Clinical trial NCT03958955
Conditions: Discoid Lupus Erythematosus
Sponsor: LEO Pharma
Start date: 2019-07-09; Completion date: 2020-04-30
Enrollment: 27 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This was a double-blind, multi-centre, randomised, vehicle-controlled, within-subject phase 2a trial. The trial was designed to establish the efficacy and safety of delgocitinib cream in the treatment of adult subjects with discoid lupus erythematosus (DLE).

Detailed description:

Arms: arm 1: Delgocitinib cream applied twice daily for 6 weeks arm 2: Delgocitinib cream vehicle applied twice daily for 6 weeks
Interventions: intervention 1: Delgocitinib cream intervention 2: Delgocitinib cream vehicle
Intervention descriptions: intervention 1: Cream for topical application. intervention 2: The cream vehicle is similar to the delgocitinib cream except that it does not contain any active ingredient.

Protocol documents:
Prot_SAP_000.pdf: 
C o ver Pa ge 
O f f i c i a l  t i t l e : Effi c a c y a n d s af et y of t wi c e- d ail y a p pli c ati o n of d el g o citi ni b cr e a m 2 0 m g/ g f or 6 w e e k s i n s u bj e ct s wit h a cti v e 
di s c oi d l u p u s er yt h e m at o s u s . A p h a s e 2 a e x pl or at or y, r a n d o mi s e d, d o u bl e- bli n d, v e hi cl e- c o ntr oll e d, wit hi n- s u bj e ct, m ulti- c e ntr e 
tri al.
L E O  P h a r m a  n u m b e r : E X P - 1 3 7 3  
N C T  n u m b e r : N C T 0 3 9 5 8 9 5 5  
D a t e : 2 2 -O ct - 2 0 1 9  


C O N FI D E N TI A L  
T HI S D O C U M E N T C O N T AI N S C O N FI D E N TI A L I N F O R M A TI O N A N D M U S T N O T B E C O PI E D O R M A D E A V AI L A B L E T O A N Y T HI R D P A R T Y WI T H O U T 
T H E P RI O R W RI T T E N C O N S E N T O F T H E L E O G R O U P  
Cli nic al Tri al Pr ot oc ol  
E X P -1 3 7 3  
Effic ac y a n d safet y of t wice -dail y a p plicati o n of del g ociti ni b crea m 2 0 m g/ g f or 6 wee ks i n 
s u bjects wit h acti ve disc oi d l u p us er yt he mat os us  
A p hase 2a e x pl orat or y, ra n d o mise d, d o u ble- bli n d, ve hicle-c o ntr olle d, wit hi n-s u bject, 
m ulti -ce ntre trial 
T h is cli nic al tri al will be c o n d ucte d i n c o m pli a nce wit h t he cli nic al tri al pr ot oc ol, I C H-G C P 
a n d t he a p plic a ble re g ul at ory re q uire me nt(s). 
L E O P h ar m a A/ S  
Tri al I D:  
E X P - 1 3 7 3 
D ate:  
2 2 -Oct -2 0 1 9
E u dr a C T n o:  
2 0 1 8 -0 0 3 6 1 5 -2 2  
Versi o n:  
4. 0 


Trial I D: E X P -1 3 7 3  
Date:  2 2 -Oct -2 0 1 9  
Versi o n: 4. 0  
Pa ge 2 of 1 2 2  
 
 
Cli nic al tri al pr ot oc ol st ate me nts  
A p pr o v al st ate me nt L E O P h ar m a A/ S  
Electr o nic si g nat ures ma de wit hi n e T M F L E O are c o nsi dere d t o be a le gall y bi n di n g 
e q ui vale nt of tra diti o nal ha n d writte n si g nat ures. T he f oll o wi n g pers o ns ha ve a p pr o ve d t his 
cli nical trial pr ot oc ol b y usi n g electr o nic si g nat ures as prese nte d o n t he last pa ge of t his 
d oc u me nt: 
, M Sc 
Bi ostatistics Lea d, Me dical Scie nces  
, M D 
Vice P resi de nt, Me dical Scie nces 
, P h D 
Cli nical O perati o ns Lea d, Gl o bal Cli nical O perati o ns  
A p pr o v al st ate me nt si g n at or y i n vesti g at or  
T he si g nat or y i n vesti gat or a p pr o ves t he cli nical trial pr ot oc ol b y ma n uall y si g ni n g t he 
si g nat or y in vesti gat or cli nical trial p r ot oc ol a p pr o val f or m, w hic h is a se parate d oc u me nt 
a p pe n de d t o t his d oc u me nt. 
T he f oll o wi n g pers o n has a p pr o ve d t his cli nical tr ial pr ot oc ol: 
Mar gitta Wor m, U ni v. Pr of. Dr. Me d  
Si g nat or y i n vesti gat or  
Ac k n o w le d ge me nt st ate me nt i n vesti g at or(s) 
Eac h partici pati n g i n vesti gat or m ust a gree t o t he a p pr o ve d cli nical trial pr ot oc ol b y si g ni n g a 
cli nical trial p r ot oc ol ac k n o wle d ge me nt f or m or si milar d oc u me nt.  
P P D
P P D
P P D


Trial I D: E X P -1 3 7 3  
Date:  2 2 -Oct -2 0 1 9  
Versi o n: 4. 0  
Pa ge 3 of 1 2 2  
 
 
Pr ot oc ol a me n d me nt s u m m ar y of c h a n ges t a ble  
D oc u me nt hist or y  
D oc u me nt  
D ate  
Ty pe of pr ot oc ol a me n d me nt  
A me n d me nt 2 
(s u bsta ntial) 
( versi o n 4. 0) 
2 2- Oct - 2 0 1 9
Gl o bal 
A me n d me nt 1 
(s u bsta ntial)  
( versi o n 3. 0) 
1 5- Ma y - 2 0 1 9
Gl o bal  
Ori gi nal pr ot oc ol 
( versi o n 2. 0) 
2 2- Fe b - 2 0 1 9
N A  
N ote t hat t he pr ot oc ol a me n d me nt s u m mar y of c ha n ges ta ble f or t he pre vi o us a me n d me nt is 
l ocate d in A p pe n di x 9 . 
A me n d me nt 2  ( 2 2-Oct - 2 0 1 9) 
T his a me n d me nt is c o nsi dere d t o be s u bsta ntial base d o n t he criteria set f ort h i n Article 1 0(a) 
of Directi ve 2 0 0 1/ 2 0/ E C of t he E ur o pea n Parlia me nt a n d t he C o u ncil of t he E ur o pea n U ni o n 
or s u bse q ue nt re g ulati o n. 
O ver all r ati o n ale f or t he a me n d me nt 
T he pr ot oc ol is a me n de d t o a d dress recr uit me nt iss ues . D L E is a rare disease, a n d t he n u m ber 
of patie nts eli gi ble f or t his trial is ver y li mite d.  T he e xcl usi o n criteria c o ncer ni n g t o bacc o use 
a n d he patitis B ser ol o g y ha ve bee n m o difie d t o ease recr uit me nt wit h o ut c o m pr o misi n g t he 
safet y of t he s u bjects a n d t he e val uati o n of trial res ults.  
S u bjects w h o are i n scree ni n g w he n t his a me n d me nt is a p pr o ve d will be re-assesse d f or  
eli gi bilit y acc or di n g t o t he a me n de d eli gi bilit y criteria.  
All c ha n ges t o t he pr ot oc ol are s u m marise d bel o w.  


Trial I D: E X P -1 3 7 3  
Date:  2 2 -Oct -2 0 1 9  
Versi o n: 4. 0  
Pa ge 4 of 1 2 2  
 
 
Secti o n n o. 
a n d n a me  
Descri pti o n of c h a n ge  
Brief r ati o n ale  
8. 3  
E xcl usi o n 
criteria 
(als o pr ot oc ol 
s y n o psis a n d 
A p pe n di x 4) 
E xcl usi o n criteri o n n o. 1 7  was 
c ha n ge d fr o m a pre- defi ne d  
li mit ( > 7 0 ci garettes/ wee k or 
> 7 0 g t o bacc o/ wee k) t o i nstea d
e xcl u de s u bjects wit h u nsta ble
or fl uct uati n g use of t o bacc o.
To all o w ra n d o misati o n of s u bjects 
s m o ki n g >1 0 ci garettes/ da y. To bacc o  
ma y affect t he c o urse of D L E  a n d t h us 
t he trial res ults, b ut as l o n g as t he 
t o bacc o use is sta ble f or at least 1 
m o nt h pri or t o scree ni n g , t he act ual 
c o ns u m pti o n is c o nsi dere d less 
i m p orta nt. 
E xcl usi o n criteri o n n o. 2 6  was 
m o difie d t o o nl y e xcl u de 
p ositi ve h u ma n 
i m m u n o deficie nc y vir us 
a nti b o d y, he patitis B s urface 
a nti ge n, a n d he patitis C vir us 
a nti b o d y ser ol o g y (a n d n ot 
p ositi ve he patitis B s urface 
a nti b o d y a n d he patitis B c ore 
a nti b o d y ser ol o g y). 
R eacti vati o n of he patitis B is 
c o nsi dere d o nl y a t he oretical ris k, as  
t he treat me nt is t o pical a n d o nl y 
a p plie d t o a ver y s mall area ( ≤1 % of 
B S A ), a n d t heref ore t he s yste mic 
e x p os ure is ne gli gi ble . F urt her m ore, 
s u bjects will n ot be ra n d o mise d if t he y 
ha ve si g ns of acti ve i nfecti o n, a n d 
ra n d o mise d s u bjects will be m o nit or e d 
f or si g ns of acti ve i nfecti o n  d uri n g t he 
trial.   
Secti o n 1 1. 5. 2  
N o n -i n vasi ve 
s ki n sa m pli n g 
It was a d de d t hat n o n-i n vasi ve 
s ki n sa m pli n g will n ot be d o ne 
f or s u bjects w h o ha ve plaster 
or ba n da ge aller g y. 
To a v oi d aller gic reacti o ns t o t he 
a d hesi ve patc hes use d f or 
n o n-i n vasi ve s ki n sa m pli n g. 
A p pe n di x 9  
Pr ot oc ol 
a me n d me nt 
hist or y  
Ne w a p pe n di x a d de d  
c o ntai ni n g t he s u m mar y of t he 
pre vi o us pr ot oc ol a me n d me nt. 
To d oc u me nt t he pr ot oc ol a me n d me nt 
hist or y, a n d t o kee p o nl y t he m ost 
rece nt a me n d me nt s u m mar y at t he 
start of t he pr ot oc ol. 
T hr o u g h o ut  
d oc u me nt 
Mi n or  e dit orial re visi o ns. 
Mi n or, ha ve t heref ore n ot bee n 
s u m marise d. 


Trial I D: E X P -1 3 7 3  
Date:  2 2 -Oct -2 0 1 9  
Versi o n: 4. 0  
Pa ge 5 of 1 2 2  
 
 
Ta ble of c o nte nts  
Pr ot oc ol a me n d me nt s u m m ar y of c h a n ges t a ble  ................................................................... 3 
Ta ble of c o nte nts  ....................................................................................................................... 5 
List of p a nels  ........................................................................................................................... 1 0 
List of a b bre vi ati o ns ............................................................................................................... 11  
1  Pr ot oc ol s y n o psis ................................................................................................................ 1 3  
2  Tri al i de ntific ati o n  ............................................................................................................. 1 8 
3  Sc he m atic of tri al desi g n  ................................................................................................... 1 8 
4  Sc he d ule of tri al pr oce d ures  ............................................................................................. 1 9 
5  I ntr o d ucti o n a n d tri al r ati o n ale ....................................................................................... 2 3 
5. 1  Disc oi d l u p us er yt he mat os us ...................................................................................... 2 3  
5. 2  E x perie nce wit h i n vesti gati o nal me dici nal pr o d uct .................................................... 2 4  
5. 3  Trial rati o nale  .............................................................................................................. 2 5 
5. 4  Et hical c o nsi derati o ns  ................................................................................................. 2 6 
5. 5  Be nefit/ris k assess me nt  ............................................................................................... 2 7 
6  Tri al o bjecti ves a n d e n d p oi nts  .......................................................................................... 2 9 
7  Tri al desi g n  ......................................................................................................................... 3 1 
7. 1  O verall trial desi g n  ..................................................................................................... 3 1 
7. 2  N u m ber of s u bjects nee de d  ......................................................................................... 3 2 
7. 3  E n d of trial defi niti o n  ................................................................................................. 3 2 
7. 4  S oft ware  ...................................................................................................................... 3 2 
8  Tri al p o p ul ati o n  ................................................................................................................. 3 3 
8. 1  S u bject eli gi bilit y  ........................................................................................................ 3 3 
8. 2  I ncl usi o n criteria ......................................................................................................... 3 3 
8. 3  E xcl usi o n criteria  ........................................................................................................ 3 4 
8. 4  Scree ni n g a n d scree ni n g fail ures  ................................................................................ 3 7 
9  Tre at me nts  .......................................................................................................................... 3 9 
9. 1  Trial pr o d uct descri pti o n  ............................................................................................. 3 9 
9. 2  A d mi nistrati o n of I M P  ................................................................................................ 4 0 
9. 3  Treat me nt assi g n me nt  ................................................................................................. 4 1 


Trial I D: E X P -1 3 7 3  
Date:  2 2 -Oct -2 0 1 9  
Versi o n: 4. 0  
Pa ge 6 of 1 2 2  
 
 
9. 3. 1  
Bl i n di n g ......................................................................................................... 4 2 
9. 3. 2  
E mer ge nc y u n bli n di n g of i n di vi d ual s u bject treat me nt ................................ 4 2  
9. 4  Bac k gr o u n d treat me nt ................................................................................................. 4 3  
9. 5  Resc ue treat me nt  ......................................................................................................... 4 3 
9. 6  C o nc o mita nt me dicati o n a n d c o nc urre nt pr oce d ures ................................................. 4 3  
9. 7  Pr o hi bite d me dicati o n a n d pr oce d ures ....................................................................... 4 4  
9. 8  Treat me nt l o gistics a n d acc o u nta bilit y  ....................................................................... 4 6 
9. 8. 1  
La belli n g a n d pac ka gi n g of trial pr o d ucts ..................................................... 4 6  
9. 8. 2  
St ora ge of trial pr o d ucts ................................................................................ 4 6  
9. 8. 3  
Dr u g acc o u nta bilit y ....................................................................................... 4 7  
9. 8. 4  
Treat me nt c o m plia nce  ................................................................................... 4 8 
9. 8. 5  
Trial pr o d uct destr ucti o n  ............................................................................... 4 8 
9. 9  Pr o visi o n f or s u bject care f oll o wi n g trial c o m pleti o n  ................................................ 4 8 
9. 1 0  Re p orti n g pr o d uct c o m plai nts .................................................................................... 4 9  
1 0  Disc o nti n u ati o n a n d wit h dr a w al  ...................................................................................... 4 9 
1 0. 1  Ge neral pri nci ples  ....................................................................................................... 4 9 
1 0. 2  I M P disc o nti n uati o n r ules ........................................................................................... 5 0 
1 0. 2. 1  Reas o ns f or disc o nti n uati o n of I M P .............................................................. 5 0  
1 0. 3  Earl y ter mi nati o n assess me nts  .................................................................................... 5 0 
1 0. 4  L ost t o f oll o w - u p ........................................................................................................ 5 1 
11  Tri al assess me nts a n d pr oce d ures  .................................................................................... 5 2 
1 1. 1  O ver vie w .................................................................................................................... 5 2  
1 1. 2  Assess me nts perf or me d o nl y at scree ni n g/ baseli ne  .................................................... 5 3 
1 1. 2. 1  De m o gra p hics ............................................................................................... 5 3  
1 1. 2. 2  Fitz patric k s ki n t y pe ...................................................................................... 5 3  
1 1. 2. 3  Me dical hist or y  .............................................................................................. 5 4 
1 1. 2. 4  Hei g ht a n d wei g ht  ......................................................................................... 5 5 
1 1. 2. 5  Classificati o n of s yste mic l u p us er yt he mat os us  ............................................ 5 5 
1 1. 2. 6  C uta ne o us L u p us Er yt he mat os us Disease Area a n d Se verit y I n de x  ............. 5 6 
1 1. 2. 7  Re vise d C uta ne o us L u p us Er yt he mat os us Disease Area a n d Se verit y 
I n de x .............................................................................................................. 5 7 
1 1. 2. 8  I de ntificati o n of tar get lesi o ns ....................................................................... 5 7 
1 1. 3  Efficac y assess me nts  .................................................................................................. 5 8 
1 1. 3. 1  I n vesti gat or’s Gl o bal Assess me nt ................................................................. 5 8 
1 1. 3. 2  S ki n lesi o n acti vit y  ........................................................................................ 5 9 


Trial I D: E X P -1 3 7 3  
Date:  2 2 -Oct -2 0 1 9  
Versi o n: 4. 0  
Pa ge 7 of 1 2 2  
 
 
1 1. 3. 3  S ki n lesi o n da ma ge ........................................................................................ 6 0 
1 1. 4  Safet y assess me nts  ...................................................................................................... 6 1 
1 1. 4. 1  Vital si g ns  ...................................................................................................... 6 1 
1 1. 4. 2  P h ysica l e xa mi nati o n..................................................................................... 6 1 
1 1. 4. 3  Electr ocar di o gra m  ......................................................................................... 6 2 
1 1. 4. 4  La b orat or y testi n g  ......................................................................................... 6 3 
1 1. 5  P har mac o d y na mics a n d bi o mar kers  ........................................................................... 6 6 
1 1. 5. 1  O ver vie w ....................................................................................................... 6 6  
1 1. 5. 2  N o n -i n vasi ve s ki n sa m pli n g .......................................................................... 6 7 
1 1. 5. 3  S ki n bi o psies ( o pti o nal) ................................................................................. 6 7  
1 1 . 6 Ot her assess me nts  ....................................................................................................... 6 8 
1 1. 6. 1  S u bject assess me nts ....................................................................................... 6 8 
1 1. 6. 2  Size of tar get lesi o ns  ..................................................................................... 6 9 
1 1. 6. 3  P h ot o gra p h y ( o pti o nal) .................................................................................. 7 0  
1 1. 7  Esti mate of t otal bl o o d v ol u me c ollecte d  ................................................................... 7 0 
1 1. 8  E n d of trial .................................................................................................................. 7 0  
1 1. 9  St ora ge of bi ol o gical sa m ples  ..................................................................................... 7 1 
1 2  Scie ntific r ati o n ale f or tri al desi g n a n d a p pr o pri ate ness of assess me nts  ..................... 7 2 
1 2. 1  Scie ntific rati o nale f or trial desi g n  ............................................................................. 7 2 
1 2. 2  A p pr o priate ness of assess me nts  ................................................................................. 7 3 
1 3  A d verse e ve nts  ................................................................................................................... 7 5 
1 3. 1  Defi niti o n a n d classificati o n of a d verse e ve nts .......................................................... 7 5  
1 3. 2  C ollecti o n of a d verse e ve nt re p orts  ............................................................................ 7 5 
1 3. 3  Re p orti n g of a d verse e ve nts........................................................................................ 7 5  
1 3. 4  Re p orti n g of seri o us a d verse e ve nts  ........................................................................... 7 6 
1 3. 4. 1  I n vesti gat or re p orti n g res p o nsi bilities ........................................................... 7 6 
1 3. 4. 2  L E O re p orti n g res p o nsi bilities  ...................................................................... 7 7 
1 3. 5  Ot her e ve nts t hat re q uire e x pe dite d re p orti n g ............................................................ 7 8  
1 3. 5. 1  Pre g na nc y ...................................................................................................... 7 8  
1 3. 6  Re p orti n g of ot her e ve nts ........................................................................................... 7 8  
1 3. 6. 1  A d verse e ve nts of s pecial i nterest  ................................................................. 7 8 
1 3. 6. 2  O ver d ose........................................................................................................ 7 9  
1 3. 6. 3  Me dicati o n err or  ............................................................................................ 7 9 
1 3. 6. 4  Mis use  ........................................................................................................... 7 9 
1 3. 6. 5  A b use ............................................................................................................. 7 9  


Trial I D: E X P -1 3 7 3  
Date:  2 2 -Oct -2 0 1 9  
Versi o n: 4. 0  
Pa ge 8 of 1 2 2  
 
 
1 3. 6. 6  A g gra vati o n of c o n diti o n .............................................................................. 8 0  
1 3. 7  F oll o w- u p f or fi nal o utc o me of a d verse e ve nts .......................................................... 8 0  
1 3. 8  Ha n dli n g of a n ur ge nt safet y meas ure ........................................................................ 8 0  
1 4  St atistic al met h o ds  ............................................................................................................. 8 1 
1 4. 1  Sa m ple size  ................................................................................................................. 8 1 
1 4. 2  Trial a nal ysis sets  ........................................................................................................ 8 1 
1 4. 3  Statistical a nal ysis  ....................................................................................................... 8 2 
1 4. 3. 1  Dis p ositi o n of s u bjects  .................................................................................. 8 2 
1 4. 3. 2  De m o gra p hics a n d ot her baseli ne c haracteristics  .......................................... 8 2 
1 4. 3. 3  E x p os ure a n d treat me nt c o m plia nce ............................................................. 8 2  
1 4. 3. 4  A nal ysis of pri mar y e n d p oi nt ........................................................................ 8 2  
1 4. 3. 5  A nal ysis of sec o n dar y e n d p oi nts  ................................................................... 8 3 
1 4. 3. 6  A nal ysis of e x pl orat or y e n d p oi nts  ................................................................ 8 3 
1 4. 3. 7  A nal ysis of p har mac o d y na mics a n d bi o mar kers  ........................................... 8 4 
1 4. 3. 8  E x pl orat or y a nal yses  ..................................................................................... 8 4 
1 4. 3. 9  A nal ysis of safet y  .......................................................................................... 8 4 
1 4. 3. 1 0  I nteri m a nal ysis ............................................................................................. 8 6 
1 4. 3. 1 1  Ge neral pri nci ples  ......................................................................................... 8 6 
1 4. 3. 1 2  Ha n dli n g of missi n g val ues ........................................................................... 8 6  
1 5  Refere nces  ........................................................................................................................... 8 7 
A p pe n di x 1: Defi niti o ns of a d verse e ve nts a n d seri o us a d verse e ve nts  ............................. 9 0 
A p pe n di x 2: Cl assific ati o n of a d verse e ve nts  ....................................................................... 9 2 
A p pe n di x 3: Tri al g o ver n a nce c o nsi der ati o ns  ..................................................................... 9 5 
A p pe n di x 3 A: Re g ulat or y a n d et hical c o nsi derati o ns ................................................ 9 5  
A p pe n di x 3 B: I nf or me d c o nse nt pr ocess ................................................................... 9 6  
A p pe n di x 3 C: S u bject a n d data c o nfi de ntialit y ......................................................... 9 6  
A p pe n di x 3 D: Rec or d kee pi n g, q ualit y c o ntr ol, a n d data ha n dli n g ........................... 9 7  
A p pe n di x 3 E: Re gistrati o n, re p orti n g a n d p u blicati o n p olic y ................................. 1 0 2  
A p pe n di x 3 F: I ns ura nce ........................................................................................... 1 0 3  
A p pe n di x 3 G: Fi na ncial discl os ure .......................................................................... 1 0 3  
A p pe n di x 3 H: Trial a n d site cl os ure  ........................................................................ 1 0 4 
A p pe n di x 3I: Res p o nsi bilities .................................................................................. 1 0 5  
A p pe n di x 4: J ustific ati o n f or eli gi bilit y criteri a  ................................................................ 1 0 6 
A p pe n di x 5: C o nt act list  ...................................................................................................... 11 0  


Trial I D: E X P -1 3 7 3  
Date:  2 2 -Oct -2 0 1 9  
Versi o n: 4. 0  
Pa ge 9 of 1 2 2  
 
 
A p pe n di x 6: A meric a n C olle ge of R he u m at ol o g y re vise d criteri a f or cl assific ati o n of 
s yste mic l u p us er yt he m at os us ( 1 9 9 7 u p d ate of t he 1 9 8 2 criteri a) ( 2 6) ........................ 111  
A p pe n di x 7: C ut a ne o us L u p us Er yt he m at os us Dise ase Are a a n d Se verit y I n de x ( 2 7)  . 11 3  
A p pe n di x 8: Re vise d C ut a ne o us L u p us Er yt he m at os us Dise ase Are a a n d Se verit y I n de x 
( 2 8) .................................................................................................................................... 11 4  
A p pe n di x 9: Pr ot oc ol a me n d me nt hist or y  ......................................................................... 11 6  


Trial I D: E X P -1 3 7 3  
Date:  2 2 -Oct -2 0 1 9  
Versi o n: 4. 0  
Pa ge 1 0  of 1 2 2  
 
 
List of p a nels  
Pa nel 1: Trial desi g n  ................................................................................................................. 1 8 
Pa nel 2: Sc he d ule of trial pr oce d ures ....................................................................................... 1 9  
Pa nel 3: O bjecti ves a n d e n d p oi nts ........................................................................................... 2 9  
Pa nel 4: I de ntificati o n of i n vesti gati o nal me dici nal pr o d ucts  .................................................. 4 0 
Pa nel 5: Pr o hi bite d me dicati o n a n d pr oce d ures ....................................................................... 4 5  
Pa nel 6: Se q ue nce of assess me nts  ............................................................................................ 5 2 
Pa nel 7: Fitz patric k s ki n classificati o n  ..................................................................................... 5 4 
Pa nel 8: Sc ori n g i nstr ucti o ns f or t he A merica n C olle ge of R he u mat ol o g y criteria f or 
classificati o n of s yste mic l u p us er yt he mat os us  ................................................ 5 6 
Pa nel 9: I n vesti gat or’s Gl o bal Assess me nt f or disc oi d l u p us er yt he mat os us  .......................... 5 9 
Pa nel 1 0: Cli nical la b orat or y tests  ............................................................................................ 6 4 
Pa nel 1 1: A d verse e ve nt of s pecial i nterest  .............................................................................. 7 8 
Pa nel 1 2: Tra ns missi o n of electr o nic data  .............................................................................. 1 0 1 


Trial I D: E X P -1 3 7 3  
Date: 2 2 -Oct -2 0 1 9  
Versi o n: 4. 0  
Pa ge 1 1  of 1 2 2  
 
 
List of 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  
at o pic der matitis 
A E  
a d verse e ve nt  
A E SI  
a d verse e ve nt of s pecial i nterest 
A L T  
ala ni ne a mi n otra nsferase  
A S T  
as partate a mi n otra nsferase  
B S A  
b o d y s urface area 
C DI S C  
Cli nical Data I nterc ha n ge Sta n dar ds C o ns orti u m  
C H E  
c hr o nic ha n d ecze ma  
C L A SI  
C uta ne o us L u p us Er yt he mat os us Disease Area a n d Se verit y I n de x  
C L E  
c uta ne o us l u p us er yt he mat os us  
C M O  
c o ntract ma n ufact uri n g or ga nisati o n  
C R A  
cli nical researc h ass ociate  
C R O  
c o ntract researc h or ga nisati o n  
C T R  
cli nical trial re p ort  
C X C L  
c he m o ki ne ( C- X- C m otif) li ga n d  
D L E  
disc oi d l u p us er yt he mat os us  
D L QI  
Der mat ol o g y Life Q ualit y I n de x  
E C G  
electr ocar di o gra m  
e C R F  
electr o nic case re p ort f or m  
F A S  
f ull a nal ysis set 
G C P  
G o o d Cli nical Practice  
H R Q o L  
healt h -relate d q ualit y of life 
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 D 
i de ntificati o n n u m ber 
I E C 
i n de pe n de nt et hics c o m mittee 
I F N 
i nterfer o n 
I G A 
I n vesti gat or’s Gl o bal Assess me nt 
I L 
i nterle u ki n 
I M P 
i n vesti gati o nal me dici nal pr o d uct 


Trial I D: E X P -1 3 7 3  
Date: 2 2 -Oct -2 0 1 9  
Versi o n: 4. 0  
Pa ge 1 2  of 1 2 2  
 
 
I R B 
i nstit uti o nal re vie w b oar d 
I R T 
i nteracti ve res p o nse tec h n ol o g y 
J A K 
ja n us ki nase 
L E  
l u p us er yt he mat os us 
Me d D R A  
Me dical Dicti o nar y f or Re g ulat or y Acti vities  
Pa G A  
Patie nt’s Gl o bal Assess me nt  
P D E - 4 
p h os p h o diesterase- 4 
P P  
per pr ot oc ol 
R C L A SI  
Re vise d C uta ne o us L u p us Er yt he mat os us Disease Area a n d Se verit y I n de x 
S A E  
seri o us a d verse e ve nt 
S D  
sta n dar d de viati o n 
S L E  
s yste mic l u p us er yt he mat os us 
S O C  
s yste m or ga n class 
S P F  
s u n pr otecti o n fact or 
S T A T  
si g nal tra ns d ucer a n d acti vat or of tra nscri pti o n  
T h  
T hel per  
U V  
ultra vi olet 


Trial I D: E X P -1 3 7 3  
Date: 2 2 -Oct -2 0 1 9  
Versi o n: 4. 0  
Pa ge 1 3  of 1 2 2  
 
 
1  Pr ot oc ol s y n o psis  
Trial I D  
E u dra C T n o.  
E X P -1 3 7 3  
2 0 1 8 -0 0 3 6 1 5 -2 2  
Title of trial  
Efficac y a n d safet y of t wice -dail y a p plicati o n of del g ociti ni b crea m 2 0 m g/ g 
f or 6 wee ks i n s u bjects wit h acti ve disc oi d l u p us er yt he mat os us. 
A p hase 2a e x pl orat or y, ra n d o mise d, d o u ble -bli n d, ve hicle -c o ntr olle d, wit hi n -
s u bject, m ulti-ce ntre trial.  
S h ort title of trial  
Effect a n d safet y of del g ociti ni b crea m i n disc oi d l u p us er yt he mat os us.  
Mai n o bjecti ves 
a n d e n d p oi nts 
O bje cti ves  
E n d p oi nts  
Pri mar y o bjecti ve  
Pri mar y e n d p oi nt  
T o i n vesti gate t he efficac y of 
del g ociti ni b crea m 2 0 m g/ g t wice 
dail y o n acti ve disc oi d l u p us 
er yt he mat os us  ( D L E) tar get 
lesi o ns. 
•
Tar get lesi o ns wit h
I n vesti gat or’s Gl o bal
Assess me nt (I G A) a sc ore of 0 or
1 at Wee k 6.
Sec o n dar y o bjecti ve  
Sec o n dar y e n d p oi nts  
T o e val uate t he safet y of 
del g ociti ni b crea m 2 0 m g/ g t wice 
dail y o n acti ve D L E tar get lesi o ns.  
•
A d verse e ve nts ( n u m ber of A Es
a n d n u m ber of s u bjects wit h
A Es) u p t o Wee k 6.
•
N u m ber of lesi o n -s pecific,
treat me nt-relate d A Es u p t o
Wee k 6.
T o f urt her i n vesti gate t he efficac y 
of del g ociti ni b crea m 2 0 m g/ g 
t wice dail y o n acti ve D L E tar get 
lesi o ns. 
•
A ≥2 -p oi nt re d ucti o n i n I G A
sc ore at Wee k 6 c o m pare d t o
baseli ne.
•
A ≥2 -p oi nt re d ucti o n i n
er yt he ma sc ore b at Wee k 6
c o m pare d t o baseli ne.
•
Er yt he ma sc ore at Wee k 6.
•
T otal s ki n disease acti vit y sc ore
(s u m of sc ores f or er yt he ma,
scali n g/ h y per kerat osis, a n d
oe de ma/i nfiltrati o n) b at Wee k 6.
a) T he I G A is a n i nstr u me nt use d i n t his cli nical trial t o rate t he se verit y of t he s u bject's
D L E  tar get lesi o ns o n a 5-p oi nt scale ra n gi n g fr o m 0 (clear) t o 4 (se vere).
b) T he disease acti vit y sc or es are base d o n t he C uta ne o us L u p us Er yt he mat os us
Disease Area a n d Se verit y I n de x ( C L A SI) a n d t he Re vise d C L A SI ( R C L A SI) w hic h
are vali date d sc ori n g s yste ms t o  assess disease acti vit y a n d da ma ge i n patie nts wit h
c uta ne o us l u p us er y t he mat os us.
A b bre vi ati o n:  A E = a d verse e ve nt .


Trial I D: E X P -1 3 7 3  
Date: 2 2 -Oct -2 0 1 9  
Versi o n: 4. 0  
Pa ge 1 4  of 1 2 2  
 
 
 
 
 
Fi nal c ollecti o n of 
data f or t he 
pri mar y e n d p oi nt  
Wee k 6.  
Trial desi g n  
T his is a p hase 2a m ulti -ce ntre, d o u ble -bli n d, ra n d o mise d, wit hi n -s u bject, 
ve hicle -c o ntr olle d trial. Eac h s u bject m ust ha ve at least 2 acti ve D L E tar get 
lesi o ns of at least m o derate se verit y. T he tar get lesi o ns will be ra n d o mise d 1: 1 
t o treat me nt wit h del gociti ni b crea m 2 0 m g/ g or ve hicle t wice dail y f or 6 
wee ks.  
 
T he trial c o nsists of a scree ni n g peri o d, a treat me nt peri o d, a n d a f oll o w -u p 
peri o d.  
 
Scree ni n g peri o d  
T he scree ni n g peri o d has a d urati o n of u p t o 4 wee ks. At t he scree ni n g visit, t he 
s u bjects’ eli gi bilit y t o e nter t he trial will be c hec ke d. F or eac h s u bject, 
2 p ote ntial D L E tar get lesi o ns will be i de ntifie d a n d e val uate d. Bl o o d a n d uri ne 
sa m ples will be ta ke n f or safet y la b orat or y a nal ysis, a n d a n electr ocar di o gra m 
( E C G) will be rec or de d. F urt her m ore, t he s u bjects will be as ke d t o fill o ut t he 
Der mat ol o g y Life Q ualit y I n de x ( D L QI).  
Treat me nt peri o d  
At baseli ne ( Da y 1), t he eli gi bilit y of t he s u bjects a n d t heir tar get lesi o ns will 
be c o nfir me d. F or eli gi ble s u bjects, t he 2 tar get lesi o ns will be ra n d o mise d 1: 1 
t o treat me nt wit h del g ociti ni b crea m or ve hicle.  
T he first a p plicati o n of t he i n vesti gati o nal me dici nal pr o d ucts (I M Ps) will 
occ ur at baseli ne at t he trial site. T he s u bse q ue nt I M P a p plicati o ns will be 
perf or me d b y t he s u bjects at h o me t wice dail y f or 6 wee ks. D uri n g t he 
treat me nt peri o d, t he s u bjects will be re q uire d t o ret ur n t o t he trial site f or visits 
sc he d ule d at Wee ks 2, 4, a n d 6. T he last I M P a p plicati o ns will occ ur t he 
e ve ni n g bef ore t he s u bjects atte n d t he visit sc he d ule d at Wee k 6.  
Safet y f oll o w -u p peri o d  
All s u bjects will atte n d a safet y f oll o w -u p visit 2 wee ks after t he last I M P 
a pplicati o ns.  
 


Trial I D: E X P -1 3 7 3  
Date: 2 2 -Oct -2 0 1 9  
Versi o n: 4. 0  
Pa ge 1 5  of 1 2 2  
 
 
 
 
 
Mai n assess me nts  
I n vesti gat or efficac y assess me nts: 
•  I G A of eac h tar get lesi o n. 
•  S ki n lesi o n acti vit y a n d da ma ge sc ores: er yt he ma, scali n g/ h y per kerat osis, 
oe de ma/i nfiltrati o n, d ys pi g me ntati o n, scarri n g/atr o p h y ( base d o n  
c o m p o ne nts of t he C L A SI a n d  R C L A SI) f or eac h tar get lesi o n.  
S u bject assess me nts of efficac y a n d healt h -relate d q ualit y of life: 
Patie nt’s Gl o bal Assess me nt ( Pa G A) of se verit y of eac h tar get lesi o n.  
Safet y assess me nts:  
Vital si g ns, p h ysical e xa mi nati o n, safet y la b orat or y tests, a n d a d verse e ve nt 
re p orti n g. 
Mai n criteria f or 
i ncl usi o n 
•  
A ge 1 8 -7 0 years.  
•  
Hist o pat h ol o gical  fi n di n gs (c urre nt or pre vi o us) c o nsiste nt wit h cli nical 
dia g n osis of D L E.  
•  
U ne q ui v ocal cli nical dia g n osis of 2 acti ve D L E tar get lesi o ns t hat are 
< 6 m o nt hs ol d a n d a me na ble f or cli nical e val uati o n. T his i ncl u des 
lesi o ns l ocate d o n t he scal p if t he y f ulfil all lesi o n-s pecific eli gi bilit y 
criteria.  
•  
Tar get lesi o n I G A sc ore of at least m o derate se verit y ( ≥3) at scree ni n g 
a n d baseli ne.  
•  
Tar get lesi o n er yt he m a sc ore ≥2 at scree ni n g a n d baseli ne.  
Mai n criteria f or 
e xcl usi o n  
•  
Tar get lesi o n d ys pi g me ntati o n sc ore of 2 at scree ni n g or baseli ne.  
•  
Tar get lesi o n scarri n g/atr o p h y sc ore of 2 at scree ni n g or baseli ne.  
•  
Tar get lesi o n scarri n g al o pecia sc ore of > 0 i n scal p lesi o ns at scree ni n g 
or baseli ne.  
•  
Me dical hist or y of s yste mic l u p us er yt he mat os us ( S L E) wit h cli nicall y 
si g nifica nt or ga n i n v ol ve me nt ( A merica n C olle ge of R he u mat ol o g y 
S L E classificati o n criteria n o. 6  t o 9) i ncl u di n g S L E -relate d ple uritis or 
pericar ditis ( b y cli nical e v al uati o n a n d  electr ocar di o gra m ), a n d 
ne ur ol o gic, re nal, a n d/ or ot her maj or S L E -relate d or ga n s yste m 
i n v ol ve me nt. S L E j oi nt i n v ol ve me nt is acce pta ble. 
•  
S u bjects wit h u nsta ble or si g nifica nt S L E disease acti vit y fi n di n gs t hat 
w o ul d, b y its pr o gr essi ve nat ure a n d/ or se verit y, i nterfere wit h t he trial 
e val uati o n, c o m pleti o n, a n d/ or pr oce d ures per t he i n vesti gat or's 
discreti o n.  
•  
Ot her s ki n c o n diti o ns at scree ni n g or baseli ne t hat w o ul d i nterfere wit h 
t he e val uati o n of D L E. 
•  
I m m u n os u p pressi ve/i m m u n o m o dulati n g t hera p y wit h e. g. 
met h otre xate, c ycl os p ori ne, azat hi o pri ne, reti n oi ds ( b ot h t o pical a n d 
s yste mic), or da ps o ne wit hi n 4 wee ks pri or t o baseli ne. 
•  
S yste mic pre d nis ol o ne > 7. 5 m g/ da y or c ha n ge d d ose wit hi n 4 wee ks 
pri or t o baseli ne ( nasal a n d i n hale d c ortic oster oi ds are all o we d).  
•  
Treat me nt wit h t he f oll o wi n g me dicati o ns:  
•  
Oral a nti malarial treat me nt wit h h y dr o x yc hl or o q ui ne > 6. 5  m g/ k g 
b o d y wei g ht/ da y, or c hl or o q ui ne > 4 m g/ k g b o d y wei g ht/ da y, or 
c ha n ge d d ose wit hi n 1 2 wee ks pri or t o baseli ne.  


Trial I D: E X P -1 3 7 3  
Date: 2 2 -Oct -2 0 1 9  
Versi o n: 4 . 0 
Pa ge 1 6  of 1 2 2  
 
 
 
 
 
•  
Q ui nacri ne c o m bi ne d wit h eit her h y dr o x yc hl or o q ui ne or 
c hl or o q ui ne wit hi n 1 2 wee ks pri or t o baseli ne.  
•  
Dr u gs k n o w n t o i nteract wit h a nti malarials (e. g. di g o xi n, 
ci meti di ne) wit hi n 1 2 wee ks pri or t o baseli ne.  
•  
Treat me nt wit h t o pical c ortic oster oi ds, calci ne ur i n i n hi bit ors, a n d 
p h os p h o diesterase -4 ( P D E -4) i n hi bit ors wit hi n 2 wee ks pri or t o 
baseli ne.  
•  
Use of s yste mic a nti bi otics or c uta ne o usl y a p plie d a nti bi otics o n t he 
tar get lesi o ns wit hi n 2 wee ks pri or t o baseli ne. 
•  
Ultra vi olet ( U V) t hera p y wit hi n 2 wee ks pri or  t o baseli ne. 
•  
A n y pr oce d ure i m pairi n g t he s ki n barrier (e. g. i ncisi o n) wit hi n 2 c m 
fr o m t he b or der of a n y of t he tar get lesi o ns wit hi n 4 wee ks pri or t o 
baseli ne.  
•  
Recei pt of li ve (atte n uate d) vacci nes wit hi n 4 wee ks pri or t o baseli ne.  
•  
Treat me nt wit h a n y mar kete d bi ol o gical t hera p y or i n vesti gati o nal 
bi ol o gic a ge nts:  
•  
A n y cell -de pleti n g a ge nts i ncl u di n g b ut n ot li mite d t o rit u xi ma b: 
wit hi n 6 m o nt hs pri or t o baseli ne, or u ntil l y m p h oc yte c o u nt ret ur ns 
t o n or mal, w hic he ver is l o n ger. 
•  
Ot her bi ol o gics: wit hi n 3 m o nt hs or 5 half -li ves, w hic he ver is 
l o n ger, pri or t o baseli ne.  
•  
U nsta ble or fl uct uati n g use of t o bacc o wit hi n 1 m o nt h pri or t o 
scree ni n g w hic h, i n t he o pi ni o n of t he i n vesti gat or, ma y affect t he 
nat ural c o urse of t he disease a n d t h us affect t he e val uati o n of t he 
treat me nt. 
•  
Hist or y of a n y acti ve s ki n i nfecti o n wit hi n 1 wee k pri or t o baseli ne.  
•  
Cli nicall y si g nifica nt i nfecti o n wit hi n 4 wee ks pri or t o baseli ne w hic h, 
i n t he o pi ni o n of t he i n vesti gat or, ma y c o m pr o mise t he safet y of t he 
s u bject i n t he trial, i nterfere wit h e val uati o n of t he I M P, or re d uce t he 
s u bject’s a bilit y t o partici pate i n t he trial. Cli nicall y si g nifica nt 
i nfecti o ns are defi ne d as: 
•  
A s yste mic i nfecti o n.  
•  
A seri o us s ki n i nfecti o n re q uiri n g pare nteral (i ntra ve n o us or 
intra m usc ular) a nti bi otics, a nti viral, or a ntif u n gal me dicati o n.  
•  
T u berc ul osis re q uiri n g treat me nt wit hi n 1 2 m o nt hs pri or t o scree ni n g 
a n d/ or s u bjects wit h a p ositi ve bl o o d test f or t u berc ul osis at scree ni n g. 
S u bjects wit h hi g h ris k of late nt t u berc ul osis (e . g. pri or resi de nce i n or 
tra vel t o c o u ntries wit h hi g h pre vale nce of t u berc ul osis, cl ose c o ntact 
wit h a pers o n wit h acti ve t u berc ul osis, or a hist or y of acti ve or late nt 
t u berc ul osis w here a n a de q uate c o urse of treat me nt ca n n ot be 
c o nfir me d) m ust be teste d at scree ni n g.   
I n vesti gati o nal 
me dici nal 
pr o d ucts  
•  
Na me of I M P: del g ociti ni b crea m.  
•  
Acti ve s u bsta nce: del g ociti ni b.  
•  
F or m ulati o n: crea m.  
•  
F or m ulati o n stre n gt h: 2 0 m g/ g a n d ve hicle.  
•  
D ose a n d met h o d of a d mi nistrati o n: t o pical a p plicati o n t wice dail y.  


