, and AEs 
leading to IP discontinuation. Listings will clearly indicate AEs to be treatment-emergent or not. 
In addition, AEs related to SARS-Cov-2 will be listed separately. 
6.3.1.9. 
EudraCT Adverse Events Reporting 
For the purpose of EudraCT reporting, the following tabulations will be created: 
Frequency tabulations, by system organ class and preferred term, of the number (percent) of 
subjects and number of events with non-serious TEAE will be presented. A similar table will be 




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6.3.2.4. 
Definition of Non-Graded Abnormalities 
For all laboratory tests provided by the laboratory, the position of the actual analysis values 
versus their normal ranges will be determined directly by using the derived position indicator, 
expressing the classes for these analysis values as low (L), normal (N) or high (H). L, N and H 
are further referred to as non-graded abnormalities. 
6.3.2.5. 
Urinalysis Tests with Categorical Results 
Results of urinalysis with qualitative results will be tabulated by time point. No toxicity grading 
or non-graded abnormalities will be derived. 
6.3.2.6. 
Treatment-Emergent Principle 
Toxicity Grades 
A post-baseline toxicity grade 1, 2, 3 or 4 is defined as treatment-emergent when higher than the 
toxicity grade of the baseline result or when there is a change in direction (from H to L or from L 
to H). If the baseline result is missing, a post-baseline toxicity grade 1, 2, 3 or 4 will be 
considered as treatment-emergent. 
Non-graded Abnormalities 
A post-baseline non-graded abnormality class L or H is defined as treatment-emergent when it 
differs from the abnormality class of the baseline result. If the baseline result is missing, a post-
baseline abnormality L or H will be considered as treatment-emergent. 
6.3.2.7. 
Worst-Case Principle 
Toxicity Grading 
The worst-case post-baseline toxicity grade 0, 1, 2, 3 or 4 will be determined per subject, per 
laboratory test (and direction, increases and decreases) and for each analysis period, using all 
non-missing post-baseline records (including unscheduled and FU visits). 
The worst-case toxicity grade is the highest toxicity grade corresponding to the highest laboratory 
test value (by direction, increases and decreases). In case of several equal highest post-baseline 
actual values, the earliest occurrence will be taken for the analyses and will be flagged in the 
listings.   
− 
Grade 0: all post-baseline toxicity grades are classified as 0 
− 
Grade 1: all post-baseline toxicity grades are classified as ≤1 
− 
Grade 2: all post-baseline toxicity grades are classified as ≤2 
− 
Grade 3: all post-baseline toxicity grades are classified as ≤3 
− 
Grade 4: all post-baseline toxicity grades are classified as ≤4 
 
If any record is missing, then the toxicity grade is considered as ‘missing’. 




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 3 0 6 _ 3 4 1 1 6  
G L P G 3 9 7 0 -C L -2 0 7  
 
