Clinical trial NCT03683719
Conditions: Chronic Hand Eczema
Sponsor: LEO Pharma
Start date: 2018-11-28; Completion date: 2020-04-20
Enrollment: 258 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The purpose of this research trial was to test different strengths of a new trial medication, delgocitinib cream 1, 3, 8, and 20 mg/g, and to investigate how treatment with delgocitinib cream affects chronic hand eczema. This was judged by a range of assessments that rate the severity and extent of chronic hand eczema and its symptoms, as well as general health status and quality of life.

Detailed description:

Arms: arm 1: Delgocitinib cream applied twice daily for 16 weeks. arm 2: Delgocitinib cream applied twice daily for 16 weeks. arm 3: Delgocitinib cream applied twice daily for 16 weeks. arm 4: Delgocitinib cream applied twice daily for 16 weeks. arm 5: Delgocitinib cream vehicle applied twice daily for 16 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 
 
 
Offi ci al titl e:  A  p h a s e  2 b,  d o u bl e -bli n d,  r a n d o mi s e d,  5 -ar m,  v e hi cl e -c o ntr oll e d,  d o s e -r a n gi n g  tri al  t o  e v al u at e  t h e  effi c a c y  a n d 
s af et y of t wi c e d ail y t o pi c al a p pli c ati o n of d el g o citi ni b cr e a m 1, 3, 8, a n d 2 0 m g/ g f or 1 6 w e e k s i n a d ult s u bj e ct s wit h mil d t o s e v er e 
c hr o ni c h a n d e c z e m a  
L E O P h ar m a n u m b er:  L P 0 1 3 3 -1 2 7 3  
N C T  n u m b er:  N C T 0 3 6 8 3 7 1 9  
D at e: 0 7 -D e c -2 0 1 8  
 


 
U p d ate d Cli nic al Tri al Pr ot oc ol 
L P 0 1 3 3- 1 2 7 3 
P hase 2 b d ose-ra n gi n g trial t o e val uate del g o citi ni b crea m 1, 3, 8, a n d 2 0 m g/ g c o m pa red t o 
del g o citi ni b crea m ve hi cle o ver a 1 6- wee k treat me nt peri o d i n a d ult s u bjects wit h c hr o nic 
ha n d ecze ma 
P hase 2 b – d ose-ra n gi n g trial 
A p ha se 2 b, d o u bl e- bli n d, ra n d o mise d, 5-ar m, ve hicle-c o ntr olle d, d ose-ra n gi n g trial t o 
e val uate t he efficac y a n d safet y of t wice dail y t o pical a p plicati o n of d el g o citi ni b crea m 1, 3, 
8, a n d 2 0 m g / g f or 1 6 wee ks i n a d ult s u bjects wit h mil d t o se vere c hr o nic h a n d ecze ma 
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 p rot 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:  
L P 0 1 3 3 -1 2 7 3  
D ate:  
0 7 -Dec -2 0 1 8
E u dr a C T n o:  
2 0 1 8 -0 0 0 9 0 0 -4 0  
Versi o n:  
3. 0  


P D D
P D D
P D D
P D D


Trial I D: L P 0 1 3 3 -1 2 7 3  
Date:  0 7 -Dec -2 0 1 8  
Versi o n: 3. 0  
P a ge 3  of 1 2 8  
 
 
 
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  
Pr ot oc ol v ersi o n  
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) 
3. 0  
0 7 -Dec -2 0 1 8  
Gl o bal  
A me n d me nt 1 
(s u bsta ntial) 
2. 0  
1 1 -J ul-2 0 1 8  
Gl o bal  
Ori gi nal pr ot oc ol  
1. 0  
0 8 -Ma y -2 0 1 8  
N ot a p plica ble  
 
N ote t hat t he pr ot oc ol a m e n d me nt s u m mar y of c h a n ges ta bl e f or t he pre vi o us a me n d me nt is 
pr o vi de d i n A p pe n di x 6 . 
A me n d me nt 2  ( 0 7-Dec -2 0 1 8)  
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 criteri a 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 n cil of t he E ur o pea n U ni o n 
or s u bse q ue nt re g ul ati o n.  
O ver all r ati o n ale f or t he a me n d me nt  
T he mai n reas o n f or t he a me n d me nt is t o a d dress c o m me nts t o t he pr ot oc ol recei v e d fr o m t he 
U. S. F o o d a n d Dr u g A d mi nistrati o n . Miscella ne o us  ot her c ha n ges/ u p dates ha ve als o be e n 
i m ple me nte d. 
T he ta ble bel o w prese nts c ha n ges ma d e i n eac h secti o n a n d a brief rati o nal e f or eac h c ha n ge. 
C ha n ges h a ve b ee n eit her s u m marise d ( writte n wit h plai n te xt o nl y) or mar ke d as trac ke d 
c ha n ge d ( ne w te xt t hat has bee n a d d e d t o t he pr ot oc ol is hi g hl i g hte d i n b ol d  a n d te xt t hat has 
bee n re m o v e d fr o m t he pr ot oc ol is hi g hli g ht e d wit h a li ne t hr o u g h t h e te xt ). 
 
 


Trial I D: L P 0 1 3 3 -1 2 7 3  
Date:  0 7 -Dec -2 0 1 8  
Versi o n: 3. 0  
P a ge 4  of 1 2 8  
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  
Secti o n 1  
Pr ot oc ol 
s y n o psis 
C ha n ge of treat me nt s uccess a b bre viati o n 
fr o m I G A 0/ 1 t o I G A T S. 
Patie nt Gl o bal I m pr essi o n of C ha n ge ( P GI -
C) has bee n a d de d t o t he list of s u bject 
assess me nt s of efficac y a n d healt h -rel ate d 
q ualit y of life; P R Os.  
S u bject assess me nt of l ocal t olera bilit y h as 
bee n a d d e d as a s afet y assess me nt.  
E x cl usi o n criteri o n sli g htl y re vis e d: 
“C o nc urre nt s ki n diseas es o n t he ha n ds, e. g. 
ti ne a m a n u u m”. 
E x cl usi o n criteri o n  re vise d: “T u b erc 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 l ate nt
t u berc ul osis (e. g. pri or resi de nce i n or 
tr a vel t o c o u ntries wit h hi g h pre v ale nce of 
t u berc ul osis, cl ose c o nt act wit h a pers o n 
wit h acti ve t u berc ul osis, or a hist or y of 
acti ve or l ate nt t u berc ul osis w he re a n 
a de q u ate c o urse of tre at me nt c a n n ot be 
c o nfir me d) m ust be teste d. ” 
To reflect c ha n ges i n t he 
pr ot oc ol.  
Secti o n 4  
Sc he d ule of trial 
pr oce d ures  
Assess me nt of P GI -C a d de d.  
A d de d as a P R O a n c h or 
scale t o ge nerate a 
t hres h ol d f or 
i m pr o ve me nt t hat 
re pres e nts a mea ni n gf ul 
a m o u nt of c ha n ge i n t he 


Trial I D: L P 0 1 3 3 -1 2 7 3  
Date:  0 7 -Dec -2 0 1 8  
Versi o n: 3. 0  
P a ge 5  of 1 2 8  
 
 
 
 
 
T u berc ul osis test a d de d.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
S u bject a ssess me nt of local t olera bilit y 
a d de d.  
 
 
 
A ssess me nt of ne w c hr o nic ha n d ecze ma 
lesi o ns a d de d. 
 
 
 
 
 
 
C ha n ge t o f o ot n ote o n me dical hist or y: 
“Rele va nt me dic al hist or y m ust be rec or de d 
fr o m t he s u bject’s dat e of birt h. I n c ase 
me dic al hist or y is i nc o m plete at scree ni n g 
visit, missi n g d at a will be retrie ve d at D a y 
1 ( b aseli ne). ”  
tar get p o p ulatio n.  
 
To reflect t hat 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 v el 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 u ate c o urse of 
treat me nt ca n n ot b e 
c o nfir me d) m ust be 
teste d. 
 
A d de d t o ha ve a n acti ve 
s u bject assess me nt of 
l ocal t olera bilit y i n t he 
trial.  
 
To reflect t hat t he 
i n vesti gat or will c hec k 
f or ne w c hr o nic h a n d 
ecze ma lesi o ns at t he 
vis its i n dicate d i n t he 
sc he d ule of trial 
pr oce d ures.  
 
To clarif y t hat it is n ot 
t he i nte nti o n t hat f ull 
me dical hist or y  is t o be 
rec or de d b ot h at 
scree ni n g a nd  at baseli ne . 
 


Trial I D: L P 0 1 3 3 -1 2 7 3  
Date:  0 7 -Dec -2 0 1 8  
Versi o n: 3. 0  
P a ge 6  of 1 2 8  
 
 
 
 
A d diti o n of f o ot n ote o n W L Q:  ”O nl y f or 
s u bjects wit h a p ai d j o b”. 
 
To clarif y t hat o nl y 
s u bjects wit h a pai d j o b 
are t o a ns wer t he W L Q. 
Secti o n 6  
Trial o bjecti ves 
a n d e n d p oi nts  
C ha n ge of treat me nt s uccess a b bre viati o n s 
fr o m I G A 0/ 1 t o I G A T S a n d fr o m Pa G A 0/ 1 
t o Pa G A T S. 
 
 
 
 
 
 
 
 
A d diti o n of te xt t o 2  e n d p oi nts: 
“C ha n ge i n C hr o nic Ha n d Ecze ma S y m pt o m 
Diar y ( H E S D) ( wee kl y a ver a ge f or e a c h 
i n di vi d u al s y m pt o m) fr o m baseli ne t o 
Wee k 1 6 ”.  
“C ha n ge fr o m b aseli ne t o eac h wee k fr o m 
Wee k 1 t o Wee k 1 5 i n H E S D ( wee kl y 
a ver a ge f or e a c h i n di vi d u al s y m pt o m) ”.  
To a v oi d 
mis u n dersta n di n gs 
bet wee n e. g. a n I G A 
sc ore of 0 (clear) or 1 
(al m ost clear) a n d I G A 
treat me nt s uccess defi ne d 
as a n I G A sc ore of 0 
(clear) or 1 (al m ost clear) 
wit h at least a 2 -ste p 
i m pr o ve me nt. 
 
To clarif y t he e n d p oi nts . 
 
 
 
 
 
 
 
Secti o n 8. 3  
E x cl usi o n 
criteria  
Mi n or re visi o n of e x cl usi o n criteri o n 1 : 
“ 1. C o nc urre nt s ki n diseases o n t he ha n ds , 
e. g. ti ne a m a n u u m ”.  
 
 
 
Re visi o n of e x cl usi o n criteri o n 1 5 : 
“ 1 5. 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 l ate nt 
To  e ns ure e x cl usi o n of 
s u bjects wit h a dia g n osis 
of ti nea ma n u u m . 
 
 
 
To  f urt her s afeg u ar d 
s u bjects i n ris k of 
(re)acti vati o n of  late nt 
t u berc ul osis. 


Trial I D: L P 0 1 3 3 -1 2 7 3  
Date:  0 7 -Dec -2 0 1 8  
Versi o n: 3. 0  
P a ge 7  of 1 2 8  
 
 
 
t u berc ul osis (e. g. pri or resi de nce i n or 
tr a vel t o c o u ntries wit h hi g h pre v ale nce of 
t u berc ul osis, cl ose c o nt act wit h a pers o n 
wit h acti ve t u berc ul osis, or a hist or y of 
acti ve or l ate nt t u berc ul osis w here a n 
a de q u ate c o urse of tre at me nt c a n n ot be 
c o nfir me d) m ust be teste d ”. 
Secti o n 9. 6  
C o nc o mita nt 
me dicati o n a n d 
c o nc urre nt 
pr oce d ures  
T he f oll o wi n g s e nte nce h as bee n re vise d:  
“N or mal bat hi n g a n d was hi n g is all o we d 
wit h t he e xce pti o ns me nti o ne d i n t he 
i nstr ucti o ns f or useas ge nerall y perf or me d . 
Use of c os metic b o d y care pr o d ucts (e. g., 
b o d y l oti o n, s ha m p o o, bat h oil), w hic h are 
r o uti nel y use d b y t h e s u bjects, is all o we d as 
per i nstr ucti o ns f or use, b ut t he pr o d ucts 
s h o ul d n ot be c ha n ge d d uri n g t he tri al.” 
To clarif y s u bjects’ us ual 
s ki n care r o uti nes d uri n g 
t he trial. 
Secti o n 9. 7  
Pr o hi bite d 
me dicati o n a n d 
pr oce d ures  
Re visi o n of te xt  i n Pa nel 5: 
“Use of s yste mic a nti bi otics or 
cC uta ne o usl y a p plie d a nti bi otics o n t he 
ha n ds ”.  
To all o w treat me nt wit h 
s yste mic a nti bi otics 
t hr o u g h o ut t he trial, b ut 
n ot d uri n g scree ni n g . 
Secti o n 1 1. 1  
O ver vie w  
Pa nel 6 has bee n re vise d:  
 
“ I n vesti gat or ass ess me nts” has  bee n 
c ha n ge d t o “Efficac y assess me nts b y t he 
i n vesti gat or”.  
 
B o x wit h te xt: “Baseli ne visit ( Da y 1) o nl y: 
C hec k ca p pi n g li mits i n I R T bef ore 
ra n d o mizati o n” has bee n delete d.  
 
 
“Safet y a n d la b orat or y assess me nts ” has  
bee n c h a n ge d t o “Safet y assess me nts b y t h e 
i n vesti gat or”. 
 
 
F or clarificati o n . 
 
 
 
Ca p pi n g c h e c k will n ot 
be d o ne i n I R T  b ut will 
be d o ne b y L E O P har ma 
A/ S.  
 
F or clarificati o n . 
 
 


Trial I D: L P 0 1 3 3 -1 2 7 3  
Date:  0 7 -Dec -2 0 1 8  
Versi o n: 3. 0  
P a ge 8  of 1 2 8  
 
 
 
 
A ne w b o x after “Safet y assess me nts b y t h e 
i n vesti gat or” has bee n a d de d : “S u bject 
assess me nt o f local t olera bilit y ”. 
 
 
 
 
 
 
“Ot her ass ess me nts ” has bee n c h a n ge d t o 
“ La b orat or y a n d ot her assess me nts ”. 
 
To reflect t hat s u bject 
assess me nt of l ocal 
t olera bilit y is a d de d t o 
t he trial a n d t hat 
assess me nt  s h o ul d be 
perf or me d after safet y 
assess me nt s b y t h e 
i n vesti gat or. 
 
F or clarificati o n.  
Secti o n 1 1. 2. 3  
Me dical hist or y  
S m o ki n g hist or y sli g htl y re vise d:  
- D uri n g t he past year:  
    Less t ha n 1 ci garette per da y.  
    Less t ha n 5 ci garettes per da y.  
  - 1 t o 4 ci g arettes per d a y.  
  - 5 t o 1 0 ci garettes p er da y.  
   - 1 1 t o 2 0 ci garettes per da y.  
   - M ore t ha n 2 0 ci garett es per da y.  
To si m plif y cate g ories.  
Secti o n 1 1. 4. 4  
La b orat or y 
testi n g 
I n Pa n el 1 3 ( Cli nical la b orat or y tests), 
i nterfer o n ga m ma release test is a d de d . 
A d de d t o  test f or 
t u berc ul osis i n s u bjects 
w it h hi g h ris k of late nt 
t u berc ul osis. 
Secti o n 1 1. 4. 5  
S u bject 
assess me nt of 
local t olera bilit y  
Ne w secti o n.  
A d de d t o ha ve a n acti ve 
s u bject assess me nt of 
l ocal t olera bilit y 
(sti n gi n g/b u rni n g) i n t he 
trial.  


Trial I D: L P 0 1 3 3 -1 2 7 3  
Date:  0 7 -Dec -2 0 1 8  
Versi o n: 3. 0  
P a ge 9  of 1 2 8  
 
 
 
Secti o n 1 1. 6. 3  
S ki n bi o psies 
a n d p h ot o gra p hs 
(all sites, b ut 
o pti o nal)  
T he f oll o wi n g s e nte nce h as bee n a d d e d:  
“Bi o psies will n ot be t a ke n if t he 
i n vesti g at or c o nsi ders t he pr oce d ure 
u ns uit a ble f or t he s u bject (e. g. s u bjects 
recei vi n g a ntic o a g ul a nt t her a p y) ”.  
To clarif y t hat bi o psies 
are o nl y t o be ta k e n if t he 
pr oce d ure is s uita ble f or 
t he s u bject. 
Secti o n 1 1. 7 . 1 
Patie nt -re p orte d 
o utc o mes 
( P R Os) 
P GI -C a d de d t o t he list of P R Os t o be 
c o m plete d i n t he electr o nic de vice  b y t he 
s u bjects. T he n u m ber of P R Os t o be 
c o m plete d has c h a n ge d fr o m 6 t o 7.  
To reflect t he  a d diti o n  of 
P GI -C assess me nt i n t he 
trial. 
Secti o n 1 1. 7. 1. 4  
Patie nt Gl o bal 
I m pr essi o n of 
C ha n ge  ( P GI-C)  
Ne w secti o n.  
To reflect t he a d diti o n of 
P GI -C assess me nt i n t he 
trial. 
Sec ti o n 1 1. 7. 1. 8 
Wor k Li mitati o n 
Q uesti o n naire 
( W L Q) 
T he f oll o wi n g s e nte nce h as bee n re vise d:  
“T he W L Q will be c o m plete d at t he trial site 
f or s u bjects wit h a p ai d j o b acc or di n g t o 
t he sc he d ule of tri al pr oce d ures i n 
Secti o n  4 ”. 
To clarif y t hat o nl y 
s u bjects wit h a pai d j o b 
are t o a ns wer t he W L Q.  
Secti o n 1 3. 6. 1  
A d verse e ve nts 
of s pecial 
i nterest 
Ne w secti o n . 
To c ollect m ore 
i nf or mati o n o n e ve nts of 
ecze ma her petic u m i n 
ali g n me nt wit h si milar 
trials wit h del g ociti ni b 
crea m i n ot her 
i n dicati o ns t ha n c hr o nic 
ha n d ecze ma.   
Secti o n 1 4. 3. 1  
Dis p ositi o n of 
s u bjects 
T he f oll o wi n g s e nte nce h as bee n re vise d:  
T he reas o ns f or per ma ne nt disc o nti n uati o n 
of I M P a n d 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 b y last 
visit atte n de d a n d b y treat me nt gr o u p.  
Reas o ns f or per ma ne nt 
disc o nti n uati o n of I M P 
or wit h dra wal will be 
prese nte d b y tr eat me nt 
gr o u p o nl y.  


Trial I D: L P 0 1 3 3 -1 2 7 3  
Date:  0 7 -Dec -2 0 1 8  
Versi o n: 3. 0  
P a ge 1 0  of 1 2 8  
 
 
 
Secti o n 1 4. 3. 4  
Testi n g strat e g y  
 
Secti o n 1 4. 3. 5  
A nal ysis of 
pri mar y efficac y 
e n d p oi nt  
 
Secti o n 1 4. 3. 6  
A nal ysis of 
sec o n dar y 
efficac y 
e n d p oi nts  
C ha n ge of treat me nt s uccess a b bre viati o n 
fr o m I G A 0/ 1 t o I G A T S.  
To a v oi d 
mis u n dersta n di n gs 
bet wee n a n I G A sc ore of 
0 (clear) or 1  (al m ost 
clear) a n d I G A tr eat me nt 
s uccess defi ne d as a n 
I G A s c ore of 0 (clear) or 
1  (al m ost clear) wit h at 
least a 2-ste p 
i m pr o ve me nt. 
Secti o n 1 4. 3. 7. 1  
A nal ysis of 
patie nt -re p ort e d 
o utc o mes  
T he f oll o wi n g s e nte nces ha ve bee n re vise d:  
 
“T he P R Os H EI S, Pa G A, D L QI, E Q -5 D -5 L, 
Q O L H E Q,  a n d  W L Q , a n d P GI -C  will be 
s u m marise d b y tr eat me nt gr o u p a n d visit 
usi n g descri pti ve statistics. T he  s u m maries 
will be prese nte d f or t he f ull a nal ysis set. ” 
 
“ …baseli ne w ee kl y a v era ge will be defi n e d 
b y a v era ge of meas ure m e nts fr o m Da y -6 7  
t o Da y -1 (i.e., last 7 x 2 4 h o urs u ntil da y of 
baseli ne visit) , Wee k 1 wee kl y a vera ge will 
be defi ne d b y t he a vera ge of meas ure me nts 
fr o m Da y 2 1  t o Da y 8 7 , Wee k 2 wee kl y 
a vera ge will be defi ne d b y t he a vera ge of 
meas ure me nts fr o m Da y 9 8  t o Da y 1 5 1 4  a n d 
s o o n, u ntil Wee k 1 5. Wee k 1 6 will be 
calc ulate d b ase d o n t he l ast 7 d a ys x 2 4 h o urs 
meas ure me nts bef ore  p rece di n g  t he actual 
Wee k 1 6 visit  da y . 
 
“T he c h a n ge fr o m baseli ne t o Wee k 1 6 i n 
H E S D N R S ( wee kl y a ver a ge f or e ac h 
 
 
To reflect t he a d diti o n of 
P GI -C assess me nt i n t he 
trial. 
 
 
 
F or  clarificati o n. T h e last 
ti me H E D S D is 
c o m plete d is i n t he 
e ve ni n g bef ore t he Wee k 
1 6 visit . 
 
 
 
 
 
 
 
 
Clarificati o n of w or di n g.  
 


Trial I D: L P 0 1 3 3 -1 2 7 3  
Date:  0 7 -Dec -2 0 1 8  
Versi o n: 3. 0  
P a ge 1 1  of 1 2 8  
 
 
 
i n di vi d u al s y m pt o m)  ( wee kl y a v era ge), 
i.e., f or eac h i n di vi d ual s y m pt o m, H EI S (f or 
eac h i n di vi d ual ite mi m p act), D L QI, E Q-5 D -
5 L, Q O L H E Q, a n d W L Q will be 
s u m marise d b y tr eat me nt gr o u p a n d d o mai n, 
w here a p plica ble, a n d a n al yse d usi n g t he 
M M R M a p pr oac h as d es cri be d a b o v e f or t he 
a nal ysis of t he sec o n d ar y c o nti n u o us 
e n d p oi nt.  
 
C ha n ge of treat me nt s uccess a b bre viati o n 
fr o m Pa G A 0/ 1 t o Pa G A T S. 
 
 
 
 
 
 
 
 
 
 
 
To a v oi d 
mis u n dersta n di n gs 
bet wee n a Pa G A sc ore of 
0 (clear) or 1 (al m ost 
clear) a n d a Pa G A 
treat me nt s uccess defi ne d 
as ac hie vi n g:  
Pa G A sc ore of 0 (clear) 
w he n classifie d at 
baseli ne as 1 (al m ost 
clear) or 2 ( mil d)  
or  
Pa G A sc ore of 0 (clear) 
or 1 (al m ost clear) w he n 
classifie d at bas eli ne as 3  
( m o derate) or 4 (se vere). 
Secti o n 1 4. 3. 7. 2  
Efficac y o ver 
ti me 
T he f oll o wi n g s e nte nce s ha ve  bee n re vise d:  
“C ha n ge fr o m b aseli ne t o eac h wee k 
t hr o u g h Wee k 1 t o 1 5 i n H E S D N R S 
( wee kl y a ver a ge f or e a c h i n di vi d u al 
s y m pt o m) ( wee kl y a v era ge), i.e., f or eac h 
i n di vi d ual s y m pt o m”.  
 
C ha n ge fr o m bas eli ne t o eac h sc h e d ule d 
Clarificati o n of w or di n g.  
 
 
 
 
 
 
 


Trial I D: L P 0 1 3 3 -1 2 7 3  
Date:  0 7 -Dec -2 0 1 8  
Versi o n: 3. 0  
P a ge 1 2  of 1 2 8  
 
 
 
assess me nt u ntil Wee k 1 4 i n H EI S (f or eac h 
i n di vi d ual ite mi m pact). 
 
C ha n ge of treat me nt s uccess a b bre viati o n s 
fr o m I G A 0/ 1 t o I G A T S a n d fr o m Pa G A 0/ 1 
t o Pa G A T S. 
 
 
 
To a v oi d 
mis u n dersta n di n gs 
bet wee n e. g. a n I G A 
sc ore of 0 (clear) or 1 
(al m ost clear) a n d I G A 
treat me nt s uccess defi ne d 
as a n I G A sc ore of 0 
(clear) or 1 (al m ost clear) 
wit h at least a 2 -ste p 
i m pr o ve me nt. 
Secti o n 1 4. 3. 9. 1  
A d verse e ve nts  
T he f oll o wi n g s e nte nces ha ve  bee n 
a d de d/ re vise d: 
“A d verse e ve nts of s peci al i nterest will be 
t a b ul ate d b y tre at me nt gr o u p. 
A Es lea di n g t o wit h dra wal fr o m trial a n d 
A Es le a di n g t o or  per ma ne nt disc o nti n uati o n 
of I M P will be t a b ul ate d b y tre at me nt 
gr o u p  liste d a n d a narrati ve f or eac h will be 
gi ve n . ” 
A d verse e ve nt of s pecial 
i nterest was  a d d e d t o t he 
trial. 
Ta b ulati o n s are 
c o nsi dere d a m ore 
practical a n d i nf or mati ve 
wa y of prese nti n g 
a d verse e ve nts of s p ecial 
i nterest as well as  A Es 
leadi n g t o wit h dra wal 
fr o m trial a n d A Es 
lea di n g t o p er ma ne nt 
disc o nti n uati o n of I M P.  
Secti o n 1 4. 3. 9. 4  
S u bject 
assess me nt of 
l ocal t olera bilit y 
Ne w secti o n.  
To descri be statistical 
ha n dli n g of t he s u bj ect 
assess me nt of l ocal 
t olera bilit y. 
A p pe n di x 4  
S h ort versi o n of 
eli gi bilit y 
criteria  
Mi n or re visi o n of e x cl usi o n criteri o n 1 : 
“C o nc urre nt s ki n diseas es o n t he ha n ds , e. g. 
ti ne a m a n u u m”.  
 
To e ns ure e x cl usi o n of 
s u bjects wit h a dia g n osis 
of ti nea ma n u u m.  
 


Trial I D: L P 0 1 3 3 -1 2 7 3  
Date:  0 7 -Dec -2 0 1 8  
Versi o n: 3. 0  
P a ge 1 3  of 1 2 8  
 
 
 
 
Re visi o n of e x cl usi o n criteri o n 1 5:  
T u berc ul osis re q uiri n g tr eat 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 
l ate nt t u berc ul osis m ust be teste d). 
 
To f urt her s afe g u ar d 
s u bjects i n ris k of 
(re)acti vati o n of late nt 
t u berc ul osis. 
A p pe n di x 5  
C o nt act list 
List of pr ot oc ol a ut h ors d elete d.  
To reflect c ha n ges i n t he 
L E O P har ma A/ S 
i nter nal pr oce d ure f or 
pr ot oc ol writ in g.  
A p pe n di x 6  
Pr ot oc ol 
a me n d me nt 
hist or y  
Ne w a p p e n di x . 
To list c ha n ges i n t he 
pre vi o us a me n d me nt.  
T hr o u g h o ut  
Mi n or e dit orial a n d d oc u me nt f or matti n g 
c ha n ges.  
Mi n or, ha ve t heref ore n ot 
bee n s u m marise d.  
 
 
 


Trial I D: L P 0 1 3 3 -1 2 7 3  
Date:  0 7 -Dec -2 0 1 8  
Versi o n: 3. 0  
P a ge 1 4  of 1 2 8  
 
 
 
Ta ble of co nte nts  
Cli nic al tri al pr ot oc ol st ate me nts  ............................................................................................ 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  ................................................................... 3  
Ta ble of c o nte nts  ..................................................................................................................... 1 4  
List of a b bre vi ati o ns  ............................................................................................................... 2 0  
1  Pr ot oc ol s y n o psis  ................................................................................................................ 2 2  
2  Tri al i de ntific ati o n  ............................................................................................................. 2 7  
3  Sc he m atic of tri al desi g n  ................................................................................................... 2 7  
4  Sc he d ule of tri al pr oce d ures  ............................................................................................. 2 8  
5  I ntr o d ucti o n a n d tri al r ati o n ale ....................................................................................... 3 3  
5. 1  C hr o nic ha n d ecze ma  .................................................................................................. 3 3  
5. 2  E x perie nce wit h i n vesti gati o nal me dici nal pr o d uct  .................................................... 3 4  
5. 3  Trial r ati o nale  .............................................................................................................. 3 6  
5. 4  J ustificati o n f or d ose ................................................................................................... 3 6  
5. 5  Et hical c o nsi derati o ns  ................................................................................................. 3 7  
5. 6  Be nefit/ris k assess me nt  ............................................................................................... 3 8  
6  Tri al o bjecti ves a n d e n d p oi nts  .......................................................................................... 3 9  
7  Tri al desi g n  ......................................................................................................................... 4 1  
7. 1  O verall trial desi g n  ..................................................................................................... 4 1  
7. 2  N u m ber of s u bjects nee d e d  ......................................................................................... 4 2  
7. 3  E n d of trial defi niti o n .................................................................................................. 4 2  
7. 4  S oft ware  ...................................................................................................................... 4 3  
8  Tri al p o p ul ati o n  ................................................................................................................. 4 4  
8. 1  S u bject eli gi bilit y  ........................................................................................................ 4 4  
8. 2  I n cl usi o n criteria ......................................................................................................... 4 4  
8. 3  E x cl usi o n criteria  ........................................................................................................ 4 5  
8. 4  Scree ni n g a n d s cree ni n g fail ures  ................................................................................ 4 8  
9  Tre at me nts  .......................................................................................................................... 5 0  
9. 1  Trial pr o d u ct descri pti o n  ............................................................................................. 5 0  
9. 2  A d mi nistrati o n of I M P  ................................................................................................ 5 0  


Trial I D: L P 0 1 3 3 -1 2 7 3  
Date:  0 7 -Dec -2 0 1 8  
Versi o n: 3. 0  
P a ge 1 5  of 1 2 8  
 
 
 
9. 3  Treat me nt assi g n m e nt  ................................................................................................. 5 1  
9. 3. 1  
Bli n di n g  ......................................................................................................... 5 1  
9. 3. 2  
E mer ge n c y u n bli n di n g of i n di vi d ual s u bject treat me nt  ................................ 5 1  
9. 4  Bac k gr o u n d treat me nt (e m ollie nts)  ............................................................................ 5 2  
9. 5  Resc ue treat me nt  ......................................................................................................... 5 2  
9. 6  C o nc o mita nt me dicati o n a n d c o nc urre nt pr o ce d ures  ................................................. 5 2  
9. 7  Pr o hi bite d me dicati o n a n d pr oce d ures ........................................................................ 5 4  
9. 8  Treat me nt l o gistics a n d acc o u nta bilit y  ....................................................................... 5 6  
9. 8. 1  
La b elli n g a n d pac k a gi n g of trial pr o d ucts  ..................................................... 5 6  
9. 8. 2  
St ora ge of trial pr o d u cts  ................................................................................ 5 6  
9. 8. 3  
Dr u g acc o u nta bilit y  ....................................................................................... 5 7  
9. 8. 4  
Treat me nt c o m plia nce  ................................................................................... 5 7  
9. 8. 5  
Trial pr o d u ct destr ucti o n  ............................................................................... 5 8  
9. 9  Pr o visi o n f or s u bject care f oll o wi n g tri al c o m pleti o n  ................................................ 5 8  
9. 1 0  Re p orti n g pr o d u ct c o m plai nts ..................................................................................... 5 8  
1 0  Disc o nti n u ati o n a n d wit h dr a w al  ...................................................................................... 5 9  
1 0. 1  Ge neral pri nci ples  ....................................................................................................... 5 9  
1 0. 2  I M P disc o nti n uati o n r ules ........................................................................................... 5 9  
1 0. 2. 1  Reas o ns f or disc o nti n uati o n of I M P  .............................................................. 5 9  
1 0. 3  Earl y ter mi nati o n assess me nts  .................................................................................... 6 0  
1 0. 4  L ost t o f oll o w -u p  ........................................................................................................ 6 1  
11  Tri al assess me nts a n d pr oce d ures  .................................................................................... 6 2  
1 1. 1  O ver vie w ..................................................................................................................... 6 2  
1 1. 2  Assess me nts perf or m e d o nl y at scree ni n g/ bas eli ne  .................................................... 6 3  
1 1. 2. 1  De m o gra p hics ................................................................................................ 6 3  
1 1. 2. 2  Fitz patric k s ki n t y pe  ...................................................................................... 6 4  
1 1. 2. 3  Me dical hist or y  .............................................................................................. 6 4  
1 1. 2. 4  Classificati o n of c hr o nic ha n d ecze ma  .......................................................... 6 7  
1 1. 2. 5  Hei g ht a n d wei g ht  ......................................................................................... 6 7  
1 1. 2. 6  Deter mi nati o n of treat me nt area  .................................................................... 6 7  
1 1. 3  Efficac y assess me nts  .................................................................................................. 6 8  
1 1. 3. 1  I n v esti gat or’s Gl o bal Ass ess me nt (I G A) ...................................................... 6 8  
1 1. 3. 2  Ha n d Ecze ma Se verit y I n de x ( H E C SI)  ......................................................... 6 9  
1 1. 4  Safet y assess me nts  ...................................................................................................... 7 1  


Trial I D: L P 0 1 3 3 -1 2 7 3  
Date:  0 7 -Dec -2 0 1 8  
Versi o n: 3. 0  
P a ge 1 6  of 1 2 8  
 
 
 
1 1. 4. 1  Vital si g ns  ...................................................................................................... 7 1  
1 1. 4. 2  P h y sical e x a mi nati o n..................................................................................... 7 1  
1 1. 4. 3  E C G  ............................................................................................................... 7 2  
1 1. 4. 4  La b orat or y testi n g  ......................................................................................... 7 3  
1 1 . 4. 5 S u bject assess me nt of l ocal t olera bilit y  ........................................................ 7 5  
1 1. 5  P har mac o ki netic ass ess me nts  ..................................................................................... 7 6  
1 1. 5. 1  Bl o o d sa m pli n g f or a n al ysis of s yste mic c o n ce ntr ati o n of del g ociti ni b  ....... 7 6  
1 1. 6  P har mac o d y na mics a n d p har mac o ge n o mics  .............................................................. 7 6  
1 1. 6. 1  O ver vie w  ....................................................................................................... 7 6  
1 1. 6. 2  S ki n s wa bs  ..................................................................................................... 7 7  
1 1. 6. 3  S ki n bi o psies a n d p h ot o gra p hs (all sites, b ut o pti o nal)  ................................. 7 8  
1 1. 6. 4  Fila g gri n m utati o ns  ....................................................................................... 8 0  
1 1. 6. 5  N o n -i n vasi ve meas ure me nts of s ki n barrier f u ncti o n (selecte d tri al sites) ... 8 0  
1 1. 7  Ot her assess me nts  ....................................................................................................... 8 1  
1 1. 7. 1  Patie nt -re p orte d o utc o m es ( P R Os) ................................................................ 8 1  
1 1. 7. 1. 1  C hr o nic Ha n d Ecze ma S y m pt o m Diar y ( H E S D)  .................. 8 2  
1 1. 7. 1. 2  C hr o nic Ha n d Ecze ma I m pact Scale ( H EI S)  ........................ 8 2  
1 1. 7. 1. 3  Patie nt ’s Gl o bal Assess m e nt ( Pa G A) .................................... 8 2  
1 1. 7. 1. 4  Patie nt Gl o bal I m pr essi o n of C ha n ge ( P GI -C) ...................... 8 2  
1 1. 7. 1. 5  Der mat ol o g y Life Q ualit y I n d e x ( D L QI)  .............................. 8 3  
1 1. 7. 1. 6  E ur o Q o L 5 -di me nsi o n healt h q uesti o n naire 5 -le vel ( E Q-5 D -
5 L)  ......................................................................................... 8 3  
1 1. 7. 1. 7  Q ualit y of Lif e i n Ha n d Ecze ma Q uesti o n naire ( Q O L H E Q)  8 3  
1 1. 7. 1. 8  Wor k Li mitati o n Q uesti o n naire ( W L Q)  ................................ 8 3  
1 1. 8  Esti mate of t otal bl o o d v ol u me c ollecte d  ................................................................... 8 4  
1 1. 9  E n d of trial  .................................................................................................................. 8 4  
1 1. 1 0  St ora ge of bi ol o gi cal sa m ples  ..................................................................................... 8 4  
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  ..................... 8 6  
1 3  A d verse e v e nts  ................................................................................................................... 8 7  
1 3. 1  Defi niti o n a n d classificati o n of a d verse e ve nts  .......................................................... 8 7  
1 3. 2  C ollecti o n of a d verse e ve nt re p orts  ............................................................................ 8 7  
1 3. 3  Re p orti n g of a d vers e e ve nts ........................................................................................ 8 7  
1 3. 4  Re p orti n g of s eri o us a d v erse e v e nts  ........................................................................... 8 8  
1 3. 4. 1  I n v esti gat or re p orti n g res p o nsi bilities ........................................................... 8 8  
1 3. 4. 2  L E O re p orti n g res p o nsi bilities  ...................................................................... 8 9  
1 3. 5  Ot her e ve nts t hat r e q uire e x pe dite d re p orti n g  ............................................................ 9 0  