Trial I D: E X P -1 3 7 3  
Date: 2 2 -Oct -2 0 1 9  
Versi o n: 4. 0  
Pa ge 1 7  of 1 2 2  
 
 
 
 
 
 
D urati o n of 
treat me nt 
6 wee ks.  
N u m ber of 
s u bjects 
T his trial ai ms t o ha ve 3 6 s u bjects e val ua ble f or t he pri mar y e n d p oi nt. 
Ass u mi n g a dr o p -o ut rate of 2 0 %, a p pr o xi matel y 4 5 s u bjects will be 
ra n d o mise d t o ac hie ve t his.  
N u m ber a n d 
distri b uti o n of 
trial sites 
A p pr o xi matel y 2 0 sites i n se veral c o u ntries i n t he E U a n d/ or U nite d States.  
Statistical 
met h o ds  
Pri mar y e n d p oi nt:  
T he efficac y of del g ociti ni b crea m c o m pare d wit h ve hicle will be a nal yse d i n a 
wit hi n -s u bject c o m paris o n of lesi o n-s pecific treat me nt s uccess ( defi ne d as a n 
I G A sc ore of 0 or 1 at Wee k 6) usi n g Mc Ne mar’s test. 
Sec o n dar y e n d p oi nts:  
Wit hi n -s u bject c o m paris o ns of t he n u m bers of A Es, s u bjects wit h A Es, a n d 
treat me nt-relate d, lesi o n-s pecific A Es will be d o ne b y  treat me nt usi n g a 
Wilc o x o n si g ne d ra n k test.  
Wit hi n -s u bject c o m paris o ns of lesi o n-s pecific bi nar y e n d p oi nts t o assess 
treat me nt differe nce at W ee k 6 will be d o ne b y Mc Ne mar’s test.   
Wit hi n -s u bject c o m paris o ns of lesi o n-s pecific disease acti vit y sc ores t o assess 
treat me nt differe nce at W ee k 6 will be d o ne b y a Wilc o x o n si g ne d ra n k test.   
T he a nal ysis of t he pri mar y a n d sec o n dar y e n d p oi nts will be perf or me d o n t he 
per pr ot oc ol a nal ysis set a n d re peate d f or t he f ull a nal ysis set as a se nsiti vit y 
a nal ysis. 
Si g nat or y 
i n vesti gat or 
Mar gitta W or m,  U ni v. Pr of. Dr. Me d.  
De part me nt of Der mat ol o g y, Ve ner eol o g y a n d Aller g ol o g y, Ca m p us C harité 
Mitte, Berli n, Ger ma n y  
S p o ns or  
L E O P har ma A/ S, I n d ustri par ke n 5 5, D K -2 7 5 0 Baller u p, De n mar k.  


Trial I D: E X P -1 3 7 3  
Date: 2 2 -Oct -2 0 1 9  
Versi o n: 4. 0  
Pa ge 1 8  of 1 2 2  
 
 
 
 
 
2  Tri al i de ntific ati o n  
E u dra C T n u m ber: 2 0 1 8- 0 0 3 6 1 5- 2 2. 
T he cli nical trial pr ot oc ol will be re gistere d i n l ocal re gistries if re q uire d b y l ocal le gislati o n.  
3  Sc he m atic of tri al desi g n  
P a nel 1 : Tri al desi g n 
 
 


Trial I D: E X P -1 3 7 3  
Date: 2 2 -Oct -2 0 1 9  
Versi o n: 4. 0  
Pa ge 1 9  of 1 2 2  
 
 
 
 
4  Sc he d ule of tri al pr oce d ures  
P a nel 2 : Sc he d ule of tri al pr oce d ures 
 
Scree ni n g a 
Tre at me nt 
F oll o w-
u p  
U ns. visit 
(if 
a p plic a ble)  
E arl y ter m. 
(if 
a p plic a ble) c 
Pri m ar y 
e n d p oi nt 
visit (if 
a p plic a ble) d  
Refere nces 
( pr ot oc ol 
secti o n) 
Visit  
1 
2 
3 
4 
5 
6 
D a y/ Wee k 
D a y - 2 8 
t o - 7 
D a y 1  
Wee k 2  
Wee k 4  
Wee k 6  
Wee k 8  
- 
- 
Wee k 6  
Visit wi n d o w ( d a ys) b  
-2 8 t o - 7 
N A  
± 3  
± 3  
± 3  
± 3  
- 
- 
± 3  
Tri al p o p ul ati o n a n d eli gi bilit y  
I nf or me d c o nse nt(s)e 
X 
 
 
 
 
 
 
 
 
A p pe n di x 3 B  
S u bject eli gi bilit y  
X 
X 
 
 
 
 
 
 
 
8. 2 , 8. 3  
I M P a n d r a n d o mis ati o n 
Ra n d o misati o n 
 
X 
 
 
 
 
 
 
 
9. 3  
I nstr ucti o n of I M P a p plicati o n 
 
X 
 
 
 
 
 
 
 
9. 2  
Dis pe nsi n g of I M P  
 
X 
X 
X 
 
 
X 
 
 
9. 2  
Treat me nt c o m plia nce  
 
 
X 
X 
X 
 
 
X 
 
9. 8. 3  
Ret ur n of I M P  
 
 
X 
X 
X 
 
 
X 
 
9. 8. 3  
C o nc o mita nt me dicati o n  
X 
X 
X 
X 
X 
X 
X 
X 
X 
9. 4 , 9. 6 , 9. 7  
C o nc urre nt pr oce d ures  
X 
X 
X 
X 
X 
X 
X 
X 
X 
9. 6  
I n vesti g at or assess me nts at scree ni n g/ b aseli ne o nl y 
De m o gra p hics   
X 
 
 
 
 
 
 
 
 
1 1. 2. 1  
Fitz patric k s ki n t y pe  
X 
 
 
 
 
 
 
 
 
1 1. 2. 2  
Me dical hist or y
f 
X 
X 
 
 
 
 
 
 
 
1 1. 2. 3  
Hei g ht a n d wei g ht  
X 
 
 
 
 
 
 
 
 
1 1. 2. 4  


Trial I D: E X P -1 3 7 3  
Date: 2 2 -Oct -2 0 1 9  
Versi o n: 4. 0  
Pa ge 2 0  of 1 2 2  
 
 
 
 
 
Scree ni n g a 
Tre at me nt 
F oll o w-
u p  
U ns. visit 
(if 
a p plic a ble)  
E arl y ter m. 
(if 
a p plic a ble) c 
Pri m ar y 
e n d p oi nt 
visit (if 
a p plic a ble) d  
Refere nces 
( pr ot oc ol 
secti o n) 
Visit  
1 
2 
3 
4 
5 
6 
D a y/ Wee k 
D a y - 2 8 
t o - 7 
D a y 1  
Wee k 2  
Wee k 4  
Wee k 6  
Wee k 8  
- 
- 
Wee k 6  
Visit wi n d o w ( d a ys) b  
-2 8 t o - 7 
N A  
± 3  
± 3  
± 3  
± 3  
- 
- 
± 3  
Classificati o n of S L E ( A C R 
e n d orse d criteria, 1 9 9 7)  
X 
 
 
 
 
 
 
 
 
1 1. 2. 5  
C L A SI a n d R C L A SI g 
X 
( X) 
 
 
 
 
 
 
 
1 1. 2. 6 , 1 1. 2. 7  
I de ntificati o n of tar get lesi o nsh 
X 
X 
 
 
 
 
 
 
 
1 1. 2. 8  
S u bject assess m e nts of effic ac y a n d he alt h -rel ate d q u alit y of life  
D L QI  
 
X 
 
 
 
 
 
 
 
1 1. 6. 1. 2  
Pa G A  
X 
X 
X 
X 
X 
X 
 
X 
 
1 1. 6. 1. 1  
I n vesti g at or assess me nts of effic ac y i 
I G A 
X 
X 
X 
X 
X 
X 
 
X 
X 
1 1. 3. 1  
S ki n lesi o n acti vit y (er yt he ma, 
scali n g/ h y per kerat osis, 
oe de ma/i nfiltrati o n)  
X 
X 
X 
X 
X 
X 
 
X 
 
1 1. 3. 2   
S ki n lesi o n da ma ge 
( d ys pi g me ntati o n, scarri n g/atr o p h y) 
X 
X 
X 
X 
X 
X 
 
X 
 
1 1. 3. 3  
I n vesti g at or assess me nts of s afet y 
Vi tal si g ns ( bl o o d press ure, 
peri p heral p ulse, b o d y te m perat ure)  
X 
X 
 
 
X 
 
X 
X 
 
1 1. 4. 1  
P h ysical e xa mi nati o n  
X 
 
 
 
X 
 
X 
X 
 
1 1. 4. 2  
E C G 
X 
 
 
 
 
 
X 
 
 
1 1. 4. 3  
Ser ol o g y (ce ntral la b orat or y)  
X 
 
 
 
 
 
 
 
 
1 1. 4. 4  


Trial I D: E X P -1 3 7 3  
Date: 2 2 -Oct -2 0 1 9  
Versi o n: 4. 0  
Pa ge 2 1  of 1 2 2  
 
 
 
 
 
Scree ni n g a 
Tre at me nt 
F oll o w-
u p  
U ns. visit 
(if 
a p plic a ble)  
E arl y ter m. 
(if 
a p plic a ble) c 
Pri m ar y 
e n d p oi nt 
visit (if 
a p plic a ble) d  
Refere nces 
( pr ot oc ol 
secti o n) 
Visit  
1 
2 
3 
4 
5 
6 
D a y/ Wee k 
D a y - 2 8 
t o - 7 
D a y 1  
Wee k 2  
Wee k 4  
Wee k 6  
Wee k 8  
- 
- 
Wee k 6  
Visit wi n d o w ( d a ys) b  
-2 8 t o - 7 
N A  
± 3  
± 3  
± 3  
± 3  
- 
- 
± 3  
C he mistr y, hae mat ol o g y (ce ntral 
la b orat or y) 
X 
X 
 
 
X 
 
X 
X 
 
1 1. 4. 4  
Uri nal ysis (ce ntral la b orat or y)  
X j 
X 
 
 
X 
 
X 
X 
 
1 1. 4. 4  
Uri ne pre g na nc y test  
X 
X 
 
X 
X 
X 
X 
X 
 
1 1. 4. 4  
A d verse e ve nts  
X 
X 
X 
X 
X 
X 
X 
X 
X 
1 3  
Ot her assess me nts  
Size of tar get lesi o ns  
X 
X 
 
 
X 
 
 
X  
 
1 1. 6. 2  
N o n -i n vasi ve s ki n sa m pli n g ( patc h)k 
 
X 
X 
X 
X 
 
 
X  
 
1 1. 5. 2  
S ki n bi o psies ( o pti o nal) l 
 
 
 
 
X m  
 
 
X m, n  
 
1 1. 5. 3  
C hec k of bi o ps y w o u n d heali n g o 
 
 
 
 
 
X 
 
 
 
1 1. 5. 3  
E xit i nter vie ws l, p 
 
 
 
 
X 
 
X 
 
1 1. 6. 1. 3  
P h ot o gra p h y l 
X 
X 
X 
X 
X m 
X 
 
X m 
 
1 1. 6. 3  
E n d of trial f or m q 
 
 
 
 
 
X 
 
X 
X 
1 1. 8  
a) S u bjects t hat fail t o meet all eli gi bilit y criteria at scree ni n g ma y be re -assesse d f or eli gi bilit y at a later sta ge u n der certai n circ u msta nces (see Secti o n 8. 4 ). F or 
t hese s u bjects, re-assess me nt of eli gi bilit y will be perf or me d at a n a d diti o nal scree ni n g  visit  pri or t o baseli ne ( Da y 1).  
b)  If t he date of a trial visit d oes n ot c o nf or m t o t he cli nical trial pr ot oc ol, s u bse q ue nt visits s h o ul d be pla n ne d t o mai ntai n t he visit sc he d ule relati ve t o baseli ne.  
c) S u bjects w h o disc o nti n ue I M P or wit h dra w fr o m t he trial will be as ke d t o ret ur n t o t he trial site f or a n earl y ter mi nati o n visit as s o o n as p ossi ble after last I M P 
a p plicati o n (see Secti o n  1 0 ). T he y will als o be as ke d t o ret ur n at Wee k 6 f or a pri mar y e n d p oi nt visit (see f o ot n ote d) . I n ad diti o n, all s u bjects will ha ve a fi nal 
safet y f oll o w-u p visit 2  wee ks after last a p plicati o n  of I M P.  


Trial I D: E X P -1 3 7 3  
Date: 2 2 -Oct -2 0 1 9  
Versi o n: 4. 0  
Pa ge 2 2  of 1 2 2  
 
 
 
 
d)  T he pri mar y e n d p oi nt visit is a p plica ble t o s u bjects w h o disc o nti n ue I M P pri or t o Wee k 6. T he visit s h o ul d be sc he d ule d 6 wee ks after t he fi rst a p plicati on of 
I M P. 
e) T he i nf or me d c o nse nt f or m(s) m ust be si g ne d pri or t o perf or mi n g a n y pr ot oc ol -relate d pr oce d ures, i ncl u di n g b ut n ot li mite d t o scree ni n g e val uati o ns a n d 
was h -o ut of disall o we d me dicati o ns.  
f) 
Me dical hist or y is t o be rec or de d at scree ni n g.  At baseli n e ( Da y 1), me dical hist or y f or t he selecte d tar get lesi o ns is t o be re vie we d a n d u p date d, if nee de d (see 
Secti o n  1 1. 2. 3 ).  
g)  A f ull, gl o bal C L A SI/ R C L A SI assess me nt will be d o ne at scree ni n g. I n a d diti o n, if a n y of t he ( p ote ntial) tar get lesi o ns are l ocate d i n t he scal p, scarri n g 
al o pecia will be sc ore d f or eac h scal p ( p ote ntial) tar get lesi o n at scree ni n g a n d baseli ne t o e val uate e xcl usi o n criteri o n n o. 3 . 
h)  At scree ni n g, 2 p ote ntial tar get lesi o ns will be i de ntifie d a n d e val uate d. At baseli ne  ( Da y 1), t he eli gi bilit y of t he tar get lesi o ns will be c o nfir me d pri or t o 
ra n d o misati o n. I n t he u nli kel y e ve nt t hat 1 or b ot h lesi o ns are n o l o n ger eli gi ble at baseli ne, t he i n vesti gat or is all o we d t o select ne w tar get lesi o ns if a vaila ble 
(see Secti o n 1 1. 2. 8 ). 
i) 
I n vesti gat or assess me nts of efficac y m ust be d o ne pri or t o or at least 2 h o urs after a p plicati o n of I M P. 
j) 
I n a d diti o n, t he uri ne sa m ple will be teste d f or pr otei n uria wit h a uri ne di pstic k at scree ni n g (see Secti o n 1 1. 4. 4 ). 
k)  N o n -i n vasi ve s ki n sa m pli n g m ust be d o ne pri or t o or at least 4 h o urs after a p plicati o n of I M P. 
l) 
T his pr oce d ure is o pti o nal a n d re q uires t hat t he s u bject pr o vi des a d diti o nal i nf or me d c o nse nt.  
m)  F or s u bjects w h o c o nse nt t o t he s ki n bi o ps y a n d p h ot o gra p h y c o m p o ne nts, p h ot o gra p hs s h o ul d prefera bl y be ta ke n b ot h bef ore a n d after ta ki n g t he bi o ps y at 
Wee k 6 or earl y ter mi nati o n.  
n)  Bi o psies will o nl y be ta ke n at t he earl y ter mi nati o n visit if t he s u bject recei ve d treat me nt wit h t he I M Ps at least u ntil t he  Wee k 2 visit.  
o)  O nl y a p plica ble t o s u bjects w h o pr o vi d e d s ki n bi o psies at Wee k 6 or earl y ter mi nati o n.  
p)  E xit i nter vie ws will o nl y be c o n d ucte d i n selecte d c o u ntries.  
q)  A n e n d of trial f or m m ust be c o m plete d i n t he e C R F f or all ra n d o mise d s u bjects at t heir last visit (t he earl y ter mi nati o n visit, t he safet y f oll o w- u p visit, or t he 
pri mar y e n d p oi nt visit at Wee k 6, w hic he ver c o mes last).  See Secti o n  1 1. 8  f or f urt her details. 
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; C L A SI = C uta ne o us L u p us Er yt he mat os us Disease Area a n d Se verit y I n de x;  D L QI = Der mat ol o g y  
Life Q ualit y I n de x;  E C G = electr ocar di o gra m; I G A = I n vesti gat or’s  Gl o bal Assess me nt; I M P = i n vesti gati o nal me dici nal pr o d uct;  Pa G A = Patie nt’s Gl o bal 
Assess me nt; R C L A SI = Re vise d C uta ne o us L u p us Er yt he mat os us Disease Area a n d Se verit y I n de x; S L E = s yste mic l u p us er yt he mat os u s; ter m. = ter mi nati o n; 
u ns.  = u nsc he d ule d.  
 


Trial I D: E X P -1 3 7 3  
Date: 2 2 -Oct -2 0 1 9  
Versi o n: 4. 0  
Pa ge 2 3  of 1 2 2  
 
 
 
 
 
5  I ntr o d ucti o n a n d tri al r ati o n ale 
5. 1  Disc oi d l u p us er yt he m at os us  
Disc oi d l u p us er yt he mat os us ( D L E ) is a n a ut oi m m u ne disease affecti n g t he s ki n wit h 
er yt he mat o us, scal y, well -de marcate d  lesi o ns. O ver ti me, t hese lesi o ns ca n ca use scarri n g, 
atr o p h y, d ys pi g me ntati o n, a n d hair l oss, res ulti n g i n si g nifica nt disfi g ure me nt. D L E lesi o ns 
ge nerall y ra n ge i n size fr o m a fe w m m t o 1 5 c m i n dia meter a n d are pri maril y f o u n d i n 
ultra vi olet ( U V )-e x p ose d areas s uc h as t he hea d a n d nec k, a n d t o a lesser e xte nt o n t he tr u n k 
a n d e xtre mities (1 ). T he p h ysical a p peara nce affects t he q ualit y of life i n D L E patie nts a n d is 
ass ociate d wit h i ncrease d ris k of de pressi o n a n d u ne m pl o y me nt (2 ).  
D L E is o ne of t he ma nifes tati o ns of l u p us er yt he mat os us ( L E) w hic h c o vers differe nt disease 
t y pes ra n gi n g fr o m c uta ne o us t o s yste mic i n v ol ve me nt. I n s yste mic L E ( S L E), m ulti ple 
or ga ns i ncl u di n g t he heart, ki d ne ys, s ki n, a n d j oi nts ma y be i n v ol ve d. C uta ne o us L E ( C L E) 
ca n be eit her ac ute, s u bac ute, or c hr o nic, a n d D L E is t he m ost c o m m o n f or m of c hr o nic C L E, 
re prese nti n g 8 0 % of all cases (2 ). T he C L E disease t y pes prese nt wit h differe nt cli nical, 
hist ol o gical, a n d ser ol o gical feat ures, a n d differe nt pr o g n oses (3 ).  
T he pre vale nce of C L E was esti mate d t o  7 3/ 1 0 0. 0 0 0 i n a n A merica n st u d y wit h a 
pre d o mi natel y w hite p o p ulati o n ( 4 ). H o we ver, ot her st u dies ha ve s h o w n t hat D L E is m ore 
c o m m o n i n pe o ple wit h blac k s ki n (2 , 5 ). D L E has a fe male pre d o mi na nce a n d a pea k a ge of 
o nset i n t he f o urt h deca de i n w o me n a n d sli g htl y later i n me n ( 6 ). D L E is cate g orise d as eit her 
l ocalise d ( o nl y lesi o ns a b o ve t he nec k) or ge neralise d (lesi o ns b ot h a b o ve a n d bel o w t he 
nec k), of w hic h t he l ocalise d f or m is far m ore c o m m o n (7 ). Patie nts wit h ge neralise d D L E are 
m ore li kel y t o de vel o p S L E t ha n patie nts wit h l ocalise d D L E ( 8 ). I n a S we dis h c o h ort st u d y, 
t he pr o ba bilit y f or D L E patie nts t o s u bse q ue ntl y de vel o p S L E was 1 6. 7 % after 3 years (9 ). 
C o n versel y, D L E de vel o ps d uri n g t he c o urse of S L E i n 1 5- 3 0 % of S L E patie nts (1 0 ). D L E 
mi g ht pr o gress t o S L E m ore c o m m o nl y i n c hil dre n t ha n i n a d ults ( 1 1 ). 
T he disease mec ha nis m of D L E i n v ol ves da ma ge of t he kerati n oc ytes i n d uce d b y U V s u n 
li g ht a n d t he s u bse q ue nt ge nerati o n of a ut oa nti ge ns. T his i n d uces a n i nfla m mat or y res p o nse 
res ulti n g i n c haracteristic hist ol o gical feat ures (1 2 - 1 4). T he earl y i nfla m mat or y me diat ors 
i ncl u de t u m o ur necr osis fact or al p ha ( T N F-α) a n d i nterle u ki n (I L) - 1β w hic h attract s ki n -
h o mi n g T cells a n d plas ma c yt oi d de n dritic cells (1 2 , 1 3 ). E x p os ure t o t he a ut oa nti ge ns 
sti m ulates t he pr o d ucti o n of i nterfer o n al p ha (I FN- α) a n d i nterfer o n ga m ma (I F N -γ) a n d 
f urt her i nfiltrati o n a n d acti vati o n of T hel per ( T h 1) cells, w hic h i n t ur n acti vates t he ja n us 
ki nase (J A K)/si g nal tra ns d ucer a n d acti vat or of tra nscri pti o n ( S T A T) si g nalli n g pat h wa ys (1 5-
1 7 ). T he lesi o nal tiss ue s h o ws ele vate d le vels of I F N-γ a n d c he m o ki nes i ncl u di n g c he m o ki ne 


Trial I D: E X P -1 3 7 3  
Date: 2 2 -Oct -2 0 1 9  
Versi o n: 4. 0  
Pa ge 2 4  of 1 2 2  
 
 
 
 
 
( C- X- C m otif) li ga n d ( C X C L) 9, C X C L 1 0, a n d C X C L 1 1, a n d a n i ncrease d n u m ber of 
a ut oreacti ve c yt ot o xic cl uster of differe ntiati o n 8 ( C D 8) p ositi v e T cells (1 2 , 1 5 , 1 6 ). I n 
s u m mar y, t he i nfla m mat or y disease pr ofile i n dicates t hat t he J A K/ S T A T pat h wa y is ce ntral f or 
t he D L E disease mec ha nis m a n d ma y be a n i m p orta nt t hera pe utic tar get (1 8 ). 
T here is c urre ntl y n o c ure f or D L E, a n d n o treat me nts ha ve bee n a p pr o ve d f or t his i n dicati o n. 
T he c urre nt sta n dar d - of-care treat me nts are use d off -la bel a n d ha ve li mite d effect. First-li ne 
treat me nt rec o m me n dati o ns i ncl u de s u n a v oi da nce, U V pr otecti o n, a n d p ote nt t o pical 
c ortic oster oi ds. To pical calci ne uri n i n hi bit ors are als o use d. I n se vere or wi des prea d disease, 
s yste mic a nti malarials are rec o m me n de d (1 9 ).   
5. 2  E x perie nce wit h i n vesti g ati o n al me dici n al pr o d uct  
T he i n vesti gati o nal me dici nal pr o d uct (I M P) i n t his trial is del g ociti ni b crea m.  
Del g ociti ni b (rece ntl y assi g ne d as t he i nter nati o nal n o n - pr o prietar y na me [I N N] f or 
L E O  1 2 4 2 4 9) is a pa n-J A K in hi bit or. Del g ociti ni b bl oc ks se veral c yt o ki ne- me diate d 
si g nalli n g pat h wa ys a n d wi del y s u p presses t he acti vati o n of i m m u ne a n d i nfla m mat or y cells 
s uc h as T cells, B cells, mast cells, a n d m o n oc ytes acti vate d b y t hese c yt o ki nes.  
D L E is a ne w i n dicati o n f or del g ociti ni b, a n d n o n o n- cli nical or cli nical data are a vaila ble 
s pecificall y f or t his i n dicati o n. C urre nt k n o wle d ge is mai nl y deri ve d fr o m cli nical trials wit h 
del g ociti ni b oi nt me nt  i n t he i n dicati o ns at o pic der matitis ( A D) a n d c hr o nic ha n d ecze ma 
( C H E). A c o m pilati o n of n o n-cli nical a n d cli nical data f or del g ociti ni b is gi ve n i n t he c urre nt 
versi o n of t he i n vesti gat or’s br oc h ure.  
 
 
 
 
 
 
  
N o cli nical trials ha ve yet bee n c o m plete d wit h del g ociti ni b crea m. A t otal of 8 cli nical trials 
( 1 wit h del g ociti ni b oral f or m ulati o n a n d 7 wit h del g ociti ni b oi nt me nt) were c o m plete d at t he 
c ut-off date f or t he i n vesti gat or’s br oc h ure ( versi o n 2. 0).  
T he efficac y of del g ociti ni b oi nt me nt was i n vesti gate d i n 6 trials i n differe nt i n dicati o ns ( A D, 
C H E, i n verse ps oriasis, a n d al o pecia areata) a n d was pr o ve n t o be efficaci o us i n A D a n d 
C CI
C CI


Trial I D: E X P -1 3 7 3  
Date: 2 2 -Oct -2 0 1 9  
Versi o n: 4. 0  
Pa ge 2 5  of 1 2 2  
 
 
 
 
 
C H E. Base d o n n o n- cli nical der mal a bs or pti o n st u dies, it is e x pecte d t hat del g ociti ni b crea m 
will als o be efficaci o us i n t hese i n dicati o ns.  
 
 
 
 
 
 
 
5. 3  Tri al r ati o n ale  
T he p ur p ose of t his p hase 2a trial is t o b uil d disease u n dersta n di n g a n d i n vesti gate t he 
efficac y a n d safet y of del g ociti ni b crea m i n t he treat me nt of s u bjects wit h acti ve D L E lesi o ns. 
I n a d diti o n, t he trial will i ncl u de q ualitati ve patie nt i nter vie ws t o e x pl ore t he si g ns, s y m pt o ms, 
a n d i m pact of D L E.    
D L E is a rare disease, a n d t heref ore t he o pti o ns t o test p ote ntial ne w treat me nts are li mite d. To 
date, n o treat me nts ha ve bee n a p pr o ve d f or D L E. T he t o pical a n d s yste mic treat me nts use d i n 
D L E are use d off-la bel a n d are rarel y s u p p orte d b y e vi de nce fr o m ra n d o mise d c o ntr olle d 
trials (1 9 ). T his c o nstit utes a n u n met me dical nee d i n t he treat me nt of D L E.  
Del g ociti ni b bl oc ks b ot h t y pe I a n d t y pe II i nterfer o ns a n d I L- 1 2, all of w hic h are o ver-
e x presse d i n t he s ki n of C L E patie nts a n d e x pecte d t o c o ntri b ute t o t he pat h o ge nesis. 
Scie ntific e vi de nce fr o m h u ma n D L E lesi o ns s u p p orts t hat t he a ut oi nfla m mat or y pr o cess is 
me diate d via T h 1 cells a n d I F N-γ si g nalli n g w hic h acti vate t he J A K/ S T A T si g nalli n g 
pat h wa ys ( 1 2 , 1 7 ). T heref ore, it is e x pecte d t hat treat me nt wit h del g ociti ni b t hr o u g h i n hi biti o n 
of J A K/ S T A T si g nalli n g will bl oc k t he i nfla m mat or y pr ocess a n d t he ass ociate d s ki n si g ns of 
er yt he ma, scali n g, a n d i nfiltrati o n. T his is s u p p orte d b y n o n- cli nical e vi de nce t hat t he  J A K 
i n hi bit or r u x oliti ni b pre ve nte d de vel o p me nt of s ki n lesi o ns i n mice pr o ne t o de vel o p 
s p o nta ne o us C L E a n d S L E (2 0 ). T he treat me nt is n ot e x pecte d t o re verse pre-e xisti n g s ki n 
da ma ge ca use d b y D L E.  
 
 
 
 
 
C CI
C CI


Trial I D: E X P -1 3 7 3  
Date: 2 2 -Oct -2 0 1 9  
Versi o n: 4. 0  
Pa ge 2 6  of 1 2 2  
 
 
 
 
 
 
 
 
 
A s a n e x pl orat or y c o m p o ne nt of t his trial, e xit i nter vie ws will be c o n d ucte d wit h a s u b gr o u p 
of s u bjects t o gai n i nsi g ht i nt o t he patie nt e x perie nce of D L E (si g ns, s y m pt o ms, a n d i m pact 
o n differe nt d o mai ns of healt h -relate d q ualit y of life [ H R Q o L]) a n d t o hel p i nf or m t he 
selecti o n a n d de vel o p me nt of patie nt-re p orte d o utc o mes a n d ot her e n d p oi nts f or f ut ure trials. 
T he s u bjects’ e x perie nces ( p ositi ve a n d ne gati ve) wit h t he I M P a n d t he trial pr oce d ures will 
als o be e x pl ore d.      
5. 4  Et hic al c o nsi der ati o ns  
T his t rial will be c o n d ucte d i n acc or da nce wit h t he et hical pri nci ples t hat ha ve t heir ori gi ns i n 
t he Declarati o n of Helsi n ki a n d t he I nter nati o nal C o u ncil f or Har m o nisati o n (I C H) G o o d 
Cli nical Practice ( G C P) g ui deli nes , a n d i n c o m plia nce wit h t he a p pr o ve d pr ot oc ol a n d 
a p plica ble re g ulat or y re q uire me nts.  
N o c hil dre n, a d olesce nts, or ot her v ul nera ble s u bjects i nca pa ble of gi vi n g i nf or me d c o nse nt 
will be e nr olle d i n t his cli nical trial. F urt her m ore, w o me n w h o are pre g na nt, breastfee di n g, or 
tr yi n g t o bec o me pre g na nt will n ot be e nr olle d i n t his cli nical trial. Wo me n of c hil d beari n g 
p ote ntial m ust a gree t o use a hi g hl y effecti ve met h o d of c o ntrace pti o n t o pre ve nt pre g na nc y 
d uri n g t he cli nical trial. I n a d diti o n, all fe male s u bjects of c hil d beari n g p ote ntial wi ll ha ve a 
pre g na nc y test perf or me d bef ore a n d d uri n g t he trial, a n d at e n d of treat me nt a n d safet y 
f oll o w- u p t o e ns ure t hat n o f oet uses are e x p ose d t o t he I M P. N o c o ntrace pti ve meas ures are 
re q uire d f or male s u bjects e x p ose d t o del g ociti ni b crea m as n o or ne gli gi ble s yste mic 
a bs or pti o n is e x pecte d.   
Eli gi ble s u bjects wit h 2 acti ve D L E lesi o ns (tar get lesi o ns) will be ra n d o mise d t o treat me nt 
wit h del g ociti ni b crea m 2 0 m g/ g a n d ve hicle t o eac h of t he tar get lesi o ns. T h us, all trial 
s u bjects will recei ve active treat me nt o n 1 D L E lesi o n t wice dail y f or 6 wee ks. T his treat me nt 
d urati o n is e x pecte d t o be s ufficie nt t o i n d uce si g nifica nt i m pr o ve me nt i n t he disease acti vit y. 
T he c h oice of a ve hicle c o ntr ol a n d t he wit hi n- s u bject trial desi g n is c o nsi dere d a p pr o priate 
f or a d dressi n g t he o bjecti ves of t his trial. Base d o n e vi de nce fr o m a pre vi o us wit hi n-s u bject 
trial i n a si milar patie nt p o p ulati o n, t here are n o c o ncer ns t hat ve hicle treat me nt of 1  tar get 
lesi o n f or t he d urati o n of t he trial will ca use per ma ne nt s ki n da ma ge fr o m D L E (2 1 ). F or t he 
sa me reas o n, it is als o c o nsi dere d et hicall y j ustifie d t o pr o hi bit ot her t o pical D L E treat me nts 
d uri n g t he treat me nt p hase t o a v oi d acci de ntal use of t hese o n t he tar get lesi o ns. T he 
C CI


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wit hi n -s u bject trial desi g n re d uces t he re q uire d sa m ple size b y eli mi nati n g t he 
bet wee n -s u bject variati o n. Re d uci n g t he re q uire d n u m ber of s u bjects is c o nsi dere d ver y 
i m p orta nt f or recr uit me nt d ue t o t he l o w n u m ber of eli gi ble patie nts wit h t his rare disease.  
D L E lesi o ns ca n ra n ge i n size fr o m fe w m m t o 1 5 c m i n dia meter (i.e. u p t o 1 % of t otal B S A) 
(1 ), b ut t he e x pecte d a vera ge size of D L E lesi o ns is a p pr o xi matel y 2 c m 2 f or n o n-scal p lesi o ns 
a n d 6 c m 2 f or scal p lesi o ns (2 2 ). D ue t o t he s mall treat me nt area, t he ris k of s yste mic 
e x p os ure a n d si de effects i n t his trial is c o nsi dere d ver y l o w. See Secti o n 5. 2  f or f urt her 
i nf or mati o n re gar di n g n o n-cli nical a n d cli nical data f or del g ociti ni b.  
I n acc or da nce wit h t he c urre nt versi o n of t he I C H- G C P g ui deli nes, me dicall y q ualifie d 
pers o n nel e m pl o ye d b y L E O will be rea dil y a vaila ble t o a d vise o n trial- relate d me dical 
q uesti o ns. Me dical m o nit ori n g will be perf or me d t hr o u g h o ut t he trial, a n d safet y data will be 
re vie we d re g ularl y b y me dicall y q ualifie d staff at L E O t o e ns ure t hat pr o m pt acti o n is ta ke n, 
if nee de d, t o ma xi mise patie nt safet y.  
Alt h o u g h safet y meas ures are ta ke n t o miti gate a n y ris k, A Es ma y occ ur.  To e ns ure t he safet y 
a n d well- bei n g of t he s u bjects, A Es will be caref ull y m o nit ore d t hr o u g h o ut t he trial b y  trai ne d 
site staff a n d i n vesti gat ors. M ore o ver, s u bjects will u n der g o p h ysical e xa mi nati o ns a n d safet y 
la b e val uati o ns t o e ns ure t hat t heir o verall healt h is i n acc or da nce wit h t he eli gi bilit y criteria 
of t he trial a n d t o detect a n y A Es. 
D uri n g t he i nf or m e d c o nse nt pr ocess, it will be ma de clear w hic h c o m p o ne nts of t he trial t hat 
are o pti o nal a n d w hat t hese c o m p o ne nts i ncl u de. T his c o ncer ns t he e xit i nter vie ws ( o nl y 
c o n d ucte d i n selecte d c o u ntries), p h ot o gra p h y, a n d s ki n bi o psies. 
5. 5  Be nefit/ris k assess me nt  
Detaile d i nf or mati o n a b o ut k n o w n a n d e x pecte d be nefits a n d ris ks, reas o na bl y e x pecte d A Es, 
c o ntrai n dicati o ns, a n d s pecial war ni n gs ass ociate d wit h del g ociti ni b are s u m marise d i n t he 
i n vesti gat or’s br oc h ure. 
T here is a n u n met me dical nee d f or ne w t o pical tre at me nts f or patie nts wit h D L E, as t here is 
n o a p pr o ve d treat me nt f or t his i n dicati o n, a n d t he c urre nt off-la bel treat me nt o pti o ns ha ve 
ass ociate d li mitati o ns i n ter ms of efficac y a n d/ or safet y. T he p ote ntial be nefit f or t he s u bjects 
partici pati n g i n t his trial is t he p ossi bilit y of recei vi n g a n efficaci o us treat me nt o n 1 acti ve 
D L E lesi o n. T he relati ve i m p orta nce of t his be nefit will de pe n d o n t he e xte nt a n d t otal 
n u m ber of D L E lesi o ns i n t he trial s u bject (t he mea n n u m ber of D L E lesi o ns per s u bject is 


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e x pecte d t o be bet wee n 2. 6 a n d 4. 3 (2 2 , 2 3 )). All s u bjects will u n der g o a t h or o u g h me dical 
c hec k-u p as part of t he trial w hic h ma y als o be see n as a be nefit.  
T he ris k ass ociate d wit h partici pati n g i n t his trial is c o nsi dere d l o w. N o i m p orta nt i de ntifie d 
ris ks ha ve bee n d oc u me nte d d uri n g t he o verall n o n-cli nical a n d cli nical de vel o p me nt of 
del g ociti ni b t o date. Base d o n t his, t he ne w crea m f or m ulati o n is e x pecte d t o be safe a n d well 
t olerate d. I n t his trial, t he ma xi m u m e x pecte d treat me nt area is 1 % of B S A, a n d t he 
rec o m me n de d d ose is 0. 3 g of del g ociti ni b crea m 2 0 m g/g per 1 % B S A. T he treat me nt area 
a n d t he a m o u nt of I M P t o be a p plie d are well bel o w t he ma xi m u m treat me nt area a n d dail y 
d ose of del g ociti ni b a p plie d i n pre vi o us cli nical trials wit h del g ociti ni b oi nt me nt. F or e xa m ple 
i n 1 pre vi o us trial, a mea n B S A of 36 % was treate d wit h 1 0 g of del g ociti ni b oi nt me nt 3 0 
m g/ g per da y. T heref ore, n o s yste mic effects are e x pecte d i n t his trial. Treat me nt wit h 
del g ociti ni b oi nt me nt has ca use d n o se vere A Es i n pre vi o us trials, a n d mil d a n d m o derate 
reacti o ns ha ve res ol ve d after e n d of treat me nt. N o l ocal aller gic reacti o ns are e x pecte d. 
H o we ver, des pite g o o d k n o wle d ge of t he I M P, i ntr o d uci n g a ne w f or m ulati o n i n a ne w 
i n dicati o n ma y ca use yet u n k n o w n A Es. T he ris k t o t he s u bjects will be mi ni mise d b y 
e ns uri n g t hat t he y f ulfil  all eli gi bilit y criteria a n d b y cl ose me dical m o nit ori n g.  
T here is a ris k t hat s o me of t he s u bjects’ D L E lesi o ns will get w orse d uri n g t he trial, as 
1 tar get lesi o n will be treate d wit h ve hicle, a n d t o pical treat me nt of ot her D L E lesi o ns is 
pr o hi bite d d uri n g t he trial. H o we ver, a n y per ma ne nt da ma ge fr o m t his is c o nsi dere d ver y 
u nli kel y i n t his s h ort trial.  
T he safet y of t he s u bjects will be m o nit ore d as descri be d i n Secti o n 1 1. 4 . T he ris ks ass ociate d 
wit h t he i n vasi ve pr oce d ures i n t his trial ( bl o o d sa m pli n g a n d s ki n bi o psies) are c o nsi dere d 
mi ni mal. Bl o o d sa m pli n g is c o nsi dere d a l o w ris k pr oce d ure. S ki n bi o psies are o pti o nal f or 
t he s u bjects. T he size of t he s ki n bi o psies s h o ul d n ot necessitate s ut uri n g, b ut s ut uri n g ca n be 
perf or me d at t he i n vesti gat or’s discreti o n. A c hec k of s ki n bi o ps y w o u n d heali n g i ncl u di n g 
re m o val of s ut ure, if a p plica ble, will be perf or me d at t he f oll o wi n g visit. T he ris k ass ociate d 
wit h a s ki n bi o ps y, i ncl u di n g sec o n dar y i nfecti o n a n d scarri n g, is c o nsi dere d l o w. 
I n c o ncl usi o n, t he c o n d uct of t his trial is c o nsi dere d safe a n d et hicall y j ustifie d. T he 
ass ociate d ris k is l o w a n d o ut wei g he d b y t he be nefit of a p ote ntial f ut ure treat me nt f or D L E, 
w hic h is a rare disease wit h a n u n met nee d f or treat me nt.  
 
 


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6  Tri al o bjecti ves a n d e n d p oi nts  
P a nel 3 : O bjecti ves a n d e n d p oi nts   
O bjecti ves  
E n d p oi nts  
Pri mar y o bjecti ve  
Pri mar y e n d p oi nt  
T o i n vesti gate t he efficac y of del g ociti ni b 
crea m 2 0 m g/ g t wice dail y o n acti ve D L E 
tar get lesi o ns. 
•  
Tar get lesi o ns wit h I n vesti gat or’s Gl o bal 
Assess me nt (I G A) a sc ore of 0 or 1 at 
Wee k  6.  
Sec o n dar y o bjecti ves  
Sec o n dar y e n d p oi nts  
T o e val uate t he safet y of del g ociti ni b crea m 
2 0 m g/ g t wice dail y o n acti ve D L E tar get 
lesi o ns. 
•  
A d verse e ve nts ( n u m ber of A Es a n d n u m ber 
of s u bjects wit h A Es) u p t o Wee k 6.  
•  
N u m ber of lesi o n -s pecific, treat me nt-relate d 
A Es u p t o Wee k 6.  
T o f urt her i n vesti gate t he efficac y of 
del g ociti ni b crea m 2 0 m g/ g t wice dail y o n 
acti ve D L E tar get lesi o ns. 
•  
A ≥2 -p oi nt re d ucti o n i n I G A sc ore at W ee k 6 
c o m pare d t o baseli ne.  
•  
A ≥2 -p oi nt re d ucti o n i n er yt he ma sc ore b at 
Wee k 6 c o m pare d t o baseli ne.  
•  
Er yt he ma sc ore at Wee k 6.  
•  
T otal s ki n disease acti vit y sc ore (s u m of 
sc ores f or er yt he ma, scali n g/ h y per kerat osis, 
a n d oe de ma/i nfiltrati o n) b at Wee k 6. 
E x pl orat or y o bjecti ves  
E x pl orat or y e n d p oi nts  
T o f urt her i n vesti gate t he efficac y of 
del g ociti ni b crea m 2 0 m g/ g t wice dail y o n 
D L E tar get lesi o ns wit h acti ve disease.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
•  
I G A sc ore at Wee ks 2, 4, a n d 6. 
•  
Patie nt’s Gl o bal Assess me nt ( Pa G A) c sc ore 
of 0 or 1 at Wee k 6.  
•  
A ≥2 -p oi nt re d ucti o n i n Pa G A sc ore at 
Wee k  6 c o m pare d t o baseli ne.  
•  
Pa G A sc ore at Wee k 6.  
•  
Scali n g/ h y per kerat osis sc ore b at Wee k 6. 
•  
Oe de ma/i nfiltrati o n sc ore b at Wee k 6. 
•  
D ys pi g me ntati o n sc ore b at Wee k 6.  
•  
Scarri n g/atr o p h y sc ore b at Wee k 6. 
•  
T otal s ki n disease da ma ge sc ore (s u m of 
sc ores f or d ys pi g me ntati o n a n d 
scarri n g/atr o p h y) b at Wee k 6. 
•  
T otal s ki n lesi o n disease sc ore (s u m of 
sc ores f or t otal s ki n disease acti vit y a n d t otal 
s ki n disease da ma ge) b at W ee k 6. 


