A Randomized Double-blind, Placebo-controlled Study Evaluating the Effect of Dupilumab on Sleep in Adult Patients With Moderate to Severe Atopic Dermatitis (AD)
Phase: PHASE4
Conditions: Atopic Dermatitis
Sponsor: Sanofi

 
 
 
A ny a n d all i nf or m ati o n pres e nt e d i n t his d oc u m e nt s h all b e tre at e d as c o nfi d e nti al a n d s h all re mai n t h e excl usiv e pro p erty of S a n ofi ( or a ny of its 
affili at e d c o m p a ni es). T h e us e of s uc h c o nfi d e nti al i nf or m ati o n m ust b e r estrict e d t o t h e rec i pi e nt f or t h e a gre e d p urp os e a n d m ust not b e 
discl os e d, pu blis h e d or ot h er wis e c o m m u nic at e d t o a ny u n a ut h oriz e d p ers o ns, f or a ny re as o n, i n a ny f or m w h ats o ev er wit h o ut t h e pri or wr itt en 
c o ns e nt of S a n ofi (or t h e c o nc ern e d affili at e d c o m p a ny); ‘ affili at e d c o mp a ny’ m e a ns a ny c orp orati o n, p art n ers hi p or ot h er e ntity w hic h at t he d at e 
of c o m m u nic ati o n or aft er w ards (i) c o ntrols direc tly or i n dir ectly S a n ofi, (ii) is directly or i n directly c o ntroll e d by S a n ofi, wit h ‘c o ntr ol’ m e ani n g 
dir ect or i n direct o w n ers hi p of m or e t h a n 5 0 % of t h e c a pit al st ock or t h e v oti n g ri g hts i n s uc h c or p or ati o n, p art n ers hi p or ot h er e ntity  
A c c or di n g t o t e m pl at e: R D S D -0 0 2 5 4 0 V E R SI O N N° 1. 0 ( 0 2 -M A Y -2 0 1 8) b a s e d o n Tr a n s C el er at e C P T v er si o n 4  
P a g e 1  
A M E N D E D C LI NI C A L T RI A L P R O T O C O L 0 2   
Pr ot o c ol titl e:  
A r a n d o mi z e d d o u bl e -bli n d pl a c e b o -c o ntr oll e d st u d y 
e v al u ati n g t h e eff e ct of d u pil u m a b o n sl e e p i n a d ult 
p ati e nt s wit h m o d er at e t o s e v er e at o pi c d er m atiti s  
Pr ot o c ol n u m b er:  
L P S 1 5 4 9 7  
A m e n d m e nt n u m b er:  
0 2  
C o m p o u n d n u m b er 
(I N N/Tr a d e m ar k ): 
D u pil u m a b  
 
S h ort titl e:  
S A R 2 3 1 8 9 3 -L P S 1 5 4 9 7 - “ D u pil u m a b eff e ct o n Sl e e p i n 
A D p ati e nt s ” -D U PI S T A D  
S p o n s or n a m e:  
 
L e g al r e gi st er e d 
a d dr e s s : 
 
M o nit ori n g T e a m’ s 
R e pr e s e nt ati v e N a m e 
a n d C o nt a ct I nf or m ati o n 
 
R e g ul at or y a g e n c y i d e ntif yi n g n u m b er( s):  
E u dr a C T n u m b er:  
2 0 1 8 -0 0 4 7 0 5 -2 6  
I N D n u m b er: 
1 0 7 9 6 9  
W H O  n u m b er:  
U 1 1 1 1 -1 2 2 3 -4 1 4 7  
N C T  n u m b er:  
N C T 0 4 0 3 3 3 6 7  
A p pr o v al D at e:  
0 7 -A pr -2 0 2 0  
T ot al n u m b er of  p a g e s:  1 0 6  
 
 
 
 
 
 
 
 
V V- C LI N- 0 5 5 0 3 9 6 4. 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol 0 2  
L P S 1 5 4 9 7  
7 -A pr -2 0 2 0  
V er si o n n u m b er: 1  
 
Pr o p ert y of t h e S a n ofi gr o u p - stri ctl y c o nfi d e nti al  
P a g e 2  
P R O T O C O L A M E N D M E N T S U M M A R Y O F C H A N G E S T A B L E   
D O C U M E N T HI S T O R Y   
 
D o c u m e nt  
C o u ntr y / c o u ntri e s 
i m p a ct e d b y 
a m e n d m e nt  
D at e, v er si o n  
A m e n d e d Cli ni c al Tri al pr ot o c ol 0 2  
All  
0 7  A pril  2 0 2 0, v er si o n 1 ( el e ctr o ni c 4 . 0) 
A m e n d e d Cli ni c al Tri al pr ot o c ol 0 1  
All  
1 0  O ct o b er 2 0 1 9 , v er si o n 1  ( el e ctr o ni c 1 . 0) 
Ori gi n al Pr ot o c ol  
 
0 3  A pr il 2 0 1 9, v er si o n 2 ( el e ctr o ni c 3. 0)  
A m e n d e d pr ot o c ol  [0 2 ] (0 7  A pril 2 0 2 0 ) 
T his a me n de d pr ot oc o l ( a me n d me nt 0 2 ) is c o nsi d ere d t o be s u bsta ntial bas e d o n t he criteria set 
f ort h i n Article 1 0(a) of Directi ve 2 0 0 1/ 2 0/ E C of t he E ur o pea n Parlia me nt a n d t he C o u ncil of t he 
E ur o pea n U ni o n . 
 
O V E R A L L R A TI O N A L E F O R T H E A M E N D M E N T  
T his a me n d me nt i nc or p orates fe w c ha n ges i n t he i ncl usi o n /e xcl usi o n criteria a n d i n t he ti mi n g of  
Patie nt Re p orte d O utc o m es ( P R Os) assess me nts, as well as a fe w mi n or c ha n ges s u m marize d 
bel o w.  
Pr ot o c ol a m e n d m e nt s u m m ar y of c h a n g e s t a bl e  
S e cti o n # a n d N a m e  
D e s cri pti o n of C h a n g e  
Bri ef  R ati o n al e  
Titl e p a g e  
N C T n u m b er a n d W H O n u m b er h av e 
b e e n a d d e d  
T o c o m pl et e t h e pr ot oc ol i d e ntific ati o n 
i nf or m ati o n 
1. 3 Sc h e d ul e of Activiti es  ( S o A)   
 
S o A: t h e ass ess m e nt of t h e Ep w ort h 
Sl e e pi n ess Sc al e ( E S S) is d el et e d at 
w e ek s 1 , 2 , 8, 1 6 a n d 2 0. 
L ess fr e q u e nt ass ess m e nts t o r e d uc e 
p ati e nts’ b ur d e n  
3 T a bl e 1 -O bj ectiv es a n d e n d p oi nts -
Ex pl or at ory e n d p oi nts  
S ecti o n 3: c h a n g e fr o m b as eli n e i n E S S 
will b e ass ess e d at w e eks 4 a n d 1 2.   
 
1. 3 Sc h e d ul e of Activiti es  
S o A: t h e ass ess m e nt of t h e H os pit al 
A nxi ety a n d D e pr essi o n S c al e ( H A D S) 
is d el et e d at w e eks 1, 2, 8, 1 6 a n d 2 0. 
L ess fr e q u e nt ass ess m e nts t o r e d uc e 
p ati e nts’ b ur d e n , a n d as it m ay t ak e 
m or e ti m e t o o bs erv e a n i m pr ov e m e nt 
f or t his sc al e. 
3 T a bl e 1 -O bj ectiv es a n d e n d p oi nts -
Ex pl or at ory e n d p oi nts  
S ecti o n 3: c h a n g e fr o m b as eli n e i n 
H A D S will b e ass ess e d at w e eks 4 a n d 
1 2.   
 
1. 3 Sc h e d ul e of A ctiviti es  
 
T h e ass ess m e nt of t h e P ati e nt O ri e nt e d 
E cz e m a M e as ur e  ( P O E M) is d el et e d at 
w e eks 1, 2, 8, 1 6 a n d 2 0.  
L ess fr e q u e nt ass ess m e nts t o r e d uc e 
p ati e nts’ b ur d e n  
V V- C LI N- 0 5 5 0 3 9 6 4. 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol 0 2  
L P S 1 5 4 9 7  
7 -A pr -2 0 2 0  
V er si o n n u m b er: 1  
 
Pr o p ert y of t h e S a n ofi gr o u p - stri ctl y c o nfi d e nti al  
P a g e 3  
S e cti o n # a n d N a m e  
D e s cri pti o n of C h a n g e  
Bri ef  R ati o n al e  
1. 3 Sc h e d ul e of Activiti es  
T h e ass ess m e nt of t h e D er m at ol o gy 
L if e Q u ality In d ex ( D L QI) is d el et e d at 
w e eks 1, 2, 8, 1 6 a n d 2 0.  
L ess fr e q u e nt ass ess m e nts t o r e d uc e 
p ati e nts’ b ur d e n , a n d as it m ay t ak e 
m or e ti m e t o o bs erv e a n i m pr ov e m e nt 
f or t his sc al e. 
1. 3 Sc h e d ul e of Activiti es  
S o A: t h e ass ess m e nt of t h e W ork 
pr o d uctivity a n d activity i m p air m e nt –  
At o pic D er m atitis v ersi o n ( W P AI -A D) is 
d el et e d at w e eks 1, 2, 1 6 a n d 2 0.  
L ess fr e q u e nt ass ess m e nts t o r e d uc e 
p ati e nts’ b ur d e n  
3 T a bl e 1 -O bj ectiv es a n d e n d p oi nts -
Ex pl or at ory e n d p oi nts  
S ecti o n 3: c h a n g e fr o m b as eli n e i n 
W P AI -A D ass oci at e d q u esti o ns will b e 
ass ess e d at w e eks 4, 8 a n d 1 2.  
 
1. 3 Sc h e d ul e of Activiti es  
8. 1. 1. 5 P olys o m n o gr a p hy ( P S G) s u b -
st u dy 
T h er e will b e n o a n alysis of scr atc hi n g 
ti m e a n d scr atc hi n g i n d ex 
V i d e o r ec or di n g ( us e d t o assist i n 
sc ori n g sl e e p st u di es a n d r ev e al a ny 
a b n or m al b e h avi ors d uri n g t h e ni g ht ) 
h as a l o w r es ol uti o n, n ot all o wi n g f or a 
pr o p er a n alysis of scr atc hi n g. M or e ov er, 
t h e P S G s u b-st u dy o bj ectiv e is t o 
ass ess sl e e p -r el at e d p ar a m et ers, a n d 
n ot t o c o n d uct a scr atc hi n g a n alysis. 
T his w as i ncl u d e d by err or i n t h e 
pr ot oc ol  
1. 3 Sc h e d ul e of activiti es  
“ Sick l e av e” d el et e d i n t h e pr oc e d ur e 
“ Ass ess miss e d sc h o ol/ w ork d ays” 
Mi n or e dit, t o h ar m o niz e w or di n g  i n t h e 
So A  wit h t h e q u esti o n n air e o n miss e d 
sc h o ol/ w ork d ays” 
1. 3 Sc h e d ul e of activiti es - f o ot n ot e d  
5. 1 I ncl usi o n crit eri a  
8. 1. 2. 1 Sl e e p Q u ality N u m eric al R ati n g 
Sc al e ( N R S)  
8. 1. 2. 3  P e ak  pr urit us N R S  
1 0. 1 0 - A p p e n dix 1 0 P S G s u b -st u dy 
F or p ati e nts p artici p ati n g i n t h e P S G 
s u b-st u dy, t h e sl e e p q u ality N R S a n d 
t h e p e ak pr urit us N R S will b e c o m plet e d 
f or 5 d ays, fr o m D ay -7 t o D ay -3 pri or t o 
b as eli n e . 
I ncl usi o n crit eri a 7 a n d 8 h av e b e e n 
u p d at e d acc or di n gly, a n d t h e m e a n of 
t h e 5-d ay r ec or di n g will b e c alc ul at e d t o 
c h eck if t h es e i ncl usi o n crit eri a ar e m et.  
S ecti o ns 8. 1. 2. 1 a n d 8. 1. 2. 3 h av e b e e n 
u p d at e d acc or di n gly.  
A p p e n dix 1 0: t h e f oll o wi n g i nstr ucti o n 
w as a d d e d: “ Bef or e a ny P S G 
pr oc e d ur es, t h e sit e s h o ul d c alc ul at e t h e 
m e a n of t h e sl e e p q u ality N R S a n d t h e 
m e a n of t h e p e ak pr urit us N R S 
c o m pl et e d f or 5 d ays by t h e p ati e nts, t o 
c o nfir m t h at i ncl usi o n crit eri a 7 a n d 8 
ar e m et”.  
T o c o nfir m p ati e nt’s eli gi bility b ef or e 
d oi n g a ny P S G pr oc e d ur e s, i e t o c h eck 
t h at i ncl usi o n crit eri a 7 a n d 8 ar e m et 
b ef or e pr oc essi n g wit h t h e 2 P S G ni g hts 
r ec or di n g at b as eli n e. 
3 T a bl e 1 -O bj ectiv es a n d e n d p oi nts -
Ex pl or at ory e n d p oi nts  
The chang e fro m baseline in th e Asth ma 
Control Questio nnaire -5 ( A C Q-5) and in 
the Allergic Rhinitis -Visual Analo g Scale 
( A R-V A S) will be ass esse d at week 12. 
There is no assess ment of the cha nge 
fro m baseline to weeks 1, 2, 4 a nd 8.  
Mi n or e dit, t o  c orr ect a ty p o i n T a bl e 1, 
as t h er e is n o ass ess m e nt of t h e A C Q -5 
a n d A R -V A S at w e eks 1 , 2, 4 a n d 8 , as 
i n dic at e d i n t h e S o A. 
V V- C LI N- 0 5 5 0 3 9 6 4. 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol 0 2  
L P S 1 5 4 9 7  
7 -A pr -2 0 2 0  
V er si o n n u m b er: 1  
 
Pr o p ert y of t h e S a n ofi gr o u p - stri ctl y c o nfi d e nti al  
P a g e 4  
S e cti o n # a n d N a m e  
D e s cri pti o n of C h a n g e  
Bri ef  R ati o n al e  
 
“ Fr o m b as eli n e” w as a d d e d f or t h e 
a n alysis of t h e ex pl or at ory e n d p oi nt: 
“Miss e d sc h o ol/ w ork d ays fr o m b as eli n e 
t o w e ek 1 2” 
Mi n or e dit, t o c orr ect a n o missi o n i n t h e 
w or di n g of t his e n d p oi nt  
4. 1 Ov er all d esi g n  
8. 1. 1. 5 P S G s u b -st u dy 
R ef er e nc e t o a s e p ar at e I nf or m e d 
C o ns e nt F or m (I C F) f or p ati e nts 
p artici p ati n g i n t h e P S G s u b-st u dy is 
d el et e d  
Mi n or e dit, t o c orr ect an err or i n th e 
pr ot oc ol: t h er e is a s e p ar at e s ecti o n i n 
t h e gl o b al I C F f or t h e P S G s u b-st u dy, 
b ut n o s e p ar at e I C F.  
5. 1 I ncl usi o n crit eri a  
Incl usi o n crit eri o n 0 2  “Partici p a nts wit h 
c hr o nic A D di a g n os e d by a p hysici a n at 
l e ast 3  y e ars b ef or e t h e scr e e ni n g visit” 
is c h a n g e d t o:  
“ Partici p a nts wit h c hr o nic A D t h at h as 
b e e n d oc u m e nt e d f or at l e ast 2 y e ars 
b ef or e t h e scr e e ni n g visit ” 
T o f acilit at e r ecr uit m e nt  
5. 1 I ncl usi o n crit eri a  
I ncl usi o n crit eri o n 0 4 “Ecz e m a Ar e a 
S ev erity I n d ex ( E A SI) sc or e ≥1 6  at 
scr e e ni n g a n d b as eli n e visits” is 
c h a n g e d t o: 
“Ecz e m a Ar e a Sev erity I n d ex ( E A SI) 
sc or e ≥1 2 at scr e e ni n g a n d b as eli n e 
visits” 
T o f acilit at e r ecr uit m e nt  
5. 2 Excl usi o n crit eri a  
Excl usi o n crit eri o n 1 4 : 
“P ati e nts t aki n g s e d ativ e a nxi olytic or 
hy p n otic tr e at m e nts ot h er t h a n 
m el at o ni n wit hi n 3 m o nt hs b ef or e 
r a n d o miz ati o n” is c h a n g e d t o: 
“P ati e nts t aki n g s e d ativ e a nx i olytic or 
hy p n otic tr e at m e nts ot h er t h a n 
m el at o ni n  o n a r e g ul ar b asis  wit hi n 
3  m o nt hs b ef or e r a n d o miz ati o n . 
Occ asi o n al us e (i e, n o m or e t h a n t wic e 
a w e ek) is all o w e d, exc e pt wit hi n 
2  w e eks b ef or e r a n d o miz ati o n”  
T o all o w f or s o m e fl exi bility, a n d as  
t h es e dr u gs s h o ul d h av e n o i m p act o n 
sl e e p if us e d occ asi o n al ly (exc e pt wit hi n 
t h e 2 w e eks pr ec e di n g b as eli n e ) 
5. 2 Excl usi o n crit eri a  
 
Excl usi o n crit eri o n 1 5:  
“ S e d ativ e” w as a d d e d i n t h e n ot e b el o w:  
“N ot e: Pati e nts t aki n g syst e mic s e d ativ e 
a nti hist a mi n es ≤5 d a ys p er w e ek m ust 
b e o n st a bl e r e gi m e ns f or at l e ast 
1  m o nt h b ef or e r a n d o miz ati o n, a n d 
m ai nt ai n t h e s a m e r e gi m e n t hr o u g h o ut 
t h e st u dy” 
Mi n or e dit, t o c orr ect a n o missi o n i n t his 
s e nt e nc e. 
V V- C LI N- 0 5 5 0 3 9 6 4. 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol 0 2  
L P S 1 5 4 9 7  
7 -A pr -2 0 2 0  
V er si o n n u m b er: 1  
 
Pr o p ert y of t h e S a n ofi gr o u p - stri ctl y c o nfi d e nti al  
P a g e 5  
S e cti o n # a n d N a m e  
D e s cri pti o n of C h a n g e  
Bri ef  R ati o n al e  
5. 2 Excl usi o n crit eri a  
T h e w as h -o ut p eri o d is n o w d efi n e d 
b ef or e b as eli n e visit, i nst e a d of b ef or e 
scr e e ni n g visit, f or excl usi o n crit eri a 1 7 
(syst e mic cycl os p ori n e A, syst e mic 
c ortic ost er oi ds, az at hi o pri n e, 
m et h otr ex at e, myc o p h e n ol at e m of etil, 
j a n us ki n as e i n hi bit or, p h ot ot h er a py), 1 8 
(c ell-d e pl eti n g a g e nts i ncl u di n g b ut n ot 
li mit e d t o rit uxi m a b a n d ot h er bi ol o gics) 
a n d 1 9 (i nv esti g ati o n al a g e nts).  
T o all o w f or s o m e fl exi bility a n d i n 
acc or d a nc e wit h P h as e 3 piv ot al st u di es 
c o n d uct e d wit h D u pix e nt ® i n A D. 
6. 1 St u dy i nt erv e nti o n(s) a d mi nist er e d  
T h e t ext:  
“ T o tr ai n p ati ents h o w t o pr e p ar e a n d 
i nj ect I M P, t h e I nv esti g at or will first tr ai n 
t h e p ati e nt at a n o n-sit e visit d uri n g t h e 
tr e at m e nt p eri o d. At t his visit, t h e 
I nv esti g at or will p erf or m t h e first of t h e 2 
i nj ecti o ns. T h e p ati e nt will p erf or m t h e 
s ec o n d i nj ecti o n u n d er t h e s u p ervisi o n 
of t h e i nv esti g at or or d el e g at e. T his 
tr ai ni n g m ust b e d oc u m e nt e d i n t h e 
p ati e nt’s st u dy fil e. At s u bs e q u e nt st u dy 
visits, p ati e nts or t h eir c ar e giv ers will b e 
tr ai n e d t o s elf-i nj ect I M P, st u dy u ntil 
t h ey ar e pr ofici e nt a n d f e el c o mf ort a bl e 
t o s elf-i nj ect t h e dr u g at h o m e f or c ert ai n 
i nt erv als p er S ecti o n 1. 3.” 
Is r e pl ac e d by: 
“ At o n-sit e st u dy visit(s) d uri n g t h e 
tr e at m e nt p eri o d, p ati e nts or t h eir 
c ar e giv ers will b e tr ai n e d by t h e 
i nv esti g at or or d el e g at e o n h o w t o 
pr e p ar e a n d s elf -i nj ect/i nj ect t h e I M P, 
u ntil t h ey ar e pr ofici e nt a n d f e el 
c o mf ort a bl e t o s elf-i nj ect/i nj ect t h e I M P 
at h o m e f or c ert ai n i nt erv als p er 
S ecti o n  1. 3. T his tr ai ni n g m ust b e 
d oc u m e nt e d i n t h e p ati e nt’s st u dy fil e. 
At b as eli n e visit, t h e I nv esti g at or or 
d el e g at e will  p erf or m t h e first of t h e 2 
i nj ecti o ns, a n d will pr o p os e t o t h e 
p ati e nt or his/ h er c ar e giv er t o p erf or m 
t h e s ec o n d i nj ecti o n u n d er t h e 
s u p ervisi o n of t h e i nv esti g at or or 
d el e g at e. If a p ati e nt or c ar e giv er d o es 
n ot f e el c o mf ort a bl e t o s elf -i nj ect/i nj ect 
t he I M P, all i nj ecti o ns c a n b e d o n e o n -
sit e or, as a n alt er n ativ e, t h ey c a n b e 
d o n e by a h e alt hc ar e pr of essi o n al 
( n urs e) at p ati e nts’ h o m e, aft er a n 
a p pr o pri at e a n d d oc u m e nt e d tr ai ni n g.”  
T o giv e s o m e fl exi bility f or I M P 
i nj ecti o ns, as s o m e p ati e nts d o n ot f eel 
c o mf ort a bl e t o s elf-i nj ect t h e I M P. 
V V- C LI N- 0 5 5 0 3 9 6 4. 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol 0 2  
L P S 1 5 4 9 7  
7 -A pr -2 0 2 0  
V er si o n n u m b er: 1  
 
Pr o p ert y of t h e S a n ofi gr o u p - stri ctl y c o nfi d e nti al  
P a g e 6  
S e cti o n # a n d N a m e  
D e s cri pti o n of C h a n g e  
Bri ef  R ati o n al e  
6. 5. 1 Pr o hi bit e d m e dic ati o ns a n d 
pr oc e d ur es  
T h e s e nt e nc e:  
“ Tr e at m e nt wit h f oll o wi n g c o nc o mit a nt 
m e dic ati o ns is pr o hi bit e d a n d r estrict e d 
d uri n g t h e st u dy, fr o m scr e e ni n g u ntil 
t h e e n d of t h e st u dy visit” 
is c h a n g e d t o: 
“Tr e at m e nt wit h f oll o wi n g c o nc o mit a nt 
m e dic ati o ns is pr o hi bit e d u ntil t h e e n d of 
t h e st u dy”.  
 
T h e crit eri o n a b o ut f or bi d d e n syst e mic 
s e d ativ e a nti hist a mi n es w as si m plifi e d 
as f oll o ws: “ Pati e nts t aki n g syst e mic 
s e d ativ e a nti hist a mi n es m or e t h a n 
5  d ays p er w e ek ” 
F or cl arific ati o n, a n d t o c orr ect 
i nc o nsist e nci es b et w e e n s ecti o n 6. 5. 1 
a n d s ecti o n 5. 2 excl usi o n crit eri a.  
6. 5. 2 P er mitt e d m e dic ati o ns  
It is cl arifi e d t h at syst e mic n o n-s e d ativ e 
a nti hist a mi n es ar e all o w e d d uri n g t h e 
st u dy 
Ad d e d i n t h e pr ot oc ol  f or cl arific ati o n, as 
t h es e m e dic ati o ns d o n ot i nt erf er e wit h 
sl e e p.  
8. 1. 2. 1 2 W ork Pr o d uctivity a n d Activity 
I m p air m e nt Q u esti o n n air e: At o pic 
D er m atitis  
“ V ersi o n 2. 0” h as b e e n d el et e d i n t h e 
titl e of t his s ecti o n f or t h e W P AI -A D  
As diff er e nt v ersi o ns ar e us e d, 
d e p e n di n g o n t h e c o u ntry  
8. 2. 1 Vit al si g ns  
“ Bl o o d pr ess ur e a n d h e art r at e” d el et e d 
i n t h e s e nt e nc e “ Vit al si g ns ( bl o o d 
pr ess ur e a n d h e art r at e ) will b e t ak e n at 
scr e e ni n g a n d …”  
Mi n or e dit, t o c orr ect a ty p o i n t h e 
pr ot oc ol, as vit al si g ns  i ncl u d e b l o o d 
pr ess ur e , h e art r at e , r es pir at ory rat e 
a n d b o dy t e m p er at ur e.  
1 0. 1. 3 I nf or m e d c o ns e nt pr oc ess  
T h e b el o w s e nt e nc e is d el et e d: “ T h e 
I C F will c o nt ai n a s e p ar at e s ecti o n t h at 
a d dr ess es t h e us e of r e m ai ni n g 
s a m pl es f or o pti o n al ex pl or at ory 
r es e arc h” 
Mi n or e dit, t o c orr ect a n e rr or i n th e 
pr ot oc ol: t h er e ar e  n o l a b s a m pl es 
c oll ect e d f or t his st u dy; t h er ef or e, t his 
st at e m e nt is n ot a p plic a bl e 
1 0. 7 A p p e n dix 7 A b br evi ati o ns  
T h e t er m s “D T P ( Dir ect T o Pati e nt) ” a n d 
“ T CI ( T o pic al C alci n e uri n I n hi bit or)” 
w er e  a d d e d t o t h e list of a b br evi ati o ns  
F or c o m pl et e n ess  
1 0. 8 Acti gr a p hy  
D et ails a b o ut q u esti o ns i ncl u d e d i n t h e 
A D sl e e p di ary ar e  d el et e d , a n d a 
hy p erli nk is a d d e d t o t h e A D sl e e p di ary 
dis pl ay e d i n Ap p e n dix 9 Secti o n 1 0. 9 . 
D et ails o n h o w t o pr oc ess acti gr a p h y 
d at a a n d s e n d t h e m t o t h e R e a di n g 
C e nt er  ar e  d el et e d, a n d a r ef er e nc e t o 
t h e Sit e C o or di n at or M a n u al is a d d e d.  
F or c o nsist e ncy r e as o ns , a n d t o us e 
o nly o n e d oc u m e nt as r ef er e nc e  
1 0. 9 - A p p e n dix 9 Cli nici a n -r e p ort e d 
o utc o m e -E A SI  
Pr evi o us sc al e is r e pl ac e d by t h e o n e 
act u ally us e d i n t h e st u dy  
T h e sc al e act u ally us e d i n t h e st u dy 
c o nt ai ns t h e c orr ect i nstr ucti o n f or r ati n g 
t h e s ev erity of eryt h e m a, e d e m a/ 
p a p ul ati o n, exc ori ati o n, lic h e nific ati o n, 
i e, it m e nti o ns t h at h alf-p oi nts m ay b e 
us e d, exc e pt 0. 5  
V V- C LI N- 0 5 5 0 3 9 6 4. 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol 0 2  
L P S 1 5 4 9 7  
7 -A pr -2 0 2 0  
V er si o n n u m b er: 1  
 
Pr o p ert y of t h e S a n ofi gr o u p - stri ctl y c o nfi d e nti al  
P a g e 7  
S e cti o n # a n d N a m e  
D e s cri pti o n of C h a n g e  
Bri ef  R ati o n al e  
1 0. 1 0 - A p p e n dix 1 0 P S G s u b -st u dy 
-T h e b el o w s e nt e nc e:  
“T h e sl e e p c e nt er st aff will d oc u m e nt all 
c aff ei n e, t o b acc o, alc o h ol, n o n -
pr escri pti o n a n d ov er t h e c o u nt er 
m e dic ati o ns t ak e n si nc e a w ak e ni n g ” 
is c h a n g e d t o: 
“T h e sl e e p c e nt er st aff will d oc u m e nt all 
c aff ei n e, t o b acc o, alc o h ol, a n d 
pr escri pti o n or ov er t h e c o u nt er 
m e dic ati o ns t ak e n si nc e a w ak e ni n g ”. 
-Ti m eli n es f or s e n di n g t h e d at a t o t h e 
c e ntr al r evi e w er P S G sit e h av e b e e n 
c h a n g e d fr o m 3 b usi n ess d ays t o 
2  b usi n ess d ays  
-T o c orr ect a ty p o i n t his se nt e nc e  
 
 
 
 
 
 
 
 
- F or l o gistic al r e as o ns, t o e ns ur e a 
s h ort er ass ess m e nt of d at a by t h e 
c e ntr al r evi e w er P S G sit e  
I n a d diti o n, ot her mi n or e dit orial c ha n ges (e g, gra m matical, st ylistic, a n d mi n or t y p o gra p hi cal err or c orrecti o ns  or 
f or matti n g iss ues fi xe d) were i m ple me nte d t hr o u g h o ut t he pr ot oc ol.  
V V- C LI N- 0 5 5 0 3 9 6 4. 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol 0 2  
L P S 1 5 4 9 7  
7 -A pr -2 0 2 0  
V er si o n n u m b er: 1  
 
Pr o p ert y of t h e S a n ofi gr o u p - stri ctl y c o nfi d e nti al  
P a g e 8  
T A B L E O F C O N T E N T S   
A M E N D E D C LI NI C A L T RI A L P R O T O C O L 0 2  .............................................................................................. 1  
P R O T O C O L A M E N D M E N T S U M M A R Y O F C H A N G E S T A B L E  .................................................................. 2  
D O C U M E N T HI S T O R Y  ................................................................................................................................... 2  
T A B L E O F C O N T E N T S  .................................................................................................................................. 8  
LI S T O F T A B L E S  ......................................................................................................................................... 1 1  
LI S T O F FI G U R E S  ........................................................................................................................................ 1 1  
1  
P R O T O C O L S U M M A R Y  ............................................................................................................... 1 2  
1. 1  
S Y N O P SI S  ..................................................................................................................................... 1 2  
1. 2  
S C H E M A  ........................................................................................................................................ 1 6  
1. 3  
S C H E D U L E O F A C TI VI TI E S ( S O A)  .............................................................................................. 1 7  
2  
I N T R O D U C TI O N ............................................................................................................................ 2 2  
2. 1  
S T U D Y R A TI O N A L E ...................................................................................................................... 2 2  
2. 2  
B A C K G R O U N D  ............................................................................................................................. 2 3  
2. 3  
B E N E FI T/ RI S K A S S E S S M E N T  ..................................................................................................... 2 4  
3  
O B J E C TI V E S A N D E N D P O I N T S ................................................................................................. 2 6  
3. 1  
A P P R O P RI A T E N E S S O F M E A S U R E M E N T S  .............................................................................. 2 8  
4  
S T U D Y D E SI G N  ............................................................................................................................ 2 9  
4. 1  
O V E R A L L D E SI G N  ........................................................................................................................ 2 9  
4. 2  
S CI E N TI FI C  R A TI O N A L E F O R S T U D Y  D E SI G N  ......................................................................... 2 9  
4. 3  
J U S TI FI C A TI O N F O R D O S E  ........................................................................................................ 3 0  
4. 4  
E N D O F S T U D Y D E FI NI T I O N ....................................................................................................... 3 0  
5  
S T U D Y P O P U L A TI O N  .................................................................................................................. 3 1  
5. 1  
I N C L U SI O N C RI T E RI A .................................................................................................................. 3 1  
5. 2  
E X C L U SI O N C RI T E RI A  ............................................................................................................... 3 2  
5. 3  
LI F E S T Y L E C O N SI D E R A TI O N S  ................................................................................................... 3 5  
5. 4  
S C R E E N F AI L U R E S ...................................................................................................................... 3 5  
V V- C LI N- 0 5 5 0 3 9 6 4. 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol 0 2  
L P S 1 5 4 9 7  
7 -A pr -2 0 2 0  
V er si o n n u m b er: 1  
 