Trial I D: L P 0 1 3 3 -1 2 7 3  
Date:  0 7 -Dec -2 0 1 8  
Versi o n: 3. 0  
P a ge 1 7  of 1 2 8  
 
 
 
1 3. 5. 1  Pre g n a nc y  ...................................................................................................... 9 0  
1 3. 6  Re p orti n g of ot her e v e nts ............................................................................................ 9 0  
1 3. 6. 1  A d verse e ve nts of s pecial i nterest  ................................................................. 9 0  
1 3. 6. 2  O ver d ose ........................................................................................................ 9 1  
1 3. 6. 3  Me dicati o n err or  ............................................................................................ 9 1  
1 3. 6 . 4 Mis use  ........................................................................................................... 9 1  
1 3. 6. 5  A b use  ............................................................................................................. 9 1  
1 3. 6. 6  A g gra vati o n of c o n diti o n  .............................................................................. 9 2  
1 3. 7  F oll o w -u p f or fi nal o utc o me of a d verse e v e nts  .......................................................... 9 2  
1 3. 8  Ha n dli n g of a n ur ge nt safet y meas ure  ........................................................................ 9 2  
1 4  St atistic al met h o ds  ............................................................................................................. 9 3  
1 4. 1  Sa m ple siz e  ................................................................................................................. 9 3  
1 4. 2  Trial a n al ysis sets  ........................................................................................................ 9 3  
1 4. 3  Statistical a nal ysis  ....................................................................................................... 9 4  
1 4. 3. 1  Dis p ositi o n of s u bjects  .................................................................................. 9 4  
1 4. 3. 2  De m o gra p hics a n d ot her baseli ne c haracteristics .......................................... 9 4  
1 4. 3. 3  E x p os ure a n d treat me nt c o m plia nce  ............................................................. 9 4  
1 4. 3. 4  Testi n g strat e g y  ............................................................................................. 9 5  
1 4. 3. 5  A nal ysis of pri mar y efficac y e n d p oi nt  .......................................................... 9 5  
1 4. 3. 6  A nal ysis of s ec o n dar y efficac y e n d p oi nts  ..................................................... 9 6  
1 4. 3. 7  A nal ysis of ot h er e n d p oi nts  ........................................................................... 9 7  
1 4. 3. 7. 1  A nal ysis of patie nt -re p orte d o utc o mes .................................. 9 7  
1 4. 3. 7. 2  Efficac y o ver ti me  ................................................................. 9 9  
1 4. 3. 7. 3  E x pl orat or y a nal ys es  ............................................................. 9 9  
1 4. 3. 8  A nal ysis of p har mac o d y na mics a n d p har m ac o ge n o mics .............................. 9 9  
1 4. 3. 9  A nal ysis of s afet y  ........................................................................................ 1 0 0  
1 4. 3. 9. 1  A d verse e ve nts  .................................................................... 1 0 0  
1 4. 3. 9. 2  Vital si g ns  ............................................................................ 1 0 1  
1 4. 3. 9. 3  Cli nical la b orat or y e val u ati o n  ............................................. 1 0 1  
1 4. 3. 9. 4  S u bject assess me nt of l ocal t olera bilit y  ............................... 1 0 1  
1 4. 3. 1 0  P har mac o ki netics  ........................................................................................ 1 0 1  
1 4. 3. 1 1  I nteri m a nal ysis ........................................................................................... 1 0 1  
1 4. 3. 1 2  Ge neral pri nci ples  ....................................................................................... 1 0 2  
1 4. 3. 1 3  Ha n dli n g of missi n g val u es  ......................................................................... 1 0 2  
1 5  Refere nces  ......................................................................................................................... 1 0 3  
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 v e nts  ........................... 1 0 6  


Trial I D: L P 0 1 3 3 -1 2 7 3  
Date:  0 7 -Dec -2 0 1 8  
Versi o n: 3. 0  
P a ge 1 8  of 1 2 8  
 
 
 
A p pe n di x 2: Cl assific ati o n of a d verse e ve nts  ..................................................................... 1 0 8  
A p pe n di x 3: Tri al g o ver n a nce c o nsi der a ti o ns .................................................................... 111  
A p pe n di x 3 A: Re g ulat or y a n d et hical c o nsi derati o ns  .............................................. 1 1 1  
A p pe n di x 3 B: I nf or me d c o nse nt pr ocess  ................................................................. 1 1 2  
A p pe n di x 3 C: S u bject a n d data c o nfi de ntialit y  ....................................................... 1 1 2  
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 data ha n dli n g  ......................... 1 1 3  
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 1 8  
A p pe n di x 3 F: I ns ur a nce  ........................................................................................... 1 1 9  
A p pe n di x 3 G: Fi na ncial discl os ure  .......................................................................... 1 1 9  
A p pe n di x 3 H: Trial a n d site cl os ure  ........................................................................ 1 2 0  
A p pe n di x 3I: Res p o nsi bilities  .................................................................................. 1 2 1  
A p pe n di x 4: S h ort versi o n of eli gi bilit y criteri a  ................................................................ 1 2 2  
A p pe n di x 5: C o nt act list  ...................................................................................................... 1 2 4  
A p pe n di x 6: Pr ot oc ol a me n d me nt hist or y  ......................................................................... 1 2 5  
 
List of p a nel s 
Pa nel 1: Trial desi g n  ................................................................................................................. 2 7  
Pa nel 2: Sc he d ule of trial pr oce d ures  ....................................................................................... 2 8  
Pa nel 3: O bjecti ves a n d e n d p oi nts  ........................................................................................... 3 9  
Pa nel 4: I d e ntificati o n of I M Ps  ................................................................................................ 5 0  
Pa nel 5: Pr o hi bite d me dicati o n  ................................................................................................ 5 5  
Pa nel 6: Se q ue nce of ass ess me nts  ............................................................................................ 6 2  
Pa nel 7: Fitz patric k s ki n classificati o n  ..................................................................................... 6 4  
Pa nel 8: Defi niti o n of s u bt y pes of h a n d ecze ma  ...................................................................... 6 7  
Pa nel 9: I n v esti gat or ’s Gl o bal Assess me nt (I G A) .................................................................... 6 8  
Pa nel 1 0: Descri pti o n of t he se verit y of eac h I G A si g n or s y m pt o m  ....................................... 6 9  
Pa nel 1 1: H E C SI s e verit y sc ore scale a n d area sc ore scal e  ..................................................... 7 0  
Pa nel 1 2: Calc ulati o n of t he t otal H E C SI sc ore  ....................................................................... 7 0  


Trial I D: L P 0 1 3 3 -1 2 7 3  
Date:  0 7 -Dec -2 0 1 8  
Versi o n: 3. 0  
P a ge 1 9  of 1 2 8  
 
 
 
Pa nel 1 3: Cli nical la b orat or y tests  ............................................................................................ 7 4  
Pa nel 1 4: S u bject assess me nt of l ocal t olera bilit y after I M P a p plicati o n  ................................ 7 5  
Pa nel 1 5: A d vers e e ve nt of s pecial i nterest  .............................................................................. 9 0  
Pa nel 1 6: Tra ns missi o n of electr o ni c d ata  .............................................................................. 1 1 7  
 


Trial I D: L P 0 1 3 3 -1 2 7 3  
Date: 0 7 -Dec -2 0 1 8  
Versi o n: 3. 0  
P a ge 2 0  of 1 2 8  
 
 
 
List of a b bre vi ati o ns  
A E  
a d verse eve nt  
A S  
area s c ore  
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  
CI  
c o nfi de nce i nter val 
C M O  
c o ntract m a n ufact uri n g o r ga nisati o n 
C R A  
cli nical researc h ass ociat e 
C R O  
c o ntract researc h o r ga nis ati o n 
C T R  
cli nical trial re p ort 
D L QI  
Der mat ol o g y Life Q ualit y I n d e x  
E C G  
electr ocar di o gra m 
e C R F 
electr o nic case re p ort f or m 
e Diar y 
electr o nic diar y 
E M A  
E ur o pea n Me dici nes A ge nc y  
e P R O 
electr o nic p atie nt -re p orte d o utc o me 
E Q -5 D -5 L  
E ur o Q o L 5 -D i me nsi o n Healt h Q uesti o n naire 5-Le vel  
G C P  
G o o d Cli nical Practice  
H Bc A b  
he patitis B c ore a nti b o d y  
H Bs A b  
he patitis B s urface  a nti b o d y 
H Bs A g  
he patitis B s urface a nti ge n  
H D L  
hi g h de nsit y li p o pr otei n  
H E C SI  
Ha n d Ecze ma Se verit y I n de x  
H EI S  
C hr o nic Ha n d Ecze ma I m pact Scale  
H E S D  
C hr o nic Ha n d Ecze ma S y m pt o m Diar y  
HI V  
h u ma n i m m u n o deficie nc y vir us  
I C H 
I nter nati o nal C o u ncil f or Har m o nisati o n  of Tec h ni cal Re q uire me nts f or 
P har mace uticals f or H u m a n Use  
I C5 0 
half ma xi mal i n hi bit or y c o nce ntrati o n  
I D 
i de ntificati o n n u m ber 
I E C 
in de pe n de nt et hics c o m mittee  
I G A 
I n v esti gat or’s Gl o bal Ass ess me nt 
I G A T S 
I G A tr eat me nt s uc cess, i. e. a n I G A sc ore of 0 (clear) or 1 (al m ost clear) wit h 
at least a 2-ste p i m pr o ve me nt 
I g E 
i m m u n o gl o b uli n E 
I M P 
in vesti gati o nal me dici nal pr o d uct  


Trial I D: L P 0 1 3 3 -1 2 7 3  
Date: 0 7 -Dec -2 0 1 8  
Versi o n: 3. 0  
P a ge 2 1  of 1 2 8  
 
 
 
 
I N D 
i n vesti gati o nal ne w dr u g 
I N N 
i nter nati o nal n o n-pr o pri etar y n a me  
I R B 
instit uti o nal re vie w b oar d  
I RT  
interacti ve res p o nse tec h n ol o g y 
J A K 
ja n us ki nas e  
L D L  
l o w de nsit y li p o pr otei n 
L E O  
L E O P har ma A/ S  
Me d D R A  
Me dical Dicti o nar y f or R e g ul at or y Acti vities  
M M R M  
mi x e d m o del f or re peate d meas ure me nt  
N R S  
n u meric rati n g scale  
Pa G A  
Patie nt ’s Gl o bal Assess m e nt 
Pa G A T S  
Pa G A treat me nt s uccess, i.e. a Pa G A sc ore of 0 (clear) w he n cl assifie d at 
baseli ne as 1  (al m ost clear) or 2 ( mil d), or a Pa G A sc ore of 0 (clear) or 1 
(al m ost clear) w he n classifie d at baseli ne as 3 ( m o derate) or 4 (se v ere) 
P D E -4  
p h os p h o diesterase -4   
P GI -C  
Patie nt Gl o bal I m pr essi o n of C ha n ge  
P K  
p har mac o ki netics  
P R O  
p atie nt-re p ort e d o utc o me 
P T  
preferre d t er m  
P U V A  
ps orale n a n d ultra vi olet A  
Q O L H E Q  
Q ualit y of Lif e i n Ha n d Ecze ma  Q uesti o n naire  
S A E  
seri o us a d vers e e v e nt  
S D  
sta n dar d de viati o n 
S D T M  
st u d y data ta b ul ati o n m o del 
S O C  
syste m o r ga n class 
S U S A R  
seri o us a n d u ne x pecte d s us pecte d a d v erse reacti o n 
S S  
se verit y sc ore 
S T A T  
si g nal tra ns d u cer a n d acti vat or 
U L N  
u p per li mit of n or mal ra n ge  
U V B  
ultra vi olet  B  
W L Q  
Wor k Li mitati o n Q uesti o n naire  


C CI


Trial I D: L P 0 1 3 3 -1 2 7 3  
Date: 0 7 -Dec -2 0 1 8  
Versi o n: 3. 0  
P a ge 2 3  of 1 2 8  
 
 
 
Scree ni n g peri o d  
T he scree ni n g peri o d has a mi ni m u m d urati o n of 1  wee k a n d a ma xi m u m 
d urati o n of 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. T he s u bj ects will recei ve trai ni n g i n c o m pleti o n  of a n 
electr o nic diar y (e Diar y). F urt her m ore, t he s u bj ects will be as ke d t o fill  o ut 
patie nt -re p orte d o utc o mes ( P R Os). 
Treat me nt peri o d  
At baseli ne ( Da y  1),  s u bjects’ eli gi bilit y t o e nter t he trial will be c o nfir me d a n d 
if still eli gi ble a n d I G A baseli ne se verit y a n d re gi o nal ca p pi n g ha ve n ot bee n 
reac he d, t he s u bjects will be ra n d o mise d t o 1 of t he 5 treat me nt gr o u ps. T he 
ra n d o misati o n is stratifie d b y t he se verit y of c hr o nic ha n d ecze ma acc or di n g t o 
I G A ( mil d, m o derate, a n d se vere) a n d re gi o n ( E ur o pe a n d N ort h A merica ). 
T he first a p plicati o n of t he i n vesti gati o nal me dici n al pr o d uct (I M P) will occ ur 
at t he trial site  at baseli ne ( Da y  1) . T he s u bse q ue nt I M P a pplicati 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 1 6 wee ks. D uri n g t he 
treat me nt peri o d, t he s u bj ects will be re q uire d t o ret ur n t o t he trial site f or t he 
visits sc he d ule d at Wee ks 1, 2, 4, 6, 8, 1 0, 1 2, 1 4, a n d 1 6. T he last I M P 
a p plicat i o n will occ ur bef ore t he s u bjects atte n d t he visit sc he d ule d at Wee k 1 6. 
F oll o w -u p p eri o d 
All s u bj ects will atte n d a f oll o w -u p visit a p pr o xi matel y 2 wee ks after t he last 
I M P a p plicati o n f or assess me nt of safet y. 
 
Mai n assess me nts  
I n vesti gat or assess me nts of efficac y : 
 
I G A f or assess me nt of disease se verit y. 
 
H E C SI f or assess me nt of t he cli nical si g ns of c hr o nic ha n d ecze ma . 
S u bj ect assess me nt s of efficac y a n d healt h -relate d q ualit y of life; P R Os: 


Trial I D: L P 0 1 3 3 -1 2 7 3  
Date: 0 7 -Dec -2 0 1 8  
Versi o n: 3. 0  
P a ge 2 4  of 1 2 8  
 
 
 
 
C hr o nic Ha n d Ecze ma S y m pt o m Diar y ( H E S D) . 
 
C hr o nic Ha n d Ecze ma I m p act Scale ( H EI S) . 
 
P atie nt’s Gl o bal A ssess me nt ( Pa G A) of disease se verit y.  
 
Patie nt Gl o bal I m pressi o n of C ha n ge ( P GI -C)  
 
Der mat ol o g y Life Q ualit y I n de x ( D L QI ). 
 
E ur o Q o L  5 -di me nsi o n healt h q uesti o n naire 5 -le vel (E Q -5 D -5 L ). 
 
Q ualit y of Life i n Ha n d Ecze ma Q uesti o n naire ( Q O L H E Q ). 
 
W or k Li mitati o n Q uesti o n naire ( W L Q ). 
Safet y assess me nts:  
 
Vital si g ns, p h ysical e xa mi nati o ns, electr ocar di o gra ms, la b orat or y 
testi n g, s u bject assess me nt of l ocal t olera bilit y, 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  years or a b o ve.  
 
Dia g n osis of c hr o nic ha n d ecze ma defi ne d as ha n d ecze ma, w hic h has 
persiste d f or m ore t ha n 3  m o nt hs  or ret ur ne d t wice or m ore wit hi n t he 
last 1 2 m o nt hs.  
 
D isease se verit y gra de d as mil d t o se vere acc or di n g t o I G A (i.e., 
I G A ≥2).  
 
R ece nt hist or y ( wit hi n 1  year bef ore t he scree ni n g visit) of i na de q uate 
res p o nse t o t o pical c ortic oster oi d treat me nt or t o pical c ortic oster oi d 
treat me nt bei n g me dicall y i na d visa ble.  
 
Di a g n ostic patc h test i n g perf or m e d wit hi n 3  years pri or t o  t he 
scree ni n g visit. 
Mai n criteria f or 
e xcl usi o n 
 
C o nc urre nt s ki n diseases o n t he ha n ds , e. g. ti nea ma n u u m. 
 
Acti ve at o pic der matitis i n re gi o ns ot her t ha n t he ha n ds or ps oriasis 
re q uiri n g me dical treat me nt. 
 
Cli nicall y si g nifica nt i nfecti o n (e. g., i m peti gi nise d ha n d ecze ma) o n t he 
ha n ds.  
 
S yste mic treat me nt wit h i m m u n os u p pressi ve dr u gs (e. g., met h otre xate, 
c ycl os p ori ne, azat hi o pri ne), i m m u n o m o d ulati n g dr u gs (e. g., j a n us 
ki nase i n hi bit ors), reti n oi ds (e. g., alitreti n oi n), or c ortic oster oi ds wit hi n 
4  wee ks pri or t o baseli ne (i n hale d or i ntra nasal ster oi ds c orres p o n di n g 
t o u p t o 1 m g pre d nis ol o ne f or ast h ma or r hi nitis ma y b e use d).  
 
Ps orale n ultra vi olet A ( P U V A) or ultra vi olet B ( U V B) t hera p y o n t he 
ha n ds wit hi n 4  wee ks pri or t o baseli ne.  
 
Recei pt of li ve atte n uate d vacci nes 4  wee k s pri or t o baseli ne. 
 
C uta ne o usl y a p plie d treat me nt wit h i m m u n o m o d ulat ors (e. g., 
p h os p h o diesterase -4 ( P D E -4)  i n hi bit ors, pi mecr oli m us, tacr oli m us) or 
t o pical c ortic oster oi ds o n t he ha n ds 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 
ha n ds wit hi n 2  wee ks pri or t o baseli ne.  


Trial I D: L P 0 1 3 3 -1 2 7 3  
Date: 0 7 -Dec -2 0 1 8  
Versi o n: 3. 0  
P a ge 2 5  of 1 2 8  
 
 
 
 
C ha n ge i n s yste mic a nti hista mi ne t hera p y wit hi n 2  w ee ks pri or t o 
baseli ne i.e.,  s u bj ects m ust n ot start a nti hista mi ne treat me nt or c ha n ge 
t he c urre nt d osa ge re gi me wit hi n 2  wee ks pri or t o baseli ne.  
 
Ot her c uta ne o usl y a p plie d t hera p y o n t he ha n ds (e xce pt f or t he use of 
s u bj ect’s o w n e m ollie nts) wit hi n 1 wee k pri or t o baseli ne.  
 
C uta ne o usl y a p plie d treat me nts i n re gi o ns ot her t ha n t he ha n ds, w hic h 
c o ul d i nterf ere wit h cli nical trial e val uati o ns or p ose a safet y c o ncer n 
wit hi n 1  wee k 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 (i ncl u di n g i m m u n o gl o b uli n, a nti -I g E, a n d d u pil u ma b):  
o  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. 
o  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. 
 
Cli nicall y si g nifica nt i nf ecti 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 bj ect 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 bj ect’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: 
o  A s yste mic i nfecti o n.  
o  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. 
 
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 bj ects 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 bj ects 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 . 
 
Hist or y of a n y k n o w n pri mar y i m m u n o deficie nc y dis or der i ncl u di n g a 
p ositi ve h u ma n i m m u n o deficie nc y vir us  ( HI V) test at scree ni n g, or the 
s u bj ect ta ki n g a ntiretr o viral me dicati o ns as deter mi ne d b y me dical 
hist or y a n d/ or s u bject’s ver bal re p ort.  
 
P ositi ve he patitis B s urface a nti ge n ( H Bs A g), he patitis B s urface 
a nti b o d y ( H Bs A b), he patitis B c ore a nti b o d y ( H Bc A b), or he patitis C 
vir us a nti b o d y (a nti-H C V) ser ol o g y at scree ni n g. S u bjects wit h p ositi ve 
H Bs A b ma y be ra n d o mise d pr o vi de d t he y are he patitis B vacci nate d 
a n d ha ve ne gati ve H Bs A g a n d H Bc A b.  
 
A n y dis or der, i ncl u di n g b ut n ot li mite d t o car di o vasc ular, 
gastr oi ntesti nal, he patic, re nal, ne u r ol o gical, m uscu l os keletal, 
i nfecti o ns, e n d ocri ne, meta b olic, hae mat ol o gical, i m m u n ol o gical, 
ps yc hiatric, or maj or p h ysical i m pair me nt, w hic h is n ot sta ble i n t he 
o pi ni o n of t he i n vesti gat or a n d c o ul d:  
o  Affect t he safet y of t he s u bject t hr o u g h o ut t he trial.  
o  I nfl ue nce t he fi n di n gs of t he trial or t heir i nter pretati o ns. 
o  I m pe de t he s u bject’s a bilit y t o c o m plete t he e ntire d urati o n of 
t he trial. 


P D D


C CI










Trial I D: L P 0 1 3 3 -1 2 7 3  
Date:  0 7 -Dec -2 0 1 8  
Versi o n: 3. 0  
P a ge 3 2  of 1 2 8  
 
 
 
earl y ter mi n ati o n visit as s o o n as p ossi ble after t he last I M P a p plicati o n f or c o m pleti o n of all trial p r oce d ures sc he d ule d f or t h e visit at Wee k 1 6 (e xce pt f or t h e s ki n bi o ps y, if t h e 
s u bject has c o nse nte d  t o ha ve s ki n bi o psies o btai ne d). T he y will als o be as ke d t o ret ur n at Wee k  1 6 (see f o ot n ote 5).  
4)  
All s u bjects will be as ke d t o ret ur n t o t h e trial site a p pr o xi matel y 2  we e ks aft er t h e last I M P a p plicati o n  f or assess me nt of safet y at a foll o w -u p v isit. 
5)  
S u bjects  w h o disc o nti n ue I M P treat me nt pri or t o Wee k 1 6  will be as ke d t o ret ur n t o t h e trial site at Wee k 1 6 f or a p ri mar y en d p oi nt v isit. 
6)  
U nsc he d ule d visits ma y occ ur if s u bjects n ee d t o ma ke a visit i n bet we e n t h e sc he d ule d visit dates d ue t o a n A E, diffic ult y c o m pl yi n g wit h t h e trial pr ot oc ol re q uire me nts, or a 
si g nifica nt c ha n ge i n t h eir disease state. 
7)  
T he i nf or me d c o nse nt f or m m ust b e 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 u ati o ns  a n d alterati o n  of o n g oi n g 
treat me nts u nless me dicall y j ustifie d. 
8)  
All ret ur ne d I M P t u bes will be wei g he d b y t h e C M O . 
9)  
Rele va nt p ri or/c o nc o mita nt me dicati o n s h o ul d be i n cl u de d fr o m 6  m o nt hs  pri or t o Da y  1 ( baseli ne)  u ntil e n d of trial . 
1 0)  Rele va nt me dical hist or y m ust b e rec or de d fr o m t h e s u bject’s date of birt h . I n case me dical hist or y is i nc o m plete at scree ni n g visit, missi n g data will be retrie ve d at Da y 1 
( baseli ne). 
1 1)  C o m pleti o n of t h e e Diar y will be i nitiate d at t h e latest 1  wee k pri or t o  Da y 1 ( baseli ne).  
1 2)  O nl y f or s u bjects wit h a pai d j o b . 
1 3)  S u bjects d o n ot ha ve t o be fasti n g f or safet y la b orat or y sa m ples.  
1 4)  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 . 
1 5)  F or w o me n of c hil d beari n g p ote ntial, a ser u m pre g na nc y test m ust b e perf or me d at  t h e scree ni n g visit,  a n d a uri ne pre g na nc y test at Da y 1 ( baseli ne) , Wee k s 4, 8, 1 2, a n d 1 6  
(e n d of treat me nt). 
1 6)  If a s u bject re p orts a n A E, it is u p t o t he i n vesti gat or’s discreti o n t o perf or m a n u nsc he d ule d visit.  
1 7)  C ollecti o n of 1  P K  plas ma sa m pl e 2 -6  h o urs after t he m or ni n g a p plicati o n of I M P.  
1 8)  S ki n barrier f u ncti o n will be meas ure d usi n g n o n -i n vasi ve or mi ni mall y i n vasi ve tec h ni q ues at selecte d sites o nl y. 
1 9)  T he s ki n barrier f u ncti o n  meas ure me nts , t h e s ki n bi o ps y sa m pli n g a n d  t he rec o m me n de d p h ot o gra p h y  s c he d ule d at Da y 1 ( baseli ne) m ust b e o btai ne d  pri or t o t h e first I M P 
a p plicati o n . T his s h o ul d be d o ne b ot h o n lesi o nal a n d c orres p o n di n g n o n-lesi o nal s ki n if p ossi ble. 
2 0)  T he s ki n bi o ps y sc he d ule d at W e e k 1 6 will be o btai ne d 2 -1 2  h o urs after t he last I M P a p plicati o n. If a s u bject disc o nti n ues I M P treat me nt pre mat urel y or wit h dra w s fr o m t h e 
trial, t h e s ki n bi o ps y sc he d ule d at Wee k 1 6 d oes n ot ha ve t o be o btai n e d. 
2 1)  A n e n d of trial f or m m ust b e c o m plete d f o r all s u bjects, i ncl u di n g s u bjects w h o disc o nti n ue I M P treat me nt pre mat urel y or wit h dra w fr o m t h e trial, at t heir last trial visit  (t h e earl y 
ter mi n ati o n visit, t h e 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) . 
A b bre vi ati o ns:  A E, a d vers e e ve nt; C M O, c o ntract ma n ufact uri n g or ga nisati o n; D L QI,  Der mat ol o g y Life Q ualit y I n de x:  E C G, electr o car di o gra m; E Q -5 D -5 L, E ur o Q o L 5 -D i me nsi o n 
Healt h Q uesti o n naire 5 -Le vel; H E C SI, Ha n d Ecze ma Se verit y I n de x; H EI S, C hr o nic Ha n d Ecze ma I m pact Scale;  H E S D, C hr o nic Ha n d Ecze ma S y m pt o m Diar y;  I G A, I n vesti gat or 
Gl o bal  Ass ess me nt;  I g E, i m m u n o gl o b uli n E; I M P, i n vesti gati o nal me dici nal pr o d uct; P a G A, P atie n t Gl o bal Assess me nt; P GI -C, P atie nt Gl o bal I m pressi o n of C ha n ge; P K, 
p har mac o ki n etics;  Q O L H E Q , Q ualit y of Life i n Ha n d Ecze ma Q uesti o n naire ; S A E, seri o us a d verse e ve nt; W L Q, W or k Li mitati o n Q uesti o n naire . 


Trial I D: L P 0 1 3 3 -1 2 7 3  
Date: 0 7 -Dec -2 0 1 8  
Versi o n: 3. 0  
P a ge 3 3  of 1 2 8  
 
 
 
5  I ntr o d ucti o n a n d tri al rati o n ale  
5. 1  C hr o nic h a n d ecze m a  
C hr o nic ha n d ecze ma is a n i nfla m mat or y s ki n dis or der l ocate d a n y w here o n t he ha n ds a n d 
wrists. It is cli nicall y c h aracterise d b y er yt h e ma, i nfiltrati o n, h y per kerat osis, oe de ma, a n d 
vesicles. Sec o n dar y si g ns i ncl u de scali n g, fiss ures, a n d er osi o ns , a n d t he c o n diti o n ma y be 
e x acer bate d b y b acterial i nfecti o ns. I m p orta nt s y m pt o ms i ncl u de itc hi n g a n d pai n, a n d t he 
disease is ofte n c h aracterise d b y c hr o nic rela pses a n d a p o or pr o g n osis. Acc or di n g t o t he 
g ui deli ne d e vel o pe d b y t he E ur o pea n S ociet y of C o ntact Der matitis ( 1 ), c hr o nic ha n d ecze ma 
refers t o ha n d ecze ma, w hic h persists f or m ore t ha n 3 m o nt hs or rela pses t wice or m ore ofte n 
per year. 
Ha n d ecze ma is us uall y m ultifact orial a n d t here is n o relia ble c o n n ecti o n bet wee n 
m or p h ol o g y a n d aeti ol o g y of t he dis ease. Bas e d o n aeti ol o g y, ecze ma is c o m m o nl y di vi de d 
i nt o e x o ge n o us or e n d o ge n o us t y p es. T he m ost c o m m o n aeti ol o gies of h a n d ecze ma are f o u n d 
t o be t he e x o ge n o us t y pes irrita nt c o ntact der matitis ( 3 5 %) a n d aller gic c o ntact der matitis 
( 1 9 %), a n d t h e e n d o ge n o us t y pe at o pic h a n d der matitis ( 2 2 %) ( 2 ). 
T he se verit y of ha n d ecze ma varies fr o m mil d t o se vere a n d ma y ca use si g nifica nt pai n a n d 
disc o mf ort i n dail y life. G e neral e m barrass me nt is als o ass ociate d wit h t he disease d ue t o its 
visi ble l ocati o n  (3 ). Ha n d ecze ma ca n res ult i n i m paire d q ualit y of life a n d d ecrease d w or ki n g 
ca pacit y, i m p osi n g a great ec o n o mic b ur de n o n p atie nts a n d s ociet y. I n De n mar k, a n 8 -year 
f oll o w-u p st u d y i n a c o h ort of 2 7 4 pe o ple wit h ha n d ecze ma f o u n d t hat 1 2. 4 % ha d bee n o n 
sic k lea ve a n d 8. 5 % ha d c ha n ged j o bs beca us e of t heir ha n d ecze ma ( 4 ). Si milarl y, pr ol o n ge d 
sic k lea ve d ue t o o cc u pati o nal ha n d ecze ma was re p orte d i n a p pr o xi matel y 2 0 % of patie nts i n 
a st u d y fr o m 2 0 0 5 ( 5 ). A U S s ur ve y f o u n d t hat pe o ple wit h c hr o nic ha n d ecze ma re p ort w orse 
q ualit y of life a n d i m pair e d acti vit y a n d w or k p erf or ma nce c o m pare d wit h t h ose wit h o ut 
c hr o nic ha n d ecze ma ( 3 ). 
Treat me nt of c hr o ni c ha n d ecze ma i n v ol ves differe nt treat me nt strate gi es s uc h as eli mi nati o n 
of tri g gers, ge n eral s ki n care, a n d a nti -i nfla m mat or y t hera p y i n a ste p-wise a p pr oac h. Ge neral 
s ki n care i n ter ms of e m ollie nts is wi del y us e d a n d rec o m me n de d b y p h ysi cia ns, b ut e vi de nce 
of effi cac y is s parse ( 1 ). N o net heless, e li mi nati o n of tri g gers s uc h as aller ge ns a nd irrita nts is 
effecti ve a n d a prere q uisite f or s uccessf ul t hera p y o n l o n ger ter m  b ut is i n ma n y 
circ u msta nces diffic ult t o ac hie ve d u e t o t he occ u p ati o nal c haracter of t he e x p os ure. 
Alitreti n oi n is t he o nl y  t h era p y a p pr o ve d  i n t he E U f or treat me nt of c hr o ni c ha n d ecze ma; n o 
pr o d uct is yet a p pr o ve d i n t he U S A. Alitreti n oi n  is h o we ver o nl y a p pr o ve d f or use i n a d ults  


Trial I D: L P 0 1 3 3 -1 2 7 3  
Date: 0 7 -Dec -2 0 1 8  
Versi o n: 3. 0  
P a ge 3 4  of 1 2 8  
 
 
 
wit h  se vere c hr o nic ha n d ecze ma u nres p o nsi ve t o p ote nt t o pical c ortic oster oi ds . Treat me nt 
wit h alitreti n oi n is  ass ociate d w it h si g nifica nt safet y preca uti o ns. Pre g na n c y is a n a bs ol ute 
c o ntrai n dicati o n d ue t o t he terat o ge ni c pr o perties of t he pr o d uct . I n a d diti o n, t he pr o d uct ca n 
o nl y be a d mi nistere d t o w o me n of c hil d beari n g p ote ntial if ta ki n g part i n a detaile d pre g n a nc y 
pre v e nti o n pr o gra m me.  
Ot her treat me nt o pti o ns are li mite d t o off -la bel us e of pr o d ucts i n dicate d f or s ki n diseases 
wit h a n i nfla m mat or y pat h o p h ysi ol o g y. T h ese treat me nts lac k t he cli nical d oc u me ntati o n f or 
use i n c hr o nic ha n d ecze ma a n d ma y o nl y be use d i n t he  s h ort-ter m, w hic h is n ot s uita ble i n 
treati n g a c hr o nic dis or der.  
To pical c ortic oster oi ds, gr o u pe d b y p ote nc y fr o m ver y l o w t o ver y hi g h, are t he m ost wi del y 
use d treat me nt f or  c hr o ni c ha n d ecze ma. T he y are wi del y rec o g nise d t o b e effecti ve . 
H o we ver, es pe ciall y hi g h -p ote nc y t o pical c ortic oster oi ds are als o ass ociat e d wit h a variet y of 
safet y c o n cer ns, i ncl u di n g s yste mic effects of a bs or be d c ortic oster oi ds , l ocal s ki n da ma ge, 
atr o p h y, a n d i m pair m e nt of t he e pi der m al barrier f u ncti o n (i n t he l o n g-t er m use). N o n -ster oi d 
treat me nts i ncl u de t o pical calci ne uri n i n hi bit ors of w hic h pi mecr oli m us has s h o w n t o lac k 
effect w he n assesse d i n cli nical trials a d dressi n g c hr o nic ha n d ecze ma ( 6 , 7 ). Ot her s yste mic 
a nti-i nfla m mat or y t hera pies are off-la bel besi des alitreti n oi n , e. g., c ycl os p o ri ne a n d 
met h otre x ate ha ve t he p ote ntial t o ca use se v ere a n d s yste mic a d v erse e ve nts ( A Es), w hic h 
li mit t heir use t o strictl y defi ne d patie nt p o p ulati o ns wit h se vere c hr o nic ha n d ecze ma t hat 
re mai ns u nc o ntr olle d f oll o wi n g use of treat me nt o pti o ns ha vi n g a m or e be ni g n 
t olera bilit y/safet y pr ofile. N o n-p har mac ol o gical treat me nt o pti o ns i ncl u de Gre nz ra ys a n d 
p h ot ot hera p y, w hi c h ma y re q uire m ulti ple visits t o t he cli nic per wee k a n d f or t his reas o n ca n 
be percei ve d as c u m bers o me f or t he patie nts . L o n g-ter m e x p os ure t o p h ot ot hera p y a n d Gre nz 
ra ys als o raises c o ncer ns a b o ut p ossi ble i ncreas e d ris k f or s ki n mali g na n cies, es peciall y wit h 
t he c o nc o mita nt use of t o pical calci ne uri n i n hi bit ors. 
C o nse q ue ntl y, t here is a n u n met me dical nee d f or a ne w  treat me nt o pti o n of c hr o nic h a n d 
ecze ma wit h hi g h efficac y i n c o m bi nati o n wit h a n attracti ve safet y pr ofile. S uc h a treat me nt 
w o ul d p ote ntiall y facilitate t he e ver y d a y li ves of patie nts wit h t his s ki n dis or der.  
5. 2  E x perie nce wit h in vesti g ati o n al m e dici n al p r o d uct 
Del g o citi 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-ja n us ki nase (J A K) i n hi bit or, w hic h bl oc ks vari o us c yt o ki ne si g nalli n g 
pat h wa ys, a n d wi d el 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 yt es acti vat e d b y t h ese c yt o ki nes. 