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O bjecti ves  
E n d p oi nts  
T o e x pl ore t he effect of del g ociti ni b o n 
D L E -relate d ge nes a n d bi o mar kers. 
 
 
 
 
 
 
 
 
•  
C ha n ge i n s ki n bi o mar ker le vels fr o m 
baseli ne t o Wee k 6.  
•  
S ki n bi o mar ker le vels i n del g ociti ni b -treate d 
s ki n c o m pare d wit h n o n-lesi o nal s ki n at 
Wee ks 2, 4, a n d 6.  
•  
Ge ne e x pressi o n le vels i n bi o psies fr o m 
del g ociti ni b -treate d s ki n c o m pare d wit h 
ve hicle -treate d s ki n at Wee k 6. 
•  
Ge ne e x pressi o n le vels i n bi o psies fr o m 
del g ociti ni b -treate d s ki n c o m pare d wit h 
n o n -lesi o nal s ki n at Wee k 6. 
•  
Ge ne e x pressi o n le vels i n bi o psies fr o m 
ve hicle -treate d s ki n c o m pare d wit h 
n o n -lesi o nal s ki n at Wee k 6. 
T o e x pl ore t he si g ns, s y m pt o ms, a n d i m pact 
o n healt h -relate d q ualit y of life of D L E, a n d 
gai n i nsi g ht i nt o t he s u bject e x perie nce wit h 
t he I M P a n d trial pr oce d ures.  
 
•  
Q ualitati ve, se mi -str uct ure d e xit i nter vie ws 
after e n d of treat me nt t o gai n q ualitati ve 
i nsi g ht i nt o t he patie nt e x perie nce of D L E, 
a n d t he e x perie nce of t he I M P a n d t he 
partici pati o n i n t he cli nical trial.  
a)  I n t his trial, t he I G A is a lesio n -s pecific assess me nt a n d will be e val uate d se paratel y f or eac h tar get lesi o n.  
b) T he disease acti vit y  a n d da ma ge  sc ores are base d o n t he C uta ne o us L u p us Er yt he mat os us Disease Area a n d 
Se verit y I n de x ( C L A SI) a n d t he Re vise d C L A SI ( R C L A SI) w hic h  are vali date d sc ori n g s yste m s t o assess 
disease acti vit y a n d da ma ge i n patie nts wit h c uta ne o us l u p us er yt he mat os us.  
c) I n t his trial, t he Pa G A is a lesi o n-s pecific assess me nt a n d will be e val uate d se paratel y f or eac h tar get lesi o n.  
A b bre vi ati o ns:  A E = a d verse  e ve nt; D L E = disc oi d l u p us er yt he mat os us ; I M P = i n vesti gati o nal me dici nal 
pr o d uct . 
 
 


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7  Tri al desi g n  
7. 1  O ver all tri al desi g n  
O ver vie w  
T his is a p hase 2a, m ulti -ce ntre, d o u ble- bli n d, ra n d o mise d, wit hi n-s u bject, ve hicle-c o ntr olle d 
trial. T he trial will i n vesti gate t he efficac y a n d safet y of del g ociti ni b crea m 2 0 m g/ g i n a d ult 
s u bjects wit h D L E after 6 wee ks of treat me nt. T he trial desi g n is ill ustrate d i n Secti o n 3 . 
Eac h s u bject m ust ha ve at least 2 D L E tar get lesi o ns wit h acti ve disease (referre d t o as lesi o n 
1 a n d 2) f ulfilli n g t he i ncl usi o n criter ia ( Secti o n 8. 2 ). T he 2 tar get lesi o ns will be ra n d o mise d 
1: 1 t o acti ve a n d ve hicle treat me nt.  
T he differe nt trial peri o ds a n d t he visit str uct ure are f urt her desc ri be d bel o w. A n o ver vie w of 
t he sc he d ule d trial pr oce d ures is s h o w n i n Secti o n 4 . 
Scree ni n g peri o d ( D a y - 2 8 t o D a y  - 7) 
A scree ni n g visit will ta ke place 7 t o 2 8 da y s pri or t o t he first a p plicati o n of I M P. 
Bef ore a n y trial -relate d pr oce d ures are starte d, t he s u bjects will recei ve t he necessar y writte n 
a n d ver bal i nf or mati o n a n d i nstr ucti o ns a n d si g n t he i nf or me d c o nse nt f or m(s). Eac h s u bject 
will recei ve a u ni q ue s u bject i de ntificati o n n u m ber (s u bject I D), a n d eli gi bilit y will be 
assesse d b y i n vesti gat or assess me nts, cli nical la b orat or y tests, a n d E C G.  
Tre at me nt peri o d ( D a y 1 t o Wee k 6)  
At baseli ne ( Da y 1), t he s u bjects’ eli gi bilit y t o e nter t he trial will be c o nfir me d b y re -c hec ki n g 
t he eli gi bilit y criteria a n d e val uati n g t he la b orat or y res ults f or t he sa m ples ta ke n at t he 
scree ni n g visit. T he i n vesti gat or m ust e ns ure t hat la b orat or y results w hic h are nee de d t o 
assess eli gi bilit y ha ve bee n recei ve d a n d re vie we d. All eli gi ble s u bjects will c o nti n ue i n t he 
trial. T he 2 tar get lesi o ns will be ra n d o ml y assi g ne d ( 1: 1) t o treat me nt wit h del g ociti ni b crea m 
2 0 m g/ g a n d ve hicle. T he ra n d o mise d treat me nt will be a p plie d t o eac h lesi o n t wice dail y f or 
6 wee ks. T he first a p plicati o n of t he I M P will occ ur at t he trial site o n Da y 1 w he n all baseli ne 
assess me nts ha ve bee n carrie d o ut. T he s u bse q ue nt I M P a p plicati o ns will be perf or me d b y t he 
s u bject at ho me.  
D uri n g t he 6- wee k treat me nt peri o d, t he s u bjects will ret ur n t o t he trial site f or sc he d ule d 
visits at Wee ks 2, 4, a n d 6. T he last a p plicati o n of I M P will occ ur t he e ve ni n g bef ore t he 
s u bjects atte n d t he visit sc he d ule d at Wee k 6. T he efficac y a n d safet y assess me nts d uri n g t he 


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treat me nt peri o d will be perf or me d as descri be d i n Secti o n 4 . T he pri mar y e n d p oi nt is 
assesse d at Wee k 6.  
S afet y f oll o w -u p peri o d ( Wee k 6 t o Wee k 8) 
All ra n d o mise d s u bjects will atte n d a safet y f oll o w -u p visit 2 wee ks after t he last a p plicati o n 
of I M P. T his will mar k t he e n d of trial partici pati o n f or s u bjects w h o ha ve c o m plete d t he 
e ntire trial. S u bjects w h o disc o nti n ue I M P treat me nt or pre mat urel y wit h dra w fr o m t he trial 
will be f oll o we d u p as descri be d i n Secti o n 1 0 . 
7. 2  N u m ber of s u bjects nee de d  
T his trial ai ms t o ha ve 3 6 s u bjects e val ua ble f or t he pri mar y e n d p oi nt. Ass u mi n g a dr o p- o ut 
rate of 2 0 %, a p pr o xi matel y 4 5 s u bjects will be ra n d o mise d t o ac hie ve t his.  
T he statistical p o wer c o nsi derati o ns f or t his sa m ple size are descri be d i n Secti o n 1 4. 1 . 
T his trial will be c o n d ucte d at a p pr o xi matel y 2 0  sites i n se veral c o u ntries i n t he E U a n d/ or 
U nite d States. T here is n o mi ni m u m or ma xi m u m n u m ber of s u bjects per trial site.  
A s u b gr o u p of 2 0- 3 0 s u bjects fr o m selecte d c o u ntries is tar gete d f or partici pati o n i n t he 
q ualitati ve e xit i nter vie ws ( Secti o n 1 1. 6. 1. 3 ). T his sa m ple size is base d o n t y pical sa m ple 
sizes re q uire d f or q ualitati ve e x pl orati o n of patie nt e x perie nce c o nce pts (2 4 ). 
7. 3  E n d of tri al defi niti o n  
S u bjects will be c o nsi dere d t o ha ve c o m plete d t he trial if t he y ha ve c o m plete d all peri o ds of 
t he trial i ncl u di n g t he safet y f oll o w- u p visit. 
T he e n d of t he trial is defi ne d as t he date of t he last visit of t he last s u bject i n t he trial.  
Fi nal c ollecti o n of data f or t he pri mar y e n d p oi nt occ urs at Wee k 6. 
7. 4  S oft w are  
Cli nical Data I nterc ha n ge Sta n dar ds C o ns orti u m ( C DI S C) c o ntr olle d ter mi n ol o g y versi o n 
3 0- Mar - 2 0 1 8 was use d f or defi niti o n of c o ntr olle d ter mi n ol o g y use d t hr o u g h o ut t his pr ot oc ol 
a n d will be use d f or statistical pr o gra m mi n g a n d o ut p ut. St u d y data ta b ulati o n m o del ( S D T M) 
versi o n 1. 5 will be use d f or data ta b ulati o ns. 
 


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8  Tri al p o p ul ati o n  
8. 1  S u bject eli gi bilit y  
T he i n vesti gat or s h o ul d o nl y i ncl u de s u bjects w h o meet all eli gi bilit y criteria, are n ot p ut at 
u n d ue ris k b y partici pati n g i n t he trial, a n d ca n be e x pecte d t o c o m pl y wit h t he pr ot oc ol.  
T he s u bject’s eli gi bilit y f or t he cli nical trial m ust be verifie d acc or di n g t o t he i ncl usi o n a n d 
e xcl usi o n criteria at visits s pecifie d i n Secti o n 4 . It will be rec or de d i n t he e C R F if t he s u bject 
has met all t he i ncl usi o n criteria a n d n o ne o f t he e xcl usi o n criteria. 
A n y i m ple me ntati o n of nati o nal re q uire me nts/la w f or t he s u bject’s partici pati o n i n t he cli nical 
trial will be e ns ure d a n d descri be d i n s u b missi o n d oc u me ntati o n t o re g ulat or y a ut h orities a n d 
i nstit uti o nal re vie w b oar ds (I R Bs)/i n de pe n de nt et hics c o m mittees (I E Cs), as a p plica ble.  
8. 2  I ncl usi o n criteri a 
F or i ncl usi o n i nt o t his trial, s u bjects m ust f ulfil all of t he f oll o wi n g criteria:  
1.  Si g ne d a n d date d i nf or me d c o nse nt has bee n o btai ne d pri or t o a n y pr ot oc ol- relate d 
pr oce d ures. 
2.  A ge 1 8- 7 0 y ears. 
3.  Hist o pat h ol o gical fi n di n gs (c urre nt or pre vi o us) c o nsiste nt wit h cli nical dia g n osis of 
D L E.  
4.  U ne q ui v ocal cli nical dia g n osis of 2 acti ve D L E tar get lesi o ns t hat are < 6 m o nt hs ol d 
a n d a me na ble f or cli nical e val uati o n. T his i ncl u des lesi o ns l ocate d o n t he scal p if t he y 
f ulfil all lesi o n-s pecific eli gi bilit y criteria. 
5.  Tar get lesi o n I G A sc ore of at least m o derate  se verit y (I G A ≥3) at scree ni n g a n d 
baseli ne.  
6.  Tar get lesi o n er yt he ma sc ore ≥2 at scree ni n g a n d baseli ne.  
7.  F or s u bjects ta ki n g h y dr o x yc hl or o q ui ne or c hl or o q ui ne: N o a b n or mal fi n di n gs at t he 
latest r o uti ne o p ht hal m ol o gic e xa mi nati o n, a n d n o r o uti ne o p ht hal m ol o gic 
e xa mi nati o n is pla n ne d d uri n g t he trial.  
8.  Fe male s u bjects of c hil d beari n g p ote ntial * m ust use a hi g hl y effecti ve * * f or m of birt h 
c o ntr ol t hr o u g h o ut t he trial a n d f or at least 2 wee ks after last a d mi nistrati o n of I M P.  


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* A fe male s u bject is defi ne d as n ot bei n g of c hil d beari n g p ote ntial if s he is 
p ost me n o pa usal (at least 1 2  m o nt hs wit h n o me nses wit h o ut a n alter nati ve me dical 
ca use pri or t o scree ni n g), or s ur gicall y sterile ( h ysterect o m y, bilateral sal pi n gect o m y, 
or bilateral o o p h orect o m y).  
* * A hi g hl y effecti ve met h o d of birt h c o ntr ol is defi ne d as o ne w hic h res ults i n a l o w 
fail ure rate (less t ha n 1 % per year) s uc h as bilateral t u bal occl usi o n, i ntra uteri ne 
de vice (I U D), i ntra uteri ne h or m o ne -releasi n g s yste m (I U S), c o m bi ne d ( oestr o ge n a n d 
pr o gest o ge n 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 gest o ge n- o nl y h o r 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 ( w he n t his is i n li ne wit h t he preferre d a n d us ual life st yle of t he s u bject), 
vasect o mise d part ner ( gi ve n t hat t he s u bject is m o n o ga m o us). 
9.  Pr os pecti ve a bilit y t o atte n d all sc he d ule d trial visits.  
8. 3  E xcl usi o n criteri a  
S u bjects m ust n ot e nter t he trial if a n y of t he f oll o wi n g e xcl usi o n criteria are f ulfille d:  
1.  Tar get lesi o n d ys pi g me ntati o n sc ore of 2 at scree ni n g or baseli ne. 
2.  Tar get lesi o n scarri n g/ atr o p h y sc ore of 2 at scree ni n g or baseli ne. 
3.  Tar get lesi o n scarri n g al o pecia sc ore of > 0 i n scal p lesi o ns at scree ni n g or baseli ne.  
4.  Me dical hist or y of S L E wit h cli nicall y si g nifica nt or ga n i n v ol ve me nt ( A merica n 
C olle ge of R he u mat ol o g y S L E classificati o n cr iteria n o. 6 t o 9, see A p pe n di x 6 ) 
i ncl u di n g S L E-relate d ple uritis or pericar ditis ( b y cli nical e val uati o n a n d 
electr ocar di o gra m ), a n d ne ur ol o gic, re nal, a n d/ or ot her maj or S L E-relate d or ga n 
s yste m i n v ol ve me nt. S L E j oi nt i n v ol ve me nt is acce pta ble. 
5.  S u bjects wit h u nsta ble or si g nifica nt S L E disease acti vit y fi n di n gs t hat w o ul d, b y its 
pr o gressi ve nat ure a n d/ or se verit y, i nterfere wit h t he trial e val uati o n, c o m pleti o n, 
a n d/ or pr oce d ur es per t he i n vesti gat or's discreti o n.  
6.  Ot her s ki n c o n diti o ns at scree ni n g or baseli ne t hat w o ul d i nterfere wit h t he e val uati o n 
of D L E.  
7.  I m m u n os u p pressi ve/i m m u n o m o d ulati n g t hera p y wit h e. g. met h otre xate, c ycl os p ori ne, 
azat hi o pri ne, reti n oi ds ( b ot h t o pical a n d s yste mic), or da ps o ne wit hi n 4 wee ks pri or t o 
baseli ne.  


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8.  S yste mic pre d nis ol o ne > 7. 5 m g/ da y or c ha n ge d d ose wit hi n 4 wee ks pri or t o baseli ne 
( nasal a n d i n hale d c ortic oster oi ds are all o we d). 
9.  Treat me nt wit h t he f oll o wi n g me dicati o ns:  
•  Oral a nti malarial treat me nt wit h h y dr o x yc hl or o q ui ne > 6. 5 m g/ k g b o d y 
wei g ht/ da y, or c hl or o q ui ne > 4 m g/ k g b o d y wei g ht/ da y, or c ha n ge d d ose wit hi n 
1 2 wee ks pri or t o baseli ne. 
•  Q ui nacri ne c o m bi ne d wit h eit her h y dr o x yc hl or o q ui ne or c hl or o q ui ne wit hi n 
1 2 wee ks pri or t o baseli ne.  
•  Dr u gs k n o w n t o i nteract wit h a nti malarials (e. g. di g o xi n, ci meti di ne) wit hi n 
1 2 wee ks pri or t o baseli ne ( o nl y a p plica ble t o s u bjects ta ki n g a nti malarial 
treat me nt).  
1 0.  Treat me nt wit h t o pical c ortic oster oi ds, calci ne uri n i n hi bit ors, a n d p h os p h o diesterase- 4 
( P D E-4) i n hi bit ors wit hi n 2  wee ks pri or t o baseli ne.  
1 1.  Use of s yste mic a nti bi otics or c uta ne o usl y a p plie d a nti bi otics o n t he tar get lesi o ns 
wit hi n 2 wee ks pri or t o baseli ne. 
1 2.  U V t hera p y or e xcessi ve s u n e x p os ure wit hi n 2 wee ks pri or t o baseli ne.  
1 3.  A n y pr oce d ure i m pairi n g t he s ki n barrier (e. g. i ncisi o n) wit hi n 2 c m fr o m t he b or der 
of a n y of t he tar get lesi o ns wit hi n 4 wee ks pri or t o baseli ne.  
1 4.  Recei pt of li ve (atte n uate d) vacci nes wit hi n 4 wee ks pri or t o baseli ne.  
1 5.  Treat me nt wit h a n y mar kete d bi ol o gical t hera p y or i n vesti gati o nal bi ol o gic a ge nts: 
•  A n y cell- de pleti n g a ge nts i ncl u di n g b ut n ot li mite d t o rit u xi ma b: wit hi n 
6 m o nt hs pri or t o baseli ne, or u ntil l y m p h oc yte c o u nt ret ur ns t o n or mal, 
w hic he ver is l o n ger.  
•  Ot her bi ol o gics: wit hi n 3  m o nt hs or 5 half-li ves pri or t o baseli ne, w hic he ver is 
l o n ger.  
1 6.  Treat me nt wit h a n y n o n- mar kete d dr u g s u bsta nce (t hat is, a n a ge nt w hic h has n ot yet 
bee n ma de a vaila ble f or cli nical use f oll o wi n g re gistrati o n) wit hi n 4 wee ks or 5 half -
li ves pri or t o baseli ne, w hic he ver is l o n ger. 
1 7.  U nsta ble or fl uct uati n g use  of t o bacc o wit hi n 1 m o nt h pri or t o scree ni n g  w hic h , i n t he 
o pi ni o n of t he i n vesti gat or, ma y affect t he nat ural c o urse of t he disease a n d t h us affect 
t he e val uati o n of t he treat me nt. 


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1 8.  Hist or y of a n y acti ve s ki n i nfecti o n wit hi n 1 wee k pri or t o baseli ne. 
1 9.  Cli nicall y si g nifica nt i nfecti o n wit hi n 4 wee ks pri or t o baseli ne w hic h, i n t he o pi ni o n 
of t he i n vesti gat or, ma y c o m pr o mise t he safet y of t he s u bject i n t he trial, i nterfere wit h 
e val uati o n of t he I M P, or re d uce t h e s u bject’s a bilit y t o partici pate i n t he trial. 
Cli nicall y si g nifica nt i nfecti o ns are defi ne d as:  
•  A s yste mic i nfecti o n.  
•  A seri o us s ki n i nfecti o n re q uiri n g pare nteral (i ntra ve n o us or i ntra m usc ular) 
a nti bi otics, a nti viral, or a ntif u n gal me dicati o n.  
2 0.  T u berc ul osis re q uiri n g treat me nt wit hi n 1 2 m o nt hs pri or t o scree ni n g a n d/ or s u bjects 
wit h a p ositi ve bl o o d test f or t u berc ul osis at scree ni n g *. 
* S u bjects wit h hi g h ris k of late nt t u berc ul osis (e. g. pri or resi de nce i n or tra vel t o 
c o u ntries wit h hi g h pre vale nce of t u berc ul osis, cl ose c o ntact wit h a pers o n wit h acti ve 
t u berc ul osis, or a hist or y of acti ve or late nt t u berc ul osis w here a n a de q uate c o urse of 
treat me nt ca n n ot be c o nfir me d) m ust be teste d at scree ni n g.  
2 1.  I m m u n os u p presse d or i m m u n oc o m pr o mise d s u bjects. 
2 2.  Maj o r s ur ger y wit hi n 8 wee ks pri or t o scree ni n g, or pla n ne d i n- patie nt s ur ger y or 
h os pitalisati o n d uri n g t he trial peri o d.  
2 3.  Hist or y of ca ncer:  
•  S u bjects w h o ha ve ha d basal cell carci n o ma, l ocalise d s q ua m o us cell 
carci n o ma of t he s ki n, or i n sit u carci n o ma of t he cer vi x are eli gi ble pr o vi de d 
t hat t he s u bject is i n re missi o n a n d c urati ve t hera p y was c o m plete d at least 1 2 
m o nt hs pri or t o scree ni n g.  
•  S u bjects w h o ha ve ha d ot her mali g na ncies are eli gi ble pr o vi de d t hat t he 
s u bject is i n re missi o n a n d c urati ve t hera p y was c o m plete d at least 5 years 
pri or t o scree ni n g.  
2 4.  A n y dis or der w hic h is n ot sta ble a n d c o ul d: 
•  Affect t he safet y of t he s u bject t hr o u g h o ut t he trial.  
•  I nfl ue nce t he fi n di n gs of t he trial. 
•  I m pe de t he s u bject’s a bilit y t o c o m plete t he trial. 


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E xa m ples i ncl u de b ut are n ot li mite d t o car di o vasc ular, gastr oi ntesti nal, he patic, re nal, 
ne ur ol o gical, m usc ul os keletal, i nfecti o us, e n d ocri ne, meta b olic, hae mat ol o gical, 
i m m u n ol o gical, a n d ps yc hiatric dis or ders, a n d maj or p h ysical i m pair me nt. 
2 5.  A n y a b n or mal fi n di n g w hic h ma y:  
•  P ut t he s u bject at ris k beca use of t heir partici pati o n i n t he trial.  
•  I nfl ue nce t he res ults of t he trial.  
•  I nfl ue nce t he s u bject’s a bilit y t o c o m plete t he trial. 
T he a b n or mal fi n di n g m ust be cli nicall y si g nifica nt a n d o bser ve d d uri n g t he scree ni n g 
peri o d. E xa m ples i ncl u de a b n or mal fi n di n gs i n p h ysical e xa mi nati o n, vital si g ns, 
E C G, hae mat ol o g y, cli nical c he mistr y, or uri nal ysis.  
2 6.  P ositi ve h u ma n i m m u n o deficie nc y vir us a nti b o d y, he patitis B s urface a nti ge n 
( H Bs A g), or he patitis C vir us a nti b od y (a nti- H C V) ser ol o g y at scree ni n g.  
2 7.  Ala ni ne a mi n otra nsferase ( A L T) or as partate a mi n otra nsferase ( A S T) le vel ≥2 × u p per 
li mit of n or mal ( U L N) a n d/ or a ser u m creati ni ne le vel ≥1. 5 × U L N at scree ni n g.     
2 8.  K n o w n or s us pecte d h y perse nsiti vit y t o a n y c o m p o ne nt(s) of t he I M Ps.  
2 9.  C urre nt partici pati o n i n a n y ot her i nter ve nti o nal cli nical trial.  
3 0.  Pre vi o us ra n d o misati o n i n t his cli nical trial.  
3 1.  Pre vi o us partici pate d i n a cli nical trial wit h del g ociti ni b ( L E O  1 2 4 2 4 9). 
3 2.  Hist or y of c hr o nic alc o h ol or dr u g a b use wit hi n 1 2 m o nt hs pri or t o scree ni n g, or a n y 
c o n diti o n ass ociate d wit h p o or c o m plia nce as j u d ge d b y t he i n vesti gat or. 
3 3.  S u bjects w h o i n t he o pi ni o n of t he i n vesti gat or are li kel y t o be n o n -c o m plia nt or 
u na ble t o u n dersta n d t he trial a n d gi ve a de q uatel y i nf or me d c o nse nt. 
3 4.  E m pl o yees of t he trial site or a n y ot her i n di vi d uals directl y i n v ol ve d wit h t he pla n ni n g 
or c o n d uct of t he trial, or i m me diate fa mil y me m bers of s uc h i n di vi d uals.  
3 5.  S u bjects w h o are le gall y i nstit uti o nalise d.  
3 6.  Fe male s u bjects w h o are pre g na nt or lactati n g.  
8. 4  Scree ni n g a n d scree ni n g f ail ures  
S u bject i de ntific ati o n n u m ber  
Trial partici pati o n be gi ns o nce writte n i nf or me d c o nse nt is o btai ne d. Refer t o A p pe n di x 3 B  
f or details o n t he i nf or me d c o nse nt pr ocess. O nce i nf or me d c o nse nt is o btai ne d, a s u bject I D 


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will be assi g ne d b y a ce ntral i nteracti ve res p o nse tec h n ol o g y (I R T) s yste m, a n d t he scree ni n g 
e val uati o ns t o assess eli gi bilit y criteria ma y be gi n. T he s u b ject I D will be use d t o i de ntif y t he 
s u bject d uri n g t he scree ni n g pr ocess a n d t hr o u g h o ut trial partici pati o n, if a p plica ble. S u bjects 
w h o ha ve gi ve n writte n i nf or me d c o nse nt t o partici pate i n t he trial a n d w h o ha ve bee n 
assi g ne d a s u bject  I D are c o nsi dere d ‘scree ne d’ s u bjects. 
T he i n vesti gat or will mai ntai n a l o g of all c o nse nte d s u bjects at t he trial site (s u bject 
i de ntificati o n list). T his l o g will i ncl u de eac h s u bject’s i de ntit y, date of c o nse nt, a n d 
c orres p o n di n g s u bject I D s o t hat a n y s u bject ma y be i de ntifie d if re q uire d f or a n y reas o n. T he 
l o g m ust n ot be c o pie d or retai ne d b y L E O. I n a d diti o n, t he i n vesti gat or will mai ntai n a l o g of 
all s u bjects c o nsi dere d f or scree ni n g, w het her t he y ha ve pr o vi de d writte n i nf or me d c o nse nt or 
n ot (scree ni n g l o g). T his l o g will be a n o n y m o us a n d will i ncl u de t he reas o n(s) f or n ot e nteri n g 
t he trial, if a p plica ble, or t he all ocate d s u bject I D. 
Scree ni n g f ail ures  
Scree ni n g fail ures are defi ne d as s u bjects w h o c o nse nt t o partici pate i n t he trial b ut are n ot 
s u bse q ue ntl y assi g ne d t o trial treat me nt. A mi ni mal set of scree ni n g fail ure i nf or mati o n is 
re q uire d t o e ns ure tra ns pare nt re p orti n g of scree ni n g fail ure s u bjects t o meet t he C o ns oli date d 
Sta n dar ds of Re p orti n g Trials ( C O N S O R T) p u blis hi n g re q uire me nts (2 5 ) a n d t o res p o n d t o 
q ueries fr o m re g ulat or y a ut h orities.  
D L E is a rare disease, a n d t he n u m ber of eli gi ble patie nts is li mite d. T heref ore, s u bjects w h o 
fail t o meet all eli gi bilit y criteria at scree ni n g ma y be re-assesse d f or eli gi bilit y at a later sta ge 
at t he i n vesti gat or’s discreti o n. T his a p plies o nl y t o eli gi bilit y criteria t hat are li kel y t o be 
f ulfille d o ver ti me, e. g. criteria c o ncer ni n g D L E se verit y a n d pr o hi bite d me dicati o ns. 
Re -assess me nt of eli gi bilit y will be all o we d at t he i n vesti gat or’s discreti o n if o ne or m ore of 
t he f oll o wi n g eli gi bilit y criteria are n ot f ulfille d at scree ni n g: 
•  I ncl usi o n criteria n o. 5 , 6 , a n d 7 . 
•  E xcl usi o n criteria n o. 6 , 7 , 8 , 9 , 1 3 , 1 4 , 1 5 , 1 6 , a n d 1 9 . 
If a n y ot her eli gi bilit y criteria are n ot f ulfille d at scree ni n g, t he s u bject will be c o nsi dere d a 
scree ni n g fail ure. H o we ver, if t he reas o n f or scree ni n g fail ure is a d mi nistrati ve (e. g. del a ye d 
test res ults a n d n ot d ue t o t he s u bject faili n g t o f ulfil t he eli gi bilit y criteria), re-assess me nt of 
eli gi bilit y ma y als o be per mitte d.  Eac h s u bject ca n o nl y be re-assesse d f or eli gi bilit y o nce.  
At scree ni n g, it will be clearl y d oc u me nte d i n t he e C R F  a n d i n t he s o urce data if a s u bject is 
pla n ne d t o ret ur n f or re- assess me nt of eli gi bilit y. S u bjects w h o fail t o ret ur n f or re -assess me nt 


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of eli gi bilit y will be c o nsi dere d scree ni n g fail ures. Eac h  s u bject will kee p t he sa me s u bject I D 
d uri n g t he trial.  
If t he peri o d bet wee n scree ni n g a n d re-assess me nt of eli gi bilit y e xcee ds 4 wee ks, all 
scree ni n g pr oce d ures i ncl u di n g la b orat or y sa m ples m ust be re peate d at t he re-assess me nt 
visit. I n t his case, t he re -assess me nt of eli gi bilit y will be d oc u me nte d as a f ull, a d diti o nal 
scree ni n g visit i n t he e C R F. F or s h orter peri o ds ( < 4 wee ks) bet wee n scree ni n g a n d 
re-assess me nt of eli gi bilit y, t he i n vesti gat or will j u d ge w hic h assess me nts a n d pr oce d ures are 
rele va nt at t he re-assess me nt visit. 
T he f oll o wi n g data will be c olle cte d i n t he e C R F f or scree ni n g fail ures:  
•  Date of i nf or me d c o nse nt.  
•  De m o gra p hics ( date of birt h, se x, et h nicit y, race). If f ull date of birt h is n ot 
all o we d t o be rec or de d  per l ocal le gislati o n , m o nt h a n d/ or year of birt h s h o ul d 
be c ollecte d t o get her wit h t he s u bject’s a ge.  
•  Reas o n f or scree ni n g fail ure.  
o  Fail ure t o meet eli gi bilit y criteria.  
o  L ost t o f oll o w - u p. 
o  Wit h dra wal b y s u bject.  
o  Ot her.  
•  Date of scree ni n g fail ure.  
•  A n y a d verse e ve nts ( A Es) a n d seri o us A Es ( S A Es).  
 
I n case of a n y S A Es, t hese m ust be f oll o we d u p as descri be d i n Secti o n 1 3. 7 . 
9  Tre at me nts  
9. 1  Tri al pr o d uct descri pti o n  
Del g ociti ni b is a pa n -J A K i n hi bit or, w hic h is prese nte d i n t his trial as a crea m f or m ulati o n f or 
t o pical a p plicati o n. Please refer t o Pa nel 4  f or f urt her details. 
 
 
 


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Date: 2 2 -Oct -2 0 1 9  
Versi o n: 4. 0  
Pa ge 4 0  of 1 2 2  
 
 
 
 
 
P a nel 4 : I de ntific ati o n of i n vesti g ati o n al medici n al pr o d ucts  
I n vesti g ati o n al 
me dici n al pr o d uct  
D os a ge f or m  
Acti ve i n gre die nt a n d 
c o nce ntr ati o n  
P ac k size  
S o urce  
Del g ociti ni b crea m 
2 0 m g/ g.  
Crea m.  
Del g ociti ni b 2 0 m g/ g.  
1 5 g.  
 
Del g ociti ni b crea m 
ve hicle.  
Crea m.  
Ve hicle.  
1 5 g.  
 
 
9. 2  A d mi nistr ati o n of I M P  
T he I M Ps ( del g ociti ni b crea m a n d ve hicle) will be a d mi nistere d as t o pical a p plicati o ns t wice 
dail y f or 6 wee ks. T he 2 tar get lesi o ns (referre d t o as lesi o n 1 a n d 2, see Secti o n 1 1. 2. 8 ) will 
be ra n d o mise d 1: 1 t o treat me nt wit h del g ociti ni b crea m 2 0 m g/ g or ve hicle. T he s u bjects will 
a p pl y t he I M Ps i n t he m or ni n g a n d i n t he e ve ni n g, a p pr o xi matel y 1 2 h o urs a part. I nstr ucti o ns 
f or use will be pr o vi de d.  
F or eac h tar get lesi o n, t he treat me nt area will be defi ne d as t he lesi o n area at baseli ne pl us a 
mar gi n of a p pr o xi matel y 1 c m. T he first a p plicati o n of t he I M Ps will occ ur o n Da y 1 at t he 
trial site after all assess me nts ha ve bee n c o m plete d. Pri or t o t he first I M P a p plicati o n, t he 
s u bjects will be i nstr ucte d h o w m uc h crea m t o a p pl y a n d w hic h I M P t o use o n eac h treat me nt 
area. T he i nstr ucti o ns will be gi ve n b y trial site staff w h o are n ot i n v ol ve d i n cli nical 
assess me nts d uri n g t he trial. T he i de ntificati o n of t he 2 tar get lesi o ns a n d t he all ocati o n of 
treat me nt t o eac h lesi o n is f urt her descri be d i n Secti o n 9. 3 .  
T he a m o u nt of I M P t o be a p plie d t o eac h treat me nt area de pe n ds o n t he size of t he tar get 
lesi o ns. If a tar get lesi o n re mai ns u nc ha n ge d or decrease i n size, t he treat me nt area will 
re mai n c o nsta nt d uri n g t he treat me nt peri o d e ve n if t he s y m pt o ms i m pr o ve. If a tar get lesi o n 
i ncreases i n size, t he treat me nt area will i ncrease c orres p o n di n gl y. T he I M Ps s h o ul d be 
a p plie d i n a n e ve n la yer t o c o ver t he e ntire treat me nt area. T he ma xi m u m e x pecte d treat me nt 
area is 1 % of B S A c orres p o n di n g t o a lesi o n of 1 5 c m i n dia meter. F or refere nce, it is 
esti mate d t hat 0. 3 g of crea m will be a de q uate t o c o ver 1 % of B S A (a n area c orres p o n di n g t o 
t he s u bject’s ha n d; t he pal mar s urface pl us t he 5 di gits ).  
T he s u bjects will c o nti n ue treat me nt u ntil visit 5 ( Wee k 6) re gar dless of cleara nce stat us. T he 
last a p plicati o n of t he I M Ps will occ ur at t he s u bject’s h o me t he da y bef ore t he s u bject atte n ds 
t he Wee k 6 visit.  
C CI
C CI


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Date: 2 2 -Oct -2 0 1 9  
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T he s u bjects s h o ul d n ot s h o wer wit hi n 2 h o urs after a p pl yi n g t he I M Ps. At t he sc he d ule d 
visits, i n vesti gat or assess me nts a n d Pa G A s h o ul d be d o ne pri or t o or at least 2 h o urs a fter I M P 
a p plicati o n a n d/ or bat hi n g/s h o weri n g. N o n-i n vasi ve s ki n sa m pli n g s h o ul d be d o ne pri or t o or 
at least 4 h o urs after I M P a p plicati o n. N ote t hat o n t he da y of t he Wee k 6 visit, n o I M P will be 
a p plie d i n t he m or ni n g. 
I n a d diti o n t o t he I M Ps, all s u bjects s h o ul d a p pl y s u nscree n e ver y da y d uri n g t he treat me nt 
peri o d ( Secti o n 9. 4 ). T he s u nscree n s h o ul d be a p plie d t o s u n-e x p ose d areas i n t he m or ni n g, at 
least 4 5 mi n utes after a p plicati o n of I M P.  
O n t he treat me nt areas, o nl y t he I M Ps a n d s u nscree n ca n be a p plie d. O n D L E lesi o ns o utsi de 
t he treat me nt areas, o nl y s u nscree n a n d e m ollie nts are all o we d (see als o Secti o n 9. 7 ). T his is 
t o a v oi d c o nf usi n g t he s u bjects b y ha vi n g t o a p pl y m ore t ha n 2 treat me nts, as acci de ntal use 
of ot her me dicati o ns o n t he treat me nt areas c o ul d i m pact b ot h efficac y a n d safet y 
assess me nts.  
T he I M Ps will be dis pe nse d at t he visits s h o w n i n t he sc he d ule of trial pr oce d ures ( Secti o n  4 ).  
L E O d oes n ot rec o m me n d s pecific treat me nt f or a n o ver d ose. T he i n vesti gat or wi ll use 
cli nical j u d ge me nt t o treat a n y o ver d ose if necessar y ( Secti o n 1 3. 6. 2 ). 
9. 3  Tre at me nt assi g n me nt  
S u bjects w h o ha ve bee n f o u n d t o c o m pl y wit h all t he i ncl usi o n criteria a n d n ot t o vi olate a n y 
of t he e xcl usi o n criteria will be assi g ne d t o treat me nt at baseli ne ( Da y 1).  
All s u bjects will recei ve t he sa me 2 treat me nts ( del g ociti ni b crea m a n d ve hicle), s o  t here will 
be n o s u b di visi o n i nt o treat me nt gr o u ps. At scree ni n g, 2 p ote ntial tar get lesi o ns are selecte d 
a n d e val uate d. At baseli ne, t he p ote ntial tar get lesi o ns are re -e val uate d. I n t he u nli kel y e ve nt 
t hat 1 or b ot h of t he p ote ntial tar get lesi o ns selecte d at scree ni n g n o l o n ger f ulfil all t he 
eli gi bilit y criteria at baseli ne, t he i n vesti gat or is all o we d t o select ne w, eli gi ble tar get lesi o ns 
(if a vaila ble) at baseli ne, as l o n g as t his is clearl y d oc u me nte d i n t he s o urce data a n d t he 
e C R F (see Secti o n 1 1. 2. 8 ).  
After c o nfir mati o n of eli gi bilit y at baseli ne, t he selecte d tar get lesi o ns will be n u m bere d as 
lesi o n 1 a n d 2. T he n u m beri n g s h o ul d be gi n wit h t he u p per m ost or m ost pr o xi mal site o n t he 
left fr o m t he i n vesti gat or’s vie w. Lesi o ns al o n g t he sa me li ne s h o ul d be n u m bere d fr o m left t o 
ri g ht. 


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Date: 2 2 -Oct -2 0 1 9  
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Ra n d o misati o n will be perf or me d b y per m utati o n of t he treat me nt c o des A a n d B. Eac h 
s u bject will be ra n d o ml y assi g ne d t o either t he treat me nt se q ue nce A B or t he treat me nt 
se q ue nce B A wit h t he pr o ba bilit y 0. 5. T he first treat me nt liste d i n t he treat me nt se q ue nce will 
be assi g ne d t o lesi o n 1 a n d t he last treat me nt will be assi g ne d t o lesi o n 2.  
T he I R T s yste m will assi g n t he re q u ire d kit n u m ber f or eac h s u bject a n d will als o be use d f or 
I M P s u p pl y c hai n a n d e x pir y trac ki n g.  
9. 3. 1  Bli n di n g  
T he pac ka gi n g a n d la belli n g of t he I M Ps will c o ntai n n o e vi de nce of t heir i de ntit y. H o we ver, 
there is a sli g ht differe nce i n c ol o ur bet wee n t he 2 I M Ps. T he differe nce is o nl y discer ni ble o n 
cl ose i ns pecti o n wit h b ot h I M Ps c o m pare d si de b y si de. To a v oi d acci de ntal i n vesti gat or 
u n bli n di n g, t he first a p plicati o n of I M Ps a n d i nstr ucti o ns t o t he s u bjects will o nl y be d o ne b y  
desi g nate d trial site staff w h o are n ot i n v ol ve d i n cli nical e val uati o ns.  
9. 3. 2  E mer ge nc y u n bli n di n g of i n di vi d u al s u bject tre at me nt  
W hile t he safet y of a s u bject al wa ys c o mes first, it is still i m p orta nt t o caref ull y c o nsi der if 
u n bli n di n g is necessar y t o e ns ure a s u bject’s safet y. I n ma n y cases, I M P disc o nti n uati o n a n d 
k n o wle d ge of t he p ossi ble treat me nt assi g n me nt are s ufficie nt t o treat a trial s u bject w h o 
prese nts wit h a n e mer ge nc y c o n diti o n. A n e mer ge nc y u n bli n di n g re q uest ca n be ma de b y t he 
i n vesti gat ors, healt h care pr ofessi o nals w h o are n ot me m bers of t he trial staff, or a ut h orise d 
L E O pers o n nel. 
Pr o visi o ns are i n place f or 2 4- h o ur e mer ge nc y u n bli n di n g of i n di vi d ual s u bject treat me nt. If 
e mer ge nc y u n bli n di n g is re q uire d, t he i n vesti gat or ca n u n bli n d a s u bject’s treat me nt i n t he 
I R T s yste m. F or a re q uester w h o is n ot a me m ber of t he trial staff a n d w h o d oes n ot ha ve 
access t o t he I R T s yste m (e. g. a p h ysicia n at a n e mer ge nc y r o o m), a l ocal c o ntact n u m ber f or 
t he e mer ge nc y u n bli n di n g C R O is pr o vi de d o n t he s u bject car d (see A p pe n di x 3 B ) t o be use d 
if t he i n vesti gat or or dele gate d site staff ca n n ot be reac he d. T he re q uester will pr o vi de t he 
trial I D a n d s u bject I D t o t he e mer ge nc y u n bli n di n g C R O w h o will i m me diatel y re veal t he 
i n di vi d ual treat me nt all ocati o n. 
T he e mer ge nc y u n bli n di n g C R O will clarif y t hat t he re q uester re q uires i m me diate u n bli n di n g 
wit h o ut f urt her me dical c o ns ultati o n. S h o ul d t he re q uester wis h t o disc uss w het her u n bli n di n g 
is necessar y, t he e mer ge nc y u n bli n di n g C R O will pr o vi de t he re q uester wit h t he L E O 2 4/ 7 
c o ntact w hic h will be di verte d t o t he me dical c o ver.  


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Date: 2 2 -Oct -2 0 1 9  
Versi o n: 4. 0  
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9. 4  B ac k gr o u n d tre at me nt  
All s u bjects will be i nstr ucte d t o a p pl y  s u nscree n dail y t o s u n-e x p ose d areas d uri n g t he 
treat me nt peri o d. T he s u nscree n m ust ha ve a s u n pr otecti o n fact or ( S P F) of at least 5 0 a n d 
will be pr o vi de d t o all s u bjects b y t he trial site. If t he s u bject is k n o w n t o be h y perse nsiti ve t o 
t he pr o vi de d s u nscree n or has a str o n g prefere nce f or a partic ular bra n d, t he s u bject ca n be 
all o we d t o use his/ her preferre d s u nscree n wit h S P F  of at least  5 0. T he s u nscree n s h o ul d be 
a p plie d i n t he m or ni n g, at least 4 5 mi n utes after a p plicati o n of I M P.  
9. 5  Resc ue tre at me nt  
N ot a p plica ble. 
9. 6  C o nc o mit a nt me dic ati o n a n d c o nc urre nt pr oce d ures  
C urre nt me dicati o n or vacci nes fr o m baseli ne t hr o u g h safet y f oll o w -u p as well as me dicati o n 
liste d as pr o hi bite d me dicati o n i n t he e xcl usi o n criteria t hat t he s u bject recei ves fr o m 
6 m o nt hs pri or t o baseli ne m ust be rec or de d (if rele va nt) i n t he s u bject’s me dical rec or d a n d 
t he e C R F al o n g wit h details s uc h as: 
•  Me dicati o n na me.  
•  I n dicati o n. 
•  Start a n d st o p date of a d mi nistrati o n (it will als o be rec or de d if t he me dicati o n is 
o n g oi n g). 
•  D osa ge i nf or mati o n, i ncl u di n g d ose, u nit, a n d fre q ue nc y. 
•  R o ute of a d mi nistrati o n.  
•  F or t o pical treat me nt, t he b o d y l ocati o n m ust be rec or de d. It m ust als o be rec or de d 
if t he treat me nt is wit hi n 5 c m of a tar get lesi o n (a n d if s o, w hic h of t he tar get 
lesi o ns). 
A n y c o nc urre nt pr oce d ure fr o m baseli ne t hr o u g h safet y f oll o w-u p as well as pr oce d ures liste d 
as pr o hi bite d pr oce d ures i n t he e xcl usi o n criteria fr o m 4 wee ks pri or t o baseli ne m ust als o be 
rec or de d i n t he s u bject’s me dical rec or d a n d t he e C R F. T he f oll o wi n g details will be rec or de d:  
•  Pr oce d ure. 
•  B o d y l ocati o n.  
•  Dia g n osis. 