Pr o p ert y of t h e S a n ofi gr o u p - stri ctl y c o nfi d e nti al  
P a g e 9  
6  
S T U D Y I N T E R V E N TI O N  ............................................................................................................... 3 6  
6. 1  
S T U D Y I N T E R V E N TI O N( S ) A D MI NI S T E R E D .............................................................................. 3 6  
6. 2  
P R E P A R A TI O N/ H A N D LI N G / S T O R A G E/ A C C O U N T A BI LI T Y....................................................... 3 8  
6. 3  
M E A S U R E S T O MI NI MI Z E  BI A S: R A N D O MI Z A TI O N  A N D B LI N DI N G  ....................................... 3 9  
6. 4  
S T U D Y I N T E R V E N TI O N C O M P LI A N C E  ...................................................................................... 4 0  
6. 5  
C O N C O MI T A N T T H E R A P Y  .......................................................................................................... 4 1  
6. 5. 1  
Pr o hi bit e d M e di c ati o n s a n d pr o c e d ur e s ......................................................................................... 4 1  
6. 5. 2  
P er mitt e d m e di c ati o n s .................................................................................................................... 4 2  
6. 5. 3  
R e s c u e m e di ci n e  ............................................................................................................................ 4 2  
6. 6  
D O S E M O DI FI C A TI O N  .................................................................................................................. 4 3  
6. 7  
I N T E R V E N TI O N A F T E R TH E E N D O F T H E S T U D Y  ................................................................... 4 3  
7  
DI S C O N TI N U A TI O N O F S T U D Y I N T E R V E N TI O N A N D P A R TI CI P A N T 
DI S C O N TI N U A TI O N/ WI T H D R A W A L  ........................................................................................... 4 4  
7. 1  
DI S C O N TI N U A TI O N O F S T U D Y I N T E R V E N TI O N  ..................................................................... 4 4  
7. 1. 1  
D efi niti v e di s c o nti n u ati o n  ............................................................................................................... 4 4  
7. 1. 2  
T e m p or ar y di s c o nti n u ati o n  ............................................................................................................. 4 4  
7. 2  
P A R TI CI P A N T DI S C O N TI N U A TI O N/ WI T H D R A W A L F R O M T H E S T U D Y  .................................. 4 5  
7. 3  
L O S T T O F O L L O W U P  ................................................................................................................. 4 5  
8  
S T U D Y A S S E S S M E N T S A N D P R O C E D U R E S  ........................................................................... 4 7  
8. 1  
E F FI C A C Y A S S E S S M E N T S   ........................................................................................................ 4 7  
8. 1. 1  
P h y si ci a n a n d C e nt er A s s e s s e d S c al e s  ........................................................................................ 4 7  
8. 1. 2  
P ati e nt -R e p ort e d O ut c o m e S c al e s ( c o m pl et e d b y p ati e nt s)  .......................................................... 4 9  
8. 1. 3  
P erf or m a n c e -R e p ort e d O ut c o m e s c al e s ........................................................................................ 5 3  
8. 1. 4  
M ulti pli cit y c o n si d er ati o n s  .............................................................................................................. 5 4  
8. 2  
S A F E T Y A S S E S S M E N T S  ............................................................................................................ 5 4  
8. 2. 1  
Vit al si g n s  ....................................................................................................................................... 5 4  
8. 2. 2  
Cli ni c al s af et y l a b or at or y a s s e s s m e nt s  .......................................................................................... 5 4  
8. 3  
A D V E R S E E V E N T S A N D S E RI O U S A D V E R S E E V E N T S  ........................................................... 5 5  
8. 3. 1  
Ti m e p eri o d a n d fr e q u e n c y f or c oll e cti n g A E a n d S A E i nf or m ati o n  ............................................... 5 6  
8. 3. 2  
M et h o d of d et e cti n g A E s a n d S A E s  ............................................................................................... 5 6  
8. 3. 3  
F oll o w -u p of A E s a n d S A E s  ........................................................................................................... 5 6  
8. 3. 4  
P h y si c al e x a mi n ati o n s  ................................................................................................................... 5 7  
V V- C LI N- 0 5 5 0 3 9 6 4. 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol 0 2  
L P S 1 5 4 9 7  
7 -A pr -2 0 2 0  
V er si o n n u m b er: 1  
 
Pr o p ert y of t h e S a n ofi gr o u p - stri ctl y c o nfi d e nti al  
P a g e 1 0  
8. 3. 5  
R e g ul at or y r e p orti n g r e q uir e m e nt s f or S A E s  ................................................................................. 5 7  
8. 3. 6  
Pr e g n a n c y  ...................................................................................................................................... 5 7  
8. 3. 7  
G ui d eli n e s f or r e p orti n g pr o d u ct c o m pl ai nt s  .................................................................................. 5 8  
8. 4  
T R E A T M E N T O F O V E R D O S E  ...................................................................................................... 5 8  
8. 5  
P H A R M A C O KI N E TI C S  .................................................................................................................. 5 8  
8. 6  
P H A R M A C O D Y N A MI C S  ............................................................................................................... 5 8  
8. 7  
G E N E TI C S  ..................................................................................................................................... 5 8  
8. 8  
BI O M A R K E R S  ............................................................................................................................... 5 9  
8. 9  
H E A L T H E C O N O MI C S O R M E DI C A L R E S O U R C E U TI LI Z A TI O N A N D H E A L T H 
E C O N O MI C S  ................................................................................................................................. 5 9  
9  
S T A TI S TI C A L C O N SI D E R A TI O N S  .............................................................................................. 6 0  
9. 1  
S T A TI S TI C A L H Y P O T H E S E S  ....................................................................................................... 6 0  
9. 2  
S A M P L E SI Z E D E T E R MI N A TI O N  ................................................................................................ 6 0  
9. 3  
P O P U L A TI O N S F O R A N A L Y S E S  ................................................................................................. 6 1  
9. 4  
S T A TI S TI C A L A N A L Y S E S  ............................................................................................................ 6 1  
9. 4. 1  
Effi c a c y a n al y s e s  ........................................................................................................................... 6 1  
9. 4. 2  
S af et y a n al y s e s  .............................................................................................................................. 6 3  
9. 4. 3  
Ot h er a n al y s e s  ............................................................................................................................... 6 3  
9. 5  
I N T E RI M A N A L Y S E S  ................................................................................................................... 6 3  
9. 6  
D A T A M O NI T O RI N G C O M M I T T E E ( D M C) ................................................................................... 6 3  
1 0  
S U P P O R TI N G D O C U M E N T A TI O N A N D O P E R A TI O N A L  C O N SI D E R A TI O N S  ........................ 6 4  
1 0. 1  
A P P E N DI X 1: R E G U L A T O R Y, E T HI C A L, A N D S T U D Y O V E R SI G H T C O N SI D E R A TI O N S  ....... 6 4  
1 0. 1. 1  
R e g ul at or y a n d Et hi c al C o n si d er ati o n s  .......................................................................................... 6 4  
1 0. 1. 2  
Fi n a n ci al di s cl o s ur e ........................................................................................................................ 6 4  
1 0. 1. 3  
I nf or m e d C o n s e nt Pr o c e s s ............................................................................................................ 6 5  
1 0 . 1. 4 
D at a Pr ot e cti o n  .............................................................................................................................. 6 5  
1 0. 1. 5  
C o m mitt e e s Str u ct ur e  .................................................................................................................... 6 6  
1 0. 1. 6  
Di s s e mi n ati o n of Cli ni c al St u d y D at a  ............................................................................................. 6 6  
1 0. 1. 7  
D at a Q u alit y A s s ur a n c e  ................................................................................................................. 6 6  
1 0. 1 . 8 
S o ur c e d o c u m e nt s  ......................................................................................................................... 6 7  
1 0. 1. 9  
St u d y a n d Sit e Cl o s ur e  .................................................................................................................. 6 7  
1 0. 1. 1 0  P u bli c ati o n P oli c y  ........................................................................................................................... 6 8  
V V- C LI N- 0 5 5 0 3 9 6 4. 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol 0 2  
L P S 1 5 4 9 7  
7 -A pr -2 0 2 0  
V er si o n n u m b er: 1  
 
Pr o p ert y of t h e S a n ofi gr o u p - stri ctl y c o nfi d e nti al  
P a g e 1 1  
1 0. 2  
A P P E N DI X 2: C LI NI C A L  L A B O R A T O R Y T E S T S  ......................................................................... 6 8  
1 0. 3  
A P P E N DI X 3: A D V E R S E E V E N T S: D E FI NI TI O N S A N D P R O C E D U R E S F O R 
R E C O R DI N G, E V A L U A TI N G, F O L L O W -U P, A N D R E P O R TI N G  ................................................ 6 8  
1 0. 4  
A P P E N DI X 4: C O N T R A C E P TI V E G UI D A N C E A N D C O L L E C TI O N O F P R E G N A N C Y 
I N F O R M A TI O N .............................................................................................................................. 7 3  
1 0. 5  
A P P E N DI X 5: D E FI NI TI O N O F A N A P H Y L A XI S  .......................................................................... 7 6  
1 0. 6  
A P P E N DI X 6: C O U N T R Y -S P E CI FI C R E Q UI R E M E N T S  ............................................................. 7 6  
1 0. 7  
A P P E N DI X 7: A B B R E VI A TI O N S  ................................................................................................... 7 6  
1 0. 8  
A P P E N DI X 8  A C TI G R A P H Y  ........................................................................................................ 7 8  
1 0. 9  
A P P E N DI X 9: C LI NI CI A N -R E P O R T E D O U T C O M E S ( C LI N R O S) A N D P A TI E N T -
R E P O R T E D O U T C O M E S ( P R O S)  ................................................................................................ 8 0  
1 0. 1 0  
A P P E N DI X 1 0: P O L Y S O M N O G R A P H Y ( P S G) S U B -S T U D Y  .................................................... 1 0 6  
1 0. 1 1  
A P P E N DI X 1 1: P R O T O C O L A M E N D M E N T HI S T O R Y  ............................................................. 1 0 8  
1 1  
R E F E R E N C E S  ............................................................................................................................. 1 1 0  
 
LI S T O F T A B L E S   
T a bl e  1 - O bj e cti v e s a n d e n d p oi nt s  ............................................................................................................... 2 6  
T a bl e  2 - O v er vi e w of st u d y i nt er v e nti o n s a d mi ni st er e d  ............................................................................... 3 6  
T a bl e  3 - P o p ul ati o n s f or a n al y s e s  ................................................................................................................ 6 1  
T a bl e  4 - Effi c a c y a n al y s e s  ........................................................................................................................... 6 1  
T a bl e  5 - S af et y a n al y s e s  .............................................................................................................................. 6 3  
T a bl e  6 - Hi g hl y eff e cti v e c o ntr a c e pti v e m et h o d s  ......................................................................................... 7 4  
 
LI S T O F FI G U R E S   
Fi g ur e  1 - Gr a p hi c al st u d y d e si g n  ................................................................................................................. 1 6  
 
V V- C LI N- 0 5 5 0 3 9 6 4. 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol 0 2  
L P S 1 5 4 9 7  
7 -A pr -2 0 2 0  
V er si o n n u m b er: 1  
 
Pr o p ert y of t h e S a n ofi gr o u p - stri ctl y c o nfi d e nti al  
P a g e 1 2  
1  
P R O T O C O L  S U M M A R Y   
1. 1  
S Y N O P SI S   
Pr ot oc ol titl e:  A ra n d o mize d d o u ble -bli n d place b o -c o ntr olle d st u d y e v al uati n g t he effect of 
d u pil u ma b o n slee p i n a d ult patie nts wit h m o derate t o se vere at o pic der matitis  
S h ort titl e:  S A R 2 3 1 8 9 3 -L P S 1 5 4 9 7 - “ D u pil u m a b eff e ct o n Sl e e p i n A D p ati e nt s ” -
D U PI S T A D  
R ati o n ale:  
T his st u d y is desi g n e d t o pr o vi de f urt her e vi de nce of  t he effect of d u pil u ma b o n a meli orati n g 
slee p dist ur ba nce i n p atie nts wit h m o derate t o se vere at o pic der matitis (A D ). Slee p dist ur ba nce 
re pres e nts o ne  of t he pr o mi ne nt s y m pt o ms of A D , a n d was pre vi o usl y s h o w n t o i m pr o ve wit h  
d u pil u ma b. T his st u d y assesses t he effect of d u pil u ma b o n slee p dist ur ba nce usi n g d e d icate d slee p 
o utc o me meas ur es , i n a pr os pecti ve, place b o-c o ntr olle d,  d o u ble -bli n d desi g n . 
O bjecti ves a n d e n d p oi nts  
N ote t hat o n l y t he pri mar y a n d k e y sec o n dar y o bjecti ves/e n d p oi nts are liste d bel o w. A c o m plete 
list of o bjecti ves a n d e n d p oi nts i ncl u di n g e x pl orat or y e n d p oi nts ca n be f o u n d i n Secti o n  3  of t he 
pr ot oc ol.  
O bj e cti v e s  
S u p p orti n g E n d p oi nt s  
Pri m ar y  
 T o ev al u at e t h e eff ect  of d u pil u m a b o n sl e e p q u ality i n 
a d ult p ati e nts wit h m o d er at e t o s ev er e at o pic d er m atitis 
( A D). 
 
Perc e nt a g e  c h a n g e fr o m b as eli n e t o w e ek  1 2 i n sl e e p 
q u ality n u m eric al r ati n g sc al e ( N R S) . 
S e c o n d ar y  
 T o ev al u at e t h e eff ect of d u pil u m a b o n o bj ectiv e a n d 
s u bj ectiv e q u a ntit ativ e sl e e p p ar a m et ers, A D r el at e d 
o utc o m es, a n d d ayti m e c o ns e q u e nc es of sl e e p 
d e priv ati o n.  
 
Sec o n d ary E n d p oi nts  
 
C h a n g e fr o m b as eli n e t o w e ek  1 2 i n sl e e p effici e ncy 
( S E) b as e d o n actigr a p hy d at a . 
 
C h a n g e fr o m b as eli n e t o w e ek  1 2 i n t ot al sl e e p ti m e 
( T S T) b as e d o n acti gr a p hy d at a. 
 
C h a n g e fr o m b as eli n e t o w e ek  1 2 i n w ak e aft er sl e e p 
o ns et ( W A S O) b as e d o n acti gr a p hy d at a . 
 
C h a n g e fr o m b as eli n e t o w e ek  1 2 i n sl e e p o ns et l at e ncy 
( S O L) b as e d on acti gr a p hy d at a . 
 
Perc e nt c h a n g e fr o m b as eli n e t o w e ek  1 2 i n Pr urit us 
N R S . 
 
C h a n g e fr o m b as eli n e t o w e ek  1 2 i n S C O Ri n g At o pic 
D er m atitis ( S C O R A D) t ot al sc or e . 
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A m e n d e d Cli ni c al Tri al Pr ot o c ol 0 2  
L P S 1 5 4 9 7  
7 -A pr -2 0 2 0  
V er si o n n u m b er: 1  
 
Pr o p ert y of t h e S a n ofi gr o u p - stri ctl y c o nfi d e nti al  
P a g e 1 3  
 
C h a n g e fr o m b as eli n e t o w e ek  1 2 i n S C O R A D sl e e p 
V A S . 
 
Pr o p orti o n of p ati e nts wit h E A SI 5 0 (r e d ucti o n of E A SI 
sc or e by ≥5 0 % fr o m b as eli n e) at w e ek 1 2 . 
 
Pr o p orti o n of p ati e nts wit h, E A SI 7 5 (r e d ucti o n of E A SI 
sc or e by ≥7 5 % fr o m b as eli n e) at w e ek  1 2 . 
 
C h a n g e fr o m b as eli n e t o w e ek  1 2 i n P ati e nt Ori e nt e d 
Ecz e m a M e as ur e ( P O E M) t ot al sc or e . 
 
C h a n g e fr o m b as eli n e t o w e ek 1 2 i n D er m at ol o gy Lif e 
Q u ality I n d ex ( D L QI) t ot al sc or e . 
 
C h a n g e fr o m b as eli n e t o w e ek 1 2 i n P R O MI S Sl e e p 
R el at e d I m p air m e nt S F 8 a T ot al Sc or e .  
 
T o c o nti n u e t o ass ess t h e s af ety a n d t ol er a bility of 
d u pil u m a b t hr o u g h o ut t h e st u dy.  
 
I nci d e nc e of a dv ers e ev e nts t hr o u g h w e ek  1 2 . 
 
I nci d e nc e of a dv ers e ev e nts t hr o u g h w e ek 2 4.  
O ver all desi g n:  
T his is a P hase  I V, pr os p ecti ve, ra n d o mize d, m ulti nati o nal st u d y, wit h a 1 2-wee k d o u ble -bli n d 
place b o -c o ntr olle d peri o d , f oll o we d b y a 1 2-wee k o pe n la bel e xte nsi o n t o e val uate t he effect of 
d u pil u ma b o n slee p i n a d ult patie nts wit h m o derate t o se vere A D . 
N u m ber of p artici p a nts:  
A p pr o xi matel y  2 0 1  p arti ci pa nts will be ra n d o ml y assi g ne d t o st u d y i nter ve nti o n i n a 2: 1 
d u pil u ma b t o place b o rati o fr o m m ulti ple sites gl o ball y  s uc h t hat at least 1 5 0  eval ua ble 
partici pa nts  ( 1 0 0 i n t he acti ve gr o u p a n d 5 0 i n place b o) c o m plet e t he d o u bl e -bli n d p orti o n (t o 
wee k  1 2) of t he st u d y. 
I nter ve nti o n gr o u ps a n d d ur ati o n : 
T he  st u d y will c o m prise of: 
 Scree ni n g p eri o d 1 ( Da y -2 8 t o Da y -8 ). 
 Scree ni n g p erio d 2 ( Pre -baseli ne assess me nts): p atie nts eli gi ble t o c o nti n ue, will c o m plete 
assess me nts s pecifie d i n sc he d ule of acti vities (S o A ) fr o m D a y -7 t o Da y -1 (ri g ht b ef ore 
Da y  1) . If preferre d b y t h e patie nt a n d t he i n vesti gat or f or l o gistical reas o ns, scree ni n g ca n 
be d o ne d uri n g a si n gle o n -site visit. I n t hat case, all pr oce d ures pla n n e d at s cree ni n g 1 a n d 
scree ni n g 2 s h o ul d be d o ne d uri n g t his si n gle scree ni n g visit. I m p orta ntl y, t his si n gle 
scree ni n g visit will ha ve t o be d o ne at least 7 da ys bef ore t h e baseli ne visit, as patie nts 
s h o ul d wear t he acti gra p h a n d c o m plete t he diar y f or 7 da ys bef ore b aseli n e . 
 Baseli ne / Ra n d o mizati o n/A d mi nistrati o n of first d ose ( Da y  1) . 
 1 2 -wee k d o u bl e -bli n d place b o -c o ntr olle d peri o d : patie nts will be ra n d o mize d t o recei ve 
d u pil u ma b or place b o . 
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A m e n d e d Cli ni c al Tri al Pr ot o c ol 0 2  
L P S 1 5 4 9 7  
7 -A pr -2 0 2 0  
V er si o n n u m b er: 1  
 
Pr o p ert y of t h e S a n ofi gr o u p - stri ctl y c o nfi d e nti al  
P a g e 1 4  
 1 2 -wee k o p e n -la b el e xte nsi o n peri o d: f oll o wi n g c o m pleti o n of d o u ble-bli n d peri o d, 
patie nts ra n d o mize d t o d u pil u ma b will c o nti n ue t o recei v e acti ve tr eat me nt i n t he 
o pe n -la bel peri o d, w hereas patie nts ra n d o mize d t o place b o will recei ve acti ve treat me nt 
wit h d u pil u ma b.  
T he ma xi m u m st u d y d urati o n per partici pa nt will be u p t o 2 8  wee ks.  
P ol ys o m n o gra p h y ( P S G ) s u b-st u d y: Of t he 2 0 1  p artici pa nts, a p pr o xi matel y 3 0  p atie nts t otal 
(a p pro xi matel y 2 0  d u pil u ma b a n d 1 0  place b o patie nts) will partici pate i n a P S G s u b -st u d y at 
selecte d U S sites. Eac h p atie nt w h o partici pates i n t his s u b-st u d y will ha ve a t otal of 3 o ver ni g ht 
P S Gs: at baseli ne, 2  (prefera bl y ) c o nsec uti ve o v er ni g ht P S Gs t o c o ntr ol f or “first ni g ht effect” 
( ni g ht of Da y -2) a n d c ollect baseli ne dat a  (ni g ht of Da y  -1 ; w hic h  will ser ve as baseli ne 
assess me nts) ; t he n 1 o ver ni g ht P S G at w ee k 1 2 . T he assess me nt pr oce d ure  is pr o vi de d i n 
Secti o n  1 0. 1 0 . 
St u d y i nter ve n ti o ns 
I nvesti g ati o n al me dici n al pr o d ucts 
 F or m ulati o n:  
- 
D u pil u ma b: 1 5 0  m g/ m L i n pre -fille d s yri n ge t o deli ver 3 0 0 m g i n 2  m L , 
- 
Place b o: Pre -fille d s yri n ge t o deli ver 2 m L  of ve hi cle s ol uti o n, c o ntai ni n g all 
i n gre di e nts e x ce pt t he pr otei n ( d u pil u ma b), vis uall y i n disti n g uis ha ble fr o m t he 
d u pil u ma b s yri n ge . 
 R o ute  of a d mi nistrati o n:  S u bc uta ne o us  
 D ose re gi me n : 
- 
Patie nts i nitiall y assi g n e d t o d u pil u ma b will  recei ve 6 0 0 m g ( 2 x 3 0 0  m g d u pil u ma b 
i njecti o ns) o n Da y 1 (ie, t he l oa di n g d os e), f oll o we d b y 1 d u pil u ma b i njecti o n of 
3 0 0  m g e v er y 2  w ee ks ( Q 2 W ) u ntil w ee k 1 0, t he n 1 d u pil u ma b + 1 place b o i njecti o n at 
wee k  1 2 (t o pr ot ect t he bli n d w hile place b o patie nts recei ve t h eir l oa di n g d ose), 
f oll o we d b y 1 d u pil u ma b i njecti o n Q 2 W , wit h a last i njecti o n at w ee k 2 2.  
- 
Plac e b o patie nts will recei ve 2 x 2  m L pl ace b o i nj ecti o ns o n Da y  1, t he n 1 place b o 
i njecti o n Q 2 W  u ntil wee k  1 0, a n d t he n 2 x 3 0 0  m g d u pil u ma b i njecti o ns at wee k  1 2 
(ie, t he l oa di n g d ose), f oll o we d b y 1 d u pilu ma b i njecti o n Q 2 W , wit h a last i njecti o n at 
w ee k 2 2 . 
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A m e n d e d Cli ni c al Tri al Pr ot o c ol 0 2  
L P S 1 5 4 9 7  
7 -A pr -2 0 2 0  
V er si o n n u m b er: 1  
 
Pr o p ert y of t h e S a n ofi gr o u p - stri ctl y c o nfi d e nti al  
P a g e 1 5  
P ost -tri al access t o st u dy me dic ati o n 
After t he st u d y is c o m plete d, p atie nts will n ot be pr o vi de d a n y f urt her st u d y me dicati o n as part of 
t his pr ot oc ol. 
St atistic al c o nsi der ati o ns:  
 Pri m ar y a n al ysis:  
T he p erce nt c h a n ge fr o m baseli ne t o w ee k 1 2 i n sl ee p q ualit y N R S will be a nal yze d usi n g 
a mi x e d effect m o del wit h re peat e d meas ures ( M M R M ) wit h treat me nt, baseli ne val ue, 
ra n d o mizati o n strat u m, visit , treat me nt b y visit  i nteracti o n, a n d b aseli ne v al ue b y visit  
i nteracti o n ter ms (all as fi x e d effects) i n t he m o del. 
 A n al ysis of sec o n d ar y e n d p oi nts:  
F or a n al ysis o f s ec o n d ar y c o nti n u o us e n d p oi nts, a si milar a p pr oac h will be use d as a b o ve. 
Eac h e n d p oi nt will be a n al y z e d usi n g a M M R M wit h treat me nt, c orres p o n di n g bas eli ne 
val ue, ra n d o mizati o n strat um , visit, treat me nt b y visit i nteracti o n, a n d baseli ne val ue b y 
visit i nteracti o n ter ms (all as fi x e d effects) i n t he m o del.  
E n d p oi nts c o m pari n g pr o p orti o n  of patie nts meeti n g certai n criteria at a s p ecific visit will 
be a nal yz e d via t h e C oc hra n Ma ntel -Hae nszel test a dj uste d b y t he ra n d o mi zati o n strat u m . 
 
M ulti plicit y C o nsi der ati o ns:  
M ulti plicit y a dj ust me nts will be c o nsi dere d t o pr ot ect t he T y pe I err or at 0. 0 5 le vel 
(2 -si de d), d ue t o testi n g pri mar y a n d m ulti ple sec o n dar y e n d p oi nts, as des cri be d i n 
Secti o n  8. 1. 4 . 
D at a M o nit ori n g C o m mittee:  N o  
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A m e n d e d Cli ni c al Tri al Pr ot o c ol 0 2  
L P S 1 5 4 9 7  
7 -A pr -2 0 2 0  
V er si o n n u m b er: 1  
 
Pr o p ert y of t h e S a n ofi gr o u p - stri ctl y c o nfi d e nti al  
P a g e 1 6  
1. 2  
S C H E M A   
Fi g ur e  1  - Gr a p hi c al st u d y d e si g n   
 