Trial I D: L P 0 1 3 3 -1 2 7 3  
Date: 0 7 -Dec -2 0 1 8  
Versi o n: 3. 0  
P a ge 3 5  of 1 2 8  
 
 
 
J A K is a fa mil y of i ntracell ular t yr osi ne ki nases  c o nsist i n g of 4  me m bers,  J A K 1, J A K 2, 
J A K 3, a n d Ty k 2, w hic h ca n ass ociat e dir ectl y  t o t he i ntracell ular p art of vari o us c yt o ki ne 
rece pt ors i n vari o us  c o m bi nati o ns  (8 , 9 ). After a c yt o ki ne bi n ds t o its c o g n ate rece pt or, t he 
rele va nt J A K me m bers are a ut o p h os p h or ylate d, w hic h all o w t he m t o p h os p h or ylat e o ne or 
m ore si g n al tra ns d ucer a n d acti vat or ( S T A T) of pr ot ei ns ( S T A T 1, S T A T 2, S T A T 3, S T A T 4, 
S T A T 5 A/ B, a n d S T A T 6). T he p h os p h or ylate d S T A T pr otei ns are i n t ur n tra nsl ocate d t o t he 
n ucle us w here t he y i nitiate tra nscri pti o n lea di n g t o pr o m oti o n of gr o wt h a n d acti vati o n of a 
variet y of cells. T he J A K fa mil y is t h us esse ntial f or c yt o ki n es i n v ol ve d i n t he path o ge nesis of 
vari o us diseases wit h a n i m m u ne -i nfla m mat or y c o m p o ne nt t o e x hi bit t heir p h ysi ol o gical 
acti vit y. T he i m m u ne mec ha nis ms i n c hr o nic ha n d ecze ma are m ostl y dri v e n b y T  cells, a n d 
J A K i n hi bit ors i n hi bit si gnal tra ns d ucti o n of ma n y T  cell-rel ease d c yt o ki n es. 
I n n o n-cli nical st u dies, d el g o citi ni b  bl oc ke d J A K fa mil y me m bers wit h half ma xi mal 
i n hi bit or y c o nce ntrati o n (I C5 0) val ues ra n gi n g fr o m 2 -6 0  n M i n bi oc he mical assa ys a n d 
i n hi bite d acti vati o n of T cells, B cells, mast cells, a n d m o n oc yt es i n d uce d b y vari o us J A K 
c yt o ki nes i n c ell ular ass a ys. To pic all y a d mi nistere d del g o citi ni b  i n hi bite d i nfla m mati o n i n rat 
a n d m o use m o dels of c o ntact der matitis, w here T  cells acti vate d b y vari o us J A K -de pe n de nt 
c yt o ki nes we re i n v ol ve d i n t he pat h o ge nesis. F urt her m ore, d el g o citi ni b  i m pr o ve d t he 
i m paire d s ki n barrier f u n cti o n, a n d re d uce d i nterle u ki n (I L)-3 1 -i n d u ce d scratc hi n g i n mice. I n 
a st u d y b y A ma n o et al, it was s h o w n t hat I L -4 a n d I L -1 3 d o w nre g ulate d ge nes i n v ol ve d i n 
ker ati n oc yte differe ntiati o n, t hat S T A T 3 a n d S T A T 6 are i n v ol ve d i n kerati n oc yt e 
differe ntiati o n a n d c he m o ki ne pr o d ucti o n, res pecti vel y, a n d t hat t o pical a p plicati o n of 
del g o citi ni b  s u p presse d S T A T 3 acti vati o n a n d i m pr o ve d s ki n barri er f u n cti o n (1 0 ). 
Del g o citi ni b , f or m ulate d as a n oi nt me nt f or t o pical use, was effecti ve i n a cli nical p hase 2 trial 
( L P 0 1 3 3-1 1 8 0) treati n g  a d ults wit h mil d t o se vere c hr o nic ha n d ecze ma. T h e pri mar y 
e n d p oi nt was treat me nt s uccess a cc or di n g t o t he P h ysicia n ’s G l o bal A ss ess me nt of disease 
se verit y at Wee k 8, wit h treat me nt s uc cess defi n e d as s u bjects ac hie vi n g ‘cl ear’ or ‘al m ost 
clear’ wit h at le ast a 2 -ste p re d ucti o n fro m bas eli ne , a n d the o d ds of ac hie vi n g treat me nt 
s uccess w as s tatisticall y si g nifica ntl y hi g her i n t h e del g ociti ni b  3 0  m g/ g oi nt me nt gr o u p 
c o m pare d t o  t he oi nt me nt ve hicle gr o u p. T h e perce nta ge of s u bjects ac hie vi n g treat me nt 
s uccess w as n u mericall y hi g her i n t he d el g ociti ni b  oi nt me nt 3 0 m g/ g gr o u p t ha n i n t he 
oi nt me nt ve hicle gr o u p fr o m Wee k  1 u ntil e n d of t he trial. T he tr eat me nt w as well -t olerat e d 
a n d ha d a n acce pta ble safet y pr ofile. I n a d diti o n, l o w s yste mic e x p os ure of del g o citi ni b  was 
o bser ve d i n t he  trial, whi c h is e x pecte d t o li mit t he ris k of A Es relate d t o s yste mic e x p os ure. 


Trial I D: L P 0 1 3 3 -1 2 7 3  
Date: 0 7 -Dec -2 0 1 8  
Versi o n: 3. 0  
P a ge 3 6  of 1 2 8  
 
 
 
5. 3  Tri al rati o n ale  
T he p ur p ose of t hi s p has e 2 b trial is t o esta blis h a d ose-res p o ns e si g n al a n d t o e val uate t he 
efficac y a n d safet y of del g ociti ni b  ( 1, 3, 8, a n d 2 0 m g/ g), f or m ulate d as a crea m f or t o pical 
use, i n t he treat me nt of s u bjects wit h mil d t o se vere c hr o ni c ha n d ecze ma. T he res ults fr o m 
t his trial will s u p p ort f urt her de vel o p me nt i n p has e 3 wit h re gar ds t o e. g., d ose selecti o n a n d 
treat me nt d urati o n. 
T here is a c lear u n met ne e d f or ne w treat me nt o pti o ns i n t he treat me nt of patie nts s ufferi n g 
fr o m c hr o nic h a n d ecze m a. Bas e d o n c urre ntl y a v aila ble n o n -cli nical a n d cli nical data, 
del g o citi ni b  has t he p ote ntial t o bec o me a n o vel l ocal -acti n g a nti -i nfla m mat or y a n d 
i m m un os u p pressi ve a ge nt wit h s ki n barrier i m pr o vi n g pr o perties (1 0 ) f or t o pical use i n 
c hr o nic ha n d ecze ma . T h ere is a reas o n a ble e x pect ati o n t hat del g o citi ni b  i n a crea m 
f or m ulati o n will pr o ve t o be a n effecti ve a n d well-t olerate d treat me nt base d o n t he mecha nis m 
of acti o n , a n d t here b y facilitate t he e ver y da y li ves of affecte d patie nts. 
 
 
 
 
 
 
 
 
5. 4  J ustific ati o n f or d ose  
 
 
 
 
 
 
 
 
 
 
 
 
C CI
C CI
C CI
C CI


Trial I D: L P 0 1 3 3 -1 2 7 3  
Date: 0 7 -Dec -2 0 1 8  
Versi o n: 3. 0  
P a ge 3 7  of 1 2 8  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
5. 5  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 w it 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 H elsi n ki, 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, i n c o m plia nce wit h t he a p pr o ve d pr ot o c ol, a n d a p plica ble 
re g ulat or y re q uire me nts. 
Ris k s ass ociate d wit h treat me nt i n t his cli nical trial (ris ks of e x perie nci n g si g nifica nt a d verse 
reacti o ns ass o ciate d wit h der mal or s yste mic e x p os ure t o del g ociti ni b ) are c o nsi dere d 
mi ni mal.  
T he trial desi g n c h ose n f or t his efficac y a n d safet y trial wit h  del g ociti ni b  crea m is re gar de d as 
et hicall y j ustifie d a n d a d here nt wit h et hical re q uir e me nts. T he efficac y a n d safet y of 
del g o citi ni b  crea m will b e e val uat e d i n a d ults s ufferi n g fr o m mil d t o se vere c hr o nic ha n d 
ecze ma w h o ma y b e nefit fr o m treat me nt i n t he  trial. P re g na nt or breastfee di n g w o me n a n d 
w o me n tr yi n g t o be c o me pre g na nt will  n ot be e nr olle d i n t he trial. W o 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 pr e g na nc y  
d uri n g t he tri al . 
Trial s u bjects will be i nf or me d at t he scree ni n g visit  t hat trial pr oce d ures pri or t o baseli ne 
( Da y 1) ma y warra n t a n alterati o n of t heir  o n g oi n g c o n c o mita nt treat me nts. As a p plica ble f or 
t he e ntire trial, t he s u bjects will be i nstr ucte d t o c o ntact t he i n vesti gat or if t heir c hr o nic h a n d 
ecze ma w ors e ns si g nifica ntl y.  
C CI
C CI


Trial I D: L P 0 1 3 3 -1 2 7 3  
Date: 0 7 -Dec -2 0 1 8  
Versi o n: 3. 0  
P a ge 3 8  of 1 2 8  
 
 
 
I n acc or da n ce wit h t he c urre nt versi o n of t he I C H-G C P g ui deli nes, q ualifie d me dical 
pers o n nel e m pl o ye d b y L E O will be rea dil y a v aila 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 m e d t hr o u g h o ut t he tri al. Safet y dat a will be 
re vie we d re g ularl y b y Gl o bal P har mac o vi gila nce at L E O t o e ns ure r o uti ne si g nal detecti o n. 
5. 6  Be nefit/ ris k a ssess me nt 
T here is a n u n met me di cal nee d f or ne w t hera pies f or use i n patie nts wit h mil d t o se vere 
c hr o nic ha n d ecze ma. C hr o nic ha n d ecze ma is a p h ysicall y a n d ps yc h ol o gicall y c halle n gi n g 
disease ofte n acc o m p a nie d b y distress d ue t o its visi ble  l ocati o n. C urre nt treat me nt o pti o n s are 
li mite d t o o nl y o ne  a p pr o ve d t hera p e utic pr o d uct ( o nl y i n E U) wit h si g nifica nt safet y 
preca uti o ns , w hic h is o nl y a p pr o priate f or patie nts wit h se vere c hr o nic ha n d ecze ma. Ot her  
treat me nt o pti o ns i ncl u de t o pical ster oi ds a n d cal ci ne uri n i n hi bit ors , w hic h lac k a v ali d 
be nefit/ris k e val uati o n  b y c o m pete nt r e g ulat or y a ut h orities (as f urt her d escri be d i n  
Secti o n  5. 1 ). 
N o i m p orta nt  i de ntifie d ris ks ha ve bee n d o c u me nt e 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 d el g o citi ni b  t o date. A d etaile d o ver vie w  of n o n -cli nical a n d cli n ical 
data o n del g ociti ni b  is a vaila ble i n t he c urre nt I n v esti gat or’s Br oc h ure. 
T o e ns ure t he s afet y a n d wellbei n g  of s u bjects partici pati n g i n t his cli nical trial , safet y 
m o nit ori n g will be e val u ate d as des cri be d i n Secti o n 1 1. 4 . T he ris ks ass oci ate d wit h t he 
f oll o wi n g i n vasi ve trial proce d ures are c o nsi dere d mi ni mal . Bl o o d sam ples ca n be 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  t o t he s u bject. T he siz e of t he s ki n bi o psies 
s h o ul d n ot necessitate s ut uri n g, but s ut uri n g ca n b e perf or me d at t he i n vesti gat or’s discreti o n. 
T he ris k ass ociate d wit h a s ki n bi o ps y, i ncl u di n g s ec o n dar y i nfecti o n, is c o nsi dere d l o w. S ki n 
barrier f u ncti o n is meas ure d usi n g n o n -i n vasi ve or mi ni mall y i n vasi ve t ec h ni q ues, a n d t he 
ris k ass ociate d wit h t hese tec h ni q ues is c o nsi dere d l o w. 
Alt o get her, t he ris ks ass o ciate d wit h partici pati n g i n t his cli nical trial are c o nsi dere d ver y l o w 
a n d o ut wei g he d b y t he b e nefit of a p ot e ntial f ut ure treat me nt o pti o n f or c hr o nic ha n d ecze ma. 
T here is a n o p p ort u nit y f or a p ositi ve treat me nt effect f or t h e  s u bjects partici pati n g i n t his 
cli nical trial base d o n t he c urre ntl y a v aila ble cli nical data.  




Trial I D: L P 0 1 3 3 -1 2 7 3  
Date: 0 7 -Dec -2 0 1 8  
Versi o n: 3. 0  
P a ge 4 0  of 1 2 8  
 
 
 
O bjecti ves  
E n d p oi nts  
 
 
Re d ucti o n i n Der mat ol o g y Life Q ualit y I n de x ( D L QI) of 
≥4  p oi nts fr o m baseli ne t o Wee k  1 6 a m o n g s u bj ects wit h 
baseli ne D L QI ≥4.  
 
C ha n ge i n D L QI sc ore fr o m baseli ne t o Wee k  1 6.  
 
C ha n ge i n E ur o Q o L  5 -di me nsi o n 5 -le vel q uesti o n naire ( E Q-
5 D -5 L) fr o m baseli ne t o Wee k  1 6.  
 
C ha n ge i n Q ualit y of Life i n Ha n d Ecze ma Q uesti o n naire 
( Q O L H E Q) fr o m baseli ne t o Wee k 1 6.  
 
C ha n ge i n W or k Li mitati o n Q uesti o n naire ( W L Q) fr o m 
baseli ne t o Wee k  1 6 . 
Effic acy over ti me  
 
I G A T S  at eac h sc he d ule d assess me nt u ntil a n d i ncl u di n g 
Wee k  1 4.  
 
Pa G A T S  at eac h sc he d ule d assess me nt u ntil a n d i ncl u di n g 
Wee k  1 4.  
 
C ha n ge fr o m baseli ne t o eac h wee k fr o m Wee k  1 t o 
Wee k  1 5 i n H E S D  ( wee kl y a vera ge f or eac h i n di vi d ual 
s y m pt o m). 
o  Re d ucti o n of w orst pr urit us ( wee kl y a vera ge) of 
≥4  p oi nts fr o m baseli ne t o eac h wee k fr o m Wee k  1 t o 
Wee k  1 5 a m o n g s u bj ects wit h baseli ne w orst pr urit us 
( wee kl y a vera ge) ≥4. 
 
C ha n ge fr o m baseli ne t o eac h sc he d ule d assess me nt u ntil 
Wee k 1 4 i n H EI S.  
 
C ha n ge i n D L QI sc ore fr o m baseli ne t o eac h sc he d ule d 
assess me nt u ntil Wee k  1 4.  
 
Re d ucti o n of D L QI of at least 4  p oi nts fr o m baseli ne t o eac h 
sc he d ule d assess me nt u ntil Wee k 1 4.  
T o e val uate t he effect of 
del g ociti ni b o n St a p hyl oc occ us 
a ure us  c ol o nisati o n of t he 
s ki n, s ki n micr o bi o me, s ki n 
barrier f u ncti o n, a n d s ki n 
i nfla m mati o n. 
Bi o m arkers  
 
C ha n ge i n St a p hyl oc occ us a ure us  c olo nis ati o n fr o m 
baseli ne t o Wee k  1 6 . 
 
C ha n ge i n micr o bi o me c o m p ositi o n fr o m baseli ne t o 
Wee k  1 6 . 
 
C ha n ge i n s ki n barrier f u ncti o n, meas ure d as tra nse pi der mal 
water l oss, ca pacita nce, s ki n p H , a n d c o nte nt of nat ural 
m oist urisi n g  fact ors, fr o m baseli ne t o Wee k 1 6 . 
 
C ha n ge i n e x pressi o n of s ki n barrier pr otei ns a n d i n e xte nt 
of i m m u ne cells i n s ki n  bi o psies fr o m baseli ne t o Wee k  1 6 . 
 


Trial I D: L P 0 1 3 3 -1 2 7 3  
Date: 0 7 -Dec -2 0 1 8  
Versi o n: 3. 0  
P a ge 4 1  of 1 2 8  
 
 
 
7  Tri al desi g n  
7. 1  O ver all tri al d esi g n 
T his is a p hase 2 b, d o u ble -bli n d, m ulti -ce ntre, ra n d o mise d, 5 -ar m, ve hicle -c o ntr olle d, 
parallel -gr o u p trial. T he trial is desi g ne d t o  esta blis h a d ose -res p o nse si g nal a n d t o i n vesti gate 
t he effi cac y a n d safet y of del g o citi ni b  crea m i n t he treat me nt of a d ult su bjects  wit h mil d t o 
se vere c hr o nic h a n d ecze ma. T he trial desi g n is ill ustrate d i n Pa nel 1 . 
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 : b et wee n 1 a n d 4  w ee ks pri or t o t he b aseli ne visit ( D a y 1)  
T he scree ni n g peri o d h as a mi ni m u m d urati o n of 1  wee k a n d a ma xi m u m d urati o n of 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 k e d. Tri al -s pecific 
meas ure me nts will be perf or me d as d escri b e d i n Secti o n 1 1 . 
T he s u bjects will recei ve  trai ni n g i n c o m pleti o n of a n electr o ni c diar y (e Diar y) at t he 
scree ni n g visit a n d will be gi v e n an  el ectr o nic d e vice t o rec or d certai n patie nt -re p orte d 
o utc o mes ( P R Os) . F urt her m ore, t o c o m plete tr ai ni n g of t he e Diar y a n d as a n o p p ort u nit y t o 
fill o ut P R Os bef ore t he treat me nt peri o d, s u bjects will be as ke d t o c o m plet e P R Os at t he 
scree ni n g visit. C o m pleti o n of  the e Diar y will be i nit iate d at t he latest  1 wee k  pri or t o t he 
baseli ne  visit ( Da y  1 ). 
Tre at me nt peri o d : 1 6 w ee ks  
A t baseli ne ( Da y 1) , s u bj ects’ eligi bilit y t o e nt er t he trial will be c o nfir me d a n d if still eli gi ble  
a n d I n vesti gat or’s Gl o bal Assess me nt (I G A) bas eli ne se verit y a n d re gi o nal ca p pi n g  ha ve n ot 
bee n reac h e d , t he s u bjects will be ra n d o mise d t o o ne  of t he f oll o wi n g 5  treat me nt gr o u ps i n a 
1: 1: 1: 1: 1 rati o : del g ociti ni b  crea m 1 , 3, 8, or 2 0  m g/ g  or del g o citi ni b  crea m ve hicle. 
T he s u bjects will  a p pl y t he i n vesti gati o nal me di ci nal pr o d uct (I M P) (d el g o citi ni b  crea m 1, 3, 
8, or 2 0  m g/ g or d el g o citi ni b  crea m ve hi cle ) t wice dail y f or 1 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 h e s u bjects at h o me.  
D uri n g t h e 1 6 -wee k treat me nt peri o d, t he s u bjects will ret ur n t o t he trial sites f or t he visits 
sc he d ule d at Wee ks 1, 2,  4 , 6, 8, 1 0 , 1 2, 1 4, a n d 1 6 . O n Da y  4 , a me m b er of trial site 
pers o n nel will  call t he s u bject s f or a n u ns olicite d q uesti o ni n g of A Es , an d t o e n q uire a b o ut 
c o m plia nce wit h treat me nt a n d e Diar y c o m pleti o n . T he last I M P a p plicati o n will occ ur bef ore 


Trial I D: L P 0 1 3 3 -1 2 7 3  
Date: 0 7 -Dec -2 0 1 8  
Versi o n: 3. 0  
P a ge 4 2  of 1 2 8  
 
 
 
t he s u bjects atte n d t he visit sc he d ule d at Wee k 1 6. Efficac y a n d s afet y ass ess me nts d uri n g t he 
treat me nt peri o d will be perf or me d as descri be d i n Secti o n 1 1 . 
F oll o w -u p peri o d : 2 w ee ks  
All ra n d o m ise d s u bjects will atte n d a f oll o w-u p visit a p pr o xi matel y 2  wee ks after t he last I M P 
a p plicati o n f or ass ess me nt of  safet y. T his visit will mar k t he e n d of trial p artici pati o n f or 
s u bjects w h o ha ve c o m plete d t he e ntire tri al. F or s u bjects w h o  disc o nti n ue trial treat me nt 
pre mat urel y or wit h dra w  fr o m t he trial, pleas e refer t o Secti o n 1 0. 3 . 
7. 2  N u m ber of s u bjects nee de d  
T his trial will be c o n d ucte d at a p pr o xi matel y 2 5  sites i n E ur o pe a n d N ort h A merica. T he 
a ntici pate d mi ni m u m n u m ber of ra n d o mise d s u bj ects per trial site is 6 a n d t he ma xi m u m 
n u m ber of s u bjects per trial site is 3 0.  
Ass u mi n g a scree ni n g fail ure rate of 3 5 %, a p pr o xi matel y 3 8 5 s u bjects will be scree ne d a n d 
a p pr o xi matel y 2 5 0 s u bjects will be ra n d o ml y assi g ne d t o a treat me nt gr o u p i n t he trial 
( 5 0 s u bjects i n eac h of t h e 5  treat me nt gr o u ps: del g ociti ni b  crea m 1, 3, 8, a n d 2 0  m g/ g a n d 
del g o citi ni b  crea m ve hi cle ). T he statistical p o w er c o nsi derati o ns f or t his sa m ple siz e are 
descri be d i n Secti o n  1 4. 1 . 
T he ra n d o misati o n is stratifie d b y t he s e verit y of c hr o nic ha n d ecze ma acc or di n g t o I G A 
(I G A sc ore of 2 [mil d ], 3 [m o derate ], or 4 [se vere]) a n d re gi o n  ( E ur o pe a n d N ort h A merica ). 
A l o wer li mit of 2 0 % a n d a n u p per li mit of 3 0 % will be i m p ose d o n t he I G A baseli ne s e verit y 
of s u bjects wit h mil d a n d se vere c hr o nic h a n d ecz e ma, res p ecti vel y.  Bas e d o n t his ca p pi n g, 
t he o verall n u m ber of s u bjects i n eac h s e verit y gr o u p ca n ra n ge be t w ee n: 
 Mil d: 5 0 t o 7 5  s u bjects. 
 M o derate: 1 0 0 t o 1 5 0  s u bjects. 
 Se vere: 5 0 t o 7 5  s u bjects. 
A ma xi m u m  of 5 0 s u bjects will be ra n d o mise d i n t he N ort h A m erica n re gi o n . 
7. 3  E n d of tri al defi niti o n  
A s u bject is c o nsi dere d t o ha ve c o m plete d t h e trial if he/s he has c o m plete d all peri o ds (i.e., 
scree ni n g, tr eat me nt, a n d f oll o w-u p  peri o d).  


Trial I D: L P 0 1 3 3 -1 2 7 3  
Date: 0 7 -Dec -2 0 1 8  
Versi o n: 3. 0  
P a ge 4 3  of 1 2 8  
 
 
 
T he e n d of t he tri al 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 
gl o ball y.  
Fi nal c ollecti o n of d ata f or t he pri mar y e n d p oi nt o cc urs at Wee k 1 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 oll e d ter mi n ol o g y versi o n 3 0 -
Mar -2 0 1 8  or ne wer  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 Dat a Ta b ulati o n 
M o del ( S D T M ) versi o n 1. 4 will be use d f or data t a b ula ti o ns a n d S D T M I m ple me ntati o n 
G ui de versi o n 3. 2 will be a d here d t o . 
D ose -res p o nse m o delli n g  will be d o ne usi n g t he pac ka ge D ose Fi n di n g  i m ple me nte d i n 
R  statistical s oft ware versi o n 3.5 .0  or ne wer. All ot her a nal ysis will be perf or me d usi n g S A S®  
statistical s oft ware versi o n 9. 4. 


Trial I D: L P 0 1 3 3 -1 2 7 3  
Date: 0 7 -Dec -2 0 1 8  
Versi o n: 3. 0  
P a ge 4 4  of 1 2 8  
 
 
 
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 mee t all eli gi bilit y criteri a, are n ot p ut at 
u n d ue ris k b y p artici pati n g i n t he trial a n d ca n b e 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 x cl usi o n criteria at visits s pecifie d i n Pa nel 2 . It will be rec or d e d i n t he el ectr o nic case re p ort 
f or m (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 of t he e x cl usi o n criteria.  
A n y i m ple me ntati o n of n ati o nal re q uire me nts/la w f or t he s u bject ’s p artici 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 nt ati 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 criteri a: 
1.  Si g ne d a n d d ate d i nf or m e d c o nse nt has b ee n o btai ne d pri or t o a n y pr ot oc o l-relate d 
pr oce d ures . 
2.  A ge 1 8 years or a b o v e.  
3.  Dia g n osis of c hr o nic h a n d ecze ma defi n e d as ha n d ecze ma, w hic h has persiste d f or 
m ore t ha n 3  m o nt hs or ret ur ne d t wice or m ore wit hi n t he last 1 2  m o nt hs.  
4.  D isease se v erit y gra d e d as mil d t o se vere acc or di n g t o I n vesti gat or ’s Gl o bal 
Assess me nt  (i.e., a n I G A sc ore of 2 or m ore). 
5.  Rece nt hist or y ( wit hi n 1  year bef ore t h e scree ni n g visit) of i na de q uate res p o nse t o 
t o pical c orticoster oi d treat me nt or t o pical c ortic ost er oi d treat me nt bei n g  me dicall y 
i na d visa ble. 
6.  D ia g n ostic p atc h testi n g perf or me d wit hi n 3 years pri or t o  t he scree ni ng visit . 
7.  A w o ma n  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 ug h o ut t he tri al a n d f or at least 2  wee ks after last a p plicati o n of I M P. 
* A w o m a n  is defi ne d as n ot bei n g of c hil dbeari 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 us e pri or t o 
scree ni n g), or s ur gic all y sterile ( h ysterect o m y, bil ateral sal pi n gect o m y, or bilateral 
o o p h orect o m y).  


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Date: 0 7 -Dec -2 0 1 8  
Versi o n: 3. 0  
P a ge 4 5  of 1 2 8  
 
 
 
* * 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 hi c 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 occlusi o n, i ntra uteri n e 
de vice , i ntra uteri ne h or m o ne-rel easi n g s yste m, c o m bi ne d (estr 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 oci ate 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 or m o nal c o ntrace pti o n ass oci ate d wit h 
i n hi biti o n of o v ulati o n ( oral, i njecta ble, i m pla nta bl e), se x ual a bsti ne nce ( w h e n t his is 
i n li ne wit h t he preferre d a n d us ual life st yl e of t he s u bject), vasect o mise d part ner 
( gi ve n t h at t he s u bject is m o n o ga m o us). 
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 x cl usi o n criteria are f ulfille d: 
1.  C o nc urre nt s ki n diseases o n t he ha n ds , e. g. ti nea m a n u u m . 
2.  Acti ve at o pic der matitis i n re gi o ns ot her t ha n t he h a n ds or ps oriasis re q uiri n g me dical 
treat me nt. 
3.  Cli nicall y s i g nifica nt i nfecti o n (e. g., i m peti gi nise d ha n d ecze ma) o n t h e ha n ds. 
4.  S yste mic treat me nt wit h i m m u n os u p pressi ve dr u gs (e. g., met h otre x ate, c ycl os p ori ne, 
azat hi o pri ne), i m m u n o m o d ulati n g dr u gs (e. g., ja n us ki nase i n hi bit ors), reti n oi ds (e. g., 
alitreti n oi n), or c ortic oster oi ds wit hi n 4  wee ks pri or t o baseli ne (i n hale d or i ntra nasal 
steroi ds c orres p o n di n g t o u p t o 1  m g pre d nis ol o ne f or ast h ma or r hi nitis ma y be us e d).  
5.  Ps orale n ultra vi olet A ( P U V A) or ultra vi olet B ( U V B) t hera p y o n t he ha n ds wit hi n 
4  wee ks pri or t o b aseli ne.  
6.  Recei pt of li ve  atte n uat e d vacci nes 4  wee k s pri or t o baseli ne . 
7.  C uta ne o usl y a p plie d tr eat me nt wit h i m m u n o m o d ulat ors (e. g., p h os p h o diesterase -4 
( P D E-4) i n hi bit ors, pi mecr oli m us, tacr oli m us) or t o pical c ortic oster oi ds o n t he ha n ds 
wit hi n 2  wee ks pri or t o b aseli ne.  
8.  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 ha n ds wit hi n 
2  wee ks pri or t o b aseli ne.  
9.  C ha n ge i n s yste mic a nti hista mi ne t hera p y wit hi n 2  wee ks pri or t o b aseli ne i.e., 
s u bjects m ust n ot start a nti hista mi ne treat me nt or c ha n ge t he c urre nt d osa ge re gi me 
wit hi n 2  wee ks pri or t o b aseli ne.  
1 0.  Ot her  c uta n e o usl y a p plie d t hera p y o n t he ha n ds (e x ce pt f or t he use of s u bject ’s o w n 
e m ollie nts) wit hi n 1  wee k pri or t o baseli ne.  


Trial I D: L P 0 1 3 3 -1 2 7 3  
Date: 0 7 -Dec -2 0 1 8  
Versi o n: 3. 0  
P a ge 4 6  of 1 2 8  
 
 
 
1 1.  C uta ne o usl y a p plie d tr eat me nts i n re gi o ns ot her t ha n t he ha n ds, w hic h c o ul d i nterfere 
wit h cli nical trial e val uati o ns or p ose a safe t y c o n cer n wit hi n 1 wee k pri or t o baseli ne.  
1 2.  Treat me nt wit h a n y mar k ete d bi ol o gical t hera p y or i n vesti gati o nal bi ol o gic a ge nts 
(i ncl u di n g i m m u n o gl o b uli n, a nti-I g E, a n d d u pil u ma b):  
 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 . 
1 3.  T reat me nt wit h a n y n o n-mar kete d dr u g s u bsta n ce (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 t he last 4  wee ks 
pri or t o baseli ne or 5  h alf -li ves w hic he ver is t he l o n gest. 
1 4.  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 h e o pi ni o n 
of t he i n vesti g at 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 pat e 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 p are nt eral (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.  
1 5.  T u berc ul osis re q uiri n g tr eat 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 n ce 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 p ers o n wit h acti ve 
t u berc ul osis, or a hist or y of acti ve or l ate 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 b e c o nfir me d) m ust be teste d. 
1 6.  Hist or y of a n y k n o w n pri mar y i m m u n o deficie nc y dis or der i ncl u di n g a p ositi ve h u ma n 
i m m u n o deficie nc y vir us ( HI V) t est at scree ni n g, or t he s u bject ta ki n g a ntiretr o viral 
me dicati o ns as deter mi ne d b y me dical h ist or y a n d/ or s u bject’s ver bal re p ort. 
1 7.  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.  


Trial I D: L P 0 1 3 3 -1 2 7 3  
Date: 0 7 -Dec -2 0 1 8  
Versi o n: 3. 0  
P a ge 4 7  of 1 2 8  
 
 
 
1 8.  Hist or y of ca n cer:  
 S u bjects w h o ha ve ha d b asal 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 n a ncies are eli gi ble pr o vi de d t hat t h e 
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. 
1 9.  A n y dis or d er, i ncl u di n g b ut n ot li mite d t o car di o vasc ular, gastr oi ntesti nal, he patic, 
re nal, ne ur ol o gi cal, m uscu l os keletal, i nfecti o ns, e n d ocri ne, meta b olic, h ae m at ol o gical, 
i m m u n ol o gical, ps yc hiatric, or maj or p h ysical i m p air me nt, w hic h is n ot sta ble i n t he 
o pi ni o n of t he i n vesti gat or 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 or t heir i nter pret ati o ns. 
 I m pe d e t he s u bject’s a bilit y t o c o m plete t he e ntire d urati o n of t he trial. 
2 0.  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 h eir partici pati o n i n t he trial.  
 I nfl ue nce t he res ults of t h e trial. 
 I nfl ue nce t he s u bject’s a bilit y t o c o m plete t h e 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 h e scree ni n g 
peri o d. E x a m ples i ncl u de a b n or mal fi n di n gs i n p h ysical e x a mi nati o n, vital si g ns, 
E C G, hae mat ol o g y, cli ni cal c he mistr y, or uri nal ysis.  
2 1.  P ositi ve he patitis B s ur face a nti ge n ( H Bs A g), he p atitis B s urface a nti b o d y ( H Bs A b), 
he patitis B c ore a nti b o d y  ( H Bc A b), or he patitis C vir us a nti b o d y (a nti-H C V) ser ol o g y 
at scree ni n g.  S u bje cts wit h p ositi ve H Bs A b ma y b e ra n d o mise d pr o vi de d t h e y are 
he patitis B vacci nate d a n d ha ve ne gati ve H Bs A g a n d H Bc A b.  
2 2.  Ala ni ne a mi n otra nsf eras e or as partate a mi n otra nsferas e le vel ≥2 . 0 ti mes t he u p per 
li mit of n or mal ra n ge ( U L N) at scree ni n g. 
2 3.  K n o w n or s us pect e d h y p erse nsiti vit y t o a n y c o m p o ne nt(s) of t he I M P. 
2 4.  C urre nt partici pati o n i n a n y ot her i nter ve nti o nal cli nical trial. 
2 5.  Pre vi o usl y ra n d o mise d i n t his cli nical trial. 