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•  Start a n d st o p date (it will als o be rec or de d if t he pr oce d ure is o n g oi n g).  
•  F or c uta ne o us pr oce d ures , it m ust als o be rec or de d if t he pr oce d ure is i nsi de a 
tar get lesi o n (a n d if s o, w hic h of t he tar get lesi o ns).  
I n vesti gat ors ma y prescri be c o nc o mita nt me dicati o ns or treat me nts t o pr o vi de a de q uate 
s u p p orti ve care as dee me d necessar y, e xce pt f or me dicati o ns liste d i n Secti o n 9. 7 . T he 
s p o ns or’s me dical e x pert s h o ul d be c o ntacte d if t here are a n y q uesti o ns re gar di n g c o nc o mita nt 
or pri or t hera p y.  
If a nal gesic treat me nt is c o nsi dere d necessar y d uri n g t he trial, t he f oll o wi n g c o nc o mita nt 
me dicati o ns a re rec o m me n de d a n d all o we d fr o m scree ni n g t hr o u g h safet y f oll o w-u p:  
•  F or s u bjects wit h mil d S L E: i b u pr ofe n ≤1 2 0 0 m g/ da y ( or e q ui vale nts i n t heir 
c orres p o n di n g rec o m me n de d ma xi m u m dail y d ose), pr o vi de d t hat t his is k n o w n t o 
be well t olerate d b y t he s u bject.  
•  F or s u bjects wit h o ut S L E: paraceta m ol ≤4 0 0 0 m g/ da y s h o ul d be use d i nstea d of 
i b u pr ofe n.  
9. 7  Pr o hi bite d me dic ati o n a n d pr oce d ures  
T he me dicati o ns liste d i n Pa nel 5  are pr o hi bite d d uri n g t he trial. N ote t hat s o me me dicati o ns 
are pr o hi bite d pri or t o scree ni n g a n d/ or ra n d o misati o n, b ut all o we d d uri n g t he treat me nt p hase 
(see t he e xcl usi o n criteria, Secti o n 8. 3 ). N ote t hat a n y c ha n ges i n d ose or disc o nti n uati o n of 
me dicati o ns or pr oce d ures t hat are liste d as pr o hi bite d pri or t o or d uri n g t he trial s h o ul d o nl y 
be d o ne f or me dical reas o ns, n ot trial- relate d reas o ns. 
 
 


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Versi o n: 4. 0  
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P a nel 5 : Pr o hi bite d me dic ati o n a n d pr oce d ures 
Me dic ati o n/ pr oce d ure  
Pr o hi bite d fr o m  
Pr o hi bite d t o  
S yste mic pre d nis ol o ne > 7. 5 m g/ da y or c ha n ge d 
d ose ( nasal a n d i n hale d c or tic oster oi ds all o we d). 
4 wee ks pri or t o baseli ne.  
E n d of trial.  
Oral a nti malarial treat me nt wit h 
h y dr o x yc hl or o q ui ne > 6. 5 m g/ k g/ da y or 
c hl or o q ui ne > 4 m g/ k g/ da y, or c ha n ge d d ose.  
1 2 wee ks pri or t o baseli ne.  
E n d of trial.  
Q ui nacri ne c o m bi ne d wit h eit her 
h y dr o x yc hl or o q ui ne or c hl or o q ui ne.  
1 2 wee ks pri or t o baseli ne.  
E n d of tri al. 
Dr u gs k n o w n t o i nteract wit h a nti malarials (e. g. 
di g o xi n, ci meti di ne) a. 
1 2 wee ks pri or t o baseli ne.  
E n d of trial.  
I m m u n os u p pressi ve/i m m u n o m o d ulati n g t hera p y 
wit h e. g. met h otre xate, c ycl os p ori ne, 
azat hi o pri ne, reti n oi ds ( b ot h t o pical a n d 
s yste mic), or da ps o ne.  
4 wee ks pri or t o baseli ne.  
E n d of trial.  
Bi ol o gics (cell -de pleti n g a ge nts i ncl u di n g b ut n ot 
li mite d t o rit u xi ma b). 
6 m o nt hs pri or t o baseli ne or 
u ntil l y m p h oc yte c o u nt ret ur ns 
t o n or mal, w hic he ver is l o n ger. 
E n d of trial.  
Ot her bi ol o gics.  
3 m o nt hs or 5 half -li ves pri or t o 
baseli ne, w hic he ver is l o n ger.  
E n d of trial.  
T o pical c ortic oster oi ds, calci ne uri n i n hi bit ors, 
a n d P D E -4 i n hi bit ors.  
2 wee ks pri or t o baseli ne.  
E n d of trial.  
A n y c uta ne o usl y a p plie d pr o d uct ( ot her t ha n 
s u nscreen a n d I M Ps) o n t he treat me nt areas.  
Ra n d o misati o n.  
E n d of trial.  
A n y c uta ne o usl y a p plie d pr o d uct ( ot her t ha n 
s u nscree n a n d e m ollie nts) o n D L E lesi o ns 
o utsi de t he treat me nt areas.  
Ra n d o misati o n.  
E n d of trial.  
C uta ne o usl y a p plie d a nti bi otics o n t he treat me nt 
areas.  
2 wee ks pri or t o baseli ne.  
E n d of trial.  
U V t hera p y  or e xcessi ve s u n e x p os ure.  
2 wee ks pri or t o baseli ne.  
E n d of trial.  
Li ve (atte n uate d) vacci ne.  
4 wee ks pri or t o baseli ne.  
E n d of trial.  
A n y n o n -mar kete d dr u g s u bsta nce (i.e. a n a ge nt 
w hic h has n ot yet bee n ma de a vaila ble f or 
cli nical use f oll o wi n g re gistrati o n).  
4 wee ks or 5 half -li ves pri or t o 
baseli ne, w hic he ver is l o n ger.  
E n d of trial.  
A n y pr oce d ure i m pairi n g t he s ki n barrier (e. g. 
i ncisi o n) wit hi n 2 c m fr o m t he b or der of a n y of 
t he tar get lesi o ns. 
4 wee ks pri or t o baseli ne.  
E n d of trial.  
a) O nl y a p plica ble t o s u bjects ta ki n g a nti malarial treat me nt.  
A b bre vi ati o ns: D L E = disc oi d l u p us er yt he mat os us;  I M P = i n vesti gati o nal me dici nal pr o d uct; 
P D E - 4 = p h os p h o diesterase; U V = ultra vi olet.  


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I n case a n y pr o hi bite d treat me nts are use d d uri n g t he trial, t he y m ust be rec or de d as 
c o nc o mita nt me dicati o n. 
N or mal bat hi n g a n d was hi n g is all o we d f oll o wi n g t he s u bject’s n or mal r o uti ne b ut s h o ul d be 
d o ne at least 2 h o urs after a p plicati o n of t he I M Ps.  
Use of c os metic b o d y care pr o d ucts (e. g. ma ke- u p, b o d y l oti o n, bat h oil) a n d e m ollie nts is n ot 
all o we d o n t he tar get lesi o ns fr o m baseli ne t o safet y f oll o w - u p.  
9. 8  Tre at me nt l o gistics a n d acc o u nt a bilit y  
9. 8. 1  L a belli n g a n d p ac k a gi n g of tri al pr o d ucts  
I n vesti g ati o n al me dici n al pr o d ucts 
T he I M Ps will be pac ka ge d i n i n di vi d uall y n u m bere d kits. Pri mar y a n d sec o n dar y pac ka gi n g 
materials will be i n di vi d uall y la belle d. T he 2 I M Ps (treat me nt A a n d B) will ha ve la bels i n 
differe nt c ol o urs t o hel p t he s u bjects disti n g uis h bet wee n t he m.  
T he la belli n g of I M Ps will be i n acc or da nce wit h A n ne x 1 3, l ocal re g ulati o ns, a n d trial 
re q uire me nts. La bel te xt will be tra nslate d i nt o l ocal la n g ua ges, as re q uire d.  
9. 8. 2  St or a ge of tri al pr o d ucts  
All L E O s u p plie d I M Ps m ust be st ore d i n a sec ure a n d restricte d area u n der t he c o n diti o ns 
s pecifie d o n t he la bel a n d re mai n i n t he ori gi nal c o ntai ner u ntil dis pe nse d. 
T he I M Ps m ust be st ore d at 2 -8° C at t he trial site a n d at t he s u bject’s h o me. D o n ot freeze. At 
t he trial site, t he st ora ge te m perat ure m ust be m o nit ore d as descri be d bel o w de pe n di n g o n t he 
te m perat ure rec or di n g s yste m: 
•  F or electr o nic, c o nti n u o usl y rec or di n g s yste ms wit h alar m a n d bac k- u p of data: 
If n o alar m is tri g gere d, a l o g m ust be pri nte d, re vie we d, si g ne d, a n d date d 
eac h m o nt h.  
•  F or electr o nic, c o nti n u o usl y rec or di n g s yste ms wit h alar m a n d n o bac k- u p of 
data: If n o alar m is tri g gere d, a ma n ual ha n d writte n l o g is mai ntai ne d a n d 
s h o ul d be re vie we d, si g ne d, a n d date d eac h wee k. I n a d diti o n, a l o g m ust be 
pri nte d, re vie we d, si g ne d, a n d date d eac h m o nt h. 


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If t he alar m is tri g gere d (re gar dless of s yste m t y pe), t he l o g m ust be i m me diatel y pri nte d, 
re vie we d, si g ne d, a n d date d, a n d a p pr o priate f oll o w-u p acti o n will be ta ke n i n acc or da nce 
wit h t he trial pr o d uct ha n dli n g ma n ua l. 
A te m perat ure l o g fr o m t he rec or di n g s yste m m ust be ke pt t o d oc u me nt t he st ora ge wit hi n t he 
ri g ht te m perat ure i nter val. St ora ge facilities s h o ul d be c hec ke d at least e ver y w or ki n g da y. 
St ora ge of I M Ps ma y be dele gate d, e. g. t o a h os pital p har mac y, as l o call y a p plica ble. 
I n t he sit uati o ns liste d bel o w, site staff s h o ul d n ot use t he affecte d I M Ps a n d s h o ul d 
i m me diatel y c o ntact t heir cli nical researc h ass ociate ( C R A) f or f urt her g ui da nce:  
•  Te m perat ure e xc ursi o n u p o n recei pt or d uri n g st ora ge at t he trial si te.  
•  Da ma ge d kit. 
•  E x pire d kit. 
Da ma ge d I M Ps s h o ul d be d oc u me nte d i n t he I R T s yste m a n d re p orte d as a pr o d uct c o m plai nt 
t o Gl o bal Safet y, L E O (see Secti o n 9. 1 0 ). Da ma ge d I M Ps ma y n ot be use d.   
F urt her details re gar di n g st ora ge (i ncl u di n g ha n dli n g of te m perat ure e xc ursi o ns u p o n recei pt 
or d uri n g st ora ge at t he trial site) a n d ha n dli n g of da ma ge d I M Ps (i ncl u di n g da ma ge d kits) are 
pr o vi de d i n t he trial pr o d uct ha n dli n g ma n ual. 
9. 8. 3  Dr u g acc o u nt a bilit y  
I M P acc o u nt a bilit y 
T he i n vesti gat or is f ull y res p o nsi ble f or t he I M Ps at t he trial site a n d f or mai ntai ni n g a de q uate 
c o ntr ol of t he I M Ps a n d f or d oc u me nti n g all tra nsacti o ns wit h t he m.  
Dis pe nsi n g of I M Ps ma y be dele gate d, e. g. t o a h os pital p har mac y, as l ocall y a p plica ble. 
A n i n di vi d ual dr u g acc o u nta bilit y f or m  m ust be ke pt of t he I M Ps a d mi nistere d t o a n d ret ur ne d 
b y eac h s u bject ra n d o mise d i n t he trial. T his i n di vi d ual dr u g acc o u nta bilit y f or m m ust be 
a vaila ble d uri n g m o nit ori n g visits a n d will be c hec ke d b y t he C R A t o verif y c orrect 
dis pe nsi n g of t he I M Ps. Dr u g acc o u nta bilit y i nf or mati o n will be e ntere d i n t he I R T s yste m, 
w here als o i n ve nt or y stat us of all I M Ps at t he trial site will be mai ntai ne d.  
T he s u bjects will ret ur n use d, partl y use d, a n d u n use d I M Ps (i ncl u di n g pac ka gi n g material) at 
t he trial visits s pecifie d i n t he sc he d ule of trial pr oce d ures ( Secti o n 4 ). 


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Ret ur ne d trial pr o d ucts ( use d, partl y use d, a n d u n use d I M Ps i ncl u di n g pac ka gi n g material) 
ca n be st ore d at r o o m te m perat ure a n d m ust be st ore d se paratel y fr o m n o n -all ocate d trial 
pr o d ucts. 
All I M Ps (i ncl u di n g pac ka gi n g material) s u p plie d b y t he c o ntract ma n ufact uri n g or ga nisati o n 
( C M O) o n be half of L E O will be ret ur ne d t o t he C M O o n a n o n g oi n g basis. Pri or t o t heir 
ret ur n, t he I M Ps m ust be f ull y acc o u nte d f or b y t he C R A wit h t he hel p of site staff res p o nsi ble 
f or dis pe nsi n g t he I M Ps. Acc o u nta bilit y m ust be d oc u me nte d o n dr u g acc o u nta bilit y f or ms.  
All t u bes ret ur ne d t o t he C M O will be wei g he d t o deter mi ne t he a m o u nt of I M P use d b y eac h 
s u bject. T he a vera ge wei g ht of a f ull, la belle d t u be will be pr o vi de d b y t he C M O. 
Re p orti n g i n e C R F  
T he kit/t u be n u m ber, date of I M P dis pe nsati o n a n d ret ur n, a n d n u m ber of t u bes dis pe nse d a n d 
ret ur ne d will be rec or de d i n t he e C R F. 
9. 8. 4  Tre at me nt c o m pli a nce  
T he first a p plicati o n of I M Ps will occ ur at t he trial site wit h clear i nstr ucti o ns fr o m t he site 
staff o n w hic h I M P t o use o n eac h tar get lesi o n a n d h o w m uc h I M P t o use per a p plicati o n (see 
Secti o n 9. 2 ).      
At t he visits s pecifie d i n t he sc he d ule of trial pr oce d ures ( Secti o n 4 ), t he s u bject will be as ke d 
if t he y ha ve use d t he I M Ps as prescri be d. If a s u bject is f o u n d t o be n o n-c o m plia nt, t he 
i n vesti gat or s h o ul d re mi n d t he s u bject of t he i m p orta nce of f oll o wi n g t he i nstr ucti o ns gi ve n, 
i ncl u di n g a p pl yi n g t he I M Ps as prescri be d. It m ust be rec or de d i n t he e C R F w het her t he 
s u bject is c o m plia nt or n o n-c o m plia nt. F or n o n-c o m plia nt s u bjects, t he reas o n f or 
n o n-c o m plia nce a n d t he nat ure of n o n-c o m plia nce (i.e. t he n u m ber of misse d or e xcessi ve 
a p plicati o ns of I M P, or use of t he wr o n g I M P o n 1 or b ot h tar get lesi o ns) will als o be 
rec or de d. 
9. 8. 5  Tri al pr o d uct destr ucti o n  
Use d a n d u n use d I M Ps will be destr o ye d b y t he C M O acc or di n g t o a p pr o ve d pr oce d ures 
a n d/ or l ocal re q uire me nts.  
9. 9  Pr o visi o n f or s u bject c are f oll o wi n g tri al c o m pleti o n  
To e ns ure a p pr o priate treat me nt of t he s u bjects after t he y ha ve c o m plete d t he trial, t he 
s u bjects will be treate d at t he i n vesti gat or’s discreti o n or referre d t o ot her p h ysicia n(s) 
acc or di n g t o sta n dar d practice.  


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9. 1 0  Re p orti n g pr o d uct c o m pl ai nts  
A n y defects or iss ues wit h t he I M Ps (e. g. stra n ge c ol o ur or c o nsiste nc y, i na de q uate la belli n g) 
m ust be re p orte d t o Gl o bal Safet y at L E O o n t he trial -s pecific ( pa per) c o m plai nt f or m wit hi n 
3 da ys of first k n o wle d ge.  
Critical c o m plai nts ( defi ne d as a n y defect or iss ue t hat has or p ote ntiall y c o ul d ha ve a seri o us 
i m pact f or t he s u bject (e. g. a n S A E)) m ust be re p orte d t o Gl o bal Safet y, L E O wit hi n 2 4 h o urs.  
C o m plai nt f or ms s h o ul d c o ntai n a detaile d descri pti o n of t he defect or iss ue, i ncl u di n g 
w het her it le d t o a n A E. ( S) A Es w hic h occ ur d ue t o a defect or iss ue wit h t he I M Ps will be 
re p orte d b y t he i n vesti gat or as descri be d i n Secti o ns 1 3. 3  a n d 1 3. 4 .  
Refer t o t he trial pr o d uct ha n dli n g ma n ual f or i nf or mati o n o n h o w t o u p date t he kit stat us i n 
t he I R T s yste m. 
D ur i n g t he i n vesti gati o n of t he pr o d uct c o m plai nt, t he I M Ps m ust be st ore d at la belle d 
c o n diti o ns u nless ot her wise i nstr ucte d; t he trial site will be n otifie d w het her t he I M Ps nee ds t o 
be ret ur ne d f or f urt her i n vesti gati o n or ma y be destr o ye d.  
Gl o bal Safet y, L E O c o ntact i nf or mati o n f or re p orti n g pr o d uct c o m plai nts:  
Fa x n u m ber: + 4 5 7 2 2 6 3 2 8 7  
E- mail a d dress: dr u g.safet y @le o -p har ma.c o m  
1 0  Disc o nti n u ati o n a n d wit h dr a w al  
1 0. 1  Ge ner al pri nci ples  
A s u bject ma y wit h dra w fr o m t he trial (i.e. wit h dra w fr o m treat me nt a n d a n y p r ot oc ol- defi ne d 
i nter ve nti o ns) or per ma ne ntl y disc o nti n ue trial treat me nt (i.e. st o p trial treat me nt o nl y, b ut 
a gree t o c o nti n ue d pr ot oc ol- defi ne d i nter ve nti o ns) at a n y ti me ( pri or t o first a p plicati o n or 
d uri n g t he treat me nt peri o d) if t he s u bject, t he i n vesti gat or, or L E O c o nsi ders t hat it is n ot i n 
t he s u bject’s best i nterest t o c o nti n ue. 
If a s u bject wit h dra ws fr o m t he trial, he/s he ma y re q uest destr ucti o n of a n y sa m ples ta ke n a n d 
n ot teste d, a n d t he i n vesti gat or m ust d oc u me nt t his i n t he s u bject’s s o urce d oc u me ntati o n. 
S u bjects w h o disc o nti n ue I M P or wit h dra w fr o m t he trial will n ot be re place d.  
 


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D at a t o be rec or de d i n t he e C R F  
T he pri mar y reas o ns f or wit h dra wal fr o m t he trial, disc o nti n uati o n of I M P, a n d n ot atte n di n g 
t he pri mar y e n d p oi nt visit (if a p plica ble) m ust be rec or de d i n t he me dical rec or ds a n d o n t he  
e n d of trial f or m i n t he e C R F w here t he f oll o wi n g o pti o ns are a vaila ble:  
•  Lac k of efficac y.  
•  A d verse e ve nt. 
•  Wit h dra wal b y s u bject.  
•  L ost t o f oll o w - u p. 
•  Deat h.  
•  Pre g na nc y. 
•  Ot her.  
If ‘a d verse e ve nt’ or ‘ ot her’ is selecte d, a s pecificati o n m ust be pr o vi de d i n t he e C R F wit h a 
clear li n k t o t he s pecific A E if a p plica ble.  
1 0. 2  I M P disc o nti n u ati o n r ules 
1 0. 2. 1  Re as o ns f or disc o nti n u ati o n of I M P  
S u bjects will per ma ne ntl y disc o nti n ue I M P i n t he e ve nt of: 
•  A n A E t hat, i n t he o pi ni o n of t he i n vesti gat or or s p o ns or’s me dical e x pert, 
c o ntrai n dicates f urt her d osi n g.  T his i ncl u des u nacce pta ble w orse ni n g of D L E 
s y m pt o ms. 
•  E vi de nce of pre g na nc y.  
•  Cli nicall y i m p orta nt la b orat or y a b n or malities:  
o  A L T a n d/ or A S T val ues > 3 × U L N  wit h t otal bilir u bi n > 2 × U L N 
( u nless ele vate d bilir u bi n is relate d t o Gil bert- Me ule n grac ht 
s y n dr o me). 
o  C o nfir me d A L T a n d/ or A S T > 5 × U L N.  
It is n ot all o we d t o restart I M P treat me nt after disc o nti n uati o n of I M P. 
1 0. 3  E arl y ter mi n ati o n assess me nts  
A n e n d of trial f or m m ust be c o m plete d f or all s u bjects, i ncl u di n g s u bjects w h o wit h dra w 
fr o m t he trial or disc o nti n ue I M P treat me nt, at t heir last trial visit (t he earl y ter mi nati o n visit, 
pri mar y e n d p oi nt visit, or t he safet y f oll o w -u p visit, w hic he ver c o mes last) . 


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Wit h dr a w al fr o m tri al  
S u bjects w h o wit h dra w fr o m t he trial f or a n y reas o n s h o ul d atte n d a n earl y ter mi nati o n visit 
as s o o n as p ossi ble after last a d mi nistrati o n of I M P (see Secti o n  4  f or data t o be c ollecte d at 
a n earl y ter mi nati o n visit). T he i n vesti gat or will re vie w a n y A Es w hic h will be f oll o we d u p 
acc or di n g t o Secti o n  1 3. 7 , if t he s u bject a grees. 
Disc o nti n u ati o n of I M P  
S u bjects w h o disc o nti n ue I M P f or a n y reas o n pri or t o Wee k 6 will be as ke d t o atte n d a n earl y 
ter mi nati o n visit as s o o n as p ossi ble after last a d mi nistrati o n of I M P a n d ret ur n t o t he trial site 
f or 2 a d diti o nal visits as i n dicate d bel o w. See t he sc he d ule of trial pr oce d ures ( Secti o n  4 ) f or 
data t o be c ollecte d at t hese visits.  
S u bjects w h o disc o nti n ue I M P pri or t o Wee k  6 will be as ke d t o atte n d:  
•  Earl y ter mi nati o n visit.  
•  Pri mar y e n d p oi nt visit ( Wee k 6).  
•  Safet y f oll o w -u p visit ( 2 wee ks after last a d mi nistrati o n of I M P).  
T he trial site will be all o we d t o sc he d ule t he pri mar y e n d p oi nt visit a n d t he safet y f oll o w- u p 
visit o n t he sa me da y if t his c o m plies wit h t he visit wi n d o ws f or b ot h visits.  
1 0. 4  L ost t o f oll o w -u p  
A s u bject will be c o nsi dere d l ost t o f oll o w - u p if t he y re peate dl y fail t o ret ur n f or sc he d ule d 
visits a n d if t he trial site is n ot a ble t o get i n c o ntact wit h t he s u bject.  
T he f oll o wi n g acti o ns m ust be ta ke n if a s u bject fails t o ret ur n t o t he trial site f or a re q uire d 
visit:  
•  T he trial site m ust atte m pt t o c o ntact t he s u bject a n d resc he d ule t he misse d visit as 
s o o n as p ossi ble a n d c o u nsel t he s u bject o n t he i m p orta nce of mai ntai ni n g t he 
assi g ne d visit sc he d ule a n d ascertai n w het her t he s u bject wis hes t o c o nti n ue i n t he 
trial. 
•  Bef ore a s u bject is dee me d l ost t o f oll o w -u p, t he i n vesti gat or or desi g nee m ust 
ma ke e ver y eff ort t o re gai n c o ntact wit h t he s u bject. S h o ul d t he s u bject c o nti n ue t o 
be u nreac ha ble, t he y will be c o nsi dere d t o ha ve wit h dra w n fr o m t he trial wit h a 
pri mar y reas o n of l ost t o f oll o w - u p. 


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1 1  Tri al assess me nts a n d pr oce d ures  
1 1. 1  O ver vie w  
E val uati o ns t o be d o ne at eac h visit are s h o w n i n t he sc he d ule of trial pr oce d ures i n Secti o n 4 . 
Refer t o Secti o n  7. 1  f or f urt her details o n t he trial desi g n. 
T he s u bject a n d i n vesti gat or assess me nts m ust be d o ne pri or t o or at least 2 h o urs after 
a p plicati o n of I M P or bat hi n g/s h o weri n g t o e ns ure relia ble e val uati o n of t he tar get lesi o n (see 
Secti o n 9. 2 ). N o n -i n vasi ve s ki n sa m pli n g s h o ul d be d o ne pri or t o or at least 4 h o urs after I M P 
a p plicati o n. 
Assess me nts a n d pr oce d ures at eac h trial visit s h o ul d be perf or me d i n t he or der s h o w n i n 
Pa nel 6 . 
P a nel 6 : Se q ue nce of assess me nts 
 
a) At t he scree ni n g visit, t he s u bject’s eli gi bilit y t o e nter t he trial m ust be c o nfir me d bef ore a n y s u bject 
assess me nts ca n be c o m plete d.  
b)  P h ot o gra p hs of lesi o ns ( o pti o nal), n o n -i n vasi ve s ki n sa m pli n g, s ki n bi o psies ( o pti o nal). 
S u bjects partici pati n g i n t he trial will be u n der caref ul s u per visi o n of a pri nci pal i n vesti gat or 
w h o m ust be a der mat ol o gist. I n vesti gat ors m ust be p h ysicia ns w h o are e x perie nce d i n 
treati n g D L E a n d ha ve d oc u me nte d e x perie nce a n d/ or trai ni n g i n use of t he assess me nts 
S u bject assess me nts a
I n vesti gat or assess me nts
Safet y a n d la b orat or y 
assess me nts
Ot her assess me nts b


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re q uire d b y t he pr ot oc ol. I n U nite d States, t he i n vesti gat or ca n als o be a certifie d p h ysicia n’s 
assista nt or a d va nce d re gistere d n urse practiti o ner. 
A Es m ust be assesse d b y me dicall y q ualifie d pers o n nel  ( Secti o n 1 3. 2 ). 
W he ne ver p ossi ble, t he sa me i n vesti gat or s h o ul d perf or m all t he e val uati o ns f or a gi ve n 
s u bject t hr o u g h o ut t he e ntire trial peri o d t o re d uce i nter-rater varia bilit y. 
T he i n vesti gat or(s) per f or mi n g t he assess me nts m ust n ot be i n v ol ve d i n t he a d mi nistrati o n of 
I M Ps (see Secti o n 9. 3. 1 ).  
1 1. 2  Assess me nts perf or me d o nl y at scree ni n g/ b aseli ne  
1 1. 2. 1  De m o gr a p hics  
T he  f oll o wi n g de m o gra p hic data will be rec or de d: 
•  Date of birt h. If f ull date of birt h is n ot all o we d t o be rec or de d  per l ocal le gislati o n , 
m o nt h a n d/ or year of birt h s h o ul d be c ollecte d t o get her wit h t he s u bject’s a ge.  
•  Se x: fe male, male.  
•  Race: A merica n I n dia n or Alas ka nati ve, Asia n, blac k or Africa n A merica n, nati ve 
Ha waiia n or ot her Pacific isla n der, w hite, ot her (re q uires a s pecificati o n t o be 
pr o vi de d). 
•  Et h nic ori gi n (self-re p orte d b y t he s u bject): His pa nic or Lati n o, n ot His pa nic or 
Lati n o.  
1 1. 2. 2  Fitz p atric k s ki n t y pe  
T he s u bject’s s ki n t y pe will be rec or de d usi n g t he Fitz patric k s ki n classificati o n ( Pa nel 7 ). 


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P a nel 7 : Fitz p atric k s ki n cl assific ati o n  
S ki n t y pe  
Descri pti o n  
I 
I n di vi d uals w h o ne ver ta n a n d al wa ys s u n b ur n if e x p ose d t o a n y a p precia ble 
a m o u nt of s u nli g ht, pri maril y re d - hea de d i n di vi d uals a n d li g htl y c o m plecte d 
bl o n des. 
II 
I n di vi d uals w h o fre q ue ntl y b ur n b ut are a ble t o ta n t o a s mall de gree after 
e xte n de d s u n e x p os ure. 
III 
I n di vi d uals w h o b ur n i nfre q ue ntl y a n d ta n rea dil y. 
I V 
I n di vi d uals w h o rarel y b ur n a n d ta n hea vil y wit h m o derate s u n e x p os ures, 
es peciall y i n di vi d uals of Asia n, A merica n I n dia n, Me diterra nea n a n d Lati n 
A merica n desce nt.  
V 
I n di vi d uals w h o ha ve dar k c o nstit uti ve pi g me ntati o n b ut bec o me n oticea bl y 
dar ker wit h s u n e x p os ure, es peciall y li g ht c o m plecte d blac k i n di vi d uals, 
t h ose of I n dia n desce nt. 
VI  
I n di vi d uals w h o ha ve t he hea viest co nstit uti ve pi g me ntati o n, es peciall y dar k 
s ki n ne d blac k i n di vi d uals. 
 
1 1. 2. 3  Me dic al hist or y  
Rele va nt me dical hist or y fr o m t he s u bject’s birt h m ust be rec or de d:   
•  D L E -rele va nt hist or y: 
o  A ge of o nset of D L E. 
o  Pre vi o us D L E treat me nts.  
o  Ot her a ut oi m m u ne diseases.  
o  L E -n o ns pecific lesi o ns.  
o  S u nscree n use.  
o  Hist or y of s m o ki n g.  
o  Hist or y of p h ot ose nsiti vit y.  
•  S ki n disease hist or y: all past a n d c urre nt s ki n disease hist or y s h o ul d be c ollecte d; 
f or eac h dia g n osis, t he start date a n d st o p date will be rec or de d (it will als o be 
rec or de d if t he dia g n osis is o n g oi n g). It will be rec or de d if t he disease is/ has bee n 
pr ese nt i nsi de or wit hi n 2 c m of t he b or der of a n y of t he tar get lesi o ns (t his 
i nf or mati o n will be e ntere d i nt o t he e C R F at baseli ne w he n t he 2 selecte d tar get 
lesi o ns ha ve bee n c o nfir me d as eli gi ble).  


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•  Ot her me dical a n d s ur gical hist or y i ncl u di n g c o nc urre nt  dia g n oses wit hi n t he 
pre vi o us 1 2 m o nt hs. F or eac h c o n diti o n, dia g n osis, or s ur gical pr oce d ure, t he start 
date a n d st o p date will be rec or de d. It will als o be rec or de d if t he c o n diti o n, 
dia g n osis, or s ur gical pr oce d ure is o n g oi n g a n d if it is/ has bee n pres e nt i n a n y of 
t he tar get lesi o ns. 
Rele va nt me dical hist or y als o i ncl u des diseases w hic h are s pecificall y liste d as e xcl usi o n 
criteria a n d diseases f or w hic h s pecific treat me nts are liste d as e xcl usi o n criteria.  
1 1. 2. 4  Hei g ht a n d wei g ht  
T he s u bject’s hei g ht ( wit h o ut s h oes) a n d t he s u bject’s wei g ht (i n i n d o or cl ot hi n g a n d wit h o ut 
s h oes) will be meas ure d. 
1 1. 2. 5  Cl assific ati o n of s yste mic l u p us er yt he m at os us  
T he m ost wi del y use d classificati o n criteria f or S L E are t h ose de vel o pe d b y t he A merica n 
C olle ge of R he u mat ol o g y ( A C R) (re vise d i n 1 9 9 7, see A p pe n di x 6 ) (2 6 ). T he patie nt is 
classifie d wit h S L E usi n g t he A C R criteria if 4 or m ore of t he ma nifestati o ns are prese nt, 
eit her seriall y or si m ulta ne o usl y, d uri n g a n y i nter val of o bser v ati ons. T he i n vesti gat or will 
sc ore t he differe nt criteria t o deter mi ne classificati o n of S L E f or eac h s u bject base d o n 
me dical hist or y, p h ysical e xa mi nati o n ( Secti o n 1 1. 4. 2 ), a n d la b sa m ples ( Secti o n 1 1. 4. 4 ). See 
Pa nel 8  f or sc ori n g i nstr ucti o ns. 


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P a nel 8 : Sc ori n g i nstr ucti o ns f or t he A meric a n C olle ge of R he u m at ol o g y criteri a f or 
cl assific ati o n of s yste mic l u p us er yt he m at os us  
Criteri o n  Ite m 
S o urce  
Sc ore  
1  
Malar ras h.  
Me dical hist or y, p h ysical 
e xa mi nati o n. 
Yes = 1  
N o = 0  
2  
Disc oi d ras h.  
Me dical hist or y, p h ysical 
e xa mi nati o n. 
Yes = 1  
N o = 0  
3  
P h ot ose nsiti vit y.  
Me dical hist or y, p h ysical 
e xa mi nati o n. 
Yes = 1  
N o = 0  
4  
Oral ulcers.  
Me dical hist or y, p h ysical 
e xa mi nati o n. 
Yes = 1  
N o = 0  
5  
N o n -er osi ve art hritis.  
Me dical hist or y, p h ysical 
e xa mi nati o n. 
Yes = 1  
N o = 0  
6  
Ple uritis or 
pericar ditis.  
Me dical hist or y, p h ysical 
e xa mi nati o n, 
electr ocar di o gra m.  
Yes = 1  
N o = 0  
If Yes, s u bject is n ot eli gi ble. 
7  
Re nal dis or der.  
Uri nal ysis.  
Yes = 1  
N o = 0  
If Yes, s u bject is n ot eli gi ble. 
8  
Ne ur ol o gic dis or der.  
Me dical hist or y, p h ysical 
e xa mi nati o n. 
Yes = 1  
N o = 0  
If Yes, s u bject is n ot eli gi ble. 
9  
Hae mat ol o gic 
dis or der.  
Bl o o d sa m ple.  
Yes = 1  
N o = 0  
If Yes, s u bject is n ot eli gi ble. 
1 0  
I m m u n ol o gic 
dis or der.  
Bl o o d sa m ple.  
Yes = 1  
N o = 0  
1 1  
P ositi ve a nti n uclear 
a nti b o d y. 
Bl o o d sa m ple.  
Yes = 1  
N o = 0  
All sc ores of t he i n di vi d ual criteria m ust be re p orte d i n t he e C R F as well as t he t otal sc ore. 
F or eli gi ble s u bjects, t he sc ore f or criteria n o. 6 t o 9 will be 0.  
A n y a b n or mal test res ults f o u n d as part of t he classificati o n of S L E will be f oll o we d u p at t he 
discreti o n of t he i n vesti gat or.  
1 1. 2. 6  C ut a ne o us L u p us Er yt he m at os us Dise ase Are a a n d Se verit y I n de x  
T he C L A SI is a vali date d sc ori n g s yste m t o assess disease acti vit y a n d da ma ge i n patie nts 
wit h C L E, ta ki n g b ot h a nat o mical re gi o n a n d m or p h ol o gical as pects i nt o acc o u nt (2 7 ) 
(A p pe n di x 7 ). Acti vit y is sc ore d base d o n er yt he ma, scale/ h y pertr o p h y, m uc o us me m bra ne 
lesi o ns, a n d al o pecia. Da ma ge is sc ore d i n ter ms of d ys pi g me ntati o n, 


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scarri n g/atr o p h y/ pa n nic ulitis, a n d scarri n g of t he scal p. T he C L A SI sc ore is t he s u m of t he 
t otal acti vit y a n d da ma ge sc ores w hic h are calc ulate d b y si m ple a d diti o n of t he s u bt otals. A 
hi g h C L A SI sc o re i n dicates m ore se vere disease.  
At scree ni n g, t he s u bjects will be sc ore d acc or di n g t o t he C L A SI a n d its re vise d versi o n 
R C L A SI f or a gl o bal disease assess me nt. See Secti o n 1 1. 2. 7  f or c ollecti o n i n t he e C R F.  
1 1. 2. 7  Re vise d C ut a ne o us L u p us Er yt he m at os us Dise ase Are a a n d Se verit y 
I n de x 
T he R C L A SI is a re vise d, vali date d versi o n of t he C L A SI (see Secti o n 1 1. 2. 6 ). As t he C L A SI, 
t he R C L A SI is a t o ol t o assess disease acti vit y a n d da ma ge i n patie nts wit h C L E, ta ki n g b ot h 
a nat o mical re gi o n a n d m or p h ol o gical as pects i nt o acc o u nt ( A p pe n di x 8 ) (2 8 ). I n a d diti o n t o 
er yt he ma a n d scali n g/ h y per kerat osis, t he R C L A SI sc ores disease acti vit y b y 
oe de ma/i nfiltrati o n a n d s u bc uta ne o us n o d ules/ pla q ues. M uc o us me m bra ne lesi o ns, n o n -
scarri n g al o pecia, a n d ‘l u p us hair’ are als o sc ore d. Da ma ge is sc ore d i n ter ms of 
d ys pi g me ntati o n, scarri n g/atr o p h y, a n d scarri n g al o pecia. T he R C L A SI sc ore is t he s u m of t he 
t otal acti vit y a n d da ma ge sc ores w hic h are calc ulate d b y si m ple a d diti o n of t he s u bt otals. A 
hi g h R C L A SI sc ore i n dicates m ore se vere disease.  
At scree ni n g, t he s u bjects will be sc ore d acc or di n g t o t he C L A SI a n d R C L A SI f or a gl o bal 
disease assess me nt. T he i n vesti gat or will sc ore all t he ele me nts acc or di n g t o t he e C R F . To 
ease data c ollecti o n, o verla p pi n g ele me nts will o nl y be rec or de d o nce.   
At all s u bse q ue nt sc he d ule d visits, o nl y t he ele me nts c o ncer ni n g s ki n lesi o n acti vit y a n d 
da ma ge will be assesse d f or eac h of t he tar get lesi o ns (see Secti o ns 1 1. 3. 2  a n d 1 1. 3. 3 ). 
1 1. 2. 8  I de ntific ati o n of t ar get lesi o ns 
T he i n vesti gat or will i de ntif y 2 c o m para ble D L E lesi o ns w hic h are less t ha n 6 m o nt hs ol d a n d 
ha ve cli nical si g ns of disease acti vit y acc or di n g t o t he eli gi bilit y criteria. T here is n o l o wer 
li mit f or size of t he tar get lesi o ns as l o n g as t he y are c o nsi dered lar ge e n o u g h f or c o m plete 
cli nical e val uati o n. T he ma xi m u m e x pecte d lesi o n size is 1 5 c m i n dia meter c orres p o n di n g t o 
1 % of B S A ( 1 ). T he size of eac h tar get lesi o n will als o be rec or de d (see Secti o n 1 1. 6. 2 ).  
T he 2 tar get lesi o ns s h o ul d prefera bl y be l ocate d i n t he sa me a nat o mical re gi o n, b ut p ri orit y 
s h o ul d be gi ve n t o t he si milarit y i n cli nical a p peara nce of disease acti vit y si g ns. If t here are 
m ore t ha n 2 lesi o ns a me na ble f or cli nical e val uati o n, t he i n vesti gat or will select t he 2  lesi o ns 
w hic h are m ost s uita ble as tar get lesi o ns. Lesi o ns o n t he scal p ma y als o be i ncl u de d if t he y 
f ulfil t he eli gi bilit y criteria.  


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T he i n vesti gat or will i de ntif y a n d e val uate 2 p ote ntial tar get lesi o ns at scree ni n g a n d will 
assess t hese a gai n at baseli ne t o ma ke s ure t hat b ot h tar get lesi o ns meet t he necessar y 
req uire me nts. I n t he u nli kel y e ve nt t hat a p ote ntial tar get lesi o n selecte d at scree ni n g n o 
l o n ger meets all eli gi bilit y criteria at baseli ne, t he i n vesti gat or has t he o pti o n t o select a ne w 
tar get lesi o n, if a vaila ble. It will be d oc u me nte d i n t he s o urce data a n d t he e C R F w het her t he 
tar get lesi o ns selecte d f or ra n d o misati o n at baseli ne are t he sa me as t he p ote ntial tar get lesi o ns 
i de ntifie d at scree ni n g (see als o Secti o n 9. 3 ). 
At baseli ne, t he selecte d tar get lesi o ns will be n u m bere d (lesi o n 1 a n d 2) as descri be d i n 
Secti o n 9. 3 , a n d t he l ocati o n of t he tar get lesi o ns will be rec or de d i n t he e C R F (scal p, 
f ore hea d, te m ple, malar, c hee k, e ye br o w, l o wer e yeli d, u p per e yeli d, l o wer li p, u p per li p, c hi n, 
e xter nal ear, e xter nal n ose, nec k, tr u n k, ar m, or le g). T he l ocati o n of t he lesi o ns will be 
s pecifie d i n m ore detail i n t he s u bject rec or ds t o e ns ure c orrect i de ntificati o n of t he lesi o ns at 
s u bse q ue nt visits. 
1 1. 3  Effic ac y assess me nts  
1 1. 3. 1  I n vesti g at or’s Gl o b al Assess me nt 
T he I G A is a n i nstr u me nt use d i n cli nical trials t o rate t he se verit y of t he s u bject’s gl o bal 
disease a n d is base d o n a 5 - poi nt scale ra n gi n g fr o m 0 (clear) t o 4 (se vere) ( Pa nel 9 ). I n t his 
trial, t he i n vesti gat or will use t he I G A as a lesi o n-s pecific assess me nt t o rate t he se verit y of 
D L E f or eac h of t he 2 tar get lesi o ns. 
T he I G A sc ore will be assesse d acc or di n g t o t he sc he d ule of trial pr oce d ures ( Secti o n  4 ). T he 
assess me nt will be base d o n t he c o n diti o n of t he disease at t he ti me of e val uati o n a n d n ot i n 
relati o n t o t he c o n diti o n at a pre vi o us visit. 
 