-5 3 - 
N o n -gra d e d a b n or m alities a n d t o xicities gra des of t he act ual val ues will be prese nte d as s hift 
ta bles of t he w orst-case a b n or mali t y/t o xicit y gra de vers us t he baseli ne a b n or malit y/t o xicit y 
gra de. T h e ta ble will be create d p er la b orat or y test, treat me nt gr o u p a n d a nal ysis wi n d o w . T he 
res ults of n o n-gra d e d a b n or malities a n d t o xicities gra des will be s h o w n se p aratel y.   
A fre q u e nc y ta ble  of t he n u m ber ( perce nt) of s u bjects wit h treat me nt -e mer ge nt w orst -cas e 
a b n or malities/t o xicit y gra de per l a b orat or y t est, treat me nt gr o u p a n d a nal ysis peri o d will be 
prese nte d. T h e res ults of n o n -gra de d a b n or malities a n d t o xicities gra des will be s h o w n 
se parat el y.  
A fre q u e nc y ta ble of t he n u m ber ( perce nt) of s u bjects  will be als o pr o vi de d f or he pat ot o xicit y  
fla gs d efi ne d b ef ore. T hese a b n or malities will be als o fla g ge d i n t he i n di vi d ual data la b orat or y 
listi n g. 
Listi n g will be pr o vi de d f or t he la b orat or y t e st al o n g wit h fla g f or a b n or malit y res ults. I n 
a d diti o n, pre g n a nc y res ult will be liste d se paratel y.  
6. 3. 3.  
El e ctr o c ar di o gr a m  
6. 3. 3. 1.  
A v ail a bl e D at a  
T he f oll o wi n g E C G p ara meters will be a nal yse d:  heart rate  ( H R), R R i nter val, P R i nter val, Q R S 
i nter val, u nc orrecte d Q T i nter val, Q Tc F ( deri ve d).  
6. 3. 3. 2.  
D eri v ati o n R ul e s  
Deri ve d P ar a meters  
T he Fri d ericia’s c u be -r o ot c orrecte d Q T ( Q Tc F) will be calc ulate d usi n g t he f oll o wi n g f or m ula. 
Fri deri cia’s c u b e -r o ot c orrecte d Q T ( Fri derici a, 1 9 2 0): 
𝑄𝑇𝑐𝐹 (𝑚𝑠) = 𝑄𝑇 (𝑚𝑠) ×
 (
) 
If R R is missi n g, t he n it will be deri ve d fr o m H R usi n g t he f or m ula R R( ms) = 6 0 0 0 0 / H R( b p m) . 
H a n dli n g of E C Gs Me as ure d i n Tri plic ate  
If E C G is c ollecte d i n tri plicates, t he f oll o wi n g a p pr oac h will be ta ke n. 
First, a n y deri vati o n of E C G para meters will be d o ne bef ore ha n dli n g E C G tri plicates. Ne xt, t he 
mea n of t he tri plicate E C G val ues will be cal c ulat e d f or eac h i n di vi d ual E C G para meter, wit h o ut 
r o u n di n g t he res ult. T hes e calc ul ate d mea ns will c o nstit ute t he a nal ysis val ues; a n y deri vati o n 
(e. g. c ha n ge fr o m b aseli n e, assi g n m e nt of a b n or m alities) a n d statistic will be base d o n t he mea n 
val ue of t he tri pl icates.  
T he val ues of t he ori gi nal me m bers of a tri plicate will be liste d. 


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6.3.3.3. 
Abnormalities 
The actual analysis values and changes from baseline of the QT and QTcF parameters will be 
categorized into the abnormality classes as defined in the SAP Appendix II. 
Worst-Case Abnormality 
The worst-case post-baseline categorized actual analysis value and the worst-case categorized 
change from baseline for QT and QTcF will be determined per subject, per parameter, and for 
each analysis period, using all non-missing post-baseline records (including unscheduled and FU 
visits). 
The worst-case categorized actual analysis value is the category corresponding to the highest 
post-baseline actual value. In case of several equal highest post-baseline actual values, the earliest 
occurrence will be taken for the analyses and will be flagged in the listings.   
The worst-case change from baseline is the category corresponding to the largest increase 
(positive change) from baseline. In case of several equal largest increase from baseline, the 
earliest occurrence will be taken for the analyses and will be flagged in the listings.   
Treatment-Emergent Abnormalities 
Actual value: An abnormal post-baseline abnormality is defined as treatment-emergent when the 
abnormality is worse compared to the abnormality at baseline or when there is a change in 
direction (from H to L or from L to H). When the baseline value is missing, post-baseline 
abnormalities are considered as treatment-emergent. 
An abnormal category for change from baseline is always treatment-emergent. 
6.3.3.4. 
Presentation of Results 
No formal inferential statistics (p-values) will be derived. 
Continuous parameters will be summarized by means of descriptive statistics (including 90% CI 
of the mean change) by parameter, treatment group and analysis window. Actual values and 
change from baseline will be tabulated separately. 
Profile line plot by subject of all actual observed values using relative day (ADY) and profile plot 
on change from baseline by analysis window will be presented by treatment group. All values, 
including unscheduled visits will be presented in profile plot. If there is more than one visit on 
the same day, time will be considered to order them. Graphs of the mean (+- SE) actual values 
over time and of the mean (+- SE) change from baseline will be presented.  
ECG will be further explored on the subset of subjects taking anti-malaria medications. Profile 
line plot by subject of actual observed values at baseline and at 1.5, 3 and 4.5 hours postdose will 
be presented by treatment group. In addition, profile line plot of the change from baseline to 1.5, 
3 and 4.5 hours postdose will be presented. 