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Date: 0 7 -Dec -2 0 1 8  
Versi o n: 3. 0  
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2 6.  Pre vi o usl y 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).  
2 7.  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 h e i n vesti gat or.  
2 8.  E m pl o ye d at t he trial site or 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 m e m bers of s uc h i n di vi d uals.  
2 9.  L e gall y i nstit uti o nalise d. 
3 0.  P re g n a nt or lact ati n g. 
8. 4  S cree ni n g a n d scree ni n g f ail ures  
Trial  partici pati o n be gi ns o nce writte n i nf or m e 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 ns e nt is o btai ne d, a s u bject 
i de ntificati o n n u m ber (s u bject I D) will be assi g n e d b y a ce ntr al i nteracti ve res p o nse 
tec h n ol o g y (I R T) syste m a n d t he scree ni n g e v al uati o ns t o assess eli gi bilit y ma y b e gi n. T he 
s u bject 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 v e gi v e n writte n i nf or me d c o nse nt t o 
pa rtici 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 ‘s cree 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 nt e 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 bj ect ’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 nt eri 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 ra n d o ml y assi g ne d t o trial treat me nt. A mi ni mal set of i nf or m ati o n is re q uire d t o 
e ns ure tra ns p are nt re p orti n g of s cree ni n g fail ure s u bjects t o meet t he C o ns oli date d Sta n d ar ds 
of Re p orti n g Tri als ( C O N S O R T) p u blis hi n g re q uire me nts  (1 2 ) a n d t o r es p o n d t o q ueries fr o m 
re g ulat or y a ut h orities. I n di vi d uals w h o d o n ot meet t he criteria f or partici p ati o n i n t he trial 
(scree ni n g fail ures) ma y n ot be re-scree ne d. 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., dela ye d test res ults a n d n ot d u e t o t he s u bject faili n g t o meet t he eli gi bilit y 
criteria, re-scree ni n g ma y be p er mitte d. I n di vi d uals w h o are re-scree n e d will get a ne w s u bject 
I D. T he f oll o wi n g dat a will be c ollecte d i n t he e C R F f or scree ni n g fail ures : 


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 Date of i nf or m e d c o nse nt. 
 De m o gra p hics ( date  of birt h, a ge, se x, et h nicit y, race). 
 Reas o n f or screen i n g fail ure: 
 Fail ure t o meet eli gi bilit y criteria (s pecify w hi c h ). 
 Wit h dra wal b y s u bject . 
 Ca p pi n g  li mitati o n i n I G A baseli ne s e verit y. 
 O t her (s pecificati o n is re q uire d). 
 Date of screen i n g fail ure. 
 A n y A Es  a n d s eri o us A Es ( S A Es) . 
I n case of a n y S A Es, t hes e m ust be f oll o we d-u p as descri be d i n S ecti o n 1 3. 7 . 


C CI
C CI
C CI
C CI
C CI


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re gard l ess of cle ara n ce st at us. T he last I M P a p plicati o n will occ ur at t he s u bject ’s h o me 
bef ore t h e s u bject atte n ds t he visit sc he d ule d at Wee k 1 6.  
T he I M P will be dis pe ns e d b y t h e i n vesti gati o nal staff at t he visits sc he d ul e d i n Secti o n  4 . T he 
I R T will assi g n t he re q uir e d kit n u m ber(s) f or eac h s u bject at eac h dis pe nsi n g visit. 
T he i n vesti gat or will use cli nical j u d g e m e nt  t o treat a n y s y m pt o ms c o n necte d wit h a n 
o ver d ose.  
9. 3  Tre at me nt a ssi g n me nt 
S u bjects  w h o ha ve bee n f o u n d t o meet  all t he i ncl usi o n criteria a n d n ot t o f ulfil a n y of t h e 
e x cl usi o n criteria will be ra n d o mise d at baseli ne (Da y  1 ) t o recei ve treat me nt wit h eit her 
del g o citi ni b  crea m ( 1, 3, 8, or 2 0  m g/ g) or del g oci ti ni b crea m ve hicle . T he treat me nt 
assi g n me nt occ urs o n t he basis of a c o m p uter-ge n erate d ra n d o misat i o n sc h e me i n a 
1: 1: 1: 1: 1  rati o.  
S u bjects eli gi ble o n sele cti o n criteria at bas eli ne ma y b e  pre v e nte d fr o m bei n g  ra n d o mise d 
i nt o t he trial d ue t o t he a p plie d ca p pi n g li mitati o n i n I G A bas eli ne se verit y a n d re gi o nal 
e nr ol me nt  (as des cri be d i n Secti o n 7. 2 ). D ue t o t his ca p pi n g , the s p o ns or will acti vel y m o nit or 
t he s u bjects i n t he scree ni n g peri o d t o mi ni mise t he n u m ber of s u bjects t hat ma y b e e x cl u de d  
fr o m t he trial pri or t o ra n d o misati o n. 
T he I R T will be use d t o c o ntr ol ra n d o misati o n a n d stratificati o n fact ors, al o n g wit h I M P  
s up pl y c h ai n a n d e x pir y trac ki n g.  
9. 3. 1  Bli n di n g  
T he pac k a 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. It will n ot 
be p ossi ble t o differe ntiate bet wee n t he I M Ps s olel y b y se ns or y e val u ati o n.  
9. 3. 2  E mer ge nc y u n bli n di n g of in di vi d u al su bject tre at me nt  
W hile t he safet y of a s u bject al wa ys c o m es 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 bj ect ’s safet y. A n e mer ge nc y u n bli n di n g re q u est ca n b e 
ma de b y t he i n vesti gat ors, healt hcare pr ofessi o na ls 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 n c 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 n c y u n bli n di n g is re q uire d, t he i n v esti gat or ca n u n bli n d a s u bject ’s treat me nt i n t he 
I R T. F or a re q uester w h o is n ot a me m ber of t he tri al staff a n d w h o d oes n ot ha ve access t o t he 


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I R T (e. g., a p h ysici a n at a n e mer ge nc y r o o m ), a l o cal c o ntact n u m ber f or t h e e mer ge nc y 
u n bli n di n g c o ntract researc h or ga nisati o n ( C R O ) is pr o vi de d o n t he s u bje ct 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 del e gate d site staff ca n n ot be reac he d. The 
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 s u bject’s 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 uir es 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 m er ge n c y u n bli n di n g C R O will pr o vi de t he re q u ester wit h t he L E O 2 4/ 7 
c o ntact w hic h will be di v erte d t o t he me dical c o ver.  
9. 4  B ac k gr o u n d tre at me nt  (e m ollie nts) 
T he s u bjects s h o ul d n ot c ha n ge their us ual s ki n care r o uti ne re gar di n g use of e m ollie nts. 
H o we ver, t he e m ollie nt  m ust n ot be use d wit hi n 2  h o urs bef ore a n d after a p plicati o n of t he 
I M P. Use of c o nc o mita nt treat me nt is f urt her d escri be d i n Secti o n 9. 6 . 
9. 5  Resc ue tre at me nt  
If me dicall y necessar y (i. e., t o c o ntr ol i nt olera ble c hr o nic ha n d ecze ma s y m pt o ms), resc ue 
treat me nt f or c hr o nic h a n d ecze ma ma y be pr o vi de d t o t he s u bjects at t he discreti o n of t he 
i n vesti gat or. T he i n vesti gat ors s h o ul d ma ke e ver y atte m pt t o c o n d uct effi c ac y a n d safet y 
assess me nts (f or e x a m ple disease se verit y s c ores, s afet y la bs) i m me diatel y b ef ore 
a d mi nisteri n g a n y resc u e treat me nt.  
If res c ue treatme nt is i nitiate d, t he s u bject m ust st o p treat me nt wit h  I M P i m me diatel y a n d 
m ust  n ot  re-start treat me nt wit h I M P. It m ust be st ate d i n t he e C R F t hat t he s u bject recei ves 
resc ue m e dicati o n. F or t he p ur p ose of t h e pri mar y efficac y a nal ys es, s u bjects recei vi n g resc ue 
treat me nt d uri n g t he I M P treat me nt peri o d will be c o nsi dere d as n o n-res p o n ders. 
9. 6  C o nc o mit a nt me dic at i o n a n d c o nc urre nt pr oce d ures  
A n y me di cati o n or vacci ne t hat t he s u bject recei ves fr o m 6  m o nt hs  pri or  t o baseli ne (if 
rele va nt) t hr o u g h f oll o w-u p peri o d  m ust 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 al o n g wit h  details s uc h as : 
 Me dicati o n na me.  
 I n dic ati o n. 


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 S tart 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 m e dicati o n is 
o n g oi n g ). 
 D osa ge i nf or m ati 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 (a p pr o xi matel y 2 i n c hes) of t he treat me nt area.  
Si milarl y, a n y c o nc urre nt pr oce d ure m ust als o be rec or de d i n t he s u bj ect ’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.  
 S tart 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 t o pical treat me nts, it m ust als o be rec or de d if t he pr oce d ur e is i nsi de t he treat me nt 
area.  
I n v esti gat ors ma y pres cri be c o nc o mita nt me dicati o ns or treat me nts t o pr o vi de a de q uat e 
s u p p orti ve care as dee me d necessar y, e x ce pt f or m e dicati o ns liste d i n Secti o n 9. 7 . Use of 
e m ollie nts is descri be d i n Secti o n 9. 4 . 
As a r ule, t he s u bjects s h o ul d n ot c ha n ge t heir us u al s ki n ca re r o uti ne if p ossi ble. The s u bjects 
will be as ke d t o wear vi n yl gl o ves w h e n a p pl yi n g a n y ot h er s ki n treat me nts/ pr o d ucts t o ot her 
areas of t he b o d y f or ot her s ki n c o n diti o ns d uri n g t he trial. N or mal bat hi n g a n d was hi n g is 
all o we d wit h t he e x ce pti o ns me nti o ne d i n t he i nstr ucti o ns f or use . Us e of c os metic b o d y care 
pr o d ucts (e. g., b o d y l oti o n, s ha m p o o, bat h oil), w hic h are r o uti nel y us e d b y t he s u bjects, is 
all o we d as per i nstr ucti o ns f or use , b ut t he pr o d u cts s h o ul d n ot be c ha n ge d d uri n g t he tri al.  
E x cessi ve s u nli g ht a n d s u nla m ps s h o ul d be a v oi de d. S u nscree n pr o d ucts o n t he b o d y a n d 
pr otecti ve gl o ves o n t he ha n ds are rec o m me n d e d w he n e x p os ure ca n n ot b e a v oi de d.  


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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 tri al. I n cas e 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 n c o mita nt me dicati o n. 


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P a nel 5 : Pr o hi bite d me di c ati o n  
Me dic ati o n  
P r o hi bite d fr o m  
P r o hi bite d t o  
S yste mic treat me nt wit h i m m u n os u p pressi ve dr u gs (e. g., 
met h otre xate, c ycl os p ori ne, azat hi o pri ne), 
i m m u n o m o d ulati n g dr u gs (e. g., ja n us ki nase i n hi bit ors), 
reti n oi ds (e. g., alitreti n oi n), or c ortic oster oi ds (i n hale d or 
i ntra nasal ster oi ds c orres p o n di n g t o u p t o 1 m g pre d nis o ne 
f or ast h ma or r hi nitis ma y b e use d). 
4  wee ks pri or t o 
baseli ne.  
E n d of trial.  
P h ot ot hera p y e. g., P U V A or U V B t hera p y.  
4  wee ks pri or t o 
baseli ne.  
E n d of trial.  
Li ve atte n uate d vacci nes.  
4  wee k s pri or t o 
baseli ne.  
E n d of trial.  
C uta ne o usl y a p plie d treat me nt wit h i m m u n o m o d ulat ors 
(e. g., P D E-4 i n hi bit ors, pi mecr oli m us, tacr oli m us) or t o pical 
c ortic oster oi ds o n t he ha n ds.  
2 wee ks pri or t o 
baseli ne.  
E n d of trial.  
C uta ne o usl y a p plie d a nti bi otics o n t he ha n ds.  
2 wee ks pri or t o 
baseli ne.  
E n d of trial.  
C ha n ge i n s yste mic a nti hista mi ne t hera p y.  
2  wee ks pri or t o 
baseli ne.  
E n d of trial.  
Ot her c uta ne o usl y a p plie d t hera p y  o n t he ha n ds (e xce pt f or 
t he use of s u bject’s o w n e m ollie nt). 
1  wee k  pri or t o 
baseli ne.  
E n d of trial.  
C uta ne o usl y a p plie d treat me nts i n re gi o ns ot her t ha n t he 
ha n ds, w hic h c o ul d i nterfere wit h cli nical trial e val uati o ns 
or p ose a safet y c o ncer n.  
1  wee k pri or t o 
baseli ne.  
E n d of trial.  
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 (i ncl u di n g i m m u n o gl o b uli n, 
a nti-I g E, a n d d u pil u ma b):  
 
 
 
 
 
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. 
 
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, w hic he ver is 
l o n ger, 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 pri or t o 
baseli ne  or 5  half -li ves 
w hic he ver is t he 
l o n gest. 
E n d of trial.  


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9. 8  Tre at me nt l o gistics a n d a cc 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 
T he I M P s 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 d ar y p ac ka gi n g materials  will be i n di vi d uall y la belle d.  
T he la belli n g of I M Ps w ill 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 u a ges, as re q uir e 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 restri cte d area u n d er t he c o n diti o ns 
s pecifie d o n t he la b el 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 P s m ust be st ore d at 2 -8 °C  ( 3 6-4 6° F) . D o n ot freeze. T h e te m perat ure d uri n g st ora ge  
at t he trial site s h o ul d be m o nit ore d b y a cali brate d, stati o nar y, a n d c o nti n u o us electr o nic 
rec or di n g s yste m wit h al ar m a n d bac k-u p of d ata.  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 n e d a n d date d eac h m o nt h . If t he alar m is tri g gere d, t he l o g m ust be 
i m me diatel y pri nte d, re vi e we d, si g ne d a n d date d, a n d  a p pr o pri ate 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 ual .  
A te m perat ure l o g fr o m t he rec or di n g s yst e m m ust be ke pt  at t he trial site t o d oc u me nt t he 
st ora ge wit hi n t he ri g ht te m perat ur e i nter val. St or a ge facilities s h o ul d be c hec ke d at least 
e ver y w or ki n g d a y.  
St ora ge  of t he I M Ps ma y be dele gat e d, e. g. , t o a h os pital p har mac y, as l ocall 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 affect e d I M P s a n d s h o ul d 
i m me diatel y c o nta ct t heir cli nical researc h ass ociat e ( C R A ) f or f urt her g ui d a nce: 
 Te m perat ur e e x c ursi o n u p o n recei pt or d uri n g st or a ge at t he trial site.  
 Da ma ge d kit u p o n recei pt.  
Da ma ge d I M P s s h o ul d b e d oc u me nte d i n t he I R T  a n d re p ort e d as a pr o d uct c o m plai nt t o 
Gl o bal P har mac o vi gila nce, 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 p erat ur e e x c ursi o ns u p o n recei pt 
or d uri n g st or a ge at t he trial site) a n d ha n dli n g of da ma ge d I M P s (i ncl u di n g kits da ma ge d 
u p o n recei pt) are pr o vi de d i n t he trial pr o d uct ha n dli n g ma n ual.  


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9. 8. 3  Dr u g a cc 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 d e 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 gat e d, e. g. , t o a h os pital p har mac y, as l ocall y a p plica ble. 
A n in di v i d ual d r u g a cc o u nta bilit y for m  m ust be ke pt of t he I M P a d mi nistere d  t o a n d ret ur n e d 
b y eac h s u bject ra n d o mis e 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 h e C R A t o verif y c orrect 
dis pe nsi n g of t he I M P.  D r u g acc o u nt a bilit y i nf or m ati o n will be e ntere d i n t he I R T, w here als o 
i n ve nt or y stat us of all I M P at t he trial site will be mai ntai ne d. 
T he s u bject s will ret ur n use d a n d u n use d  I M Ps (i n cl u di n g pac ka gi n g material) at t he visits  
s pecifie d i n t he sc h e d ule of trial pr oce d ures ( Secti o n 4 ). 
Ret ur ne d trial pr o d uct s (use d a n d u n use d I M P s (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 ur e a n d m us t be st ore d se paratel y fr o m n o n-all ocat e d trial pr o d uct s. 
All I M Ps (i ncl u di n g pac k a gi n g mat erial) s u p plie d b y t he co ntract m a n ufact uri n g o r 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 b asis . Pri or t o 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 P s. 
All t u bes ret ur ne d t o t he C M O will be wei g h e d  t o deter mi ne t he a m o u nt of I M Ps use d.  
Re p orti n g i n e C R F  
T he kit /t u be n u m ber, dat e of 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 o r 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 P 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 areas of t h e ha n ds t he I M P m ust be a p plie d a n d w hat a m o u nt of I M P t o be  use d 
per a p plicati o n . 
At t he p h o ne call sc h e d ule d o n Da y 4  a n d at eac h visit sc he d ule d i n t he treat me nt peri o d (see 
Secti o n  4 ), t he s u bject will be as ke d if t he y ha v e use d t he I M P 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 m ust 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 P as pres cri be d. C o m plia nce or 


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n o n -c o m plia nce, i.e., n u m ber of misse d I M P a p plicati o ns  a n d t he reas o n f or i t, m ust be 
rec or de d i n t he e C R F. 
9. 8. 5  Tri al p r o d uct d estr ucti o n 
Use d a n d u n use d I M P s 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 r e 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  
I n or der t o e ns ure a p pr o priate treat me nt of t he s u bjects after t h e 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 d ar d practice.  
9. 1 0  Re p orti n g pr o d uct c o m pl ai nts  
A n y d efects or iss ues wit h t he I M P (e. g., stra n ge c ol o ur or c o nsiste nc y, i na de q uate la b elli n g) 
m ust be re p orte d t o Gl o b al P har mac o vi gila nce at L E O o n t h e trial-s pecific ( pa per) c o m plai nt 
for 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, 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., S A E]) m ust be re p ort e d t o Gl o bal P har mac o vi gila nce, 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, 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 P  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 u ct 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. 
D uri n g t h e i n vesti gati o n of t he pr o d uct c o m plai nt, t he I M P m ust be st or e 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 P nee ds t o 
be ret ur n e d f or f urt her i n vesti gati o n or ma y b e destr o ye d.  
Gl o bal P har mac o vi gila nce, L E O c o nta ct i nf or mati o n f or re p orti n g pr o d uct c o m plai nts:  
F a 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 h ar ma. c o m  


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1 0  Disc o nti n u ati o n a n d w it h dr a w al 
1 0. 1  Ge ner al pri nci ples  
A s u bject ma y wit h dr a w fr o m t he trial (i.e., wit h dr a w fr o m treat me nt a n d pr ot oc ol-defi ne d 
i nter ve nti o ns) or per m a n e ntl y disc o nti n ue trial  tr eat me nt (i.e., st o p 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 d ose or d uri n g t h e 
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 m e 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 wit h dra w fr o m t he trial a n d s u bjects w h o disc o nti n ue trial treat me nt will n ot be 
re place d. 
D at a t o be rec o r de d i n t he e C R F  
T he pri mar y reas o n s 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 at Wee k  1 6, if a p plica bl e,  m ust be rec or de d i n t h e me dical r ec or ds 
a n d o n t he e n d of tri al f or m i n t he e C R F w here t h e f oll o wi n g o pti o ns are a v aila ble:  
 Lac k of effi cac 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  
 Pre g n a nc y  
 Deat h  
 Ot her  
If ‘a d v erse e ve nt ’ or ‘ot h er ’ 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 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 n i 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.  


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 E vi de nce of pre g na n c y.  
 I nitiati o n of resc ue m e dicati o n. 
 Cli nicall y i m p orta nt la b orat or y a b n or m alities:  
o  Ala ni ne a mi n otra nsf eras e  a n d/ or as p artate a mi n otra nsferase v al ues > 3 x U L N 
wit h t otal bilir u bi n > 2 x U L N ( u nless ele v ate 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 as partat e a mi n otra nsferase a n d/ or ala ni ne a mi n otra nsferase  
> 5 x U L N (f or m ore t h a n 2  wee ks).  
It is n ot all o we d t o r e-start I M P tr eat me nt after dis c 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, 
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).  
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 m ust  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 nist rati o n of I M P (see t h e s c he d ule of tri al pr oce d ures [ Secti o n 4 ] f or 
data t o be c ollect e d at a n earl y ter mi nati o n visit).  T he i n vesti gat or will re vi e 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. 
D isc 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 pri o r t o Wee k 1 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 I M P a p plicati o n a n d ret ur n t o t he trial sit e f or 2  a d dit i o nal 
visits as i n dicate d bel o w. S ee 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 hes e visits . 
S u bjects , w h o disc o nti n ue I M P pri or t o Wee k  1 6  will be as ke d t o atte n d:  
 Earl y ter mi nati o n visit  (as s o o n as p ossi ble after t he last I M P a p plicati o n). 
 Sa fet y f oll o w-u p visit ( 2  wee ks after t he last I M P a p plicati o n ). 
 Pri mar y e n d p oi nt visit ( 1 6  wee ks after t he first I M P a p plicati o n). 


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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 he/s he  re p eate dl y fails t o ret ur n f or sc h e d ule d 
visits a n d if t he trial site is n ot a ble t o get i n c o nt act 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 f ails 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 ul e t he misse d visit as 
s o o n as p ossi ble t o retrie ve e Diar y a n d u n use d I M P 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 n e d visit sc he d ule a n d ascertai n w h et her or n ot 
t he su bject wis hes t o c o nti n ue i n t he trial.  
 Bef ore a s u bj ect is dee m e 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, h e/s he  will be c o nsi dere d as  wit h dra w n fr o m t he trial wit h a 
pri ma r y reas o n of l ost t o f oll o w-u p.  


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1 1  Tri al a ssess 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 S ecti 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. 
Assess me nts a n d pr oce d ures at eac h trial visit s h o ul d be perf or m e d i n t he f oll o wi n g or der as 
s h o w n i n Pa nel 6 : 
P a nel 6 : Se q ue nce of assess me nts  
 
*  Bl o o d sa m pli n g f or P K a n d fila g gri n m utati o nal stat us , s ki n s wa bs, s ki n barrier f u ncti o n 
assess me nts  (sele cte d sites), s ki n bi o psies ( o pti o nal) a n d p h ot o gra p h y  of  bi o psie d area s 
(rec o m me n d e d). 
Patie nt -re p orte d o utc o mes
At t he scree ni n g visit, s u bj ect's eli gi bilit y t o e nter t he trial has t o 
be c o nfir me d bef ore t he P R Os ca n be c o m plete d 
Efficac y assess me nts b y t he i n vesti gat or
Safet y assess me nts b y t he i n vesti gat or
S u bj ect assess me nt of l ocal t olera bilit y
La b orat or y a n d ot her assess me nts *


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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  or aller gist . I n v esti gat ors m ust be e x perie nce d i n treati n g 
c hr o nic ha n d ecze ma a n d ha ve d oc u me nt e d e x perie nce a n d/ or trai ni n g i n use of t he 
assess me nts re q uir e d b y t he pr ot oc ol a n d m ust be eit her a p h ysicia n, certifi e d p h ysici a n ’s 
assista nt, or a d va nce d re gistere d n urse practiti o ner.  
W he ne ver p ossi ble , t he s a 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 u ce i nter-rater vari a bilit y. 
A Es m ust be assesse d b y me dicall y q u alifie d pers o n nel  (i.e., a de q u atel y trai ne d me dical 
d oct ors ) ( Secti o n 1 3. 2 ).  
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 d e m o gra p hic data will be rec or de d:  
 D ate of birt h.  If f ull date of birt h is n ot all o we d t o be rec or de d, m o nt h a n d 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 m erica n I n dia n or Alas ka n ati ve, Asia n, blac k or Afri ca n A merica n, n ati ve 
Ha waiia n or o t h er Pacifi c isla n der, w hite, o t her (re q uires a s pecificati o n t o be 
pr o vi de d) . 
 Et h nic  ori gi n (s elf -re p ort e d b y t h e s u bject): His pa nic or Lati n o, n ot His pa nic or 
Lati n o.  


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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 p e will be rec or de d usi n g t he Fitz patric k s ki n classificati o n (Pa nel 7 ). 
P a nel 7 : Fit z 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 m aril 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 meric a 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 be c 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 os e of I n dia n desce nt.  
VI  
I n di vi d uals w h o ha ve t he hea viest c o 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 h ist or y 
Rele va nt me dical hist or y fr o m t he s u bject ’s dat e of birt h m ust be rec or de d . 
To s u p p ort selecti o n of trial s u bjects s pecificall y o n i ncl usi o n criteri o n 5  (eit her o ne or b ot h of 
t he f oll o wi n g): 
1.  Has t he s u bje ct f ulfille d t he trial i ncl usi o n  criteri o n 5 base d o n bei n g u nc o ntr olle d o n 
t o pical c ortic oster oi d treat me nt d uri n g t he last 12  m o nt hs? Y es/ No  
o  Rec or d me dic ati o n na me of pre vi o us treat me nt wit h t o pical c ortic oster oi d , 
ti me p oi nt of e x p os ure, a n d rati o nale f or dis c o nti n ui n g t he treat me nt. 
2.  Has t he s u bje ct f ulfille d t he trial i ncl usi o n criteri o n 5 base d o n t o pical c ortic oster oi ds  
bei n g me di call y i na d visa ble f or t he s u bject? Yes/ No  
o  Rec or d reas o n w h y t o pical c ortic oster oi d use is  n ot a d visa ble, me dicati o n 
na me of pre vi o us treat me nt wit h t o pical c ortic oster oi d , ti me p oi nt of e x p os ure, 
a n d rati o nale f or disc o nti n ui n g t he treat me nt . 


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C hr o ni c ha n d ecze ma hist or y:  
 Dia g n osis  of c hr o nic h a n d ecze ma : 
o  O nset of c hr o ni c ha n d ecze ma disease.  
o  Pre vi o us treat me nts f or c hr o nic ha n d ecze ma e x ce pt t he use of t o pical 
c ortic oster oi ds ( na m e or t y pe of treat me nt, ti me p oi nt of e x p os ure , rati o nale f or 
disc o nti n ui n g pre vi o us h a n d ecze ma tr eat me nts). 
o  Hist or y of f o ot der matitis.  
o  Res ult of dia g n ostic pat c h testi n g perf or me d wit hi n 3  years ( P ositi ve/ 
N e gati ve) .  
If p ositi ve, was t he i de ntifie d aller ge n c o nsi dere d rele va nt f or t h e c hr o nic h a n d 
ecze ma ( Yes/ N o). 
o  Res ults of ot her rele v a nt pre vi o us dia g n ostic pr oce d ures (e. g., pric k test). 
 Pre dicti ve fact ors  rele v a nt f or c hr o nic h a n d ecze m a: 
o  Pre vi o us or  c urre nt at o pic der matitis . 
o  Aller gic ast h ma or aller gi c r hi nitis . 
o  Prese nce of at o p y i n t he s u bject ’s fa mil y hist or y. 
 E x p os ures  rele va nt f or c hr o nic ha n d ecze ma: 
o  Occ u pati o nal or e n vir o n me ntal tri g ger fact ors  ( Yes/ N o/ D o n ot k n o w). 
o  O nset a n d w ors e ni n g of c hr o nic ha n d ecze ma s y m pt o ms  d uri n g w or k  
( Yes/ N o/ D o n ot k n o w). 
o  I m pr o v e me nt of c hr o nic ha n d ecze ma s y m pt o ms o n  t he wee k e n ds ( Yes/ N o/ D o 
n ot k n o w).  
o  Heali n g of c hr o nic ha n d ecze ma o n vacati o ns  ( Yes/ N o/ D o n ot k n o w). 
o  Rec urre n ce of c hr o nic h a n d ecze ma s y m pt o ms u p o n ret ur ni n g t o w or k  
( Yes/ N o/ D o n ot k n o w). 
o  Worse ni n g of c hr o nic ha n d ecze ma s y m pt o ms w he n n ot at w or k  ( Yes/ N o/ D o 
n ot k n o w).  
o  Wet -w or k  e x p os ure ( Yes/ N o/ D o n ot k n o w).  
o  N u m ber of dail y ha n d was hes.  


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o  S m o ki n g hist or y, defi ne d as:  
- Ne ver s m o ke d.  
- N o n -s m o ker f or m ore t ha n 1 year.  
- D uri n g t h e past year:  
- 
1 t o 4 ci garettes per da y.  
- 
5 t o 1 0  ci garettes per da y.  
- 
1 1 t o 2 0 ci garettes  p er da y.  
- 
M ore t ha n 2 0  ci garettes p er da y.  
Ot her me dical hist or y:  
 S ki n disease hist or y: all past a n d c urre nt s ki n disease hist or y (i ncl u di n g hist or y of 
at o pic der matitis) will be c ollecte d. F or eac h dia g n osis, t he start date a n d t he st o p 
date will be rec or de d. It will be rec or de d if t he di a g n osis is o n g oi n g a n d if t he 
disease is/ has bee n prese nt i n t he ha n ds.  
 Ot her me dical a n d s ur gic al hist or y i ncl u di n g c o n c 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 o ce d ure, t h e start 
date a n d st o p date or w het her it is o n g oi n g will be rec or de d.  
Rele va nt me dical hist or y als o i ncl u des diseases t h at are s p ecificall y liste d as e x cl usi o n criteria 
a n d diseases f or w hic h s p ecific tr eat me nts are liste d as e x cl usi o n criteria.  


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Date: 0 7 -Dec -2 0 1 8  
Versi o n: 3. 0  
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1 1. 2. 4  Cl assific ati o n of c hr o nic h a n d ecze m a  
Base d o n m e dical hist or y (i ncl u di n g hist or y of dia g n ostic patc h t esti n g wit hi n 3  years) a n d 
m or p h ol o g y of t he prese nt lesi o ns, t he i n vesti gat or will deter mi ne t he s u bt y p e(s) acc or di n g t o 
t he defi niti o ns i n Pa nel 8 . T he s u bt y p e(s) of t he s u bject ’s c hr o nic h a n d ecze ma will be 
rec or de d as mai n dia g n osis a n d a d diti o nal  dia g n os es, if a p plica ble.  
P a nel 8 : Defi niti on of s u bt y pes of h a n d ecze m a  
S u bt y pe  
Defi niti o n  
Aller gic c o ntact der matitis  
Ha n d ecze ma ca use d b y rele v a nt c o ntact aller ge ns or cr oss -r eact ors i de ntifie d 
b y patc h testi n g. Rele va nce mea ns t hat t here is a c urre nt e x p os ure of t he 
aller ge ns t o t he ha n ds.  
Irrita nt c o ntact der matitis 
Ha n d ecze ma wit h d oc u me nte d irrita nt e x p os ure,  w hic h is q ua ntitati vel y li kel y 
t o ca use der matitis. N o rele va nt c o ntact aller g y ( n o c urre nt e x p os ure t o 
aller ge ns t o w hic h t he patie n t has reacte d p ositi ve i n patc h t est).  
C o ntact urticaria/ pr otei n 
c o ntact der matitis  
Ha n d ecze ma i n patie nts e x p ose d t o pr otei ns (f o o d, late x, a n d ot her bi ol o gical 
material) wit h a p ositi ve pric k test, or pr o ve n s pecific I g E, t o s us pecte d ite ms. A 
c o nsi dera ble pr o p orti o n of patie nts wit h c o ntact urticar ia will als o ha ve at o pic 
s y m pt o ms.  
At o pic ha n d ecze ma  
Ha n d ecze ma i n a patie nt wit h a me dical hist or y of at o pic ecze ma, pre vi o us or 
c urre nt. N o d oc u me nte d irrita nt e x p os ure a n d/ or rele va nt c o ntact aller ge n li kel y 
t o ca use ecze ma. 
P o m p h ol y x  
Rec urre nt ha n d ecze ma wit h vesic ular er u pti o ns. N o rele va nt c o ntact aller g y, n o 
d oc u me nte d irrita nt e x p os ure li kel y t o ca use der matitis.  
H y per kerat otic ecze ma 
( h y per kerat otic der matitis 
of t he pal ms)  
C hr o nic ecze ma wit h h y per kerat osis i n t he pal ms, or p ul pitis, a n d n o  vesicles or 
p ust ules. N o d oc u me nte d irrit a nt e x p os ure t o t he i n v ol ve d s ki n areas, li kel y t o 
ca use irrita nt e x p os ure.  
Refere nce: Die p ge n et al. 2 0 1 5 ( 1 ). 
 
1 1. 2. 5  Hei g ht a n d w ei g ht  
T he s u bject ’s hei g ht ( wit h o ut s h oes) will be meas ure 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 o es) will be meas ure d . 
1 1. 2. 6  Deter mi n ati o n of tre at me nt are a  
P ri or t o t he first I M P a p plicati o n, t he i n vesti gat or will deter mi ne t he treat m e nt area(s) o n t he 
left a n d t he ri g ht ha n d usi n g t he f oll o wi n g 5 areas: fi n gerti ps, fi n gers ( e x ce pt fi n gerti ps), pal m 
of ha n d s, bac k of ha n ds, a n d wrists. T he treat me nt areas affe ct e d will be mar ke d o n a sc h e me 


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Date: 0 7 -Dec -2 0 1 8  
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s h o wi n g t he b ac k a n d t he fr o nt of t he left a n d t he ri g ht ha n d as fr o m t he pers pecti ve of t he 
s u bject. 
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 (I G A) 
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 sta ge  a n d is  base d o n a 5 -p oi nt scale ra n gi n g fr o m 0 (clear) t o 4 (s e vere)  (Pa nel 9 ). 
T he se verit y of eac h si g n or s y m pt o m is descri be d i n  Pa nel 1 0 . T he I G A sc ore will be 
assesse d at ti me p oi nts acc or di n g t o t he s c he d ule of trial pr oce d ures (S ecti 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 u ati 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. Ne w l esi o ns t hat occ urre d o n pre vi o usl y u ntr eate d 
areas will be i ncl u de d i n t he assess me nt.  
P a nel 9 : I n vesti g at o r’s Gl o b al Assess me nt (I G A) 
I G A 
se v erit y 
I G A 
sc o re 
Si g n/s y m pt o m  
I nte nsit y 
Clear  
0  
Er y t he ma, scali n g, h y per kerat osis/lic he nificati o n 
Vesic ulati o n, o e d e ma, fiss ures  
A bse nt  
A bse nt  
Al m ost clear  
1  
Er yt he ma  
Scali n g, h y per kerat osis/lic he nificati o n, 
vesic ulati o n, o e d e ma, fiss ures  
Mil d  
A bse nt  
Mil d  
2  
Er yt he ma, scali n g, h y per kerat osis/lic he nificati o n  
Vesic ulati o n, o e d e ma, fiss ures  
At least o ne mil d  
At least o ne mil d  
M o derate  
3  
Er yt he ma, scali n g, h y per kerat osis/lic he nificati o n  
Vesic ulati o n, o e d e ma, fiss ures  
At least o ne mil d or m o derate  
At least o ne m o derate  
Se vere  
4  
Er yt he ma, scali n g, h y per kerat osis/lic he nificati o n  
Vesic ulati o n, o e d e ma, fiss ures  
At least o ne m o derate or se ver e  
At least o ne se vere  
I G A V 2. 0. I ns pire d b y R uzic ka et al, 2 0 0 8 (1 1 ) a n d J F F o wl er ( pers o nal c o m m u nicati o n, 0 9 Ma y 2 0 1 7) . 
T he ter m P h ysicia n Gl o bal Assess me nt was use d b y R uzic ka/ F o wler, b ut I G A will be use d i n t his trial.  