 
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A m e n d e d Cli ni c al Tri al Pr ot o c ol  0 2  
L P S 1 5 4 9 7  
7 -A pr -2 0 2 0  
V er si o n n u m b er:  1  
 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al  
P a g e 2 1  
e  E ac h p ati e nt w h o p artici p at es i n t his s u b-st u dy will h av e a t ot al of 3 ov erni g ht P S Gs: at b as eli n e ti m e p oi nt, 2 (pref er a bly) c o ns ec utiv e ov er ni g ht P S Gs t o c o ntrol f or “first ni g ht eff ect” a n d c oll ect bas eli n e d at a, a n d 
1  m ore at w e ek  1 2 . 
f 
Not m a n d at ory, sit e prof essi o n al will b e t aki n g t h e p h ot o gra p hs wit h p ati e nt’s c o ns e nt; Sit e st aff will t ak e t h e p h ot os of t h e s a m e l esi o ne d are as f or e ac h visit, s t arti n g fro m t h e b as eli n e visit. P ati e nt s will b e ask e d 
to si g n a s e p arat e p h ot o gra p hy i nf or m e d c o ns e nt at Day 1 . 
g  If pref err e d by t h e p ati e nt a n d t h e i nv esti g at or f or l o gistical  re as o ns, scre e ni n g c a n b e d o n e d uri n g a si n gl e o n-sit e visit. I n t h at c as e, all proc e dures pl a n n ed at scr e eni n g 1 a n d scre e ni n g 2 s h oul d be d on e d uri n g 
t his si n gl e scre e ni n g visit. I m p ort a ntly, t his si n gl e scre e ni n g visit will h av e t o b e d o n e at l e ast 7 days b ef ore t h e b as eli n e visit, as p ati e nts s h oul d we ar t he acti gra ph a nd c o mpl et e t h e di ary f or 7 d ays b ef or e 
b as eli n e . 
h  V 9 ass ess m e nts are a p pli e d t o p ati e nts w h o pre mat urely  disc o nti n u e t h e st u dy, c o m pl et e t h e tre at m e nt (e n d of tre at m e nt), a n d c o m pl et e t h e st u dy ( e nd of st u dy) . 
V V- C LI N- 0 5 5 0 3 9 6 4. 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol 0 2  
L P S 1 5 4 9 7  
7 -A pr -2 0 2 0  
V er si o n n u m b er: 1  
 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al  
P a g e 2 2  
2  
I N T R O D U C TI O N  
D u pil u ma b is a rec o m bi n a nt h u ma n i m m u n o gl o b uli n -G 4  (I g-4)  m o n o cl o nal a nti b o d y t hat i n hi bits 
i nterle u ki n-4 ( I L-4 ) a n d i nterle u ki n-1 3 ( I L-1 3 ) si g nali n g b y s pecificall y bi n di n g t o t he I L-4 
rece pt or al p ha (I L 4 R α) s u b-u n it s hare d b y t he I L-4  a n d I L-1 3 rece pt or c o m ple xes. D u pil u ma b 
i n hi bits I L-4 si g n ali n g vi a t he T y pe I rece pt or ( I L 4 R α/γc), a n d b ot h I L-4 a n d I L-1 3  si g n ali n g 
t hr o u g h t he T y p e II rece pt or (I L-4 R α/I L -1 3 R α ). T hese c yt o ki nes pla y k e y r oles i n t he 
pat h o ge nesis of vari o us aller gic dis eases, i ncl u di n g A D  (1 ) a n d ast h ma  (2 ). 
D u pil u ma b 3 0 0  m g Q 2 W  is a p pr o ve d f or t h e treat me nt of a d ult A D i n t he U S, E U a n d ma n y ot her 
c o u ntries w o rl d wi de. C o m plete d p hase III st u dies ( S O L O 1 R 6 6 8-A D -1 3 3 4, S O L O 2 
R 6 6 8 -A D -1 4 1 6, C H R O N O S R 6 6 8 -A D -1 2 2 4 , a n d R 6 6 8-A D -1 4 2 4 ) ha v e de m o nstrate d t he safet y 
a n d effi cac y of d u pil u ma b 3 0 0 m g a d mi nistere d s u bc uta ne o usl y ( S C ) Q 2 W  or e ver y wee k ( Q W ) 
as a m o n ot hera p y or c o n c o mita ntl y wit h t o pical c ortic oster oi ds ( T C S ) i n patie nts wit h m o derate t o 
se vere A D i na de q u atel y c o ntr olle d wit h t o pical me dicati o ns.  
At o pic der matitis is a c hr o nic/rela psi n g i nfla m mat or y s ki n dise ase c h aracterize d b y i nte nse 
pr urit us, dr y  s ki n, a n d ecze mat o us lesi o ns. A n esti mate d 1 5 % t o 3 0 % of c hil dre n a n d 2 % t o 1 0 % 
of a d ults are affecte d b y A D  (3 ). At o pic der matitis is c o m m o nl y ass ociate d wit h ast h ma a n d ot her 
at o pic/aller gic c o n diti o ns, wit h w hic h it s hares c o m m o n pat h o p h ysi ol o gical pat h wa ys.  T he 
pat h o p h ysi ol o g y of A D is i nfl ue nc e d b y ge n etics a n d e n vir o n me ntal fact ors a n d i n v ol ves a 
c o m ple x i nter pla y bet w ee n a nti ge ns, s ki n barri er defects, a n d i m m u ne d ysre g ulati o ns, i n w hic h a 
p olariz e d i nfla m mat or y res p o nse i n d uce d b y t he mar ke d acti vati o n of t he T -hel per T y p e 2 ( T h 2 ) 
cell a xis pla ys a ce ntral r ole ( 1 ). T w o c yt o ki nes, I L -4 a n d I L -1 3, are critical i n t he i nitiati o n a n d 
mai nte na nce of t he T y pe  2/ T h 2 i nfla m mat or y p at h wa y.  
M o derate -t o-se vere A D is a n u n der-rec o g nize d p u blic healt h c o ncer n wit h a hi g h disa bilit y 
b ur de n  (4 ). I n patie nts wit h m o derate A D, a n d es p eciall y i n patie nts wit h se vere A D, t he cli nical 
ma nifestati o ns lea d t o si g nifica nt slee p dist ur ba n ces a n d se vere ps yc h ol o gical a n d s oci ol o gi cal 
se q uelae, i m pair e d q ualit y of lif e (Q o L ) wit h s u bsta ntial ne gati ve i m pact o n patie nt’s da y-t o-d a y 
f u ncti o ni n g, a n d are ass o ciate d with hi g h s o ci oec o n o mic c osts.  
2. 1  
S T U D Y R A TI O N A L E   
Slee p dist ur ba nce is a well -k n o w n de bilitati n g s y m pt o m of A D, t h o u g h fe w st u dies ha ve 
i n vesti gate d it as a pri mar y o utc o m e t o assess t he i m pact of t his c o n diti o n o n patie nt’s Q o L a n d 
ot her i m p orta nt o utc o mes t hat patie nts s uffer i n t h eir dail y li ves. T his d o u ble -bli n d, 
place b o -c o ntr olle d, pr os p ecti ve st u d y will a p pl y b ot h o bjecti ve a n d s u bjecti ve t o ols t o meas ure 
q ualitati ve a n d q ua ntitati ve slee p relate d o utc o mes a n d c o m pre h e nsi vel y assess d u pil u ma b 
treat me nt effect o n sle e p a n d o n t he c o nse q u e nces of sleep de pri v ati o n i ncl u di n g da yti me 
slee pi ness, dail y f u ncti o n, ne ur oc o g niti ve a n d ps yc h o m ot or f u ncti o n, pr o d ucti vit y, a n d Q o L i n 
a d ult patie nts wit h m o de rate t o se vere A D. 
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A m e n d e d Cli ni c al Tri al Pr ot o c ol 0 2  
L P S 1 5 4 9 7  
7 -A pr -2 0 2 0  
V er si o n n u m b er: 1  
 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al  
P a g e 2 3  
2. 2  
B A C K G R O U N D   
At o pic der matitis  is a c hr o nic t y pe 2 i nfl a m mat or y s ki n disease t hat is ass ociate d wit h 
heter o ge n e o us a n d hi g hl y varia ble si g ns a n d s y m pt o ms. T he s y m pt o ms of A D i ncl u de c uta ne o us 
itc h, pai n slee p dist ur ba n ce , a n d me nt al healt h s y m pt o ms. At o pic der mat itis patie nts als o ca n 
s uffer fr o m c o m or bi d i nfecti o us, a ut oi m m u ne, res pirat or y, ne ur o ps yc hiatri c, a n d m usc ul os keletal 
dis or ders. A t o pic der matitis mi g ht ha ve s yst e mic i n v ol ve me nt wit h gl o bal i m pact be y o n d t he s ki n 
si g ns a n d s y m pt o ms. 
At o pic der matitis patie nts ofte n e x hi bit a variet y of ps yc h os ocial s y m pt o ms s uc h as a n xiet y, 
fr ustrati o n a n d e m b arrass me nt . Acc or di n gl y, t he y als o ofte n re p ort l o wer self-estee m a n d s elf -
c o nfi de nce, a n d re d uce d a bilit y t o esta blis h a n d ma na ge relati o ns hi ps  (5 ). A m o n g t he mai n g o als 
i n treati n g A D are re d u ci n g s ki n i nfla m mati o n a n d alle viati n g s y m pt o ms, w hile i m pr o vi n g t he 
patie nts’ Q o L  a n d sleep. Lac k of pr o per slee p ma y ca use da yti me slee pi ness, i m paire d c o g niti o n 
a n d m o o d c ha n ges w hic h c o nse q ue ntl y mi g ht decrease t he pr o d ucti vit y a n d ot her i m p orta nt 
as pects of life q u alit y (6 ). A re vie w of t he rele va nt literat ure p oi nte d o ut t he fact of hi g h 
pre vale n ce of slee p dist ur ba nce i n a d ults wit h A D w hic h ca n h a ve a re mar ka ble effect o n Q o L  (7 ). 
T here are a n u m ber of p ote ntial ris k fact ors f or slee p dist ur ba nce i n A D patie nts, i ncl u di n g t he 
itc h-scratc h c ycle, l esi o nal a n d ce ntr al pai n, p o or slee p h y gi e ne, circa dia n r h yt h m -i n d uce d 
m o dificati o n of itc h, a n d sec o n dar y effects of i nfla m mat or y c yt o ki nes o n sl ee p re g ul ati o n.  
Earlier st u dies ha v e s h o w n s u bsta ntiall y i m paire d q ualit y of slee p i n b ot h c hil d h o o d a n d a d ult 
A D, wit h re d uce d slee p o verall, m ore re g ular a n d pr otracte d a wa k e n i n g, o v erall decrease d slee p 
efficie n c y, a n d i ncreas e d da yti me d ysf u ncti o n bei n g re p orte d. Acti gra p h y a n d i nfrare d vi d e o 
( o bjecti ve meas ures of sl ee p) re veale d fra g me nte d slee p wit h m ore ni g ht-ti me a wa k e ni n gs, 
pr ol o n ge d a w a ke ni n gs, l o wer o verall slee p effi cie nc y, i n crease d scratc h ti me, a n d restless 
n oct ur nal m o ve me nt i n b ot h a d ults a n d c hil dre n wit h A D.  
T he I nter n ati o nal St u d y of Lif e wit h At o pic Ecze ma perf or m e d a m ultice nter q uesti o n naire -base d 
st u d y i ncl u di n g 1, 0 9 8 a d ults a n d disc o vere d t hat p atie nts had a n a v era ge of 8. 4 ni g hts of disr u pte d 
slee p wit h a t y pi cal A D flare, w hic h w or ke d o ut as ~ 8 1 da ys p er patie nt -ye ar. A st u d y of 3 4 , 6 1 3 
a d ults fr o m t he 2 0 1 2 N HI S f o u n d t hat 2 5 – 3 3 % of U S a d ults wit h self -re p orte d ecze ma re p orte d 
fati g u e, re g ul ar da yti me slee pi ness, a n d re g ular i ns o m nia. A d ults wit h self -re p orte d ecze ma were 
als o m ore li kel y t o r e p ort eit her s h ort or l o n g slee p d urati o n. At o pic der matitis a n d fati g u e, 
slee pi ness, a n d i ns o m nia were si g nifica nt pre dict ors of p o orer o verall healt h, n u m ber of si c k da ys, 
a n d d oct or visits, wit h ecze ma i n c o m bi nati o n wit h slee p s y m pt o ms ass oci ate d wit h a greater 
c ha nce of w ors e o utc o mes t ha n eit her slee p s y m pt o ms or ecze ma al o ne. A st u d y of 5 , 5 6 3 a d ults 
fr o m t he Nati o nal H ealt h a n d N utriti o n E x a mi nati o n S ur ve y f o un d t hat U S a d ults wit h A D m ore 
c o m m o nl y re p orte d s h ort slee p d urati o n, tr o u ble falli n g asle e p, ni g ht -ti me a wa ke ni n gs, earl y 
m or ni n g a wa ke ni n gs, a n d le g jer ks a n d le g cra m ps d uri n g sle e p a n d were m ore li kel y t o f eel 
u nreste d, bei n g o verl y sl ee p y d uri n g t he da y a n d feeli n g as if t he y di d n ot get e n o u g h slee p. Slee p 
dist ur ba nces ma y ha v e v er y detri me ntal effects i n A D patie nts, i ncl u di n g p o or perf or ma nce at 
sc h o ol a n d w or k, i m paire d healt h -rel ate d Q oL, c o nsi dera ble ec o n o mic b ur de n, a n d i ncrease d ris k 
of ps yc h o l o gi cal dis or ders, m ot or ve hicle acci de nts, a n d w or k place i nj ur y. T o get h er, t hese st u dies 
V V- C LI N- 0 5 5 0 3 9 6 4. 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol 0 2  
L P S 1 5 4 9 7  
7 -A pr -2 0 2 0  
V er si o n n u m b er: 1  
 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al  
P a g e 2 4  
s u g gest t hat slee p dist ur ba nces are b ot h ver y c o m m o n a n d b ur de ns o me i n A D patie nts a n d 
warra nt i nter ve nti o ns f or t heir treat me nt a n d pre ve nti o n  (5 ). 
A nal ys es of slee p relate d o utc o mes s uc h as  S C O R i n g at o pic d er matitis (S C O R A D ) slee p l oss 
sc ores fr o m d u pil u ma b p hase III st u dies ( S O L O 1, 2, C H R O N O S, a n d C A F É) s u p p orte d str o n g 
c orrel ati o ns bet wee n t he i m pr o ve me nt of cli nical o utc o mes a n d si g nifi ca nt slee p be nefit i n 
patie nts wit h m o derate t o se vere A D . A d diti o nall y s o me ot her st u dies i n A D pr o vi de d pr o misi n g 
i m pr o ve me nt i n slee p as meas ure d b y acti gra p h y w he n t he diseas e is c o ntr olle d effecti vel y (8 ). 
2. 3  
B E N E FI T/ RI S K A S S E S S M E N T   
M o derate -t o-se vere A D is a seri o us i nfla m mat or y s ki n disease wit h a hi g h disa bilit y b ur de n. 
At o pic der matitis treat me nt is t y pic all y l o n g -ter m, gi ve n t hat A D is a c hr o ni c s yste mic disease, 
a n d e x acer bati o ns of si g ns a n d s y m pt o ms (e g, flares) ca n b e fre q ue nt, u n pr e dicta ble, a n d 
disr u pti ve. Safe a n d effecti ve t hera pies are n ot c urre ntl y a v aila ble f or a lar ge n u m ber of A D 
patie nts w h ose disease ca n n ot be a de q uat el y c o ntr olle d wit h t o pical treat me nts or f or w h o m 
t o pical treat me nts are ot h er wise i na d visa ble. S yste mic i m m u n os u p pressa nts use d i n A D are 
ass ociate d wit h t o xicit y a n d l o n g -ter m si de effects, t h us li miti n g t heir use t o s h ort c o urses a n d/ or 
i nter mitte nt t hera p y, w hic h ofte n lea ds t o rela pse or re b o u n d u p o n tr eat me nt wit h dra wal. 
As a tar get e d a ge nt, sel ecti vel y i n hi biti n g t he I L -4 a n d I L-1 3 si g nali n g, d u pil u ma b is a n o vel 
s yste mic t hera p y f or A D, de m o nstrati n g si g nifica nt a n d cli nicall y mea ni n gf ul be nefits c o m bi ne d 
wit h a fa v ora ble safet y pr ofile, c o m pare d t o e xis ti n g n o n-s electi ve s yste mic i m m u n os u p pressa nts. 
T he t otalit y of cli nical e vi de nce, w hic h i n cl u de d data fr o m patie nts wit h  m o derate -t o-se vere A D 
fr o m 1 1 st u dies, de m o nstrate d a mar ke dl y fa v ora ble be nefit/ris k rati o f or d u pil u ma b 3 0 0  m g 
Q 2 W, b ot h m o n ot hera p y u p t o 1 6  wee ks or i n c o m bi nati o n wit h T C S u p t o 5 2  wee ks. 
F urt her m ore, t he place b o -c o ntr olle d mai nte na n ce st u d y ( S O L O -C o nti n ue) als o pr o vi de d 
a d diti o nal s u p p ort f or d u pil u ma b 3 0 0  m g Q 2 W as l o n g -ter m d ose-re gi me n i n patie nts wit h 
m o derate -t o-s e vere A D. 
T he be nefits i ncl u de cleara nce of s ki n A D lesi o ns, or at least a s u bsta ntial r e d ucti o n of lesi o n 
e xte nt a n d se verit y, i n c o n j u ncti o n wit h relief of s u bjecti ve s y m pt o ms, partic ularl y pr urit us, 
hall mar k of A D a n d fre q ue nt ca use of sec o n d ar y s y m pt o ms s uc h as slee p l oss a n d ass ociate d 
disa bilit y. T h e i m pr o ve m e nts i n A D si g ns a n d s y m pt o ms were parallele d b y i m pr o ve me nts i n 
q ualit y o f life, re d uce d a n xiet y a n d d e pressi o n sc ores, a n d i m pr o ve d d a y-t o-da y f u ncti o ni n g a n d 
o verall patie nts’ w ell -bei n g. T hes e be n efits occ urre d wit hi n 1 t o 2  wee ks of treat me nt i nitiati o n 
a n d are s ustai n e d wit h c o nti n ue d treat me nt.  
Fr o m a safet y pers pecti v e, d u pil u ma b was ge nerall y well t olerate d a n d t he safet y pr ofile was 
lar gel y c o m para ble t o pla ce b o. T he a d verse dr u g reacti o ns ( A D Rs) i d e ntifie d t o date f or 
d u pil u ma b i ncl u de i njecti o n site reacti o ns, c o nj u ncti vitis, oral her pes, aller gic c o nj u ncti vitis, 
bacterial c o nj u ncti vitis, her pes si m ple x, ble p haritis, dr y e ye, e ye pr urit us, a n d e osi n o p hilia. 
E x ce pt f or i njecti o n site reacti o ns, t hese A D Rs are c o m m o nl y see n i n t he A D patie nt p o p ulati o n; 
t he y o cc urre d wit h rel ati vel y l o w fre q u e nc y wit h d u pil u ma b treat me nt, a n d were ge nerall y mil d 
a n d m o derate, tra nsie nt, a n d ma na gea ble. M ore si g nifica nt seri o us aller gi c reacti o ns w ere v er y 
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7 -A pr -2 0 2 0  
V er si o n n u m b er: 1  
 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al  
P a g e 2 5  
rare. I m p orta ntl y, n o i ncrease d o verall i nfecti o n ris k was o bser ve d i n p atie nts treate d wit h 
d u pil u ma b. F urt her m ore, t here are n o i m p orta nt safet y c o ncer ns f or l o n g -ter m treat me nt wit h 
d u pil u ma b, w hic h is critical f or a c hr o nic dis ease li ke A D. Si nce d u pil u ma b’s o nset of acti o n is 
ra pi d a n d cli nicall y e vi d e nt, patie nts a n d healt hcare pr o vi ders ca n easil y d eter mi ne if d u pil u ma b is 
ha vi n g t he i nte n d e d effect s h ortl y after i nitiati o n of treat me nt, all o wi n g f or a p pr o priate ris k 
miti gati o n b y disc o nti n ui n g treat me nt i n patie nts w h o d o n ot res p o n d t o d u pil u ma b. T here is n o 
e vi de nce of dise ase re b o u n d after disc o nti n uati o n of d u pil u ma b treat me nt, s o treat me nt ma y be 
disc o nti n ue d safel y, ta ki n g i nt o c o nsi derati o n S m P C g ui da nce i n case of s yste mic h y perse nsiti vit y 
reacti o n, hel mi nt h i nfecti o n ( u ntil res ol uti o n of t he i nfecti o n) a n d c o m or bi d ast h ma (caref ul 
m o nit ori n g).   
A d diti o nal  detaile d i nf or mati o n a b o ut t he k n o w n a n d e x pecte d be n efits a n d ris ks a n d  reas o n a bl y 
e x pecte d a d vers e e v e nts  ( A E) of d u pil u ma b ca n b e f o u n d i n t he I n vesti gat or’s Br oc h ure (I B), 
Prescri bi n g I nf or m ati o n ( PI ), or S u m mar y of Pr o d uct C haract eristics. 
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A m e n d e d Cli ni c al Tri al Pr ot o c ol 0 2  
L P S 1 5 4 9 7  
7 -A pr -2 0 2 0  
V er si o n n u m b er: 1  
 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al  
P a g e 2 6  
3  
O B J E C TI V E S A N D E N D P O I N T S  
T a bl e  1  - O bj e cti v e s a n d e n d p oi nt s   
O bj e cti v e s  
E n d p oi nt s  
Pri m ar y  
 
T o ev al u at e t h e eff ect of d u pil u m a b o n sl e e p q u ality 
i n a d ult p ati e nts wit h m o d er at e t o s ev er e at o pic 
d er m atitis ( A D)  
 
Perc e nt a g e  c h a n g e fr o m b as eli n e t o w e ek  1 2 i n sl e e p 
q u ality n u m eric al r ati n g sc al e ( N R S)  
S e c o n d ar y  
 
T o ev al u at e t h e eff ect of d u pil u m a b o n o bj ectiv e 
a n d s u bj ectiv e q u a ntit ativ e sl e e p p ar a m et ers, A D 
r el at e d o utc o m es, a n d d ayti m e c o ns e q u e nc es of 
sl e e p d e priv ati o n.  
 
Sec o n d ary E n d p oi nts  
 
C h a n g e fr o m b as eli n e t o w e ek  1 2 i n sl e e p effici e ncy 
( S E) b as e d o n actigr a p hy d at a  
 
C h a n g e fr o m b as eli n e t o w e ek  1 2 i n t ot al sl e e p ti m e 
( T S T) b as e d o n acti gr a p hy d at a 
 
C h a n g e fr o m b as eli n e t o w e ek  1 2 i n w ak e aft er sl e e p 
o ns et ( W A S O) b as e d o n acti gr a p hy d at a  
 
C h a n g e fr o m b as eli n e t o w e ek  1 2 i n sl e e p o ns et l at e ncy 
( S O L) b as e d o n acti gr a p hy d at a 
 
Perc e nt c h a n g e fr o m b as eli n e t o w e ek  1 2 i n Pr urit us 
N R S  
 
C h a n g e fr o m b as eli n e t o w e ek  1 2 i n S C O Ri n g At o pic 
D er m atitis ( S C O R A D) t ot al sc or e  
 
C h a n g e fr o m b as eli n e t o w e ek  1 2 i n S C O R A D sl e e p 
V A S  
 
Pr o p orti o n of p ati e nts wit h E A SI 5 0 (r e d ucti o n of E A SI 
sc or e by ≥5 0 % fr o m b as eli n e) at w e ek 1 2  
 
Pr o p orti o n of p ati e nts wit h, E A SI 7 5 (r e d ucti o n of E A SI 
sc or e by ≥7 5 % fr o m b as eli n e) at w e ek  1 2  
 
C h a n g e fr o m b as eli n e t o w e ek  1 2 i n P ati e nt Ori e nt e d 
Ecz e m a M e as ur e ( P O E M) t ot al sc or e  
 
C h a n g e fr o m b as eli n e t o w e ek  1 2 i n D er m at ol o gy Lif e 
Q u ality I n d ex ( D L QI) t ot al sc or e  
 
C h a n g e fr o m b as eli n e t o w e ek 1 2 i n P R O MI S Sl e e p 
R el at e d I m p air m e nt S F 8 a T ot al Sc or e  
 
 
T o c o nti n u e t o ass ess t h e s af ety a n d t ol er a bility of 
d u pil u m a b t hr o u g h o ut t h e st u dy.  
 
I nci d e nc e of a dv ers e ev e nts t hr o u g h w e ek  1 2  
 
I nci d e nc e of a dv ers e ev e nts t hr o u g h w e ek 2 4  
 
 
 
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L P S 1 5 4 9 7  
7 -A pr -2 0 2 0  
V er si o n n u m b er: 1  
 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al  
P a g e 2 7  
O bj e cti v e s  
E n d p oi nt s  
E x pl or at or y  
 
T o f urt h er ev al u at e t h e eff ect of d u pil u m a b o n 
o bj ectiv e a n d s u bj ectiv e sl e e p p ar a m et ers, A D -
r el at e d o utc o m es, a n d d ayti m e c o ns e q u e nc es of 
sl e e p d e priv ati o n. 
Ex pl or at ory E n d p oi nt s: 
 
Perc e nt c h a n g e fr o m b as eli n e  i n sl e e p q u ality N R S t o 
w e ek 1, 2, 4, a n d 8 . 
 
Perc e nt c h a n g e fr o m b as eli n e  i n pr urit us N R S t o w e ek 1, 
2, 4, a n d 8 . 
 
C h a n g e fr o m b as eli n e i n sl e e p effici e ncy b as e d o n 
acti gr a p h y t o w e ek 1, 2, 4, a n d  8 . 
 
C h a n g e fr o m b as eli n e i n W A S O b as e d o n acti gr a p h y t o 
w e ek 1, 2, 4, a n d  8 . 
 
C h a n g e fr o m b as eli n e i n T S T b as e d o n acti gr a p h y t o 
w e ek 1, 2, 4, a n d  8 . 
 
C h a n g e fr o m b as eli n e i n sl e e p l at e ncy b as e d o n 
acti gr a p h y t o w e ek 1, 2, 4, a n d  8 . 
 
C h a n g e fr o m b as eli n e i n S C O R A D t ot al sc or e a n d sl e e p 
V A S t o w e ek 1, 2, 4, a n d  8 . 
 
E A SI 5 0 a n d E A SI 7 5 at w e eks 1, 2, 4, a n d 8 . 
 
C h a n g e fr o m b as eli n e t o w e ek 1 2 i n P S G m e as ur es of 
sl e e p effici e ncy, T S T, W A S O, a n d sl e e p l at e ncy. 
 
C h a n g e fr o m b as eli n e t o w e eks 1, 2, 4, a n d 8  i n 
P R O MI S Sl e e p R el a t e d I m p air m e nt S F 8 a t ot al sc or e. 
 
C h a n g e fr o m b as eli n e t o w e ek 1, 2, 4, 8, a n d 1 2 i n ski n 
p ai n N R S . 
 
C h a n g e fr o m b as eli n e t o w e ek 1, 2, 4, 8, a n d 1 2 i n ski n 
s e nsitivity t o t o uc h N R S. 
 
C h a n g e fr o m b as eli n e t o w e ek 1, 2, 4, 8, a n d 1 2 i n ski n 
b ur n N R S . 
 
C h a n g e fr o m b as eli n e i n S O L , T S T , n u m b er of 
a w ak e ni n gs, W A S O , sl e e p effici e ncy , a n d h o w r est e d t o 
w e ek 1, 2, 4, 8, a n d 1 2 b as e d o n sl e e p di ary . 
 
C h a n g e fr o m b as eli n e t o w e ek 4 a n d 1 2 i n E p w ort h 
Sl e e pi n ess Sc al e ( E S S) . 
 
C h a n g e fr o m b as eli n e t o w e ek 1 2 i n psyc h o m ot or 
vi gil a nc e t est ( P V T). 
 
C h a n g e fr o m b as eli n e t o w e ek 1 2 i n R u n ni n g M e m ory , 
M at h e m atic al Pr oc essi n g a n d Pr oc e d ur al R e acti o n Ti m e 
sc or es b as e d o n t h e n e ur oc o g nitiv e t est  ( Aut o m at e d 
N e ur o psyc h ol o gic al Ass ess m e nt M etrics [ A N A M]) . 
 
W ork pr o d uctivity a n d activity i m p air m e nt –  At o pic 
D er m atitis v ersi o n ( W P AI-A D) ass oci at e d q u esti o ns 
c h a n g e fr o m b as eli n e t o w e eks 4, 8, a n d 1 2 . 
 
Miss e d sc h o ol/ w ork d ays fr o m b as eli n e t o w e ek 1 2. 
 
T o ev al u at e t h e r el ati o ns hi ps b et w e e n sl e e p 
dist ur b a nc e a n d ot h er o bj ectiv e a n d s u bj ectiv e 
p ar a m et ers ass oci at e d wit h A D.  
 
R el ati o ns hi p b et w e e n v ari a bl es r el ati n g t o sl e e p 
dist ur b a nc es ( e g, T S T , W A S O ) a n d o bj ectiv e a n d 
s u bj ectiv e p ar a m et ers ass oci at e d wit h  A D ( e g, E A SI, 
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Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al  
P a g e 2 8  
O bj e cti v e s  
E n d p oi nt s  
S C O R A D, pr urit us N R S, D L QI,  E A SI, ski n p ai n N R S, 
a n d ski n b ur n N R S s e nsitivity t o t o uc h N R S). 
 
T o ev al u at e t h e eff ect of d u pil u m a b i n c o m or bi d 
c o n diti o ns. 
Ex pl or at ory E n d p oi nts : 
 C h a n g e fr o m b as eli n e t o w e ek 1 2 i n A C Q -5 a m o n g t h os e 
w h o r e p ort e d ast h m a at b as eli n e . 
 C h a n g e fr o m b as eli n e t o w e ek 1 2 A R -V A S a m o n g t h os e 
w h o r e p ort e d all er gic r hi nitis at b as eli n e. 
 C h a n g e fr o m b as eli n e t o w e eks 4 a n d 1 2 i n 
H A D S -a nxi ety a n d H A D S -d e pr essi o n sc or es. 
 
T o ev al u at e t h e eff ect of d u pil u m a b o n i n divi d u al 
q u a ntit ativ e a n d n o n -sl e e p r el at e d e n d p oi nts 
ass oci at e d wit h A D at w e ek 2 4.  
 C h a n g e or p erc e nt c h a n g e ( as us e d i n a n alys es of 
w e ek  1 2 d at a) fr o m b as eli n e t o w e ek  2 4  f or pri m ary a n d 
s ec o n d ary e n d p oi nts. 
 C h a n g e or p erc e nt c h a n g e ( as us e d i n a n aly s es of 
w e ek  1 2 d at a) fr o m w e ek  1 2 t o w e ek  2 4 f or pri m ary a n d 
s ec o n d ary e n d p oi nts. 
3. 1  
A P P R O P RI A T E N E S S O F M E A S U R E M E N T S   
A p pr o priate n ess of meas ure me nts is descri be d i n Secti o n  8. 1  a n d Secti o n  8. 2 . 
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L P S 1 5 4 9 7  
7 -A pr -2 0 2 0  
V er si o n n u m b er: 1  
 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al  
P a g e 2 9  
4  
S T U D Y D E SI G N   
4. 1  
O V E R A L L D E SI G N   
T his is a p hase I V ra n d o mize d, d o u ble -bli n d, place b o -c o ntr olle d st u d y e v al uati n g t he effect of 
d u pil u ma b o n slee p i n a d ult patie nts wit h m o derate t o se vere A D . 
T he  st u d y will c o m prise of: 
 
Scree ni n g P eri o d 1 ( Da y -2 8 t o -8 ): Patie nts will be e val uat e d acc or di n g t o i ncl usi o n a n d 
e x cl usi o n criteria.  
 
Scree ni n g Peri o d 2 ( Da y  -7 t o -1; Pre -bas eli ne ass ess me nts): e li gi ble p atie nts will 
c o m plete t he dail y slee p, q ualit y,  dail y pr urit us, s ki n pai n , s ki n se nsiti vit y, a n d t o uc h s ki n 
b ur n, slee p diar y, a n d will wear a n acti gra p h at ni g ht -ti me d uri n g t he 7 da ys i m me diatel y 
prece di n g t he Baseli ne visit  ( Da y 1). If preferre d b y t he patie nt a n d t he i n vesti gat or f or 
l o gistical reas o ns, scree ni n g ca n be d o ne d uri n g a si n gle o n-site visit. I n t hat case, all 
pr oce d ures pla n ne d at scree ni n g 1 a n d scree ni n g 2 s h o ul d be d o ne d uri n g t his si n gle 
scree ni n g visit. I m p orta ntl y, t his si n gle scree ni n g visit will ha ve t o be d o ne at least 7 da ys 
bef ore t h e baseli ne visit, as patie nts s h o ul d wear t he acti gra p h a n d c o m plet e t he diar y f or 
7  da ys b ef or e baseli ne. 
 