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The analysis of abnormalities will focus on assessments reported during the treatment period. 
Results reported during the screening period will only be listed. 
Abnormalities of the actual values will be presented as shift tables of the worst-case abnormality 
versus the baseline abnormality. The table will be created per parameter, treatment group and 
analysis period. 
A frequency table of the number (percent) of subjects with treatment-emergent worst-case 
abnormalities and the worst change per parameter, treatment group and analysis period will be 
presented. 
A frequency table per treatment group and time point of the ECG interpretations as recorded in 
the case report form (CRF) will be provided. 
A listing will be provided along with abnormality. 
6.3.4. 
Vital Signs 
6.3.4.1. 
Available Data 
The following vital signs parameters will be analyzed: weight (kg), diastolic and systolic blood 
pressure (mmHG), heart rate (beats/min) and body temperature (C). 
6.3.4.2. 
Derivation Rules 
Derived Parameters 
Not applicable. 
6.3.4.3. 
Abnormalities 
Vital signs data will be categorized according to the cutoffs provided in the SAP Appendix II.  
6.3.4.4. 
Treatment-Emergent Principle 
A post-baseline abnormality class L or H is defined as treatment-emergent when it differs from 
the abnormality class at baseline. If the baseline result is missing, a post-baseline abnormality 
L or H will be considered as treatment-emergent. 
An abnormal category for change from baseline is always treatment-emergent. 
6.3.4.5. 
Worst-Case Abnormality 
The worst-case post-baseline categorized actual analysis value will be determined per subject, per 
parameter and for each analysis period, using all non-missing post-baseline records (including 
unscheduled and FU visits). 


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The worst-case categorized actual analysis value is the category corresponding to the highest 
post-baseline actual value. In case of several equal highest post-baseline actual values, the earliest 
occurrence will be taken for the analyses and will be flagged in the listings. 
6.3.4.6. 
Presentation of Results 
No formal inferential statistics (p-values) will be derived. 
Continuous parameters will be summarized by means of descriptive statistics (including 90% CI 
of the mean change) by parameter, treatment group and analysis window. Actual values and 
change from baseline will be tabulated separately. 
Graphs of the mean (+- SE) actual values over time and of the mean (+- SE) change from 
baseline will be presented. 
The analysis of abnormalities will focus on assessments reported during the treatment period. 
Results reported during the screening or post-treatment (if defined) period will only be listed. 
Abnormalities of the actual values will be presented as shift tables of the worst-case abnormality 
versus the baseline abnormality. The table will be created per parameter (and position if 
applicable), treatment group and analysis period. 
A frequency table of the number (percent) of subjects with treatment-emergent worst-case 
abnormalities per parameter, treatment group and analysis period will be presented. 
A listing will be provided along with abnormality. 
6.3.5. 
Physical Examinations 
Physical examination results will only be listed. 
6.3.6. 
SARS-CoV-2 Infection 
Results of the SARS-CoV-2 infection test will be listed for the subjects who have at least one 
positive test. 
6.3.7. 
Subgroup Analyses 
No subgroup analysis is planned for this clinical study as the study sample size is too small.  
6.4. 
Pharmacokinetic Analysis 
6.4.1. 
Available Data 
Blood samples for the PK assessment of GLPG3970 should be collected on the visits specified in 
the Schedule of Assessments in Section 2.5. 