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P a nel 9 : I n vesti g at or’s Gl o b al Assess me nt f or disc oi d l u p us er yt he m at os us 
Sc ore  
Dise ase 
se verit y 
M or p h ol o gic al descri pti o n  
0 
Clear.  
N o acti vit y si g ns of D L E ( n o er yt he ma, n o scali n g/ h y per kerat osis, n o 
oe de ma/i nfiltrati o n). Da ma ge si g ns ma y be prese nt ( d ys pi g me ntati o n a n d/ or 
scarri n g/atr o p h y). 
1 
Al m ost 
clear.  
Pi n k or fai nt er yt he ma o nl y. N o scali n g/ h y per kerat osis, n o 
oe de ma/i nfiltrati o n.  
2 
Mil d.  
Pi n k or fai nt er yt he ma. Sli g ht scali n g ( m ostl y fi ne scales) a n d/ or sli g ht 
der mal oe de ma.  
3 
M o derate.  
Pr o mi ne nt er yt he ma. Sli g ht scali n g ( m ostl y fi ne t o circ u mscri be d a d here nt 
scales) a n d/ or sli g ht t o defi nite der mal oe de ma.  
4 
Se vere.  
Pr o mi ne nt re d, dar k re d, p ur ple, or vi olace o us c ol o ur. Cr usti n g ma y be 
prese nt. Se vere scali n g wit h f ollic ular pl u g gi n g a n d/ or der mal oe de ma wit h 
s ki n i n d urati o n. 
A b bre vi ati o n: D L E = disc oi d l u p us er yt he mat os us.  
1 1. 3. 2  S ki n lesi o n acti vit y  
T he assess me nt of s ki n lesi o n acti vit y a n d s ki n lesi o n da ma ge ( Secti o n 1 1. 3. 3 ) are base d o n 
t he C L A SI a n d R C L A SI sc ori n g scales f or rele va nt disease si g ns (see Secti o ns 1 1. 2. 6  a n d 
1 1. 2. 7 ). T he i n vesti gat or will assess eac h tar get lesi o n f or s ki n lesi o n acti vit y at t he visits 
i n dicate d i n t he sc he d ule of trial pr oce d ures ( Secti o n 4 ). T he t otal s ki n disease acti vit y sc ore 
is defi ne d as t he s u m of sc ores f or er yt he ma, scali n g/ h y per kerat osis, a n d oe de ma/i nfiltrati o n. 
Er yt he m a  
T he i n vesti gat or will sc ore er yt he ma f or eac h tar get lesi o n o n a 4- p oi nt scale:  
 0 = A bse nt.  
1 = Pi n k, fai nt. 
2 = Re d. 
3 = Dar k re d, p ur ple/ vi olace o us/cr uste d/ hae m orr ha gic. 
Sc ali n g/ h y per ker at osis 
T he i n vesti gat or will gi ve a c o m bi ne d sc ore f or scali n g a n d h y per kerat osis f or eac h tar get 
lesi o n o n a 3- p oi nt scale: 


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0 = A bs e nt. 
1 = Circ u mscri be d a d here nt scali n g/f ollic ular pl u g gi n g. 
2 = Verr uc o us h y per kerat osis.  
Oe de m a/i nfiltr ati o n  
T he i n vesti gat or will gi ve a c o m bi ne d sc ore f or oe de ma a n d i nfiltrati o n f or eac h tar get lesi o n 
o n a 3- p oi nt scale:  
0 = A bse nt.  
1 = Sli g ht, j ust p al pa ble. 
2 = Pal pa ble a n d visi ble. 
1 1. 3. 3  S ki n lesi o n d a m a ge  
T he assess me nt of s ki n lesi o n acti vit y ( Secti o n 1 1. 3. 2 ) a n d s ki n lesi o n da ma ge are base d o n 
t he C L A SI a n d R C L A SI sc ori n g scales f or rele va nt disease si g ns. T he i n vesti gat or will assess 
eac h tar get lesi o n f or s ki n lesi o n da ma ge at t he visits i n dic ate d i n t he sc he d ule of trial 
pr oce d ures ( Secti o n 4 ). T he t otal s ki n disease da ma ge sc ore is defi ne d as t he s u m of sc ores f or 
d ys pi g me ntati o n a n d scarri n g/atr o p h y. 
D ys pi g me nt ati o n 
T he i n vesti gat or will sc ore d ys pi g me ntati o n f or eac h tar get lesi o n o n a 4- p oi nt scale: 
0 = A bse nt.  
1a = H y p o pi g me ntati o n. 
1 b = H y per pi g me ntati o n. 
2 = H y p o- a n d h y per pi g me ntati o n. 
Sc arri n g/ atr o p h y  
T he i n vesti gat or will gi ve a c o m bi ne d sc ore f or scarri n g a n d atr o p h y f or eac h tar get lesi o n o n 
a 3-p oi nt scale:  
0 = A bse nt.  
1 = I nitial scarri n g.  
2 = Se vere fir m/atr o p hic/ ver mic ular scarri n g.  


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1 1. 4  S afet y assess me nts  
1 1. 4. 1  Vit al si g ns  
Vital si g ns (resti n g bl o o d press ure, peri p heral p ulse, a n d b o d y te m perat ure) m ust be assesse d 
acc or di n g t o t he sc he d ule of trial pr oce d ures ( Secti o n  4 ). Vital si g ns will be meas ure d i n a 
s u pi ne p ositi o n f oll o wi n g at least 5 mi n utes of rest.  
If a n a b n or mal vital si g n at scree ni n g is c o nsi dere d cli nicall y si g nifica nt b y t he i n vesti gat or, it 
will be at t he discreti o n of t he i n vesti gat or if t he s u bject s h o ul d be ra n d o mise d i nt o t he trial.  
I n case of a b n or mal fi n di n gs, t he vital si g n meas ure me nt ca n be re peate d a p pr o xi matel y 
1 5 mi n utes later wit h s u bjects resti n g i n a s u pi ne p ositi o n t o verif y t he first meas ure me nt. 
S h o ul d t he re peate d meas ure me nt res ult i n a n or mal val ue, t he meas ure me nt m ust be re peate d 
o nce m ore. If t he t hir d meas ure me nt verifies t he sec o n d ( n or mal) val ue, t he first meas ure me nt 
s h o ul d be c o nsi dere d false. If t he t hir d meas ure me nt c o nfir ms t he first meas ure me nt 
(a b n or mal), t he sec o n d meas ure me nt will be c o nsi dere d false. O nl y t he last val ue meas ure d 
a n d c o nsi dere d c orrect will be rec or de d i n t he e C R F. 
Re p orti n g i n e C R F  
Vital si g ns a n d t he date a n d ti me t he y were meas ure d will be rec or de d i n t he e C R F . If vital 
si g ns were n ot meas ure d, a reas o n s h o ul d be gi ve n. Cli nicall y si g nifica nt a b n or mal vital si g ns 
at t he scree ni n g visit will be d oc u me nte d as me dical hist or y i n t he e C R F. At s u bse q ue nt visits, 
a n y cli nicall y si g nifica nt deteri orati o n of a pre -e xisti n g c o n diti o n as well as a n y ne w 
cli nicall y si g nifica nt si g n, s y m pt o m, or ill ness will be re p orte d as a n A E i n acc or da nce wit h 
Secti o n  1 3. 3 . 
1 1. 4. 2  P h ysic al e x a mi n ati o n  
A ge neral p h ysical e xa mi nati o n of t he s u bject m ust be perf or me d acc or di n g t o t he sc he d ule of 
trial pr oce d ures ( Secti o n 4 ). T his i ncl u des der mat ol o gic e xa mi nati o n of t he s ki n, pal pati o n of 
t he a b d o mi nal or ga ns, a usc ultati o n of heart, l u n gs, a n d a b d o me n, basic ne ur ol o gical stat us, 
a n d ge neral e xa mi nati o n of t he e yes, ears, n ose, a n d t hr oat.  
If a n a b n or mal p h ysical fi n di n g at scree ni n g is c o nsi dere d cli nicall y si g nifica nt b y t he 
i n vesti gat or, it will be at t he discreti o n of t he i n vesti gat or if t he s u bject s h o ul d be ra n d o mise d 
i nt o t he trial.  


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Re p orti n g i n e C R F  
It will be rec or de d i n t he e C R F if a p h ysical e xa mi nati o n was perf or me d a n d, if a p plica ble, 
t he i n vesti gat or’s e val uati o n (‘ n or mal’, ‘a b n or mal, n ot cli nicall y si g nifica nt’, ‘a b n or mal, 
cli nicall y si g nifica nt’); if a p h ysical e xa mi nati o n was n ot perf or me d, a reas o n s h o ul d be 
gi ve n. 
Cli nicall y si g nifica nt a b n or mal fi n di n gs at t he scree ni n g visit will be d oc u me nte d as me dical 
hist or y i n t he e C R F. At s u bse q ue nt visits, a n y cli nicall y si g nifica nt deteri orati o n of a pre-
e xisti n g c o n d iti o n as well as a n y ne w cli nicall y si g nifica nt si g n, s y m pt o m, or ill ness will be 
re p orte d as a n A E i n acc or da nce wit h Secti o n 1 3. 3 . 
1 1. 4. 3  Electr oc ar di o gr a m  
A si n gle 1 2-lea d resti n g di gital E C G will be rec or de d after t he s u bject has bee n s u pi ne f or at 
least 5 mi n utes at t he visit i n dicate d i n t he sc he d ule of trial pr oce d ures ( Secti o n 4 ). 
A preli mi nar y e val uati o n of t he E C Gs will be perf or me d b y t he i n vesti gat or t o e val uate 
i m me diate s u bject safet y. As a mi ni m u m, t he date of E C G c ollecti o n will be rec or de d i n t he 
s o urce d oc u me nts. 
T he E C G data will be tra nsferre d t o a ce ntral E C G ser vice c o m pa n y f or ce ntral e val uati o n. A 
car di ol o gist at t he E C G ser vice c o m pa n y will a nal yse a n d i nter pret t he E C G data. T he E C G 
ser vice c o m pa n y will pr o vi de E C G e val uati o n re p orts t o t he trial sites. 
T he i n vesti gat or m ust e val uate all a b n or m al E C G res ults (‘cli nicall y si g nifica nt’ or ‘ n ot 
cli nicall y si g nifica nt’) a n d si g n a n d date. T he i n vesti gat or has t he fi nal decisi o n o n t he cli nical 
si g nifica nce of E C G a b n or malities. 
If t he scree ni n g E C G res ults i n a fi n di n g, w hic h is a b n or mal a n d of cli nical si g nifica nce, it 
will be at t he i n vesti gat or’s discreti o n t o deci de if t he s u bject s h o ul d be ra n d o mise d i nt o t he 
trial (res pecti n g e xcl usi o n criteri o n n o. 2 5 ). 
T he c ollecti o n a n d tra ns missi o n of E C G data will be descri be d i n a se parate E C G ma n ual. 
Test d u m m y tra ns missi o ns will be u n derta ke n pri or t o t he trial c o n d uct t o e ns ure t hat 
tra ns missi o ns ca n be ma de a n d t hat date a n d ti me setti n gs are c orrectl y set. 
Re p orti n g i n e C R F  
It will be rec or de d i n t he e C R F if a n E C G was perf or me d a n d t he i n vesti gat or’s assess me nt of 
E C G res ults (‘ n or mal’, ‘a b n or mal, n ot cli nicall y si g nifica nt’, ‘a b n or mal, cli nicall y 
si g nifica nt’); if a n E C G was n ot perf or me d, a reas o n m ust be gi ve n. 


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Cli nicall y si g nifica nt a b n or mal fi n di n gs at t he scree ni n g visit will be d oc u me nte d as me dical 
hist or y i n t he e C R F.  
1 1. 4. 4  L a b or at or y testi n g  
1 1. 4. 4. 1  O ver vie w  
Bl o o d a n d uri ne sa m ples will be c ollecte d acc or di n g t o t he sc he d ule of trial pr oce d ures 
( Secti o n 4 ).  
T he e val uati o ns s h o w n i n Pa nel 1 0  will be perf or me d.  


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P a nel 1 0 : Cli nic al l a b or at or y tests 
C he mistr y  
H ae m at ol o g y  
S o di u m  
P otassi u m  
Creati ni ne  
Urea nitr o ge n  
Calci u m  
Al kali ne p h os p hatase  
As partate a mi n otra nsferase  
Ala ni ne a mi n otra nsferase  
Ga m ma gl uta m yl tra nsferase  
Bilir u bi n a 
Lactate de h y dr o ge nase  
C h olester ol  
L D L c h olester ol  
H D L c h olester ol  
Tri gl yceri des  
Hae m o gl o bi n A 1c  
Al b u mi n  
Pr otei n  
 
Er yt hr oc ytes  
Hae mat ocrit  
Hae m o gl o bi n  
Er yt hr oc yte mea n c or p usc ular v ol u me  
Er yt hr oc yte mea n c or p usc ular hae m o gl o bi n 
c o nce ntrati o n  
Le u k oc ytes  
Ne utr o p hils   
Ne utr o p hils/t otal cells  
L y m p h oc ytes  
L y m p h oc ytes/t otal cells  
M o n oc ytes  
M o n oc ytes/t otal cells  
E osi n o p hils  
E osi n o p hils/t otal cells  
Bas o p hils  
Bas o p hils/t otal cells  
T hr o m b oc ytes  
Retic ul oc ytes  
Uri n al ysis b  
Ser ol o g y c 
A p peara nce  
Bilir u bi n  
Bl o o d d 
C ol o ur  
Gl uc ose  
Ket o nes  
Le u k oc yte esterase d 
Nitrite d  
Pr otei n d 
S pecific gra vit y  
Ur o bili n o ge n  
p H  
He patitis B vir us s urface a nti ge n  
He patitis B vir us s urface a nti b o d y  
He patitis B vir us c ore a nti b o d y  
He patitis C vir us a nti b o d y  
HI V -1 a nti b o d y  
HI V -2 a nti b o d y  
A nti n uclear a nti b o d y  
A nti -D N A  
A nti -S mit h a nti b o d y  
I m m u n o gl o b uli n G a nticar di oli pi n a nti b o d y 
I m m u n o gl o b uli n M a nticar di oli pi n a nti b o d y 
L u p us a ntic oa g ula nt  
I nterfer o n ga m ma release testf 
Uri ne pre g n a nc y test e 
H u ma n c h ori o nic g o na d otr o pi n  
a) 
If bilir u bi n is a b o ve U L N, direct a n d i n direct bilir u bi n will als o be meas ure d. 
b)  At scree ni n g, t he uri ne sa m ple will als o be teste d at t he trial site wit h a uri ne di pstic k t o assess S L E -relate d re nal 
dis or der (see Secti o n 1 1. 2. 5  a n d 1 1. 4. 4. 2 ). 
c) 
Meas ure d at scree ni n g o nl y.  
d)  I n case of val ues o utsi de t he refere nce ra n ges, micr osc o pic a nal ysis will be perf or me d. 
e) 
O nl y fe male s u b jects of c hil d beari n g p ote ntial. T he uri ne pre g na nc y test will ha ve a mi ni m u m se nsiti vit y of 2 5 
mI U/ m L.  
f) 
O nl y s u bjects wit h hi g h ris k of late nt t u berc ul osis.  
A b bre vi ati o ns: 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; L D L = l o w de nsit y 
li p o pr otei n; U L N = u p per li mit of n or mal. 
 


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1 1. 4. 4. 2  I n vesti g at or e v al u ati o n of l a b or at or y s a m ples 
Ce ntr al l a b or at or y  
C he mistr y, hae mat ol o g y, uri nal ysis, a n d ser ol o g y will be d o ne b y a ce ntral la b orat or y w hic h 
will pr o vi de res ults t o t he trial sites. T he i n vesti gat or m ust e val uate all res ults o utsi de t he 
refere nce ra n ge (‘cli nicall y si g nifica nt’ or ‘ n ot cli nicall y si g nifica nt’) a n d si g n a n d date. T he 
si g ne d a n d date d versi o n will be file d wit h t he i n vesti gat or’s trial d oc u me ntati o n. Cli nicall y 
si g nifica nt a b n or mal tests ma y be re peate d if dee me d rele va nt b y t he i n vesti gat or. 
If a scree ni n g la b orat or y res ult is a b n or mal a n d cli nicall y si g nifica nt, it will be at t he 
i n vesti gat or’s discreti o n t o deci de if t he s u bject s h o ul d be ra n d o mise d i nt o t he trial.  
A la b orat or y ma n ual will be pr o vi de d t o t he trial sites s pecif yi n g t he pr oce d ures f or 
c ollecti o n, pr ocessi n g, st ora ge, a n d s hi p me nt of sa m ples, as well as la b orat or y c o ntact 
i nf or mati o n s pecific t o t his trial. 
Tests perf or me d at t he tri al site  
Fe male s u bjects o f c hil d beari n g p ote ntial will ha ve a uri ne pre g na nc y test perf or me d at t he 
trial site at scree ni n g a n d at baseli ne pri or t o ra n d o misati o n. T he test will be re peate d at t he 
visits s h o w n i n t he sc he d ule of trial pr oce d ures ( Secti o n  4 ). T he date a n d t he o utc o me of t he 
uri ne pre g na nc y test will be rec or de d i n t he e C R F (‘ p ositi ve’, ‘ ne gati ve’).  
At scree ni n g, t he uri ne sa m ples will be teste d f or pr otei n uria wit h a uri ne d i pstic k t o assess 
S L E -relate d re nal dis or der ( A C R criteri o n n o. 7, see Secti o n 1 1. 2. 5  a n d A p pe n di x 6 ). If t he 
test is p ositi ve f or pr otei n uria, t he uri ne di pstic k test m ust be re peate d at least 1 wee k after t he 
first test. If t he sec o n d test is als o p ositi ve, t he s u bject is c o nsi dere d a scree ni n g fail ure d ue t o 
vi olati o n of e xcl usi o n criteri o n n o. 4 . If t he sec o n d uri ne di pstic k test is ne gati ve, t he s u bject 
ca n be i ncl u de d i n t he trial, as t he o bser ve d pr otei n uria is t he n c o nsi dere d tra nsie nt a n d n o t a 
si g n of re nal dis or der as s uc h. 
Re p orti n g i n e C R F  
At eac h visit, t he site staff will rec or d i n t he e C R F if a sa m ple was ta ke n a n d, if a p plica ble, 
t he date as well as t he i n vesti gat or’s assess me nt of t he res ults (‘ n or mal’, ‘a b n or mal, n ot 
cli nicall y si g n ifica nt’, ‘a b n or mal, cli nicall y si g nifica nt’). If a sa m ple was n ot ta ke n, a reas o n 
will be pr o vi de d. 
Cli nicall y si g nifica nt a b n or mal la b orat or y res ults at t he scree ni n g visit will be d oc u me nte d as 
me dical hist or y i n t he e C R F. At s u bse q ue nt visits, a n y cli n icall y si g nifica nt deteri orati o n of a 


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pre- e xisti n g c o n diti o n as well as a n y ne w cli nicall y si g nifica nt si g n, s y m pt o m, or ill ness will 
be re p orte d as a n A E i n acc or da nce wit h Secti o n  1 3. 3 . 
1 1. 5  P h ar m ac o d y n a mics a n d bi o m ar kers  
1 1. 5. 1  O ver vie w  
T he pat h o ge nesis of D L E is c haracterise d b y a n i nfla m mat or y i nfiltrate l ocalise d i n t he 
der mis wit h prese nce of plas mac yt oi d de n dritic cells a n d T cells. At t he m olec ular le vel, t he 
i nfla m mat or y res p o nse is d o mi nate d b y t y pe I a n d t y pe II i nterfer o ns a n d t he c he m o ki nes 
C X C L 9, C X C L 1 0, a n d C X C L 1 1, w hic h are hall mar ks of T h 1 res p o nses. 
As a n e x pl orat or y c o m p o ne nt of t his trial, n o n-i n vasi ve s ki n sa m ples a n d s ki n bi o psies will be 
c ollecte d t o create a ge neral m olec ular pr ofile of D L E a n d i n vesti gate h o w t his pr ofile 
c ha n ges u p o n treat me nt wit h del g ociti ni b. B y c o m pari n g t he e x pressi o n of rele va nt 
bi o mar kers at t he s ki n s urface le vel ( w here dr u g e x p os ure will be hi g h) wit h c ha n ges acr oss 
t he w h ole s ki n de pt h i n bi o psies, it will be esti mate d t o w hic h e xte nt t he dr u g e x p os ure i n t he 
der mis has bee n a ble t o i n hi bit t he pat h o ge nic pr ocesses.  
At all visits fr o m baseli ne u ntil e n d of treat me nt, n o n -i n vasi ve s ki n sa m ples will be ta ke n b y 
a p pl yi n g a patc h t o t he s ki n s urface t o a bs or b s ol u ble material fr o m t he s ki n (see Secti o n 
1 1. 5. 2 ). After t he trial, t hese patc hes will be a nal yse d f or disease-rele va nt c yt oki nes a n d 
c he m o ki nes at t he pr otei n le vel. If n o cli nicall y rele va nt res p o nse t o del g ociti ni b is see n, o nl y 
patc hes fr o m t he baseli ne a n d e n d of treat me nt visits will be a nal yse d.  
S ki n bi o psies will be o btai ne d at t he e n d of treat me nt visit ( Wee k 6) t o a na l yse differe nces i n 
ge ne e x pressi o n ( Secti o n 1 1. 5. 3 ). D ue t o t he i n vasi ve nat ure of t his pr oce d ure, bi o psies will 
be o pti o nal f or t he s u bjects. A f oc use d pa nel of i nfla m mat or y a n d disease-relate d ge nes will 
be a nal yse d b y q ua ntitati ve p ol y merase c hai n reacti o n ( q P C R). A ge neral e x pressi o n a nal ysis 
b y micr oarra y will be perf or me d o nl y if a cli nicall y rele va nt res p o nse t o del g ociti ni b is see n 
a n d if a s ufficie nt n u m be r of bi o psies is o btai ne d t o d o a mea ni n gf ul a nal ysis. 
C ollecti o n, ha n dli n g, a n d s hi p me nt i nstr ucti o ns f or s ki n sa m ples are pr o vi de d i n a se parate 
la b orat or y ma n ual. F or s u bjects w h o d o n ot c o m plete t he trial, t he bi o psies a n d n o n-i n vasi ve 
s ki n sa m ples liste d f or Wee k 6 s h o ul d be ta ke n at t he earl y ter mi nati o n visit. 
A s u m mar y of t he res ults will be i ncl u de d i n t he cli nical trial re p ort ( C T R) if a vaila ble at t his 
ti me. T he f ull res ults fr o m t he p har mac o d y na mics/ bi o mar ker a nal ysis of all s ki n sa m ples will 
be descri be d se paratel y i n a n a d de n d u m t o t he C T R.  


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1 1. 5. 2  N o n -i n v asi ve s ki n s a m pli n g 
N o n -i n vasi ve sa m pli n g of t he s ki n will be d o ne b y a p pl yi n g a s mall patc h t o t he selecte d s ki n 
area f or 1 5 mi n utes. T his will all o w t he patc h t o a bs or b s ol u ble pr otei ns t hat ca n di ff use 
t hr o u g h t he s ki n. T he patc h will t he n be st ore d fr oze n i n a vial u ntil it will be a nal yse d after 
t he trial. N o n -i n vasi ve s ki n sa m pli n g will n ot be d o ne f or s u bjects w h o ha ve plaster or 
ba n da ge aller g y. 
At baseli ne ( pri or t o t he first a p plicati o n of I M Ps) a n d at t he visits i n dicate d i n t he sc he d ule of 
trial pr oce d ures ( Secti o n 4 ), patc hes will be a p plie d t o eac h of t he 2 tar get lesi o ns. A 
re prese ntati ve area of eac h lesi o n s h o ul d be selecte d. A n ot her patc h will be a p plie d t o a 
n o n-lesi o nal s ki n l ocati o n of si milar a nat o mical ori gi n. T his pr oce d ure m ust be d o ne pri or t o 
or at least 4 h o urs after I M P a p plicati o n.  
It will be rec or de d i n t he e CR F if t he sa m ples were ta ke n; if n ot, a c o m me nt s h o ul d be 
pr o vi de d. T he n o n -lesi o nal l ocati o ns will be d oc u me nte d i n t he e C R F (scal p, f ore hea d, 
te m ple, malar, c hee k, e ye br o w, l o wer e yeli d, u p per e yeli d, l o wer li p, u p per li p, c hi n, e xter nal 
ear, e xter nal n o se, nec k, tr u n k, ar m, or le g). 
1 1. 5. 3  S ki n bi o psies ( o pti o n al)  
S u bjects will be as ke d t o pr o vi de s ki n bi o psies. Partici pati o n i n t his c o m p o ne nt of t he trial is 
o pti o nal a n d re q uires t hat t he s u bject pr o vi des a d diti o nal i nf or me d c o nse nt. Bi o psies will n ot 
be ta ke n if t he i n vesti gat or c o nsi ders t he pr oce d ure u ns uita ble f or t he s u bject (e. g. s u bjects 
recei vi n g a ntic oa g ula nt t hera p y). 
3 s ki n p u nc h bi o psies ( 2 m m) f or ge ne e x pressi o n a nal ysis will be ta ke n at Wee k 6 or t he 
earl y ter mi nati o n visit as s pecifie d i n the sc he d ule of trial pr oce d ures ( Secti o n  4 ). I n case of 
a n earl y ter mi nati o n visit, bi o psies will o nl y be ta ke n if t he s u bject has recei ve d treat me nt 
wit h t he I M Ps at least u ntil t he Wee k 2 visit.  
Bi o psies will be ta ke n fr o m eac h of t he tar get lesi o ns, a n d  1 bi o ps y will be ta ke n fr o m a 
n o n- lesi o nal s ki n l ocati o n of si milar a nat o mical ori gi n (sa me l ocati o n use d f or n o n-i n vasi ve 
s ki n sa m pli n g at Wee k 6, see Secti o n 1 1. 5. 2 ). Wit hi n eac h tar get lesi o n, t he bi o ps y s h o ul d be 
ta ke n fr o m a re prese ntati ve area of t he lesi o n. F or s u bjects w h o c o nse nt t o ha vi n g 
p h ot o gra p hs ta ke n, eac h tar get lesi o n s h o ul d be p h ot o gra p he d b ot h bef ore a n d after t he bi o ps y 
t o d oc u me nt t he bi o ps y site. 
T he bi o psies will be st ore d i n t u bes c o ntai ni n g R N Alater at a m bie nt te m perat ure u ntil t he ne xt 
da y a n d t he n st ore d fr oze n u ntil a nal ysis.  


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F or s u bjects w h o ha ve pr o vi de d c o nse nt t o t his part, it will be rec or de d i n t he e C R F if t he 
bi o psies were ta ke n; if n ot, a c o m me nt s h o ul d be pr o vi de d. T he n o n- lesi o nal bi o ps y site will 
be d oc u me nte d i n t he e C R F.  
A c hec k of s ki n bi o ps y w o u n d heali n g i ncl u di n g re m o val of s ut ure, if a p plica ble, will be 
perf or me d at t he safet y f oll o w - u p visit. 
1 1. 6  Ot her assess me nts  
1 1. 6. 1  S u bject assess me nts  
1 1. 6. 1. 1  P atie nt’s Gl o b al Assess me nt  
S u bjects will assess t he disease se verit y of eac h tar get lesi o n usi n g t he Pa G A at t he visits 
s pecifie d in t he sc he d ule of trial pr oce d ures ( Secti o n  4 ). T he assess me nt will be ma de usi n g 
t he 5-p oi nt scale:  
0 = Clear.  
1 = Al m ost clear.  
2 = Mil d. 
3 = M o derate.  
4 = Se ve re. 
T he assess me nt will be base d o n t he se verit y of t he D L E lesi o ns at t he ti me of t he assess me nt 
(a n d n ot i n relati o n t o t he se verit y at pre vi o us visits). T he Pa G A s h o ul d be c o m plete d bef ore 
t he i n vesti gat or’s assess me nts a n d wit h o ut t he i n vesti gat or or site staff disc ussi n g t he se verit y 
of t he tar get lesi o ns wit h t he s u bject. T he i n vesti gat or will e x plai n t he cate g ories of t he scale 
t o t he s u bject w h o will t he n i n dicate w hic h cate g or y s h o ul d be tic ke d. 
1 1. 6. 1. 2  Der m at ol o g y Life Q u alit y I n de x  
T he D L QI is a vali date d q uesti o n naire wit h c o nte nt s pecific t o t h ose wit h der mat ol o g y 
c o n diti o ns. It c o nsists of 1 0 ite ms a d dressi n g t he s u bject’s perce pti o n of t he i m pact of t heir 
s ki n disease o n differe nt as pects of t heir q ualit y of life o ver t he last wee k s uc h as 
der mat ol o g y-relate d s y m pt o ms a n d feeli n gs, dail y acti vities, leis ure, w or k or sc h o ol, pers o nal 
relati o ns hi ps, a n d t he treat me nt (2 9 ). Eac h ite m is sc ore d o n a 4- p oi nt Li kert scale ( 0 = ‘ n ot at 
all ⁄ n ot rele va nt’; 1  = ‘a little’; 2 = ‘a l ot’; 3 = ‘ ver y m uc h’). T he t otal sc ore is t he s u m of t he 
1 0 ite ms ( 0 t o 3 0); a hi g h sc ore is i n dicati ve of a p o or q ualit y of life. T he D L QI will be 
c o m plete d at t he trial site acc or di n g t o t he sc he d ule of trial pr oce d ures ( Secti o n  4 ).  


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1 1. 6. 1. 3   E xit i nter vie ws ( o pti o n al, selecte d c o u ntries o nl y)  
Q ualitati ve, se mi -str uct ure d e xit i nter vie ws will be c o n d ucte d wit h a s u b gr o u p of 2 0-3 0 
s u bjects b y e x perie nce d q ualitati ve i nter vie wers after t he e n d of t he treat me nt peri o d (i.e. after 
Wee k 6 or earl y ter mi nati o n). T he e xit i nter vie ws will o nl y be c o n d ucte d i n selecte d c o u ntries 
t o re d uce t he n u m ber of la n g ua ges. 
T he e xit i nter vie ws will be c o n d ucte d b y tele p h o ne, i n t he s u bject’s nati ve la n g ua ge, at a date 
a n d ti me a gree d wit h t he s u bject at t he Wee k 6 visit. T he i nter vie ws will be sc he d ule d t o 
occ ur as s o o n as p ossi ble after Wee k 6 a n d wit hi n a ma xi m u m of 2 wee ks. T he partici pa nts 
will be t he first 2 0 - 3 0 s u bjects w h o a gree t o ta ke part i n t he e xit i nter vie ws. U p t o 8 of t he 
i nter vie w partici pa nts ca n be s u bjects w h o wit h dra w fr o m t he trial pri or t o Wee k 6. T hese 
s u bjects will be i nter vie we d wit hi n 2 wee ks after t heir wit h dra wal fr o m t he trial.  
Eff orts will be ma de t o e ns ure t hat t he s u b gr o u p is re prese ntati ve of t he ge neral patie nt 
p o p ulati o n wit h re gar ds t o a ge, se x, a n d baseli ne D L E se verit y.  
Eac h i nter vie w is e x pecte d t o last a p pr o xi matel y 6 0 mi n utes. A s e mi-str uct ure d i nter vie w 
g ui de will be use d t o e x pl ore t he li ve d e x perie nce of D L E fr o m t he patie nt pers pecti ve 
i ncl u di n g si g ns/s y m pt o ms a n d t heir i m pact o n d o mai ns of H R Q o L. T he fi n di n gs fr o m t his 
part ma y be use d t o i nf or m t he selecti o n, de vel o p me nt, or m o dificati o n of patie nt -re p orte d 
o utc o mes a n d ot her e n d p oi nts f or use i n f ut ure D L E trials. S u bjects will be as ke d a b o ut t heir 
e x perie nce of si g ns/s y m pt o ms a n d t he i m pact o n H R Q o L d o mai ns, a n d a n y c ha n ges i n t h ose 
c o nce pts pri or t o, d uri n g, a n d f oll o wi n g p artici pati o n i n t he trial. T he i nter vie ws will als o 
i ncl u de q uesti o ns ai mi n g t o u n dersta n d t he s u bjects’ e x perie nce wit h t he I M P a n d wit h trial 
pr oce d ures. S u bjects w h o wit h dra w fr o m t he trial pri or t o Wee k 6 will als o be as ke d a b o ut t he 
reas o n f or lea vi n g t he trial. 
I nter vie wers will use t he se mi-str uct ure d i nter vie w g ui de t o g ui de t he disc ussi o n, a n d t he 
i nter vie ws will be a u di o-rec or de d a n d tra nscri be d ver bati m f or t he p ur p ose of acc urate 
a nal ysis. Q ualitati ve a nal ysis of t he ver bati m tra nscri pts (tra nsl ate d i nt o E n glis h) will be 
perf or me d usi n g t he matic a nal ysis. T he a nal ysis of t he e xit i nter vie w data will be re p orte d 
se paratel y as a n a d de n d u m t o t he C T R. T he i nter vie wers will be trai ne d i n p ote ntial A E 
re p orti n g a n d will re p ort a n y p ote ntial A Es as per  trial re p orti n g pr oce d ures ( Secti o n 1 3. 2 ). 
1 1. 6. 2  Size of t ar get lesi o ns  
T he size of eac h tar get lesi o n will be assesse d at t he visits i n dicate d i n Secti o n 4  a n d rec or de d 
i n t he e C R F. T he l o n gest dia meter will be meas ure d i n c m ( or i nc hes) t o get her wit h t he 


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dia meter per pe n dic ular t o t his. T he area will be calc ulate d i n c m 2 ( or i n2). T he tar get lesi o n 
area will be esti mate d b y m ulti pl yi n g t hese 2 di me nsi o ns (i.e. l o n gest dia meter × 
per pe n dic ular dia meter). 
1 1. 6. 3   P h ot o gr a p h y ( o pti o n al)  
S u bjects will be as ke d t o partici pate i n a p h ot o gra p h y c o m p o ne nt i n v ol vi n g di gital 
p h ot o gra p h y f or d oc u me ntati o n. Partici pati o n i n t his p h ot o gra p h y c o m p o ne nt is o pti o nal a n d 
re q uires t hat t he s u bject pr o vi des a d diti o nal i nf or me d c o nse nt. 
Di gital c ol o ur p h ot o gra p hs will be ta ke n of eac h tar get lesi o n acc or di n g t o t he sc he d ule of 
trial pr oce d ures ( Secti o n 4 ). At Wee k 6, p h ot o gra p hs s h o ul d prefera bl y be ta ke n b ot h bef ore 
a n d after ta ki n g t he bi o ps y (see Secti o n 1 1. 5. 3 ). 
F or s u bjects w h o ha ve pr o vi de d c o nse nt t o t his part, it will be rec or de d i n t he e C R F if t he 
p h ot o gra p hs were ta ke n; if n ot, a c o m me nt s h o ul d be pr o vi de d.  
T he trial sites will use t heir o w n or s p o ns or - pr o vi de d e q ui p me nt t o ta ke t he p h ot o gra p hs. 
I nstr ucti o ns f or p h ot o gra p h y sta n dar ds a n d pr oce d ures will be pr o vi de d t o t he sites i n a 
p h ot o gra p h y ma n ual.  
T he p h ot o gra p hs will ha ve n o ot her s u bject i de ntifier t ha n t he s u bject I D a n d will be u pl oa de d 
electr o nicall y t o t he e C R F u n der t he rele va nt trial visit.  
L E O ma y at its discreti o n use t he p h ot o gra p hs i n p u blicati o ns, p osters, a n d si milar t y pes of 
i nf or mati o n material or me dia tar geti n g patie nts a n d healt h care pr ofessi o nals. T he 
p h ot o gra p hs ma y als o be part of trai ni n g material use d f or trai ni n g a n d e d ucati o nal p ur p oses. 
Ste ps will be ta ke n t o e ns ure t hat t he i de ntit y of t he s u bject is pr otecte d t o t he e xte nt p ossi ble.   
1 1. 7  Esti m a te of t ot al bl o o d v ol u me c ollecte d 
Bl o o d sa m ples will be dra w n f or hae mat ol o g y, bi oc he mistr y, a n d ser ol o g y. T he t otal v ol u me 
of bl o o d t o be dra w n is less t ha n 1 0 0 m L w hic h is m uc h less t ha n t he v ol u me of bl o o d dra w n 
d uri n g a bl o o d d o nati o n ( 5 0 0 m L).  
1 1. 8  E n d of  tri al 
A n e n d of trial f or m m ust be c o m plete d i n t he e C R F f or all ra n d o mise d s u bjects (i ncl u di n g 
s u bjects w h o disc o nti n ue I M P a n d s u bjects w h o wit h dra w fr o m trial). T he f oll o wi n g data will 
be c ollecte d:  


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•  W het her t he s u bject c o m plete d t he trial.  
•  Date of tri al c o m pleti o n or disc o nti n uati o n.  
•  Date a n d ti me of last a d mi nistrati o n of I M Ps.  
•  Last sc he d ule d visit n u m ber f or w hic h data is rec or de d. 
•  If a p plica ble, pri mar y reas o ns f or disc o nti n uati o n fr o m I M P, wit h dra wal fr o m trial, 
a n d n ot atte n di n g t he pri mar y e n d p oi nt visit (lac k of efficac y, A E, wit h dra wal b y 
s u bject, l ost t o f oll o w- u p, pre g na nc y, deat h, ot her). 
T he e n d of trial f or m will be c o m plete d w he n t he s u bject has ha d t heir last visit (t hat is, t he 
earl y ter mi nati o n visit, t he safet y f oll o w - u p visit, or t he pri mar y e n d p oi nt visit, w hic he ver 
c o mes last). 
1 1. 9  St or a ge of bi ol o gic al s a m ples  
Bl o o d a n d uri ne safet y la b orat or y sa m ples will n ot be st ore d after t he safet y la b orat or y 
a nal ysis is c o m plete d. S ki n bi o psies a n d n o n- i n vasi ve s ki n sa m ples ( patc hes) will be retai ne d 
f or as l o n g as t he q ualit y of t he material per mits e val uati o n b ut f or n o l o n ger t ha n 1 2 m o nt hs 
after c o m pleti o n of t he C T R, u nless s pecific a d diti o nal c o nse nt has bee n o btai ne d t hat all o ws 
st ora ge of s ki n bi o psies f or f ut ure researc h (see bel o w). 
Bi o b a nk 
T his pr ot oc ol i ncl u des t he c ollecti o n a n d a nal ysis of differe nt bi ol o gical sa m ples. If c o nse nt is 
gi ve n b y t he s u bject, L E O will st ore t he re mai ni n g material fr o m t he s ki n bi o psies c ollecte d i n 
a bi o ba n k esta blis he d b y L E O a n d h oste d b y Bi o St ora ge Tec h n ol o gies G m b H. T he resi d ual 
bi ol o gical sa m ples will be use d f or f ut ure researc h perf or me d b y L E O. D o nati o n of t he 
sa m ples f or f ut ure researc h is v ol u ntar y a n d s u bjects m ust gi ve t heir se parate writte n c o nse nt 
t o c o nfir m d o nati o n a n d st ora ge a n d t he ter ms ass ociate d here wit h. T he sa m ples will be 
tra nsferre d fr o m t he rele va nt la b orat or y t o t he bi o ba n k. T he sa m ples will be la belle d wit h t he 
trial I D, s u bject I D, a n d t he sa m ple date t o pr otect t he pri vac y of t he s u bjects a n d t o all o w 
c o nti n ue d bli n di n g f or f ut ure a nal yses. T he sa m ples fr o m t his trial will be st ore d i n t he 
bi o ba n k f or u p t o 1 0 years after t he e n d of t he trial a n d will t he n be destr o ye d.  


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1 2  Scie ntific r ati o n ale f or tri al desi g n a n d a p pr o pri ate ness of assess me nts  
1 2. 1  Scie ntific r ati o n ale f or tri al desi g n  
T his is a m ulti -ce ntre, wit hi n -s u bject, ra n d o mise d, ve hicle-c o ntr olle d, d o u ble-bli n d trial 
w hic h will be c o n d ucte d i n acc or da nce wit h t he pr ot oc ol, I C H- G C P, a n d a p plica ble re g ulat or y 
re q uire me nts. T he pri mar y  o bjecti ve is t o de m o nstrate efficac y of del g ociti ni b crea m 2 0 m g/ g 
i n D L E. 
A d o u ble- bli n d desi g n is c h ose n t o pre ve nt a n y bias fr o m b ot h s u bject a n d i n vesti gat or. T he 
ra n d o misati o n will mi ni mise selecti o n bias a n d is c o nsi dere d t he m ost relia ble a n d i m partial 
met h o d of deter mi ni n g differe nces bet wee n treat me nts. Si nce t his is t he first trial wit h 
del g ociti ni b crea m i n D L E s u bjects, t he crea m ve hicle will ser ve as refere nce t o esta blis h t he 
efficac y a n d safet y of del g ociti ni b.  
T he wit hi n -s u bject trial desi g n is c h ose n beca use it all o ws direct c o m paris o n of del g ociti ni b 
crea m a n d ve hicle re gar di n g si g ns of D L E wit h eac h s u bject bei n g t heir o w n c o ntr ol w hic h 
eli mi nates bet wee n -s u bject variati o n. T his mi ni mises t he n u m ber of s u bjects nee de d w hic h is 
a great a d va nta ge i n a rare disease wit h a scarce pa tie nt p o p ulati o n. 
 
 
  
T he trial p o p ulati o n is selecte d t o be h o m o ge ne o us t o re d uce t he bi ol o gical variati o n a n d 
t here b y re d uce t he n u m ber of s u bjects nee de d t o e val uate t he efficac y of del g ociti ni b. T he 
eli gi bilit y criteria are desi g ne d t o mi ni mise a n y ris k ass ociate d wit h trial partici pati o n (e. g. 
e xcl usi o n of S L E patie nts wit h maj or or ga n i n v ol ve me nt).   
To pical a p plicati o n is c o nsi dere d t he preferre d r o ute of a d mi nistrati o n f or treat me nts of D L E, 
si nce t his is a c uta ne o us disease m ost ofte n c haracterise d b y fe w lesi o ns affecti n g s mall areas 
of t he s ki n. 
 