Baseli ne ( Da y 1 ): Patie nts w h o re mai n eli gi ble will be ra n d o mize d 
 
1 2 -wee k d o u bl e -bli n d place b o -c o ntr olle d peri o d : Patie nts will be ra n d o mize d t o recei ve 
d u pil u ma b or place b o  
 
1 2 -wee k o p e n -la b el e xte nsi o n peri o d: F oll o wi n g c o m pleti o n of d o u ble-bl i n d peri o d, 
patie nts ra n d o mize d t o d u pil u ma b will c o nti n ue t o recei v e acti ve tr eat me nt f or o pe n -la bel 
peri o d, w hereas p atie nts ra n d o mize d t o place b o will recei ve acti ve treat me nt wit h 
d u pil u ma b.  
T he ma xi m u m st u d y d urati o n per partici pa nt will be 2 8  wee ks . 
P ol ys o m n o gra p h y ( P S G)  s u b-st u d y will be c o n d ucte d at selecte d U S sites  i n u p t o 3 0 patie nts t otal 
( u p t o 2 0 d u pil u ma b a n d 1 0 place b o patie nts). Eac h patie nt w h o partici pates i n t his s u b-st u d y will 
ha ve a t otal of 3 o ver ni g ht P S Gs: at baseli ne ti me p oi nt, 2 (prefera bl y ) c o nsec uti ve o ver ni g ht P S Gs 
t o c o ntr ol f or “first ni g ht effect” ( ni g ht of Da y -2)  a n d c ollect baseli ne data ( ni g ht of Da y -1) ; t he n 1 
o ver ni g ht P S G at w ee k 1 2.  Selecti o n of patie nts f or t he P S G s u b -st u d y will be base d o n t heir 
pr o xi mit y t o part ici pati n g slee p ce nters a n d a vaila bilit y f or o ver ni g ht sta y. 
4. 2  
S CI E N TI FI C R A TI O N A L E  F O R S T U D Y D E SI G N   
Slee p dist ur ba nce is a well -k n o w n de bilitati n g s y m pt o m of A D, t h o u g h fe w st u dies ha ve 
i n vesti gate d it as a pri mar y o utc o m e t o assess t he i m pact of t his c o n diti o n o n patie nt’s Q o L  a n d 
ot her i m p orta nt o utc o mes t hat patie nts s uffer i n t h eir dail y li ves. T his d o u ble -bli n d pr os pecti ve 
st ud y will a p pl y b ot h o bj ecti ve a n d s u bjecti ve t o ols t o meas ure slee p relate d o utc o mes a n d 
c o m pre he nsi vel y assess d u pil u ma b treat me nt effect o n slee p dist ur ba nce, a n d c o nse q ue ntial 
V V- C LI N- 0 5 5 0 3 9 6 4. 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol 0 2  
L P S 1 5 4 9 7  
7 -A pr -2 0 2 0  
V er si o n n u m b er: 1  
 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al  
P a g e 3 0  
as pects of slee p de pri vati o n i ncl u di n g da yti me slee pi ness, dail y f u ncti o n, n e u r oc o g niti ve a n d 
ps yc h o m ot or f u ncti o n, pr o d ucti vit y, a n d Q o L f or a d ult patie nts wit h A D disease.  
T he d o u ble -bli n d desi g n i nte n ds t o miti gate p ote ntial bias a n d place b o c o ntr ol is necessar y t o 
assess t he net effect  of acti ve d u pil u ma b treat me nt.  
Place b o pati e nts will be recei vi n g acti ve d u pil u ma b at w ee k 1 2; w hic h will e n ha nce recr uit me nt 
a n d retai ni n g patie nts i n a p hase I V trial w here t h e i n vesti gati o nal pr o d uct has alrea d y bee n 
c o m merciall y a v aila ble f or t heir usa ge. It will als o hel p t o ca pt ure rare e ve nt s s uc h as healt h care 
res o urce utilizati o n a n d w or k pr o d ucti vit y w hic h mi g ht ta ke a l o n ger ti me t o occ ur. 
4. 3  
J U S TI FI C A TI O N F O R D O S E   
T he d ose sele cte d i n t his st u d y is t he d ose a p pr o ve d f or t he treat me nt of m o derate t o se v ere A D  
f or D u pi x e nt i n U S, E U, a n d all ot her c o u ntri es t hat t his st u d y will be c o n d ucte d.  
4. 4  
E N D O F S T U D Y D E FI NI T I O N  
A partici pa nt is  c o nsi dere d t o ha ve c o m plet e d t he st u d y if he/s he h as c o m plete d all  p hases of t he 
st u d y i ncl u di n g t h e last sc he d ule d visit  s h o w n i n t he S o A  (Secti o n  1. 3 ). 
T he e n d of t he st u d y is d efi ne d as t he d ate of t he l ast sc he d ule d visit  s h o w n i n t he S O A 
(Secti o n  1. 3 ) f or t he l ast partici pa nt i n t he trial gl o ball y. 
V V- C LI N- 0 5 5 0 3 9 6 4. 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol 0 2  
L P S 1 5 4 9 7  
7 -A pr -2 0 2 0  
V er si o n n u m b er: 1  
 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al  
P a g e 3 1  
5  
S T U D Y P O P U L A TI O N   
Pr os pecti ve a p pr o val of pr ot oc ol de viati o ns t o recr uit me nt a n d e nr oll me nt criteria, als o k n o w n as 
pr ot oc ol wai vers o r e x e m pti o ns, is n ot per mitte d. 
5. 1  
I N C L U SI O N C RI T E RI A  
Partici pa nts are eli gi ble t o be i ncl u de d i n t he st u d y o nl y if all of t he f oll o wi n g criteria a p pl y:  
A ge  
I 0 1. P artici pa nt m ust be 1 8  ye ars of a ge or ol der , at t he ti me of si g ni n g t he i nf or me d c o nse nt  
T y pe of p artici p a nt a n d dise ase c h ar acteristics  
I 0 2. Partici pa nts wit h c hr o nic A D  t hat has bee n d oc u m e nte d f or at least 2  years bef ore t h e 
scree ni n g visit 
I 0 3. I n a de q uat e res p o ns e t o t o pical me dicati o ns or ot her wise ca n di d ate f or s yste mic A D 
treat me nt 
I 0 4. Ecze ma Area Se verit y I n de x ( E A SI ) sc ore ≥1 2  at scree ni n g a n d baseli ne visits  
I 0 5. I n v esti gat or’s gl o bal assess me nt (I G A) sc ore ≥3 ( o n t he 0 t o 4 I G A scal e) at t he scree ni n g 
a n d baseli ne visits  
I 0 6. ≥1 0 % b o d y s urface area ( B S A ) of A D i n v ol ve me nt at t he scree ni n g a n d baseli ne visits  
I 0 7. Baseli ne pr urit us N R S sc ore f or ma xi m u m itc h i nte nsit y ≥3 ( bas e d o n wee kl y a v erag e of 
dail y sc ores d uri n g t he 7  da ys i m me diatel y prece di n g baseli ne , or base d o n a vera ge of 
dail y sc ores c o m plete d f or 5 da ys (fr o m Da y -7 t o D a y -3  pri or t o b aseli ne ) f or patie nts 
partici pa ti n g i n t he P S G s u b -st u d y; at least 4 r ati n gs o ver t he pri or wee k / o v er t he 5 da ys 
are re q uire d t o c alc ulate t he a vera ge) 
I 0 8. Baseli ne Sle e p  Q ualit y  N R S sc ore ≤5 ( base d o n wee kl y a vera ge of dail y sc ores d uri n g t he 
7  da ys i m me diatel y prece di n g b aseli ne , or base d o n a vera ge of dail y sc ores c o m plete d f or 
5 da ys (fr o m Da y -7 t o D a y -3  pri or t o bas eli ne ) f or patie nts partici pati n g i n t he P S G s u b-
st u d y; at least 4 r ati n gs o ver t he pri or wee k/ o ver t he 5 da ys are re q uire d t o calc ulate t he 
a vera ge)  
I 0 9. Ha ve bee n a p pl yi n g s ki n e m olie nts ( m oist urizers) t wice dail y ( o nce dail y o n areas 
recei vi n g bac k g o u n d t o pical me dicati o ns –  see I 1 0 bel o w a n d Secti o n  6 ) f or at least 7 da ys 
pri or t o ra n d o mizati o n  
I 1 0. Ha ve bee n a p pl yi n g me di u m -p ote nc y T C S o n all acti ve A D lesi o ns, o nce dail y f or at least 
7  da ys b ef ore ra n d o mizati o n, usi n g t he sta n dar dize d re gi me n p r o vi de d i n t h e pr ot oc ol. 
V V- C LI N- 0 5 5 0 3 9 6 4. 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol 0 2  
L P S 1 5 4 9 7  
7 -A pr -2 0 2 0  
V er si o n n u m b er: 1  
 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al  
P a g e 3 2  
N ote : L o w-p ote nc y T C S or t o pical calci n e uri n i n hi bit or (T CI ) m a y be use d o n areas t h at 
ca n n ot be safel y treate d wit h me di u m - p ote nc y T C S (e g, face, ge nital, fle x ural ar eas, or 
areas of s ki n atr o p h y)  
I 1 1. Willi n g a n d a ble t o c o m pl y wit h all cli nic visits a n d st u d y -relate d pr oce d ures 
Wei g ht  
N ot a p plica ble . 
Se x  
Male or fe m ale  
I nf or me d C o nse nt  
I 1 2. Ca pa ble  of gi vi n g si g n e d i nf or me d c o nse nt as d es cri be d i n Secti o n  1 0. 1  (A p pe n di x 1 ) 
w hic h i ncl u des c o m plia n ce wit h t he re q uire me nts a n d restricti o ns liste d i n t he i nf or me d 
c o nse nt f or m ( I C F) a n d i n t his pr otoc ol. I n c o u ntries w here le gal a ge of a d ult h o o d is a b o ve 
1 8  years, a s p ecific I C F m ust als o be si g ne d b y t h e partici pa nt’s le gall y a ut h orize d 
re pres e ntati ve. 
5. 2  
E X C L U SI O N C RI T E RI A   
Partici pa nts are e x cl u de d fr o m t he st u d y if a n y of t he f oll o wi n g criteria a p pl y:  
Me dic al c o n diti o ns  
E 0 1.  K n o w n h y p erse nsiti vit y t o D u pi x e nt i ncl u di n g all e x ci pie nts  
E 0 2.  E vi de nce of dr u g a b use i n past 2  years  
E 0 3.  Slee p dist ur ba nces n ot relate d t o A D, i ncl u di n g sl ee p a p n ea, h y pers o m nia , or i ns o m nia 
sec o n dar y t o c hr o nic pai n, u nc o ntr olle d ast h ma, c hr o nic o bstr ucti ve p ul m o nar y disease, 
etc., as deter mi ne d b y t he In v esti gat or  
E 0 4.  Patie nts w h o w or k ni g ht s hifts (ie, a n y  w or k b et w ee n 8  p m a n d 6  a m)  
E 0 5.  Pat ie nts wit h erratic slee p ha bits, as deter mi ne d b y t he I n v esti gat or 
E 0 6.  E vi de nce of restless le g s y n dr o me  or peri o dic li m b m o ve me nt dis or der  
E 0 7.  Ac ute i nfecti o n re q uiri n g s yste mic treat me nt wit hi n 1 wee k bef ore t h e scree ni n g visit  
N ote : Patie nts ma y be res cree n e d n o s o o ner t ha n 1 wee k after t he i nf ecti o n res ol ves, a n d 
wit h per missi o n of t he S p o ns or’s M e dical M o nit or  
V V- C LI N- 0 5 5 0 3 9 6 4. 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol 0 2  
L P S 1 5 4 9 7  
7 -A pr -2 0 2 0  
V er si o n n u m b er: 1  
 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al  
P a g e 3 3  
E 0 8.  Acti ve e n d o parasitic i nfecti o ns ( hel mi nt hs); s us pecte d or hi g h ris k of e n d o parasitic 
i nfecti o n, u nless cli nical a n d (if necessar y) la b orat or y assess me nt ha v e r ule d o ut acti ve 
i nfecti o n bef ore ra n d o mizati o n 
E 0 9.  Se vere c o n c o mita nt ill ness(es) t hat, i n t he i n vesti gat or’s j u d g me nt, w o ul d a d versel y affect 
t he patie nt’s partici pati o n i n t he st u d y. E x a m ples i ncl u de, b ut are n ot li mite d t o, patie nts 
wit h s h ort life e x pecta nc y, patie nts wit h u nc o ntr olle d dia betes ( h e m o gl o bi n A 1c [ H b A 1c] 
≥9 %), patie nts wit h car di o vasc ular c o n diti o ns (e g, sta ge III or I V car diac fail ure acc or di n g 
t o t he Ne w Y or k Heart Ass ociati o n classificati o n), se vere re nal c o n diti o ns (e g, p atie nts o n 
dial ysis), he p at o -biliar y c o n diti o ns (e g, C hil d -P u g h class B or C), n e ur ol o gical c o n diti o ns 
(e g, de m yeli nati n g diseas es), acti ve m aj or a ut oi m m u ne diseases (e g, l u p us, i nfla m mat or y 
b o wel disease, r he u mat oi d art hritis, etc.), ne ur o -i nfla m mat or y disease, ot h er severe 
e n d ocri n ol o gical, gastr oi ntesti nal, meta b olic, p ul m o nar y or l y m p h atic diseases. T he 
s pecific j ustificati o n f or patie nts e x cl u de d u n der t his criteri o n will be n ote d i n st u d y 
d oc u me nts (c hart n otes, case re p ort f or ms [ C R Fs ], etc.) 
E 1 0.  A n y ot her me dical or ps yc h ol o gical c o n diti o n (i ncl u di n g rele va nt la b orat or y a b n or malities) 
t hat i n o pi ni o n of i n vesti gat or m a y pres e nt a n u nreas o na ble ris k t o t he st u d y patie nt as a 
res ult of his/ her partici p ati o n i n cli nical trial, ma y ma ke patie nt’s partici pati o n u nrelia ble 
or ma y i nterfere wit h st u d y ass ess me nts. T he s pecific j ustificati o n f or patie nts e x cl u de d 
u n der t his criteri o n will b e n ote d i n st u d y d oc u m e nts (c hart n otes, C R Fs, et c.)  
E 1 1.  Prese nce of s ki n c o n diti o ns  t hat may i nterfere wit h st u d y assess me nts  
E 1 2.  C o ntra i ndic ati o ns or i m p orta nt si de effects of T C S  (e g, i nt olera nce t o treat me nt, 
h y perse nsiti vit y reacti o ns, si g nifica nt s ki n atr o p h y, s yste mic effects), as assesse d b y t he 
In v esti gat or  
E 1 3.  At baseli ne, pres e nce of a n y c o n di ti o ns liste d as criteria f or st u d y dr u g disc o nti n uati o n 
(see Secti o n  7. 1 ) 
Pri or/c o nc o mit a nt t her a p y  
E 1 4.  Patie nts ta ki n g se dati ve a n xi ol ytic or h y p n otic treat me nts  ot her t ha n melat o ni n  o n a re g ular 
basis wit hi n 3  m o nt hs bef ore ra n d o mizati o n . Occasi o nal use (ie, n o m ore t h a n t wice a 
wee k) is all o w e d, e x ce pt wit hi n 2 wee ks bef ore ra n d o mizati o n  
E 1 5.  Patie nts ta ki n g s yst e mic se dati ve a nti hista mi nes m ore t ha n 5 da ys a wee k.  N ote : Patie nts 
ta ki n g s yste mic se d ati ve a nti hista mi nes ≤5 da ys p er wee k m ust be o n sta ble re gi me ns f or 
at least 1  m o nt h bef ore ra n d o mizati o n, a n d mai ntai n t he sa me re gi me n t hr o u g h o ut t he 
st u d y 
E 1 6.  C urre n t treat me nt wit h a nti de pressa nts, li p o p hilic beta bl oc kers, cl o ni di ne, o pi oi ds, 
t he o p h ylli ne, or ot her me dicati o ns k n o w n t o i nterfere wit h slee p a n d ma y c o nf o u n d t he 
st u d y assess me nts, as d et er mi ne d b y t he In v esti gat or . N ote : I n m ost cases, c hr o nic 
treat ments a d mi nistere d re g ul arl y a n d at sta bl e d osi n g s h o ul d be acce pt a ble. I n v esti gat ors 
V V- C LI N- 0 5 5 0 3 9 6 4. 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol 0 2  
L P S 1 5 4 9 7  
7 -A pr -2 0 2 0  
V er si o n n u m b er: 1  
 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al  
P a g e 3 4  
s h o ul d assess t he de gree t o w hic h a n i n di vi d ual me dicati o n ma y ca us e c h a n ges i n slee p 
patter n or slee p q u alit y d uri n g t he st u d y, c o m p are d t o t he pre -bas eli ne state  
E 1 7.  S yste mic  c ycl os p ori n e A  (Cs A ), s yste mic c ortic oster oi ds, azat hi o pri ne ( A Z A), 
met h otre x ate  ( M T X), m yc o p he n olate mo fetil ( M M F), or ja n us ki nas e (J A K) i n hi bit ors, or 
p h ot ot hera p y  wit hi n 4  wee ks pri or t o bas eli ne visit  
E 1 8.  Treat me nt wit h bi ol o gics as f oll o ws:  
 
Pre vi o us treat me nt wit h 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 bef ore 
t he baseli ne  visit, 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 5 half -li ves (if k n o w n) or 1 6 wee ks pri or t o b aseli ne visit , 
w hic he ver is l o n ger  
E 1 9.  Treat me nt wit h a n i n vesti gati o nal dr u g wit hi n 8  wee ks or wit hi n 5 half -li ves (if k n o w n), 
w hic he ver is l o n ger, pri or t o baseli ne  
E 2 0.  Re g ular use ( m ore t ha n 2 visits  per wee k) of a ta n ni n g b o ot h/ parl or wit hi n 4  wee ks of t he 
scree ni n g visit 
E 2 1.  Pla n ne d or a ntici pate d us e of a n y pr o hi bite d me di cati o ns a n d pr oce d ures (see Secti o n  6. 5 ) 
E 2 2.  Treat me nt wit h li ve (atte n uate d) vacci ne wit hi n 1 2 wee ks bef ore t h e scree ni n g visit  
Pri or/c o nc urre nt cli nic al st u d y e x perie nce  
E 2 3.  C urre nt partici pati o n i n a n ot her i n vesti gati o nal cli nical st u d y  
Di a g n ostic assess me nts  
E 2 4.  N ot a p plica ble . 
Ot her e xcl usi o ns  
E 2 5.  A n y  ot her c o n diti o n ( me dical, pers o nal, f a milial, s ocial, e n vir o n me ntal, et c.) as ass esse d 
b y t he In vesti gat or, t hat c o ul d si g nifica ntl y alter sl ee p para meters a n d c o nf o u n d st u d y 
assess me nts  
E 2 6.  Pla n ne d or a ntici pate d m aj or s ur gical pr o ce d ure d uri n g t he patie nt’s  partici pati o n i n t his 
st u d y 
E 2 7.  Pre g n a nt or breast -fee di n g w o me n, or were pla n ni n g t o bec o me pre g n a nt  or breastfee d 
d uri n g t he p atie nt’s parti ci pati o n i n t his st u d y  
E 2 8.  W o me n u n willi n g t o use a de q uate birt h c o ntr ol, if of re pr o d ucti ve p ote ntial
* a n d se x uall y 
acti ve. A de q u ate birt h c o ntr ol is defi ne d as a gree me nt t o c o nsiste ntl y practice a n effecti ve 
V V- C LI N- 0 5 5 0 3 9 6 4. 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol 0 2  
L P S 1 5 4 9 7  
7 -A pr -2 0 2 0  
V er si o n n u m b er: 1  
 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al  
P a g e 3 5  
a n d acce pte d met h o d of c o ntrace pti o n t hr o u g h o ut t he d urati o n of t he st u d y a n d f or at least 
1 2 wee ks after last d ose of st u d y dr u g. T h ese i ncl u de h or m o nal c o ntrace pti ves, i ntra uteri ne 
de vice, or d o u ble b arri er c o ntrace pti o n (ie, c o n d o m + dia p hra g m) or a mal e part ner wit h 
d oc u me nte d vasect o m y. A d diti o nal re q uire me nts f or acce pta bl e c o ntrace pti o n ma y a p pl y 
i n certai n c o u ntries, b ase d o n l ocal re g ulati o ns. I n vesti gat ors i n t hes e c o u ntries will be 
n otifie d acc or di n gl y i n a pr ot oc ol clarificati o n letter  
* F or fe males, me n o pa us e is defi ne d as at least 1 2  c o nsec uti ve m o nt hs wit h o ut me nses; if i n 
q uesti o n, a f ollicle sti m ulati n g h or m o ne ( F S H ) le v el of ≥2 5 m U/ m L m ust b e d oc u me nte d. 
H ysterect o m y, bilateral o o p h orect o m y, or bilateral t u bal li gati o n m ust be d oc u me nte d, as 
a p plica ble; if d oc u me nt e d, w o me n wit h t hese c o n diti o ns are n ot re q uire d t o use a d diti o nal 
c o ntrace pti o n . 
5. 3  
LI F E S T Y L E C O N SI D E R A TI O N S   
N ot a p plica ble . 
5. 4  
S C R E E N F AI L U R E S   
Scree n fail ure s are defi ne d as partici pa nts w h o c o nse nt t o partici pate i n t he cli nical st u d y b ut are 
n ot s u bse q ue ntl y  eli gi ble t o be e nr olle d i n t he st u d y. A mi ni mal set of scree n fail ure i nf or m ati o n 
is re q uire d t o e ns ure tra ns pare nt re p orti n g of scree n fail ure partici pa nts t o meet t he C o ns oli date d 
Sta n dar ds of Re p orti n g Trials p u blis hi n g re q uir e me nts a n d t o res p o n d t o q u eries fr o m r e g ulat or y 
a ut h orities. Mi ni mal i nf or mati o n i ncl u des de m o gra p h y, s cree n fail ure details, eli gi bilit y criteria, 
a n d a n y A E . 
I n di vi d uals w h o d o n ot meet t he criteri a f or p arti ci pati o n i n t his st u d y (scree n fail ure) ma y b e 
re-scree n e d, t y picall y o n ce.  
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Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al  
P a g e 3 6  
6  
S T U D Y I N T E R V E N TI O N   
St u d y i nter ve nti o n is defi ne d as a n y i n vesti gati o nal i nter ve nti o ns, mar kete d pr o d ucts, place b o, or 
me dical de vice s i nte n d e d t o be a d mi nistere d t o a st u d y partici p a nt acc or di n g t o t he st u d y pr ot oc ol. 
6. 1  
S T U D Y I N T E R V E N TI O N( S ) A D MI NI S T E R E D  
T a bl e  2  - O v er vi e w of st u d y i nt er v e nti o n s a d mi ni st er e d   
St u d y i nt er v e nti o n n a m e  
D u pil u m a b  
Pl a c e b o  
D os a g e f or m ul ati o n  
D u pil u m a b 3 0 0  m g f or S C 
a d mi nistr ati o n is s u p pli e d as 
1 5 0  m g/ m L s ol uti o n i n 2. 2 5  m L 
pr e -fill e d gl ass syri n g es t o d eliv er 
3 0 0  m g i n 2. 0  m L  
Pl ac e b o f or d u pil u m a b will b e 
pr ovi d e d i n i d e ntic ally m atc h e d gl ass 
pr e -fill e d syri n g e t o d eliv er 2 m L, 
w hic h will m atc h d u pil u m a b 3 0 0  m g.  
U nit d os e str e n gt h(s)/ D os a g e l ev el(s)  
3 0 0  m g  
N ot a p plic a bl e  
R o ut e of a d mi nistr ati o n  
Su bc ut a n e o us  
Su bc ut a n e o us  
D osi n g i nstr ucti o ns  
D u pil u m a b 3 0 0 m g S C Q 2 W ( wit h a 
6 0 0 m g l o a di n g d os e at 
r a n d o miz ati o n D ay 1, t h e n f oll o w e d 
wit h d u pil u m a b 3 0 0 m g S C Q 2 W  
u ntil w e ek 1 0 );  
A t w e ek 1 2, d u pil u m a b 3 0 0 m g pl us 
1 pl ac e b o t o m ask pr i or bli n di n g; 
t h e n f oll o w e d wit h 3 0 0 m g S C Q 2 W 
wit h a l ast i nj ecti o n at w e ek 2 2  
Pl ac e b o S C Q 2 W t o d eliv er 2 m L 
( wit h pl ac e b o l o a di n g d os e at 
r a n d o miz ati o n D ay 1, t h e n f oll o w e d 
wit h 1 pl ac e b o d os e Q 2 W  u ntil w e ek 
1 0 ); 
A t w e ek 1 2, d u pil u m a b 6 0 0 m g 
l o a di n g d os e; t h e n f oll o w e d wit h 
d u pil u m a b 3 0 0 m g S C q 2 w wit h a l ast 
i nj ecti o n at w e ek 2 2  
P ack a gi n g a n d l a b eli n g  
D u pil u m a b will b e s u p pli e d as 
1  gl ass pr e -fill e d syri n ge p ack e d i n a 
p ati e nt kit b ox. Bot h gl ass pr e -fill e d 
syri n ge a n d b ox will b e l a b el e d as 
r e q uir e d p er c o u ntry r e q uir e m e nt. 
Pl ac e b o will b e s u p pli e d as 1 gl ass 
pr e -fill e d syri n g e p ack e d i n a p ati e nt 
kit b ox. Bot h gl ass pr e -fill e d syri n g e 
a n d b ox will b e l a b el e d as r e q uir e d 
p er c o u ntry r e q uir e m e nt.  
A b br evi ati o ns:  S C =s u bc ut a n e o us; Q 2 W = ev ery 2 w e eks  
I N V E S TI G A TI O N A L M E DI CI N A L P R O D U C T( S) 
I n v esti gati o nal me dici nal pr o d uct (I M P) will be a d mi nistere d b y t he I n vesti gat or/ h ealt h care 
pr ofessi o nal or d esi g n ee f oll o wi n g cli nic pr o ce d ures a n d bl o o d c ollecti o n. Patie nts s h o ul d be 
m o n it ore d b y site pers o n nel or b y care gi ver[s] (if at h o me) f or at least 3 0 mi n utes after 
a d mi nistrati o n of all I M P i njecti o ns.  
S u bc uta ne o us i njecti o n sites s h o ul d alter n ate bet w ee n t he u p per t hi g hs, 4  q ua dra nts of t he 
a b d o me n or t he u p per ar ms, s o t hat t he sa me site is n ot i njecte d t wice d uri n g c o ns ec uti ve visits.  
At o n -site st u d y visit(s) d uri n g t he treat me nt peri o d , patie nts or t heir care gi vers will be  trai ne d b y 
t he i n vesti gat or or dele gate o n h o w t o pre pare a n d self-i nject/i nject t he I M P, u ntil t he y are 
pr oficie nt  a n d feel c o mf orta ble t o self-i nject/i nject t he I M P at h o me f or cert ai n i nter vals per 
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Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al  
P a g e 3 7  
Secti o n  1. 3 . T his trai ni n g m ust be d oc u me nte d i n t he patie nt’s st u d y file. At baseli ne visit, t he 
I n v esti gat or or del e gate will perf or m t he first of t he 2 i njecti o ns, a n d will pr o p ose t o t he patie nt or 
his/ her care gi ver t o perf or m t he sec o n d i njecti o n u n der t he s u per visi o n of t he i n vesti gat or or 
dele gate. If a p atie nt or care gi ver d oes n ot feel c o mf orta ble t o self -i nject/i nject t he I M P, all 
i njecti o ns ca n be d o ne o n-site or, as a n alter nati ve, t he y ca n be d o n e b y a h ealt hcare pr ofessi o nal 
( n urse) at patie nts’ h o me, after a n a p pr o priate a n d d oc u me nte d trai ni n g. 
Patie nt or care gi ver i njecti o n s h o ul d o nl y be p erf or me d i n t he a b d o m e n or u p per t hi g hs. Patie nt 
s h o ul d als o be i nstr ucte d t o m o nit or f or a n y reacti o n f or at least 3 0  mi n utes ( or l o n ger per  
c o u ntr y-s pecific or l ocal site-s pecific re q uire me nts) f oll o wi n g i njecti o n. 
F or d oses n ot gi ve n at t he st u d y site, diari es will be pr o vi de d t o rec or d i nf or mati o n relate d t o t he 
i njecti o ns. T he diar y will be ke pt as s o urce data i n t he patie nt’s st u d y file . 
Bet wee n t he pr ot o c ol -sc h e d ule d o n-site visits, i nteri m visits ma y b e re q uir e d f or I M P dis pe nsi n g. 
As a n alter nati ve t o t hese visits, I M P ma y b e s u p plie d fr o m t he site t o t he pa rtici pant via a 
S p o ns or -a p pr o ve d c o urier c o m pa n y w here all o we d b y l ocal re g ulati o ns a n d a p pr o ve d b y t he 
s u bject. 
N O NI N V E S TI G A TI O N A L M E DI CI N A L P R O D U C T( S)  
Patie nts will recei ve sta n dar dize d bac k gr o u n d tr eat me nt ( ie, n o n -i nvesti gati o nal me dical pr o d ucts 
[NI M P ]) c o nsisti n g of T C S as n ote d bel o w.  Bet w ee n t he pr ot oc ol -sc he d ul e d o n-site visits, i nteri m 
visits ma y b e re q uire d f or NI M P dis pe nsi n g. As a n alter nati ve t o t hese visits, T C S  ma y b e 
s u p plie d fr o m t he site t o t he partici pant via a S p o ns or -a p pr o ve d c o uri er c o m pa n y w here all o we d 
b y l oc al re g ulati o ns a n d a p pr o ve d b y t he s u bject.  
Starti n g o n D a y -7 , all patie nts are re q uire d t o u n d er g o treat me nt wit h me di u m -p ote nc y T C S 
usi n g a sta n d ar dize d re gi me n acc or di n g t o t he f oll o wi n g g ui deli nes:  
- 
A p pl y me di u m -p ote n c y T C S , 1 fi n gerti p u nit f or eac h 2 % B S A, o nce dail y t o areas 
wit h acti ve lesi o ns . L o w -p ote nc y T C S or T CI m a y  be use d o n areas t hat ca n n ot be 
treate d safel y wit h me di u m-p ote nc y T C S (e g, face, nec k, i ntertri gi n o us, a n d ge nital 
areas, areas of s ki n atr o p h y, et c.)  
- 
W he n lesi o ns are u n der c o ntr ol, a p pl y t o pical me dicati o n t wice wee kl y; res u me dail y 
a p plicati o ns w he n lesi o ns reacti vat e  
 