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7. 
REFERENCES 
Chan, I. S. F., and Zhang, Z. (1999). “Test-Based Exact Confidence Intervals for the Difference 
of Two Binomial Proportions.” Biometrics 55:1202–1209. 
Fridericia, L. (1920). Die Systolendauer im Elektrokardiogramm bei normalen Menschen und bei 
Herzkranken. Acta Medica Scandinavia 53:469-486. 
ICH E3 Structure and Content of Clinical Study Reports (Step 4 Version). 
ICH E9 Statistical Principles for Clinical Trials (Step 4 Version). 
ICH E14 The Clinical Evaluation of QT/QTc Interval Prolongation and Proarrhythmic Potential 
for Non-Antiarrhythmic Drugs (Step 4 Version). 
ICH E6 Intergrated Addendum to ICH E6 (R1): Guideline for good clinical practice 
(Step 4 Version). 
ICH E9(R1) Estimands and Sensitivity Analysis in Clinical Trials (Step 2 Version).




















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Appendix III: EULAR Sjögren’s Syndrome Disease Activity Index (ESSDAI) Score 
 
 
 
 
 
 


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Appendix IV: EULAR Sjögren’s Syndrome Patient Reported Index (ESSPRI) 
Score 
 
 
 
 
 


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Appendix XI: SAS Code 
  Mixed Model for Repeated Measures  
The SAS code for MMRM model with unstructured variance-covariance matrix for the primary 
efficacy endpoint is: 
PROC SQL data = dataset NOPRINT; 
          SELECT mean(AVAL)   INTO : b   FROM ADXX where paramcd = ‘XXX’ and fasfl = ‘Y’ 
and avisit = ‘Baseline’;           
QUIT;     
For parameters planned to be collected/measured at Week 4, Week 8 and Week 12 the following 
SAS code will be used: 
PROC MIXED data = dataset; 
       CLASS subjid trt visit ; 
       MODEL change =  visit*trt bsl*visit/ NOINT DDFM=KenwardRoger; 
       REPEATED visit / SUBJECT=subjid TYPE=un; 
      LSMEANS visit*trt / cl alpha=0.1 at (bsl) = (&meanbsl.);  
      ESTIMATE 'GLPG3970 vs. Placebo: Week 4'  avisit*trtp 1 0 0 -1  0  0 /CL ALPHA = 0.1; 
      ESTIMATE 'GLPG3970 vs. Placebo: Week 8'  avisit*trtp 0 1 0  0 -1  0 /CL ALPHA = 0.1; 
      ESTIMATE 'GLPG3970 vs. Placebo: Week 12' avisit*trtp 0 0 1  0 -0 -1 /CL ALPHA = 0.1; 
      ESTIMATE 'AUEC GLPG3970'  avisit*trtp 4 4 2 0 0 0  bsl*avisit %sysevalf(4*&meanbsl.) 
%sysevalf(4*&meanbsl.)                     
 %sysevalf(2*&meanbsl.)  / divisor = 12  CL ALPHA = 0.1; 
      ESTIMATE 'AUEC Placebo'   avisit*trtp 0 0 0 4 4 2     bsl*avisit %sysevalf(4*&meanbsl.) 
%sysevalf(4*&meanbsl.)  
   %sysevalf(2*&meanbsl.)  / divisor = 12  CL ALPHA = 0.1; 
       ESTIMATE 'AUEC GLPG3970 vs. Placebo'  avisit*trtp 4 4 2 -4 -4 -2 / divisor = 12  CL 
ALPHA = 0.1; 
RUN; 
 
Code for endpoints measured at Baseline, Week 8 and Week 12: 
       LSMESTIMATE trt*visit 
                ' GLPG3970 vs Placebo: Week 8'   1 0      -1 0, 
                ' GLPG3970 vs Placebo: Week 12’   0 1   0 -1; 
RUN; 
For the log transformed parameters the following will be applied: 
- 
In the PROC SQL: AVAL will be replaced by log(AVAL) 
- 
In the PROC MIXED: 
o Change will be replaced by geopchg=log(aval)-log(bsl) 
o And bsl will be replaced by log(bsl) 
 