 
 
 
 
 
 
  
C CI
C CI


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. Base d o n t hese c o nsi derati o ns, treat me nt 
of D L E patie nts wit h del g ociti ni b crea m 2 0 m g/ g t wice dail y ( o n a B S A of a p pr o xi matel y 
1 %) is e x pecte d t o be safe a n d well t ole rate d.     
1 2. 2  A p pr o pri ate ness of assess me nts  
T he trial e n d p oi nts ha ve bee n selecte d t o e val uate t he efficac y of del g ociti ni b i n re d uci n g t he 
disease acti vit y of D L E. T he cli nical efficac y of del g ociti ni b will be assesse d usi n g t he I G A 
a n d s pecific disease act i vit y sc ores fr o m t he C L A SI a n d R C L A SI.  
T here is n o si n gle, sta n dar dise d gra di n g s yste m f or disease se verit y i n D L E. T he I G A scale is 
a static, or di nal, 5 -p oi nt scale use d t o rate t he s u bjects’ disease fr o m ‘clear’ t o ’se vere’ (see 
Secti o n 1 1. 3. 1 ). T he scale is defi ne d b y disti nct a n d cli nicall y rele va nt m or p h ol o gical 
descri pti o ns t o mi ni mise i nter -rater variati o n. 
T he 2 tar get lesi o ns will be e val uate d a n d sc ore d se paratel y. T he I G A scale will all o w f or a n 
o verall q ualitati ve assess me nt of t he disease se verit y of t he tar get lesi o ns. T he scale ca n be 
dic h ot o mise d t o treat me nt s uccess (sc ore 0 or 1 at Wee k 6, t hat is, a ≥2 - p oi nt re d ucti o n i n I G A 
sc ore fr o m baseli ne) a n d fail ure, re prese nti n g a mea ni n gf ul cli nical o utc o me. 
T he C L A SI a n d R C L A SI ha ve bee n de vel o pe d a n d vali date d f or assess me nt of disease 
se verit y i n C L E patie nts. B ot h t he C L A SI a n d R C L A SI sc ore t he acti vit y a n d da ma ge of t he 
disease se paratel y, c o nsi deri n g b ot h a nat o mical re gi o n a n d m or p h ol o gical as pects of s ki n 
lesi o ns. I n t his trial, t he s ki n lesi o n acti vit y a n d da ma ge si g ns sc ores are a p plie d t o t he tar get 
lesi o ns o nl y. T he i n di vi d ual si g n sc ores a n d s u m will gi ve a q ua ntitati ve assess me nt of t he 
treatme nt effect. I n a d diti o n, f ull C L A SI a n d R C L A SI assess me nts  will be d o ne at scree ni n g 
t o descri be t he o verall C L E disease b ur de n i n t he trial p o p ulati o n. 
T he Pa G A is i ncl u de d t o ca pt ure t he s u bjects’ perce pti o n of disease se verit y. 
T he safet y of t he I M P will be assesse d b y vital si g ns a n d cli nical la b orat or y meas ure me nts 
a n d A E m o nit ori n g w hic h will i ncl u de l ocal t olera bilit y.  
C CI


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S ki n bi o psies ( o pti o nal) a n d n o n- i n vasi ve s ki n sa m ples will be ta ke n f or a nal ysis of 
e x pressi o n of i nfla m mat or y a n d disease- relate d ge nes a n d bi o mar kers t o e x pl ore t he 
m olec ular c o m p o ne nts of t he disease a n d dr u g tar get e n ga ge me nt (see Secti o n  1 1. 5. 1 ). 
E xit i nter vie ws ha ve bee n i ncl u de d as a rec o g nise d mea ns of gai ni n g better u n dersta n di n g of 
t he patie nt e x perie nce of disease si g ns/s y m pt o ms a n d H R Q o L i m pacts, a n d t he I M P a n d trial 
pr oce d ures ( 3 0 ). E xit i nter vie ws are c o nsi dere d partic ularl y val ua ble i n a rare disease s uc h as 
D L E w here t here is li mite d pri or literat ure a n d k n o wle d ge a b o ut t he patie nt e x perie nce.  


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1 3  A d verse e ve nts  
1 3. 1  Defi niti o n a n d cl assific ati o n of a d verse e ve nts  
A Es a n d seri o us a d verse e ve nts ( S A Es) are defi ne d i n A p pe n di x 1 . 
Classificati o n of A Es i n ter ms of se verit y, ca usalit y , a n d o utc o me is defi ne d i n A p pe n di x 2 . 
1 3. 2  C ollecti o n of a d verse e ve nt re p orts  
A Es m ust be c ollecte d fr o m ti me of first trial -relate d acti vit y after t he s u bject has si g ne d t he 
i nf or me d c o nse nt f or m (I C F) u ntil c o m pleti o n of t he cli nical trial f or t he i n di vi d ual s u bject 
( defi ne d as t he safet y f oll o w- u p visit 2 wee ks after last a d mi nistrati o n of I M P).  
A Es m ust be assesse d b y me dicall y q ualifie d pers o n nel.  
At all visits, t he s u bject will be as ke d a n o n -lea di n g q uesti o n b y t he i n vesti gat or a b o ut A Es, 
f or e xa m ple: “ H o w ha ve y o u felt si nce I sa w y o u last?” N o s pecific s y m pt o ms s h o ul d be 
aske d f or. It is i m p orta nt t hat t he i n vesti gat or als o o bser ves t he s u bject f or a n y c ha n ges n ot 
re p orte d b y t he s u bject a n d rec or ds t hese c ha n ges. 
A n y  p ote ntial A Es re p orte d b y t he s u bjects d uri n g t he e xit i nter vie ws m ust be c ollecte d a n d 
d oc u me nte d i n t he C R O E xit I nter vie w P ote ntial A E C ollecti o n F or m. T he C R O m ust 
f or war d t he C R O E xit I nter vie w P ote ntial A E C ollecti o n F or m t o t he i n vesti gat or wit hi n 2 4 
h o urs. T he i n vesti gat or m ust c hec k if t hese p ote ntial A Es are alrea d y rec or de d i n t he e C R F. If 
n ot, t he i n vesti gat or s h o ul d c o ntact t he s u bjects f or f urt her i nf or mati o n t o e ns ure t he p ote ntial 
A Es c ollecte d b y t he C R O are rec or de d i n t he e C R F as rele va nt ( Secti o n 1 3. 3 ). If a p ote ntial 
A E q ualifies as a n S A E, t he S A E m ust be re p orte d as descri be d i n Secti o n 1 3. 4 .  
Refer t o Secti o ns 1 1. 4. 1  t o 1 1. 4. 4  f or pri nci ples f or data e ntr y i n t he e C R F. 
1 3. 3  Re p orti n g of  a d verse e ve nts  
A Es re p orte d b y t he s u bject or o bser ve d b y t he i n vesti gat or m ust be rec or de d o n t he A E f or m 
of t he e C R F a n d s h o ul d be descri be d i n t he f oll o wi n g ma n ner: 
T he A E ter m  m ust be i n precise E n glis h me dical ter mi n ol o g y (t hat is, n ot necessaril y t h e e xact 
w or ds use d b y t he s u bject). W he ne ver p ossi ble, a s pecific dia g n osis s h o ul d be state d (f or 
e xa m ple ‘aller gic c o ntact der matitis’).  
F or c uta ne o us A Es, t he l oc ati o n m ust be part of t he A E descri pti o n a n d ma y be descri be d as 
scal p, f ore hea d, te m ple, malar, c hee k, e ye br o w, l o wer e yeli d, u p per e yeli d, l o wer li p, u p per 


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li p, c hi n, e xter nal ear, e xter nal n ose, nec k, tr u n k, ar m, or le g. A d diti o nall y, t he l ocati o n s h o ul d 
be re p orte d as:  
•  Lesi o nal/ perilesi o nal ( ≤2 c m fr o m t he b or der of tar get lesi o n(s) treate d wit h I M P s).  
•  Dista nt ( > 2 c m fr o m t he  tar get lesi o n b or der). 
F or tar get lesi o nal/ perilesi o nal A Es, t he i de ntit y of t he affecte d tar get lesi o n s h o ul d be 
rec or de d (tar get lesi o n 1 or 2). 
T he d ur ati o n  of t he A E m ust be re p orte d b y t he start date a n d st o p date of t he e ve nt (it will 
als o be rec or de d if t he e ve nt is o n g oi n g). I n a d diti o n, it will be rec or de d if t he A E starte d pri or 
t o first a d mi nistrati o n of I M P. 
A Es m ust be classifie d i n ter ms of se verit y, ca usalit y, a n d o utc o me acc or di n g t o t he 
defi niti o ns i n A p pe n di x 2 . 
Acti o n t ake n wit h I M P:  a n y acti o n ta ke n wit h I M P as a c o nse q ue nce of t he A E m ust be 
rec or de d ( d ose n ot c ha n ge d, d ose re d uce d, d ose i ncrease d, dr u g i nterr u pte d, dr u g wit h dra w n, 
n ot a p plica ble, u n k n o w n). 
Ot her acti o n t ake n:  a n y ot her acti o n ta ke n as a res ult of t he A E m ust be rec or de d ( n o ne, 
c o nc o mita nt me dicati o n, c o nc urre nt pr oce d ure). 
Wit h dr a w n fr o m tri al d ue t o t his A E:  it m ust be rec or de d w het her t he A E le d t o wit h dra wal 
fr o m t he trial. 
1 3. 4  Re p ort i n g of seri o us a d verse e ve nts 
T he criteria t hat defi ne a n A E as seri o us (t hat is, a n S A E) are defi ne d i n A p pe n di x 1 . S A E 
criteria are als o liste d o n t he S A E f or m.  
1 3. 4. 1  I n vesti g at or re p orti n g res p o nsi bilities  
A n y S A E m ust be re p orte d t o L E O o n t he ( pa per) S A E f or m wit hi n 2 4 h o urs of first 
k n o wle d ge. T his re p ort s h o ul d c o ntai n a n assess me nt of a vaila ble i nf or mati o n o n seri o us ness, 
se verit y, ca usal relati o ns hi p t o t he I M P or trial pr oce d ure, t he acti o n ta ke n, t he o utc o me t o 
date, a n d a narrati ve descri pti o n of t he c o urse of t he e ve nt.  
T he c o m plete d S A E f or m m ust be fa xe d or sca n ne d a n d e- maile d t o Gl o bal Safet y at L E O 
usi n g t he e - mail a d dress or fa x n u m ber bel o w: 


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Gl o bal Safet y at L E O  
E- mail a d dress: dr u g.safet y @le o -p har ma.c o m  
Fa x n u m ber: + 4 5 7 2 2 6 3 2 8 7 
If rele va nt, t he i n vesti gat or will e ncl ose ot her i nf or mati o n wit h t he S A E f or m, s uc h as 
a n o n y mise d re p orts of dia g n ostic pr oce d ures, h os pital rec or ds, a ut o ps y re p orts, etc. 
A d diti o nall y,  Gl o bal Safet y at L E O ma y re q uest f urt her i nf or mati o n i n or der t o f ull y assess 
t he S A E. T he i n vesti gat or m ust f or war d s uc h i nf or mati o n t o L E O u p o n re q uest b y fa x or 
e-mail (see c o ntact details a b o ve).  
T he i n vesti gat or m ust n otif y t he l ocal I R B(s)/I E C(s) of  S A Es, as re q uire d b y c urre nt 
a p plica ble le gislati o n f or t he c o ncer ne d c o u ntr y.  
S A Es occ urri n g after t he c o m pleti o n of t he cli nical trial s h o ul d n ot be r o uti nel y s o u g ht or 
c ollecte d. H o we ver, s uc h e ve nts s h o ul d be re p orte d t o Gl o bal Safet y at L E O ( see c o ntact 
details a b o ve ) if t he i n vesti gat or bec o mes a ware of t he m. 
1 3. 4. 2  L E O re p orti n g res p o nsi bilities  
Gl o bal Safet y at L E O is res p o nsi ble f or assessi n g w het her or n ot a n S A E is e x pecte d. T he 
rele va nt refere nce safet y i nf or mati o n d oc u me nt f or t he I M P i n t his cli nical trial is:  
•  T he I n vesti gat or’s Br oc h ure f or del g ociti ni b, e diti o n 2. 0 a n d s u bse q ue nt 
u p dates.  
Gl o bal Safet y at L E O will n otif y t he re g ulat or y a ut h orities a n d c o ncer ne d i n vesti gat ors of 
S A Es acc or di n g t o t he c urre nt a p plica ble le gislati o n f or t he c o ncer ne d c o u ntries.  
T he I R B(s)/I E C(s) will be n otifie d of S A Es acc or di n g t o t he c urre nt a p plica ble le gislati o n f or 
t he c o ncer ne d c o u ntries.  
F or all n o n- U S c o u ntries, t he f oll o wi n g re p orti n g re q uire me nts a p pl y: all S A Es w hic h are 
assesse d as ca usall y relate d t o t he I M P(s) b y eit her t he i n vesti g at or or L E O  (I C H E 2 A 
G ui deli ne), a n d w hic h are u ne x pecte d ( S us pecte d, U ne x pecte d Seri o us A d verse Reacti o ns 
[ S U S A Rs]), are s u bject t o e x pe dite d re p orti n g t o re g ulat or y a ut h orities a n d/ or I E C(s)/I R B(s) 
acc or di n g t o t he c urre n t a p plica ble le gislati o n i n t he c o ncer ne d c o u ntries. I n vesti gat ors will be 
n otifie d of t he e v ol vi n g safet y pr ofile of t he I M P o n a n o n g oi n g basis.  


Trial I D: E X P -1 3 7 3  
Date: 2 2 -Oct -2 0 1 9  
Versi o n: 4. 0  
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1 3. 5  Ot her e ve nts t h at re q uire e x pe dite d re p orti n g  
1 3. 5. 1  Pre g n a nc y  
A n y pre g na nc y occ urri n g after first e x p os ure t o I M P a n d u ntil t he s u bject has c o m plete d t he 
trial m ust be re p orte d t o L E O wit hi n 2 4 h o urs of first k n o wle d ge usi n g t he ( pa per) Pre g na nc y 
F or m ( Part  I). All pre g na ncies m ust be f oll o we d u p u ntil deli ver y or ter mi nati o n a n d fi nal 
o utc o me m ust be re p orte d o n t he ( pa per) Pre g na nc y F or m ( Part  II) wit hi n 2 4 h o urs of first 
k n o wle d ge.   
T he c o m plete d Pre g na nc y F or ms m ust be fa xe d or sca n ne d a n d e- maile d t o Gl o bal Safet y at 
L E O. C o ntact details are gi ve n i n Secti o n 1 3. 4. 1 . 
Pre g na nt s u bjects m ust i m me diatel y disc o nti n ue I M P per ma ne ntl y ( Secti o ns 1 0. 2. 1  a n d 1 0. 3 ). 
1 3. 6  Re p orti n g of ot her e ve nts  
1 3. 6. 1  A d verse e ve nts of s peci al i nterest  
T he e ve nt liste d i n Pa nel 1 1  is c o nsi dere d a n A E of s pecial i nterest ( A E SI) i n t his trial base d 
o n o bser vati o ns fr o m a trial wit h del g ociti ni b crea m i n s u bjects wit h A D. Ecze ma her petic u m 
is a k n o w n ris k f or A D patie nts, b ut is n ot e x pecte d i n D L E patie nts. If t his A E SI is o bser ve d, 
t he i n vesti gat or m ust pr o vi de a d diti o nal details t o be rec or de d i n t he e C R F. A n A E SI ma y be 
seri o us (re q uiri n g e x pe dite d re p orti n g, Secti o n 1 3. 4 ) or n o n-seri o us. 
P a nel 11 : A d verse e ve nt of s peci al i nterest 
A d verse e ve nt of s peci al i nterest  
A d diti o n al i nf or m ati o n t o be pr o vi de d  
Ecze ma her p etic u m.  
S ki n fi n di n gs:  
•  
Lesi o n t y pe.  
•  
Disse mi nate d/l ocalise d.  
•  
L ocati o n.  
•  
Prese nt i n area wit h visi ble ecze ma/ n o 
visi ble ecze ma/ prese nt i n areas wit h a n d 
wit h o ut ecze ma.  
•  
M o n o m or p hic/ p ol y m or p hic.  
C o nfir mati o n of her pes si m ple x vir us.  
 


Trial I D: E X P -1 3 7 3  
Date: 2 2 -Oct -2 0 1 9  
Versi o n: 4. 0  
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1 3. 6. 2  O ver d ose  
A n o ver d ose is defi ne d as a s u bject usi n g m ore t ha n d o u ble t he rec o m me n de d q ua ntit y of I M P 
s pecifie d i n t his pr ot oc ol i n Secti o n 9. 2 . A n o ver d ose is eit her accide ntal or i nte nti o nal.  
T he ter m ‘ o ver d ose’ i ncl u di n g a s pecificati o n of w h y it occ urre d (acci de ntal or i nte nti o nal) 
m ust be rec or de d o n t he A E f or m of t he e C R F. I n a d diti o n, A Es ori gi nati n g fr o m o ver d ose 
m ust be rec or de d as se parate e ve nts. If t he A E ori gi nati n g fr o m t he o ver d os e q ualifies as a n 
S A E, e x pe dite d re p orti n g is re q uire d ( Secti o n 1 3. 4 ). 
1 3. 6. 3  Me dic ati o n err or  
Me dicati o n err or refers t o a n y u ni nte nti o nal err or i n t he dis pe nsi n g or a d mi nistrati o n of a n 
I M P w hile i n t he c o ntr ol of t he i n vesti gat or or s u bject. Br oa dl y, me dicati o n err ors fall i nt o 
4 cate g ories: wr o n g me dicati o n, wr o n g d ose (i ncl u di n g stre n gt h, f or m, c o nce ntrati o n, 
a m o u nt), wr o n g r o ute of a d mi nistrati o n, or wr o n g s u bject. 
T h e me dicati o n err or cate g or y m ust be d oc u me nte d o n t he A E f or m i n t he e C R F. I n a d diti o n, 
A Es ori gi nati n g fr o m a me dicati o n err or m ust be rec or de d as se parate e ve nts. If t he A E 
ori gi nati n g fr o m t he me dicati o n err or q ualifies as a n S A E, e x pe dite d re p orti n g is re q uire d 
( Secti o n 1 3. 4 ). 
1 3. 6. 4  Mis use  
Mis use refers t o sit uati o ns w here t he I M 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 nce wit h t he pr ot oc ol.  
T he ter m ‘ mis use’ m ust be rec or de d o n t he A E f or m i n t he e C R F. I n a d diti o n, A Es ori gi nati n g 
fr o m mis use m ust be rec or de d as se parate e ve nts. If t he A E ori gi nati n g fr o m mis use q ualifies 
as a n S A E, e x pe dite d re p orti n g is re q uire d ( Secti o n 1 3. 4 ). 
1 3. 6. 5  A b use  
A b use relates t o t he s p ora dic or persiste nt, i nte nti o nal e xcessi ve use of a n I M P w hic h is 
acc o m pa nie d b y har mf ul p h ysical or ps yc h ol o gical effects. 
T he ter m ‘a b use’ m ust be rec or de d o n t he A E f or m i n t he e C R F. I n a d diti o n, A Es ori gi nati n g 
fr o m a b use m ust be rec or de d as se parate e ve nts. If t he A E ori gi nati n g fr o m a b use q ualifies as 
a n S A E, e x pe dite d re p orti n g is re q uire d ( Secti o n 1 3. 4 ). 


Trial I D: E X P -1 3 7 3  
Date: 2 2 -Oct -2 0 1 9  
Versi o n: 4. 0  
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1 3. 6. 6  A g gr a v ati o n of c o n diti o n  
A n y cli nicall y si g nifica nt a g gra vati o n/e xacer bati o n/ w orse ni n g of a n y me dical c o n diti o n(s) 
(i ncl u di n g t he trial disease), c o m pare d t o scree ni n g, m ust be re p orte d as a n ( S) A E in 
acc or da nce wit h Secti o ns  1 3. 3  a n d 1 3. 4 . 
1 3. 7  F oll o w -u p f or fi n al o utc o me of a d verse e ve nts  
D uri n g t he trial, t he i n vesti gat or s h o ul d f oll o w u p f or fi nal o utc o me o n all A Es (i ncl u di n g 
S A Es). O nce a s u bject lea ves t he cli nical trial, t he i n vesti gat or s h o ul d f oll o w u p o n t he 
o utc o me of all n o n- seri o us A Es classifie d as of p ossi ble/ pr o ba ble relati o ns hi p t o t he I M P f or 
1 4 da ys or u ntil t he fi nal o utc o me is deter mi ne d, w hic he ver c o mes first. S A Es m ust be 
f oll o we d u p u ntil a fi nal o utc o me has bee n esta blis he d, t hat is, t he f oll o w- u p ma y c o nti n ue 
be y o n d t he e n d of t he cli nical trial. F or S A Es w hic h ha ve sta bilise d a n d fr o m w hic h t he 
s u bject ca n n ot be e x pecte d t o rec o ver d uri n g t he trial or t he safet y f oll o w-u p peri o ds, f or 
e xa m ple c hr o nic or sta bilise d c o n diti o ns, t he fi nal o utc o me s h o ul d be re p orte d as ‘ n ot 
rec o vere d’. I n a d diti o n, a state me nt t hat t he S A E has sta bilise d or is c hr o nic s h o ul d be a d de d 
t o t he narrati ve descri pti o n of t he S A E o n t he S A E f or m.  
1 3. 8  H a n dli n g of a n ur ge nt s afet y me as ure  
A n ur ge nt safet y meas ure is a meas ure ta ke n t o i m ple me nt a n acti o n/ pr ot oc ol de viati o n u n der 
a n e mer ge nc y. T his is defi ne d as “ …t he occ urre nce of a ny ne w eve nt rel ati n g t o t he c o n d uct 
of t he tri al or t he devel o p me nt of t he i nvesti g ati o n al me dici n al pr o d uct w here t h at ne w eve nt 
is likely t o affect t he s afety of t he s u bjects, t he s p o ns or a n d t he i nvesti g at or s h all t ake 
a p pr o pri ate ur ge nt s afety me as ures t o pr otect t he s u bjects a g ai nst a ny i m me di ate 
h az ar d. ” (3 1 ). 
If t he i n vesti gat or bec o mes a ware of i nf or mati o n t hat necessitates a n i m me diate c ha n ge i n t he 
cli nical trial pr oce d ure or a te m p orar y halt t o t he cli nical trial i n or der t o pr otect cli nical trial 
s u bjects fr o m a n y i m me diate hazar d t o t heir healt h a n d safet y, t he i n vesti gat or ca n d o s o 
wit h o ut pri or a p pr o val f r o m L E O, re g ulat or y a ut h orities, or I R Bs/I E Cs. 
T he i n vesti gat or m ust i m me diatel y i nf or m L E O – b y c o ntacti n g t he cli nical pr oject ma na ger 
or me dical e x pert – of t his c ha n ge i n t he cli nical trial pr oce d ure or of t he te m p orar y halt 
pr o vi di n g f ull details of t he i nf or mati o n a n d t he decisi o n ma ki n g pr ocess lea di n g t o t he 
i m ple me ntati o n of t he ur ge nt safet y meas ure. 
L E O m ust act i m me diatel y u p o n recei pt of t he ur ge nt safet y meas ure n otificati o n i n 
acc or da nce wit h i nter nal pr oce d ures a n d l ocal le gislati o n.  


Trial I D: E X P -1 3 7 3  
Date: 2 2 -Oct -2 0 1 9  
Versi o n: 4. 0  
Pa ge 8 1  of 1 2 2  
 
 
 
 
 
1 4  St atis tic al met h o ds 
1 4. 1  S a m ple size  
T his trial ai ms t o ac hie ve a t otal of 3 6 s u bjects c o m pleti n g t he trial acc or di n g t o t he pr ot oc ol. 
Ass u mi n g a dr o p - o ut rate of 2 0 %, a t otal of 4 5 s u bjects will be ra n d o mise d. T he scree ni n g 
fail ure rate is e x pecte d t o be a p pr o xi matel y 2 0 %. 
Wit h 3 6 s u bjects c o m pleti n g t he trial, a wit hi n -s u bject c o m paris o n of lesi o n-s pecific I G A 
sc ores acc or di n g t o t he pri mar y e n d p oi nt will detect a treat me nt differe nce wit h at least 9 0 % 
p o wer, ass u mi n g a pr o ba bilit y of cleara nce of 5 % f or ve hicle a n d  3 5 % f or del g ociti ni b crea m. 
T he p o wer calc ulati o n is base d o n a Wal d c o ntrast test f or e q ualit y of cleara nce pr o ba bilities 
e val uate d at a 5 % si g nifica nce le vel.  
1 4. 2  Tri al a n al ysis sets  
All s u bjects scree ne d i n t he trial will be acc o u nte d f or i n t he C T R.  
All ra n d o mise d s u bjects will be i ncl u de d i n t he f ull a nal ysis set ( F A S). E xcl usi o ns fr o m t he 
F A S ca n be c o nsi dere d i n s pecial cases as descri be d i n I C H E 9, Secti o n 5. 2. 1 ( F ull A nal ysis 
Set). If it is deci de d t o e xcl u de a ra n d o mise d s u bject fr o m t he F A S, a j ustificati o n a d dressi n g 
I C H E 9 will be gi ve n. 
A per pr ot oc ol ( P P) a nal ysis set will be defi ne d b y e xcl u di n g s u bjects fr o m t he F A S w h o f ulfil 
a n y of t he f oll o wi n g criteria:  
•  Recei ve n o treat me nt wit h t he I M Ps.  
•  D o n ot c o m plete t he trial u p t o a n d i ncl u di n g t he Wee k 6 visit. 
•  Fail t o pr o vi de efficac y data at t he Wee k 6 visit. 
•  Are k n o w n t o ha ve use d t he wr o n g I M P o n 1 or b ot h tar get lesi o ns. 
•  D o n ot f ulfil t he disease- defi ni n g i ncl usi o n criteria (t hat is, i ncl usi o n criteria n o. 3 -6 ). 
F urt her e xcl usi o n of s u bjects or s u bject data will be deci de d u p o n after a bli n d re vie w of t he 
data, re vie wi n g all t he re mai ni n g i n- a n d e xcl usi o n criteria, b ut f oc usi n g o n c o nc o mita nt 
me dicati o n t hat ma y affect D L E a n d als o c o nsi deri n g c o m plia nce a n d vi olati o ns of visit 
wi n d o ws. 


Trial I D: E X P -1 3 7 3  
Date: 2 2 -Oct -2 0 1 9  
Versi o n: 4. 0  
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A safet y a nal ysis set will be defi ne d as all s u bjects w h o recei ve d I M P.  
T he decisi o ns re gar di n g i ncl usi o n/e xcl usi o n of s u bjects or s u bject data fr o m t he trial a nal ysis 
sets will be d oc u me nte d i n t he a nal ysis set defi niti o n d oc u me nt bef ore brea ki n g t he 
ra n d o misati o n c o de. 
1 4. 3  St atistic al a n al ysis  
1 4. 3. 1  Dis p ositi o n of s u bjects  
T he reas o ns  f or disc o nti n uati o n of I M P or wit h dra wal fr o m trial will be prese nte d f or all 
ra n d o mise d s u bjects. 
1 4. 3. 2  De m o gr a p hics a n d ot her b aseli ne c h ar acteristics  
Descri pti ve statistics of de m o gra p hics a n d ot her baseli ne c haracteristics will be prese nte d f or 
all ra n d o mise d s u bjects b y site. Lesi o n-s pecific baseli ne c haracteristics will be prese nte d f or 
all ra n d o mise d s u bjects b y site a n d treat me nt.  
1 4. 3. 3  E x p os ure a n d tre at me nt c o m pli a nce  
T he d urati o n of e x p os ure t o treat me nt will be calc ulate d as t he n u m ber of da ys fr o m t he da te 
of first a p plicati o n of I M Ps t o t he date of last a p plicati o n of I M Ps, b ot h da ys i ncl u de d. 
E x p os ure will be prese nte d f or t he F A S as da ys of e x p os ure.  
Dr u g acc o u nta bilit y data will be calc ulate d b y s u btracti n g t he wei g ht of t he use d t u bes fr o m 
t he mea n n or mal wei g ht of f ull t u bes. Avera ge t otal usa ge will be prese nte d f or eac h treat me nt 
f or t he e ntire treat me nt peri o d.  
C o m plia nce wit h treat me nt re gi me n will be rec or de d i n t he e C R F. If a n y c o m plicati o ns or 
de viati o ns i n a d mi nistrati o n are o bser ve d, t hese will be descri be d as pr ot oc ol de viati o ns. 
Treat me nt c o m plia nce will be prese nte d f or t he safet y a nal ysis set f or eac h treat me nt via t he 
perce nta ges of misse d a n d/ or e xcessi ve a p plicati o ns, a n d a p plicati o ns of wr o n g I M P.  
1 4. 3. 4  A n al ysis of pri m ar y e n d p oi nt  
T he ef ficac y of del g ociti ni b crea m c o m pare d wit h ve hicle will be a nal yse d i n a wit hi n-s u bject 
c o m paris o n of lesi o n -s pecific treat me nt s uccess ( defi ne d as a n I G A sc ore of 0 or 1 at Wee k 6) 
usi n g Mc Ne mar’s test.  


Trial I D: E X P -1 3 7 3  
Date: 2 2 -Oct -2 0 1 9  
Versi o n: 4. 0  
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T he P P a nal ysis set will be t he pri mar y a nal ysis set  f or t he pri mar y e n d p oi nt. T he a nal ysis 
will be re peate d o n t he F A S as a se nsiti vit y a nal ysis.  
1 4. 3. 5  A n al ysis of sec o n d ar y e n d p oi nts  
Wit hi n -s u bject c o m paris o ns of t he n u m bers of lesi o n-s pecific, treat me nt-relate d A Es will be 
d o ne b y treat me nt usi n g a Wilc o x o n si g ne d ra n k test.  
Wit hi n -s u bject c o m paris o ns of lesi o n-s pecific bi nar y e n d p oi nts ( ≥2-p oi nt re d ucti o n i n 
er yt he ma sc ore , a n d ≥2 - p oi nt re d ucti o n i n I G A sc ore fr o m baseli ne t o Wee k 6) t o assess 
treat me nt differe nce will be d o ne b y Mc Ne mar’s test.   
Wit hi n -s u bject c o m paris o n of lesi o n-s pecific er yt he ma sc ore a n d t otal s ki n disease acti vit y 
sc ore t o assess treat me nt differe nce at Wee k 6 will be d o ne b y a Wilc o x o n si g ne d ra n k test. 
T he P P a nal ysis set will be t he pri mar y a nal ysis set f or t he sec o n dar y e n d p oi nts. T he a nal ysis 
will be re peate d f or t he F A S as a se nsiti vit y a nal ysis.  
1 4. 3. 6  A n al ysis of e x pl or at or y e n d p oi nts  
1 4. 3. 6. 1  A n al ysis of e x pl or at or y effic ac y e n d p oi nts  
Wit hi n -s u bject c o m paris o ns of lesi o n-s pecific bi nar y e n d p oi nts ( Pa G A sc ore of 0 or 1 at 
Wee k  6, a n d ≥2 -p oi nt re d ucti o n i n Pa G A sc ore fr o m baseli ne t o Wee k 6) t o assess treat me nt 
differe nce will be d o ne b y Mc Ne mar’s test.   
Wit hi n -s u bject c o m paris o ns of lesi o n -s pecific I G A, Pa G A, scali n g/ h y per kerat osis, 
oe de ma/i nfiltrati o n, d ys pi g me ntati o n, scarri n g/atr o p h y, t otal s ki n disease da ma ge sc ore, a n d 
t otal s ki n lesi o n disease sc ore t o assess treat me nt differe nce at Wee k 6 will be d o ne b y a 
Wi lc o x o n si g ne d ra n k test. 
T he P P a nal ysis set will be t he pri mar y a nal ysis set f or e x pl orat or y e n d p oi nts. T he a nal ysis 
will be re peate d f or t he F A S as a se nsiti vit y a nal ysis.  
1 4. 3. 6. 2  A n al ysis of s u bject assess me nts 
T he D L QI a n d Pa G A sc ores will be s u m marise d usi n g descri pti ve statistics. T he e x pl orat or y 
e n d p oi nts c o ncer ni n g Pa G A will be a nal yse d as descri be d i n Secti o n 1 4. 3. 6. 1 . 
T he e xit i nter vie ws will be re p orte d se paratel y (see Secti o n 1 4. 3. 6. 3 ). 


Trial I D: E X P -1 3 7 3  
Date: 2 2 -Oct -2 0 1 9  
Versi o n: 4. 0  
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1 4. 3. 6. 3  E xit i nter vie ws  
T he q ualitati ve e xit i nter vie ws will be a u di o -rec or de d, tra nscri be d ver bati m, a n d tra nslate d 
i nt o E n glis h f or a nal ysis. Q ualitati ve, t he matic a nal ysis met h o ds will be use d t o a nal yse t he 
ver bati m tra nscri pts. T he res ults a n d a nal ysis of t he e xit i nter vie ws will be re p orte d se paratel y 
fr o m t he C T R. 
1 4. 3. 7  A n al ysis of p h ar m ac o d y n a mics a n d bi o m ar kers  
T he f ull res ults fr o m t he p har mac o d y na mics/ bi o mar ker a nal ysis of all s ki n sa m ples will be 
descri be d se paratel y i n a n a d de n d u m t o t he C T R. A s u m mar y of t he res ults will be i ncl u de d i n 
t he C T R if a vaila ble bef ore fi nalisati o n of the C T R.  
1 4. 3. 8  E x pl or at or y a n al yses  
To assess t he effect of del g ociti ni b crea m c o m pare d wit h ve hicle o ver ti me, wit hi n -s u bject 
c o m paris o ns of lesi o n- s pecific cleara nce acc or di n g t o I G A will be d o ne b y Mc Ne mar’s test at 
baseli ne a n d at Wee ks 2, 4, a n d 8.  T his a nal ysis will be d o ne o n b ot h t he P P a nal ysis set a n d 
t he F A S.  
1 4. 3. 9  A n al ysis of s afet y  
T he a nal ysis of safet y will be base d o n t he safet y a nal ysis set.  
1 4. 3. 9. 1  A d verse e ve nts  
A Es will be c o de d d uri n g t he trial acc or di n g t o Me dical Dicti o nar y f or Re g ulat or y Acti vities 
( Me d D R A). A Es will be prese nte d b y preferre d ter m a n d pri mar y s yste m or ga n class ( S O C).  
Treat me nt -e mer ge nt A Es will be s u m marise d; h o we ver, all A Es rec or de d d uri n g t he trial will 
be i ncl u de d i n s u bject data listi n gs. A n e ve nt will be c o nsi dere d treat me nt- e mer ge nt if starte d 
after t he first a p plicati o n of I M P, or if starte d bef ore t he first a p plicati o n of I M P a n d w orse ne d 
i n se verit y after first d ose of I M P. T he ta b ulati o ns descri be d i n t he f oll o wi n g will o nl y i ncl u de 
t he treat me nt-e mer ge nt e ve nts. I n eac h of t he ta b ulati o ns, A Es are defi ne d b y Me d D R A 
preferre d ter ms wit hi n pri mar y S O C.  
A n o verall s u m mar y of t he n u m ber of e ve nts a n d t he n u m ber ( perce nta ge) of s u bjects wit h 
a n y treat me nt- e mer ge nt A Es, deat hs, S A Es, pre mat ure disc o nti n uati o ns fr o m t he trial d ue t o 
A Es, treat me nt -relate d A Es, a n d se vere A Es will be prese nte d. 


Trial I D: E X P -1 3 7 3  
Date: 2 2 -Oct -2 0 1 9  
Versi o n: 4 . 0 
Pa ge 8 5  of 1 2 2  
 
 
 
 
 
T he n u m ber of A Es a n d n u m ber of s u bjects wit h eac h t y pe of A Es will be ta b ulate d. T he 
n u m ber of lesi o n -s pecific A Es will be ta b ulate d b y treat me nt. T he n u m ber of lesi o ns wit h 
lesi o n-s pecific AEs will be cr oss -ta b ulate d wit hi n s u bject b y treat me nt. T he perce nta ge of 
lesi o ns wit h A Es will be c o m pare d bet wee n treat me nts b y Mc Ne mar’s test.  
T he se verit y f or eac h t y pe of A E will be ta b ulate d. W here t here are se veral rec or di n gs of 
se verit y f or a gi ve n t y pe of A E, se verit y will be ta ke n as t he m ost se vere rec or di n g f or t hat 
A E. T he se verit y f or eac h t y pe of lesi o n- s pecific A E will be ta b ulate d b y treat me nt. 
T he ca usal relati o ns hi p t o I M P f or eac h t y pe of A E will be ta b ulate d. W here t he i n vesti gat or 
has pr o vi de d se veral ca usalit y assess me nts f or a gi ve n t y pe of A E, t he i nf or mati o n pr o vi de d 
i n t he last A E re p ort will be use d f or t he fi nal ca usalit y assess me nt. T he rati o nale is t hat b y t he 
ti me t he last A E re p ort is c o m plete d, t he i n vesti gat or will be i n possessi o n of m ost 
i nf or mati o n a n d s h o ul d be a ble t o pr o vi de t heir best ca usalit y assess me nt. 
Relate d A Es are defi ne d as A Es f or w hic h t he i n vesti gat or has n ot descri be d t he ca usal 
relati o ns hi p t o I M P as ‘ n ot relate d’. T he n u m ber of relate d A Es a n d t he n u m ber of s u bjects 
wit h eac h t y pe of relate d A E will be ta b ulate d. T he n u m ber of lesi o n -s pecific, relate d A Es will 
be cr oss -ta b ulate d wit hi n s u bject b y treat me nt. T he n u m ber of lesi o ns wit h lesi o n-s pecific, 
relate d A Es will be ta b ulate d b y treat me nt. T he perce nta ge of lesi o ns wit h relate d A Es will be 
c o m pare d bet wee n treat me nts b y Mc Ne mar’s test.  
S A E s will be e val uate d se paratel y a n d a narrati ve f or eac h will be gi ve n.  
A E SIs a n d A Es lea di n g t o wit h dra wal fr o m trial or disc o nti n uati o n of I M P will be liste d.  
1 4. 3. 9. 2  Vit al si g ns  
T he c ha n ge i n vital si g ns ( bl o o d press ure, peri p heral p ulse , b o d y te m perat ure) fr o m baseli ne 
( Da y 1) t o Wee k 6 will be s u m marise d as mea n, sta n dar d de viati o n ( S D), me dia n, a n d 
mi ni m u m a n d ma xi m u m val ues.  
1 4. 3. 9. 3  Cli nic al l a b or at or y e v al u ati o n  
T he c ha n ge i n eac h of t he la b orat or y para meters fr o m baseli ne ( Da y 1) t o Wee k 6 will be 
s u m marise d as mea n, S D, me dia n, a n d mi ni m u m a n d ma xi m u m val ues. 
La b orat or y para meters will be classifie d as ‘l o w’, ‘ n or mal’, or ‘ hi g h’, de pe n di n g o n w het her 
t he val ue is bel o w, wit hi n, or a b o ve t he refere nce ra n ge. A s hift ta ble will be pr o d uce d 
s h o wi n g t he cate g ories at baseli ne ( Da y 1) a gai nst t h ose at Wee k 6. 


Trial I D: E X P -1 3 7 3  
Date: 2 2 -Oct -2 0 1 9  
Versi o n: 4. 0  
Pa ge 8 6  of 1 2 2  
 
 
 
 
 
S u bjects wit h la b orat or y para meters o utsi de t he refere nce ra n ge will be liste d.  
1 4. 3. 1 0  
I nteri m a n al ysis 
N o i nteri m a nal ysis is pla n ne d. 
1 4. 3. 1 1  
Ge ner al pri nci ples  
All si g nifica nce tests will be 2 -si de d usi n g t he 5 % si g nifica nce le vel. All tests will be 
i nter prete d e xcl usi vel y i n a descri pti ve ma n ner, i.e. i n de pe n de ntl y of ot her tests. All 
c o nfi de nce i nter vals will be prese nte d wit h 9 5 % de gree of c o nfi de nce, u nless ot her wise 
s pecifie d.  
A n o bser ve d- cases a p pr oac h will be use d f or ta b ulati o ns of data b y visit (t hat is, i n v ol vi n g 
o nl y t h ose s u bjects w h o atte n de d eac h s pecific visit).  
Cate g orical data will be s u m marise d usi n g t he n u m ber a n d perce nta ge of s u bjects i n eac h 
cate g or y. Lesi o n -s pecific cate g orical data will be s u m marised b y cr oss -ta b ulati o n wit hi n 
s u bject b y treat me nt. C o nti n u o us data will be s u m marise d usi n g t he mea n, me dia n, S D, a n d 
mi ni m u m a n d ma xi m u m val ues.  
All t he a nal yses s pecifie d i n t he pr ot oc ol will be re vie we d i n relati o n t o t he bli n de d data 
act uall y o btai ne d , a n d t he statistical a nal ysis pla n will be fi nalise d bef ore brea ki n g t he 
ra n d o misati o n c o de. 
1 4. 3. 1 2  
H a n dli n g of missi n g v al ues  
Missi n g val ues will be ass u me d missi n g at ra n d o m a n d will n ot be i m p ute d. 
 
 


Trial I D: E X P -1 3 7 3  
Date: 2 2 -Oct -2 0 1 9  
Versi o n: 4. 0  
Pa ge 8 7  of 1 2 2  
 
 
 
 
 
1 5  Refere nces  
1.  
Cr o ws o n A N, Ma gr o C. T he c uta ne o us pat h ol o g y of l u p us er yt he mat os us: a re vie w. J 
C uta n Pat h ol. 2 0 0 1; 2 8( 1): 1- 2 3. 
2.  
Gr ö n ha ge n C M, N y ber g F. C uta ne o us l u p us er yt he mat os us: A n u p date. I n dia n 
Der mat ol O nli ne J. 2 0 1 4; 5( 1): 7 - 1 3. 
3. 
Gillia m J N, S o nt hei mer R D. Disti ncti ve c uta ne o us s u bsets i n t he s pectr u m of l u p us 
er yt he mat os us. J A m Aca d Der mat ol. 1 9 8 1; 4( 4): 4 7 1- 5. 
4.  
D ur osar o O, Da vis M D, Ree d K B, R o hli n ger A L. I nci de nce of c uta ne o us l u p us 
er yt he mat os us, 1 9 6 5- 2 0 0 5: a p o p ulati o n- base d st u d y. Arc h Der mat ol. 
2 0 0 9; 1 4 5( 3): 2 4 9- 5 3. 
5. 
J o nes T E, Dre n kar d C, Ba o G, Li m S S, Par ker S. I nci de nce of disc oi d l u p us 
er yt he mat os us wit h o ut s yste mic l u p us: Data fr o m t he Ge or gia l u p us re gistr y. J A m 
Aca d Der mat ol. 2 0 1 3; 6 8( 4): A B 7 1. 
6. 
Griffit hs C, Bar ker J, Blei ker T, C hal mers R, Crea mer D. R o o k' s Te xt b o o k of 
Der mat ol o g y . 2 0 1 7. 
7.  
Walli n g H W, S o nt hei mer R D. C uta ne o us l u p us er yt he mat os us: iss ues i n dia g n osis a n d 
treat me nt. A merica n j o ur nal of cli nical der mat ol o g y. 2 0 0 9; 1 0( 6): 3 6 5- 8 1. 
8.  
Patel P, Wert h V. C uta ne o us l u p us er yt he mat os us: a re vie w. De r mat ol Cli n. 
2 0 0 2; 2 0( 3): 3 7 3- 8 5. 
9.  
Gr ö n ha ge n C M, F ore d C M, Gra nat h F, N y ber g F. C uta ne o us l u p us er yt he mat os us a n d 
t he ass ociati o n wit h s yste mic l u p us er yt he mat os us: a p o p ulati o n- base d c o h ort of 1 0 8 8 
patie nts i n S we de n. Br J Der mat ol. 2 0 1 1; 1 6 4( 6): 1 3 3 5- 4 1. 
1 0.  
K u h n A, Le h ma n n P, R uzic ka T. C uta ne o us L u p us Er yt he mat os us . S pri n ger Scie nce & 
B usi ness Me dia. 2 0 0 5. 
1 1.   
Ge or ge P M, T u n nesse n W W. C hil d h o o d disc oi d l u p us er yt he mat os us. Arc h Der mat ol. 
1 9 9 3; 1 2 9( 5): 6 1 3- 7. 
1 2. 
Meller S, Wi nter ber g F, Gilliet M, M üller A, La uce vici ute I, Rie ker J, et al. Ultra vi olet 
ra diati o n-i n d uce d i nj ur y, c he m o ki nes, a n d le u k oc yte recr uit me nt: A n a m plificati o n 
c ycle tri g geri n g c uta ne o us l u p us er yt he mat os us. Art hritis R he u m. 2 0 0 5; 5 2( 5): 1 5 0 4- 1 6.  
1 3.  
Meller S, Gilliet M, H o me y B. C he m o ki nes i n t he pat h o ge nesis of lic he n oi d tiss ue 
reacti o ns. J I n vest Der mat ol. 2 0 0 9; 1 2 9( 2): 3 1 5- 9. 
1 4.  
K u h n A, We nzel J, We y d H. P h ot ose nsiti vit y, a p o pt osis, a n d c yt o ki nes i n t he 
pat h o ge nesis of l u p us er yt he mat os us: a critical re vie w. Cli n Re v Aller g y I m m u n ol. 
2 0 1 4; 4 7( 2): 1 4 8- 6 2. 
1 5. 
We nzel J, W öre n kä m per E, Fre utel S, He nze S, Haller O, Bie ber T, et al. E n ha nce d 
t y pe I i nterfer o n si g nalli n g pr o m otes T h 1- biase d i nfla m mati o n i n c uta ne o us l u p us 
er yt he mat os us. J Pat h ol. 2 0 0 5; 2 0 5( 4): 4 3 5- 4 2. 
1 6.  
We nzel J, Za h n S, Bie ber T, T üti n g T. Ty pe I i nterfer o n-ass ociate d c yt ot o xic 
i nfla m mati o n i n c uta ne o us l u p us er yt he mat os us. Arc h Der mat ol Res. 2 0 0 9; 3 0 1( 1): 8 3-
6. 
1 7. 
Ja b bari A, S uárez-Fari ñas M, F ue ntes - D uc ula n J, G o nzalez J, C uet o I, Fra n ks A G, et 
al. D o mi na nt T h 1 a n d mi ni mal T h 1 7 s ke wi n g i n disc oi d l u p us re veale d b y 
tra nscri pt o mic c o m paris o n wit h ps oriasis. J I n vest Der mat ol. 2 0 1 4; 1 3 4( 1): 8 7- 9 5. 