M o nit or t he patie nt f or si g ns of l ocal or s yste mic T C S t o xicit y a n d st o p /a dj ust treat me nt as 
nec essar y 
T y pic al T C S pr o d ucts t o be use d as sta n d ar dize d bac k gr o u n d tr eat me nt i ncl u de  tria mci n ol o ne 
acet o ni de 0. 1 % crea m or fl u oci n ol o ne acet o ni de 0. 0 2 5 % oi nt me nt f or me di u m -p ote nc y, a n d 
h y dr oc ortis o ne 1 % crea m f or l o w -p ote nc y. If patie nts ha ve t olera n ce iss ues wit h a n y of t h ese 
pr o d ucts  or if t he y are n ot c o m merciall y a vaila bl e i n s o me c o u ntries, t he y ma y s u bstit ute wit h 
pr o d ucts of t he sa me p ot e nc y fr o m t he list pr o vi d e d i n t he S t u d y R efere n ce M a n ual. O n areas 
treate d wit h T C S, m oist uriz ers s h o ul d be a p plie d o nce dail y o nl y at t he ti me w he n T C S is n ot 
a p plie d (ie, d o n ot use m oist urizers a n d T C S o n t he sa me areas at t he sa me ti me of t he da y). F or 
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Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al  
P a g e 3 8  
e x a m ple, if T C S are a p plie d i n t he e ve ni n g, m oist urizers will n ot be use d i n t he e ve ni n g o n areas 
treate d wit h T C S; h o we v er,  will be a p plie d t o t h os e areas i n t he m or ni n g. O n areas n ot tr eate d 
wit h T C S, m oist urizers will be a p plie d t wice dail y –  m or ni n g a n d e ve ni n g. T he t y p e, a m o u nt, a n d 
fre q ue n c y of t o pical pr o d ucts use d d uri n g t he st u d y will be rec or de d at h o me b y p atie nts i n a 
me dicati o n l o g if p ossi bl e, i ncl u di n g t he a m o u nt ( n u m ber of fi n gerti p u nits) use d . 
6. 2  
P R E P A R A TI O N/ H A N D LI N G / S T O R A G E/ A C C O U N T A BI LI T Y  
St or a ge a n d h a n dli n g  
1.  I n v esti gat ors or ot her a ut h orize d pers o ns (e g, p h ar macists) are res p o nsi ble f or st ori n g t he 
I M P i n a sec ure a n d safe place i n acc or da nce wit h l ocal re g ulati o ns, la beli n g 
s pecificati o ns, p olicies, a n d pr oce d ures. 
2.  C o ntr ol of I M P st ora ge c o n diti o ns, es peciall y c o ntr ol of te m perat ure ( e g, refri gerat e d 
st ora ge) a n d i nf or mati o n o n i n-use sta bilit y a n d i nstr ucti o ns f or ha n dli n g t h e Sa n ofi 
c o m p o u n d m ust be ma na ge d acc or di n g t o t he r ules pr o vi de d b y t h e S p o ns or i n t he 
P har mac y M a n u al.  
3.  T he e x pir y dat e is me nti o ne d o n t he I M P la bels ( w he n re q uir e d b y c o u ntr y re g ul ati o n), 
a n d st ora ge c o n diti o ns are writte n o n t he I M P la bels.  
4.  T he I n vesti gat or or desi g nee m ust c o nfir m a p pr o priate te m perat ure c o n diti o ns ha ve bee n 
mai ntai ne d d uri n g tra nsit f or all st u d y i nter ve nti o n recei v e d a n d a n y dis cre p a ncies are 
re p orte d a n d res ol ve d b ef ore use of t he st u d y i nter ve nti o n. 
5.  O nl y partici pa nts e nr olle d i n t he st u d y ma y recei v e st u d y i nter ve nti o n a n d o nl y a ut h orize d 
site staff ma y s u p pl y or a d mi nister st u d y i nter ve nti o n. All st u d y i nter ve nti o n m ust be 
st ore d i n a sec ure, e n vir o n me ntall y c o ntr olle d, a n d m o nit ore d ( ma n ual or a ut o mate d) area 
i n acc or da nce wit h t he la bele d st ora ge c o n diti o ns wit h access li mite d t o t he I n v esti gat or 
a n d a ut h orize d site staff.  
6.  T he I n vesti gat or, i nstit uti o n, or t he head of t he me dical i nstit uti o n ( w here a p plica ble) is 
res p o nsi ble f or st u d y i nter ve nti o n acc o u nt a bilit y, rec o nciliati o n, a n d rec or d mai nte na nce 
(ie, recei pt, rec o nciliati o n, a n d fi nal dis p ositi o n rec or ds). 
7.  F urt her g ui d a nce a n d i nf or mati o n f or t he fi nal dis p os iti o n of u n use d st u d y i nter ve nti o ns 
are pr o vi d e d i n t he St u d y Refere n ce M a n ual.  
Pre p ar ati o n of I M P  
D u pil u ma b or matc hi n g place b o i n glass pre -fille d s yri n ges will be dis pe nse d t o t he patie nts. 
Res p o nsi bilities  
T he I n vesti gat or, t he h os pital p har macist, or ot her pers o n nel all o we d t o st ore a n d dis pe nse t he 
I M P/ NI M P will be res p o nsi ble f or e ns uri n g t hat t he I M P use d i n t he cli nical trial is sec urel y 
mai ntai ne d as s pecifie d b y t he S p o ns or a n d i n acc or da nce wit h a p plica ble re g ulat or y re q uire me nts.  
All I M Ps will be dis pe ns e d i n acc or da nce wit h t he I n v esti gat or's pres cri pti o n a n d it is t he 
I n v esti gat or's res p o nsi bilit y t o e ns ure t h at a n acc urate rec or d of I M P iss ue d a n d ret ur n e d is 
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Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al  
P a g e 3 9  
mai ntai ne d. F or d os es n ot gi ve n at st u d y site, t he h o me d osi n g diar y will be use d t o  rec or d 
i njecti o ns. 
A n y q u alit y iss ue n otice d wit h t he recei pt or use of a n I M P/ NI M P/ de vice  ( deficie nc y i n c o n diti o n, 
a p peara nce, pert ai ni n g d oc u me ntati o n, la beli n g, e x pirati o n date, etc .) m ust be pr o m ptl y n otifie d t o 
t he S p o ns or . S o me deficie ncies ma y be rec or de d t hr o u g h a c o m plai nt pr oce d ure (see  
Secti o n  8. 3. 7 ). 
A p ote ntial defect i n t he q ualit y of I M P/ NI M P/ de vice ma y be s u bject t o i nitiati o n of a recall 
pr oce d ure b y t he S p o ns or . I n t his case, t he I n vesti gat or will be res p o nsi ble f or pr o m ptl y 
a d dressi n g a n y re q uest m a de b y t he S p o ns or , i n or der t o recall t he I M P/ NI M P/ de vice a n d 
eli mi nate p ote ntial hazar ds. 
U n der n o cir c u msta nces will t he I n vesti gat or s u p pl y I M P/ NI M P/ de vice t o a t hir d part y (e x ce pt f or 
Direct T o Patie nt  [D T P ] s hi p me nt, f or w hic h a c o urier c o m pa n y h as bee n a p pr o ve d b y t he 
S p o n s or), all o w t he I M P/ NI M P/ de vice t o be use d ot her t ha n as directe d b y t his cli nical trial 
pr ot oc ol, or dis p ose of I M P/ NI M P/ de vice i n a n y ot her ma n ner.  
6. 3  
M E A S U R E S T O MI NI M I Z E BI A S: R A N D O MI Z A TI O N A N D B LIN DI N G   
A ra n d o mize d treat me nt kit n u m ber list will be ge nerate d ce ntr all y b y Sa n ofi f or t he I M Ps. T he 
I M Ps ( d u pil u ma b or mat c hi n g pla ce b o) will be pac ka ge d i n acc or da nce wit h t he list. T he Sa n ofi 
Cli nical S u p pl y C hai n tea m will pr o vi de t he ra n d o mize d treat me nt kit n u m ber list a n d t he St u d y 
Bi ostatisticia n will pr o vi de t he ra n d o mizati o n sc h e me t o t he ce ntr alize d treat me nt all ocati o n 
s yste m (I nt eracti ve V oice Res p o nse S yste m/I nteracti ve We b Res p o nse S yste m [ I V R S/I W R S]). 
T his ce ntralize d treat me nt all ocati o n s yste m will ge nerat e t he patie nt r a n d o mizati o n list acc or di n g 
t o w hic h it will all ocate t he I M P t o t he patie nts. T he I n vesti gat or o btai ns tr eat me nt kit n u m ber at 
ra n d o mizati o n a n d s u bse q ue nt sc he d ule d visits via a n I V R S/I W R S t hat will be a vaila ble 2 4 h o urs 
a da y.  
At s o me site visits, t he i nteracti ve res p o nse tec h n ol o g y (I R T) will all ocate e n o u g h kits f or site 
a d mi nistrati o n o n sa me da y a n d h o me a d mi nistrati o n t hat w ill be perf or me d 2 wee ks later. 
Ra n d o mizati o n will be stratifie d: P S G (re gar dless of ge o gra p hi c l ocati o n ), U S ( n o n-P S G), E ur o pe  
( n o n-P S G) a n d R O W ( n o n -P S G) . 
A partici pa nt w h o has b ee n all ocate d t o a ra n d o mi ze d i nter ve nti o n re gar dl ess w het her t he 
i nter ve nti o n kit was use d or n ot (ie, partici pa nt re gistere d b y t he I R T) will b e c o nsi dere d a 
ra n d o mize d s u bject. A partici pa nt ca n n ot be ra n d o mize d m ore t ha n o nce i n t he st u d y.  
D u pil u ma b a n d place b o will be pr o vi de d i n i de nticall y m atc he d 2  m L pre -fille d s yri n ges. T o 
pr otect t he  bli n d, eac h treat me nt kit of 2  m L ( d u pil u ma b / place b o) glass pre -fille d s yri n ges will 
be  pre pare d s uc h t h at t he treat me nts ( d u pil u ma b a n d its matc hi n g place b o) are i de ntical a n d 
i n disti n g uis ha ble a n d will be la bele d wit h a tr eat m e nt kit n u m ber 
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Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al  
P a g e 4 0  
Patie nts will recei ve eit h er;  
 D u pil u ma b 6 0 0  m g ( 2 x 3 0 0  m g d u pil u ma b i njecti o ns) o n Da y 1 (ie, t he l o a di n g d os e), 
f oll o we d b y 1 d u pil u ma b i njecti o n of 3 0 0  m g Q 2 W  u ntil w ee k 1 0, t he n 1 d u p il u ma b + 1 
place b o i njecti o n at w ee k  1 2 (t o pr otect t he bli n d w hile place b o p atie nts recei ve t heir 
l oa di n g d ose), f oll o we d b y 1 du pil u ma b i njecti o n Q 2 W  wit h last i njecti o n at wee k 2 2  or,  
 Matc hi n g pla ce b o f or d u pil u ma b ( 2  x 2 m L place b o i njecti o ns) o n D a y 1 (ie, t he l oa di n g 
d ose), t he n 1 p lace b o i njecti o n Q 2 W  u ntil wee k  1 0, a n d t he n 2 x 3 0 0  m g d u pil u ma b 
i njecti o ns at wee k 1 2 (i e, t he l oa di n g d ose), f oll o we d b y d upil u ma b i njecti o ns Q 2 W  wit h 
last i njecti o n at wee k 2 2.  
I n case of a n A E, t h e c o d e m ust o nl y be br o ke n i n circ u msta nces w he n k n o wle d ge of t he I M P is 
re q uire d f or treati n g t he patie nt. 
C o de brea ki n g ca n be p erf or me d at a n y ti me b y usi n g t he pr o p er m o d ule of t he I V R S/I W R S 
a n d/ or b y calli n g a n y ot h er p h o ne n u m ber pr o vi de d b y t he S p o ns or f or t hat p ur p ose. If t he bli n d is 
br o ke n, t he I n v esti gat or m ust d oc u me nt t he date, ti me of da y a n d reas o n f or c o de brea ki n g.  
Patie nt wit h dra wal will o nl y occ ur w he n t he c o de brea k call is ma de at t he site le vel, n ot t he st u d y 
le vel. T his mea ns t hat if t he E mer ge n c y U n bli n di n g tra ns acti o n is perf or me d b y t he I n vesti gat or 
(ie, at t he site le vel), t h e n t he patie nt will be wit h dra w n fr o m treat me nt. H o we ver, if t h e 
E mer g e nc y U n bli n di n g tr a nsacti o n is perf or me d b y t he Gl o b al Safet y Officer ( G S O ) (ie, at t he 
st u d y le vel, as t h e G S O is n ot site base d), t he n t he patie nt will n ot be wit h dra w n fr o m treat me nt.  
6. 4  
S T U D Y I N T E R V E N TI O N C O M P LI A N C E   
 Met h o ds use d b y t h e I n v esti gat or or his/ her dele gate t o e ns ure t h at t he I M P was 
a d mi nistere d  
 I M P acc o u nta bilit y: 
- 
T he I n vesti gat or or p h ar macist will kee p acc urate rec or ds of t he q ua ntities of t he I M P 
recei v e d, dis pe nse d, use d, u n use d, a n d ret ur ne d/ destr o ye d. T he pr o d u ct acc o u nta bilit y 
a n d i n ve nt or y f or m/s yste m is t o be u p date d eac h ti me I M P is dis pe nse d. It m ust be 
esta blis he d wit h t he I n vesti gat or or ot her  pers o n nel desi g n ate d b y t he I n v esti gat or, a n d 
c o u ntersi g ne d b y t he I n v esti gat or a n d t he m o nit ori n g tea m. T h e st u d y m o nit or will 
peri o dicall y c hec k t he s u p plies of t he I M P hel d b y t he I n v esti gat or or p h ar macist t o 
verif y acc o u nta bilit y a n d i n ve nt or y.  
- 
Treat me nt kit n u m ber has t o be rec or de d o n t he a p pr o priate pa ge of t he electr o nic cas e 
re p ort f or m (e C R F) a n d als o o n t he pr o d uct acc o u nta bilit y a n d i n ve nt or y f or m/s yste m.  
- 
T he m o nit or i n c har ge of t h e st u d y t he n c h ec ks t h e C R F data b y c o m p ari n g t he m wit h 
t he I M P w hic h h e/s he has retrie ve d a n d i nter ve nti o n l o g f or ms 
- 
All use d, partiall y us e d, or u n use d treat me nts will be destr o ye d at eac h res pecti ve site, 
after acc o u nt a bilit y a n d rec o nciliati o n ha ve b ee n p erf or me d. T he site m ust n ot destr o y 
t he u n use d I M P u nless t he S p o ns or pr o vi des writt e n a ut h orizati o n. C o nfir mati o n of 
destr ucti o n will be pr o vi de d t o t he S p o ns or.  
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Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al  
P a g e 4 1  
- 
F or m ore d etails re gar di n g acc o u nta bilit y, please refer t o P har m ac y Ma n u al.  
- 
I nter ve nti o n units ret ur ne d b y t he partici pa nt at eac h visit. I n case of D T P pr ocess, t he 
i nter ve nti o n u nits ca n be ret ur ne d b y t he carrier (if defi ne d i n t he c o ntr act). 
6. 5  
C O N C O MI T A N T T H E R A P Y   
A n y me di cati o n or vacci ne (i ncl u di n g o v er -t h e-c o u nter or pres cri pti o n me dici nes, vita mi ns, 
a n d/ or her bal s u p ple me nts) t hat t he partici pa nt is recei vi n g at t he ti me of e nr oll me nt or recei ves 
d uri n g t he st u d y m ust be rec or de d al o n g wit h:  
 Reas o n f or use  
 Dat es of a d mi nistrati o n i ncl u di n g start a n d e n d dates  
 D osa ge i nf or m ati o n i ncl u di n g d ose a n d fre q ue nc y  
6. 5. 1  Pr o hi bit e d M e di c ati o n s a n d pr o c e d ur e s   
Treat me nt wit h f oll o wi n g c o n c o mita nt me dicati o ns is pr o hi bite d  u ntil t he e n d of t he st u d y: 
 
Se dati ve a n xi ol ytic or h y p n otic treat me nts ot her t ha n melat o ni n 
 
Patie nts ta ki n g s yst e mic se dati ve a nti hista mi nes m ore t ha n 5 da ys per wee k  
 
Li p o p hilic beta bl oc k ers, o pi oi ds, t he o p h ylli ne, cl o ni di ne, a n ti de pressa nts or ot her 
me dicati o ns k n o w n t o i nterfere wit h sle e p a n d A D as deter mi ne d b y t he I n v esti gat ors  
 
Li ve (atte n uate d) vacci ne  
 
I m m u n o m o d ulati n g bi ol o gics 
 
In v esti gati o nal dr u g s 
 
H i g h-p ot e nc y a n d s u p er-p ote nt T C S, e x ce pt w he n use d f or resc ue  
 
S yste mic c o rtic oster oi ds or n o n-ster oi dal s yste mic i m m u n os u p pressi ve dr u gs (e g, CsA, 
A Z A, M T X, M M F, J A K i n hi bit ors, etc.) , e x ce pt w he n use d f or resc u e 
St u d y dr u g will be i m me diatel y disc o nti n ue d if a n y of t he f oll o wi n g are us e d t hr o u g h wee k  2 4 : 
 
Treat me nt wit h a li ve (atte n uate d) v acci n e 
 
Treat me nt wit h i m m u n o m o d ulati n g bi ol o gics  
 
Treat me nt wit h a n i n vesti gati o nal dr u g  
 
Treat me nt wit h s yste mic c ortic oster oi ds or n o n -ster oi dal s yste mic i m m u n os u p pressi ve 
dr u gs (e g, C sA, A Z A , M T X, M M F, J A K i n hi bit ors, etc.)  
N ote : If a p atie nt recei ves resc ue tr eat me nt wit h s yste mic c ortic oster oi ds or ot her s yste mic 
i m m u n os u p pressi ve dr u gs ( CsA, A Z A, M T X, M M F, J A K i n hi bit ors, etc .), st u d y treat me nt ma y 
be res u me d if d ee me d a p pr o priate b y t he In v esti gat or a n d t he m e dical m o nit or, b ut n ot s o o ner 
t ha n 5 half-li ves after t he last d ose of s yst e mic res c ue me dicati o n.  
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P a g e 4 2  
 
T he f oll o wi n g pr oce d ures are pr o hi bite d d uri n g st u d y partici pati o n:  
 
P h ot ot hera p y  
 
Ta n ni n g i n a b e d/ b o ot h  
6. 5. 2  P er mitt e d m e di c ati o n s   
T he treat me nt wit h certai n c o nc o mita nt me dicati o ns is per mitte d d uri n g t he st u d y. T his i ncl u de s: 
- basic s ki n ca re (clea nsi n g a n d b at hi n g, i n cl u di n g bleac h bat hs),  
- e m ollie nts (re q uire d as bac k gr o u n d tr eat me nt),  
- t o pical a nest hetics,  
- t o pical a nti hista mi nes,  
- s yste mic n o n -se dati ve a nti hista mi nes ,  
- s yste mic s e dati ve a nti hista mi nes if ta ke n ≤5 da ys per wee k o n sta ble re gi me n f or at least 
1  m o nt h bef ore ra n d o mizati o n a n d sta ble re gi me ns mai ntai ne d t hr o u g h o ut t he st u d y,  
- a n d t o pical a n d s yste mi c a nti -i nfecti ve me dicati o ns f or a n y d urati o n. 
If n ot s pecificall y pr o hi bite d i n Secti o n  6. 5. 1  a b o ve, me dicati o ns use d t o treat c hr o nic disease s 
s uc h as dia betes, h y p erte nsi o n, a n d ast h ma are als o per mitte d; if t here is a n y q uesti o n re gar di n g 
w het her a c o nc o mita nt m e dicati o n ma y be use d d uri n g t he st u d y, t he st u d y site s h o ul d c o ntact t he 
m e dical m o nit or. T he t y p e, (acti ve i n gre die nt, f or m ulati o n, stre n gt h, a m o u nt, fre q ue n c y)  of 
t o pical pr o d ucts use d d uri n g t he st u d y will be rec or de d (e g, C R F, t h e s o urce d oc u me nt). T h e 
a m o u nt of T C S use d  will be deter mi ne d b y e val uati n g t he t u be at eac h visit (see S t u d y R efere nce 
M a n ual f or det ails).  
6. 5. 3  R e s c u e m e di ci n e   
If me dicall y necessar y (i e, t o c o ntr ol i nt olera ble A D s y m pt o ms), resc ue tr eat me nt f or A D ma y be 
pr o vi de d t o st u d y patie nts at t he discreti o n of t he i n vesti gat or. If p ossi ble, In vesti gat ors s h o ul d 
atte m pt t o li mit t he first ste p of resc u e t hera p y t o hi g h -p ote nc y T C S a n d/ or T CIs, a n d escalate t o 
s yste mic me dic ati o ns o nly f or patie nts w h o d o n ot res p o n d a de q u atel y aft er at least 7  da ys of 
t o pical treat me nt. 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 cac y a n d safet y 
assess me nts (e g, dise ase se verit y sc ores, safet y la bs) i m me diatel y b ef ore a d mi nisteri n g a n y resc ue 
treat me nt. A n u nsc h e d ule d visit ma y be us e d f or t his, if necessar y. 
N ote t hat : 
1.  T h ose w h o recei ve hi g h -p ote nc y  or s u per p ote nt  T C S will be all o we d t o c o nti n ue st u d y 
treat me nt. 
2.  T h ose w h o recei ve s yste mic c ortic oster oi ds or n o n -ster oi dal s yste mic i m m u n os u p pressi ve 
dr u gs (e g, C S A, A Z A, M T X, M M F, or J A K i n hi bit ors) will disc o nti n ue st u d y treat me nt 
f or t he d urati o n of resc u e + 5 half -li ves of t h e res c ue a ge nt. 
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Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al  
P a g e 4 3  
3.  All patie nts will  be e nc o ura ge d t o  c o m plete t h e e ntire sc he d ule of st u d y visits a n d 
assess me nts w het her or n ot t he y c o m plet e st u d y tr eat me nt a n d w het her or n ot t he y recei v e 
resc ue tr eat me nt f or A D. 
6. 6  
D O S E M O DI FI C A TI O N   
D ose m o difica ti o n of I M P  f or a n i n di vi d ual patie nt is n ot all o we d. 
6. 7  
I N T E R V E N TI O N A F T E R T H E E N D O F T H E S T U D Y   
I nter ve nti o n aft er t he e n d of t he st u d y tr eat me nt is at t he discreti o n of t he I n vesti gat or or ot her 
treati n g p h ysi cia n. 
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L P S 1 5 4 9 7  
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V er si o n n u m b er: 1  
 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al  
P a g e 4 4  
7  
DI S C O N TI N U A TI O N  O F S T U D Y I N T E R V E N TI O N A N D 
P A R TI CI P A N T DI S C O N TI N U A TI O N / WI T H D R A W A L  
7. 1  
DI S C O N TI N U A TI O N O F S T U D Y I N T E R V E N TI O N   
7. 1. 1  D efi niti v e di s c o nti n u ati o n   
T he I M P s h o ul d be c o nti n ue d w he ne v er p ossi ble.  
I n case t h e I M P is st o p pe d, it s h o ul d be deter mi ne d w het her t he st o p ca n be ma de te m p oraril y; 
defi niti ve  I M P disc o nti n uati o n s h o ul d be a last res ort. A n y I M P disc o nti n u ati o n m ust be f ull y 
d oc u me nte d i n t he C R F/ e C R F. I n a n y case, t he p artici pa nt  s h o ul d re mai n i n t he st u d y f or as l o n g 
as p ossi ble t hr o u g h w ee k 2 4. 
Defi niti ve  i nter ve nti o n disc o nti n uati o n is a n y i nter ve nti o n disc o nti n uati o n ass ociate d wit h t he 
defi niti ve ( per ma n e nt) decisi o n fr o m t he I n vesti gat or n ot t o re -e x p ose t he pa rtici pant t o t he I M P at 
a n y ti me d uri n g t he st u d y, or fr o m t he partici pa nt  n ot t o be re -e x p ose d t o t he I M P w hate ver t he 
reas o n. 
Se e t he S o A (Secti o n  1. 3 ) f or data t o b e c ollect e d at t he ti me of i nter ve nti o n disc o nti n uati o n a n d 
f oll o w-u p a n d f or a n y f urt her e val uati o ns t hat nee d t o be c o m plete d.  
H a n dli n g of p artici p a nts after  defi niti ve  i nter ve nti o n disc o nti n u ati o n  
Partici pa nts will be f oll o we d -u p acc or di n g t o t he st u d y pr oce d ures s pecifie d i n t his pr ot oc ol u p t o 
t he sc he d ule d dat e of st u d y c o m pleti o n, or u p t o r ec o ver y or sta bilizati o n of a n y A E t o be 
f oll o we d-u p as s pe cifie d i n t his pr ot oc ol, w hic he ver c o mes last.  
If p ossi ble, a n d after t he defi niti ve  disc o nti n uati o n of i nter ve nti o n, t he partici pa nts will be 
assesse d usi n g t he pr oce d ure n or mall y pla n ne d f or t he last d osi n g da y wit h t he I M P .  
All cases of d efi niti ve  i nter ve nti o n disc o nti n uati o n m ust be rec or de d b y t he I n v esti gat or i n t he 
a p pr o priate p a ges of t h e C R F or e C R F w he n c o nsi dere d as c o nfir me d.  
7. 1. 2  T e m p or ar y di s c o nti n u ati o n   
St u d y dr u g d osi n g m a y b e te m p oraril y s us pe n de d i n t he e ve nt of:  
 
Interc urre nt ill nesses or maj or s ur ger y  
 
Treat me nt wit h a n y pr o hi bite d c o nc o mita nt me dicati o n or pr oce d ure ( Secti o n  6. 5 ) 
T he In vesti gat or ma y s us pe n d  st u d y tr eat me nt at a n y ti me, e v e n wit h o ut c o ns ultati o n wit h  t he 
m e dical m o nit or if t he ur ge n c y of  t he sit uati o n re q uires i m me diate acti o n a n d if t his is deter mi ne d 
t o be i n t he patie nt’s best i nterest. H o we v er, t he m e dical m o nit or s h o ul d be c o ntacte d as s o o n as 
p ossi ble i n a n y case of st u d y dr u g disc o nti n uati o n. Res u m pti o n of st u d y i nt er ve nti o n aft er 
te m p orar y disc o nti n uati o n s h o ul d al wa ys b e disc usse d wit h t he me dical m o nit or. 
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Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al  
P a g e 4 5  
7. 2  
P A R TI CI P A N T DI S C O N TI N U A TI O N/ WI T H D R A W A L F R O M T H E S T U D Y   
 A partici pa nt ma y wit h dr a w fr o m t he st u d y at a n y ti me at his/ her o w n re q uest, or ma y b e 
wit h dra w n at a n y ti me at t he discreti o n of t he In v esti gat or  f or safet y, b e ha vi oral, 
c o m plia nce, or a d mi nistrati ve reas o ns . 
 If t he partici p a nt wit h dra ws c o nse nt f or discl os ur e of f ut ure i nf or mati o n, t he S p o ns or  ma y 
retai n a n d c o nti n ue t o us e a n y data c ollecte d bef ore s uc h a wit h dra wal of c o nse nt. 
 If a partici pa nt wit h dra ws fr o m t he st u d y, h e/s he ma y re q uest destr u cti 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 v esti gat or m ust d oc u me nt t his i n t he site st u d y rec or ds . 
 See S o A (Secti o n  1. 3 ) f or data t o be c ollecte d at t he ti me of st u d y disc o nti n uati o n a n d 
f oll o w-u p a n d f or a n y f urt her e val uati o ns t hat nee d t o be c o m plete d.  
If partici pa nts n o l o n ger wis h t o ta ke t he I M P, t he y will be e n c o ura ge d t o r e mai n i n t he st u d y. 
T he I n vesti gat ors s h o ul d disc uss wit h t he m ke y visits t o atte n d. T he val ue of all t heir st u d y d ata 
c ollecte d d uri n g t heir c o nti n ue d i n v ol ve me nt will be e m p hasize d as i m p orta nt t o t he p u blic healt h 
val ue of t he st u d y.  
Partici pa nts w h o wit h dra w fr o m t he st u d y i nter ve nti o n s h o ul d be e x plicitl y as ke d a b o ut t he 
c o ntri b uti o n of p ossi ble A Es t o t heir decisi o n, a n d a n y A E i nf or mati o n eli cite d m ust be 
d oc u me nte d.  
All st u d y wit h dra w als s h o ul d be rec or de d b y t he I n vesti gat or i n t he a p pr o priate scree ns of t he 
C R F or e C R F a n d i n t he partici pa nt ’s me dical rec or ds. I n t he me dical rec or d, at least t he dat e of 
t he wit h dra wal a n d t h e reas o n s h o ul d be d oc u me nt e d. 
I n a d diti o n, a partici pa nt  ma y wit h dr a w his/ her c o nse nt t o st o p partici pati n g i n t he st u d y. 
Wit h dra wal of c o nse nt f or i nter ve nti o n s h o ul d be disti n g uis he d fr o m wit h dra wal of c o nse nt f or 
f oll o w-u p visits a n d fr o m wit h dra wal of c o nse nt f or n o n -partici pa nt  c o ntact f oll o w -u p, e g, 
me dic al rec or d c h ec ks. T he site s h o ul d d oc u me nt a n y case of wit h dra wal of c o nse nt.  
Partici pa nts w h o ha ve wit h dra w n fr o m t he st u d y ca n n ot be re -ra n d o mize d/r eall ocate d (treat e d) i n 
t he st u d y. T heir i n cl usi o n a n d i nter ve nti o n n u m bers m ust n ot be re use d . 
7. 3  
L O S T T O F O L L O W U P   
A partici pa nt will be c o nsi dere d l ost t o f oll o w -u p if he or s he re peate dl y fails t o ret ur n f or 
sc he d ule d visits a n d is u na ble t o be c o ntacte d b y t he st u d y site.  
T he f oll o wi n g acti o ns m ust be ta ke n if a p artici pa nt fails t o ret ur n t o t he cli nic f or a re q uire d st u d y 
visit:  
 T he site m ust atte m pt t o c o ntact t he partici pa nt a n d resc he d ul e t he misse d visit as s o o n as 
p ossi ble a n d c o u nsel t he partici pa nt o n t he i m p orta nce of  m ai ntai ni n g t he assi g ne d visit 
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sc he d ule a n d ascertai n w het her or n ot t he p artici p a nt wis hes t o a n d/ or s h o ul d c o nti n ue i n 
t he st u d y. 
 Bef ore a p arti ci pa nt is dee me d l ost t o f oll o w -u p, t he I n vesti gat or or desi g n ee m ust ma ke 
e ver y eff ort t o r e gai n c o ntact wit h t he partici pa nt ( w here p ossi ble, 3 tele p h o ne calls a n d, if 
necessar y, a certifie d lett er t o t he partici pa nt’s last k n o w n maili n g a d dress or l ocal 
e q ui vale nt met h o ds). T hese c o ntact atte m pts s h o ul d be d oc u me nte d i n t he p artici pa nt’s 
me dical rec or d . 
 S h o ul d  t he partici pa nt c o nti n ue t o be u nreac ha ble, he/s he will be c o nsi dere d t o ha ve 
wit h dra w n fr o m t he st u d y . 
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L P S 1 5 4 9 7  
7 -A pr -2 0 2 0  
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P a g e 4 7  
8  
S T U D Y A S S E S S M E N T S A N D P R O C E D U R E S   
 St u d y pr oce d ures a n d t heir ti mi n g are s u m marize d i n t he S o A  (Secti o n  1. 3 ). Pr ot oc ol 
wai vers or e x e m pti o ns are n ot all o we d.  
 I m me diat e safet y c o ncer ns s h o ul d be disc usse d wit h t he S p o ns or  i m me diatel y u p o n 
occ urre nce or a w are ness t o deter mi ne if t he partici pa nt s h o ul d c o nti n ue or disc o nti n ue 
st u d y i nter ve nti o n. 
 A d here n ce t o t he st u d y d esi g n re q uire me nts, i ncl u di n g t h ose s pecifie d i n t he S o A  
(Secti o n  1. 3 ), is esse ntial a n d re q uir e d f or st u d y c o n d uct. 
 All scree ni n g e v al uati o ns m ust be c o m plete d a n d re vie we d t o c o nfir m t hat p ote ntial 
partici pa nts meet all eli gi bilit y criteria. T h e I n vesti gat or will mai ntai n a scree ni n g l o g t o 
rec or d details of all parti ci pa nts scree ne d a n d t o c o nfir m eli gi bilit y or rec or d reas o ns f or 
scree ni n g fail ure, as a p plica ble. 
 Patie nt -Re p orte d O utc o me ( P R O) q uesti o n naires a n d N R S s h o ul d be c o m plete d b y t h e 
patie nts bef ore  t h e c o ns ultati o n a n d/ or cli nical tests, i n a q uiet place. T h e q uesti o n naires 
s h o ul d be c o m plete d b y t he patie nts t he msel ves, i n de pe n de ntl y fr o m t heir p h ysicia n, t he 
st u d y n urse or a n y ot her me dical pers o n n el a n d wit h o ut a n y hel p fr o m frie n ds or relati ves.  
8. 1  
E F FI C A C Y A S S E S S M E N T S    
8. 1. 1  P h y si ci a n a n d C e nt er A s s e s s e d S c al e s   
8. 1. 1. 1  I n v e sti g at or’ s Gl o b al A s s e s s m e nt (I G A) (f or eli gi bilit y d uri n g s cr e e ni n g a n d 
b a s eli n e vi sit s o nl y)   
Base d o n a 5 -p oi nt scal e ra n gi n g fr o m 0 ( clear) t o 4 (se vere ), the I G A sc ore is assesse d at 
scree ni n g a n d baseli ne visits o nl y, us e d as o ne of t he i ncl usi o n criteria f or d eter mi ni n g p atie nt’s 
eli gi bilit y. T he assess me nt t o ol is pr o vi de d i n Secti o n  1 0. 9  ( A p pe n di x 9). 
8. 1. 1. 2  B o d y S urf a c e Ar e a ( B S A) I n v ol v e m e nt of At o pi c D er m atiti s (f or eli gi bilit y d uri n g 
s cr e e ni n g a n d b a s eli n e vi s it s o nl y )  
T he B S A  affecte d b y A D will be assesse d f or eac h secti o n of t he b o d y (t he p ossi ble hi g hest sc ore 
f or eac h re gi o n is: he a d a n d nec k ( 9 %), a nteri or tr u n k ( 1 8 %), bac k ( 1 8 %), u p per li m bs ( 1 8 %), 
l o wer li m bs ( 3 6 %) a n d ge nitals ( 1 %) a n d will be re p orte d as p erce nta ge of all maj or b o d y s ecti o ns 
c o m bi ne d. B S A is assess e d at scree ni n g a n d b aseli ne visits o nl y, use d as 1  of t he i ncl usi o n criteria 
f or deter mi ni n g patie nt’s eli gi bilit y. T he assess me nt t o ol is pr o vi de d i n  Secti o n  1 0. 9  
( A p pe n di x 9 ). 
8. 1. 1. 3  E c z e m a Ar e a S e v erit y I n d e x ( E A SI )  
T he E A SI is a vali date d meas ure use d i n cli nical practice a n d cli nical trials t o assess t he se verit y 
a n d e xte nt of A D ( 1 8). T he E A SI is a c o m p osite i n de x wit h sc ores ra n gi n g fr o m 0 t o 7 2. F o ur A D 
V V- C LI N- 0 5 5 0 3 9 6 4. 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol 0 2  
L P S 1 5 4 9 7  
7 -A pr -2 0 2 0  
V er si o n n u m b er: 1  
 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al  
P a g e 4 8  
disease c h aracteristics (er yt he ma, t hic k ness [i n d urati o n, pa p ula ti o n, a n d e d e ma], scratc hi n g 
[e x c oriati o n], a n d lic he nificati o n) will eac h be ass esse d f or se verit y b y t he i n vesti gat or or 
desi g nee o n a s cale of “ 0 ” (a bse nt) t hr o u g h “ 3” (se vere). I n a d diti o n, t he area of A D i n v ol ve me nt 
will be assesse d as a perce nta ge b y  b o d y area of hea d, tr u n k, u p per li m bs, a n d l o wer li m bs, a n d 
c o n verte d t o a s c ore of 0 t o 6. I n eac h b o d y re gi o n, t he area is e x presse d as 0, 1 ( 1 % t o 9 %), 
2  ( 1 0 % t o 2 9 %), 3 ( 3 0 % t o 4 9 %), 4 ( 5 0 % t o 6 9 %), 5 ( 7 0 % t o 8 9 %), or 6 ( 9 0 % t o 1 0 0 %). T he 
E A SI will be  c ollecte d at ti me p oi nts acc or di n g t o Secti o n  1. 3 . T he assess m e nt t o ol is pr o vi de d i n 
Secti o n  1 0. 9  ( A p pe n di x 9). 
8. 1. 1. 4  S C O Ri n g of At o pi c D er m atiti s ( S C O R A D )  
T he S C O R A D is a vali date d t o ol use d i n cli nical researc h a n d cli nical practice t hat was de v el o pe d 
t o sta n dar dize t he e val uati o n of t he e xte nt a n d se verit y of A D ( E ur o pea n T as k F orce o n At o pic 
Der matitis 1 9 9 3). T here are 3 c o m p o n e nts t o t he assess me nt: A = e xte nt or affecte d B S A , 
B  =  se v erit y, a n d C = s u bjecti ve s y m pt o ms. T he e xte nt of A D is assesse d as a perce nta ge of eac h 
defi ne d b o d y area a n d re p orte d as t he s u m of all areas, wit h a ma xi m u m sc ore of 1 0 0 % (assi g ne d 
as “ A” i n t he o v erall S C O R A D calc ul ati o n) . T he se verit y of 6 s pecific s y m pt o ms of A D (re d ness, 
s welli n g, o ozi n g/cr usti n g, e x c oriati o n, s ki n t hic ke ni n g/lic he nificati o n, dr y n ess) is assesse d usi n g 
t he f oll o wi n g scale: n o ne ( 0), mil d ( 1), m o derat e ( 2), or se vere ( 3) (f or a m a xi m u m of 1 8 t otal 
p oi nts , assi g ne d as “ B” i n t he o verall S C O R A D calc ulati o n). S u bjecti ve assess me nt of itc h a n d 
slee pless ness is rec or de d f or eac h s y m pt o m b y t he patie nt or relati ve o n a  vis ual a nal o g scal e 
( V A S, w here 0 is n o itc h ( or slee pless n ess) a n d 1 0 is t he w orst i ma gi na ble it c h ( or slee pl ess ness), 
wit h a ma xi m u m p ossi ble sc ore of 2 0. T his para meter is assi g ne d as “ C” i n t he o verall S C O R A D 
calc ulati o n. T he S C O R A D is calc ulate d as: A/ 5 + 7 B/ 2 + C w here t he ma xi m u m is 1 0 3. P atie nts 
will u n der g o t his assess me nt at ti me p oi nts acc or di n g t o Secti o n 1. 3. T he assess me nt t o ol is 
pr o vi de d i n  Secti o n  1 0. 9  ( A p pe n di x 9 ). 
8. 1. 1. 5  P ol y s o m n o gr a p h y ( P S G) ( s u b-st u d y; c o n d u ct e d b y t h e tr ai n e d pr of e s si o n al)   
P ol ys o m n o g ra p h y is a m ulti-para metric test use d i n t he st u d y of slee p (e g, bi o p h ysi o l o gical 
c ha n ges t hat occ ur d uri n g slee p) a n d as a dia g n ostic t o ol i n slee p me dici ne. P ol ys o m n o gra p h y is 
t y picall y perf or me d at ni g ht a n d m o nit ors ma n y b o d y f u ncti o ns. I n t his st u d y, P S G is use d t o 
rec or d slee p o nset late n c y (S O L ), wa k e after slee p o nset (W A S O ), t otal slee p ti me (T S T ), l o n gest 
slee p e pis o de, sta ges of slee p, slee p efficie n c y a n d ar o usal i n de x.  
F or t his P S G s u b -st u d y: 3 0 patie nts t otal (a p pr o xi matel y 2 0 d u pil u ma b a n d 1 0 place b o patie nts) 
will partici pate i n t he P S G s u b -st u d y. E ac h patie nt w h o partici pates i n t his s u b -st u d y will ha ve a 
t otal of 3 o ver ni g ht P S Gs: at baseli ne ti me p oi nt, 2 ( prefera bl y) c o nsec uti ve o ver ni g ht P S Gs t o 
c o ntr ol f or “first ni g ht effect” a n d c ollect bas eli ne data; t he n 1 o ver ni g ht P S G at wee k 1 2.  T he 
pr oce d ure  is detaile d  i n Secti o n  1 0. 1 0  ( A p pe n di x 1 0). 
V V- C LI N- 0 5 5 0 3 9 6 4. 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol 0 2  
L P S 1 5 4 9 7  
7 -A pr -2 0 2 0  
V er si o n n u m b er: 1  
 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al  
P a g e 4 9  
8. 1. 1. 6  P h ot o gr a p h y of S ki n  ( n ot m a n d at or y, sit e pr of e s si o n al will b e t a ki n g t h e 
p h ot o gr a p h s wit h p ati e nt’ s c o n s e nt)   
P h ot o gra p hs will be ta k e n of re prese ntati ve areas of A D i n v ol ve me nt usi n g sta n dar d p h ot o gra p h y 
met h o d ol o g y at bas eli ne. P h ot o gra p hs of t h e sa me area will be ta ke n at s u bse q ue nt cli nic visits. 
Partici pati n g patie nts will be as ke d t o si g n a se parate p h ot o gra p h y i nf or m e d c o nse nt at 
D a y 1/ baseli ne.  
I nstr u cti o ns f or ta ki n g t h e p h ot o gra p hs are pr o vi d e d i n t he p h ot o gra p h y ma n ual. 
8. 1. 2  P ati e nt -R e p ort e d O ut c o m e S c al e s ( c o m pl et e d b y p ati e nt s)   
Patie nts will be i nstr ucte d o n h o w t o use t he diar y t o rec or d t he re q uir e d assess me nts at t he 
scree ni n g visit. Cli nical sites will recei ve al erts w he n patie nts d o n ot c o m plete dia r y ite ms. Sites 
will be e x pecte d t o c o nta ct patie nts w h o ha ve misse d 2 c o nsec uti ve di ar y e ntries t o e nc o ura ge 
patie nt c o m plia nce.  
8. 1. 2. 1  Sl e e p Q u alit y N u m eri c al R ati n g S c al e ( N R S )  
 