Trial I D: L P 0 1 3 3 -1 2 7 3  
Date: 0 7 -Dec -2 0 1 8  
Versi o n: 3. 0  
P a ge 6 9  of 1 2 8  
 
 
 
P a nel 1 0 : D escri pti o n of t he se verit y of e ac h I G A si g n or s y m pt o m  
S ig n/s y m pt o m  
 
Se verit y  
Descri pti o n of se verit y  
Er yt he ma  
Mil d  
M o derate  
Se vere  
Fai nt er yt he ma  
Pr o mi ne nt re d ness  
Dee p i nte nse re d c ol o ur  
Scali n g  
Mil d  
M o derate  
Se vere  
Sli g ht fla ki n g, m ostl y fi ne scales  
Fla ki n g, t hic ker scales 
Des q ua mati o n wit h t hic k scal es  
Lic he nificati o n  / 
h y per kerat osis  
Mil d  
M o derate  
Se vere  
Mil d t hic ke ni n g wit h e xa g gerate d s ki n li nes  
P al pa ble t hic ke ni n g 
Pr o mi ne nt t hic ke ni n g  wit h e xa g gerati o n of n or mal s ki n mar ki n gs  
Vesic ulati o n  
Mil d  
M o derate  
Se vere  
Scattere d vesicles, wit h o ut er osi o n  
C l ustere d vesicles, wit h o ut visi ble er osi o n or e xc oriati o n 
Hi g h de nsit y of vesicles, or wit h er osi o n or e xc oriati o n  
Oe d e ma  
Mil d  
M o derate  
Se vere  
Sli g ht d er mal s welli n g  
Defi nite der mal s welli n g  
Der mal s welli n g wit h s ki n i n d urati o n  
Fiss ures  
Mil d  
M o derate  
Se vere  
S u perficial fiss ures  
Defi nite fiss ures  
O ne or m ore dee p fiss ures wit h/ wit h o ut  blee di n g  
I ns pire d b y R uzic ka et al ( 1 1 ) a n d F o wler J F ( pers o nal c o m m u nicati o n, 0 9 Ma y 2 0 1 7). T he ter m P h ysicia n 
Gl o bal Assess me nt was use d b y R u zic ka/ F o wler, b ut I G A will be  use d i n t his trial.  
 
1 1. 3. 2  H a n d E cze m a S e verit y In de x  ( H E C SI) 
T he H E C SI is a n i nstr u me nt use d i n cli nical trials t o rate t he se v erit y o f 6 cli nical si g ns 
(er yt he ma [ E], i nfiltrati o n/ pa p ulati o n [I], vesicles [ V], fiss ures [ F], scali n g [S] , oe de ma [ O]) 
a n d t he e xte nt of t he lesi o ns o n eac h of t h e 5  ha n d areas (fi n gerti ps, fi n gers [e x ce pt 
fi n gerti ps], pal m of ha n ds, bac k of ha n ds, a n d wrists) b y use of sta n dar d scales (1 3 ). 
F or eac h ha n d area (t otal of b ot h ha n ds e. g., 1 0 fi n gers), t he i n vesti gat or rat es t he a vera ge 
se verit y of eac h of t h e 6 cli nical si g ns of ha n d ecz e ma usi n g a 4-p oi nt se verit y scale ra n gi n g 
fr o m 0 ( n o ne/a bs e nt) t o 3 (se vere) (Pa n el 1 1 ). T h e i n vesti gat or als o rates t he e xte nt of t he 
lesi o ns b y assessi n g t he p erce nt a ge of t h e areas t hese lesi o ns occ u p y, a n d c o n verti n g it t o a 


Trial I D: L P 0 1 3 3 -1 2 7 3  
Date: 0 7 -Dec -2 0 1 8  
Versi o n: 3. 0  
P a ge 7 0  of 1 2 8  
 
 
 
sc ore bas e d o n a 5-p oi nt scale (t he affecte d area s c ore [ A S]) (Pa nel 1 1 ). F or eac h of t he ha n d 
areas, t h e gra d es f or 6 s electe d cli nical si g ns of ha n d ecze ma are t otalle d ( E + I + V + F  + S + 
O = t otal gra de ) a n d t his t otal gra d e  will be m ulti plie d b y t he c o n verte d affecte d A S  bas e d o n 
t he area of b ot h ha n ds (P a nel 1 2 ). T h e hi g h est p ossi ble H E C SI sc ore is 3 6 0.  
T he H E C SI will be assesse d at ti me p oi nts acc or di n g t o t he sc h e d ule of trial pr oce d ures 
( Secti o n 4 ). T he assess m e 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. Ne w lesi o ns t hat occ urre d o n 
pre vi o usl y u ntr eate d areas will be i ncl u de d i n t he assess me nt.  
P a nel 11 : H E C SI se verit y sc ore sc ale a n d are a s c ore s c ale  
Se verit y sc o re  ( S S) sc ale 
( b ase d o n b ot h h a n ds) 
 
Are a sc ore ( A S) sc ale  
( b ase d o n t he are a of b ot h h a n ds) 
0  
N o ne/a bse nt  
 
0  
0 % affecte d area  
1  
Mil d  
 
1  
1 % t o 2 5 % affecte d area  
2  
M o derate  
 
2  
2 6 % t o 5 0 % affecte d area  
3  
Se vere  
 
3  
5 1 % t o 7 5 % affecte d area  
N ote: half -ste ps ( 0.5, 1. 5, 2. 5) are n ot  all o we d.  
 
4  
7 6 % t o 1 0 0 % affecte d area  
 
 
N ote: half -ste ps ( 0. 5, 1. 5, 2. 5, 3. 5) are n ot  all o we d.  
 
P a nel 1 2 : C al c ul ati o n of t he t ot al H E C SI  sc ore 
H a n d re gi o n  
Er yt he m a  
I nfiltrati o n/ 
p a p ul ati o n  
Vesicles  
Fiss ures  
Sc ali n g  
Oe de m a  
Are a sc ore  
Sc ore  
Fi n gerti ps  
( S S +  
  S S  +  
  S S +  
  S S  +  
  S S +  
  S S )  
x A S  
 
Fi n gers (e xce pt 
fi n gerti ps) 
( S S +  
  S S  +  
  S S  +  
  S S  +  
  S S +  
  S S )  
x A S  
 
P al m  of h a n d s 
( S S +  
  S S +  
  S S  +  
  S S  +  
  S S  +  
  S S )  
x A S  
 
B ac k of h a n ds  
( S S +  
  S S +  
  S S  +  
  S S  +  
  S S  +  
  S S )  
x A S  
 
Wrists  
( S S +  
  S S +  
  S S  +  
  S S +  
  S S +  
  S S )  
x A S  
 
T he t otal H E C SI sc ore e q uals t he s u m of t he 5 a b o ve re gi o n sc ores:  
 
  A S, area sc ore; S S, se verit y s c ore.  


Trial I D: L P 0 1 3 3 -1 2 7 3  
Date: 0 7 -Dec -2 0 1 8  
Versi o n: 3. 0  
P a ge 7 1  of 1 2 8  
 
 
 
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, p ulse , a n d b o d y te m perat ur e) will  be assesse d acc or di n g t o 
t he sc he d ule of tri al pr oce d ures (S ecti 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 d ere d t o be 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 w het her  t he s u bj ect s h o ul d be 
ra n d o mise d i nt o t he trial (res pecti n g e x cl usi o n criteri o n n o.  2 0) . 
I n case of a b n or m al fi n di n gs, t he vital si g n meas ure me nt ca n b e re p eate d a p pr o xi matel y 
1 5  mi n utes later wit h  t he s u bject 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 m al val ue, t he meas ure me nt m ust be re peate d 
o nce m ore. If t he t hir d m eas ure m e nt verifies t he s ec o n d ( n or m al) val ue, t h e first meas ure m e nt 
s h o ul d be c o nsi dere d fals e. 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 s ec o n d m eas ure m e 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  
V ital si g ns will be rec or de d i n t he e C R F. Cli nicall y si g nifica nt a b n or mal vital si g ns at 
scree ni n g will be d o c 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 d eteri orati o n of a pre -e xisti n g c o n diti o n as well as a n y n e 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 
S ecti o n 1 3. 3 . 
1 1. 4. 2  P h ysic al ex a mi n ati o n  
A t h or o u g h p h ysical e x a mi nati o n  of t he s u bject i ncl u di n g  w h ole b o d y i ns p ecti o n of t he s ki n, 
a usc ultati o n of heart, l u n gs, a n d a b d o me n, pal pati o n of t he a b d o mi nal or ga ns, a n d basic 
ne ur ol o gi cal stat us  m ust be perf or me d acc or di n g t o t he sc he d ule of tri al pr oce d ures 
(S ecti o n 4 ). Prese n ce of f o ot der matitis will be d oc u me nte d. T he i n vesti gat or s h o ul d perf or m 
t he sa me e x a mi nati o ns as i n cli nical practice as a mi ni m u m. 
If t he scree ni n g p h ysical e x a mi nati o n res ults i n a fi n di n g, w hic h is a b n or m al a n d of cli nical 
si g nifica n ce, 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 x cl usi o n criteri o n n o. 2 0) . 


Trial I D: L P 0 1 3 3 -1 2 7 3  
Date: 0 7 -Dec -2 0 1 8  
Versi o n: 3. 0  
P a ge 7 2  of 1 2 8  
 
 
 
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 x a mi nati o n was perf or me d a n d 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 ysic al e xa mi nati o n was n ot perf or me d, a reas o n m ust be gi ve n . 
Cli n icall y si g nifica nt a b n or mal fi n di n gs at s cree ni n g will be d oc u m e nte d as me dical hist or y i n 
t he e C R F. At s u bse q u e 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 n ess will be re p orte d 
as a n A E i n acc or da n ce wit h Secti o n  1 3. 3 . 
1 1. 4. 3  E C G  
A si n gl e 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 visits i n dicate d i n t he sc he d ule of trial pr oce d ures (S ecti o n 4 ). 
A pre li mi nar y e val uati o n of t he E C Gs will be perf or me d b y t h e i n vesti gat ors 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 m e 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 ys e 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 v al 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 d ate.  T he i n v esti gat or has t he fi nal decisi o n o n t he cli nical 
si g nifica n ce 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 n ce, 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 x cl usi o n criteri o n n o. 2 0) . 
T he c ollecti o n a n d tr a ns missi o n of E C G data will b e descri b e d  i n a se parat e 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 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 s et.  
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 CG was perf or me d a n d t he i n v esti 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.  


Trial I D: L P 0 1 3 3 -1 2 7 3  
Date: 0 7 -Dec -2 0 1 8  
Versi o n: 3. 0  
P a ge 7 3  of 1 2 8  
 
 
 
Cli nicall y si g ni fica nt a b n or mal fi n di n gs at s cree ni n g will be d oc u m e nte d as me dical hist or y i n 
t he e C R F. At s u bse q u e 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 n ce wit h Secti o n  1 3. 3 . 
1 1. 4. 4  L a b or at or y  testi n g 
Bl o o d a n d uri ne s a m ples will be c ollecte d acc or di n g t o t he sc h e d ule of trial pr oce d ures 
( Secti o n 4 ). See  Pa nel 1 3  f or a n o ver vie w of t h e i n di vi d ual cli nical la b orat or y p ara m eters t o 
be assess e d i n t his trial. 
Ce ntr al l a b or at or y  
C he mistr y, h ae mat ol o g y, uri nal ysis (if a p plica ble), ser ol o g y, a n d s er u m pre g na n c y tests will 
be a nal yse d b y a ce ntral l a 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 u ate all res ults o utsi de t he refere n ce 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 d ate. 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 o c u me ntati o n. Cli nicall y si g nifica nt a b n or mal tests m ust be re peat e d 
t o c o nfir m t he a b n or malit y. 
If a scree ni n g la b orat or y res ult 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 x cl usi o n criteria n o. 1 6, 2 0, 2 1, 2 2 , a n d 3 0). 
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 h e 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 s a m ples, as well as la b orat or y c o nt act 
i nf or mati o n s pecific t o t his trial. 
Tests perf or me d a t t he tri al site 
Uri ne sa m ples will be teste d at t he trial site wit h a di pstic k; if a b n or mal, a uri ne sa m ple will 
be se nt t o t he ce ntr al la b orat or y f or f urt her a nal ysis.  
Wo me n of c hil d beari n g p ote ntial will ha ve uri ne pre g na nc y t ests perf or me d at t he trial  site at 
t he visits i n dicate d i n t he sc he d ule of trial pr oce d ures i n Secti o n  4 . 
 




Trial I D: L P 0 1 3 3 -1 2 7 3  
Date: 0 7 -Dec -2 0 1 8  
Versi o n: 3. 0  
P a ge 7 5  of 1 2 8  
 
 
 
Re p orti n g i n e C R F  
T he site staff will r ec or d i n t he e C R F if a sa m ple was ta ke n a n d 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 nifica nt ’, ‘a b n or mal, cli nicall y 
si g nifica nt’). 
T he date a n d t h e o utc o m e of t he uri ne pre g na n c y test will be rec or de d i n t he e C R F (‘p ositi ve ’, 
‘ne gati ve ’). 
Cli nicall y si g nifica nt a b n or mal la b orat or y res ults at scree ni n g  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 n e 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. 5  S u bject assess me nt of l oc al t oler a bilit y  
S u bjects will pr o vi de a n assess me nt of l ocal t olera bilit y acc or di n g t o t he s c he d ule of tri al 
pr oce d ures ( Secti o n 4 ).  
T he s u bject will retr os pecti vel y b e as ke d b y t he i n vesti gat or t o assess sti n gi n g/b ur ni n g i n 
c o n necti o n wit h t he I M P a p plicati o ns si nce t heir last visit. T he hi g hest ( w orst) s ki n reacti o n 
sc ore acr oss treat me nt area(s) will be rec or de d i n t he e C R F b y use of t he 4 -p oi nt scale  s h o w n 
i n Pa nel 1 4 . 
P a nel 1 4 : S u bject as s ess me nt of l oc al t oler a bilit y after I M P a p plic ati o n  
Gr a de  
S ti n gi n g/ b ur ni n g 
0 ( n o ne)  
N o sti n gi n g or b ur ni n g  
1 ( mil d)  
Sli g ht war m, ti n gli n g se nsati o n, n ot reall y b ot h ers o me  
2 ( m o derate)  
Defi niti ve war m, ti n gli n g se nsati o n, t hat is s o me w hat b ot hers o me  
3 (se vere) 
H ot, ti n gli n g/sti n gi n g s e nsati o n t hat has ca use d d efi nite disc o mf ort.  
 
S u bject a ssess me nt of l ocal t olera bilit y will be perf or me d after s afet y ass ess me nts b y t he 
i n vesti gat or (Pa n el 6 ). L o c al t olera bilit y reacti o ns are n ot  re p orte d as A Es; h o we ver, if t h e y 
q ualif y as a n S A E, t he y will be re p orte d as descri be d i n Secti o n 1 3. 4. 1 . 


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Date: 0 7 -Dec -2 0 1 8  
Versi o n: 3. 0  
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1 1. 5   P h ar m ac o ki netic a ssess me nts 
1 1. 5. 1  Bl o o d s a m pli n g f or a n al ysis of  s yste mic c o nce ntr ati o n of del g ociti ni b  
O ne  b l o o d sa m ple fr o m eac h s u bject will be c ollecte d  f or P K assess me nts 2 -6 h o urs after t h e 
m or ni n g a p plicati o n of I M P as s pecifie d i n t he sc he d ule of trial pr o ce d ures  i n Secti o n  4 . 
It will be rec or de d i n t he e C R F if t he P K sa m ple was ta ke n; if n ot, a reas o n will be pr o vi de d.  
T he date a n d ti me of t he last I M P a p plicati o n pri or t o t he P K sa m ple bei n g ta ke n m ust be 
rec or de d i n t he e C R F. 
C ollecti o n, ha n dli n g , a n d s hi p me nt i nstr ucti o ns f or P K bl o o d sa m ples are pr o vi de d i n a 
la b orat or y ma n u al. 
Plas ma sa m ples f or deter mi nati o n of del g ociti ni b  c o nce ntr ati o ns will be a n al yse d b y a 
la b orat or y usi n g a vali dat e d bi oa nal ytical met h o d. Details of t he a n al ytical met h o d use d will 
be descri b e d i n t he bi oa n al ytical re p ort.  
Sa m ples fr o m  del g o citi ni b  crea m v e hicle -tr eate d s u bjects will n ot be a nal ys e d.  Writte n 
pr oce d ures are i n place t o a v oi d u n bli n di n g of t he trial a n d a n y trial s u bjects i n relati o n t o 
a nal ysis of t he P K sa m ples.  
1 1. 6  P h ar m ac o d y n a mic s a n d p h ar m ac o ge n o mics 
1 1. 6. 1  O ver vie w  
A hall mar k of c hr o nic h a n d ecze ma is a n i m paire d s ki n barrier f u ncti o n lea d i n g t o dr y s ki n, 
e x c oriati o ns, a n d s u peri nfecti o n b y St a p hyl oc occ us a ure us . Base d o n its me c ha nis m of acti o n 
a n d o n fi n di n gs i n a pre vi o us cli nical trial (1 0 ), del g ociti ni b  is belie ve d t o b e a ble t o i m pr o ve 
t he s ki n barrier i n p e o ple wit h ecze ma. It is t he p ur p ose t o i n vesti gat e t his f urt her i n a selecte d 
s u bject gr o up i n t his trial b y de m o nstr atin g i m pr o ve d s ki n barrier o n t he bac k of t he ha n d b y 
n o n -i n vasi ve met h o ds c o m bi ne d wit h hist ol o g y. T he s ki n barrier f u ncti o n will be c o m pare d t o 
fila g gri n m utati o n stat us of t he s u bjects. M utati o ns i n fila g gri n lea d t o decrease d s ki n barrier 
f u ncti o n a n d may t h us be li n ke d t o a hi g her diseas e pre val e nce as well as t o a lesser 
i m pr o ve me nt of s ki n barrier f u ncti o n i n res p o nse t o treat me nt. 
Little is k n o w n a b o ut t he s ki n micr o bi o me a n d St a p hyl oc occ us a ure us i n c hr o nic ha n d 
ecze ma. D ue t o t he si milarit y of t he p at h o p h ysi ol o g y of c hr o nic h a n d ecze ma a n d at o pic 
der matitis it is hi g hl y li kel y t hat t here will be si milarities t o at o pic der matitis, w hic h is 
ass ociate d wit h i ncrease d s ki n c ol o nis ati o n wit h St a p hyl oc occ us a ure us acc o m pa nie d b y 
decrease d c ol o nis ati o n wit h  ma n y c o m me nsal b acterial s pecies . To i n vesti gate t he effect of 


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Versi o n: 3. 0  
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treat me nt wit h del g ociti ni b  o n t he s ki n micr o bi o me i n ge neral a n d o n c ol o nis ati o n wit h 
St a p hyl oc occ us a ure us , s ki n s wa bs will be ta ke n. 
Fi nall y, treat me nt wit h del g o citi ni b  is s u p p ose d t o lea d t o a re d u cti o n of i m m u ne cells a n d 
i nfla m mati o n i n t he s ki n a n d a n or malisati o n of t h e e pi der mis, w hic h will b e f urt her e x pl ore d 
i n t his trial. 
T he f oll o wi n g p ara m eters will be assesse d:  
 St a p hyl oc occ us a ure us  c ol o nis ati o n i n s ki n s wa bs meas ure d b y q P C R.  
 Micr o bi o me di versit y i n a s u bset of s ki n s wa bs i n vesti gate d b y us e of ne xt ge n erati o n 
se q ue nci n g met h o ds.  
 E pi der mal t hic k ness a n d i nfla m mat or y i nfiltrat e i n t he s ki n b y hist ol o g y.  
 E x pressi o n of pr otei ns i n v ol ve d i n s ki n barrier i nt e grit y a n d s ki n matri x m o d ulati o n 
i ncl u di n g b ut n ot li mite d t o fila g gri n a n d l oricri n b y i m m u n o hist oc he mistr y.  
 E x pressi o n of  disease mar kers of c hr o nic h a n d ecz e ma  a n d mar k ers of i m m u ne cells 
i ncl u di n g b ut n ot li mite d t o C D 3 a n d C D 4 5. 
 Fila g gri n ge ne m utati o n st at us. 
 C ha n ge i n s ki n barrier f u ncti o n meas ure d as tra ns e pi der mal wat er l oss, s ki n p H, a n d 
c o nte nt of nat ur al m oist urisi n g fact ors  i n ta pe stri ps. T hese meas ure me nts will be 
carri e d o ut o nl y at select e d sites, w hic h ha ve t h e nee de d e x pertise a n d e q ui p me nt . 
Si nce t he s ki n str uct ure, micr o bi o me , a n d i m pact of c o nta mi nati o n are pr of o u n dl y differe nt 
bet wee n t he d orsal si de a n d t he pal m, o nl y t he wrist or d orsal as pect of t he ha n d a n d fi n gers 
will be use d f or i n vesti gati o n of t he a b o ve para met ers. S u bjects  w h o d o  n ot ha ve a n y dise ase 
i n v ol ve me nt of t hese l oc ati o ns will n ot ta ke part i n a n y of t hese assess me nts. 
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 t he y are 
a vaila ble i n ti me f or t his. T he f ull p har mac o d y na mics / bi o mar ker res ults will be re p orte d i n 
a n a d de n d u m r e p ort t o t he C T R . 
1 1. 6. 2  S ki n s w a bs  
A t otal of 4  s ki n s wa bs f or micr o bi o me a n d St a p hyl oc occ us a ure us  m eas ure me nt s will be 
ta ke n at t he ti me p oi nts s pecifie d i n t he sc h e d ule of trial pr oce d ures ( Secti o n  4 ). 


Trial I D: L P 0 1 3 3 -1 2 7 3  
Date: 0 7 -Dec -2 0 1 8  
Versi o n: 3. 0  
P a ge 7 8  of 1 2 8  
 
 
 
At baseli ne ( Da y  1), 2 s ki n s wa bs are t o b e ta ke n:  
 1 s ki n s wa b fr o m a re prese ntati ve lesi o nal area  fr o m t he d orsal si de of t he ha n d or 
fi n gers or fr o m t he wrist.  
 1  s ki n s wa b fr o m a n o n-l esi o nal area at a n a nat o micall y si milar site t o t he l esi o nal s ki n 
s wa b. 
At Wee k 1 6  (e n d of tr eat me nt), 2  s ki n s wa bs will be ta ke n at t he s a me l ocati o ns as t he 
baseli ne s ki n s wa b s. 
If bi o psies are t o be ta ke n (see Secti o n 1 1. 6. 3 ), t he baseli ne bi o psies s h o ul d be ta ke n fr o m t he 
sa me area as t he s ki n s w a bs, s o t he sites selecte d f or s ki n s wa bs m ust t he n als o be a p pr o priate 
f or bi o ps yi n g. 
It will be rec or de d i n t he e C R F if t he s ki n s wa bs w ere ta ke n a n d fr o m w hi c h l ocati o n ( d orsal 
ha n d, d orsal or v olar wrist, fi n ger); if s ki n s wa b s w ere n ot ta ke n, a c o m me nt will be pr o vi de d . 
S u bjects  will be i nstr ucte d n ot t o was h t heir ha n ds or a p pl y d isi nfecta nts/ ha n d sa nitizers f or at 
least 1 h o ur pri or t o t he b aseli ne visit a n d Wee k 1 6 visit.  
F urt her i nstr u cti o ns f or c ollecti o n, ha n dli n g a n d s hi p me nt f or s ki n s wa bs are pr o vi de d i n a 
la b orat or y ma n u al. 
1 1. 6. 3  S ki n bi o psies  a n d p h ot o gr a p h s (all sites, b ut  o pti o n al ) 
S u bjects , w h o have  lesi o ns at a l ocati o n s uita ble f or bi o ps yi n g (i.e., d orsal ha n d, fi n gers , or 
wrist)  will be as ke d t o partici pate i n a n e x pl orat or y c o m p o n e nt i n v ol vi n g 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 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 a n d is N O T ma n dat or y f or partici pati o n i n t he trial. Bi o psies wil l 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 o a g ula nt t hera p y). 
It is e x pecte d t hat a p pr o xi matel y half of eli gi ble s u bjects will acce pt t o partici pate i n t his 
e x pl orat or y c o m p o n e nt of t he trial. If bi o psies are o btai ne d fr o m less t ha n 1 0 % of s u bjects, 
a nal ysis ma y n ot b e carri e d o ut as t he n u m ber of bi o psies ma y be t o o l o w t o all o w f or a 
mea ni n gf ul a nal ysis. A fi nal decisi o n will be ma de after u n bli n di n g. O nce bi o psies ha ve bee n 
o btai ne d  fr o m 1 0 0 s u bjects ( 4 0 % of trial p o p ulati o n), n o f urt her bi o psies will be ta ke n as 
i ncl usi o n of f urt her bi o psies are n ot belie ve d t o i m pr o ve t he q ualit y of res ults si g nifica ntl y. If 
at least 1 0 % of s u bjects ha ve c o nse nt e d t o bi o psies, fila g gri n e x pressi o n a n d e pi der mal 


Trial I D: L P 0 1 3 3 -1 2 7 3  
Date: 0 7 -Dec -2 0 1 8  
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P a ge 7 9  of 1 2 8  
 
 
 
t hic k ness will be meas ur e d i n all bi o psies. L ori cri n, C D 4 5, C D 3 a n d p ote ntiall y ot her dise ase 
mar kers will be meas ure d i n a s u bset of bi o psies selecte d after u n bli n di n g. T his s u bset will 
i ncl u de bi o psies fr o m 1 0-1 2 ve hicle -tr eate d s u bj ects a nd 3 0 -4 0 s u bjects treate d wit h 
del g o citi ni b  selecte d fr o m t he hi g hest f or m ulati o n stre n gt hs. If bi o psies are o btai ne d fr o m less 
t ha n 5 0 s u bjects, t hese m ar kers will be meas ure d i n all bi o psies. 
A t otal of 3 s ki n bi o psies ( 3 m m p u nc h bi o psies) f or hist ol o g y/i m m u n o hist oc he mistr y will be 
ta ke n at t he ti me p oi nts s pecifie d i n t he sc h e d ule of trial pr oce d ures ( Secti o n 4 ). 
At baseli ne ( Da y 1), 2 bi o psies are t o be ta k e n fr o m t he sa me areas a n d acc or di n g t o t he sa m e 
criteria as t he s ki n s wa bs (see Secti o n 1 1. 6. 2 ): 
 1 bi o ps y fr o m a re prese nt ati ve lesi o nal area, fr o m t he d orsal si de of t he h a n d , wrist, or 
fi n ger. 
 1 bi o ps y fr o m a n o n -lesi o nal area at a n a nat o micall y si milar site t o t he lesi o nal bi o ps y. 
If a n a n at o micall y si milar n o n-lesi o nal area ca n n ot be f o u n d, t his bi o ps y m a y b e 
o mitte d.  
T he t hir d bi o ps y s h o ul d be ta ke n at Wee k 1 6. T he area fr o m w hic h t he t hir d bi o ps y will be 
ta ke n is t o be s pecifie d at baseli ne. T his m ust be at a n a nat o micall y si milar site a n d of si milar 
baseli ne lesi o n se verit y t o t he baseli ne lesi o nal bi o ps y. 
It will be rec or de d i n t he e C R F if t he bi o psies w ere ta ke n a n d fr o m w hic h l ocati o n ( d orsal 
ha n d, d orsal wrist, or  fi n ger); if bi o psies were n ot ta ke n a n d t he s u bject has gi ve n c o nse nt t o 
bi o psies , a c o m me nt will be p r o vi de d. 
A c hec k of s ki n bi o ps y w o u n d heali n g i n cl 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 ne xt trial visit as s pecifie d i n t he sc he d ule of trial pr oce d ures  (Secti o n 4 ). 
T he bi o psies will be s u b mer g e d i n 1 0 % f or mali n i m me diatel y after ac q uisiti o n a n d s hi p pe d t o 
t he ce ntral la b orat or y f or f urt her pr ocessi n g. F urt h er i nstr ucti o ns f or c ollecti o n, ha n dli n g, a n d 
s hi p me nt f or s ki n bi o ps y sa m ples are pr o vi de d i n a la b orat or y ma n ual . 
It is rec o m me n de d to d oc u me nt  t he bi o psie d areas wit h p h ot o gra p hs ta k e n b ef ore bi o ps yi n g 
a n d i m me diatel y after, b ot h at baseli ne a n d at Wee k 1 6, usi n g di gital p h ot o gra p h y 
assess me nts . T his will ser ve b ot h as a d o c u me ntati o n of t he bi o ps y site a n d t o s h o w disease 
pr o gressi o n o ver ti me. T his p h ot o gra p h y c o m p o ne nt f or t he s ki n bi o psies is rec o m me n de d 
a n d n ot ma n dat or y . 


Trial I D: L P 0 1 3 3 -1 2 7 3  
Date: 0 7 -Dec -2 0 1 8  
Versi o n: 3. 0  
P a ge 8 0  of 1 2 8  
 
 
 
T he trial sites partici pati n g i n t his p h ot o gra p h y c o m p o ne nt will  be e x pecte d t o  use t heir o w n 
e q ui p me nt t o ta ke t he p h ot o gra p hs. I nstr ucti o ns a n d s pecificati o ns f or p h ot o gra p h y will be 
pr o vi de d i n a  p h ot o gra p h y ma n u al.  
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 visit n u m ber a n d 
will b e tra ns mitte d electr o nicall y usi n g a s ec ure file tra nsfer pr ot oc ol . 
Pri nte d c o pies of t he p h ot o gra p hs m ust be i ncl u d e d as part of t he i n di vi d ual s u bject s o urce 
d oc u me ntati o n.  
L E O m a 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 mil ar t y pes of 
i nf or mati o n material or me dia tar geti n g patie nts a n d healt hcare pr ofessi o n als. 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 u cati 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 p r otecte d t o t he e xte nt p ossi ble. 
1 1. 6. 4  Fil a g gri n m ut ati o ns  
A  bl o o d sa m ple will be c ollecte d at baseli ne  ( Da y 1) f or meas ure me nt of fila g gri n m utati o nal 
stat us. 
1 1. 6. 5  N o n -i n v asi ve me as ure me nts of ski n b arrier f u ncti o n  (selecte d tri al 
sites) 
T he s ki n barrier f u ncti o n will be meas ure d usi n g n o n -i n vasi ve or mi ni mall y i n vasi ve 
tec h ni q ues at selecte d sites o nl y. T he sites partici p ati n g i n t hese meas ure m e nts will be defi ne d 
pri or t o trial start. T h us, t he bel o w meas ure me nts are n ot ma n dat or y, b ut will be i ncl u de d o nl y 
as a gree d wit h i n di vi d ual sites. 
Tra ns e pi der mal w ater l oss, s ki n ca pacita n ce, s ki n p H, a n d nat ur al m oist urisi n g fact ors will be 
meas ure d at t he ti me p oi nts s pecifie d i n t he sc he d ule of trial pr oce d ures ( Secti o n 4 ) fr o m a 
re pres e ntati ve lesi o nal area fr o m t he d orsal si de of t he ha n d or fi n gers  or  fr o m t he wrist . 
T he sa me meas ure me nts will be perf or me d b ot h o n t he site of t he lesi o nal  bi o ps y a n d o n a 
n o n -lesi o nal area w hich is  a nat o micall y si milar t o t he lesi o nal bi o ps y  site. If p ossi ble, t he 
sa me area sele cte d f or s wa bs s h o ul d als o be use d f or t hese meas ure me nts. If a n a nat o micall y 
si milar n o n-lesi o nal area ca n n ot be f o u n d o n t he ha n ds , t he v olar f orear m  ma y b e us e d 
i nstead . 
T he meas ur e me nts will be re peate d o n b ot h t he lesi o nal a n d n o n -lesi o nal areas at t he ti me 
p oi nts s pecifie d i n t he sc he d ule of trial pr o ce d ures ( Secti o n  4 ). 


Trial I D: L P 0 1 3 3 -1 2 7 3  
Date: 0 7 -Dec -2 0 1 8  
Versi o n: 3. 0  
P a ge 8 1  of 1 2 8  
 
 
 
S u bjec ts will be i nstr ucte d n ot t o a p pl y a n y e m ollie nts o n  t heir ha n ds a n d wrist s f or at least 
1 2  h o u rs pri or t o t he visits, a n d n ot t o was h t heir h a n ds or use d isi nfecta nts / ha n d sa nitizer f or 
at least 1  h o ur pri or t o t h e visits  at w hic h t hese meas ure m e nts will be ta ke n . T he ti me fr o m 
last I M P a p plicati o n t o s ki n barrier meas ure m e nt will be rec or de d. F urt her i nstr ucti o ns f or 
t hese meas ur e me nts are pr o vi de d i n a la b orat or y ma n ual. 
1 1. 7  Ot her assess me nts  
1 1. 7. 1  P atie nt -re p orte d o utc o mes  ( P R Os) 
Eac h s u bject m ust ma ke i n di vi d ual assess me nts  rel ati n g t o t heir perce pti o n of t heir disease 
a n d q ualit y of lif e. T hes e will be perf or me d  pri or t o t he i n vesti gat or p e rf or mi n g his/ her 
efficac y assess me nts.  At t he scree ni n g visit, t he s u bject’s eli gi bilit y n ee ds t o be esta blis he d 
bef ore t h e P R Os ca n be c o m plete d.  
T he s u bjects will recei ve a n e Diar y d e vice a n d e Di ar y trai ni n g, as well c o m plete all of t he 
P R Os,  at t he scree ni n g visit ( mi ni m u m 7 da ys bef ore baseli ne [ D a y 1] ) a n d start c o m pleti n g 
t he e Diar y. 
O ne P R O will be assesse d dail y usi n g a n e Diar y:  
 C hr o nic Ha n d Ecze ma S y m pt o m Diar y ( H E S D ) 
T he s u bjects m ust c o m plete t he H E S D eac h da y i n t he e ve ni n g , a n d c o m plia nce wit h t he 
e Diar y c o m pleti o n will b e re vie we d b y t he trial sit e staff t hr o u g h o ut t he tri al. 
I n a d diti o n, 7  P R Os will be c o m plete d  i n a n electr o nic de vice b y t he s u bjects at t he trial sites  
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 ) i n t he f oll o wi n g or der: 
 C hr o nic Ha n d Ecze ma I m pact Scale ( H EI S ) 
 Patie nt ’s Gl o bal Assess m e nt (Pa G A ) 
 Patie nt Gl o bal I m pr essi o n of C ha n ge ( P GI -C)  
 Der mat ol o g y Life Q u alit y I n d e x ( D L QI ) 
 E ur o Q o L 5 -di me nsi o n healt h q uesti o n naire 5 -le vel (E Q -5 D -5 L ) 
 Q ualit y of Lif e i n Ha n d Ecze ma Q uesti o n naire ( Q O L H E Q ) 


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 Wor k Li mitati o n Q uesti o n naire ( W L Q ) 
1 1. 7. 1. 1  C hr o nic H a n d Ecze m a S y m pt o m Di ar y ( H E S D)  
S u bjects will assess t he w orst se verit y of 1 1  s y m pt o ms of c hr o nic ha n d ecze ma (itc h, b ur ni n g 
feeli n g, pai n, crac ki n g, re d ness, dr y ness, s welli n g, blee di n g, t hic k e ni n g, fla ki n g, 
o ozi n g/ wee pi n g ) o ver t he past 2 4 h o urs usi n g a n 1 1 -p oi nt N R S wit h 0 i n dicati n g e. g., ‘n o itc h ’ 
a n d 1 0 i n dicati n g ‘se vere itc h’/‘w orst itc h i ma gi na ble ’. S u bjects will c o m plete t he H E S D as 
a n e Diar y eac h e veni n g  at t he latest fr o m Wee k -1 u ntil Wee k 1 6  (see Secti o n 4 ). 
1 1. 7. 1. 2  C hr o nic H a n d Ecze m a I m p act Sc ale ( H EI S)  
T he H EI S i ncl u des 9  ite ms a d dressi n g t h e s u bject ’s perce pti on of t h e i m pact of ha n d ecze ma 
o n t heir dail y acti vities, e m oti o nal well bei n g, slee p, a n d w or k o ver t he past  7  da ys. E ac h ite m 
is sc ore d o n a 5-p oi nt scale ( 0 = ‘n ot at all ’, 1 =‘a little’, 2 =‘m o der atel y’, 3 =‘a l ot’, 
4 = ‘e xtre mel y’). T h e t otal sc ore is t he s u m of t he 9  ite ms. T he  hi g h est p ossi ble sc ore is 3 6  a n d 
a hi g h sc ore is  i n dicati ve of a hi g h i m pact. D o mai n sc ores ca n be calc ulate d f or dail y 
acti vities ( 4  ite ms), e m oti o nal well bei n g ( 3 ite ms), slee p ( 1 ite m), a n d w or k ( 1 ite m). T he 
H EI S 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 i n 
Secti o n 4 . 
1 1. 7. 1. 3  P atie n t’s Gl o b al Assess me nt ( P a G A) 
S u bjects will ma ke a gl o bal assess me nt of t he se v erit y of  t heir ha n d ecze m a acc or di n g t o t he 
sc he d ule of trial pr oce d ures i n Secti o n 4 . T he ass ess me nt will be ma de usi n g a 5 -p oi nt scale  
( 0 =‘cl ear ’, 1 =‘al m ost clear ’, 2 =‘mil d ’, 3 =‘m o derate ’, 4 =‘se vere’) a n d will be base d o n t he  
se verit y of t heir h a n d ecz e ma  at t he ti me of t he  assess me nt . T he Pa G A 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 tri al pr oce d ures i n Secti o n 4 . 
1 1. 7. 1. 4  P atie nt Gl o b al I m pressi o n of C h a n ge ( P GI -C)  
T h e P GI-C is a 1 -ite m q u esti o n naire desi g ne d t o assess t he s u bject’s i m pressi o n of c ha n ges 
(2 1 ). T he s u bjects ha ve t o select t he o ne res p o nse fr o m t he res p o ns e o pti o ns (‘m uc h better ’,  
‘a little better’, ‘n o c ha n ge ’, ‘a little w orse ’, or ‘m uc h w orse ’) t hat best des cri bes t he o verall 
c ha n ge i n t heir c hr o nic h a n d ecze ma si nce t he y st arte d I M P treat me nt. T he P GI -C will be 
c o m plete d at t he trial site acc or di n g t o t he s c he d ul e of trial pr oce d ures i n Secti o n 4 . 
 