Trial I D: E X P -1 3 7 3  
Date: 2 2 -Oct -2 0 1 9  
Versi o n: 4. 0  
Pa ge 8 8  of 1 2 2  
 
 
 
 
 
1 8.  
Ka h n J S, De vera palli S C, R os mari n D M. J A K- S T A T si g nali n g pat h wa y i n hi biti o n: a 
r ole f or treat me nt of disc oi d l u p us er yt he mat os us a n d der mat o m y ositis. I nt J 
Der mat ol. 2 0 1 8; 5 7( 8): 1 0 0 7- 1 4. 
1 9. 
K u h n A, A berer E, Bata -Cs ör g ő Z, Ca pr o ni M, Dre her A, Fra nces C, et al. S 2 k 
g ui deli ne f or treat me nt of c uta ne o us l u p us er yt he mat os us - g ui de d b y t he E ur o pea n 
Der mat ol o g y F or u m ( E D F) i n c o o perati o n wit h  t he E ur o pea n Aca de m y of 
Der mat ol o g y a n d Ve nere ol o g y ( E A D V). J E ur Aca d Der mat ol Ve nere ol. 
2 0 1 7; 3 1( 3): 3 8 9- 4 0 4. 
2 0.  
C ha n E S, Herlitz L C, Ali J. R u x oliti ni b Atte n uates C uta ne o us L u p us De vel o p me nt i n 
a M o use L u p us M o del. J I n vest Der mat ol. 2 0 1 5; 1 3 5( 9): 2 3 3 8- 9. 
2 1.  
K u h n A, Ge nsc h K, Ha ust M, Sc h nei der S W, B o ns ma n n G, Gae belei n- Wissi n g N, et 
al. Efficac y of tacr oli m us 0. 1 % oi nt me nt i n c uta ne o us l u p us er yt he mat os us: a 
m ultice nter, ra n d o mize d, d o u ble - bli n d, ve hicle-c o ntr olle d trial. J A m A ca d Der mat ol. 
2 0 1 1; 6 5( 1): 5 4- 6 4, 6 4. e 1- 2. 
2 2.  
Prest o J K, O k o n L G, Fe n g R, Wallace DJ, F urie R, Fi ore nti n o D, et al. C o m p uterize d 
pla ni metr y t o assess cli nical res p o nsi ve ness i n a p hase II ra n d o mize d trial of t o pical 
R 3 3 3 f or disc oi d l u p us er yt he mat os us. Br J Der mat ol. 2 0 1 8; 1 7 8( 6): 1 3 0 8- 1 4. 
2 3.  
Erce g A, De J o n g E M, Va n Li n ge n R G, De B o o T M, Va n De Ker k h of P C, Se y ger 
M M. Vali dati o n of cli nical a n d i ma ge s ki n sc ori n g s yste ms f or a si n gle c hr o nic disc oi d 
l u p us er yt he mat os us lesi o n. J Der mat ol o g Treat. 2 0 0 9; 2 0( 1): 3 2- 5. 
2 4.  
T ur ner- B o w ker D M , La m o ure u x R E, St o kes J, Litc her-Kell y L, Gali pea u N, 
Ya w ors k y A, et al. I nf or mi n g a pri ori Sa m ple Size Esti mati o n i n Q ualitati ve C o nce pt 
Elicitati o n I nter vie w St u dies f or Cli nical O utc o me Assess me nt I nstr u me nt 
De vel o p me nt. Val ue i n Healt h. 2 0 1 8; 2 1( 7): 8 3 9- 4 2.  
2 5.  
Sc h ulz K F, Alt ma n D G, M o her D. C O N S O R T 2 0 1 0 State me nt: u p date d g ui deli nes f or 
re p orti n g parallel gr o u p ra n d o mise d trials. B M C Me d. 2 0 1 0; 8: 1 8. 
2 6.  
A merica n C olle ge of R he u mat ol o g y. 1 9 9 7 u p date of t he 1 9 8 2 A merica n C olle ge of 
R he u mat ol o g y re vise d criteria f or classificati o n of s yste mic l u p us er yt he mat os us 
[I nter net pa ge]. Availa ble fr o m: 
htt ps:// w w w.r he u mat ol o g y. or g/ P ortals/ 0/ Files/ 1 9 9 7 % 2 0 U p date % 2 0 of % 2 0 1 9 8 2 % 2 0 Re
vise d. p df [last accesse d 1 8-Fe b - 2 0 1 9]. 
2 7.  
Al brec ht J, Ta yl or L, Berli n J A, D ula y S, A n g G, Fa k harza de h S, et al. T he C L A SI 
( C uta ne o us L u p us Er yt he mat os us Disease Area a n d Se verit y I n de x): a n o utc o me 
i nstr u me nt f or c uta ne o us l u p us er yt he mat os us. J I n vest Der mat ol. 2 0 0 5; 1 2 5( 5): 8 8 9-
9 4. 
2 8.  
K u h n A, Me ut h A M, Bei n D, A mler S, Beissert S, B ö h m M, et al. Re vise d C uta ne o us 
L u p us Er yt he mat os us Disease Area a n d Se verit y I n de x ( R C L A SI): a m o difie d 
o utc o me i nstr u me nt f or c uta ne o us l u p us er yt he mat os us. Br J Der mat ol. 
2 0 1 0; 1 6 3( 1): 8 3- 9 2. 
2 9.  
Fi nla y A Y, K ha n G K. Der mat ol o g y Life Q ualit y I n de x ( D L QI) --a si m ple practical 
meas ure f or r o uti ne cli nical use. Cli n E x p Der mat ol. 1 9 9 4; 1 9( 3): 2 1 0- 6. 
3 0.  
F o o d a n d Dr u g A d mi nistrati o n. Met h o ds t o I de ntif y W hat is I m p orta nt t o Patie nts & 
Select, De vel o p or M o dif y Fit- f or-P ur p ose Cli nical O utc o mes Assess me nts - 
Disc ussi o n D oc u me nt f or Patie nt- F oc use d Dr u g De vel o p me nt P u blic Wor ks h o p o n 
G ui da nce 3 . 2 0 1 8. 


Trial I D: E X P -1 3 7 3  
Date: 2 2 -Oct -2 0 1 9  
Versi o n: 4. 0  
Pa ge 8 9  of 1 2 2  
 
 
 
 
 
3 1.  
Directi ve 2 0 0 1/ 2 0/ E C of 4 A pril 2 0 0 1 o n t he a p pr o xi mati o n of t he la ws, re g ulati o ns 
a n d a d mi nistrati ve pr o visi o ns of t he Me m ber States relati n g t o t he i m ple me ntati o n of 
g o o d cli nical practice i n t he c o n d uct of cli nical trials o n m e dici nal pr o d ucts f or h u ma n 
use.  2 0 0 1. 
3 2. 
W M A. Worl d Me dical Ass ociati o n. Declarati o n of Helsi n ki – et hical pri nci ples f or 
me dical researc h i n v ol vi n g h u ma n s u bjects. A me n de d b y t he 6 4t h W M A Ge neral 
Asse m bl y, F ortaleza, Brazil. 2 0 1 3. 
3 3. 
CI O M S. I nter nati o nal Et hical G ui deli nes f or Healt h -relate d Researc h I n v ol vi n g 
H u ma ns. C o u ncil f or I nter nati o nal Or ga nizati o ns of Me dical Scie nces. 4t h e d. Ge ne va. 
2 0 1 6. 
3 4. 
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 nte grate d a d de n d u m t o I C H E 6( R 1): G ui deli ne f or 
g o o d cli nical practice E 6( R 2). 2 0 1 6. 
 


Trial I D: E X P -1 3 7 3  
Date: 2 2 -Oct -2 0 1 9  
Versi o n: 4. 0  
Pa ge 9 0  of 1 2 2  
 
 
 
 
 
A p pe n di x 1: Defi niti o ns of a d verse e ve nts a n d seri o us a d verse e ve nts  
A d verse e ve nt defi niti o n  
A n A E is defi ne d as a ny u nt o w ar d me dic al occ urre nce i n a p atie nt or cli nic al i nvesti g ati o n 
s u bject a d mi nistere d a p h ar m ace utic al pr o d uct a n d w hic h d oes n ot necess arily h ave a c a us al 
rel ati o ns hi p wit h t his tre at me nt. A n A E c a n t heref ore be a ny u nf av o ur a ble a n d u ni nte n de d 
si g n (i ncl u di n g a n a b n or m al l a b or at ory fi n di n g), sy m pt o m, or dise ase te m p or ally ass oci ate d 
wit h t he use of a me dici n al (i nvesti g ati o n al) pr o d uct, w het her or n ot rel ate d t o t he me dici n al 
(i nvesti g ati o n al) pr o d uct. (I C H Har m o nise d Tri partite G ui deli ne f or G o o d Cli nical Practice, 
E 6 ( R 1)).  
T his defi niti o n i ncl u des: 
•  Acci de ntal i nj uries.  
•  E ve nts relate d t o trial pr oce d ures. 
•  Reas o ns f or a n y u nfa v o ura ble a n d u n pla n ne d c ha n ge i n me dicati o n ( dr u g 
a n d/ or d ose). 
•  Cli nicall y si g nifica nt w orse ni n g of pre -e xisti n g c o n diti o ns. 
•  Reas o ns f or a d missi o n t o h os pital or s ur gical pr oce d ures u nless t hese were 
pla n ne d bef ore t he s u bject c o nse nte d t o trial partici pati o n. 
•  A Es c o m m o nl y o bser ve d a n d A Es a ntici pate d base d o n t he p har mac ol o gical 
effect of t he I M P.  
•  A n y la b orat or y a b n or malit y assesse d as cli nicall y si g nifica nt b y t he 
i n vesti gat or (see Secti o n 1 1. 4. 4. 2 ). 
Seri o us a d verse e ve nt defi niti o n  
A n S A E is a n y u nt o war d me dical occ urre nce t hat 
•  Res ults i n deat h.  
•  Is life-t hreate ni n g. 


Trial I D: E X P -1 3 7 3  
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•  Re q uires i n -patie nt h os pitalisati o n or pr ol o n gati o n of e xisti n g h os pitalisati o n. 
Pla n ne d h os pitalisati o n or pla n ne d pr ol o n ge d h os pitalisati o n d o n ot f ulfil t he 
criteria f or bei n g a n S A E b ut s h o ul d be d oc u me nte d i n t he s u bject’s me dical 
rec or d. 
•  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. 
or  
•  Is a me dicall y i m p orta nt c o n diti o n. E ve nts t hat ma y n ot be i m me diatel y 
life-t hreate ni n g or res ult i n deat h or h os pitalisati o n b ut ma y je o par dise t he 
s u bject or ma y re q uire i nter ve nti o n t o pre ve nt o ne of t he ot her o utc o mes liste d 
i n t he defi niti o n a b o ve. Exa m ples are i nte nsi ve treat me nt i n a n e mer ge nc y 
r o o m or at h o me f or aller gic br o nc h os pas m, bl o o d d yscrasias a n d c o n v ulsi o ns 
t hat d o n ot res ult i n h os pitalisati o n, de vel o p me nt of dr u g de pe n de nc y or dr u g 
a b use. 


Trial I D: E X P -1 3 7 3  
Date: 2 2 -Oct -2 0 1 9  
Versi o n: 4. 0  
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A p pe n di x 2: Cl assific ati o n of a d verse e ve nts  
Se verit y  
T he severity of t he A E s h o ul d be descri be d i n ter ms of mil d, m o derate or se vere acc or di n g t o 
t he i n vesti gat or’s cli nical j u d ge me nt. 
Mil d  
A n A E t hat is us uall y tra nsie nt a n d ma y re q uire o nl y mi ni mal treat me nt or 
t hera pe utic i nter ve nti o n. T he e ve nt d oes n ot ge nerall y i nterfere wit h us ual 
acti vities of dail y li vi n g.  
M o derate  
A n A E  t hat is us uall y alle viate d wit h a d diti o nal s pecific t hera pe utic 
i nter ve nti o n. T he e ve nt i nterferes wit h us ual acti vities of dail y li vi n g, 
ca usi n g disc o mf ort b ut p oses n o si g n ifica nt or per ma ne nt ris k of har m t o t he 
s u bject. 
Se vere  
A n A E  t hat i nterr u pts us ual acti vities of dail y li vi n g, or si g nifica ntl y affects 
cli nical stat us, or ma y re q uire i nte nsi ve t hera pe utic i nter ve nti o n.  
If t he se verit y of a n A E w orse ns, a ne w A E s h o ul d be rec or de d. 
C a us alit y  
T he c a us al rel ati o n  of t he A E t o t he use of t he I M P s h o ul d be descri be d i n ter ms of pr o ba ble, 
p ossi ble, or n ot relate d acc or di n g t o t he i n vesti gat or’s cli nical j u d ge me nt. T he cate g ories are 
defi ne d bel o w. 
Pr o ba bl y 
relate d 
F oll o ws a reas o na ble te m p oral se q ue nce fr o m a d mi nistrati o n of t he I M P.  
 
C o ul d n ot be reas o na bl y e x plai ne d b y t he s u bject’s cli nical state, 
e n vir o n me ntal or t o xic fact ors or ot her t hera pies a d mi nistere d t o t he 
s u bject. 
 
F oll o ws a k n o w n patter n of res p o nse t o t h e I M P. 
 
Disa p pears or decreases o n cessati o n or re d ucti o n i n d ose of t he I M P.  
 
Rea p pears or w orse ns u p o n re -c halle n ge. 


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P ossi bl y 
relate d 
 
F oll o ws a reas o na ble te m p oral se q ue nce fr o m t he a d mi nistrati o n of t he 
I  M P. 
 
C o ul d als o be reas o na bl y e x plai ne d b y t he s u bject’s cli nical state, 
e n vir o n me ntal or t o xic fact ors or ot her t hera pies a d mi nistere d t o t he 
s u bject. 
 
F oll o ws a k n o w n patter n of res p o nse t o t he I M P. 
N ot relate d  
 
D oes n ot f oll o w a reas o na ble te m p oral se q ue nce fr o m a d mi nistrati o n of t he 
I  M P. 
 
Is better e x plai ne d b y ot her fact ors li ke t he s u bject’s cli nical state, 
e n vir o n me ntal or t o xic fact ors or ot her t hera pies a d mi nistere d t o t he 
s u bject. 
 
D oes n ot rea p pear or w orse n u p o n re- c halle n ge. 
 
D oes n ot f oll o w a k n o w n patter n of res p o nse t o t he I M P. 
 
O utc o me  
T he o utc o me  of t he e ve nt acc or di n g t o t he i n vesti gat or’s cli nical j u d ge me nt s h o ul d be 
classifie d usi n g t he cate g ories bel o w.  


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Rec o vere d/  
res ol ve d 
T he e ve nt has st o p pe d. T he st o p date of t he e ve nt m ust be rec or de d.  
Rec o veri n g/  
res ol vi n g 
T he s u bject is clearl y rec o veri n g fr o m a n e ve nt. T he e ve nt is n ot yet 
c o m pletel y res ol ve d.  
N ot 
rec o vere d/ 
n ot res ol ve d 
E ve nt is still o n g oi n g.  
Rec o vere d/    
res ol ve d wit h 
se q uelae 
T he e ve nt has reac he d a state w here n o f urt her c ha n ges are e x pecte d a n d t he 
resi d ual s y m pt o ms are ass u me d t o persist. A n e xa m ple is he mi paresis after 
str o ke. 
 
T he st o p date of t he e ve nt m ust be rec or de d. I n case of a S A E, t he se q uelae 
s h o ul d be s pecifie d. 
Fatal  
T he s u bject has die d as a c o nse q ue nce of t he e ve nt. Date of deat h is rec or de d 
as st o p date f or t he A E. 
U n k n o w n 
U n k n o w n t o i n vesti gat or, e. g. s u bject l ost t o f oll o w- u p. 
 
N ote t hat as per t he a b o ve defi niti o n, L E O uses “rec o vere d/res ol ve d” o nl y if a n e ve nt has 
act uall y st o p pe d. Acc or di n g t o t he C DI S C defi niti o n, t he cate g or y “rec o vere d/res ol ve d” als o 
i ncl u des e ve nts w hic h ha ve i m pr o ve d. H o we ver, f oll o wi n g t he L E O defi niti o ns a b o ve, s uc h 
a n i m pr o ve d e ve nt will i nstea d be classifie d as “ n ot rec o vere d/ n ot res ol ve d” or 
“rec o veri n g/res ol vi n g”. 
Si milarl y, it s h o ul d be n ote d t hat as per t he a b o ve defi niti o n, L E O uses “rec o vere d/res ol ve d 
wit h se q uelae” o nl y if a n e ve nt has reac he d a state w here t he resi d ual s y m pt o ms are ass u me d 
t o persist. Acc or di n g t o C DI S C, a n e ve nt is c o nsi dere d “ wit h se q uelae”, if it has “retai ne d 
pat h ol o gical c o n diti o ns”. C o nse q ue ntl y, it is li kel y t hat s o me of t he e ve nts classifie d b y L E O 
wit h t he o utc o me “rec o vere d/res ol ve d wit h se q uelae” c o ul d ha ve bee n classifie d wit h t he 
o utc o me “rec o vere d/res ol ve d” acc or di n g t o t he C DI S C defi niti o n.  
I n s u m mar y, t he defi niti o ns use d b y L E O are m ore c o nser vati ve t ha n t h ose use d b y C DI S C. 
F or S A Es w hic h ha ve sta bilise d a n d fr o m w hic h t he s u bject ca n n ot be e x pecte d t o rec o ver 
d uri n g t he trial or t he safet y f oll o w -u p peri o ds, f or e xa m ple c hr o nic ill nesses, t he fi nal 
o utc o me s h o ul d be re p orte d as ‘ n ot rec o vere d’; i n a d diti o n, a state me nt t hat t he S A E has 
sta bilise d or is c hr o nic s h o ul d be a d de d t o t he narrati ve descri pti o n of t he S A E o n t he S A E 
f or m.  


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A p pe n di x 3: Tri al g o ver n a nce c o nsi der ati o ns  
A p pe n di x 3 A: Re g ul at or y a n d et hic al c o nsi der ati o ns  
T his trial will be c o n d ucte d i n acc or da nce wit h t he pr ot oc ol a n d wit h t he f oll o wi n g: 
•  C o nse ns us et hical pri nci ples deri ve d fr o m i nter nati o nal g ui deli nes i ncl u di n g t he 
c urre nt versi o n of t he Declarati o n of Helsi n ki (3 2 ) a n d C o u ncil f or I nter nati o nal 
Or ga nizati o ns of Me dical Scie nces ( CI O M S) I nter nati o nal Et hical G ui deli nes (3 3 ). 
•  C urre nt versi o n of a p plica ble I nter nati o nal C o u ncil f or Har m o nisati o n (I C H) G o o d 
Cli nical Practice ( G C P) G ui deli nes (3 4 ). 
•  E U’s Ge neral Data Pr otecti o n Re g ulati o n 2 0 1 6/ 6 7 9 of 2 7 A pril 2 0 1 6. 
•  A p plica ble la ws a n d re g ulati o ns.  
T he a p pr o priate re g ulat or y a ut h orit y(ies) m ust be n otifie d of/a p pr o ve t he cli nical trial as 
re q uire d.  
A n y d oc u me nts t hat t he I R B/I E C ma y nee d t o f ulfil its res p o nsi bilities (s uc h as t he trial 
pr ot oc ol, pr ot oc ol a me n d me nts, i n vesti gat or’s br oc h ure [as a p plica ble], s u bject i nf or mati o n 
s heet a n d i nf or me d c o nse nt f or m(s), or a d vertise me nts) will be s u b mitte d t o t he I R B/I E C. 
T hese d oc u me nts m ust be re vie we d a n d a p pr o ve d b y t he I R B/I E C bef ore t he trial is i nitiate d. 
A n y a me n d me nts t o t he pr ot oc ol m ust be a p pr o ve d b y/recei ve fa v o ura ble o pi ni o n fr o m 
rele va nt re g ulat or y a ut h orities a n d I R Bs/I E Cs, as re q uire d, pri or t o i m ple me ntati o n. 
T he pri nci pal i n vesti gat or will be res p o nsi ble f or t he f oll o wi n g, if re q uire d b y l ocal 
le gislati o n: 
•  P r o vi di n g writte n s u m maries of t he stat us of t he trial t o t he I R B/I E C a n n uall y or m ore 
fre q ue ntl y i n acc or da nce wit h t he re q uire me nts, p olicies, a n d pr oce d ures esta blis he d 
b y t he I R B/I E C.  
•  N otif yi n g t he l ocal I R B/I E C of S A Es or ot her si g nifica nt safet y fi n di n gs as re q uire d 
b y I R B/I E C pr oce d ures. 
•  Pr o vi di n g o versi g ht of t he c o n d uct of t he trial at t he trial site a n d e ns uri n g a d here nce 
t o a p plica ble nati o nal a n d i nter nati o nal le gislati o n. 


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A p pe n di x 3 B: I nf or me d c o nse nt pr ocess  
S u bjects will recei ve writte n a n d v er bal i nf or mati o n c o ncer ni n g t he cli nical trial. T his 
i nf or mati o n will e m p hasise t hat partici pati o n i n t he cli nical trial is v ol u ntar y a n d t hat t he 
s u bject ma y wit h dra w fr o m t he cli nical trial at a n y ti me a n d f or a n y reas o n. All s u bjects will 
be gi ve n a n o p p ort u nit y t o as k q uesti o ns a n d will be gi ve n s ufficie nt ti me t o c o nsi der bef ore 
c o nse nti n g. 
T he s u bject’s si g ne d a n d date d i nf or me d c o nse nt t o partici pate i n t he cli nical trial will be 
o btai ne d pri or t o a n y cli nical trial -relate d pr oce d ure bei n g carrie d out i n acc or da nce wit h 
I C H- G C P ( 4. 8) a n d all a p plica ble la ws a n d re g ulati o ns. T he a ut h orise d pers o n o btai ni n g t he 
i nf or me d c o nse nt m ust als o si g n t he I C F. 
S u bjects will be re -c o nse nte d t o t he m ost c urre nt versi o n of t he I C F(s) d uri n g t heir 
partici pati o n i n t he trial, if re q uire d.  
A c o p y of t he I C F(s) m ust be pr o vi de d t o t he s u bject.  
S u bject c ar d  
At scree ni n g, s u bjects will be pr o vi de d wit h a car d stati n g t hat t he y are partici pati n g i n a 
cli nical trial a n d w hic h c o ntai ns c o ntact a d dresses a n d tele p h o ne n u m bers of rele va nt trial site 
staff i ncl u di n g t he n u m ber f or t he i n vesti gat or i n case of e mer ge nc y sit uati o ns. T he s u bject 
car d als o i ncl u des a l ocal tele p h o ne n u m ber f or t he e mer ge nc y u n bli n di n g C R O t o be use d if 
t he i n vesti gat or or dele gate d site staff ca n n ot be reac he d or if u n bli n di n g i n t he I R T s yste m 
ca n n ot be perf or me d.  
A p pe n di x 3 C: S u bject a n d d at a c o nfi de nti alit y  
T his cli nical trial pr ot oc ol as well as all ot her i nf or mati o n, data, a n d res ults relati n g t o t his 
cli nical trial a n d/ or t o t he I M P is c o nfi de ntial i nf or mati o n of L E O a n d s hall n ot be use d b y t he 
i n vesti gat or f or p ur p oses ot her t ha n t his cli nical trial. 
T he i n vesti gat or a grees t hat L E O ma y use a n y a n d all i nf or mati o n, data, a n d res ults fr o m t his 
cli nical trial i n c o n necti o n wit h  t he de vel o p me nt of t he I M Ps a n d, t heref ore, ma y discl ose 
a n d/ or tra nsfer i nf or mati o n, data a n d/ or res ults t o ot her i n vesti gat ors, re g ulat or y a ut h orities 
a n d/ or c o m mercial part ners.  
Trial s u bjects will be assi g ne d a u ni q ue i de ntifier (s u bject  I D) b y L E O. An y s u bject’s rec or ds 
or datasets t hat are tra nsferre d t o L E O will c o ntai n t he i de ntifier o nl y; s u bject na mes or a n y 
i nf or mati o n w hic h w o ul d ma ke t he s u bject i de ntifia ble will n ot be tra nsferre d.  


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Trial s u bjects m ust be i nf or me d a n d c o nse nt t o t hat t heir pe rs o nal trial-relate d data will be 
use d b y L E O i n acc or da nce wit h l ocal data pr otecti o n la w.   
Trial s u bjects m ust be i nf or me d a n d c o nse nt t o t hat t heir me dical rec or ds ma y be e xa mi ne d b y 
Cli nical Q ualit y Ass ura nce a u dit ors or ot her a ut h orise d pers o n nel a p p oi nte d b y L E O, b y 
a p pr o priate I R B/I E C me m bers, a n d b y i ns pect ors fr o m re g ulat or y a ut h orities. 
Pr ocessi n g of pers o n al d at a  
T his pr ot oc ol s pecifies t he pers o nal data o n trial s u bjects (f or e xa m ple race, et h nicit y, a ge, 
ge n der, healt h c o n diti o n, me dical hist or y, test res ults, etc.) w hic h s hall be c ollecte d as part of 
t he cli nical trial a n d pr ocesse d d uri n g a n d after trial c o m pleti o n. 
Pers o nal data c ollecte d as part of t he cli nical trial will be tra nsferre d t o/fr o m t he 
i nstit uti o n/i n vesti gat or, L E O a n d t hir d parties acti n g o n be half of L E O. 
Pr ocessi n g of pers o nal data o n be half of L E O re q uires a writte n a gree me nt bet wee n L E O a n d 
t he rele va nt part y w hic h c o vers c ollecti o n, pr ocessi n g a n d tra nsfer of pers o nal data i n t he 
cli nical trial. I n certai n cas es a n a gree me nt o n tra nsfer of pers o nal data ma y als o be re q uire d.  
I n vesti gat ors a n d L E O m ust e ns ure t hat c ollecti o n, pr ocessi n g a n d tra nsfer of pers o nal data 
are i n c o m plia nce wit h a p plica ble le gislati o n o n data pr otecti o n a n d pri vac y, i ncl u di n g b ut n ot 
li mite d t o t he E U Ge neral Data Pri vac y Re g ulati o n. 
S u bjects m ust be as ke d t o c o nse nt t o t he c ollecti o n, pr ocessi n g a n d tra nsfer of t heir pers o nal 
data t o E U a n d n o n- E U c o u ntries f or t he p ur p ose of c o n d ucti n g t he cli nical trial, researc h a n d 
de vel o p me nt of n e w or e xisti n g pr o d ucts/ser vices, i m pr o vi n g e xisti n g pr o d ucts/ser vices, 
a p pl yi n g f or mar keti n g a ut h orisati o ns f or pr o d ucts/ser vices, mar keti n g of pr o d ucts/ser vices 
a n d ot her relate d acti vities.  
L E O has o btai ne d t he necessar y a ut h orisati o ns f or t he pr ocessi n g of pers o nal data c ollecte d i n 
t he trial. 
A p pe n di x 3 D: Rec or d kee pi n g, q u alit y c o ntr ol, a n d d at a h a n dli n g  
S o urce d at a  
F or all data rec or de d, t he s o urce d oc u me nt m ust be defi ne d i n a s o urce d oc u me nt a gree me nt 
or si milar d oc u me nt at eac h trial site. T here m ust o nl y be 1 s o urce defi ne d at a n y ti me f or a n y 
data ele me nts.  


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S o urce data s h o ul d as a ge neral r ule be rec or de d i n t he s u bject’s me dical rec or d or ot her 
defi ne d d oc u me nt n or mall y use d at t he trial site. S o urce data n ot n or mall y c ollecte d as a 
r o uti ne part of t he cli nical practice at t he site ma y be e ntere d o n a w or ks heet. Cli nical 
assess me nts/safet y e val uati o ns m ust be si g ne d a n d date d b y me dicall y q ualifie d i n vesti gat ors.  
If t he w or ks heet d oes n ot bec o me part of t he s u bject’s me dical rec or d, t he f oll o wi ng s h o ul d as 
a mi ni m u m be a d de d t o t he s u bject’s me dical rec or d: 
•  Date(s) of c o n d ucti n g t he i nf or me d c o nse nt pr ocess, i ncl u di n g date of 
pr o visi o n of s u bject i nf or mati o n. 
•  A state me nt fr o m t he i n vesti gat or t o verif y t hat eac h of t he eli gi bilit y criteria 
are met a n d d oc u me nte d. 
•  S u bject I D.  
•  Assi g ne d kit n u m ber.  
•  T he fact t hat t he s u bject is partici pati n g i n a cli nical trial i n D L E  i ncl u di n g 
treat me nt wit h del g ociti ni b crea m a n d ve hicle f or 6 wee ks. 
•  Ot her rele va nt me dical i nf or mati o n.  
Tri al m o nit ori n g  
D uri n g t he c o urse of t he trial, C R A(s) will visit t he trial site. T hese visits ha ve t he f oll o wi n g 
o bjecti ves: (i) t o c o nti n uall y verif y s o urce data t o c o nfir m t hat data e ntere d i nt o t he e C R F b y 
a ut h orise d site pers o n nel are acc urate, c o m plete, a n d verifia ble fr o m s o urce d oc u me nts; (ii) t o 
c o nfir m t hat t he safet y a n d ri g hts of s u bjects are bei n g pr otecte d; a n d (iii) t o c o nfir m t hat t he 
trial is bei n g c o n d ucte d i n acc or da nce wit h t he c urre ntl y a p pr o ve d pr ot oc ol a n d a n y ot her trial 
a gree me nts, I C H - G C P, a n d all a p plica ble re g ulat or y re q uire me nts. 
T he m o nit ori n g visit i nter vals will de pe n d o n t he trial site’s recr uit me nt rate a n d t he 
c o m plia nce of t he trial site wit h t he pr ot oc ol a n d I C H -G C P.  
I n or der t o perf or m t heir r ole effecti vel y, C R As a n d pers o ns i n v ol ve d i n q ualit y ass ura nce a n d 
i ns pecti o ns will nee d direct access  t o s o urce data, e. g. me dical rec or ds, la b orat or y re p orts, 
a p p oi nt me nt b o o ks, etc. If t he electr o nic me dical rec or d d oes n ot ha ve a visi ble a u dit trail, t he 
i n vesti gat or m ust pr o vi de t he C R A wit h si g ne d a n d date d pri nt o uts. I n a d diti o n, rele va nt site 
staff s h o ul d be a vaila ble f or disc ussi o ns at m o nit ori n g visits a n d bet wee n m o nit ori n g visits 
(e. g. b y tele p h o ne). 


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Pr ot oc ol c o m pli a nce  
Pr ot oc ol de viati o ns will be d oc u me nte d a n d n otifie d t o t he i n vesti gat or. Pr ot oc ol de viati o ns 
will be assesse d b y L E O a n d maj or de viati o ns descri be d i n t he C T R.  
S p o ns or a u dits, I R B/I E C re vie w, a n d re g ul at or y a ge nc y i ns pecti o ns 
T he cli nical trial will be s u bject t o a u dits c o n d ucte d b y L E O or i ns pecti o ns fr o m d o mestic or 
f orei g n re g ulator y a ut h orities or fr o m I R Bs/I E Cs. A u dits a n d i ns pecti o ns ma y ta ke place 
d uri n g or after t he trial. T he i n vesti gat or a n d t he site staff as well as L E O staff ha ve a n 
o bli gati o n t o c o o perate a n d assist i n a u dits a n d i ns pecti o ns. T his i ncl u des gi vi n g a u dit ors a n d 
i ns pect ors direct access t o all s o urce d oc u me nts a n d ot her d oc u me nts at t he trial site rele va nt 
t o t he cli nical trial. T his i ncl u des per missi o n t o e xa mi ne, verif y a n d re pr o d uce a n y rec or ds 
a n d re p orts t hat are i m p orta nt t o t he e val uati o n of t he trial.  
If t he trial site is c o ntacte d f or a n i ns pecti o n b y c o m pete nt a ut h orities, L E O m ust be n otifie d 
i m me diatel y. 
Ris k assess me nt  
I n t his trial, t he ris ks t o critical trial pr ocesses a n d data ha ve bee n e val uate d. T he mai n ris k is 
recr uit me nt pr o ble ms, as D L E is a rare disease. T his ris k will be a d dresse d b y t h or o u g h 
feasi bilit y a nal ysis d uri n g t he trial pla n ni n g p hase. 
Ot her i de ntifie d ris ks are:  
•  I nc o nsiste nc y wit hi n t he pri mar y e n d p oi nt data d ue t o I G A i nter-rater 
varia bilit y.  
•  Acci de ntal i n vesti gat or u n bli n di n g d ue t o sli g ht differe nces i n c ol o ur bet wee n 
t he 2 I M Ps. 
•  Acci de ntal use  of t he wr o n g I M P o n 1 or b ot h tar get lesi o ns. 
Ris k miti gati o n acti vities t o e ns ure data q ualit y a n d s u bject safet y i ncl u de:  
•  To e ns ure c o nsiste nt efficac y assess me nts (I G A), all assess ors will recei ve 
trai ni n g bef ore starti n g t he trial. W he ne ver p ossi ble, t he efficac y assess me nts 
will be ma de b y t he sa me i n vesti gat or at eac h visit f or a gi ve n s u bject t o 
re d uce i nter-rater varia bilit y. 
•  T o a v oi d u n bli n di n g, sites will be re q uire d t o assi g n a staff me m ber w h o is n ot 
i n v ol ve d i n cli nical assess me nts t o a p pl y t he first I M P d oses at t he baseli ne 
visit.  


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•  To e ns ure t hat t he s u bjects a p pl y t he I M Ps t o t he c orrect lesi o ns t hr o u g h o ut t he 
trial, t he s u bjects will recei ve a b o d y dia gra m ill ustrati n g t he l ocati o n a n d 
assi g ne d treat me nt of eac h tar get lesi o n at t he baseli ne visit as a 
refere nce/re mi n der. 
I n a d diti o n, t o e ns ure c o nsiste nt A E m o nit ori n g a n d a v oi d d u plicate A E re p orts, C R O staff 
c o n d ucti n g t he e xit i nter vie ws will be pr o perl y trai ne d t o detect a n d re p ort a n y A Es t hat mi g ht 
be re p orte d d uri n g t he se i nter vie ws ( Secti o n 1 3. 2 ). 
T hr o u g h o ut t he trial, re g ular data q ualit y re vie w meeti n gs will be hel d t o e ns ure c o nti n u o us 
i m pr o ve me nt of data q ualit y a n d pre ve nti o n of mista kes. D uri n g m o nit ori n g visits at t he trial 
sites, t he C R As will verif y t hat i n vesti gat ors w or k acc or di n g t o t he pr ot oc ol. 
D at a h a n dli n g  
Data will be c ollecte d b y mea ns  of electr o nic data ca pt ure u nless tra ns mitte d electr o nicall y t o 
L E O or desi g nee (e. g. la b orat or y data). T he i n vesti gat or or staff a ut h orise d b y t he i n vesti gat or 
will e nter s u bject data i nt o t he e C R F. Data rec or de d i n t he e C R F will be accessi ble t o t he tri al 
site a n d L E O pers o n nel i m me diatel y after e ntr y. T he e C R F m ust be mai ntai ne d i n a n 
u p- t o-date state b y t he trial site at all ti mes.  
T he i n vesti gat or m ust verif y t he c orrect ness of t he data e ntere d b y t he site b y electr o nicall y 
dati n g a n d si g ni n g all e C R F pa ges use d. T his si g nat ure i nf or mati o n will be ke pt i n t he a u dit 
trail a n d ca n n ot be altere d. A n y c orrecti o n(s) ma de b y t he i n vesti gat or or a ut h orise d site staff 
t o t he e C R F after ori gi nal e ntr y will be d oc u me nte d i n t he a u dit trail. C ha n ges t o data alread y 
a p pr o ve d will re q uire t he re-si g nat ure b y t he i n vesti gat or. T he pers o n ma ki n g t he c ha n ge t o 
t he data, a n d t he date, ti me, a n d reas o n f or t he c ha n ge will be i de ntifie d i n t he a u dit trail. 
S u bject data s h o ul d be e ntere d i nt o t he e C R F n o later t ha n 5 w or ki n g da ys after eac h visit, 
u nless a differe nt dea dli ne is state d i n t he Cli nical Trial A gree me nt. Q ueries f or discre pa nt 
data will be ge nerate d a ut o maticall y b y t he s yste m u p o n e ntr y or ma n uall y b y t he C R A, 
s p o ns or’s me dical e x pert, or t he data ma na ger. All q ueries will be raise d electr o nicall y wit hi n 
t he electr o nic data ca pt ure s yste m. T his s yste matic vali dati o n will e ns ure t hat a clea n a n d 
c o nsiste nt data base is pr o vi de d f or t he statistical a nal ysis.  
E xter nal data tra nsfers fr o m ve n d ors t o L E O will be tra ns mitte d a n d ha n dle d via a sec ure file 
tra nsfer pr ot oc ol site.  
Tra ns missi o ns of electr o nic data fr o m e xter nal data pr o vi ders t o t he cli nical data base are 
ill ustrate d i n Pa nel 1 2 . 


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P a nel 1 2 : Tr a ns missi o n of electr o nic d at a 
 
A b bre vi ati o ns:  C R O = c o ntract researc h or ga nisati o n; C T R = cli nical trial re p ort; E C G = 
electr ocar di o gra m; e C R F = electr o nic case re p ort f or m; S D T M = st u d y data ta b ulati o n m o del.  
 
Arc hi vi n g of tri al d oc u me nt ati o n  
T he i n vesti gat or at eac h trial site m ust ma ke arra n ge me nts t o st ore t he esse ntial trial 
d oc u me nts, i ncl u di n g t he i n vesti gat or trial file ( 3 4 ). Esse ntial trial d oc u me nts m ust be st ore d 
u ntil L E O i nf or ms t he i n vesti gat or t hat t he d oc u me nts are n o l o n ger t o be retai ne d, or l o n ger 
if re q uire d b y l ocal re g ulati o ns. 
I n a d diti o n, t he i n vesti gat or is res p o nsi ble f or t he arc hi vi n g of all rele va nt s o urce d oc u me nts 
s o t hat t he trial data ca n be c o m pare d a gai nst s o urce data after t he c o m pleti o n of t he trial (f or 
e xa m ple, i n case of a n i ns pecti o n fr o m re g ulat or y a ut h orities). 
T he i n vesti gat or is re q uire d t o e ns ure t he c o nti n ue d st ora ge of t he d oc u me nts e ve n if t he 
i n vesti gat or lea ves t he trial site or retires bef ore t he e n d of t he re q uire d st ora ge peri o d. 


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N o d oc u me nts ma y be destr o ye d d uri n g t he rete nti o n peri o d wit h o ut t he writte n a p pr o val of 
L E O. N o d oc u me nts ma y be tra nsferre d t o a n ot her l ocati o n or part y wit h o ut writte n 
acce pta nce fr o m L E O.  
T he destr ucti o n pr ocess m ust e ns ure c o nfi de ntialit y of data a n d m ust be d o ne i n acc or da nce 
wit h l ocal re g ulat or y re q uire me nts.  
F or arc hi vi n g p ur p oses, eac h i n vesti gat or will be s u p plie d wit h a n electr o nic c o p y of t he 
e C R Fs f or all scree ne d s u bjects at t he trial site. T his is d o ne after c o m pleti o n of t he trial a n d 
bef ore access t o t he e C R F is re v o ke d. A u dit trail i nf or m ati o n will be i ncl u de d. e C R Fs m ust be 
a vaila ble f or i ns pecti o n b y a ut h orise d re prese ntati ves fr o m L E O, fr o m re g ulat or y a ut h orities 
a n d/ or I R Bs/ I E Cs.  
A p pe n di x 3 E: Re gistr ati o n, re p orti n g a n d p u blic ati o n p olic y  
Tri al discl os ure  
L E O is c o m mitte d t o be tra ns pare nt wit h res pect t o its cli nical trials. 
Basic i nf or mati o n of t his cli nical trial will be re gistere d i n t he gl o bal data re gistr y, 
w w w. Cli nical Trials. g o v bef ore t he first s u bject e nters i nt o t he trial. T he trial ma y als o bec o me 
re gistere d i n ot her onli ne data re gistries, acc or di n g t o a p plica ble la w a n d re g ulati o ns. 
Res ults of t his cli nical trial will be p oste d o n t he c or p orate we bsite of L E O i n acc or da nce wit h 
o ur P ositi o n o n P u blic Access t o Cli nical Trial I nf or mati o n n o later t ha n 1 2  m o nt hs after trial 
c o m pleti o n. Trial res ults ma y als o bec o me re p orte d i n w w w. Cli nical Trials. g o v, 
w w w.cli nicaltrialsre gister.e u a n d nati o nal data re gistries i n acc or da nce wit h a p plica ble la w 
a n d re g ulati o ns after cli nical trial c o m pleti o n or pre mat ure ter mi nati o n.   
L E O ma y als o pr o vi de researc hers access t o a n o n y mise d patie nt le vel data f or f urt her 
researc h. P u blicati o n a n d access will be i n acc or da nce wit h t he P ositi o n o n P u blic Access t o 
Cli nical Trials w hic h ca n be f o u n d o n t he L E O we bsite.  
P u blic ati o ns  
I n a d diti o n t o ma ki n g t he res ults a vaila ble o n cli nical re gistries as descri be d a b o ve, peer -
re vie we d p u blicati o ns (c o n gress a bstracts a n d p osters a n d j o ur nal p u blicati o ns) ma y be 
c o nsi dere d f or t his e x pl orat or y cli nical trial. S h o ul d peer-re vie we d p u blicati o ns be p urs ue d, 
beca use t his a m ulti -ce ntre trial, t he first p u blicati o n will be a j oi nt m ulti -ce ntre p u blicati o n. 
M ulti -ce ntre p u blicati o ns will be pre pare d i n c olla b orati o n bet wee n L E O a n d t he me m bers of 
a writi n g c o m mittee, w hic h s hall be a p p oi nte d b y L E O. 