Slee p  Q ualit y N R S ( 0 -1 0), c ollecte d dail y i ncl u di n g 7 da ys i m me diatel y prece di n g t he 
baseli ne visit  ( or dail y f or 5 da ys (fr o m Da y -7 t o Da y -3 pri or t o b aseli ne) f or patie nts 
partici pati n g i n t he P S G s u b-st u d y), a n d dail y f or 4 wee ks (t hr o u g h v isit 4), t he n dail y 
d uri n g t he wee k b ef ore eac h pla n ne d visit . 
 
Slee p Q ualit y N R S t o  c ollect i nf or mati o n o n patie nt -re p orte d q u alit y of slee p. N u merical 
rati n g s cale ra n ge is fr o m 0 (“ w orst p ossi ble slee p ”) t o 1 0 (“ b est p ossi ble slee p”). T he 
assess me nt t o ol is pr o vi de d i n Secti o n  1 0. 9  ( A p pe n di x 9 ). 
N ote: T he a nal ytic pla n t o defi ne a cli nicall y rele va nt, wit hi n -pers o n res p o nse t hres h ol d o n 
t he slee p N R S will be descri be d i n a se p arat e vali dati o n pla n . 
8. 1. 2. 2  Sl e e p Di ar y   
C ollecte d dail y i ncl u di n g 7 da ys i m me diatel y prece di n g t he baseli ne visit, a n d dail y f or 4 wee ks 
(t hro u g h v isit 4), t he n dail y d uri n g t he wee k bef ore eac h pla n ne d visit.  
A slee p diar y is desi g ne d t o gat her i nf or mati o n a b o ut patie nt’s dail y sle e p patter n. Slee p diar y will 
meas ure ni g ht -ti me slee p assess me nts. 
If p ossi ble, it s h o ul d be c o m plete d wit hi n 1 h o ur of getti n g o ut of b e d i n t he m or ni n g. T he 
assess me nt t o ol is pr o vi de d i n Secti o n  1 0. 9  ( A p pe n di x 9 ). 
V V- C LI N- 0 5 5 0 3 9 6 4. 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol 0 2  
L P S 1 5 4 9 7  
7 -A pr -2 0 2 0  
V er si o n n u m b er: 1  
 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al  
P a g e 5 0  
8. 1. 2. 3  P e a k pr urit u s  N u m eri c al R ati n g S c al e ( N R S )  
T he Pea k Pr urit us N R S is a si m ple assess me nt t o ol t hat patie nts will use t o re p ort t he i nte nsit y of 
t heir pr urit us (itc h) d uri n g a d ail y recall perio d. Patie nts will be as ke d t he f oll o wi n g q uesti o ns:  
“ O n a scale of 0 t o 1 0, wit h 0 bei n g ‘ n o itc h’ a n d 1 0 bei n g t he ‘ w orst itc h i ma gi na bl e’, h o w w o ul d 
y o u rate y o ur itc h at t he w orst m o me nt d uri n g t he pre vi o us 2 4 h o urs? ”  
Patie nts will c o m plete t he rati n g s cal e dail y f or 7 da ys pri or t o baseli ne ( or dail y f or 5 da ys (fr o m 
Da y -7 t o Da y -3  pri or t o baseli ne ) f or patie nts partici pati n g i n t he P S G s u b-st u d y), a n d dail y f or 4 
wee ks ( t hr o u g h visit 4), a n d t he n dail y d uri n g t he wee k bef ore eac h pla n ne d visit. T he assess me nt 
t o ol is pr o vi de d i n Secti o n  1 0. 9  ( A p pe n di x 9 ). 
8. 1. 2. 4  S ki n p ai n N u m eri c al R ati n g S c al e ( N R S)   
Patie nts will be as ke d t o rate t heir s ki n pai n usi n g a 0 t o 1 0 N R S. Patie nts will be as ke d t he 
f oll o wi n g q uesti o n: 
“ T hi n k a b o ut all t he areas o f y o ur s ki n wit h ecze ma. H o w w o ul d y o u rat e y o ur s ki n pai n at its 
w orst i n t he past 2 4 h o urs? ”  
Patie nts will be as ke d t o c o m plete t his assess me nt scale dail y fr o m 7 d a ys pri or t o baseli ne 
t hr o u g h w ee k 4 ( visit 4), a n d t he n dail y d uri n g t he wee k bef ore eac h pla n ne d visit. T he 
assess me nt t o o l is pr o vi de d i n Secti o n  1 0. 9  ( A p pe n di x 9 ). 
8. 1. 2. 5  S ki n s e n siti vit y t o t o u c h N u m eri c al R ati n g S c al e ( N R S )  
Patie nts will a ns wer t he q uesti o n: “ T hi n k a b o ut all t he areas of y o ur s ki n wit h ecze ma. H o w 
se nsiti ve was y o ur s ki n at its w orst i n t he past 2 4 h o urs? ” 
Patie nts will be as ke d t o c o m plete t his assess me nt scale dail y fr o m 7 d a ys pri or t o baseli ne 
t hr o u g h w ee k 4 ( visit 4), a n d t he n dail y d uri n g t he wee k bef ore eac h pla n ne d visit. T he 
assess me nt t o ol is pr o vi de d i n Secti o n  1 0. 9  ( A p pe n di x 9 ). 
8. 1. 2. 6  S ki n b ur n N u m eri c al R ati n g S c al e ( N R S )  
Patie nts will a ns wer t he q uesti o n: “ T hi n k a b o ut all t he areas of y o ur s ki n wit h ecze ma. H o w m uc h 
di d y o ur s ki n b ur n at its w orst i n t he past 2 4  h o urs? ”  
Patie nts will be as ke d t o c o m plete t his assess me nt scale dail y fr o m 7 d a ys pri or t o baseli ne 
t hr o u g h w eek 4 ( visit 4), a n d t he n dail y d uri n g t he wee k bef ore eac h pla n ne d visit. T he 
assess me nt t o ol is pr o vi de d i n Secti o n  1 0. 9  (A p pe n di x 9 ). 
V V- C LI N- 0 5 5 0 3 9 6 4. 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol 0 2  
L P S 1 5 4 9 7  
7 -A pr -2 0 2 0  
V er si o n n u m b er: 1  
 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al  
P a g e 5 1  
8. 1. 2. 7  P R O MI S Sl e e p R el at e d I m p air m e nt S h ort F or m 8 a   
T he patie nt -re p orte d o utc o mes meas ure me nt i nf or mati o n s yste m ( P R O MI S) is a D S M-5, Le vel 2, 
slee p dist ur ba nce m eas ure. T his st u d y uses t he 8 -ite m P R O MI S Slee p Relat e d I m p air me nt S h ort 
F or m t hat assess es t he d o mai n of slee p rel ate d i m pair me nt i n t he past 7 da ys i n i n di vi d uals a ge 1 8 
a n d ol der.  
Eac h ite m as ks t he patie nt t o rate t he se verit y of t he patie nt’s slee p relate d  i m pair me nt d uri n g t h e 
past 7 da ys. Eac h ite m o n t he meas ure is r ate d o n a 5 -p oi nt scale ( 1  =  n ot at all; 2  =  a little bit; 
3  =  s o me w hat; 4 =  q uite a bit; a n d 5  =  ver y m uc h) wit h a ra n ge i n sc ore fr o m 8 t o 4 0 wit h hi g her 
sc ores i n dicati n g greater se verit y of slee p i m pair m e nt. T he assess me nt t o ol is pr o vi de d i n  
Secti o n  1 0. 9  ( A p pe n di x 9 ). 
8. 1. 2. 8  E p w ort h Sl e e pi n e s s S c al e ( E S S)   
T he E S S is a self -a d mi nistere d q uesti o n nair e wit h 8 q uesti o ns. Res p o n de nts are as k e d t o rate, o n a 
4 -p oi nt scale ( 0 -3), t heir us ual c ha nces of d ozi n g off or falli n g asle e p w hil e e n ga ge d i n ei g ht 
differe nt acti vities. M ost pe o ple e n ga ge i n t h ose acti vities at least occasi o n all y, alt h o u g h n ot 
necessaril y e ver y d a y. T h e E S S sc ore (t he s u m of 8 i te m sc ores, 0-3) ca n ra n ge fr o m 0 t o 2 4. T he 
hi g her t h e E S S sc ore, t he hi g her t h at pers o n’s a vera ge slee p pr o pe nsit y i n d ail y life ( A S P), or t heir 
‘ da yti me sl ee pi ness’. 
8. 1. 2. 9  P ati e nt  ori e nt e d e c z e m a m e a s ur e ( P O E M )  
T he P O E M is a 7-ite m, vali date d q uesti o n naire us e d i n cli nical practice a n d cli nical trials t o assess 
fre q ue n c y of disease s y m pt o ms i n c hil dre n a n d a d ults (9 ). T he f or mat is a res p o nse t o 7 ite ms 
( dr y ness, itc hi n g, fla ki n g, crac ki n g, sle e p l oss, blee di n g, a n d wee pi n g) base d o n fre q ue n c y d uri n g 
t he past wee k (ie, 0 = no da ys, 1 = 1 t o 2 da ys, 2 = 3 t o 4 da ys, 3 = 5 t o 6 da ys, a n d 4 = all da ys) 
wit h a sc ori n g s yst e m of 0 t o 2 8; t he t otal sc ore reflects disease -rel ate d se v erit y. T h e q uesti o n nair e 
will be a d mi nistere d at ti me p oi nts acc or di n g t o  S o A ( Secti o n  1. 3 ). T he ass ess me nt t o ol is 
pr o vi de d i n Secti o n  1 0. 9  ( A p pe n di x 9 ). 
8. 1. 2. 1 0  D er m at ol o g y lif e q u alit y i n d e x ( D L QI )  
T he D L QI is a 1 0 -ite m, vali date d q uesti o n naire us e d i n cli nical practice a n d cli nical trials t o 
assess t he i m pact of A D disease s y m pt o ms a n d treat me nt o n Q o L (1 0 ). T h e f or mat is a si m ple 
res p o nse ( 0 t o 3 w h ere 0 is “ n ot at all” a n d 3 is “ v er y m uc h”) t o 1 0 q uesti o ns, w hic h assess Q o L 
o ver t he past w ee k, wit h a n o verall sc ori n g s yste m of 0 t o 3 0; a hi g h sc ore is i n dicati ve of a p o or 
Q o L . T h e q uesti o n nair e will be a d mi nistere d at ti me p oi nts acc or di n g t o S o A ( Secti o n  1. 3 ). T he 
assess me nt t o ol is pr o vi de d i n Secti o n  1 0. 9  ( A p pe n di x 9 ) 
8. 1. 2. 1 1  H o s pit al a n xi et y a n d d e pr e s si o n s c al e ( H A D S )  
T he h os pital a n xiet y a n d de pressi o n scal e ( H A D S  is a n i nstr u me nt f or assessi n g s y m pt o ms of 
a n xiet y a n d de pressi o n i n n o n -ps yc hiatric p o p ulati o ns; re peate d a d mi nistrati o n als o pr o vi des 
V V- C LI N- 0 5 5 0 3 9 6 4. 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol 0 2  
L P S 1 5 4 9 7  
7 -A pr -2 0 2 0  
V er si o n n u m b er: 1  
 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al  
P a g e 5 2  
i nf or mati o n a b o ut c ha n ges t o a patie nt’s e m oti o nal state (1 1 , 1 2 ). T he H A D S c o nsists of 1 4 ite ms, 
7 eac h f or a n xiet y a n d de pressi o n s y m pt o ms; p ossi b le sc ores ra n ge fr o m 0 t o 2 1 f or eac h s u bscal e. 
T he q uesti o n naire will be a d mi nistere d at ti me p oi nts acc or di n g t o Secti o n 1. 3. T he assess me nt 
t o ol is pr o vi de d i n Secti o n  1 0. 9  ( A p pe n di x 9 ). 
8. 1. 2. 1 2  W or k Pr o d u cti vit y a n d A cti vit y I m p air m e nt Q u e sti o n n air e: At o pi c D er m atiti s   
T he W or k Pr o d ucti vit y a n d Acti vit y I m pair m e nt Q uesti o n naire f or A D ( W P AI -A D ) is desi g n e d t o 
assess t he i m pact of A D o n t he patie nt’s pr o d ucti vit y. T he W P AI is a 6 -ite m, vali date d 
q uesti o n naire t o meas ur e i m pair me nts i n w or k a n d acti vities o ver a 7 -d a y recall peri o d. T h e 
W P AI -A D o utc o m es are e x presse d as i m pair me nt perce nt a ges, wit h hi g her n u m bers i n dicati n g 
greater i m pair me nt a n d l ess pr o d ucti vit y. T h e q uesti o n naire wil l be a d mi nistere d at ti me p oi nts 
acc or di n g t o S o A ( Secti o n  1. 3 ). T he W P AI-A D is pr o vi de d i n Secti o n  1 0. 9  ( A p pe n di x 9 ). 
8. 1. 2. 1 3  D a y s mi s s e d fr o m s c h o ol or fr o m w or k d u e t o A D   
Patie nts will c o m plete q uesti o ns a b o ut t heir c urre nt e m pl o y me nt stat us a n d da ys misse d fr o m 
w or k/sc h o ol d ue t o t heir A D f or all patie nts w h o are w or ki n g/ g oi n g t o sc h o ol (i nter nall y 
de vel o pe d). T his q uesti o n naire is pr o vi de d i n Secti o n  1 0. 9  ( A p pe n di x 9 ). 
8. 1. 2. 1 4  A C Q -5 ( a m o n g t h o s e r e p orti n g a st h m a at b a s eli n e)   
T he 5 -q uesti o n versi o n of t he J u ni per  ast h ma c o n tr ol q uesti o n naire ( A C Q) is a vali date d 
q uesti o n naire t o e val u ate ast h ma c o ntr ol. T he q uesti o n naire will be a d mi nistere d o nl y t o t he 
s u bset of patie nts wit h a me dical hist or y of ast h m a, at ti me p oi nts acc or di n g t o  S o A ( Secti o n  1. 3 ). 
T he assess me nt t o ol is pr o vi de d i n Secti o n  1 0. 9  ( A p pe n di x 9). 
8. 1. 2. 1 5  All er gi c R hi niti s -vi s u al a n al o g ( A R -V A S ) ( a m o n g t h o s e r e p orti n g all er gi c r hi niti s 
at b a s eli n e)   
T he aller gic r hi nitis -vis ual a nal o g scal e ( A R -V A S ) is a vali date d i nstr u me nt f or t he 
d oc u me ntati o n of s y m pt o ms a n d t hera p y m o nit ori n g i n aller gi c r hi nitis. Patie nts wit h c o m or bi d 
A R will be pr o vi de d wit h a n u n gra de d V A S a n d will be as ke d t o place a mar k o n t he scale t o 
i n dicate t he se verit y of A R s y m pt o ms. Patie nts will be as ke d: “ O v erall h o w m uc h are y o ur 
aller gic s y m pt o ms b ot heri n g y o u t o da y? ” T he V A S e xtre mities will be n ote d as “ N ot at all 
b ot hers o me” t o t he left a n d “ E xtre mel y b ot hers o me” t o t he ri g ht. T his q uesti o n naire will be 
a d mi nistere d at baseli n e a n d t he n q uarterl y ( ± 2 wee ks) t hr o u g h o ut t he st u d y t o t he patie nts wit h 
A R at baseli ne a n d t o patie nts w h o de vel o p A R d uri n g t he st u d y. T he assess me nt t o ol is pr o vi de d 
i n Secti o n  1 0. 9  ( A p pe n di x 9 ). 
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8. 1. 3  P erf or m a n c e -R e p ort e d O ut c o m e s c al e s   
8. 1. 3. 1  A cti gr a p h ( p ati e nt s will b e tr ai n e d h o w t o w e ar t h e a cti gr a p h  7 d a y s b ef or e 
b a s eli n e) :  
Wrist acti gra p h y is a t ec h ni q ue f or meas uri n g m o v e me nt of a li m b o ver a n e xte n de d rec or di n g 
peri o d ( da ys t o w ee ks). T he si g nals ge nerate d b y wrist m o ve m e nt are s e nse d b y a ti n y 
micr oc o m p uter c o nt ai ne d wit hi n t he watc h a n d tr a nslate d i nt o acti vit y c o u nts.  
Acti gra p h y is bei n g w or n o n t he wrist of t he n o n -d o mi na nt ha n d i n t his st u d y t o pr o vi de esti mates 
of t he d urati o n, ti mi n g a n d patter ns of slee p i n st u d y  partici pa nts (e g, T S T, S O L, W A S O, a n d 
slee p effi cie nc y). Eli gi bl e patie nts will wear a n Acti watc h d uri n g t he 7 da ys i m me diatel y 
prece di n g t he b aseli ne visit, dail y t hr o u g h wee k 4 ( visit 4), a n d t he n dail y d uri n g t he  wee k b ef ore 
eac h pla n n e d visit.  A detai le d descri pti o n of t he d e vice is pr o vi de d i n Secti o n  1 0. 8  ( A p pe n di x 8 ). 
A n o perati o nal ma n u al will be pr o vi de d t o I n v esti gat ors.  
8. 1. 3. 2  P s y c h o m ot or vi gil a n c e t e st ( p ati e nt s will b e i n str u ct e d b y t h e sit e pr of e s si o n al 
a n d will a d mi ni st er t h e t e st s  t h e m s el v e s)  
T he ps yc h o m ot or vi gila n ce t est (P V T ) is a wi del y use d meas ure of be h a vi oral alert n ess, ha vi n g a 
hi g h se nsiti vit y t o s lee p d e pri vati o n (1 3 ). T h ere are se veral versi o ns of t he P V T, b ut t he sta n dar d 
f or m lasts 1 0 mi n utes a n d assesses s ustai ne d atte nti o n/ vi gila nce b y rec or di n g res p o nse ti mes t o 
sti m uli t hat occ ur at var yi n g i nter-sti m ul us i nter vals. T he P V T assesses vi gila nce b y sa m pli n g 
ma n y res p o nses t o sti m uli a p peari n g at ra n d o m i nter -sti m ul us i nter vals (e g, bet wee n 2 sec o n ds 
a n d 1 0 sec o n ds) o cc urri n g o ver a peri o d of ti me ( i e, 1 0 mi n utes). T he patie nt is i nstr ucte d t o 
m o nit or a n area o n a c o m p uter /iP a d/electr o nic scree n a n d t he n t o press a res p o nse b utt o n as s o o n 
as t he sti m ul us a p pears i n or der t o kee p t he res p o nse ti me as l o w as p ossi ble wi t h o ut pressi n g t he 
b utt o n pre mat urel y . 
8. 1. 3. 3  N e ur o c o g niti v e t e st ( p ati e nt s will b e i n str u ct e d b y t h e sit e pr of e s si o n al a n d will 
a d mi ni st er t h e t e st s t h e m s el v e s)   
T he a ut o mate d ne ur o ps yc h ol o gic al assess me nt m etrics ( A N A M  c o m p uteri ze d c o g niti ve testi n g 
batter y i ncl u des tests s uita ble f or st u dies of h u ma n perf or ma n ce as well as f or st u dies i n t he areas 
of b ot h o perati o nal a n d tra diti o nal cli nical me dici ne. T he tests are a d mi nistere d b y a 
c o m p uter/iP a d/electr o nic de vice  a n d s u bjects nee d o nl y t o use t he 2 m o use b utt o ns t o res p o n d. 
F or eac h of t h e tests, patie nts will be pr o vi de d i nstr ucti o ns t hat descri be h o w t o ta ke t he test a n d 
i n dicate a c orrect res p o ns e. Researc h has s h o w n t h at A N A M’s se nsiti vit y e na bles it t o detect t he 
s u btle c o g niti ve deficits ofte n o bser ve d i n vari o us me dical c o n diti o ns (1 4 ). F urt her, cli nical trial 
data i n dicati n g t hat A N A M ca n dete ct s u btle me dicati o n -rel ate d c o g niti ve c ha n ges, s u g gest t hat it 
is i deal f or use i n t he c urre nt i n vesti gati o n (1 5 ). T h e f oll o wi n g is a list of i n di vi d ual A N A M 
meas ures a n d a des cri pti o n of eac h t est t o be use d i n t his st u d y.  
 R u n ni n g Me m or y  ass esses s ust ai ne d atte nti o n, w or ki n g me m or y, a n d resista nce t o 
i nterfere nce. T he test re q uires s ustai ne d atte nti o n i n res p o nse t o a sti m ul us o n t he 
c o m p uter scree n d uri n g a f orce d -pace, ra pi d tas k. N u m bers are pres e nte d o n t he scree n 
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a n d t he user m ust press a s pecifie d ke y i n dicati n g w het her t he n u m ber is t he sa me as or 
differe nt t ha n t h e pre vi o us n u m ber. T he s u btest ta kes a p pr o xi matel y 5  mi n utes t o 
c o m plete.  
 Mat he matical Pr ocessi n g  assesses mat he matical c o m p utati o n a n d w or ki n g me m or y.  T h e 
test i n v ol ves Mat h pr o ble ms bei n g prese nte d o n t h e scree n. T he a ns wer m ust be fi g ure d 
o ut a n d t he n t he user m ust deci de if t he a ns w er is > or < t he n u m ber 4. T h e s u btest ta kes 
a p pr o xi matel y 5  mi n utes t o c o m plete . 
 Pr oce d ural Reacti o n Ti me  is a n assess me nt of c h oice reacti o n ti me. T he us er m ust ta p t he 
left m o use b utt o n if t he n u m ber s h o w n o n t he scree n is 2 or 3 a n d t he ri g ht m o use b utt o n if 
t he n u m ber s h o w n o n t he scree n is 4 or 5. T he s u btest ta kes a p pr o xi matel y 3 mi n utes t o 
c o m plete.  
8. 1. 4  M ulti pli cit y c o n si d er ati o n s   
M ulti plicit y is c o nsi dere d f or testi n g m ulti ple e n d p oi nts. I n or der f or a n y s ec o n dar y e n d p oi nts t o 
be eli gi ble f or bei n g d ecl are d si g nifica nt, t he pri mar y e n d p oi nt m ust be si g nifica nt.  
F or t he sec o n dar y e n d p oi nts, t he o verall t y p e I err or rate will be c o ntr olle d at t he 2 -si de d 0. 0 5 
le vel usi n g a s e q ue ntial t esti n g pr oce d ure. T he or der i n w hic h t he sec o n dar y e n d p oi nts are test e d 
will be s pecifie d i n t he Statistical A nal ysis Pla n .  
Eac h e n d p oi nt w ill be teste d at 0. 0 5 (2 -si de d) l e vel of si g nifica n ce. If at a n y ste p t he n ull 
h y p ot hesis of s u peri orit y is rejecte d, t he e n d p oi nts liste d bel o w t hat will n ot be tec h nicall y eli gi ble 
f or bei n g declare d si g nifi ca nt. Re gar dl ess of eli gi bilit y, all e n d p oi nts will be teste d.  
8. 2  
S A F E T Y A S S E S S M E N T S   
Pla n ne d ti me p oi nts f or all safet y assess me nts are pr o vi de d i n t he S o A  (Secti o n  1. 3 ). 
8. 2. 1  Vit al si g n s   
Vital si g ns, i ncl u di n g h eart rate, sitti n g bl o o d press ure, b o d y te m perat ure, a n d res pirati o n rat e, 
will be c ollecte d pre -d os e at ti me p oi nts acc or di n g t o  Secti o n  1. 3 . All v ital si g ns will be ta ke n at 
scree ni n g visit a n d all s u bse q ue nt visits bef ore i nj ecti o n a n d at 3 0  mi n utes ( ± 1 0 mi n utes) p ost -
i njecti o n (d uri n g t h e i n -cli nic 3 0-mi n utes p ost -i njecti o n o bser vati o n). I n case a patie nt c o mes t o 
t he st u d y site f or I M P i njecti o n b y t h e st u d y staff at wee k s 6, 1 0, 1 4, 1 8, a n d/ or 2 2, vital si g ns will 
als o be meas ur e d at t hese visits, as f or ot her pla n n e d o n -site visits. 
8. 2. 2  Cli ni c al s af et y l a b or at or y a s s e s s m e nt s   
All pr ot oc ol -re q uir e d la b orat or y assess me nts, as defi ne d i n Secti o n  1 0. 2  ( A p pe n di x 2), m ust be 
c o n d ucte d i n acc or da nce wit h t he S o A  (Secti o n  1. 3 ). 
 If la b orat or y val ues fr o m n o n-pr ot oc ol s pecifi e d la b orat or y assess me nts perf or me d at t he 
i nstit uti o n’s l ocal la b orat or y re q uire a c h a n ge i n p artici pa nt ma na ge me nt or are c o nsi d ere d 
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cli nical l y si g nifica nt b y t he I n vesti gat or (e g, S A E or A E or d ose m o dificati o n), t he n t he 
res ults m ust be rec or de d i n t he C R F. 
8. 3  
A D V E R S E E V E N T S  A N D S E RI O U S A D V E R S E  E V E N T S   
A d verse e v e nt  of s peci al i nterest 
A n a d vers e e ve nt of s pecial i nterest ( A E SI ) is a n A E (seri o us or n o ns eri o us) of scie ntific a n d 
me dical c o ncer n s pecific t o t he S p o ns or ’s pr o d uct or pr o gra m, f or w hic h o n g oi n g m o nit ori n g a n d 
i m me diate n otificati o n b y t he I n v esti gat or t o t he S p o ns or  is re q uire d. S uc h e ve nts ma y re q uir e 
f urt her i n vesti gati o n i n or der t o c h aracterize a n d u n dersta n d t he m. A d verse e ve nts of s peci al 
i nterest may be a d d e d, m o difie d or re m o ve d d uri n g a st u d y b y pr ot o c ol a m e n d me nt.  
T he f oll o wi n g e ve nts are A E SIs a n d re q uir e re p orti n g t o t he S p o ns or wit hi n 2 4 h o urs of lear ni n g 
of t he e ve nt:  
 A na p h yl a ctic reacti o ns  
 S yste mic or se v ere h y p erse nsiti vit y reacti o ns  
 Mali g na n c y (e x ce pt i n sit u carci n o ma of t he cer vi x, n o n -metastatic s q ua m o us or basal cell 
carci n o ma of t he s ki n)  
 Hel mi nt hic i nfecti o ns  
 S uici de -relate d e ve nts 
 A n y t y pe of c o nj u ncti vitis or ble p haritis (se vere or seri o us)  
 Keratitis  
T he f oll o wi n g e ve nts als o re q uire  re p orti n g t o t he S p o ns or wit hi n 2 4 h o urs of lear ni n g of t he 
e ve nt:  
 Pre g n a nc y of a fe m ale s u bject e ntere d i n a st u d y as well as pre g n a nc y occ urri n g i n a 
fe male part ner of a male s u bject e ntere d i n a st u d y wit h I M P/ NI M P: 
- 
Pre g n a nc y occ urri n g i n a fe male part ici pa nt e ntere d i n t he cli nical trial or i n a fe male 
part ner of a male p artici p a nt  e ntere d i n t he cli nical trial. It will be q ualifie d as a n S A E 
o nl y if it f ulfills 1 of t he seri o us ness criteria (see  Secti o n  1 0. 3  [A p pe n di x 3 ]). 
- 
I n t he e ve nt of pre g na n c y i n a fe male p artici pa nt, I M P s h o ul d be disc o nti n ue d.  
- 
F oll o w -u p of t he pre g na n c y i n a fe mal e partici pa nt or i n a fe mal e part ner of a male 
partici pa nt s h o ul d be c o n d ucte d u ntil t he o utc o me has bee n det er mi ne d   
( See Secti o n  1 0. 4  [A p pe n di x 4 ]). 
 S y m pt o matic o v er d ose (s eri o us or n o nseri o us) wit h I M P/ n o ni n vesti gati o nal me dici nal 
pr o d uct ( NI M P ): 
- 
A n o ver d ose (acci de ntal or i nte nti o nal) wit h t he I M P/ NI M P is a n e ve nt s us pecte d b y 
t he I n v esti gat or or s p o nta ne o usl y n otifie d b y t he p artici pa nt  a n d defi ne d as at least 
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t wice t he i nte n de d d ose wit hi n t he i nte n de d t hera pe utic i nter val, a dj uste d acc or di n g t o 
t he teste d dr u g. 
- 
I nje cta ble a d mi nistrati o n: at least t wice t he d ose d uri n g t he pla n n e d i nter vals 
 T he circ u msta n ces (ie, acci de ntal or i nte nti o nal) s h o ul d be clearl y s p ecifie d i n t he 
ver bati m a n d s y m pt o ms, if a n y, e ntere d o n se parat e A E f or ms.  
T he defi niti o ns of a n A E or S A E ca n be f o u n d i n  Secti o n  1 0. 3  ( A p pe n di x 3). 
A E will be re p orte d b y t h e partici pa nt ( or, w he n a p pr o priate, b y a care gi ver, s urr o gate, or t he 
partici pa nt's le gall y a ut h orize d re pres e ntat i ve). 
T he I n vesti gat or a n d a n y q ualifie d desi g nees are res p o nsi ble f or detecti n g, d oc u me nti n g, a n d 
rec or di n g e ve nts t hat meet t he defi niti o n of a n A E or S A E a n d re m ai n res p o nsi ble f or f oll o wi n g 
u p A Es t hat are s eri o us, c o nsi dere d rel ate d t o t he st u d y pr oce d ures, or t hat ca use d t he partici pa nt 
t o disc o nti n ue t he st u d y (see Secti o n  7 ).  
8. 3. 1  Ti m e p eri o d a n d fr e q u e n c y f or c oll e cti n g A E a n d S A E i nf or m ati o n   
All A Es , seri o us or n o ns eri o us, will be c ollecte d fr o m t he si g ni n g of t he I C F u ntil t he e n d of st u d y 
at t he ti me p oi nts s pecifie d i n t he S o A (Secti o n  1. 3 ). 
All S A Es a n d A E SI  will be rec or de d a n d re p orte d t o t he S p o ns or  or desi g n ee wit hi n 2 4 h o urs, as 
i n dicate d i n Secti o n  1 0. 3  ( A p pe n di x 3). T he I n vesti gat or will s u b mit a n y u p date d S A E data t o t he 
S p o ns or  wit hi n 2 4  h o urs of it bei n g a v aila ble.  
I n v esti gat ors are n ot o bli gat e d t o acti vel y see k A E or S A E after c o ncl usi o n of t he st u d y 
partici pa ti o n. H o we v er, if t he I n vesti gat or lear ns of a n y S A E, at a n y ti me after a partici pa nt has 
bee n disc har ge d fr o m t he st u d y, a n d h e/s he c o nsi d ers t he e v e nt t o be reas o n a bl y relate d t o t he 
st u d y i nter ve nti o n or st u d y partici pati o n, t he  I n vesti gat or s h o ul d pr o m ptl y n otif y t he S p o ns or . 
T he met h o d of rec or di n g, e val uati n g, a n d ass essi n g ca usalit y of A E a n d S A E a n d t he pr oce d ures 
f or c o m pleti n g a n d tra ns mitti n g S A E re p orts are pr o vi de d i n Secti o n  1 0. 3  ( A p pe n di x 3). 
8. 3. 2  M et h o d of d et e cti n g A E s a n d S A E s   
Care will be ta ke n n ot t o i ntr o d uce bias w he n d etecti n g A Es a n d/ or S A Es. O pe n-e n d e d a n d 
n o n -lea di n g ver bal q uesti o ni n g of t he p artici pa nt is t he preferre d m et h o d to i n q uire a b o ut 
A E  occ urre nces.  
8. 3. 3  F oll o w -u p of A E s a n d S A E s   
After t he i nitial A E/ A E SI/ S A E re p ort, t he I n v esti gat or is re q uire d t o pr o acti vel y f oll o w eac h 
partici pa nt at s u bse q ue nt visits/c o ntacts. At t he pre -s pecifie d st u d y e n d-date, a ll S A Es, an d 
n o n seri o us A Es of s pecial i nterest (as defi n e d i n Secti o n  8. 3 ), will be f oll o we d u ntil res ol uti o n, 
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sta bilizati o n, t he e ve nt is ot her wise e x plai ne d, or t he partici pa nt is l ost t o f oll o w-u p (as defi n e d i n 
Secti o n  7. 3 ). F urt her i nf or mati o n o n f oll o w-u p pr o ce d ures is gi ve n i n  Secti o n  1 0. 3  ( A p pe n di x 3). 
8. 3. 4  P h y si c al e x a mi n ati o n s   
 A t h or o u g h  a n d c o m plete p h ysical e x a mi nati o n will be perf or me d at ti me p oi nts acc or di n g 
t o Secti o n  1. 3 . 
 Care s h o ul d be ta k e n t o e x a mi ne a n d assess a n y a b n or malities t hat ma y be prese nt, as 
i n dicate d b y t he patie nt’s me dical hist or y.  
 I n v esti gat ors s h o ul d pa y s pecial atte nti o n t o cli nical si g ns relate d t o pre vi o us seri o us 
ill nesses. 
 A n y n e w fi n di n g or w orse ni n g of pre vi o us fi n d i n g s h o ul d be re p orte d as a n e w a d verse 
e ve nt.  
8. 3. 5  R e g ul at or y r e p orti n g r e q uir e m e nt s f or S A E s   
 Pr o m pt n otificati o n b y t he I n vesti gat or t o t he S p o ns or  of a S A E is esse ntial s o t hat le g al 
o bli gati o ns a n d et hical res p o nsi bilities t o war ds t he safet y of partici pa nts a n d t he safet y of 
a st u d y i nter ve nti o n u n der cli nical i n vesti gati o n are met.  
 T he S p o ns or  has a le gal r es p o nsi bilit y t o n otif y b ot h t he l ocal re g ulat or y a ut h orit y a n d 
ot her re g ul at or y a ge n cies a b o ut t he safet y of a st u d y i nter ve nti o n u n der cli nical 
i n vesti gati o n. T he S p o ns or  will c o m pl y wit h c o u ntr y -s p ecific re g ulat or y re q uire me nts 
relati n g t o s afet y re p orti n g t o t he re g ulat or y a ut h orit y, I R B/ I E C, a n d I n vesti gat ors. 
 I n v esti gat or safet y re p orts m ust be pre pare d f or s us pecte d u ne x pecte d s eri o us a d verse 
reacti o ns acc or di n g t o l o cal re g ulat or y re q uir e me nts a n d S p o ns or  p olic y a n d f or war de d t o 
I n v esti gat ors as necessar y. 
 A d verse e ve nts t hat are c o nsi dere d e x pecte d will be s pecifie d i n t he refere nce safet y 
i nf or mati o n. 
 A n I n vesti gat or w h o recei ves a n I n vesti gat or safet y re p ort descri bi n g a S A E or ot her 
s pecific safet y i nf or mati o n (e g, s u m mar y or listi n g of S A Es) fr o m t he S p o ns or  will re vie w 
a n d t he n file it al o n g wit h t he I B a n d will n otif y t he I R B/I E C, if a p pr o priat e acc or di n g t o 
l ocal re q uir e me nts. 
8. 3. 6  Pr e g n a n c y   
 Details of all pre g n a ncies i n fe male partici pa nts a n d, if i n dicate d, fe m ale part ners of male 
partici pa nts  will be c ollecte d after t he start of st u d y i nter ve nti o n a n d u ntil o utc o me is 
k n o w n . 
If a pre g na nc y is r e p orte d, t he I n v esti gat or s h o ul d i nf or m t he S p o ns or  wit hi n 2 4 h o urs  of lear ni n g 
of t he pre g n a nc y a n d s h o ul d f oll o w t he pr oce d ures o utli ne d i n  Secti o n  1 0. 4  ( A p pe n di x 4). 
V V- C LI N- 0 5 5 0 3 9 6 4. 0