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1 1. 7. 1. 5  Der m at ol o g y Life Q u alit y I n de x ( D L QI)  
D L QI is a vali date d q u esti o n naire wit h c o nte nt s p ecific t o t h ose wit h der m at ol o g ical 
c o n diti o ns. It c o nsists of 1 0 ite ms a d dressi n g t h e 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 u alit y of life o ver t he last w ee k . T hese i ncl u de  
der mat ol o g y -rel ate 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 (1 4 ). Eac h ite m is sc ore d o n a 4-p oi nt scale ( 0  =  ‘n ot at all ⁄n ot 
rele va nt’; 1 =  ‘a li ttle’; 2 =  ‘a l ot’; 3 =  ‘v er y m uc h ’). T he t otal sc ore is t he s u m of t he 
1 0  ite ms. T he hi g h est p ossi ble sc ore is 3 0 a n d 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 h e d ule of trial pr oce d ures 
i n Secti o n 4 . 
1 1. 7. 1. 6  E ur o Q o L  5 -di me nsi o n he alt h q uesti o n n aire 5 -le vel ( E Q-5 D -5 L)  
E Q -5 D -5 L is a sta n dar dis e d meas ur e of healt h stat us de vel o pe d b y t he E ur o Q o L  gr o u p  t o 
pr o vi de a si m ple, ge neric meas ure of healt h f or cli nical a n d ec o n o mic a p praisal ( 1 5 ). T h e 
E Q -5 D -5 L is a self -a d mi nistere d q uesti o n naire us e d t o assess healt h s tat us ‘t o da y’ a n d is 
di vi de d i nt o 2  secti o ns: t he first secti o n i ncl u des 5 di me nsi o ns ( m o bilit y, s elf -care, us ual 
acti vit y, p ai n/ disc o mf ort, a n d a n xiet y/ de pressi o n); eac h di me nsi o n will be assesse d b y t h e 
s u bject usi n g a 5-p oi nt scale (‘n o pr o bl e ms ’, ‘sli ght pr o ble ms ’, ‘m o derat e pr o ble ms ’, ‘se vere 
pr o ble ms ’, a n d ‘e xtre me pr o ble ms ’). T he s ec o n d s ecti o n c o nsists of a vertical vis ual a nal o g ue 
scale a n c h ore d at 0 (‘t he w ors t healt h y o u ca n i ma gi ne’) a n d 1 0 0 (‘t he be st healt h y o u ca n 
i ma gi ne’). T he E Q -5 D -5 L will  be c o m plete d a t t h e trial site acc or di n g t o t he sc he d ule of trial 
pr oce d ures i n Secti o n  4 . 
1 1. 7. 1. 7  Q u alit y of Life i n H a n d Ecze m a  Q uesti o n n aire ( Q O L H E Q ) 
Q O L H E Q  is a v ali date d q uesti o n naire use d t o ass ess disease-s p ecific h ealt h-relate d q u alit y of 
life i n s u bjects wit h ha n d ecze ma (1 6 , 1 7 , 1 8 , 1 9 ). It c o nsists of  3 0 ite ms  a n d assesses diseas e -
relate d i m pair me nt o ver t he last 7  da ys wit hi n  4  d o mai ns : (i) s y m pt o ms, (ii) e m oti o ns, (iii) 
f u ncti o ni n g, a n d (i v) treat me nt/ pre ve nti o n. Eac h it e m is sc ore d o n a 5 -p oi nt scale (‘n e ver ’, 
‘rarel y’, ‘s o meti mes’, ‘ofte n ’, ‘all t he ti me’). T h e t otal sc ore as well as s u m mar y s c ores f or 
eac h d o mai n is calc ulat e d. A hi g h sc ore is i n dicati ve of a hi g h i m pact o n healt h -relate d q u alit y 
of life. T he Q O L H E Q  will be c o m plete d at t he trial site acc or di n g t o t he sc h e d ule of trial 
pr oce d ures i n Secti o n  4 . 
1 1. 7. 1. 8  Wor k Li mit ati o n Q uesti o n n aire ( W L Q)  
W L Q is a vali date d q u esti o n naire t o meas ure t he de gree t o w hi c h healt h pr o ble ms i nterfere 
wit h s pecific as pects of j o b perf or ma n ce a n d t he pr o d ucti vit y i m pact of t hese w or k 


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li mitati o ns (2 0 ). It as ks s u bjects t o rate t heir le v el of diffic ult y or a bilit y t o perf or m 
2 5  s pecific j o b de ma n ds i n t he last 2 wee ks. Res p o nses t o the 2 5 ite ms are c o m bi ne d i n t o 
4  w or k li mitati o n scales: ti me ma na ge me nt, p h ysical de ma n ds, me ntal/i nter pers o nal, a n d 
o ut p ut de ma n ds. T hese ca pt ure t he m ulti di me nsi o nalit y of j o b r oles a n d als o reflect a n 
i m p orta nt c haracteristic of ma n y c hr o nic ill nesses, i n t hat t he y ma y res ult i n li mitati o ns i n 
perf or mi n g s o me acti vities b ut n ot ot hers. Scale s c ore ra n ge fr o m 0 (‘li mite d n o ne of t he 
ti me’) t o 1 0 0 (‘li mite d all t he ti me’). T he W L Q will be c o m plete d at t he trial site f or s u bjects 
wit h a pai d j o b acc or di n g t o t he sc he d ule of trial pr o ce d ures i n Secti o n  4 . 
1 1. 8  Esti m ate 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 o c he mistr y, ser ol o g y, P K , fila g gri n, a n d 
pre g na nc y t est. T he t otal v ol u me of bl o o d t o be dra w n in t he trial i s a p pr o xi matel y 4 0  m L . 
1 1. 9  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 per ma n e ntl y 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: 
 W het her t he s u bject c o m plete d t he trial.  
 L ast trial site visit  or c o ntact  f or w hic h d ata is rec or de d. 
 D ate a n d ti me of last a p plicati o n  of I M P . 
 P ri mar y reas o ns f or disc o nti n uati o n of I M P, wit h dra wal fr o m trial, a n d n ot 
atte n di n g pri mar y e n d p oi nt visit , if a p plica ble (lac k of efficac y, A E, wit h dr a 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 h e n t he s u bject s ha ve  ha d t h eir last visit  (at t he earl y 
ter mi nati on 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. 1 0  
St or a ge of b i ol o gic al sa m ples  
Fila g gri n a n d P K  sa m ples ( bl o o d) a n d s ki n bi o psies will be retai ne d f or as l o n g as t he q u alit 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 f or f ut ure 
researc h (s ee bel o w). 


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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 gi cal sa m ples. I f c o nse nt is 
gi ve n b y t he s u bject, L E O will st ore 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 p erf or me d b y L E O or ma y be gi ve n t o aca d e mic part ners t o be use d f or 
f ut ure res earc h i n c hr o ni c ha n d ecze ma a n d relate d diseases. D o nati o n of t he sa m ples f or 
f ut ure res earc h is v ol u ntar y a n d s u bjects m ust gi v e 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  h ere 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 d ate 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 h e s a 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  
T his is a m ulti -ce ntre, ra n d o mise d, ve hicle -c o ntr olle d, d o u ble -bli n d, parall el -gr o u p 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 trial will be c o n d uct e d at m ulti ple trial sites l ocate d b ot h i n E ur o pe a n d i n N ort h A meric a. 
Hi g h -q u alit y trial sites wit h s hare d sta n dar ds of practice a n d val ues will be sele cte d; all trial 
sites f oll o w t he gl o ball y acce pte d g ui deli nes f or dia g n osis, pre ve nti o n, a n d treat me nt of ha n d 
ecze ma (1 ). 
Patie nts wit h ha n d ecze ma re prese nt a heter o ge ne o us patie nt p o p ulati o n as ha n d ecze ma is 
ass ociate d wit h differe nt aeti ol o gies a n d m or p h ol o gies a n d t h e se verit y ma y ra n ge fr o m mil d 
t o se vere. To miti gate a n y  p ote ntial differe nce i n trial o utc o me base d o n b aseli ne 
c haracteristics, t he trial s u bjects will be ra n d o mise d i n stratifie d ma n ner as descri be d i n 
Secti o n 9. 3 . T h e ra n d o misati o n will mi ni mise selecti o n bias  a n d mi ni mise i nfl ue nce of 
(i ntri nsic) c o nf o u n di n g fact ors a n d t he stratificati o n will  e ns ure a certai n b ala nce of t he 
treat me nt gr o u ps wit h res pect t o disease se v erit y a n d re gi o n . T he e nr ol me nt is c o ntr olle d b y 
d isease se verit y t o all o w f or assess me nt of c o -vari a bilit y  i n patie nts wit h mil d, m o derate, a n d 
se vere dise ase state. 
T he i ncl usi o n of 4  acti ve treat me nt gr o u ps wit h 1, 3, 8, a n d 2 0  m g/ g of d el g ociti ni b  crea m a n d 
a ve hicle c o ntr ol gr o u p is c o nsi dere d e n o u g h t o esta blis h a  d ose -res p o nse si g nal. T h e ve hicl e 
c o ntr ol gr o u p will ser ve as refere n ce a n d has bee n a d de d t o esta blis h t he efficac y a n d s afet y 
of del g o citi ni b  crea m  i n a bli n de d trial desi g n. 
T he trial e n d p oi nts ha ve bee n sele cte d t o e val u ate t he ef fi cac y of del g ociti ni b  i n i m pr o vi n g 
t he se verit y a n d e xte nt of c hr o nic ha n d ecze ma. B ot h I G A a n d H E C SI  will be use d i n t his 
cli nical trial as i n vesti gat or-rate d assess me nts of disease se verit y. T h e I G A is a n assess me nt of 
t he o verall diseas e se verit y at a gi v e n ti me p oi nt a n d is base d o n a 5 -p oi nt s cale des cri bi n g t he 
se verit y of t he dise ase fr o m “clear ” t o “se v ere”. T he H E C SI is an i nstr u me nt use d t o  sc ore 
b ot h t he e xte nt a n d t he i nte nsit y of t he dise ase. T h e pri mar y e n d p oi nt of t he trial is t o e val uate 
t he perce nta ge of s u bjects ac hie vi n g treat me nt s uc cess defi ne d as a n I G A s c ore of 0 (clear) or 
1  (al m ost clear) wit h at least a 2-ste p i m pr o ve me nt fr o m baseli ne t o Wee k 1 6.  T he trial 
e n d p oi nts will als o a d dress s u bject ’s perce pti o n of disease se verit y a n d t he i m pact o n slee p, 
dail y acti vit y, a n d healt h -relate d q ualit y of life. 


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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 d verse e ve nts ( A E s) a n d seri o us a d verse e v e nts ( S A Es) are defi ne d i n  A p pe n di x 1 . 
Classificati o n of A E s i n t er ms of se verit y, ca usalit y a n d o ut c 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 eve nt  re p ort s 
A Es m ust be c ollecte d fr o m ti me of first trial -relat e d acti vit y after t h e s u bject has si g n e d t he 
i nf or me d co nse n t for m  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. 
A Es m ust be assesse d b y me dicall y q u alifie d pers o n nel.  
At all visits / p h o ne call, 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 x a m ple : “H o w ha v e y o u felt si nce I s a w y o u last?” N o s pecific s y m pt o ms 
s h o ul d be as ke 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 h ese c ha n ges.  If a s u bject re p orts a n A E 
d uri n g t he p h o n e call o n Da y  4 , it is u p t o t he i n vesti gat or’s discreti o n t o perf or m a n 
u nsc he d ule d visit.  
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 eve nts  
A E s 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 eC R F a n d s h o ul d be descri b e 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 h at is, n ot necessaril y t he e x act 
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 x a m ple ‘aller gic c o nt act der matitis ’). 
F or c uta n e o us A Es t he l oc ati o n m ust be part of t he A E d escri pti o n a n d ma y be d escri b e d as 
e. g., t h e face, scal p, bac k, c hest, ar m, le g, tr u n k, o r li m b. A d diti o nall y, t he l ocati o n s h o ul d be 
descri be d usi n g t he f oll o wi n g ter mi n ol o g y:  
 Lesi o n al/ perilesi o nal ( ≤2  c m fr o m t he b or der of lesi o n(s) treate d wit h I M P) . 
 Dista nt ( > 2 c m fr o m t he l esi o n b or der). 


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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 dat e of t he e ve nt (it will 
als o be rec or de d if t h e e v e 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 start of I M P. 
A Es m ust be classifie d i n ter ms of se verit y, ca us alit y a n d o utc o m e 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 IM P  as a c o nse q u e nce of t he A E m ust  be 
rec or de d (d ose n ot c ha n ge 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:  an 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 n e, 
c o nc o mita nt me d icati 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 orti n g of seri o us a d verse e ve nts 
T he criteri a t hat defi ne a n A E as seri o us ( t hat is, a n S A E) are d efi 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 for 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 ort e d t o L E O o n t he ( pa p er) S A E for 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 m e nt of a vaila ble i nf or mati o n o n seri o us ness, 
se verit y, ca usal r elati o ns hi p t o t he I M P or trial pr oce d ure, t h e acti o n ta ke n, t he o utc o me t o 
date, a n d a n arrati ve descri pti o n of t he c o urse of t h e e ve nt.  
T he c o m plete d S A E f or m m ust be fa x e d or sca n ne d a n d e -m aile d t o Gl o bal 
P har mac o vi gila nce at  L E O usi n g t he e-mail a d dress or fa x n u m ber bel o w : 
Gl o bal P har mac o vi gila nce at  L E O  
E -mail a d dress: dr u g.safet y @le o -p h ar ma. c o m  
Fa x n u m ber: + 4 5 7 2 2 6 3 2 8 7  
If rele v a 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 di a g n ostic pr oce d ures, h os pital rec or ds, a ut o ps y re p orts , etc. 


Trial I D: L P 0 1 3 3 -1 2 7 3  
Date: 0 7 -Dec -2 0 1 8  
Versi o n: 3. 0  
P a ge 8 9  of 1 2 8  
 
 
 
A d diti o n all y, Gl o bal P har mac o vi gila nce 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 h e 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 o tif 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 w e ver, s u c h e ve nts s h o ul d be re p orte d t o  Gl o bal P har mac o vi gila nce  at L E O ( see 
c o ntact details a b o v e ) if t he i n vesti gat or bec o m es a ware of t he m. 
1 3. 4. 2  L E O r e p orti n g res p o nsi bilities  
Gl o bal P har mac o vi gila nce 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 n ce safet y inf or m ati o n d oc u me nt f or t his cli nical trial is: 
F or t he I M P, t he I n v esti gat or ’s Br oc h ure, e diti o n 1  a n d s u bse q ue nt u p dates  m ust be use d.  
Gl o bal P har mac o vi gila nce at L E O will n otif y t h e re g ul at 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 gis lati o n f or t h e c o ncer ne d 
c o u ntries. 
T he I R B(s)/I E C(s) will b e n otifie d of S A Es acc or di n g t o t he c urre nt a p plica ble le gis lati 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 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 pect e 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 r e g ul at or y a ut h orities  a n d I E C(s)/I R B(s) 
acc or di n g t o t he c urre nt a p plica ble le gis lati 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 b asis.  
F or t he U S, t he f oll o wi n g re p ortin g re q uir e me nts a p pl y: a ll S A Es w hic h are assesse d as 
ca usall y rel ate d t o t he I M P b y L E O  ( G ui da nce f or I n d ustr y a n d I n vesti gat ors - Safet y 
Re p orti n g Re q uir e me nts f or I N Ds a n d B A/ B E St u dies ; G ui da nce f or Cli nical I n v esti gat ors, 
S p o ns ors, a n d I R Bs: A d v erse E ve nt Re p orti n g t o I R Bs –  I m pr o vi n g H u ma n S u bject 
Pr otecti o n ) a n d w hic h are u ne x pecte d ( Seri o us a n d U ne x pecte d S us pecte d A d verse Reacti o ns 
[I N D safet y re port] ) 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 I R B(s). 
I n v esti 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: L P 0 1 3 3 -1 2 7 3  
Date: 0 7 -Dec -2 0 1 8  
Versi o n: 3. 0  
P a ge 9 0  of 1 2 8  
 
 
 
1 3. 5  Ot her  eve nts t h at re q uire e x pe dite d re port i n g 
1 3. 5. 1  Pre g n a nc y  
A n y pre g na n c y  occ urri n g d uri n g t he cli nical trial m u st 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 the ( pa per) Pre g na n c y F or m ( Part  I). All pre g na n cies m ust be f oll o we d 
u p u ntil deli ver y or t er 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 n a nc y F or ms m ust be fa x e d or sca n ne d  a n d e-m ail e d t o Gl o bal 
P har mac o vi gila nce at L E O . C o ntact details are gi v e n i n Secti o n  1 3. 4. 1 . 
Pre g n a 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 5  is c o nsi dere d a n a d verse e ve nt of s p ecial i nterest i n t his trial a n d 
will re q uire t hat t he i n vesti gat or pr o vi d es a d diti o nal details t o be rec or de d i n t he e C R F. A n 
a d verse e ve nt of s p ecial i nterest 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 1 5 : A d vers e e ve nt of s peci al i nterest 
A d verse e v e 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 petic 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 m a/ 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: L P 0 1 3 3 -1 2 7 3  
Date: 0 7 -Dec -2 0 1 8  
Versi o n: 3. 0  
P a ge 9 1  of 1 2 8  
 
 
 
1 3. 6. 2  O ver d ose  
A n o ver d ose is defi ne d as a s u bject us i n g m or e t h a 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 acci de ntal or i nte nti o nal.  
T he ter m ‘o ver d ose ’ i n cl u di n g a s p ecificati o n of w h y it occ urre d ( acci de nt al or i nte nti o nal ) 
m ust be d oc u me nte d o n t he A E  f or m of  t he eC R F . I n a d diti o n, A Es ori gi nati n g fr o m a n 
o ver d ose m ust be d oc u m e nte d  o n a se p arat e li ne.  If t he A E ori gi n ati n g fr o m t he o ver d ose 
q ualifies as a n S A E, e x pe dite d re p orti n g is re q uir e d ( Secti o n 1 3. 4 ). 
1 3. 6. 3  Me dic ati o n e rr 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 di cati 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 he me dicati o n err or cat e g or y m ust be d oc u me nt e d o n t he A E  f or m i n t he eC R F . I n a d diti o n, 
A Es ori gi n ati n g fr o m a me dicati o n err or m ust be d oc u me nte d o n a se p arate li ne.  If t he A E 
ori gi nati n g fr o m t h e m e dicati o n err or q u alifies as a n S A E, e x pe dite d re p orti n g is re q uir e d 
(S ecti 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 d oc u me nte d o n t he A E  f or m i n t he eC R F . I n a d diti o n, A Es 
ori gi nati n g fr o m mis use m ust be d oc u me nte d o n a se parat e li ne.  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 relat es t o t he s p or a dic or persiste nt, i nte nti o nal e x cessi ve use of a n IM P  w hi c h is 
acc o m pa ni e d b y har mf ul p h ysical or ps yc h ol o gical effects.  
T he ter m ‘a b us e’ m ust be d oc u me nte d  o n t he A E  f or m i n t he eC 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  d oc u me nte d o n a s e parat e li ne.  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: L P 0 1 3 3 -1 2 7 3  
Date: 0 7 -Dec -2 0 1 8  
Versi o n: 3. 0  
P a ge 9 2  of 1 2 8  
 
 
 
1 3. 6. 6  A g gr a v ati o n of co 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 di cal c o n diti o n(s)  
(i ncl u di n g t he tri al diseas e), c o m pare d t o scree ni n g, m ust be re p orte d as a n ( S)A E  i n 
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 eve nts  
D uri n g t h e 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 le a 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 bly / pr o ba bly  rel ati 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 h e e n d of t he cli nical trial . F or S A Es w hi c h ha ve sta bilise d a n d ca n n ot be e x p ecte d t o 
res ol ve d uri n g t he trial or t he safet y f oll o w-u p p eri o ds, f or e x a m ple c hr o nic or sta bilise d 
c o n diti o ns , ‘n ot re s ol ved ’ is acce pte d as a fi n al o utc o me a n d a stat e 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 i n t he  S A E f or m. 
1 3. 8  H a n dli n g of a n u r ge nt safet y m e as ure 
A n u r ge nt safet y m eas ur e 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. ” (2 2 ). 
If t he i n vesti gat or bec o m es 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 h alt 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 va l fr 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 nt acti 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 h e 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 d ecisi o n ma ki n g pr ocess l ea 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 otifi cati 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: L P 0 1 3 3 -1 2 7 3  
Date: 0 7 -Dec -2 0 1 8  
Versi o n: 3. 0  
P a ge 9 3  of 1 2 8  
 
 
 
1 4  St atistic al m et h o ds 
1 4. 1  S a m ple size 
A t otal of 2 5 0 s u bjects will be di vi de d i nt o 5  treat me nt gr o u ps a n d ra n d o mis e d 1: 1: 1: 1: 1 t o 
o ne of eac h d ose le v el of del g o citi ni b  crea m ( 1, 3, 8, or 2 0 m g/ g) or del g ociti ni b  crea m 
ve hicle.  
T he sa m ple siz e is base d o n t he f oll o wi n g pair wise c o nsi derati o n, e ve n t h o u g h t he pri mar y 
o bjecti ve of t he trial is t o esta blis h t he d ose -res p o nse relati o ns hi p. Wit h a si g nifica n ce le vel of 
5 % w he n c o m p ari n g 2  tr eat me nt gr o u ps a n d ass u mi n g treat me nt s u ccess r ates (acc or di n g t o 
I G A) of 45 % a n d 1 5 %, res pecti vel y of t he i n v esti gati ve tr eat me nt gr o u p ( d el g o citi ni b  crea m) 
a n d del g o citi ni b crea m  ve hicle, t he n 5 0  s u bjects p er treat me nt gr o u p will pr o vi de a p o wer 
sli g htl y a b o v e 9 0 % f or fi n di n g si g nifica ntl y differe nt s uccess rates bet w ee n treat me nt gr o u ps. 
1 4. 2  Tri al a n al ysis sets 
All scree n e d s u bjects will be acc o u nt e 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 a n d will be a nal ys e d f or 
efficac y p ara met ers u p t o Wee k 1 6 . E x cl usi o ns fr o m t he f ull a nal ysis set ca n be c o nsi dere d i n 
s pecial cas es as des cri be d i n I C H E 9, S ecti o n 5. 2. 1., F ull A nal ysis Set. If  it is deci de d t o 
e x cl u de a ra n d o mise d s u bject fr o m t he f ull a n al ysis set, a j ustificati o n a d dressi n g I C H E 9 will 
be gi v e n.  
A per pr ot oc ol a nal ysis s et will be defi ne d b y e x cl u di n g s u bjects fr o m t he f ull a nal ysis set 
w h o f ulfil a n y of t he f oll o wi n g criteri a:  
 Di d n ot r ecei ve treat me nt wit h t he I M P.  
 Di d n ot p r o vi de I G A or H E C SI dat a f oll o wi n g st art of treat me nt.  
 Are k n o w n t o ha v e ta ke n t he wr o n g I M P t hr o u g h o ut t he treat me nt peri o d  of t he 
trial. 
 D i d n ot f ulfil t he disease defi ni n g i ncl usi o n criteri a (t hat is, i ncl usi o n criteria 3 , 
4, a n d 5 ). 
 Di d n ot a p pl y I M P at least 8 0 % of t he ti me i n t he peri o d fr o m date of first 
a p plicati o n of I M P t o dat e of last a p plicati o n of I M P.  
A safet y a nal ysis set will be defi ne d b y e x cl u di n g s u bjects fr o m t he f ull a nal ysis set w h o 
recei v e n o treat me nt wit h I M P.  


Trial I D: L P 0 1 3 3 -1 2 7 3  
Date: 0 7 -Dec -2 0 1 8  
Versi o n: 3. 0  
P a ge 9 4  of 1 2 8  
 
 
 
Base d o n t h e a b o ve r ules, t he decisi o ns re gar di n g i ncl usi o n/e xcl usi o n of s u bjects a n d/ 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 su bjects  
T he reas o ns f or per ma ne nt disc o nti n uati o n of I M P a n d 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 b y treat me nt gr o u p. 
1 4. 3. 2  De m o gr a p hics a n d o t her b aseli ne ch ar acteristics  
Descri pti ve statistics of d e m o gra p hics a n d ot h er baseli ne c haracteristics will be prese nte d f or 
all ra n d o mise d s u bjects b y treat me nt gr o u p. Pres e ntati o ns of de m o gra p hics , baseli ne disease 
se verit y, a n d pr o p orti o n of s u bjects wit h baseli ne w orst pr urit us ( wee kl y a vera ge) 
a b o ve/ bel o w 4  o n t he n u meric rati n g scale ( N R S) , i.e., o ne of t he s y m pt o ms ca pt ure d i n t he 
H E S D , will als o be gi ve n b y re gi o n a n d bas eli ne disease se verit y.  
De m o gra p h ics i ncl u d e a ge, se x, et h nicit y, a n d race . Ot her baseli ne c haracteristics incl u de vital 
si g ns, hei g ht, wei g ht, b o d y mass i n de x, t otal I g E , Fitz patric k s ki n t y pe, d urati o n a n d 
classificati o n  of c hr o nic ha n d ecze ma , c o nc urre nt dia g n oses (fr o m me dical hist or y a n d 
i n dicati o ns f or c o nc o mita nt me dicati o n), c o nc o mit a nt me dicati o n, a n d pre vi o us c hr o nic ha n d 
ecze ma treat me nts. 
1 4. 3. 3  E x p os ure a n d tre at me nt co m pli a nce  
T he d urati o n of e x p os ure t o treat me nt i n a s pecifi c visit i nter val will be calc ulate d as t he 
n u m ber of da ys fr o m dat e of first a p plicati o n of I M P i n t hat peri o d t o t he date of last 
a p plicati o n of I M P i n t hat peri o d, b ot h da ys i n cl u de d.  
E x p os ure t o treat me nt will be prese nte d f or t he safet y a nal ysis set as da ys of e x p o s ure per 
treat me nt gr o u p. 
Dr u g acc o u nta bilit y dat a will be calc ulate d b y s u btracti n g t he wei g ht of t h e use d t u bes fr o m 
t he mea n n or mal w ei g ht of f ull t u bes. Avera ge wee kl y/ bi -wee kl y a n d t otal usa ge will be  
prese nte d p er treat me nt gr o u p, res pecti vel y, b ot h f or ti me i nter vals bet wee n visits ( 1 or 2-
wee k peri o ds de pe n di n g o n t he ti me bet wee n site visits) a n d t otal peri o d . 
A d here n ce t o treat me nt r e 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 hes e will b e descri be d as pr ot oc ol de viati o ns.  


Trial I D: L P 0 1 3 3 -1 2 7 3  
Date: 0 7 -Dec -2 0 1 8  
Versi o n: 3. 0  
P a ge 9 5  of 1 2 8  
 
 
 
A d here n ce will be prese nte d f or t he safet y a n al ysis set f or eac h treat me nt gr o u p via t he 
perce nt a ge of a p plicati o ns misse d.  
1 4. 3. 4  Testi n g str ate g y  
T his is a d ose -ra n gi n g tri al wit h t he pri mar y o bjecti ve t o esta blis h t he d ose-res p o nse 
relati o ns hi p. F or t he pri mar y e n d p oi nt I G A T S  a n d t he sec o n dar y e n d p oi nt c ha n ge i n H E C SI 
fr o m baseli ne t o Wee k 1 6 , t he selecti o n of t he d ose-res p o nse m o del t hat fits data best will be 
c o ntr olle d usi n g a fa mil y -wise err or rate of 5 %. T here will be n o a dj ust me nt f or t he m ulti ple 
testi n g of pri mar y a n d sec o n dar y e n d p oi nts, all p-val ues will be c o nsi dere d n o mi nal.  
1 4. 3. 5  A n al ysis of pri m ar y effic ac y e n d p oi nt  
T he pri mar y e n d p oi nt I G A  T S  at Wee k 1 6 will be a nal ys e d f or t h e f ull a nal ysis set a n d f or t he 
per pr ot oc ol a n al ysis set. T he per pr ot o c ol a nal ysis is re gar de d as s u p p orti ve.  
I G A T S  refers t o I G A sc ore of 0 (clear) or 1 (al m ost clear) wit h ≥2 -ste p i m pr o ve me nt fr o m 
baseli ne.  
F or t h e a nal ysis  of t he pri mar y e n d p oi nt , s u bjects w h o i nitiate resc ue m e dicati o n bef ore 
Wee k  1 6 or wit h dra w fr o m t he trial a n d ha ve n o retrie ve d data at Wee k 1 6, will all be 
c o nsi dere d n o n -res p o n d ers. 
T he M ulti ple C o m paris o n Pr oce d ure –  M o d elli n g ( M C P -M o d) a p pr oac h (see e. g., E M A 
Q ualificati o n O pi ni o n of M C P -M o d [ 2 3 ] or Bretz et al [2 4 ] f or f urt her details of t he 
fra me w or k) will be use d t o g ui de d ose s electi o n. T he d ose-res p o nse relati o ns hi p f or t he 
bi nar y e n d p oi nt I G A T S  will be m o delle d b y t he f oll o wi n g 3 i de ntifie d ca n di date m o dels. 
T hese ca n di date m o dels are sel ecte d b ase d o n  t he e x pecte d d ose -res p o nse. 
Li ne ar i n l o g: E 0 + δ ×  l o g( d + c), 
E ma x : E0 + E ma x  ×  d / ( E D 5 0 + d),  
Si g m oi d E ma x : E0 + E ma x  ×  d h / ( E D5 0 h + d h), 
w here d is t he d os e (i ncl. ve hicle), E 0 is t he efficac y offset (a ntici pate d v e hicle effect), Ema x  is 
t he as y m pt otic ma xi m u m effect, E D5 0 is t he half-life val ue of Ema x , h is t he stee p ness at E D5 0, 
δ is t he sl o pe para met er, a n d c is a fi x e d offset p ara meter. 
T he m o dels will be a dj uste d f or t he stratificati o n varia bles re gi o n a n d bas eli ne I G A. T h e 
m o del para meters ( E D 5 0, h) will be pres pecifie d a pri ori b y s uita ble g u esses base d o n data 
fr o m J a pa n To bacc o ’s d ose-ra n gi n g trial Q B A 2-1  (2 5 ). A kai ke ’s I nf or mati o n Criteria will be 


Trial I D: L P 0 1 3 3 -1 2 7 3  
Date: 0 7 -Dec -2 0 1 8  
Versi o n: 3. 0  
P a ge 9 6  of 1 2 8  
 
 
 
use d as t he g o o d ness -of -fit criteri o n t hat will dri ve t he selecti o n of t he d ose-res p o nse m o del 
t hat fits data best w hile c o ntr olli n g the fa mil y -wis e err or rat e  at 5 %. Base d o n t he selecte d 
m o del , t he d ose-res p o ns e relati o ns hi p will be esti mate d a n d pres e nte d wit h  2 -si de d 9 5 % CI. If 
n o ne of t he ca n di date m o dels c o n ver ge, ot her p ossi bilities of m o dels a n d g o o d ness -of -fit 
criteria will be e x pl ore d.  T he d ose -res p o nse m o delli n g will be perf or me d  o n b ot h t he t otal 
p o p ulati o n a n d s u bjects ha vi n g a baseli n e I G A of 3 or 4 , i n or der t o f urt her e x pl ore 
heter o ge n eit y i n t he dise ase p o p ulati o n . 
I n a d diti o n t o t he d ose -res p o nse m o delli n g a p pr oac h, the differe n ce i n r es p o nse rates bet wee n 
t he del g o citi ni b d oses a n d ve hicle will be a n al ys e d se parat el y f or eac h of t he d ose gr o u ps 
usi n g t he C oc hra n -Ma ntel -Hae nszel test stratifie d b y re gi o n ( E ur o p e a n d N ort h A merica) a n d 
disease se verit y ( baseli ne I G A of 2, 3, a n d 4). T he n ull h y p ot hesis of n o differe nce i n res p o ns e 
rates bet w ee n del g o citi ni b  a nd ve hicle will be test e d a gai nst t he 2 -si de d alter nati ve t hat t here 
is a differe nce. 
Se nsiti vit y a n al ysis will be perf or me d as a p plica ble i n or der t o assess t he r o b ust ness of res ults 
of t he pri mar y a n al ysis wit h res pect t o t he retrie ve d data at Wee k 1 6 , use of resc ue 
me dicati o n,  a n d ass u m pti o ns re gar di n g missi n g d ata. T his will be descri be d i n f urt her detail i n 
t he statistical a nal ysis pla n. 
1 4. 3. 6  A n al ysis of sec o n d ar y effic ac y en d p oi nt s 
T he sec o n d ar y e n d p oi nts c ha n ge fr o m baseli ne  t o Wee k 1 6  i n H E C SI a n d ti me t o I G A T S  will 
be a nal yse d f or t he f ull a nal ysis set a n d f or t he per pr ot oc ol a nal ysis set. T he per pr ot o c ol 
a nal ysis is r e gar de d as s u p p orti ve.  
F or t he a nal ysis of t he c h a n ge fr o m b aseli ne t o Wee k 1 6 i n H E C SI, d ata c ollecte d aft er 
per ma ne nt disc o nti n uati o n of I M P or aft er i nitiati o n of resc u e me dicati o n will n ot be i ncl u de d 
i n t he a nal ysis. Missi n g d ata at Wee k 1 6 will be i m p ute d usi n g t he mi x e d m o del f or re p eate d 
meas ure me nts ( M M R M ) pre dicte d val u es fr o m t he bel o w s pecifie d m o d el f or re peate d 
meas ure me nts . 
T he d ose -res p o nse m o delli n g a p pr oac h s u g geste d f or t he pri mar y e n d p oi nt will als o be 
a p plie d f or t he c o nti n u o us e n d p oi nt c ha n ge fr o m baseli ne t o Wee k 1 6 i n H E C SI.  
I n a d diti o n t o t he d ose-res p o nse m o delli n g a p pr oac h, the c o nti n u o us e n d p oi nt will be 
a nal ys e d  usi n g  a M M R M  o n t he p ost baseli ne res p o nses u p t o Wee k 1 6 wit h a n u nstr uct ure d 