Galapagos 
  CONFIDENTIAL 
 
43952_17306_34116 
GLPG3970-CL-207 
 
-82- 
If the default Newton–Raphson algorithm used by SAS PROC MIXED fails to converge, the 
following will be tried to avoid lack of convergence while maintaining an unstructured variance: 
A. The Fisher scoring algorithm (via the SCORING option of the PROC MIXED 
statement) will be used to obtain the initial values of covariance parameters:  
PROC MIXED data = dataset SCORING=5; 
… 
The rest of the code is the same as the first full proc mixed code provided. 
 
B. If the above fails, the no-diagonal factor analytic structure will be used which 
effectively performs the Cholesky decomposition via the TYPE=FA0(V) option of 
the REPEATED statement, where V is the total number of visits in the response 
vector (V = 3): 
PROC MIXED data = dataset; 
… 
       REPEATED visit / subject=subjid type=FA0(3); 
… 
The rest of the code is the same as the first full proc mixed code provided. 
 
C. If all the above fails, the variance-and-correlations parameterization will be 
attempted using TYPE =UNR: 
PROC MIXED data = dataset; 
… 
       REPEATED visit / subject=subjid type=UNR; 
… 
The rest of the code is the same as the first full proc mixed code provided. 
 
In the rare case where all the above fails, the Toeplitz structure with the sandwich variance 
estimator (EMPIRICAL option) will be used: 
PROC MIXED data = dataset EMPIRICAL; 
… 
       REPEATED visit / subject=subjid type=TOEP; 
… 
The rest of the code is the same as the first full proc mixed code provided. 
 
If this option also fails, the AR(1) + random intercept model will be tried with the sandwich 
variance estimator: 
PROC MIXED data = dataset EMPIRICAL; 


Galapagos 
  CONFIDENTIAL 
 
43952_17306_34116 
GLPG3970-CL-207 
 
-83- 
… 
       REPEATED visit / subject=subjid type=AR(1); 
       RANDOM intercept / subject=subjid; 
… 
The rest of the code is the same as the first full proc mixed code provided. 
 
 


Galapagos 
  CONFIDENTIAL 
 
43952_17306_34116 
GLPG3970-CL-207 
 
-84- 
Appendix XII: Prednisolone Conversion Table 
Glucocorticoid Name 
Dose Equivalent to 5 mg Prednisolone 
Prednisone oral 
5 mg 
Betamethasone oral, topical, IM, IV 
0.6 mg 
Cortisol (hydrocortisone) oral, topical, IM, IV 
20 mg 
Cortisone oral, IV, intra-articular, transcutaneous 
25 mg 
Deflazacort oral, IM, IV 
7.5 mg 
Dexamethasone oral, IM, IV 
0.75 mg 
Methylprednisolone Oral IM, IV 
4 mg 
Methylprednisolone Acetate Oral IM, IV 
4 mg 
Methylprednisolone Sodium Succinate 
4 mg 
Paramethasone oral, IM, intra-articular 
2 mg 
Prednisolone oral, topical, eyes drops, IV 
5 mg 
Triamcinolone oral, IM, inhalation 
4 mg 
Beclometasone Dipropionate oral, topical, nasal, 
inhalation 
1.25 mg 
Budesonide oral, nasal, inhalation, rectal  
1.5 mg 
Hydrocortisone Sodium Succinate IM, IV 
20 mg 
(Steroid Conversion Calculator) 
 
 


Signature Page for glpg3970-cl-207-sap 19634
Signature Page for glpg3970-cl-207-sap43952_33739_62673
Approval
Senior Medical Director
Clinical Development
17-Dec-2021 09:19:08 GMT+0000
Approval
Consultant Biostatistics
Biometrics
17-Dec-2021 09:48:52 GMT+0000