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L P S 1 5 4 9 7  
7 -A pr -2 0 2 0  
V er si o n n u m b er: 1  
 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al  
P a g e 5 8  
 A b n or mal pre g n a nc y o ut c o mes (e g, s p o nta n e o us a b orti o n, fetal deat h, still birt h, c o n ge nital 
a n o malies, a n d ect o pic pre g n a nc y) are c o nsi dere d S A Es.  
8. 3. 7  G ui d eli n e s f or r e p orti n g pr o d u ct c o m pl ai nt s   
A n y d efect i n t he I M P/ NI M P/ de vice m ust be re p orte d as s o o n as p ossi ble b y t he I n v esti gat or t o 
t he m o nit ori n g tea m t hat will c o m plete a pr o d uct c o m plai nt f or m wit hi n re q uire d ti meli nes. 
A p pr o priate i nf or mati o n (e g, sa m ples, la bels or d o c u me nts li ke pict ures or p h ot oc o pies) relat e d t o 
pr o d uct i de ntificati o n a n d t o t he p ote ntial deficie ncies ma y nee d t o b e gat h ere d. T h e I n vesti gat or 
will assess w het her or n ot t he q ualit y iss ue has t o be re p ort e d t o get her wit h a n A E or S A E.  
8. 4  
T R E A T M E N T O F O V E R D O S E   
S y m pt o matic o v er d ose of I M P is a n A E SI ( defi n e d i n Secti o n  8. 3 ). N o s pecific treat me nt is 
a vaila ble f or I M P o ver d ose.  
I n t he e ve nt of a s y m pt o matic o ver d ose, t he I n vesti gat or/treati n g p h ysici a n s h o ul d:  
1.  C o ntact t he m e dical m o nit or i m me diatel y  
2.  Cl osel y m o nit or t he parti ci pa nt f or a n y A E/ S A E a n d la b orat or y a b n or malities u ntil st u d y 
i nter ve nti o ns ca n n o l o n ger be det ecte d s yste maticall y 
3.  O btai n a plas ma sa m ple f or P K a nal ysis wit hi n as s o o n as p ossi ble, fr o m t he date of t he 
last d ose of st u d y i nter ve nti o n if re q ueste d b y t he m e dical m o nit or ( deter mi ne d o n a case -
b y -case b asis)  
4.  D oc u me nt t he q ua ntit y of e x cess d ose as w ell as t he d urati o n of  t he o ver d ose i n t he C R F. 
Decisi o ns re gar di n g d ose i nterr u pti o ns or m o dificati o ns will be ma de b y t h e I n vesti gat or i n 
c o ns ultati o n wit h t he m e dical m o nit or base d o n t h e cli nical e val u ati o n of t he partici pa nt.  
8. 5  
P H A R M A C O KI N E TI C S   
P K para meters a re n ot e v al uate d i n t his st u d y. 
8. 6  
P H A R M A C O D Y N A MI C S   
P har mac o d y na mic p ara m eters a re n ot e val u ate d i n t his st u d y. 
8. 7  
G E N E TI C S   
N ot ap plica ble . 
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L P S 1 5 4 9 7  
7 -A pr -2 0 2 0  
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Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al  
P a g e 5 9  
8. 8  
BI O M A R K E R S   
N ot ap plica ble . 
8. 9  
H E A L T H E C O N O MI C S O R M E DI C A L R E S O U R C E U TI LI Z A TI O N A N D H E A L T H 
E C O N O MI C S   
W or k pr o d ucti vit y a n d A cti vit y I m pair me nt Q uesti o n naire  A D a n d Da ys misse d fr o m sc h o ol or 
fr o m w or k d ue t o A D are i ncl u de d f or ass essi n g t his cate g or y. 
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A m e n d e d Cli ni c al Tri al Pr ot o c ol 0 2  
L P S 1 5 4 9 7  
7 -A pr -2 0 2 0  
V er si o n n u m b er: 1  
 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al  
P a g e 6 0  
9  
S T A TI S TI C A L C O N SI D E R A TI O N S   
9. 1  
S T A TI S TI C A L H Y P O T H E S E S   
T he alter nati ve statistical h y p ot hesis teste d is t hat t he effect of d u pil u ma b o n slee p q ualit y a n d 
q ua ntitati ve c o m p o ne nts ( e g, slee p effici e nc y, T S T , etc.) as w ell as o n ge n eral A D relate d effi cac y 
assess me nts i n a d ult patie nts wit h m o derate t o se v ere A D a n d slee p dist ur ba nce is s u peri or t o 
place b o.  
9. 2  
S A M P L E SI Z E D E T E R MI N A TI O N   
T he sa m ple siz e calc ul ati o ns were b ase d o n t he s u bset of patie nts w h o re p orte d ≥5 u ni ts of 
baseli ne slee p l oss a n d ≥3 u nits of baseli ne pr urit us sc ores o n t he S C O R A D i nstr u me nt i n a 
pre vi o us st u d y ( A D 1 4 2 4) e val uati n g efficac y of d u pil u ma b f or A D.  
Si nce n o pre vi o us data are a vaila ble o n dail y sle e p o n t he N R S scale, t he S C O R A D slee p 
c o m p o ne nt ( V A S) dat a was use d as a basis f or t h e sa m ple siz e deter mi nati o n f or t he pri mar y 
e n d p oi nt. T he varia bilit y (sta n dar d de vi ati o n) esti mate f or t he s u bset of p ati e nts me nti o ne d a b o ve 
was 3 7 % f or t h e % c h a n ge fr o m baseli ne t o w ee k 1 2. Gi ve n t he u ncertai nt y i n t he varia bilit y fr o m 
t his varia ble t o t he N R S wee kl y a v era ge slee p sc ore, t he a b o v e vari a bilit y was i nflate d b y ~ 2 0 %, 
a n d ass u me d t o be 4 4 % f or t he pri mar y sle e p para meter. Wit h t hese ass u m pti o ns, a t otal sa m ple of 
1 5 0 ( 5 0 i n place b o a n d 1 0 0 i n d u pil u ma b gr o u p) p atie nts will pr o vi de 9 0 % p o wer (al p ha  =  0. 0 5, 
2 -si de d) t o detect a treat me nt differe n ce of 2 5 % (effect size, Δ/ σ = 0. 5 7) f or t he perce nt c h a n ge 
fr o m baseli ne.  
F or sec o n dar y acti gra p h y e n d p oi nts, sa m ple size esti mates are pr o vi de d i n refere nce t o 
ne m oliz u ma b P h 2 data at wee k 4.  F or T S T , t o detect a 3 0 mi n ute s differe nce bet wee n treat me nts: 
( 2: 1 all ocati o n rati o; al p h a = 0. 0 5, 2 -si de d), ass u mi n g t he sa m e varia bilit y at wee k 1 6 wee ks as 
see n f or n e m oliz u ma b at wee k 4 ( = 5 6 mi n), t he n 1 6 7 s u bjects are n ee de d t o pr o vi de 9 0 % p o wer. 
F urt her m ore, t he pr o p os e d sa m ple siz e w o ul d ha ve > 9 0 % p o wer t o detect a differe n ce of 1 0 % f or 
c ha n ge fr o m baseli ne i n acti gra p h bas e d s lee p effi cie nc y, ass u mi n g a v aria bilit y of 1 1 % 
(al p ha = 0. 0 5, 2 -si de d). T h e varia bilit y esti mate was base d o n (8 ) f or acti gra p h y bas e d slee p 
efficie n c y at w ee k 4, i nfl ate d b y 5 0 % t o acc o u nt f or p ossi ble i ncreas e i n varia bilit y o ver ti me 
(fr o m wee k 4 t o wee k 1 6). Of n ote, t he d ata use d f or acti gra p h y p ara m eters are li mite d . 
All o wi n g f or dr o p o uts, a t otal of a p pr o xi matel y 2 0 1 patie nts will be e nr ol le d i n t he st u d y. 
C o nsi deri n g t he u ncertai nt y of t he v aria bilit y of t he pri mar y e n d p oi nt, w he n data are a v aila ble f or 
t his e n d p oi nt fr o m a b o ut 5 0 % of t he patie nts, t he v aria bilit y will be ass esse d i n a bli n de d ma n ner, 
a n d t he sa m ple siz e will be re -esti mate d. If t he re-esti mate d sa m ple siz e is hi g her t h a n t he ori gi nal 
esti mate, t he sa m ple siz e ma y b e i ncrease d acc or di n gl y, n ot t o e x cee d a t otal of 1 5 0 a d diti o nal 
patie nts.  
Si nce t his a nal ysis will be perf or me d i n a bli n de d ma n ner, n o a dj ust me nt t o t he t y pe I err or will be 
ma de i n t he fi nal a n al ysis.  
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A m e n d e d Cli ni c al Tri al Pr ot o c ol 0 2  
L P S 1 5 4 9 7  
7 -A pr -2 0 2 0  
V er si o n n u m b er: 1  
 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al  
P a g e 6 1  
9. 3  
P O P U L A TI O N S F O R A N A L Y S E S   
F or p ur p os es of a n al ysis, t he f oll o wi n g p o p ulati o ns are defi ne d  i n Ta ble  3 . 
T a bl e  3  - P o p ul ati o n s f or a n al y s e s   
P o p ul ati o n  
D e s cri pti o n  
E nr oll e d  
All p artici p a nts w h o si g n t h e I C F . 
R a n d o m iz e d 
T h e r a n d o miz e d p o p ul ati o n i ncl u d es all p ati e nts wit h a tr e at m e nt kit n u m b er 
all oc at e d  a n d r ec or d e d i n t h e I R T d at a b as e, a n d r e g ar dl ess of w h et h er t h e 
tr e at m e nt kit w as us e d or n ot.  
P ati e nts tr e at e d wit h o ut b ei n g r a n d o miz e d will n ot b e c o nsi d er e d r a n d o miz e d a n d 
will  n ot b e i ncl u d e d i n a ny effic acy p o p ul ati o n, b ut will b e i ncl u d e d i n t h e s af ety  
p o p ul ati o n.  
I nt e nt-t o-tr e at (I T T)  
All r a n d o miz e d p ati e nts , a n d will b e a n alyz e d acc or di n g t o t h e tr e at m e nt gr o u p 
all oc at e d  by  r a n d o miz ati o n  
Effic acy  
T h e I T T P o p ul ati o n  
S af ety  
T h e s af ety p o p ul ati o n i ncl u d es all p ati e nts w h o act u ally r ec eiv e d at l e ast 1  d os e or  
p arti al d os e of t h e I M P, a n alyz e d acc or di n g t o t h e tr e at m e nt act u ally r ec eiv e d.  
R a n d o miz e d p ati e nts f or w h o m it is u ncl e ar w h et h er  t h e st u dy m e dic ati o n w as 
t ak e n will b e i ncl u d e d i n t h e s af ety p o p ul ati o n as r a n d o miz e d.  
A b br evi ati o ns: I C F = i nf or m e d c o ns e nt f or m;  I R T = i nt er activ e r es p o ns e t ec h n ol o gy; I T T = i nt e nt-t o-tr e at 
9. 4  
S T A TI S TI C A L A N A L Y S E S   
T he statistical a nal ysis pla n will be de vel o pe d a n d fi nalize d bef ore d ata bas e l oc k. T his secti o n is a 
s u m mar y of t he pla n ne d statistical a nal ys es of t he pri mar y a n d sec o n dar y e n d p oi nts.  
9. 4. 1  Effi c a c y a n al y s e s   
N ote : All dail y ass ess me nts (e g, sl ee p N R S, acti gra p h y p ara m eters, slee p diar y, etc.) will be 
a nal yz e d as wee kl y a vera ges f or t he wee k i m me di atel y prece di n g t he st u d y visit. T h us , t he 
baseli ne val ue will c orres p o n d t o t he assess me nts c o m plete d d uri n g t he wee k prece di n g 
ra n d o mizati o n. 
T a bl e  4  - Effi c a c y a n al y s e s   
E n d p oi nt  
St ati sti c al A n al y si s M et h o d s  
Pri m ary  
P erc e nt c h a n g e fr o m 
b as eli n e t o w e ek 1 2 i n 
sl e e p N R S 
P erc e nt c h a n g e fr o m b as eli n e will b e a n alyz e d usi n g a mix e d eff ect m o d el wit h r e p e at e d m e as ur es 
( M M R M) wit h tr e at m e nt, b as eli n e v al u e, r a n d omiz ati o n str at u m, w e ek , tr e at m e nt by w e ek 
i nt er acti o n, a n d b as eli n e v al u e by w e ek i nt er acti o n t er ms ( all as fix e d eff ects) i n t h e m o d el. A n 
u nstr uct ur e d c orr el ati o n m atrix will b e us e d t o m o d el t h e wit hi n -p ati e nt err ors.  N o i m p ut ati o ns f or 
missi n g v al u es will b e c arri e d o ut f or t h e pri m ary a n alysis.  
L S m e a n c h a n g es b et w e e n t h e d u pil u m a b gr o u p a n d pl ac e b o, t h e c orr es p o n di n g 9 5 % CI of t h e 
diff er e nc es  a n d p -v al u es will b e pr ovi d e d. 
V V- C LI N- 0 5 5 0 3 9 6 4. 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol 0 2  
L P S 1 5 4 9 7  
7 -A pr -2 0 2 0  
V er si o n n u m b er: 1  
 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al  
P a g e 6 2  
S ec o n d ary  
C h a n g e fr o m b as eli n e t o 
w e ek 1 2 i n sl e e p 
effici e ncy , t ot al sl e e p 
ti m e, w ak e aft er sl e e p 
o ns et , sl e e p o ns et 
l at e ncy b as e d o n 
acti gr a p h d at a  
 
P erc e nt c h a n g e fr o m 
b as eli n e t o w e ek 1 2 i n 
Pr urit us N R S  
 
C h a n g e fr o m b as eli n e t o 
w e ek  1 2 i n S C O Ri n g 
At o pic D er m atitis 
( S C O R A D) t ot al sc or e 
 
C h a n g e fr o m b as eli n e t o 
w e ek 1 2 i n  S C O R A D 
sl e e p V A S 
 
C h a n g e fr o m b as eli n e t o 
w e ek 1 2 i n D er m at ol o gy 
Q u ality Lif e I n d ex 
( D L QI) 
 
C h a n g e fr o m b as eli n e t o 
w e ek 1 2 i n P ati e nt 
Ori e nt e d Ecz e m a 
M e as ur e ( P O E M) t ot al 
sc or e 
C h a n g e fr o m b as eli n e t o 
w e ek 1 2 i n P R O MI S 
Sl e e p R e l at e d 
I m p air m e nt S F 8 a t ot al 
sc or e 
Pr o p orti o n of p ati e nts 
wit h E A SI 5 0, E A SI 7 5 
(r e d ucti o n of E A SI sc or e 
by ≥5 0 % a n d ≥7 5 % 
fr o m b as eli n e, 
r es p ectiv ely) at e ac h 
ti m e p oi nt 
 
T h e si mil ar a p pr o ac h as f or t h e a n alysis of pri m ary e n d p oi nt will b e us e d . 
 
A  si mil ar a ppr o ac h as f or t h e a n alysis of pri m ary e n d p oi nt will b e us e d . 
 
 
A  si mil ar a p pr o ac h as f or t h e a n alysis of pri m ary e n d p oi nt will b e us e d . 
 
 
 
A  si mil ar a p pr o ac h as f or t h e a n alysis of pri m ary e n d p oi nt will b e us e d . 
 
 
A  si mil ar a p pr o ac h as f or t h e a n alysis of pri m ary e n d p oi nt will b e us e d . 
 
 
A  si mil ar a p pr o ac h as f or t h e a n alysis of pri m ary e n d p oi nt will b e us e d . 
 
 
 
A  si mil ar a p pr o ac h as f or t h e a n alysis of pri m ary e n d p oi nt will b e us e d . 
 
 
 
 
 
will b e a n alyz e d vi a t h e C oc hr a n -m a nt el -H a e nsz el t est a dj ust e d by t h e r a n d o miz ati o n str at u m  at 
e ac h ti m e p oi nt  
 
 
 