Trial I D: L P 0 1 3 3 -1 2 7 3  
Date: 0 7 -Dec -2 0 1 8  
Versi o n: 3. 0  
P a ge 9 7  of 1 2 8  
 
 
 
c o varia n ce matri x, Ke n w ar d -R o ger a p pr o xi mati o n t o esti mate de n o mi nat or de grees of 
free d o m, a n d t he mea n m o delle d as f oll o ws: 
C ha n ge fr o m bas eli ne i n H E C SI  
 
= treat me nt × visit + b aseli ne H E C SI × visit + re gi o n + baseli ne I G A  
T he esti mates will be prese nte d wit h n o mi nal p -val ues a n d 9 5 % CI at eac h visit. T he pri mar y 
c o m paris o n bet wee n eac h del g o citi ni b  d ose  a n d ve hicle will be at Wee k 1 6.  
Ti me t o I G A T S  res p onse  is defi ne d as t he ti me fr o m baseli ne t o first assess me nt of a n I G A 
T S . S u bjects will be ce ns ore d at t he dat e of t he last assess me nt visit or at i nitiati o n of resc ue 
me dicati o n, w hic he v er occ urs first. K a pla n -M eier c ur ves of ti me t o I G A T S  will be esti mate d 
a n d prese nt e d b y treat me nt f or t he f ull a nal ysis set. Treat me nt gr o u ps will be c o m pare d usi n g 
a 2-si de d l o g-ra n k test stratifie d b y re gi o n a n d bas eli ne I G A. 
Se nsiti vit y a n al ysis will be perf or me d as a p plica ble i n or der t o assess t he r o b u st ness of res ults 
of t he pri mar y a n al ysis wit h res pect t o t he retrie ve d data at Wee k 1 6 a n d ass u m pti o ns 
re gar di n g missi n g d ata. T his will be descri be d i n f urt her detail i n t he statistical a nal ysis pla n. 
1 4. 3. 7  A n al ysis of ot her e n d p oi nts  
1 4. 3. 7. 1  A n al ysis of p atie nt -re p or te d o utc o mes 
T he P R Os H EI S, Pa G A, D L QI, E Q -5 D -5 L, Q O L H E Q , W L Q , a n d P GI-C  will be s u m marise d 
b y treat me nt gr o u p a n d visit usi n g descri pti ve statistics. T he s u m maries will be prese nt e d f or 
t he f ull a nal ysis set. 
T he H E S D c ollect e d i n t he e Diari es o n a dail y basis (all i n di vi d ual s y m pt o ms) will be 
s u m marise d o ver ti me b y treat me nt gr o u p usi n g descri pti ve statistics. T he s u m maries will be 
prese nte d f or t he f ull a n al ysis set.  
T he dail y di ar y rec or di n gs of t he H E S D  N R S  sc ores will be deri ve d i nt o discrete wee kl y 
e n d p oi nts base d o n ca l e n dar ti me ( wit h t he e x ce pti o n of Wee k 1 6) fr o m b aseli ne visit i.e., t he 
e n d p oi nts re pres e nt t he n o mi nal wee k a n d are n ot directl y relate d t o t he act ual visit i n c o ntrast 
t o ot her visit base d assess me nts. T he al g orit h m f or deri vi n g t he e n d p oi nts at eac h ti me p oi nt is 
descri be d as f oll o ws: bas eli ne wee kl y a vera ge will be defi ne d b y a v era ge of meas ure m e nts 
fr o m Da y -7  t o Da y -1, Wee k 1 wee kl y a v era ge will be defi ne d b y t h e a v era ge of 
meas ure me nts fr o m Da y 1  t o Da y 7 , Wee k 2 wee kl y a v era ge will be defi n e d b y t he a vera ge of 
meas ure me nts fr o m Da y 8  t o Da y 14  a n d s o o n, u ntil Wee k 1 5 . Wee k  1 6 will be calc ulate d 


Trial I D: L P 0 1 3 3 -1 2 7 3  
Date: 0 7 -Dec -2 0 1 8  
Versi o n: 3. 0  
P a ge 9 8  of 1 2 8  
 
 
 
base d o n t he 7  da ys  prece di n g  t he Wee k 1 6 visit. A mi ni m u m of 4  H E S D  N R S sc ores o ut of 
t he 7 da ys are re q uir e d t o calc ulate t he a vera ge s c ore. T his will be deri v e d f or eac h s y m pt o m, 
res pecti vel y. 
I n t he s u b gr o u p of s u bjects wit h a baseli ne w orst pr urit us  ( wee kl y a vera ge) –  o ne of t he 
s y m pt o ms ca pt ure d i n t h e H E S D –  sc ore of at least 4, t he pr o p orti on of s u bjects wit h 
red ucti o n i n w orst pr urit us  ( wee kl y a v era ge) of at least 4 fr o m baseli ne t o Wee k  1 6 will be 
s u m marise d b y tr eat me nt gr o u p a n d a n al ys e d usi n g t he C oc hra n -M a ntel -Hae nszel a p pr oac h  
as descri be d f or t he a nal ysis of t he pri mar y e n d p oi nt.  
Pa G A  T S  refers t o ac hie vi n g: 
 Pa G A sc ore of 0 (cle ar) w he n classifie d at baseli ne as 1 (al m ost clear) or 2 ( mil d)  
or  
 Pa G A sc ore of 0 (cle ar) or 1 (al m ost clear) w he n classifie d at baseli ne as 3 ( m o derate) 
or 4 (se vere).  
T he pr o p orti o n of s u bjects ac hie vi n g Pa G A T S  at Wee k 1 6 will be s u m marise d b y tr eat me nt 
gr o u p a n d a nal ys e d usi n g t he C oc hra n -M a ntel -Hae nszel a p pr oac h as d escri b e d f or t he 
a nal ysis of t he pri mar y e n d p oi nt.  
T he ti me t o Pa G A T S  will be s u m marise d b y treat me nt  gr o u p a n d a nal ys e d as descri be d f or 
t he pri mar y a n al ysis of t h e sec o n dar y ti me t o e ve nt e n d p oi nt. 
I n t he s u b gr o u p of s u bjects wit h a baseli ne D L QI s c ore of at least 4, t he pr o p orti o n of s u bjects 
wit h a re d ucti o n i n D L QI sc ore of at least 4 at Wee k 1 6 will  be s u m marise d b y treat me nt 
gr o u p a n d a nal ys e d usi n g t he C oc hra n -M a ntel -Hae nszel a p pr oac h as d escri b e d f or t he 
a nal ysis of t he pri mar y e n d p oi nt.  
T he c ha n ge fr o m bas eli ne t o Wee k 1 6 i n H E S D  N R S  ( wee kl y a verage f or eac h i n di vi d ual 
s y m pt o m), H EI S  (f or eac h i ndi vi d ual ite m), D L QI, E Q -5 D -5 L, Q O L H E Q , a n d W L Q will be 
s u m marise d b y tr eat me nt gr o u p a n d d o mai n, w here a p plica ble, a n d a nal ys e d  usi n g t he 
M M R M a p pr oac h  as d es cri be d a b o v e f or t he a nal ysis of t he sec o n dar y c o nti n u o us e n d p oi nt.   


Trial I D: L P 0 1 3 3 -1 2 7 3  
Date: 0 7 -Dec -2 0 1 8  
Versi o n: 3. 0  
P a ge 9 9  of 1 2 8  
 
 
 
1 4. 3. 7. 2  Effic ac y o ver ti me  
To f urt her e x pl ore p ossi ble earl y o nset of effect a n d ge n eral effi cac y o v er ti me, t he f oll o wi n g 
e n d p oi nts will be e val uat e d at eac h sc he d ul e d assess me nt u p t o Wee k  1 4 or eac h wee k u p t o 
Wee k  1 5:  
 I G A T S  at eac h s c he d ule d assess me nt u ntil Wee k 1 4.  
 Pa G A T S  at eac h sc h e d ul e d assess me nt u ntil Wee k 1 4.  
 C ha n ge fr o m bas eli ne t o eac h wee k t hr o u g h Wee k  1 t o 1 5 i n H E S D N R S 
( wee kl y a v era ge f or eac h in di vi d ual s y m pt o m) . 
o  Re d ucti o n of w orst pr urit us  ( wee kl y a v era ge) –  o n e of t he 
s y m pt o ms ca pt ure d i n t h e H E S D –  of at least  4 fr o m baseli ne t o 
eac h w ee k t hr o u g h Wee k 1 t o 1 5  a m o n g s u bjects wit h baseli ne 
w orst pr urit us ( wee kl y a vera ge) of at least 4 . 
 C ha n ge fr o m bas eli ne t o eac h sc h e d ule d ass ess me nt u ntil Wee k  1 4 i n H EI S 
(f or eac h i n di vi d ual ite m). 
 C ha n ge i n D L QI sc ore fr o m bas eli ne t o eac h s c he d ule d assess me nt u ntil 
Wee k  1 4.  
 Re d ucti o n of D L QI of at least 4 fr o m baseli ne t o eac h sc he d ul e d assess me nt 
u ntil Wee k  1 4.  
F or t he bi nar y e n d p oi nts, t he sa me C oc hra n -Ma nt el -Hae nszel test as f or t h e Wee k  1 6 
assess me nt will be a p plie d. F or t he c o nti n u o us e n d p oi nts, t he re peate d m eas ure me nts m o del 
alrea d y d escri be d pre vi o usl y f or t h e Wee k  1 6 assess me nts facilitates t hat t he p -val ues, 
treat me nt differe n ces a n d 9 5 % CIs ca n be d eri ve d f or eac h visit u p t o Wee k 1 4 ( or Wee k  1 5 
f or t he c h a n ge i n H E S D  N R S  ( wee kl y a vera ge)). 
1 4. 3. 7. 3  E x pl or at or y a n al yses  
T reat me nt effect wit hi n e ac h s u bt y p e of c hr o nic h a n d ecze ma  i n ter ms of disease aeti ol o g y 
will be e x pl ore d f or t he pri mar y a n d sec o n dar y e n d p oi nts usi n g t he sa me a nal ysis met h o ds as 
descri be d pre vi o usl y. 
1 4. 3. 8  A n al ysis of p h ar m ac o d y n a mics a n d p h ar m ac o ge n o mics  
E x pl orat or y a nal ys es of bi o mar kers  will be perf or me d f or  t he t otal p o p ulati o n as well as f or 
s u bt y pe of c hr o nic h a n d ecze ma  a n d b y  dise ase se verit y.  


Trial I D: L P 0 1 3 3 -1 2 7 3  
Date: 0 7 -Dec -2 0 1 8  
Versi o n: 3. 0  
P a ge 1 0 0  of 1 2 8  
 
 
 
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 it is a vaila ble i n ti me f or t his. T he f ull 
set of bi o mar ker res ults will be re p orte d i n a n a d de n d u m re p ort t o t he C T R. 
1 4. 3. 9  A n al ysis of safet y  
T he a nal ysis of safet y will be base d o n t he safet y a nal ysis s et.  
1 4. 3. 9. 1  A d verse eve nts  
A Es will be c o de d d uri n g t he c o urse of t h e trial acc or di n g t o M e dical Dicti o nar y f or 
Re g ulat or y Acti vities ( M e d D R A). A Es will be prese nte d b y preferre d ter ms 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 c o urse of 
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 use of I M P or if starte d bef ore t h e first use of I M P 
a n d w orse n e 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 o ll o wi n g 
will o nl y i n cl u de t he treat me nt -e mer ge nt e ve nts. I n eac h of t h e ta b ulati o ns, A Es are d efi ne d 
b y Me d D R A preferre d t er 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 nt a ge) of s u bjects wit h 
a n y tr eat me nt -e mer ge n t A Es, deat hs, S A Es, pre m at 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 nt e d. 
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 b y 
treat me nt gr o u p. 
T he se verit y f or eac h t y p e of A E will be ta b ulate d b y treat me nt gr o u p. W here t here are se veral 
rec or di n gs of s e verit y f or a gi v e n t y p e of A E, se v erit 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 ca us al 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 b y  treat me nt gr o u p. 
W here t here are s e veral r ec or di n gs of ca usal r elati o ns hi p t o t he I M P f or a gi ve n t y pe of A E, 
ca usal r elati o ns hi p will be ta ke n as t he m ost -relate d rec or di n g fr o m t he last re p ort of t hat A E, 
si nce t hat is w he n t he i n v esti gat or will be i n possessi o n of m ost i nf or mati o n a n d s o best a ble 
t o j u d ge ca usal r elati o ns hi p. 
Relate d A Es are d efi ne d as A Es f or w hic h t he i n v esti gat or h as n ot descri b e d t he ca usal 
relati o ns hi p t o I M P as ‘n ot relate d ’. T h e n u m ber of s u bjects wit h eac h t y p e of relate d A E wi ll 
be ta b ulate d . 


Trial I D: L P 0 1 3 3 -1 2 7 3  
Date: 0 7 -Dec -2 0 1 8  
Versi o n: 3. 0  
P a ge 1 0 1  of 1 2 8  
 
 
 
S A Es will be e val uate d s e parat el y a n d a n arrati ve f or eac h will be gi ve n.  
A d verse e ve nts of s pecial i nterest will be ta b ulate d b y treat me nt gr o u p.  
A Es lea di n g t o wit h dra w al fr o m trial a n d A Es lea di n g t o  per ma n e nt disc o nti n uati o n of I M P 
will be  ta b ulate d b y treat me nt gr o u p . 
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, p ulse , b o d y te m perat ur e) fr o m b aseli ne t o eac h visit 
will be s u m marise d as mea n, sta n dar d de viati o n , me dia n, mi ni m u m, a n d ma xi m u m  val ues f or 
eac h tr eat me nt gr o u p.  
1 4. 3. 9. 3  Cli nic al la b or at or y ev al u ati o n  
T he c ha n ge i n eac h of t h e la b orat or y p ara m eters fr o m baseli ne t o eac h visit will be 
s u m marise d b y visit a n d treat me nt gr o u p as me a n, sta n dar d de viati o n, me di a n, mi ni m u m , a n d 
ma xi m u m val ues.  
L a b orat or y p ara m eters will be classifie d as ‘l o w’, ‘n or mal ’ or ‘hi g h ’, d e pe n di n g o n w het h er 
t he val ue is bel o w, wit hi n or a b o ve t he refere n ce ra n ge, res pecti vel y. A s hift ta ble will be 
pr o d uce d s h o wi n g t he cate g ori es at baseli ne a gai nst t h ose at e n d of trea t me nt. S u bjects wit h 
la b orat or y para meters o utsi de t he refere n ce ra n ge will be liste d. 
1 4. 3. 9. 4  S u bject assess me nt of l oc al t oler a bilit y  
S u bject assess me nt of l ocal t olera bilit y will be s u m marise d b y visit a n d treat me nt gr o u p .  
1 4. 3. 1 0  
P h ar m ac o ki netics  
A se parate re p ort will be writte n b y t he res pecti ve bi oa nal ytical C R O a n d a d de d as a n 
a d de n d u m t o t he C T R. 
Plas ma c o nce ntr ati o ns of del g o citi ni b  will be liste d a n d pl otte d vers us ti me si nce last I M P 
a p plicati o n b y tr eat me nt gr o u p.  
1 4. 3. 1 1  
I nteri m a n al ysis  
N o i nter i m a nal ysis is pla n ne d. 


Trial I D: L P 0 1 3 3 -1 2 7 3  
Date: 0 7 -Dec -2 0 1 8  
Versi o n: 3. 0  
P a ge 1 0 2  of 1 2 8  
 
 
 
1 4. 3. 1 2  
Ge ner al p ri nci ples 
U nless ot her wise state d, all si g nifica n ce tests will be 2 -si de d usi n g t he 5 % si g nifica n ce le vel. 
All CIs will be pres e nte d wit h 9 5 % de gree of c o nfi de nce.  
A n o bser ve d -cas es a p pr oac h will be use d f or ta b ul ati o ns of data b y visit (i.e. , 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 pecifi c 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 nt a ge of s u bjects i n eac h 
cate g or y a n d treat me nt gr o u p. C o nti n u o us data will be s u m marise d usi n g t he mea n, m e dia n, 
sta n dar d de viati o n, mi ni m u m, a n d ma xi m u m val ues.  
All t he a nal ys es s pecifie d i n t he pr ot oc ol will be re vie we d i n r elati 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.  
A n y c ha n ges fr o m t he statistical a nal ysis pla n ne d i n t his cli nical trial pr ot oc ol will be 
descri be d a n d j ustifie d i n a pr ot oc ol a me n d me nt, t he statistical a nal ysis pla n a n d/ or i n t he 
C T R de pe n de nt o n t he t y pe of de viati o n.  
1 4. 3. 1 3  
H a n dli n g of m issi n g v al ues  
Pr oce d ures f or ha n dli n g of missi n g val ues are i ncl u de d u n der t he s ecti o ns descri bi n g t he 
i n di vi d ual a nal yses. 


Trial I D: L P 0 1 3 3 -1 2 7 3  
Date: 0 7 -Dec -2 0 1 8  
Versi o n: 3. 0  
P a ge 1 0 3  of 1 2 8  
 
 
 
1 5  Refere nces  
1.  Die p ge n T L, A n derse n K E, C h osi d o w O, C oe nraa ds PJ, Els ner P, E n glis h J , et al. 
G ui deli nes f or dia g n osis, pre ve nti o n a n d tr eat me nt of h a n d ecze ma. J Dtsc h Der mat ol 
Ges. 2 0 1 5;  1 3( 1): e 1 -e 2 2. 
2.  Ha bif  T P. Cli nical der mat ol o g y: a c ol or g ui de t o dia g n osis a n d t hera p y ( 5t h e diti o n). Ne w 
Yor k: M os b y. 2 0 1 0.  
3.  F o wler J F, G h os h A, S u n g J, E ma ni S, C ha n g J, De n E, T h or n D, Pers o n J, S he n g D u h M. 
I m pa ct of c hr o nic ha n d d er matitis o n q ualit y of life, w or k pr o d u cti vit y, acti vit y 
i m pair me nt, a n d me dical c osts. J A m Aca d Der mat ol. 2 0 0 6; 5 4: 4 4 8-5 7.  
4.  Ler bae k A, K y vi k K O, Ra v n H, Me n né T, A g ner T. Cli nical c haract eristics a n d 
c o nse q ue nces of h a n d ecze ma –  a n 8-y ear f oll o w-u p st u d y of a p o p ul ati o n -base d t wi n 
c o h ort. C o ntact Der m atitis. 2 0 0 8; 5 8: 2 1 0 -2 1 6.  
5.  C vet k o vs ki R S, R ot h ma n n KJ, Olse n J, Mat hiese n B, I verse n L, J o ha nse n J D, A g ner T. 
Relati o n bet wee n dia g n oses o n se verit y, sic k l ea v e a n d l oss of j o b a m o n g patie n ts wit h 
occ u pati o nal ha n d ecze m a. B J Der mat ol. 2 0 0 5; 1 5 2: 9 3 -9 8.  
6.  Belsit o D V, F o wler J F, Mar ks J G, Pariser D M, Ha nifi n J, D uarte I A G, Pires M C, Cr uz 
P D, La n gl e y R G B, Patel P, B us h C, T h urst o n M, Grae b er M, C herill R a n d t he 
M ultice nter Gr o u p. Pi mecr oli m us crea m 1 %: A p ote ntial ne w treat me nt f or c hr o nic ha n d 
der matitis. C utis. 2 0 0 4; 7 3: 3 1 -3 8.  
7.  H or di ns k y M, Fleisc her A, Ri vers J K, P o uli n Y, Belsit o D, H ultsc h T. Effi cac y a n d safet y 
of pi mecr oli m us crea m 1 % i n mil d -t o-m o derate c hr o nic ha n d der matitis: A ra n d o m ize d, 
d o u ble -bli n d trial. Der mat ol o g y. 2 0 1 0; 2 2 1: 7 1 -7 7.  
8.  Pes u M, Ca n d otti F, H usa M, H of ma n n S R, N otaraa n gel o L D, O ’S hea JJ. Ja k 3, se vere 
c o m bi ne d i m m u n o deficie nc y, a n d a ne w class of i m m u n os u p pressi ve dr u gs. I m m u n ol o g 
Re v. 2 0 0 5; 2 0 3: 1 2 7 -1 4 2.  
9.  M urra y PJ. T he  J A K-S T A T si g n alli n g pat h w a ys: i n p ut a n d o ut p ut i nte grati o n. J o ur nal of 
I m m u n ol o g y. 2 0 0 7; 1 7 8: 2 6 2 3-2 6 2 9.  
1 0.  A ma n o W, Na kaji ma S, K u n u gi H, N u m ata Y, Kit o h A, E ga wa G, et al. T h e J a n us ki nase 
i n hi bit or J T E-0 5 2 i m pr o ves s ki n barrier f u ncti o n t hr o u g h s u p pressi n g si g n al tra ns d ucer 
a n d acti vat or of tra nscri pti o n 3 si g nali n g. J Aller g y Cli n I m m u n ol. 2 0 1 5; 1 3 6: 6 6 7 -7 7.  


Trial I D: L P 0 1 3 3 -1 2 7 3  
Date: 0 7 -Dec -2 0 1 8  
Versi o n: 3. 0  
P a ge 1 0 4  of 1 2 8  
 
 
 
1 1.  R uzic ka T, Ly n de C W, J e mec G B E, Die p ge n T, Bert h -J o nes J, C oe nraa ds PJ, et al. 
Efficac y a n d s afet y of oral alitreti n oi n ( 9 -cis reti n oic aci d) i n patie nts  wit h se vere c hr o nic 
ha n d ecze ma refract or y t o t o pical c ortic oster oi ds: res ults of a ra n d o mize d, d o u ble -bli n d, 
place b o -c o ntr olle d, m ultice ntre tri al.  Britis h J o ur nal of Der m at ol o g y. 2 0 0 8; 1 5 8: 8 0 8 -8 1 7.  
1 2.  Sc h ulz K F, Alt ma n D G, M o her D, C O N S O R T Gr o u p. 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.  
1 3.  Hel d E, S k oet R, J o ha nse n J D, A g ner T. T he ha n d ecze ma se verit y i n de x ( H E C SI): a 
sc ori n g s yste m f or cli nic al assess me nt of ha n d ecze ma. A st u d y of i nter- an d i ntra o bser ver 
relia bilit y. Br J Der mat ol. 2 0 0 5  Fe b; 1 5 2( 2): 3 0 2 -7.  
1 4.  Fi nla y A Y, K ha n G K. Der mat ol o g y Lif e Q ualit y I n de x ( D L QI) –  a si m ple practical 
meas ure f or r o uti ne cli ni cal use. Cli n E x p Der mat ol. 1 9 9 4; 1 9( 3): 2 1 0 -2 1 6.  
1 5.  Grei ner W, Weij ne n T, Nie u we n h uize n M, O p pe S, Ba dia X, B ussc h bac h J, et al. A si n gle 
E ur o pea n c urre nc y f or E Q -5 D healt h states. Res ults fr o m a si x -c o u ntr y st u d y. E ur J Healt h 
Ec o n. 2 0 0 3; 4( 3): 2 2 2 -2 3 1.  
1 6.  O oster ha ve n  J A F, Sc h utt elaar M L A, A pfel bac h er C, Die p gen T L, Ofe nl oc h  R F. G ui deli ne 
f or tra nslati o n a n d n ati o nal vali dati o n of t he Q ualit y of Lif e i n Ha n d E cze ma 
Q uesti o n naire ( Q O L H E Q ). C o ntact Der matitis. 2 0 1 7; 7 7:1 0 6 -1 1 5 . 
1 7.  Ofe nl oc h R F, O oster ha v e n J A F, S usit ai val P, et al. Cr oss -c ult ural vali dati o n of t he Q ualit y 
of Lif e i n H a n d E cze ma Q uesti o n naire ( Q O L H E Q ). J I n vest Der mat ol. 2 0 1 7; 1 3 7:1 4 5 4 -
1 4 6 0 . 
1 8.  Ofe nl oc h R F, Weiss haar E, D u m ke A K et al. T h e Q ualit y of Lif e i n Ha n d Ecze ma 
Q uesti o n naire ( Q O L H E Q): vali dati o n of t he Ger ma n versi o n of a n e w dis ease -s p ecific 
meas ure of q ualit y of life f or patie nts wit h ha n d ecze ma. Br J Der mat ol 2 0 1 4 ;1 7 1: 3 0 4 –
3 1 2.  
1 9.  Ofe nl oc h R, S usitai vel P, S ve nss o n A et al. First r es ults fr o m t he de vel o p me nt of a ne w 
disease -s pecific q ualit y of life i nstr u me nt. 6t h I nt er nati o nal Der m at o -E pi de mi ol o g y 
Ass ociati o n C o n gress. Br J Der mat ol 2 0 1 2; 1 6 7:e 1 – 2 5.  
2 0.  Ler ner D, A mic k B C III, R o gers W H, Mals peis S, B u n ga y K, C y n n D. T he Wor k 
Li mitati o ns Q uesti o n nair e. Me d Care. 2 0 0 1; 3 9: 7 2 -8 5.  
2 1.  F D A . Attac h me nt t o disc ussi o n d oc u me nt f or pati e nt -f oc used dr u g de v el o p me nt p u blic 
w or ks h o p o n G ui da nce 3: Select, de vel o p or m o dif y fit -f or-p ur p ose cli nical o utc o me 
assess me nts, A p pe n di ces. 2 0 1 8.  


Trial I D: L P 0 1 3 3 -1 2 7 3  
Date: 0 7 -Dec -2 0 1 8  
Versi o n: 3. 0  
P a ge 1 0 5  of 1 2 8  
 
 
 
2 2.  E ur o pea n Parlia m e nt a n d C o u ncil of T he E ur o pea n U ni o n. 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 r elati 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 me dici nal pr o d ucts f or h u ma n use [ 2 0 0 1], article  1 0 . 
2 3.  E M A. ”Q ualificati o n O pi ni o n of M C P -M o d as a n effici e nt statistical met h o d ol o g y f or 
m o del -base d desi g n a n d a nal ysis of P hase II d os efi n di n g st u dies u n der m o d el u ncertai nt y ” 
( 2 0 1 4). 
htt p:// w w w.e ma.e ur o pa.e u/ d ocs/e n _ G B/ d oc u m e nt _li brar y/ Re g ul at or y _a n d _ pr oce d ural _ g u
i deli ne/ 2 0 1 4/ 0 2/ W C 5 0 0 1 6 1 0 2 7. p df 
2 4.  Bretz F,  Pi n heir o J C, Bra ns o n M. C o m bi ni n g M ulti ple C o m paris o ns a n d M o deli n g 
Tec h ni q ues i n D ose -Res p o nse S t u dies. Bi o metrics. 2 0 0 5; 6 1:7 3 8 -7 4 8 . 
2 5.  Na ka ga wa H, Ne m ot o O, I garas hi A, Na gata T. Efficac y a n d safet y of t o pical J T E -0 5 2, a 
J a n us ki nase i n hi bit or, i n J a pa nese a d ult patie nts wit h m o derate-t o-se v ere at o pic 
der matitis: a p hase II, m ultice ntre ra n d o mize d, ve hicle -c o ntr olle d cli nical st u d y. Br J 
Der mat ol . 2 0 1 8; 1 7 8: 4 2 4 -4 3 2.  
2 6.  Worl d Me dical Ass ociati o n 2 0 1 3. Declarati o n of Helsi n ki  –  et hical pri nci ples f or me di cal 
researc h i n v ol vi n g h u m a n s u bjects. 7 t h ( F ortaleza) a me n d me nt. 
2 7.  I nter nati o nal Et hical G ui deli nes f or Healt h-rel ate d Researc h I n v ol vi n g H u ma ns, F o urt h 
E diti o n. Ge ne va. C o u ncil f or I nter n ati o nal Or ga nizati o ns of Me dical Scie nces ( CI O M S); 
2 0 1 6.  
2 8.  I nter nati o nal C o u ncil f or Har m o nisati o n of Tec h ni cal Re q uire me nts f or P har mace uticals 
f or H u ma n Us e (I C H) 2 0 1 6. I nte grate d a d de n d u m t o I C H E 6( R 1): G ui d eli ne f or g o o d 
cli nical practice E 6( R 2) . 


Trial I D: L P 0 1 3 3 -1 2 7 3  
Date: 0 7 -Dec -2 0 1 8  
Versi o n: 3. 0  
P a ge 1 0 6  of 1 2 8  
 
 
 
A p pe n di x 1 : Defi niti o ns of a d verse eve nts a n d seri o us a d verse eve nts  
A d verse eve nt d efi 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 a v 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 nv esti 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 nv esti g ati o n al) pr o d u ct. (I CH Har m o nize 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 n ts relate d t o trial pr o ce d ures. 
 R eas o ns f or a n y u nfa v o ura ble a n d u n pla n ne d c h a n ge i n  me di cati o n ( dr u g 
a n d/ or d ose).  
 C li nicall y si g nific a nt w orse ni n g of pre -e xisti n g c o n diti o ns.  
 R eas o ns f or a d missi o n t o h os pital or s ur gi cal pr oce d ures u nless t hes e 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 bas e d o n t he p har mac ol o gical 
effect of t he IM 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 (s ee Secti o n 1 1. 4. 4 ). 
Seri o us a d verse eve nt d efi niti o n 
A n S A E is a n y u nt o w ar d me dical occ urre n ce t hat  
 R es ults i n deat h . 
 Is life-t hreate ni n g. 


Trial I D: L P 0 1 3 3 -1 2 7 3  
Date: 0 7 -Dec -2 0 1 8  
Versi o n: 3. 0  
P a ge 1 0 7  of 1 2 8  
 
 
 
 R e 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. 
 R es ults i n persiste nt or si g nifica nt disa bilit y/i n ca p acit 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 hreat e 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 n e of t he ot her o utc o mes liste d 
i n t he defi niti o n a b o ve. E x a 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 n c 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 d e nc y or dr u g 
a b use.  


Trial I D: L P 0 1 3 3 -1 2 7 3  
Date: 0 7 -Dec -2 0 1 8  
Versi o n: 3. 0  
P a ge 1 0 8  of 1 2 8  
 
 
 
A p pe n di x 2 : Cl assific atio n of a d verse eve 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 uir e 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 all e viate d wit h a d diti o nal s pecific t hera pe utic 
i nter ve nti o n. T he e v e nt i nterferes wit h us ual acti vities of dail y li vi n g, 
ca usi n g dis c o mf ort b ut p oses n o si g nifica nt or per ma ne nt ris k of har m t o t h e 
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 p e utic i nter ve nti o n.  
If t he se verit y of a n A E w orse ns, a n e 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 h e A E t o t he use of t he IM P  s h o ul d be descri be d i n ter ms of pr o ba bl y, 
p ossi bl y, or n ot r elate 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 n ce fr o m a d mi nistrati o n of t he IM 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 he IM P. 
 
Disa p pears or decreas es o n cessati o n or re d ucti o n i n d ose of t he IM P . 
 
Rea p pears or w ors e ns u p o n re -c h alle n ge. 


Trial I D: L P 0 1 3 3 -1 2 7 3  
Date: 0 7 -Dec -2 0 1 8  
Versi o n: 3. 0  
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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 n ce fr o m t he a d mi nistrati o n of t he 
IM 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 m i 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 IM P. 
N ot relate d  
 
D oes n ot f oll o w a reas o n a ble te m p oral se q u e nce fr o m a d mi nistrati o n of t he 
IM P . 
 
Is b etter 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 p ear 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 IM P. 
 
O utc o me  
T he o utc o me  of t he e v e 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 h e cat e g ories bel o w.  


Trial I D: L P 0 1 3 3 -1 2 7 3  
Date: 0 7 -Dec -2 0 1 8  
Versi o n: 3. 0  
P a ge 1 1 0  of 1 2 8  
 
 
 
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 h a 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 x a 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 u elae 
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 bj ect l ost t o f oll o w-u p.  
 
N ote t hat as per t h e a b o v e defi niti o n, L E O uses “R E C O V E R E D/ R E S O L V E D ” o nl y if a n 
e ve nt has act uall y st o p p e d. Acc or di n g t o t he C DI S C defi niti o n, t he cate g or y 
“R E C O V E R E D/ R E S O L V E 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 d efi 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 O T R E C O V E R E D/ N O T R E S O L V E D ” or “R E C O V E RI N G/ R E S O L 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 us es 
“R E C O V E R E D/ R E S O L V E D WI T H S E Q U E L A E ” o nl y if a n e v e nt ha s 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 v e nt is c o nsi dere d 
“WI T H S E Q U E L A E ”, if it has “retai ne d p at 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 cl assifie d b y L E O wit h t he o u tc o me “R E C O V E R E D/ R E S O L V E D 
WI T H S E Q U E L A E ” c o ul d ha ve bee n classifie d wit h t he o utc o me 
“R E C O V E R E D/ R E S O L V E D ” acc or di n g t o t he C DI S C defi niti o n.  
F or S A Es w hic h h a ve sta bilise d a n d ca n n ot be e x pecte d t o re s ol v e d uri n g st u d y or safet y 
f oll o w-u p peri o ds, f or e x a m ple c hr o nic ill nesses, ‘n ot res ol v e d’ is acce pte d as t he fi nal 
o utc o me a n d a state m e 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 i n t he S A E f or m.  


Trial I D: L P 0 1 3 3 -1 2 7 3  
Date: 0 7 -Dec -2 0 1 8  
Versi o n: 3. 0  
P a ge 1 1 1  of 1 2 8  
 
 
 
A p pe n di x  3 : Tri al  g o ver n a nce co 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 co 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 v ersi o n of t he D eclarati o n of Helsi n ki (2 6 ) a n d C o u ncil f or I nter n ati o nal 
Or ga niz ati o ns of Me dical Scie nces ( CI O M S) I nter nati o nal Et hical G ui deli nes  (2 7 ). 
 C urre nt versi o n of a p plica ble I nter n ati 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  (2 8 ). 
 E U ’s Ge n eral D ata 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 pri ate re g ulat or y a ut h orities  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 o c u me nts t hat  t he I R B/I E C ma y n ee 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, In v esti gat or ’s B r oc h ure, s u bject i nf or mati o n leaflet, i nf or me d 
c o nse nt f or ms, or a d vertise me nts) will be s u b mitte d t o t he I R B/I E C. T h ese 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 r e 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 uir e d b y l ocal 
le gislati o n: 
 Pr o vi di n g writte n s u m maries of t he stat us of t he tri al 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 a cc 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 local 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 h e c o n d uct of t he trial at t he trial site a n d a d h ere n ce t o 
a p plica ble nati o nal a n d i nter nati o nal le gislati o n . 