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F oll o wi n g s uc h a m ulti-ce ntre p u blicati o n, t he i n vesti gat or s hall ha ve t he ri g ht t o p u blis h t he 
res ults fr o m t he cli nical trial ge nerate d b y t he i n vesti gat or, pr o vi de d t hat t he i de ntit y of t he 
s u bjects is n ot re veale d a n d t heir c o nse nt has bee n o btai ne d, s u bject t o t he f oll o wi n g n otice 
re q uire me nts. 
Pri or t o s u b mitti n g or prese nti n g a ma n uscri pt relate d t o t he cli nical trial t o a p u blis her, 
re vie wer, or ot her o utsi de pers o n, t he i n vesti gat or s hall pr o vi de t o L E O a c o p y of all s uc h 
ma n uscri pts, a n d L E O s hall ha ve ri g hts t o re vie w a n d c o m me nt. U p o n t he re q uest of L E O, t he 
i n vesti gat or s hall re m o ve a n y c o nfi de ntial i nf or mati o n ( ot her t ha n res ults ge nerate d b y t he 
i n vesti gat or) pri or t o s u b mitti n g or prese nti n g t he ma n uscri pts. T he i n vesti gat or s hall, u p o n 
t he re q uest of L E O, dela y t he p u blicati o n or prese ntati o n t o all o w L E O t o pr otect its 
i n ve nti o ns a n d ot her i ntellect ual pr o pert y ri g hts descri be d i n a n y s uc h ma n uscri pts. I n case t he 
first m ulti-ce ntre p u blicati o n is still o n g oi n g a n d has n ot bee n ma de p u blic at t he ti me of 
n otificati o n, L E O a n d t he writi n g c o m mittee gr o u p ma y als o dela y t he p u blicati o n or 
prese ntati o n if t he ma n uscri pt is dee me d t o har m t he o n g oi n g m ulti -ce ntre p u blicati o n. 
I n case of p u blicati o ns ma de b y t he i n vesti gat or after t he first m ulti-ce ntre p u blicati o n has 
bee n p u blis he d, t he a b o ve- me nti o ne d re q uire me nts m ust still be f oll o we d.  
A n y p u blicati o n m ust c o m pl y wit h G o o d P u blicati o n Practice ( G P P 3) sta n dar ds. 
L E O c o m plies wit h G P P 3 sta n dar ds a n d t he rec o m me n dati o ns fr o m t he I nter nati o nal 
C o m mittee of  Me dical J o ur nal E dit ors. L E O c o m plies wit h t he p ositi o ns of t he I nter nati o nal 
Fe derati o n of P har mace utical Ma n ufact urers & Ass ociati o ns (I F P M A), E ur o pea n Fe derati o n 
of P har mace utical I n d ustries a n d Ass ociati o ns ( E F PI A), Ja pa n P har mace utical Ma n ufact urers 
Ass ociati o n (J P M A), P har mace utical Researc h a n d Ma n ufact urers of A merica ( P h R M A), a n d 
t he j oi nt p ositi o n state me nt b y t he A merica n Me dical Writers Ass ociati o n ( A M W A), t he 
E ur o pea n Me dical Writers Ass ociati o n ( E M W A), a n d t he I nter nati o nal S ociet y f or Me dica l 
P u blicati o n Pr ofessi o nals (I S M P P) o n discl os ure of i nf or mati o n a b o ut cli nical trials, trial 
res ults a n d a ut h ors hi p. L E O als o f oll o ws t he C O N S O R T re p orti n g g ui deli nes (2 5 ). 
A p pe n di x 3 F: I ns ur a nce  
L E O has ta ke n o ut rele va nt i ns ura nces c o veri n g t he s u bjects i n t he prese nt cli nical trial i n 
acc or da nce wit h a p plica ble la ws a n d re g ulati o ns.  
A p pe n di x 3 G: Fi n a nci al discl os ure  
I n vesti gat ors will pr o vi de L E O wit h s ufficie nt, acc urate fi na ncial i nf or mati o n as re q ueste d t o 
all o w L E O t o s u b mit c o m plete a n d acc urate fi na ncial certificati o n or discl os ure state me nts t o 


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t he a p pr o priate re g ulat or y a ut h orities. I n vesti gat ors are res p o nsi ble f or pr o vi di n g i nf or mati o n 
o n fi na ncial i nterests d uri n g t he c o urse of t he cli nical trial a n d f or 1  year after c o m pleti o n of 
t he cli nical trial, or f or a l o n ger peri o d of ti me if re q uire d b y l ocal le gislati o n. 
A p pe n di x 3 H: Tri al a n d site cl os ure  
Pre m at ure ter mi n ati o n of tri al or tri al site  
L E O, t he i n vesti gat or, t he I R B/I E Cs or c o m pete nt a ut h orities ma y deci de t o st o p t he cli nical 
trial, part of t he trial or a trial site at a n y ti me, b ut a gree me nt o n pr oce d ures t o be f oll o we d 
m ust be o btai ne d. 
If a cli nical trial is s us pe n de d or pre mat urel y ter mi nate d, t he i n vesti gat or m ust i nf or m t he 
s u bjects pr o m ptl y a n d e ns ure a p pr o priate t hera p y a n d f oll o w- u p. As s pecifie d b y a p plica ble 
re g ulat or y re q uire me nts, t he i n vesti gat or or L E O m ust pr o m ptl y i nf or m I R B/I E Cs a n d 
pr o vi de a detaile d writte n e x pla nati o n. Rele va nt c o m pete nt a ut h orities m ust be i nf or me d. 
T he trial m ust be ter mi nate d if t he perce pti o n of t he be nefit/ris k rati o (j u d ge d fr o m cli nical 
si g ns a n d s y m pt o ms, ( S) A Es a n d/ or re mar ka ble safet y la b orat or y c ha n ges) bec o mes 
u nfa v o ura ble f o r t he c o nti n uati o n of t he trial. 
Reas o ns f or t he earl y cl os ure of a trial site b y L E O or i n vesti gat or ma y i ncl u de b ut are n ot 
li mite d t o: 
•  Fail ure of t he i n vesti gat or t o c o m pl y wit h t he pr ot oc ol, t he re q uire me nts of t he 
I R B/I E C or l ocal healt h a ut h orities, L E O pr oce d ures, or G C P g ui deli nes. 
•  I na de q uate recr uit me nt of s u bjects b y t he i n vesti gat or. 
C o m pleti o n of tri al  
I n vesti gat ors will be i nf or me d w he n s u bject recr uit me nt is t o cease. Scree ni n g acti vities will 
be st o p pe d at a trial site w he n t he t otal re q ueste d n u m ber of s u bjects f or t he cli nical trial has 
bee n o btai ne d, irres pecti ve of t he s pecific site’s pla n ne d i ncl usi o n n u m ber. 
Trial sites will be cl ose d u p o n trial c o m pleti o n. L E O will u n derta ke arra n ge me nts f or t he 
c ollecti o n a n d dis p osal of a n y u n use d trial material t hat t he i n vesti gat or is n ot re q uire d t o 
kee p i n his/ her files. A trial site is c o nsi dere d cl ose d w he n all re q uire d d oc u me nts a n d trial 
s u p plies ha ve bee n c ollecte d a n d a trial site cl os ure visit has bee n perf or me d. 
W he n t he ra n d o misati o n c o de has bee n br o ke n, t he i n vesti gat ors will recei ve i nf or mati o n 
a b o ut t he treat me nt all ocati o n t o eac h tar get lesi o n f or t he s u bjects ra n d o mise d at t heir 
res pecti ve sites a n d will be as ke d t o rec or d t his i n t he s u bject’s me dical rec or d. 


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A p pe n di x 3 I: Res p o nsi bilities 
T he si g n at or y i n vesti g at or is res p o nsi ble f or t he a p pr o val of t he cli nical trial pr ot oc ol a n d 
t he C T R o n be half of all cli nical trial i n vesti gat ors a n d as a gree d t o i n a Si g nat or y I n vesti gat or 
A gree me nt.  
T he n ati o n al c o or di n ati n g i n vesti g at ors are res p o nsi ble f or nati o nal iss ues relati n g t o t he 
cli nical trial as a gree d t o i n a Nati o nal C o or di nati n g I n vesti gat or A gree me nt.  
E ac h p artici p ati n g i n vesti g at or  is res p o nsi ble f or all as pects of t he cli nical trial c o n d uct at 
his/ her trial s ite as a gree d t o i n a Cli nical Trial A gree me nt. 
 
 
 
 
 


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A p pe n di x 4: J ustific ati o n f or eli gi bilit y criteri a  
I ncl usi o n criteri a 
N o.  
S h ort f or m of i ncl usi o n criteri a  
J ustific ati o n  
1 
Si g ne d a n d date d i nf or me d c o nse nt has bee n 
o btai ne d pri or t o a n y pr ot oc ol -relate d 
pr oce d ures.  
Re q uire me nt i n acc or da nce wit h I C H -G C P.  
2 
A ge 1 8 -7 0 years.  
T o a v oi d i ncl u di n g v ul nera ble s u bjects.  
3 
Hist o pat h ol o gical fi n di n gs (c urre nt or 
pre vi o us) c o nsiste nt wit h cli nical dia g n osis 
of D L E.  
T o e ns ure rele va nt tar get p o p ulati o n.  
4 
U ne q ui v ocal cli nical dia g n osis of 2 acti ve 
D L E tar get lesi o ns t hat are less t ha n 6 
m o nt hs ol d a n d a me na ble f or cli nical 
e val uati o n. 
T o e ns ure rele va nt tar get p o p ulati o n wit h lesi o ns 
s uita ble f or treat me nt, i.e. lesi o ns wit h re versi ble 
D L E acti vit y si g ns.  
5 
Tar get lesi o n I G A sc ore of at least m o derate  
se verit y at scree ni n g a n d baseli ne.  
T o e ns ure t hat t he s u bject has a se verit y of 
disease t hat ma kes assess me nt of i m pr o ve me nt 
p ossi ble.  
6 
Tar get lesi o n er yt he ma sc ore of at least 2 at 
scree ni n g a n d baseli ne. 
T o e ns ure t hat t he s u bject has a se verit y of 
disease t hat ma kes assess me nt of i m pr o ve me nt 
p ossi ble.  
7 
F or s u bjects ta ki n g h y dr o x yc hl or o q ui ne or 
c hl or o q ui ne: N o a b n or mal fi n di n gs at t he 
latest r o uti ne o p ht hal m ol o gic e xa mi nati o n, 
a n d n o r o uti ne o p ht hal m ol o gic e xa mi nati o n 
is pla n ne d d uri n g t he trial. 
T o pre ve nt i nterfere nce wit h safet y e n d p oi nts.  
8 
Fe male s u bjects of c hil d beari n g p ote ntial 
m ust use a hi g hl y effecti ve f or m of birt h 
c o ntr ol t hr o u g h o ut t he trial a n d at least f or 2 
wee ks after last a d mi nistrati o n of I M P.  
T o e xcl u de a n y ris k f or t he occ urre nce of 
ge n ot o xicit y/terat o ge nicit y/fet ot o xicit y.  
9 
Pr os pecti ve a bilit y t o atte n d all sc he d ule d 
trial visits. 
T o e ns ure rele va nt tar get p o p ulati o n a n d mi ni mise 
t he a m o u nt of missi n g data.  
 
 
E xcl usi o n criteri a  
N o.  
S h ort f or m of e xcl usi o n criteri a  
J ustific ati o n  
1 
Tar get lesi o n d ys pi g me ntati o n sc ore of 2 at 
scree ni n g or baseli ne. 
T o e ns ure t hat t he s u bject d oes n ot ha ve a hi g h 
de gree of da ma ge of disease t hat ma kes 
assess me nt of i m pr o ve me nt i m p ossi ble.  
2 
Tar get lesi o n scarri n g/atr o p h y sc ore of 2 at 
scree ni n g or baseli ne. 
T o e ns ure t hat t he s u bject d oes n ot ha ve a hi g h 
de gree of da ma ge of disease t hat ma kes 
assess me nt of i m pr o ve me nt i m p ossi ble.  
3 
Tar get lesi o n  scarri n g al o pecia sc ore of 
greater t ha n 0 i n scal p lesi o ns at scree ni n g or 
baseli ne.  
T o e ns ure t hat t he s u bject d oes n ot ha ve a hi g h 
de gree of da ma ge of disease t hat ma kes 
assess me nt of i m pr o ve me nt i m p ossi ble.  


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4 
Me dical hist or y of S L E wit h cli nicall y 
si gnifica nt or ga n i n v ol ve me nt ( A C R S L E 
criteria n o. 6 t o 9).  
F or t he safet y of t he s u bjects a n d t o pre ve nt 
i nterfere nce wit h efficac y a n d safet y e n d p oi nts. 
5 
S u bjects wit h u nsta ble or si g nifica nt S L E 
disease acti vit y fi n di n gs t hat w o ul d i nterfere 
wit h t he trial e val uati o n, c o m pleti o n, a n d/ or 
pr oce d ures per t he i n vesti gat or's discreti o n.  
F or t he safet y of t he s u bjects a n d t o pre ve nt 
i nterfere nce wit h efficac y a n d safet y e n d p oi nts. 
6 
Ot her s ki n c o n diti o ns at scree ni n g or 
baseli ne t hat w o ul d i nterfere wit h e val uati o n 
of D L E.  
T o pre ve nt i nterfere nce wit h efficac y a n d safet y 
e n d p oi nts. 
7 
S yste mic 
i m m u n os u p pressi ve/i m m u n o m o d ulati n g 
t hera p y wit hi n 4 wee ks pri or t o baseli ne.  
F or t he safet y of t he s u bjects a n d t o pre ve nt 
i nterfere nce wit h efficac y a n d safet y e n dp oi nts.  
8 
S yste mic pre d nis ol o ne o ver 7. 5 m g/ da y or 
c ha n ge d d ose wit hi n 4 wee ks pri or t o 
baseli ne.  
F or t he safet y of t he s u bjects a n d t o pre ve nt 
i nterfere nce wit h efficac y a n d safet y e n d p oi nts. 
9 
Treat me nt wit h oral a nti malarial dr u gs 
a n d/ or dr u gs k n o w n t o i nteract wit h 
a nti malarials.  
F or t he safet y of t he s u bjects a n d t o pre ve nt 
i nterfere nce wit h efficac y a n d safet y e n d p oi nts. 
1 0  
Treat me nt wit h t o pical c ortic oster oi ds, 
calci ne uri n i n hi bit ors, a n d 
p h os p h o diesterase -4 i n hi bit ors wit hi n 2 
wee ks pri or  t o baseli ne. 
F or t he safet y of t he s u bjects a n d t o pre ve nt 
i nterfere nce wit h efficac y a n d safet y e n d p oi nts. 
1 1  
Use of s yste mic a nti bi otics or c uta ne o usl y 
a p plie d a nti bi otics o n t he tar get lesi o ns 
wit hi n 2 wee ks pri or t o baseli ne.  
F or t he safet y of t he s u bjects a n d t o pre ve nt 
i nterfere nce wit h efficac y a n d safet y e n d p oi nts. 
1 2  
U V t hera p y  or e xcessi ve s u n e x p os ure 
wit hi n 2 wee ks pri or t o baseli ne.  
T o pre ve nt i nterfere nce wit h efficac y a n d safet y 
e n d p oi nts. 
1 3  
A n y pr oce d ure i m pairi n g t he s ki n barrier 
(e.g. i ncisi o n) wit hi n 2 c m fr o m t he b or der 
of a n y of t he tar get lesi o ns wit hi n 4 wee ks 
pri or t o baseli ne.  
T o pre ve nt i nterfere nce wit h efficac y a n d safet y 
e n d p oi nts. 
1 4  
Recei pt of li ve (atte n uate d) vacci nes wit hi n 
4 wee ks pri or t o baseli ne.  
F or t he safet y of t he s u bjects a n d t o pre ve nt 
i nterfere nce wit h efficac y a n d safet y e n d p oi nts. 
1 5 
Treat me nt wit h a n y mar kete d bi ol o gical 
t hera p y or i n vesti gati o nal bi ol o gic a ge nts. 
F or t he safet y of t he s u bjects a n d t o pre ve nt 
i nterfere nce wit h efficac y a n d safet y e n d p oi nts.  
1 6 
Treat me nt wit h a n y n o n -mar kete d s u bsta nce 
wit hi n 4 wee ks pri or t o baseli ne.  
F or t he safet y of t he s u bjects a n d t o pre ve nt 
i nterfere nce wit h efficac y a n d safet y e n d p oi nts. 
1 7 
U nsta ble or fl uct uati n g use of t o bacc o wit hi n 
1 m o nt h pri or t o scree ni n g. 
T o pre ve nt i nterfere nce wit h efficac y a n d safet y 
e n d p oi nts. 
1 8 
Hist or y of a n y acti ve s ki n i nfecti o n wit hi n 1 
wee k pri or t o baseli ne.  
F or t he safet y of t he s u bjects.  
 
1 9  
Cli nicall y si g nifica nt i nfecti o n wit hi n 4 
wee ks pri or t o baseli ne.  
F or t he safet y of t he s u bjects.  
 


Trial I D: E X P -1 3 7 3  
Date: 2 2 -Oct -2 0 1 9  
Versi o n: 4 . 0 
Pa ge 1 0 8  of 1 2 2  
 
 
 
 
 
2 0 
T u berc ul osis re q uiri n g treat me nt wit hi n 1 2 
m o nt hs pri or t o scree ni n g a n d/ or s u bjects 
wit h a p ositi ve bl o o d test f or t u berc ul osis at 
scree ni n g. 
F or t he safet y of t he s u bjects.  
 
2 1 
I m m u n os u p presse d or i m m u n oc o mpr o mise d 
s u bjects. 
F or t he safet y of t he s u bjects.  
 
2 2 
Maj or s ur ger y wit hi n 8 wee ks pri or t o 
scree ni n g, or pla n ne d i n-patie nt s ur ger y or 
h os pitalisati o n d uri n g t he trial peri o d.  
F or t he safet y of t he s u bjects.  
 
2 3 
Hist or y of ca ncer.  
F or t he safet y of t he s u bjects. 
2 4 
A n y dis or der w hic h is n ot sta ble a n d c o ul d 
affect t he safet y of t he s u bject t hr o u g h o ut 
t he trial, i nfl ue nce t he fi n di n gs, or i m pe de 
t he s u bject’s a bilit y t o c o m plete t he trial. 
F or t he safet y of t he s u bjects a n d t o pre ve nt 
i nterfere nce wit h efficac y a n d safet y e n d p oi nts. 
2 5 
A n y a b n or mal fi n di n g w hic h ma y p ut t he 
s u bject at ris k, or i nfl ue nce t he res ults or t he 
s u bject’s a bilit y t o c o m plete t he trial.   
F or t he safet y of t he s u bjects a n d t o pre ve nt 
i nterfere nce wit h efficac y a n d safet y e n d p oi nts.  
2 6 
P ositi ve HI V a nti b o d y, he patitis B s urface 
a nti ge n, or he patitis C vir us a nti b o d y 
ser ol o g y at scree ni n g. 
F or t he safet y of t he s u bjects.  
2 7 
Ala ni ne a mi n otra nsferase ( A L T) or as partate 
a mi n otra nsferase ( A S T) le vel m ore t ha n 2 
ti mes U L N a n d/ or a ser u m creati ni ne le vel 
m ore t ha n 1. 5 ti mes U L N at scree ni n g.     
F or t he safet y of t he s u bjects.  
2 8 
K n o w n or s us pecte d h y perse nsiti vit y t o a n y 
c o m p o ne nt(s) of t he I M P.  
F or t he safet y of t he s u bjects.  
2 9  
C urre nt partici pati o n i n a n y ot her 
i nter ve nti o nal cli nical trial. 
T o pre ve nt i nterfere nce wit h efficac y a n d safet y 
e n d p oi nts. 
3 0 
Pre vi o us ra n d o misati o n i n t his cli nical trial.  
T o e ns ure data i nt e grit y. 
3 1 
Pre vi o usl y ra n d o mise d i n a cli nical trial wit h 
del g ociti ni b ( L E O 1 2 4 2 4 9).  
T o e ns ure data i nte grit y.  
3 2 
Hist or y of c hr o nic alc o h ol or dr u g a b use 
wit hi n 1 2 m o nt hs pri or t o scree ni n g, or a n y 
c o n diti o n ass ociate d wit h p o or c o m plia nce 
as j u d ge d b y t he i n vesti gat or. 
F or t he safet y of t he s u bjects a n d t o e ns ure 
c o m plia nce wit h trial pr oce d ures a n d pr o per 
q ualit y of t he data t o be c ollecte d.  
3 3 
S u bjects w h o i n t he o pi ni o n of t he 
i n vesti gat or are li kel y t o be n o n-c o m plia nt or 
u na ble t o u n ders ta n d t he trial a n d gi ve 
a de q uatel y i nf or me d c o nse nt.  
Re q uire me nt i n acc or da nce wit h I C H -G C P.  
3 4 
E m pl o yees of t he trial site or a n y ot her 
i n di vi d uals directl y i n v ol ve d wit h t he 
pla n ni n g or c o n d uct of t he trial, or 
i m me diate fa mil y me m bers of s uc h 
i n di vi d uals. 
Re q uire me nt i n acc or da nce wit h I C H -G C P.  
3 5 
S u bjects w h o are le gall y i nstit uti o nalise d.  
Re q uire me nt i n acc or da nce wit h I C H -G C P.  


Trial I D: E X P -1 3 7 3  
Date: 2 2 -Oct -2 0 1 9  
Versi o n: 4. 0  
Pa ge 1 0 9  of 1 2 2  
 
 
 
 
 
3 6 
Fe male s u bjects w h o are pre g na nt or 
lactati n g. 
F or t he safet y of t he u n b or n/ ne w b or n c hil d.  
 
 


Trial I D: E X P -1 3 7 3  
Date: 2 2 -Oct -2 0 1 9  
Versi o n: 4. 0  
Pa ge 1 1 0  of 1 2 2  
 
 
 
 
 
A p pe n di x 5: C o nt act list  
C o ntact details f or t he cli nical pr oject ma na ger, a p p oi nte d C R A, s p o ns or’s me dical e x pert, 
a n d t he nati o nal c o or di nati n g i n vesti gat ors are pr o vi de d t o t he trial sites as a se parate c o ntact 
list. 
S p o ns or  
L E O P har ma A/ S  (referre d t o as ‘ L E O’ or ‘t he s p o ns or’ i n t his cli nical trial pr ot oc ol) is t he 
s p o ns or of t he cli nical trial: 
L E O P har ma A/ S  
I n d ustri par ke n 5 5 
D K - 2 7 5 0 Baller u p 
De n mar k  
Si g n at or y i n vesti g at or 
Mar gitta Wor m, U ni v. Pr of. Dr. Me d. 
De part me nt of Der mat ol o g y, Ve ner e ol o g y a nd Aller g ol o g y  
Ca m p us C harité Mitte  
C harité platz 1  
D- 1 0 1 1 7 Berli n, Ger ma n y 
Tele p h o ne: + 4 9 ( 3 0) 4 5 0 5 1 8 1 0 5 
 


Trial I D: E X P -1 3 7 3  
Date: 2 2 -Oct -2 0 1 9  
Versi o n: 4. 0  
Pa ge 1 1 1  of 1 2 2  
 
 
 
 
 
A p pe n di x 6: A meric a n C olle ge of R he u m at ol o g y re vise d criteri a f or 
cl assific ati o n of s yste mic l u p us er yt he m at os us ( 1 9 9 7 u p d ate of t he 1 9 8 2 
criteri a) (2 6 ) 


Trial I D: E X P -1 3 7 3  
Date: 2 2 -Oct -2 0 1 9  
Versi o n: 4. 0  
Pa ge 1 1 2  of 1 2 2  
 
 
 
 
 
 
 
 


Trial I D: E X P -1 3 7 3  
Date: 2 2 -Oct -2 0 1 9  
Versi o n: 4. 0  
Pa ge 1 1 3  of 1 2 2  
 
 
 
 
 
A p pe n di x 7: C ut a ne o us L u p us Er yt he m at os us Dise ase Are a a n d Se verit y 
I n de x (2 7 ) 
 


Trial I D: E X P -1 3 7 3  
Date: 2 2 -Oct -2 0 1 9  
Versi o n: 4. 0  
Pa ge 1 1 4  of 1 2 2  
 
 
 
 
 
A p pe n di x 8 : Re vise d C ut a ne o us L u p us Er yt he m at os us Dise ase Are a a n d 
Se verit y I n de x (2 8 ) 
 


Trial I D: E X P -1 3 7 3  
Date: 2 2 -Oct -2 0 1 9  
Versi o n: 4. 0  
Pa ge 1 1 5  of 1 2 2  
 
 
 
 
 
 


Trial I D: E X P -1 3 7 3  
Date: 2 2 -Oct -2 0 1 9  
Versi o n: 4. 0  
Pa ge 1 1 6  of 1 2 2  
 
 
 
 
 
A p pe n di x 9 : Pr ot oc ol a me n d me nt hist or y  
T he pr ot oc ol a me n d me nt s u m mar y of c ha n ges ta ble f or t he c urre nt a me n d m e nt is l ocate d 
directl y bef ore t he ta ble of c o nte nts.  
S u m m ar y of c h a n ges t a ble  f or a me n d me nt 1 ( 1 5- M a y- 2 0 1 9) 
Secti o n n o. 
a n d n a me  
Descri pti o n of c h a n ge  
Brief r ati o n ale  
Pr ot oc ol 
s y n o psis 
( Statistical 
met h o ds) 
T he descri pti o n of t he pri mar y 
e n d p oi nt is c orrecte d fr o m ‘ a n 
I G A sc ore of 0 or 1 at Wee k 6 
a n d a ≥2-p oi nt re d ucti o n fr o m 
baseli ne’ t o ‘a n I G A sc ore of 0 
or 1 at Wee k 6’. 
To ali g n t he w or di n g of t he pri mar y 
e n d p oi nt wit h t hat i n Secti o n 6  a n d 
a v oi d a m bi g uit y. 
4  
Sc he d ule of 
trial pr oce d ures 
E C G was a d de d at t he 
u nsc he d ule d visit. 
To clarif y t hat t he i n vesti gat or ca n 
rec or d a n E C G at t he u nsc he d ule d 
visit if c o nsi dere d rele va nt.  
4  
Sc he d ule of 
trial pr oce d ures 
A uri ne pre g na nc y test was 
a d de d at t he f oll o w - u p visit. 
To r ule o ut ( or i de ntif y) a n y 
pre g na nc y d uri n g t he trial u p t o a n d 
i ncl u di n g t he f oll o w- u p visit. 
4  
Sc he d ule of 
trial pr oce d ures 
A n ‘( X)’ a n d a ne w f o ot n ote g) 
is a d de d f or C L A SI a n d 
R C L A SI at baseli ne t o s pecif y 
t hat scarri n g al o pecia will be 
sc ore d f or eac h tar get lesi o n at 
scree ni n g a n d baseli ne 
(a p plica ble t o scal p lesi o ns 
o nl y).  
To s pecif y c ollecti o n of t he data use d 
t o e val uate e xcl usi o n criteri o n n o. 3. 
5. 2  
E x perie nce 
wit h 
i n vesti gati o nal 
T he refere nce t o t he 
i n vesti gat or’s br oc h ure is 
u p date d fr o m versi o n 1. 0 t o 
2. 0, a n d t he n u m bers of 
c o m plete d cli nical trials a n d 
s u bjects e x p ose d t o 
T he i n vesti gat or’s  br oc h ure has bee n 
u p date d si nce fi nalisati o n of t he 
pr ot oc ol. 


Trial I D: E X P -1 3 7 3  
Date: 2 2 -Oct -2 0 1 9  
Versi o n: 4. 0  
Pa ge 1 1 7  of 1 2 2  
 
 
 
 
 
Secti o n n o. 
a n d n a me  
Descri pti o n of c h a n ge  
Brief r ati o n ale  
me dici nal 
pr o d uct 
del g ociti ni b are u p date d 
acc or di n gl y. 
5. 4  
Et hical 
c o nsi derati o ns 
It is a d de d t hat a uri ne 
pre g na nc y test will be ta ke n at 
t he f oll o w-u p visit.  
To r ule o ut ( or i de ntif y) a n y 
pre g na nc y d uri n g t he trial u p t o a n d 
i ncl u di n g t he f oll o w- u p visit. 
5. 4  
Et hical 
c o nsi derati o ns 
It is a d de d t hat n o 
c o ntrace pti ve meas ures are 
re q uire d f or male s u bjects i n 
t his trial.   
To clarif y et hical c o nsi derati o ns 
ar o u n d c o ntrace pti o n. 
8. 3  
E xcl usi o n 
criteria 
T he e xcl usi o n criteri o n 
re gar di n g use of pr o d ucts 
c o ntai ni n g H y peric u m 
perf orat u m ( St J o h n’s Wort) is 
delete d (e xcl usi o n criteri o n n o. 
1 5 i n versi o n 2. 0 of t he 
pr ot oc ol).  
T his e xcl usi o n criteri o n was i ncl u de d 
i n t he ori gi nal pr ot oc ol b y err or a n d is 
n ot c o nsi dere d rele va nt f or t his trial. 
H y peric u m perf orat u m is a n i n d ucer 
of t he li ver e nz y mes w hic h meta b olise 
del g ociti ni b, b ut n o or ne gli gi ble 
s yste mic a bs or pti o n of del g ociti ni b is 
e x pecte d i n t his trial.  
8. 4  
Scree ni n g a n d 
scree ni n g 
fail ures 
It is a d de d t hat eac h s u bject 
ca n o nl y be re-assesse d f or 
eli gi bilit y o nce.  
To defi ne t he u p per li mit f or t he 
n u m ber of re -assess me nts of 
eli gi bilit y. 
8. 4  
Scree ni n g a n d 
scree ni n g 
fail ures 
I ncl usi o n criteri o n n o. 7 is 
a d de d t o t he list of i ncl usi o n 
criteria f or w hic h re -
assess me nt will be all o we d.  
Si nce D L E is a rare disease, a n d t he 
n u m ber of eli gi ble patie nts is li mite d, 
s u bjects f or w h o m a r o uti ne 
o p ht hal m ol o gic e xa mi nati o n is 
pla n ne d d uri n g t he trial will be 
all o we d t o be re -assesse d f or 
eli gi bilit y after t he e xa mi nati o n.  


Trial I D: E X P -1 3 7 3  
Date: 2 2 -Oct -2 0 1 9  
Versi o n: 4. 0  
Pa ge 1 1 8  of 1 2 2  
 
 
 
 
 
Secti o n n o. 
a n d n a me  
Descri pti o n of c h a n ge  
Brief r ati o n ale  
8. 4  
Scree ni n g a n d 
scree ni n g 
fail ures 
E xcl usi o n criteri o n n o. 1 5 (i n 
versi o n 2. 0 of t he pr ot oc ol) is 
delete d fr o m t he list of 
e xcl usi o n criteria f or w hic h re -
assess me nt of eli gi bilit y will be 
all o we d. 
T his e xcl usi o n criteri o n was i ncl u de d 
i n t he ori gi nal pr ot ocol b y err or a n d is 
n ot c o nsi dere d rele va nt f or t his trial.  
9. 2  
A d mi nistrati o n 
of I M P  
I nf or mati o n a b o ut t he I R T 
s yste m assi g ni n g t he kit 
n u m ber is m o ve d t o 
Secti o n  9. 3 . 
T his te xt bel o n gs i n Secti o n 9. 3  a n d is 
m o ve d t o re place t he pre vi o us, 
i nc orrect te xt (see r o w bel o w). 
9. 3  
Treat me nt 
assi g n me nt 
Deleti o n of i nc orrect te xt:  
Eli gi ble s u bjects will recei ve a 
ra n d o misati o n c o de n u m ber i n 
t he or der of t heir 
ra n d o misati o n t o treat me nt at 
t he trial site. 
Eac h trial site will recei ve a list 
of 1 2 c o nsec uti ve 
ra n d o misati o n c o de n u m bers. 
T he ra n d o misati o n c o de 
n u m bers will c o ntai n 5 di gits, 
starti n g fr o m 1 0 1 0 1 at t he first 
trial site i n t he first c o u ntr y, 
fr o m 1 0 2 0 1 at t he sec o n d trial 
site i n t he first c o u ntr y, fr o m 
2 0 1 0 1 at t he first trial site i n 
t he sec o n d c o u ntr y, fr o m 
2 0 2 0 1 at t he sec o n d trial site i n 
t he sec o n d c o u ntr y, a n d s o 
f ort h. 
T his te xt was i ncl u de d i n t he ori gi nal 
pr ot oc ol b y err or. T h e s u bjects will 
n ot ha ve ra n d o misati o n c o de n u m bers; 
i nstea d t he i nteracti ve res p o nse 
tec h n ol o g y s yste m will assi g n t he kit 
n u m ber. 


Trial I D: E X P -1 3 7 3  
Date: 2 2 -Oct -2 0 1 9  
Versi o n: 4. 0  
Pa ge 1 1 9  of 1 2 2  
 
 
 
 
 
Secti o n n o. 
a n d n a me  
Descri pti o n of c h a n ge  
Brief r ati o n ale  
D uri n g t he trial, t he 
ra n d o misati o n lists will be ke pt 
secure b y L E O, i naccessi ble t o 
all staff i n v ol ve d wit h t he 
c o n d uct or a d mi nistrati o n of 
t he trial, u ntil t he trial is 
u n bli n de d. 
I n a d diti o n, i nf or mati o n a b o ut 
t he I R T s yste m assi g ni n g t he 
kit n u m ber is  m o ve d fr o m 
Secti o n 9. 2  t o Secti o n 9. 3 . 
9. 7  
Pr o hi bite d 
me dicati o n a n d 
pr oce d ures 
It is a d de d t hat c ha n ges i n d ose 
or disc o nti n uati o n of 
me dicati o ns or pr oce d ures 
liste d as pr o hi bite d s h o ul d o nl y 
be d o ne f or me dical reas o ns, 
n ot trial -relate d reas o ns.  
To clarif y t hat me dicall y i n dicate d 
treat me nts s h o ul d ne ver be c ha n ge d or 
disc o nti n ue d o nl y t o all o w t he s u bject 
t o partici pate i n t he trial. 
9. 7  
Pr o hi bite d 
me dicati o n a n d 
pr oce d ures  
H y peric u m perf orat u m is 
delete d fr o m t he list of 
pr o hi bite d me dicati o n.  
T his was i ncl u de d as pr o hi bite d 
me dicati o n i n t he ori gi nal pr ot oc ol b y 
err or a n d is n ot c o nsi dere d rele va nt 
f or t his trial. H y peric u m perf orat u m is 
a n i n d ucer of t he li ver e nz y mes w hic h 
meta b olise del g ociti ni b, b ut n o or 
ne gli gi ble s yste mic a bs or pti o n of 
del g ociti ni b is e x pecte d i n t his trial.  
1 0. 2. 1  
Disc o nti n uati o n 
of I M P  
It was a d de d t hat A Es t hat, i n 
t he o pi ni o n of t he i n vesti gat or 
or s p o ns or’s me dical e x pert, 
c o ntrai n dicate f urt her d osi n g 
i ncl u de u nacce pta ble 
w orse ni n g of D L E s y m pt o ms. 
To clarif y t hat s u bjects wit h 
u nacce pta ble w orse ni n g of D L E (i n 
t he o pi ni o n of t he i n vesti gat or or 
s p o ns or’s me dical e x pert) s h o ul d be 
disc o nti n ue d fr o m I M P, afte r w hic h 
t he s u bject ca n be treate d at t he 
i n vesti gat or’s discreti o n. 


Trial I D: E X P -1 3 7 3  
Date: 2 2 -Oct -2 0 1 9  
Versi o n: 4. 0  
Pa ge 1 2 0  of 1 2 2  
 
 
 
 
 
Secti o n n o. 
a n d n a me  
Descri pti o n of c h a n ge  
Brief r ati o n ale  
1 0. 2. 1  
Disc o nti n uati o n 
of I M P  
O ne of t he reas o ns f or 
per ma ne nt disc o nti n uati o n of 
I M P is c orrecte d as f oll o ws: 
C o nfir me d A L T a n d/ or A S T 
> 5 × U L N  (f or m ore t ha n 2 
wee ks) . 
I M P will be disc o nti n ue d i m me diatel y 
i n case of c o nfir me d A L T a n d/ or A S T 
> 5 × U L N, as t his c o ul d i n dicate e. g. 
t o xic he patitis.  
1 1. 2. 5  
Classificati o n 
of s yste mic 
l u p us 
er yt he mat os us  
It is a d de d t hat a n y a b n or mal 
test res ults f o u n d as part of t he 
classificati o n of S L E will be 
f oll o we d u p at t he discreti o n of 
t he i n vesti gat or. 
To clarif y ha n dli n g of a b n or mal test 
res ults f o u n d d uri n g t he classificati o n 
of S L E.  
1 1. 4. 4. 1  
O ver vie w 
Mi ni m u m se nsiti vit y of t he 
uri ne pre g na nc y test ( 2 5 
mI U/ m L) is a d de d i n f o ot n ote 
e) t o Pa nel 1 0 . 
To s pecif y t he se nsiti vit y of t he 
pre g na nc y test as re q ueste d b y t he 
Ger ma n a ut h orities.  
1 1. 5. 2  
N o n -i n vasi ve 
s ki n sa m pli n g 
Patc hes f or n o n -i n vasive s ki n 
sa m pli n g will be a p plie d f or 1 5 
mi n utes ( n ot 2 0 mi n utes). 
U p date d i nstr ucti o ns f or use fr o m t he 
ma n ufact urer.  
1 1. 6. 1. 3  
E xit i nter vie ws 
( o pti o nal, 
selecte d 
c o u ntries o nl y) 
E ve nts re p orte d b y t he C R O 
c o n d ucti n g e xit i nter vie ws are 
referre d t o as ‘ p ote ntial A Es’ 
rat her t ha n ‘ A Es’. 
To clarif y t hat e ve nts re p orte d b y t he 
i nter vie wers ( w h o are n ot me dicall y 
q ualifie d) will n ot necessaril y be 
re gar de d as A Es b y t he i n vesti gat or. 
1 1. 6. 3  
P h ot o gra p h y 
( o pti o nal) 
It was delete d t hat p h ot o gra p hs 
ma y u n der g o pla ni metric 
a nal ysis t o deter mi ne t he area 
of t he tar get lesi o ns.  
Pla ni metric a nal ysis will n ot be 
perf or me d u n der t his pr ot oc ol.  
1 3. 2  
E ve nts re p orte d b y t he C R O 
c o n d ucti n g e xit i nter vie ws are 
To clarif y t hat e ve nts re p orte d b y t he 
i nter vie wers ( w h o are n ot me dicall y 


Trial I D: E X P -1 3 7 3  
Date: 2 2 -Oct -2 0 1 9  
Versi o n: 4. 0  
Pa ge 1 2 1  of 1 2 2  
 
 
 
 
 
Secti o n n o. 
a n d n a me  
Descri pti o n of c h a n ge  
Brief r ati o n ale  
C ollecti o n of 
a d verse e ve nt 
re p orts 
referre d t o as ‘ p ote ntial A Es’ 
rat her t ha n ‘ A Es’. 
q ualifie d) will n ot necessaril y be 
re gar de d as A Es b y t he i n vesti gat or. 
1 3. 4. 2  
L E O re p orti n g 
res p o nsi bilities 
T he refere nce safet y 
i nf or mati o n is u p date d t o t he 
i n vesti gat or’s br oc h ure versi o n 
2. 0. 
T he i n vesti gat or’s br oc h ure has bee n 
u p date d si nce fi nalisati o n of t he 
pr ot oc ol. 
1 4. 3. 4  
A nal ysis of 
pri mar y 
e n d p oi nt 
T he descri pti o n of t he pri mar y 
e n d p oi nt is c orrecte d fr o m ‘ a n 
I G A sc ore of 0 or 1 at Wee k 6 
a n d a ≥2-p oi nt re d ucti o n fr o m 
baseli ne’ t o ‘a n I G A sc ore of 0 
or 1 at Wee k 6’. 
To ali g n t he w or di n g of t he pri mar y 
e n d p oi nt wit h t hat i n Secti o n 6  a n d 
a v oi d a m bi g uit y. 
1 4. 3. 5  
A nal ysis of 
sec o n dar y 
e n d p oi nts 
Wor di n g of t he sec o n dar y 
e n d p oi nts are c orrecte d.  
To ali g n t he w or di n g of t he sec o n dar y 
e n d p oi nts wit h t hat i n Secti o n 6 . 
1 4. 3. 6. 1  
A nal ysis of 
e x pl orat or y 
efficac y 
e n d p oi nts 
Wor di n g of t he e x pl orat or y 
efficac y e n d p oi nts are 
c orrecte d. 
To ali g n t he w or di n g of t he 
e xpl orat or y e n d p oi nts wit h t hat i n 
Secti o n 6 . 
1 4. 3. 1 1  
Ge neral 
pri nci ples  
It is a d de d t hat all tests will be 
i nter prete d e xcl usi vel y i n a 
descri pti ve ma n ner, i.e. 
i n de pe n de ntl y of ot her tests. 
To clarif y t he ge neral pri nci ples i n t he 
statistical a nal ysis. 
A p pe n di x 3 D  
Rec or d 
kee pi n g, 
q ualit y c o ntr ol, 
‘ Ra n d o misati o n c o de n u m ber’ 
is c ha n ge d t o ’ Assi g ne d kit 
n u m ber’. 
T his te xt was i ncl u de d i n t he ori gi nal 
pr ot oc ol b y err or. T he s u bjects will 
n ot ha ve ra n d o misati o n c o de n u m bers; 
i nstea d t he i nteracti ve res p o nse 


Trial I D: E X P -1 3 7 3  
Date: 2 2 -Oct -2 0 1 9  
Versi o n: 4. 0  
Pa ge 1 2 2  of 1 2 2  
 
 
 
 
 
Secti o n n o. 
a n d n a me  
Descri pti o n of c h a n ge  
Brief r ati o n ale  
a n d data 
ha n dli n g 
tec h n ol o g y s yste m will assi g n t he 
re q uire d kit n u m ber. 
A p pe n di x 4  
J ustificati o n f or 
eli gi bilit y 
criteria 
T he e xcl usi o n criteri o n 
re gar di n g use of pr o d ucts 
c o ntai ni n g H y peric u m 
perf orat u m ( St J o h n’s Wort) is 
delete d (e xcl usi o n criteri o n n o. 
1 5 i n versi o n 2. 0 of t he 
pr ot oc ol).  
T his e xcl usi o n criteri o n was i ncl u de d 
i n t he ori gi nal pr ot oc ol b y err or a n d is 
n ot c o nsi d ere d rele va nt f or t his trial.  
T hr o u g h o ut 
d oc u me nt 
Mi n or e dit orial re visi o ns.  
Mi n or, ha ve t heref ore n ot bee n 
s u m marise d.