Trial I D: L P 0 1 3 3 -1 2 7 3  
Date: 0 7 -Dec -2 0 1 8  
Versi o n: 3. 0  
P a ge 1 1 2  of 1 2 8  
 
 
 
A p pe n di x 3 B: I nf or me d co nse nt p r ocess  
S u bjects  will  recei ve writte n a n d ver 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 h at 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 an d f or a n y reas o n. All s u bjects will 
be gi v e n a n o p p ort u nit y t o as k q uesti o ns a n d will be gi v e n s uffici e 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 -rel ate d pr oce d ure bei n g carrie d o ut 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 nf or me d c o nse nt f or m. 
S u bjects  will be re -c o ns e nte d t o t he m ost c urre nt versi o n of t he i nf or me d c o nse nt f or m d uri n g 
t heir partici pati o n i n t he trial, if a p plica ble. 
A c o p y of t he i nf or me d c o nse nt f or m (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 wi t 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 dress(es) a n d tele p h o ne n u m b er(s) 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 u ati o ns. T he 
s u bject car d als o incl u des a l ocal tele p h o ne n u m b er 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 
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 nsf er i nf or mati o n, data a n d/ or res ults t o ot her i n vesti gat ors , re g ul at or y a ut h orities 
a n d/ or c o m mercial part n ers.  
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 . A n 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 bj ect 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 ntifi a ble will n ot be tra nsferre d.  


Trial I D: L P 0 1 3 3 -1 2 7 3  
Date: 0 7 -Dec -2 0 1 8  
Versi o n: 3. 0  
P a ge 1 1 3  of 1 2 8  
 
 
 
Trial s u bject s m ust be i nf or me d a n d c o ns e nt t o t hat t heir pers o nal trial-relat e d data will be 
use d b y L E O i n acc or da n ce 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 ns e nt t o t hat t heir me dical rec or ds m a y b e e x a mi ne d b y 
Cli nical Q ualit y Ass ura n ce 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 p ers o n al d at a  
T his pr ot oc ol s pecifies t h e pers o nal d ata o n trial s u bjects ( f or e x a m ple race, a ge, ge n d er, 
healt h c o n diti o n, me dical hist or y, test res ults, etc.) w hic h s hall be c ollect e 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 d ata 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 h alf of L E O.  
Pr ocessi n g of pers o n al 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 p arty w hic h c o vers c ollecti o n, pr ocessi n g a n d tr a nsfer of pers o nal data i n t he 
cli nical trial. I n certai n c ases , a n a gree m e nt o n tra nsfer of p ers o nal dat a ma y als o be re q uir e d.  
I n v esti 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 tr a nsfer of pers o nal dat a 
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 tr a n sfer 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 os e 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 ne 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 k eti n g of pr o d ucts/ser vices 
a n d ot her relate d acti vities.  
L E O h as o btai ne d t he n ecessar y a ut h orisati o ns f or t he pr ocessi n g of pers o n al data c ollect e d i n 
t he trial. 
A p pe n di x 3 D: R ec 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 m e nt m ust be defi ne d i n a s o urce d o c u me nt a gree m e 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 d efi ne d at a n y ti me f or a n y 
data ele me nts.  


Trial I D: L P 0 1 3 3 -1 2 7 3  
Date: 0 7 -Dec -2 0 1 8  
Versi o n: 3. 0  
P a ge 1 1 4  of 1 2 8  
 
 
 
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 tri al site. S o urce dat a 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 v al uati o ns m ust be si g ne d b y me dicall y q u alifie d i n vesti gat ors. 
If t he w or ks h eet d oes n ot bec o me part of t he s u bject’s me dical r ec or d, t h e f oll o wi n g 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 o cess,  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 v erif y t hat eac h of the eli gi bilit y criteria 
are met  a n d d o c u me nte d . 
 S u bject I D . 
 T he fact t hat t he s u bject is partici pati n g i n a cli nical trial i n c hr o nic ha n d 
ecze ma  i ncl u di n g treat m e nt wit h  del g o citi ni b  crea m ( 1, 3, 8, or 2 0  m g/ g) or 
del g o citi ni b  crea m ve hi cle f or 1 6 wee ks of treat me nt pl us 2  wee ks of f oll o w -
u p . 
 Ot her rel e va nt me dical i nf or mati o n . 
Tri al m o nit ori n g  
D uri n g t h e c o urs e 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 eC 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 b ei n g pr ot ecte d; a n d (iii) t o c o nfir m t hat t he 
trial is bei n g c o n d u cte 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 tri al 
a gree m e nts, I C H -G C P, a n d all a p plica ble re g ulat or y re q uire m e nts.  
T he m o n it ori n g visit i nter vals will de pe n d o n t he trial site’s recr uit me nt rat e 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 ur a nce a n d 
i ns pecti o ns will need direct access  t o s o urce data, e. g. m e dical r ec 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 h a 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 v aila 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).  


Trial I D: L P 0 1 3 3 -1 2 7 3  
Date: 0 7 -Dec -2 0 1 8  
Versi o n: 3. 0  
P a ge 1 1 5  of 1 2 8  
 
 
 
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  des cri 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 uct e d b y L E O or i ns pe cti o ns fr o m d o mestic or 
f orei g n re g ul at or 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 t a 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 st aff 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 m e nts a n d ot her d oc u me nts at t h e 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 x a 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 ntact e 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 ocess es a n d data ha ve b ee n e val uate d. 
Ris k miti gati o n acti vities f or e n d p oi nts i ncl u de:  
 E ns uri n g c o nsiste nt data wit h res pect t o assess me nts of efficac y (I G A a n d 
H E C SI), all assess ors will recei ve trai ni n g a n d w he ne ver p ossi ble, t he efficac y 
assess me nts will be ma de b y t h e 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-rat er vari a bilit y. 
 E ns uri n g  s u bjects a n d i n vesti gati o nal staff are well i nstr ucte d a n d trai ne d a b o ut 
t he use of t he e Diar y a n d t he e De vice  w hic h will be  use d t o c ollect t he P R Os 
( H E S D, H EI S, Pa G A, D L QI, E Q-5 D -5 L, Q O L H E Q , W L Q, P GI-C ). 
 E ns uri n g i n vesti gati o nal staff are well i nstr ucte d a n d trai ne d i n c ollecti n g 
bi o mar ker sa m ples.  
 E ns uri n g a d mi nistrati o n of I M P is c o ntr olle d a n d d oc u me nte d at t he site. T his 
will be d o ne b y pr o vi di n g trai ni n g a n d clear i nstr ucti o ns t o trial sites. 
 E ns uri n g t hat trial sites are well trai n e d i n safet y pr oce d ures s uc h as c ollecti o n 
a n d re p orti n g of A Es . 


Trial I D: L P 0 1 3 3 -1 2 7 3  
Date: 0 7 -Dec -2 0 1 8  
Versi o n: 3. 0  
P a ge 1 1 6  of 1 2 8  
 
 
 
 E ns uri n g i n vesti gati o nal staff are well i nstr ucte d a n d trai ne d i n i nf or mi n g 
s u bjects a b o ut t he ca p pi n g li mits i.e., t he ris k of n ot bei n g ra n d o mise d i n s pite 
of meeti n g eli gi bilit y crit eria.  
T hr o u g h o ut t he tr i al, data q ualit y re vi e w meeti n gs will be hel d t o e ns ure t hat data c ollecti o n 
ca n be i m pr o ve d , a n d mista kes pre ve nt e d. D uri n g m o nit ori n g visits t o t he trial sites, t he C R As 
will verif y t h at 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 ele ctr o nic dat a ca pt ure u nless tr a ns mitte d t o L E O or 
desi g nee electr o nicall y (e. g., la b orat or y dat a). T h e i n vesti gat or or st aff a ut h orise d b y t h e 
i n vesti gat or will e nter s u bject data i nt o electr o nic C R Fs (e C R Fs). Data rec or de d i n t he e C R Fs 
will be accessi ble t o t he trial 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 Fs 
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 h e c orrect n ess of t he data e ntere d b y t he site b y el ectr o nicall y 
dati n g a n d si g ni n g all eC R Fs use d. T his si g n at 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 m e nte d i n t he a u dit trail. C ha n ges t o data alrea d y 
a p pr o ve d will re q uir e re -si g nat ur e b y t he i n vesti gat or. T h e pers o n ma ki n g t he c ha n ge t o t he 
data, a n d t he d ate, ti me , a n d reas o n f or t he c h a 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 eC 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 C li nical T rial A gree me nt. Q ueries f or discre p a 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 n a ger. All q ueries will be rais e d electr o nicall y wit hi n 
t he electr o nic d ata ca pt ur e  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.  
A n e lectr o nic P R O (e PR O) s ol uti o n will be use d t o  ca pt ure p atie nt -re p orte d data (data fr o m 
q uesti o n naires c o m plete d at t he trial site a n d e Diar y dat a). B y t he use of a n e P R O, data will 
be a vaila ble i m me diatel y after data e ntr y  or data tra ns missi o n  a n d a vaila ble f or m o nit ors a n d 
site pers o n nel, i ncl u di n g t he i n vesti gat or, wit h rea d access o nl y. T he e P R O s yste m is a 
se parat e a p plicati o n fr o m t he e C R F a n d dat a ca pt ure d fr o m t he e C R F a n d t he e P R O will be 
st ore d o n differe nt ser v ers d uri n g dat a ca pt ur e. Data fr o m b ot h s yste ms will be i ncl u de d i n t he 
fi nal trial databas e.  


Trial I D: L P 0 1 3 3 -1 2 7 3  
Date: 0 7 -Dec -2 0 1 8  
Versi o n: 3. 0  
P a ge 1 1 7  of 1 2 8  
 
 
 
E xter nal data tra nsfers fr o m ve n d ors t o L E O will be tra ns mitt e d a n d ha n dl e 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 dat a pr o vi ders a n d of  
e P R O data t o t he cli nical data base are ill ustrate d i n Pa nel 1 6 . 
P a nel 1 6 : Tr a ns missi o n of electr o nic d at a  
 
 
 
A b bre vi ati o ns:  C T R, cli nical trial re p ort; E C G, electr ocar di o gra m; e CR F, electr o nic case re p ort f or m; e P R O, 
electr o nic patie nt -re p orte d o utc o me 
 
Arc hi vi n g of tri al d oc u me nt ati o n  
T he i n vesti gat or at e ac h trial site m ust ma ke arra n ge m e nts t o  st ore t he esse ntial trial 
d oc u me nts , i ncl u di n g t he in vesti gat or trial file (2 8 ). 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 h at t he d oc u m e nts are n o l o n ger t o be reta i ne d, or l o n ger 
if re q uire d b y l oc al re g ul ati 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 m e 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 x a m ple i n case of a n i ns pecti o n fr o m re g ul at or y a ut h orities).  
T he i n vesti gat or is re q uir e d t o e ns ure t he c o nti n ue d st ora ge of t he d o c u me nts e ve n if t he 
i n vesti gat or lea ves t he tri al site or retires b ef ore t he e n d of t he re q uire d st ora ge peri o d.  
N o d oc u me nts ma y be de str o ye d d uri n g t he ret e 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 . 


Trial I D: L P 0 1 3 3 -1 2 7 3  
Date: 0 7 -Dec -2 0 1 8  
Versi o n: 3. 0  
P a ge 1 1 8  of 1 2 8  
 
 
 
T he destr ucti o n pr o cess m ust e ns ure c o nfi de ntialit y of dat a 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 ves ti gat or will be s u p plie d wit h a n electr o ni c c o p y of t he 
eC R Fs a n d e P R O data f or all scree ne d a n d ra n d o mise d s u bjects e nr olle d 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/e P R O is re v o ke d. A u dit 
trail i nf or mati o n will be i ncl u de d. eC R Fs a n d e P R O data m ust be a vaila bl e 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 r e 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: R e 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 T rials. g o v bef ore t h e first s u bject e nters i nt o t he trial. T he trial ma y als o be c o me 
re gistere d i n ot her o nli ne data re gistries, acc or di n g t o a p plica ble la w a n d re g ul ati 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 A ccess t o Cli nical  Tri al 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 r es 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 aft er cli nical trial c o m pleti o n or pre mat ure ter mi nati o n.  
L E O m a y als o pr o vi de researc h ers access t o a n o n y mise d patie nt le v el 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 Acces s 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  
T he i n vesti gat or s hall be e ntitle d t o ma ke p u blicati o ns of t he res ults ge nerat e d b y i n v esti gat or 
i n acc or da nce wit h t he pr ocess descri be d here. 
A  m ulti -ce ntre p u blicati o n will be  s u b mitte d f or p u blicati o n wit hi n 1 8 m o nt hs after t he 
cli nical trial has bee n c o m plete d or ter mi nate d at all trial sites a n d all data ha ve bee n recei ve d, 
defi ne d as d ata base l o c k of t he cli nical trial . After s uc h m ulti -ce ntre p u blicati o n is ma de 
p u blic , or  if n o m ulti-ce ntre p u blicati o n has bee n s u b mitte d wit h t he a b o ve -descri be d 
dea dli ne,  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 n erat e d b y t he i n vesti gat or, s u bject t o t h e f oll o wi n g n otice re q uire m e nts:  


Trial I D: L P 0 1 3 3 -1 2 7 3  
Date: 0 7 -Dec -2 0 1 8  
Versi o n: 3. 0  
P a ge 1 1 9  of 1 2 8  
 
 
 
Pri or t o  s u b missi o n f or p u blicati o n or prese nti n g a ma n uscri pt relati n g t o t he cli nical trial, t he 
i n vesti gat or s hall pr o vi d e t o L E O a c o p y of all s uc h ma n uscri pts a n d/ or prese ntati o n s. L E O 
s hall ha ve ri g hts t o re vie w a n d c o m me nt. T he i n v esti gat or s h all c o nsi der c o m me nts  pr o vi de d 
b y  L E O  b ut is n ot re q uir e d t o m o dif y t he ma n us cri pt a n d/ or prese ntati o n base d o n s uc h 
c o m me nts, pr o vi de d , h o we ver, t hat t he in v esti gat or u p o n t he re q u est of L E O re m o ves a n y 
c o nfi de ntial i nf or mati o n ( ot her t ha n res ults ge n erate d b y t he i n v e sti gat or) pri or t o s u b mitti n g 
or prese nti n g t he ma n us cri pts. T he i n vesti gat or s h all, u p o n t he re q uest of L E O  wit h h ol d  t he 
p u blicati o n or prese ntati o n t o all o w L E O t o pr ot ect 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 u c h ma n usc ri pts. 
I n case n o m ulti -ce ntre p u blicati o n has bee n ma de p u blic at t he ti me of i n vesti gat or’s 
n otificati o n  of a n i n de pe n de nt p u blicati o n t o L E O , L E O a n d t he writi n g gr o u p ma y als o dela y 
t he p u blicati o n or prese nt ati 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 ntr e 
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 v e -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 P ractice ( 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 nt er 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), J a pa n P har m ace uti cal M a n ufact urers 
Ass ociati o n (J P M A), P har mace utical Researc h a n d Ma n ufact ur ers 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 di cal  Writers Ass o ciati o n ( A M W A), t he 
E ur o pea n Me dical Writer s Ass ociati o n ( E M W A), a n d t he I nt er nati o nal S oci et y f or Me dical 
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 ( 1 2 ). 
A p pe n di x 3 F: I ns ur a nce 
L E O h as ta ke n o ut r ele va nt i ns ura nces c o v eri n g t h e s u bjects i n t he pres e 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 d iscl os ure 
I n v esti gat ors will pr o vi de L E O wit h s uffici e nt, acc urate fi na ncial i nf or m ati 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 urat e fi na ncial certificati o n or discl os ure state me nts t o 
t he a p pr o priat e re g ulat or y a ut h orities. I n v esti gat ors are res p o nsi ble f or pr o vi di n g i nf or mati o n 


Trial I D: L P 0 1 3 3 -1 2 7 3  
Date: 0 7 -Dec -2 0 1 8  
Versi o n: 3. 0  
P a ge 1 2 0  of 1 2 8  
 
 
 
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 aft er 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 h e i n vesti gat or, t h e I R B/I E Cs or c o m pete nt a ut h orities ma y d eci 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 m e 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 nic al trial is s us pe n de d or pre m at 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 pecifi e 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 h e 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 m ar ka ble s afet y la b orat or y c h a n ges) bec o mes 
u nfa v o ura bl e f or 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 tri al 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 g at or t o c o m pl y wit h t he pr ot oc ol, t he re q uir e me nts of t he 
I R B/I E C or l ocal h ealt h a ut h orities, L E O pr oce d ures, or G C P g ui d eli nes. 
 I n a de q uat e 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 v esti 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 u este d n u m ber of s u bjects f or t he cli nical trial  or 
partici pati n g c o u ntr y  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 tri al site is c o nsi dere d cl ose d w he n all re q uir e d d oc u me nt s a n d trial 
s u p plies ha ve bee n c ollecte d a n d a trial site cl os ur e visit has bee n perf or me d.  


Trial I D: L P 0 1 3 3 -1 2 7 3  
Date: 0 7 -Dec -2 0 1 8  
Versi o n: 3. 0  
P a ge 1 2 1  of 1 2 8  
 
 
 
W he n t he ra n d o misati o n c o de has bee n br o k e 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 oc ati o n f or t he s u bjects r a 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. 
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 v esti gat or A gree m e 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 h e cli nical trial c o n d uct at 
his/ her trial site as a gree d t o i n a Cli nical Trial A gree me nt.  
 


Trial I D:  L P 0 1 3 3 -1 2 7 3  
Date: 0 7 -Dec -2 0 1 8  
Versi o n: 3. 0  
P a ge 1 2 2  of 1 2 8  
 
 
 
A p pe n di x 4 : S h ort versi o n of  eli gi bilit y criteri a 
T his a p pe n di x pr o vi des a s h ort f or m  ( ma xi m u m 2 0 0 c haracters) of eac h of t he eli gi bilit y 
criteria t o be us e d w he n data are s u b mitte d t o re g ulat or y a ut h orities  i n C DI S C f or mat. 
I ncl usi o n criteri a 
N o.  
 
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 years or a b o ve.  
3  
Dia g n osis of c hr o nic ha n d ecze ma defi ne d as ha n d ecze ma, w hic h has persiste d f or m ore t ha n 
3  m o nt hs or ret ur ne d t wice or m ore wit hi n t he last 1 2  m o nt hs.  
4  
Disease se verit y gra d e d as mil d t o se vere  acc or di n g t o I G A  (i.e., a n I G A sc ore of 2 or m ore).  
5  
Rece nt hist or y ( wit hi n 1  year bef ore t he scree ni n g visit) of i na de q uate res p o nse t o t o pical 
c ortic oster oi d treat me nt or t o pical c ortic oster oi d treat me nt bei n g me dicall y i na d visa ble.  
6  
Dia g n ostic patc h testi n g perf or me d wit hi n 3  years pri or t o t he scree ni n g visit.  
7  
A w o ma n 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 p plicati o n of I M P. 
 
 
E xcl usi o n criteri a  
N o.  
 
1  
C o nc urre nt s ki n diseases o n t he ha n ds , e. g. ti nea ma n u u m.  
2  
Acti ve at o pic der matitis i n re gi o ns ot her t ha n t he ha n ds or ps oriasis re q uiri n g me dical treat me nt.  
3  
Cli nicall y si g nifica nt i nfecti o n (e. g., i m peti gi nise d ha n d ecze ma) o n t he ha n ds.  
4  
S yste mi c treat me nt wit h i m m u n os u p pressi ve dr u gs, i m m u n o m o d ulati n g dr u gs, reti n oi ds, or 
c ortic oster oi ds wit hi n 4  wee ks pri or t o baseli ne.  
5  
Ps orale n ultra vi olet A ( P U V A ) or ultra vi olet B ( U V B ) t hera p y o n t he ha n ds wit hi n 4 wee ks pri or t o 
baseli ne.  
6  
Recei pt of l i ve atte n uate d vac ci nes 4 wee ks pri or t o baseli ne. 
7  
C uta ne o usl y a p plie d treat me nt wit h i m m u n o m o d ulat ors (e. g., P D E -4 i n hi bit ors, pi mecr oli m us, 
tacr oli m us) or t o pical c ortic oster oi ds o n t he ha n ds wit hi n 2 wee ks pri or t o baseli ne.  
8  
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 ha n ds wit hi n 2  wee ks pri or t o 
baseli ne.  
9  
C ha n ge i n s yste mic a nti hista mi ne t hera p y wit hi n 2  wee ks pri or t o baseli ne i.e., s u bj ects m ust n ot 
start a nti hista mi ne treat me nt or c ha n ge t he c urre nt d osa ge re gi me wit hi n 2 wee ks pri or t o baseli ne.  
1 0  
Ot her c uta ne o usl y a p plie d t hera p y o n t he ha n ds (e xce pt f or t he use of s u bj ect’s o w n e m olli e nts) 
wit hi n 1  wee k pri or t o baseli ne.  
1 1  
C uta ne o usl y a p plie d treat me nts i n re gi o ns ot her t ha n t he ha n ds, w hic h c o ul d i n terfere wit h cli nical 
trial e val uati o ns or p ose a safet y c o ncer n wit hi n 1 wee k pri or t o baseli ne.  
1 2  
Recei pt of a n y mar kete d or i n vesti gati o nal bi ol o gic a ge nt s wit hi n 6  m o nt hs  or 5 half -li ves pri or t o 
baseli ne or u ntil cells c o u nts r et ur ns t o n or mal, w hic he ver is l o n ger.  


Trial I D:  L P 0 1 3 3 -1 2 7 3  
Date: 0 7 -Dec -2 0 1 8  
Versi o n: 3. 0  
P a ge 1 2 3  of 1 2 8  
 
 
 
1 3  
Recei ve d treat me nt wit h a n y n o n -mar kete d dr u g s u bsta nce wit hi n t he last 4  wee ks pri or t o baseli ne 
or 5  half -li ves w hic he ver is t he l o n gest. 
1 4  
Cli nicall y si g nifica nt i nfe cti o n (s yste mic i nfecti o n or seri o us s ki n i nfecti o n re q uiri n g pare nteral 
treat me nt) wit hi n 4 wee ks pri or t o baseli ne . 
1 5  
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 bj ects wit h a p ositi ve 
bl o o d test f or t u berc ul osis at s c ree ni n g (su bj ects wit h hi g h ris k of late nt t u berc ul osis m ust be teste d ). 
1 6  
Hist or y of a n y k n o w n pri mar y i m m u n o deficie nc y dis or der i ncl u di n g a p ositi ve HI V test at scree ni n g , 
or t he s u bj ect ta ki n g a ntiretr o viral me dicati o ns.  
1 7  
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 pitalis ati o n 
d uri n g t he trial peri o d.  
1 8  
Hist or y of ca ncer.  
1 9  
A n y dis or der w hic h is n ot sta ble a n d i n t he i n vesti gat or’s o pi ni o n c o ul d  a ffect t he safet y of t he 
s u bj ect, infl ue nce t he fi n di n gs of t he trial , or im pe de t he s u bj ect’s a bilit y t o c o m plete t he trial.  
2 0  
A n y a b n or mal fi n di n g w hic h i n t he i n vesti gat or’s o pi ni o n ma y put t he s u bj ect at ris k, i nfl ue nce t he 
res ults of t he trial, or infl ue nc e t he s u bj ect’s a bilit y t o c o m plete t he trial.  
2 1  
P ositi ve H Bs A g, H Bs A b, H B c A b, or a nti-H C V  ser ol o g y at scree ni n g. S u bj ects wit h p ositi ve H Bs A b 
ma y be ra n d o mise d pr o vi de d t he y are he patitis B vacci nate d a n d ha ve ne gati ve H Bs A g a n d H B c A b.  
2 2  
Ala ni ne a mi n otra nsferase or as partate a mi n otra nsferase le vel 2. 0  ti mes t he U L N ra n ge or m ore at 
scree ni n g. 
2 3  
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.  
2 4  
C urre nt p artici pati o n i n a n y ot her i nter ve nti o nal cli nical trial.  
2 5  
Pre vi o usl y ra n d o mise d i n t his cli nical trial.  
2 6  
Pre vi o usl y 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).  
2 7  
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.  
2 8  
E m pl o ye d at t he trial site or 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. 
2 9  
Le gall y i nstit uti o nalise d.  
3 0  
Pre g na nt or lactati n g . 
A b bre vi ati o ns:  a nti -H C V, he patitis C vir us a nti b o d y; H B c A b, he patitis B c ore a nti b o d y ; H Bs A b, he patitis B 
s urface a nti b o d y; H Bs A g, he p atitis B s urface a nti ge n; HI V, h u ma n i m m u n o deficie nc y vir us;  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 di ci nal pr o d uct ; P D E -4, p h os p h o diesterase -4; 
U L N, u p per li mit of n or mal . 
 
 


Trial I D: L P 0 1 3 3 -1 2 7 3  
Date: 0 7 -Dec -2 0 1 8  
Versi o n: 3. 0  
P a ge 1 2 4  of 1 2 8  
 
 
 
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 n a ger ( C P M ), a p p oi nte d C R A, a n d s p o ns or ’s 
me dical e x pert are pr o vi de d t o t he trial sites as a se parat e 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 tri al: 
L E O P har ma A/ S  
I n d ustri p ar ke n 5 5 
D K -2 7 5 0 Baller u p  
De n mar k  


Trial I D: L P 0 1 3 3 -1 2 7 3  
Date: 0 7 -Dec -2 0 1 8  
Versi o n: 3. 0  
P a ge 1 2 5  of 1 2 8  
 
 
 
A p pe n di x 6: Pr ot o c ol a me n d me nt hist or y  
 
T he pr ot oc ol a me n d m e nt s u m mar y of c ha n ges ta ble f or t he c urre nt a me n d me nt is l ocate d 
directl y b ef ore t he ta ble of c o nte nts.  
A me n d me nt 1  ( 1 1-J ul-2 0 1 8)  
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 criteri a 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 ul ati o n.  
O ver all r ati o n ale f or t he a me n d me nt  
T he mai n reas o n f or t he a me n d me nt is t o a d d a n e x cl usi o n criteri o n t o e ns ure t hat s u bjects 
w h o pre vi o usl y p artici pa t e d i n a cli nical trial wit h del g o citi ni b ( L E O 1 2 4 2 4 9) are n ot all o we d 
t o partici pate i n t his trial. I n a d diti o n, t he a me n d m e nt i ncl u des ot her c h a n ges, as prese nte d i n 
t he ta ble bel o w. 
T he ta ble bel o w prese nts c ha n ges ma d e i n eac h secti o n a n d a brief rati o nal e f or eac h c ha n ge. 
C ha n ges h a ve eit her bee n s u m marise d ( writte n wit h plai n te xt o nl y) or mar ke d as trac ke d 
c ha n ges ( n e w te xt t hat has bee n a d de d t o t he pr ot o c ol is hi g hli g hte d i n b ol d  a n d te xt t hat has 
bee n re m o v e d fr o m t he pr ot oc ol is hi g hli g ht e d wit h a li ne t hr o u g h t h e te xt ). 
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  
Secti o n 4 
Sc he d ule of trial 
pr oce d ures  
T he ‘X ’ at Wee k 1 a n d at Wee k  1 2 
f or t he W L Q q uesti o n naire in t he 
sc he d ule of trial pr oce d ures ha ve 
bee n re m o v e d.  
T he W L Q will be assesse d less 
fre q ue ntl y t o re d u ce t he b ur de n o n 
t he trial s u bjects.  
Secti o n 8. 3 
E x cl usi o n criteria,  
A p pe n di x 4: 
S h ort versi o n of 
eli gi bilit y criteria  
A ne w e x cl usi o n criteri o n has 
bee n a d d e d:  
Pre vi o usl y p artici p ate d i n a 
cli nic al tri al wit h del g ociti ni b 
( L E O 1 2 4 2 4 9).  
To a v oi d recr uit me nt of s u bjects 
w h o ha ve bee n e v al uate d i n 
pre vi o us del g ociti ni b trials.  


Trial I D: L P 0 1 3 3 -1 2 7 3  
Date: 0 7 -Dec -2 0 1 8  
Versi o n: 3. 0  
P a ge 1 2 6  of 1 2 8  
 
 
 
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  
Secti o n 8. 3 
E x cl usi o n criteria,  
A p pe n di x 4: 
S h ort versi o n of 
eli gi bilit y criteria  
E x cl usi o n criteri o n 2 5 has bee n 
c ha n ge d t o:  
Pre vi o usl y r a n d o mise d scree n e d 
i n t his cli nical trial. 
T his has bee n c h a n ge d t o all o w 
f or re-scree ni n g i n cas e of 
a d mi nistrati ve reas o ns.  
Secti o n 8. 4 
Scree ni n g a n d 
scree ni n g fail ures 
T he te xt i n t his secti o n has bee n 
c ha n ge d t o:  
Re scree ni n g of scree ni n g fail ures 
is n ot all o we d. I n di vi d u als w h o 
d o n ot meet t he crit eri a f or 
p artici p ati o n i n t he tri al 
(scree ni n g f ail ures) m a y n ot be 
re-s cree ne d. H o w e ver, if t he 
re as o n f or scree ni n g f ail ure is 
a d mi nistr ati ve e. g., del a ye d test 
res ults a n d n ot d ue t o t he 
s u bject f aili n g t o meet t he 
eli gi bilit y criteri a, re -scree ni n g 
m a y be per mitte d. I n di vi d u als 
w h o are re -scree ne d will get a 
ne w s u bject I D.  
T his has bee n c h a n ge d t o all o w 
f or re-scree ni n g i n cas e of 
a d mi nistrati ve reas o ns.  
Secti o n 9. 2 
A d mi nistrati o n of 
I M P 
T he f oll o wi n g s e nte nce h as bee n 
a d de d:  
T he s u bjects will be a d vise d t o 
c o nt act t he i n vesti g at o r bef ore 
i niti ati n g tre at me nt of ne w 
lesi o ns. 
T his has bee n a d d e d t o descri be  
t hat t he deter mi nati o n of ne w 
lesi o ns s h o ul d be c o nsi dere d b y 
t he i n vesti gat or. 
Secti o n 9. 8. 2 
St ora ge of trial 
pr o d ucts  
T he f oll o wi n g s e nte nce h as bee n 
c ha n ge d t o:  
T he I M Ps m ust be st ore d at 2 -8° C  
( 3 6-4 6° F) . D o n ot freeze.  
T his has bee n a d d e d t o f urt her 
clarif y t he st ora ge c o n diti o n of t he 
I M P.  


Trial I D: L P 0 1 3 3 -1 2 7 3  
Date: 0 7 -Dec -2 0 1 8  
Versi o n: 3. 0  
P a ge 1 2 7  of 1 2 8  
 
 
 
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  
Secti o n 1 0. 1 
Ge neral 
pri nci ples  
T he te xt i n t his secti o n has bee n 
c ha n ge d t o:  
T he pri mar y reas o n s f or 
wit h dra wal fr o m t he trial, a n d 
disc o nti n uati o n of I M P, a n d n ot 
atte n di n g t he pri m ar y e n d p oi nt 
visit at Wee k  1 6, if a p plic a 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: 
T his se nte nce has b ee n c ha n ge d 
f or c o nsiste nc y wit h ot her 
secti o ns i n t he pr ot oc ol. 
Secti o n 1 1. 4. 4 
La b orat o r y 
testi n g 
T he te xt i n t his secti o n has bee n 
c ha n ge d t o:  
If a scree ni n g la b orat or y res ult is 
a b n or mal a n d of cli nical 
si g nifica n ce, 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 x cl usio n criteria n o. 
1 6, 2 0, 2 1, a n d 2 2 , a n d 3 0). 
T his se nte nce has b ee n c ha n ge d t o 
clarif y t hat t he pre g na n c y testi n g 
s h o ul d als o be c o nsi dere d t o 
deter mi ne if a s u bject is eli gi ble.  
Secti o n 1 1. 5. 1 
Bl o o d sa m pli n g 
f or a nal ysis of 
s yste mic 
c o nce ntr ati o n of 
del g o citi ni b  
T he f oll o wi n g s e nte nce h as bee n 
a d de d i n t he last para gra p h:  
Sa m ples fr o m del g o citi ni b crea m 
ve hicle -tr eate d s u bjects will n ot 
be a nal yse d. Writte n pr oce d ures 
are i n pl ace t o a v oi d u n bli n di n g 
of t he tri al a n d a n y tri al 
s u bjects i n rel ati o n t o a n alysis 
of t he P K s a m ples.  
T his se nte nce has b ee n a d de d t o 
clarif y t hat writte n pr oce d ures are 
i n place t o a v oi d p ote ntial 
u n bli n di n g.  
Secti o n 1 1. 6. 1 
O ver vie w  
T he last se nte nce i n t he 2 n d b ullet 
p oi nt has bee n delete d:  
T his se nte nce has b ee n d elete d t o 
all o w f or fle xi bilit y a n d n ot 


Trial I D: L P 0 1 3 3 -1 2 7 3  
Date: 0 7 -Dec -2 0 1 8  
Versi o n: 3. 0  
P a ge 1 2 8  of 1 2 8  
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  
Micr o bi o me di versit y i n a s u bset 
of s ki n s wa bs i n vesti gate d b y use 
of ne xt ge nerati o n se q ue nci n g 
met h o ds. T he s u bset will be 
selecte d after u n bli n di n g fr o m 
s u bjects fr o m t he hi g hest d ose 
gr o u p a n d fr o m t he v e hicle
c o ntr olle d gr o u p.  
restrict t his s u bset t o t he hi g hest 
del g o citi ni b d ose gr o u p.  
Secti o n 1 1. 6. 5 
N o n -i n vasi ve 
meas ure me nts of 
s ki n barrier 
f u ncti o n (select e d 
trial sites) 
T he f oll o wi n g s e nte nce h as bee n 
a d de d:  
T he ti me fr o m l ast I M P 
a p plic ati o n t o s ki n b arrier 
me as ure me nt will be rec or de d. 
T his se nte nce has b ee n a d de d t o 
all o w f or assessi n g w het her t here 
is a n y c orrel ati o n bet wee n t he 
ti me fr o m last I M P a p plicati o n 
a n d t he meas ure d val ues of s ki n 
barrier f u ncti o n.  
Secti o n 1 1. 1 0 
St ora ge of 
bi ol o gical 
sa m ples 
T he f oll o wi n g s e nte nce i n t he 
secti o n descri bi n g t he bi o ba n k has 
bee n c h a n ge d t o:  
T he resi d ual bi ol o gical s a m ples 
will be use d f or f ut ure researc h 
perf or me d b y L E O or m a y be  
gi ve n t o ac a de mic p art ners t o be 
u se d f or f ut ure res e arc h i n 
c hr o nic h a n d ecze m a a n d 
rel ate d dise ases . 
T his has bee n a d d e d t o cl arif y t hat 
c olla b orati o n part n ers ma y be 
i n v ol ve d i n f ut ure res earc h of t he 
sa m ples. 
T hr o u g h o ut  
Mi n or e dit orial a n d d oc u me nt 
f or matti n g re visi o ns. 
Mi n or, ha ve t heref ore n ot bee n 
s u m marise d. 


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P D D
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