 
Ex pl or at ory  
Will b e d escri b e d i n t h e st atistic al a n alysis pl a n fi n aliz e d b ef or e d at a b as e l ock  pri or t o t h e w e ek  1 2 
i nt eri m a n alysis. Of n ot e, f or m al st atistic al c o m p aris o ns will n ot b e p erf or m e d o n t h e P S G e n d p oi nts 
d u e t o t h e li mit e d s a m pl e siz e of t h e s u b -st u dy; t h e a n alys es will b e li mit e d t o pr ovi di n g s u m m ary 
st atistics f or t h e s p ecifi e d e n d p oi nts. 
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A m e n d e d Cli ni c al Tri al Pr ot o c ol 0 2  
L P S 1 5 4 9 7  
7 -A pr -2 0 2 0  
V er si o n n u m b er: 1  
 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al  
P a g e 6 3  
9. 4. 2  S af et y a n al y s e s   
All safet y a nal yses will be perf or me d o n t he Safet y P o p ulati o n.   
T a bl e  5  - S af et y a n al y s e s   
E n d p oi nt  
St ati sti c al A n al y si s M et h o d s  
A E, S A E, A E  
l e a di n g t o d e at h, 
A E l e a di n g t o  
p er m a n e nt  
tr e at m e nt 
disc o nti n u ati o n  
T r e at m e nt e m er g e nt a dv ers e ev e nt ( T E A E) i nci d e nc e t a bl es will b e pr es e nt e d by syst e m or g a n cl ass 
( S O C), hi gh -l ev el gr o u p t er m ( H L G T), hi g h-l ev el t er m ( H L T) a n d pref err e d t er m ( P T) f or e ac h tr e at me nt 
gr o u p a n d ov er all, s h o wi n g t h e n u m b er ( n) a n d p erc e nt a g e ( %) of p ati e nts ex p eri e nci n g a T E A E. M ulti pl e 
occ urr e nc es  of t h e s a m e ev e nt i n t h e s a m e p ati e nt will b e c o u nt e d o nly o nc e i n t h e t a bl es. T h e 
d e n o mi n at or f or c o m p ut ati o n of p erc e nt a g es is t h e s af ety p o p ul ati o n wit hi n e ac h tr e at m e nt gr o u p. I n 
a d diti o n, T E A Es will b e d escri b e d acc or di n g t o m axi m u m i nt e nsity a n d r el ati o n t o t h e st u dy dr u g. A Es 
t h at occ ur outsi d e t h e tr e at m e nt e m er g e nt p eri o d will b e s u m m ariz e d s e p ar at ely.   
Pr o p orti o n of p ati e nts wit h at l e ast 1 T E A E, tr e at m e nt e m er g e nt S A E, T E A E l e a di n g t o d e at h, a n d T E A E 
l e a di n g t o p er m a n e nt tr e at m e nt disc o nti n u ati on will b e t a b ul at e d by tr e at m e nt gr o u p a n d ov er all.  
All T a bl es will b e pr o vi d e d s e p ar at ely f or t h e d o u bl e-bl i n d tr e at m e nt p eri o d, a n d f or t h e e ntir e st u dy. 
9. 4. 3  Ot h er a n al y s e s   
N ot a p plica ble.  
9. 5  
I N T E RI M A N A L Y S E S   
After all patie nts ha v e c o m plete d t he 1 2 wee ks of d o u ble -bli n d, ra n d o mize d treat me nt peri o d, t he 
data base f or t his p orti o n of t he st u d y will be l oc ke d, a n d t he st u d y will be u n bli n de d; C o m parati ve 
effic ac y dat a will be a nal yz e d f oll o wi n g t his data base l oc k.  
Si nce t he u n bli n di n g will be perf or me d after t he ra n d o mize d treat me nt peri o d, n o a dj ust me nts t o 
t he t y pe I err or is nee d e d.  
O nce all patie nts c o m plet e t he 2 4 wee ks p ost ra n d o mizati o n, t he fi nal data base l oc k will be 
perf or me d, a n d t he re mai ni n g data will be a nal yz e d.   
9. 6  
D A T A M O NI T O RI N G C O M M I T T E E ( D M C)  
N o D M C is pla n ne d f or t his st u d y.  
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P a g e 6 4  
1 0  
S U P P O R TI N G D O C U M E N T A TI O N A N D O P E R A TI O N A L  
C O N SI D E R A TI O N S   
1 0. 1  
A P P E N DI X 1: R E G U L A T O R Y, E T HI C A L,  A N D S T U D Y O V E R SI G H T  
C O N SI D E R A TI O N S   
1 0. 1. 1  R e g ul at or y a n d Et hi c al C o n si d er ati o n s   
 T his  st u d y will be c o n d u cte d i n acc or da n ce wit h t he 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 
Declarati o n of Helsi n ki a n d t he a p plica ble a me n d me nts a n d C o u ncil f or I nter nati o nal 
Or g a niz ati o ns of Me dical Scie nces  CI O M S ) I nter nati o nal Et hical G ui deli nes. 
- 
A p plica ble I C H G o o d Cli nical Practice ( G C P) G ui deli nes . 
- 
A p plica ble la ws a n d re g ulati o ns . 
 T he pr o t oc ol, pr ot oc ol a me n d me nts, I C F, I n vesti gat or Br oc h ure, a n d ot her rele va nt 
d oc u me nts (e g, a d v ertise me nts) m ust be s u b mitte d t o a n I R B/I E C b y t he I n vesti gat or a n d 
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 st u d y is i nitiate d. 
 A n y a me n d me nts t o t he pr ot oc ol will re q uire I R B/I E C a p pr o val bef ore i m ple me ntati o n of 
c ha n ges ma d e t o t he st u d y desi g n, e x ce pt f or c ha n ges n ecess ar y t o eli mi nat e a n i m me diate 
hazar d t o st u d y partici pa nts.  
 T he I n vesti gat or will be res p o nsi ble f or t he f oll o wi n g:  
- 
Pr o vi di n g writte n s u m maries of t he stat us of t he st u d y t o t he I R B/I E C a n n uall y or 
m ore fre q u e ntl y i n acc or da nce wit h t he re q uire m e nts, p olicies, a n d pr oce d ures 
esta blis he d b y t h e I R B/I E C . 
- 
N otif yi n g t he 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 st u d y at t he site a n d a d here nce t o 
re q uire me nts of 2 1 C F R, I C H g ui deli nes, t he I R B/I E C, E ur o pea n re g ulati o n 5 3 6/ 2 0 1 4 
f or cli nical st u dies (if a p plica ble), a n d all ot her a p plica ble l ocal r e g ulati o ns. 
1 0. 1. 2  Fi n a n ci al di s cl o s ur e   
I n v esti gat ors a n d s u b-I n v esti gat ors will pr o vi de t he S p o ns or  wit h s ufficie nt, acc urate fi n a ncial 
i nf or mati o n as re q u este d t o all o w t he S p o ns or  t o s u b mit c o m plete a n d acc urate fi na ncial 
certificati o n or discl os ure state me nts t o t he a p pr o priate re g ul at 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 o n fi na ncial i nterests d uri n g t h e c o urse of t he st u d y a n d f or 
1  year after c o m pleti o n of t he st u d y.  
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Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al  
P a g e 6 5  
1 0. 1. 3  I nf or m e d C o n s e nt Pr o c e s s  
 T he I n vesti gat or or his/ h er re prese nt ati ve will e x plai n t he nat ure of t h e st u d y t o t he 
partici pa nt or his/ her le gall y a ut h orize d re pres e nt ati ve a n d a ns w er all q uesti o ns re gar di n g 
t he st u d y. 
 Partici pa nts m ust be i nf or me d t hat t heir partici p ati o n is v ol u ntar y. Partici pa nts or t heir 
le gall y a ut h orize d re pres e ntati ve (if acce pt a ble b y l ocal re g ulati o ns) will be re q uire d t o 
si g n a state m e nt of i nf or me d c o nse nt t hat meets t he re q uir e me nts of 2 1 C F R 5 0, l ocal 
re g ulati o ns, I C H g ui deli nes, Healt h I ns ura nce P orta bilit y a n d Acc o u nta b ilit y Act 
re q uire me nts, w h ere a p plica ble, a n d t he I R B/I E C or st u d y ce nter. 
 T he me dical r ec or d m ust i ncl u de a state me nt t hat writte n i nf or me d c o ns e nt was o btai ne d 
bef ore t h e partici pa nt w as e nr olle d i n t he st u d y a n d t he date t he writte n c o nse nt was 
o btai ne d . T he a ut h orize d pers o n o btai ni n g t h e i nf or me d c o nse nt m ust als o si g n t he I C F. 
 Partici pa nts m ust be re -c o nse nte d t o t he m ost c urre nt versi o n of t he I C F(s) d uri n g t heir 
partici pati o n i n t he st u d y.  
 A c o p y of t he I C F(s) m ust be pr o vi de d t o t he partici pa nt or t he partici pa nt’s le gall y 
a ut h orize d re pres e ntati ve.  
Partici pa nts w h o are rescree ne d are re q uir e d t o si g n a ne w I C F.  
T he I n vesti gat or or a ut h orize d desi g nee will e x plai n t o eac h partici p a nt t he o bjecti ves of t he 
e x pl orat or y researc h. Partici pa nts will be t ol d t hat t he y are free t o ref use t o partici pate a n d m a y 
wit h dra w t heir c o ns e nt at a n y ti me a n d f or a n y reas o n d uri n g t he st ora ge peri o d. A se parate 
si g nat ur e will be re q uir e d t o d oc u me nt a partici pa nt's a gree me nt t o all o w a n y re mai ni n g 
s peci me ns t o be use d f or e x pl orat or y researc h. Partici pa nts w h o decli ne t o partici pate i n t his 
o pti o nal researc h will n ot pr o vi de t his se parat e si g nat ure.  
1 0. 1. 4  D at a Pr ot e cti o n   
All pers o nal data c ollecte d  relate d t o partici pa nts, I n v esti gat ors, or a n y p ers o n i n v ol ve d i n t he 
st u d y, w hic h ma y b e i ncl u de d i n t he S p o ns or’s dat a bases, s hall be treate d i n c o m plia nce wit h all 
a p plica ble la ws a n d re g ul ati o ns i ncl u di n g t he Gl o b al Data Pr otecti o n  Re g ul ati o n.  
Data c o llecte d m ust be a de q uate, rele va nt a n d n ot e x cessi ve, i n relati o n t o t he p ur p oses f or w hic h 
t he y are c ollecte d. Eac h cate g or y of data m ust be pr o perl y j ustifie d a n d i n li ne wit h t he st u d y 
o bjecti ve.  
S u bject race a n d et h nicit y will be c ollecte d i n t his st u d y beca use t hes e data are re q uire d b y s e veral 
re g ulat or y a ge ncies (e g, o n afr o A merica n p o p ulati o n f or t he F D A or o n Ja pa nese p o p ulati o n f or 
t he P har mace uticals a n d Me dical De vices A ge n c y i n J a pa n). 
 Partici pa nts will be assi g ne d a u ni q ue i de ntifier b y t he S p o ns or . A n y p arti ci pa nt rec or ds or 
datasets t hat are tra nsf erre d t o t he S p o ns or  will c o ntai n t he i de ntifier o nl y; partici pa nt 
na mes or a n y i nf or mati o n w hic h w o ul d ma ke t he partici pa nt i de ntifia ble will n ot be 
tra nsferre d. 
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Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al  
P a g e 6 6  
 T he partici pa nt m ust be i nf or m e d t hat his/ her pers o nal st u d y -relate d d ata will be use d b y 
t he S p o ns or  i n acc or da nce wit h l ocal data pr ot ecti o n la w. T he le vel of discl os ure m ust als o 
be e x plai ne d t o t he partici pa nt.  
 T he partici pa nt m ust be i nf or me d t hat his/ her me dical rec or ds ma y be 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 orize d pers o n nel a p p oi nte d b y t he 
S p o ns or , 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. 
 W he n arc hi vi n g or pr ocessi n g pers o nal data pertai ni n g t o t he I n vesti gat or a n d/ or t o t he 
partici pa nts, t he S p o ns or s hall ta ke all a p pr o pri ate meas ures t o safe g uar d a n d pre ve nt 
access t o t his data b y a n y u na ut h orize d t hir d part y.  
1 0. 1. 5  C o m mitt e e s Str u ct ur e   
N ot a p plica ble. 
1 0. 1. 6  Di s s e mi n ati o n of Cli ni c al St u d y D at a   
Sa n ofi s hares i nf or m ati o n a b o ut cli nical trials a n d res ults o n p u blicl y accessi ble we bsites, base d 
o n c o m pa n y c o m mit me nts, i nter n ati o nal a n d l ocal le gal a n d re g ul at or y re q uire me nts, a n d ot her 
cli nical trial discl os ure c o m mit me nts esta blis he d b y p har mace utical i n d ustr y ass ociati o ns.  T hese 
we bsites i ncl u de cli nicaltrials. g o v, E U cli nicaltrialre gister (e u.ctr), a n d sa n ofi.c o m, as well as 
s o me nati o nal re gistries. 
I n a d diti o n, res ults fr o m cli nical trials i n patie nts are re q uire d t o be s u b mitte d t o peer-re vie we d 
j o ur nals f oll o wi n g i nter nal c o m pa n y re vi e w f or acc urac y, fair b ala nce a n d i ntellect ual pr o pert y. 
F or t h ose j o ur n als t hat re q ues t s hari n g of t he a n al yz a ble dat a sets t hat are re p orte d i n t he 
p u blicati o n, i ntereste d researc h ers are dir ecte d t o s u b mit t heir re q uest t o 
cli nicalst u d y dat are q u est.c o m.  
I n di vi d ual partici pa nt dat a a n d s u p p orti n g cli nical d oc u me nts are a vaila ble f or re q u est  at 
cli nicalst u d y dat are q u est.c o m. W hile ma ki n g i nf or mati o n a vaila ble we c o nti n ue t o pr otect t he 
pri vac y of partici pa nts i n o ur cli nical trials.  Details o n data s hari n g criteria a n d pr ocess f or 
re q uesti n g access c a n be f o u n d at t his we b a d dress: cli nicalst u d y datare q uest.c o m . 
1 0. 1. 7  D at a Q u alit y A s s ur a n c e   
 All partici pa nt data relati n g t o t he st u d y will be rec or de d o n pri nte d or electr o nic C R F 
u nless tra ns mitte d t o t he S p o ns or  or desi g n ee el ectr o nicall y (e g, la b orat or y data). T he 
I n v esti gat or is res p o nsi ble f or verif yi n g t hat data e ntries are acc urate a n d c orrect b y 
p h ysicall y or electr o ni call y si g ni n g t he C R F.  
 T he I n vesti gat or m ust mai ntai n acc urate d oc u me ntati o n (s o urce dat a)  t hat s u p p orts t he 
i nf or mati o n e ntere d i n t h e C R F. 
 T he I n vesti gat or m ust per mit st u d y -rel ate d m o nit ori n g, a u dits, I R B/I E C re vie w, a n d 
re g ulat or y a ge nc y i ns pe cti o ns a n d pr o vi de direct access t o s o urce data d oc u me nts. 
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V er si o n n u m b er: 1  
 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al  
P a g e 6 7  
 T he S p o ns or  or desi g nee is res p o nsi ble f or t he dat a ma na ge m e nt of t his st u d y i ncl u di n g 
q ualit y c h ec ki n g of t he d ata.  
 St u d y m o nit ors will perf or m o n g oi n g s o urce data verificati o n t o c o nfir m t hat data e ntere d 
i nt o t he C R F b y a ut h orize 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 m e nts; t hat t he safet y a n d ri g hts of partici pa nts are b ei n g pr otecte d; a n d t hat 
t he st u d y 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 st u d y a gree me nts, I C H G C P, a n d all a p plica ble re g ulat or y re q uire m e nts.  
 Rec or ds a n d d o c u me nts, i ncl u di n g si g n e d I C Fs, p ertai ni n g t o t he c o n d uct of t his st u d y 
m ust be retai ne d b y t he I n vesti gat or f or 2 5 years after t he e n d of t he cli nical st u d y u nless 
l ocal re g ulati o ns or i nstit uti o nal p olicies re q uire a l o n ger rete nti o n peri o d. N o rec or ds ma y 
be destr o ye d d uri n g t he rete nti o n peri o d wit h o ut t he writte n a p pr o val of t h e S p o ns or . N o 
rec or ds ma y b e tra nsferre d t o a n ot her l ocati o n or p art y wit h o ut writte n n otificati o n t o t he 
S p o ns or . 
1 0. 1. 8  S o ur c e d o c u m e nt s   
 S o urce d oc u me nts pr o vi d e e vi de nce f or t h e e xiste nce of t he p artici pa nt a n d s u bsta ntiate 
t he i nte grit y of t h e data c ollecte d. S o urce d o c u me nts are file d at t he I n vesti gat or’s site. 
 Data re p orte d o n t he C R F or e n tere d i n t he e C R F t hat are tr a nscri be d fr o m s o urce 
d oc u me nts m ust be c o nsiste nt wit h t he s o urce d oc u me nts or t he discre p a ncies m ust be 
e x plai ne d. T he I n vesti gat or ma y n ee d t o r e q uest pr e vi o us me dical rec or ds or tra nsfer 
rec or ds, d e pe n di n g o n t h e st u d y. Also, c urre nt me dical rec or ds m ust be a vaila ble.  
 Defi niti o n of w hat c o nstit utes s o urce data ca n b e f o u n d i n St u d y R efere nce Ma n ual . 
1 0. 1. 9  St u d y a n d Sit e Cl o s ur e   
T he S p o ns or  or desi g nee re ser ves t he ri g ht t o cl ose t he st u d y site or ter mi nate t he st u d y at a n y 
ti me f or a n y reas o n at t he s ole discreti o n of t he S p o ns or . St u d y sites will be cl ose d u p o n st u d y 
c o m pleti o n. A st u d y site is c o nsi dere d cl ose d w he n all re q uire d d o c u me nts a n d st u d y s u p p lies 
ha ve bee n c ollecte d a n d a st u d y site cl os ur e visit has bee n perf or m e d. 
T he I n vesti gat or ma y i nitiate st u d y  site cl os ur e at a n y ti me, pr o vi d e d t here is reas o na ble ca use a n d 
s ufficie nt n otice is gi ve n i n a d va nce of t he i nte n de d ter mi nati o n. 
Reas o ns f or t he earl y cl os ure of a st u d y site b y t he S p o ns or  or I n v esti gat or ma y i ncl u d e b ut are 
n ot li mite d t o:  
 Fail ure of t he I n vesti gat or t o c o m pl y wit h t he pr ot oc ol, t he re q uir e me nts of t he I R B/I E C or 
l ocal healt h a ut h orities, t he S p o ns or 's pr oce d ures, or G C P g ui deli nes . 
 I n a de q uat e recr uit me nt of partici pa nts b y t he I n v esti gat or. 
 Disc o nti n uati o n of f urt her st u d y i nter ve nti o n de vel o p me nt . 
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Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al  
P a g e 6 8  
1 0. 1. 1 0  
P u bli c ati o n P oli c y   
 T he res ults of t his st u d y ma y b e p u blis he d or pres e nte d at scie ntific meeti n gs. If t his is 
f oresee n, t he I n v esti gat or a grees t o s u b mit all ma n uscri pts or a bstracts t o t he S p o ns or  
bef ore s u b missi o n. T his all o ws t he S p o ns or  t o pr otect pr o prietar y i nf or mati o n a n d t o 
pr o vi de c o m m e nts.  
 T he S p o ns or  will c o m pl y wit h t he re q uire me nts f or p u blicati o n of st u d y res ults. I n 
acc or da nce wit h sta n dar d e dit orial a n d et hical pr actice, t he S p o ns or  will ge n erall y s u p p ort 
p u blicati o n of m ultice nter st u dies o nl y i n t heir e ntiret y a n d n ot as i n di vi d ual site data. I n 
t his case, a c o or di nati n g I n v esti gat or will be desi g nate d b y m ut ual a gree me nt.  
 A ut h ors hi p will be deter mi ne d b y m ut ual a gree m e nt a n d i n li ne wit h I nt er nati o nal 
C o m mittee of Me dical J o ur nal E dit ors a ut h ors hi p re q uire me nts.  
1 0. 2  
A P P E N DI X 2: C LI NI C A L L A B O R A T O R Y T E S T S   
 Uri ne h u ma n c h ori o nic g o na d otr o pi n pre g na n c y test (as nee de d f or w o m e n of c hil d beari n g 
p ote ntial) will be perf or me d b y t he l o cal la b orat or y.  
 T he l ocal  la b orat or y res ults use d t o ma ke a st u d y i nter ve nti o n decisi o n or res p o nse 
e val uati o n m ust be e ntere d i nt o t he C R F . 
 Pr ot oc ol -s pecific re q uire me nts f or i ncl usi o n or e x cl usi o n of partici pa nts are detaile d i n 
Secti o n  5  of t he pr ot oc ol.  
 A d diti o nal tests ma y be p erf or me d at a n y ti me d uri n g t he st u d y as d eter mi ne d necessar y 
b y t he I n vesti gat or or re q uire d b y l o cal r e g ulati o ns.  
I n v esti gat ors m ust d oc u me nt t heir re vie w of eac h la b orat or y safet y re p ort. 
La b orat or y/a n al yt e res ults  t hat c o ul d u n bli n d t he st u d y will n ot be re p orte d t o i n vesti gati ve sites 
or ot her bli n de d pers o n n el u ntil t he st u d y h as bee n u n bli n de d . 
1 0. 3  
A P P E N DI X 3: A D V E R S E E V E N T S: D E FI NI TI O N S A N D P R O C E D U R E S F O R 
R E C O R DI N G, E V A L U A TI N G, F O L L O W -U P, A N D R E P O R TI N G   
D E FI NI TI O N O F A E  
A E defi niti o n  
 A n A E is a n y u nt o war d me dical occ urre n ce i n a patie nt or cli nical st u d y p artici pa nt, 
te m p orall y ass ociate d wit h t he use of st u d y i nter ve nti o n, w het her or n ot c o nsi dere d rel ate d 
t o t he st u d y i nter ve nti o n. 
 N ote : A n A E ca n t heref ore be a n y u nfa v ora ble a n d u ni nte n de d si g n (i n cl u di n g a n 
a b n or mal la b orat or y fi n di n g), s y m pt o m, or diseas e ( ne w or e x acer bate d) t e m p orall y 
ass ociate d wit h t he use of st u d y i nter ve nti o n. 
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7 -A pr -2 0 2 0  
V er si o n n u m b er: 1  
 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al  
P a g e 6 9  
E ve nts meeti n g  t he A E defi niti o n 
 A n y a b n or mal la b orat or y test res ults ( he mat ol o g y, cli nical c he mistr y, or uri nal ysis) or 
ot her safet y assess me nts (e g, electr ocar di o gra m [ E C G ], ra di ol o gical sc a ns, vital si g ns 
meas ure me nts), i n cl u di n g t h ose  t hat w orse n fr o m baseli ne, c o nsi dere d cli ni call y 
si g nifica nt i n t he me dic al a n d scie ntific j u d g me nt of t he I n vesti gat or (i e, n ot relate d t o 
pr o gressi o n of u n derl yi n g diseas e).  
 E x acer bati o n of a c hr o ni c or i nter mitte nt pre -e xisti n g c o n diti o n i ncl u di n g eit h er a n 
i ncreas e i n fre q u e nc y a n d/ or i nte nsit y of t he c o n diti o n. 
 Ne w c o n diti o ns detect e d or dia g n os e d after st u d y i nter ve nti o n a d mi nistrati o n e ve n t h o u g h 
it ma y ha v e bee n prese nt bef ore t h e start of t he st u d y. 
 Si g ns, s y m pt o ms, or t he cli nical se q uelae of a s us pecte d dr u g -dr u g i nteracti o n.  
 Si g ns, s y m pt o ms, or t he cli nical se q uelae of a s us pecte d o ver d ose of eit her st u d y 
i nter ve nti o n or a c o n c o mita nt me dicati o n.  
 " Lac k of effic ac y" or "fail ure of e x pecte d p har mac ol o gical acti o n" p er se will n ot be 
re p orte d as a n A E or S A E. S uc h i nsta nces will be ca pt ure d i n t he efficac y assess me nts. 
H o we ver, t he si g ns, s y m pt o ms, a n d/ or cli nical se q uelae res ulti n g fr o m lac k of efficac y 
will be re p orte d as A E or S A E if t he y f ulfil t he defi niti o n of a n A E or S A E.  
 T he si g ns, s y m pt o m s, a n d/ or cli nical se q uelae res ulti n g fr o m lac k of efficac y will be 
re p orte d as A E or S A E if t he y f ulfil t he defi niti o n of a n A E or S A E. Als o, "lac k of 
effic ac y" or "fail ure of e x pecte d p har mac ol o gical acti o n" als o c o nstit utes a n A E or S A E.  
E ve nts N O T meet i n g t he A E defi niti o n 
 A n y cli nicall y si g nifica nt a b n or mal la b orat or y fi n di n gs or ot her a b n or mal s afet y 
assess me nts w hic h are ass ociate d wit h t he u n derl yi n g diseas e, u nless j u d ge d b y t he 
I n v esti gat or t o be m ore s e vere t h a n e x pecte d f or t he partici pa nt’s c o nditi o n.  
 T he disease/ dis or der bei n g st u die d or e x pecte d pr o gressi o n, si g ns, or s y m pt o ms of t he 
disease/ dis or der bei n g st u die d, u nless m ore se vere t ha n e x pecte d f or t he p artici pa nt’s 
c o n diti o n.  
 Me dical or s ur gic al pr oce d ure (e g, e n d osc o p y, a p pe n dect o m y): t he  c o n diti o n t hat lea ds t o 
t he pr oce d ure is t he A E. 
 Sit uati o ns i n w hic h a n u nt o war d me dical o cc urre n ce di d n ot occ ur (s ocial a n d/ or 
c o n ve nie nce a d missi o n t o a h os pital).  
 A ntici pate d da y -t o-d a y fl uct uati o ns of pre -e xisti n g disease(s) or c o n diti o n(s) prese nt o r 
detecte d at t he start of t h e st u d y t hat d o n ot w ors e n . 
D E FI NI TI O N O F S A E  
If a n e v e nt is n ot a n A E per defi niti o n a b o ve, t h e n it ca n n ot be a n S A E e v e n if seri o us c o n diti o ns 
are met (e g, h os pitaliz ati o n f or si g ns/s y m pt o ms of t he disease u n der st u d y, deat h d ue t o 
pr o gressi o n of diseas e).  
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Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al  
P a g e 7 0  
A S A E is defi ne d as a n y u nt o w ar d me dic al occ urre nce t h at, at a n y d ose:  
A)  Res ults i n de at h  
a)  Is lif e-t hre ate ni n g 
T he ter m “ life-t hreate ni n g” i n t he d efi niti o n of “seri o us” refers t o a n e ve nt i n w hic h t he 
partici pa nt was at ris k of deat h at t he ti me of t he e ve nt. It d o es n ot refer t o a n e ve nt, w hic h 
h y p ot hetic all y mi g ht ha v e ca use d d eat h, if it were m ore se vere.  
b)  Re q uires i n p atie nt h os pit aliz ati o n or pr ol o n g ati o n of e xisti n g h os pit aliz ati o n  
I n ge neral, h os pitalizati o n si g nifies t hat t he partici pa nt has bee n d etai ne d ( us uall y 
i n v ol vi n g at least a n o v er ni g ht sta y) at t he h os pital or e mer ge nc y war d f or o bser vati o n 
a n d/ or treat me nt t hat w o ul d n ot ha ve bee n a p pr o priate i n t he p h ysicia n’s office or 
o ut patie nt setti n g. C o m plicati o ns t hat occ ur d uri n g h os pitalizati o n are A Es. If a 
c o m plicati o n pr ol o n gs h os pitalizati o n or f ulfills a n y ot her s eri o us criteria, t he e ve nt is 
seri o us. W he n i n d o u bt as t o w het her “ h os pitalizati o n” occ urre d or was necessar y, t he A E 
s h o ul d be c o nsi dere d s eri o us. 
H os pitalizati o n f or electi ve treat me nt of a pre -e xisti n g c o n diti o n t hat di d n ot w orse n fr o m 
baseli ne is n ot c o nsi dere d a n A E.  
c)  Res ults i n persiste nt dis a bilit y/i nc a p acit y  
- 
T he ter m disa bilit y me a ns a s u bst a ntial disr u pti o n of a pers o n’s a bilit y t o c o n d uct 
n or mal life f u ncti o ns.  
- 
T his defi niti o n is n ot i nte n de d t o i ncl u de e x perie n ces of relati vel y mi n or me dical 
si g nifica n ce s uc h as u nc o m plicate d hea dac he, n a usea, v o miti n g, diarr hea, i nfl ue nza, 
a n d acci de ntal tra u ma (e g, s prai ne d a n kle) w hic h ma y i nterfere wit h or pre ve nt 
e ver y da y life f u ncti o ns b ut d o n ot c o nstit ute a s u bsta ntial disr u pti o n.  
d)  Is a c o n ge nit al a n o m al y/ birt h defect 
e)  Ot her sit u ati o ns:  
- 
Me dical or scie ntifi c j u d g me nt s h o ul d be e x ercise d i n deci di n g w het her S A E re p orti n g 
is a p pr o priate i n ot her sit uati o ns s uc h as i m p orta nt me dical 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 pitalizati o n b ut ma y je o par dize 
the partici pa nt or ma y re q uire me dical or s ur gical i nter ve nti o n t o pre ve nt 1 of t he ot her 
o utc o mes liste d i n t he a b o ve defi niti o n. T hese e v e nts s h o ul d us uall y b e c o nsi dere d 
seri o us. 
E x a m ples of s uc h e ve nts i ncl u de i n vasi ve or mali g na nt ca ncers, i nte nsi ve tr eat me nt i n 
a n e mer ge nc y r o o m  or at h o me f or aller gi c br o nc h o s pas m, bl o o d d yscrasias or 
c o n v ulsi o ns t hat d o n ot res ult i n h os pitalizati o n, or de vel o p me nt of dr u g d e pe n de nc y 
or dr u g a b use.  
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V er si o n n u m b er: 1  
 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al  
P a g e 7 1  
R E C O R DI N G A N D F O L L O W -U P O F A E A N D/ O R S A E  
A E a n d S A E r ec or di n g 
 W he n a n A E/ S A E occ urs, it is t he res p o nsi bilit y of t he I n v esti gat or t o re vi e w all 
d oc u me ntati o n (e g, h os pital pr o gress n otes, la b orat or y re p orts, a n d dia g n ostics re p orts) 
relate d t o t he e v e nt. 
 T he I n vesti gat or will t he n rec or d all rele va nt A E/ S A E i nf or mati o n i n t h e C R F.  
 It is n ot  acce pta bl e f or t h e I n vesti gat or t o se n d p h ot oc o pies of t he partici p a nt’s me dical 
rec or ds t o S p o ns or  i n lie u of c o m pleti o n of t he A E/ S A E C R F pa ge. 
 T here ma y b e i nsta nces w he n c o pies of m e dical r ec or ds f or certai n cas es are re q u este d b y 
S p o n s or. I n t his cas e, all partici pa nt i de ntifiers, wit h t he e x ce pti o n of t he partici pa nt 
n u m ber, will be re d acte d o n t he c o pies of t he me di cal rec or ds bef ore s u b missi o n t o 
S p o ns or . 
 T he I n vesti gat or will att e m pt t o esta blis h a dia g n osis of t he e ve nt base d o n si g ns, 
s y m pt o ms, a n d/ or ot her cli nical i nf or mati o n. W he ne ver p ossi ble, t he dia g n osis ( n ot t he 
i n di vi d ual si g ns/s y m pt o ms) will be d oc u me nte d as t he A E/ S A E. 
Assess me nt of i nte nsit y  
T he I n vesti gat or will ma ke a n assess me nt of i nte nsit y f or eac h A E a n d S A E re p orte d d uri n g t h e 
st u d y a n d assi g n it t o 1 of t he f oll o wi n g cate g ories: 
 Mil d: A n e ve nt t hat is easil y t olerate d b y t h e parti ci pa nt, ca usi n g mi ni mal disc o mf ort a n d 
n ot i nterferi n g wit h e ver y d a y acti vities.  
 M o derate: A n e ve nt t hat ca uses s ufficie nt disc o mf ort  a n d i nterferes wit h n or mal e ver y d a y 
acti vities.  
 Se vere: A n e v e nt t hat pre ve nts n or mal e ver y d a y acti vities. A n A E t hat is assesse d as 
se vere s h o ul d n ot be c o nf use d wit h a S A E. Se vere is a cate g or y utilize d f or rati n g t he 
i nte nsit y of a n e ve nt; a n d b ot h A Es a n d S A Es ca n be assesse d as se vere.  
A n e ve nt is defi ne d as “ s eri o us” w he n it meets at least 1 of t he pre defi n e d o utc o mes as descri be d 
i n t he defi niti o n of a n S A E, N O T w he n it is rate d as se vere. 
Assess me nt of c a us alit y  
 T he I n vesti gat or is o bli gate d t o assess t he relati o ns hi p bet wee n st u d y i nter ve nti o n a n d 
eac h o cc urre nce of eac h A E/ S A E.  
 A "reas o na bl e p ossi bilit y" of a relati o ns hi p c o n ve ys t hat t here are facts, e vi de nce, a n d/ or 
ar g u me nts t o s u g gest a ca usal relati o ns hi p, rat h er t ha n a re lati o ns hi p ca n n ot be r ule d o ut. 
 T he I n vesti gat or will use cli nical j u d g me nt t o deter mi ne t he relati o ns hi p.  
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V er si o n n u m b er: 1  
 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al  
P a g e 7 2  
 Alter nati ve ca uses, s uc h as u n derl yi n g disease(s), c o nc o mita nt t hera p y, a n d ot her ris k 
fact ors, as well as t he te m p oral relati o ns hi p of t h e e ve nt t o st u d y i nter ve nti o n 
a d mi nistrati o n will be c o nsi dere d a n d i n vesti gate d.  
 T he I n vesti gat or will als o c o ns u lt t he I B a n d/ or Pr o d uct I nf or m ati o n, f or mar kete d 
pr o d ucts, i n his/ her assess me nt.  
 F or eac h A E/ S A E, t he I n vesti gat or m ust  d oc u me nt i n t he me dical n otes t hat he/s he has 
re vie we d t h e A E/ S A E a n d has pr o vi de d a n assess me nt of ca usalit y. 
 T here ma y b e sit uati o ns i n w hic h a n S A E has occ urre d , a n d t h e I n vesti gat or has mi ni mal 
i nf or mati o n t o i ncl u de i n t he i nitial re p ort t o S p o ns or . H o we v er, it is ver y i m p ort a nt th at 
t he I n vesti g at or al w a ys m a ke a n assess me nt of c a us alit y f or e ver y e ve nt bef ore t he 
i niti al tr a ns missi o n of t he S A E d at a t o S p o ns or . 
 T he I n vesti gat or ma y c ha n ge his/ her o pi ni o n of ca usalit y i n li g ht of f oll o w -u p i nf or mati o n 
a n d se n d a S A E f oll o w -u p re p o rt wit h t he u p date d ca usalit y assess me nt. 
 T he ca us alit y ass ess me nt is 1 of t he criteria us e d w he n deter mi ni n g re g ul at or y re p orti n g 
re q uire me nts. 
F oll o w -u p of A Es a n d S A Es  
 T he I n vesti gat or is o bli gate d t o perf or m or arra n ge f or t he c o n d uct of s u p ple me ntal 
me as ure me nts a n d/ or e val uati o ns as me dicall y i n dicate d or as re q uest e d b y S p o ns or  t o 
el uci date t he nat ure a n d/ or ca usalit y of t he A E or S A E as f ull y as p ossi ble. T his ma y 
i ncl u de a d diti o nal la b orat or y tests or i n v esti gati o ns, hist o pat h ol o gical e xa mi nati o ns, or 
c o ns ultati o n wit h ot her healt h care pr ofessi o nals.  
 If a partici pa nt dies d uri n g partici pati o n i n t he st u d y or d uri n g a rec o g nize d f oll o w-u p 
peri o d, t he I n vesti gat or will pr o vi de S p o ns or wit h a c o p y of a n y p ost -m orte m fi n di n gs 
i ncl u di n g hist o pat h ol o g y. 
 Ne w or u p d ate d i nf or mati o n will be rec or de d i n t he ori gi n all y c o m plete d C R F.  
 T he I n vesti gat or will s u b mit a n y u p date d S A E d ata t o t he S p o ns or  wit hi n 2 4 h o urs of 
recei pt of t h e i nf or mati o n. 
R E P O R TI N G O F S A E S  
S A E re p orti n g t o S p o ns or  vi a a n electr o nic d at a c ollecti o n t o ol  
 T he pri mar y me c ha nis m f or re p orti n g a n S A E t o S p o ns or  will be t he electr o nic data 
c ollecti o n t o ol.  
 If t he ele ctr o nic s yste m is u na vaila ble f or m ore t h a n 2 4 h o urs, t he n t he site will use t he 
pa per S A E dat a c ollecti o n t o ol (see ne xt secti o n).  
 T he site will e nter t he S A E data i nt o t he electr o nic s yste m as s o o n as it bec o mes a vaila ble.  
 After t he st u d y is c o m plete d at a gi ve n site, t he el ectr o nic data c ollecti o n t o ol will be ta ke n 
off -li ne t o pre v e nt t he e ntr y of ne w data or c ha n ges t o e xisti n g data. 
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Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al  
P a g e 7 3  
 If a site recei v es a re p ort of a ne w S A E fr o m a st u d y partici pa nt or recei v es u p date d data 
o n a pre vi o usl y re p orte d S A E after t he electr o ni c data c ollecti o n t o ol has b ee n ta ke n off -
li ne, t he n t he site ca n re p ort t his i nf or mati o n o n a pa per S A E f or m (see n e xt secti o n) or t o 
t he [me dical m o nit or/ S A E c o or di nat or ] b y t ele p h o ne.  
 C o ntacts f or S A E re p orti n g ca n be f o u n d i n  St u d y Refere n ce M a n ual . 
S A E re p orti n g t o S p o ns or  vi a p a per C R F  
 Facsi mile tra ns missi o n of t he S A E pa per C R F is t he preferre d met h o d t o  re p ort t he S A Es 
w he n t he ele ctr o nic s yste m is u na vaila ble f or m ore t ha n 2 4 h o urs or w h e n t he electr o ni c 
s yste m has b ee n ta ke n off-li ne. T he g ui deli nes f or re p orti n g S A Es via pa per C R F will be 
pr o vi de d i n t he St u d y Refere n ce Ma n u al . 
 I n rare cir c u msta nces a nd i n t he a bse nce of facsi mile e q ui p me nt, n otificati o n b y tele p h o n e 
is acce pta bl e wit h a c o p y of t he S A E data c ollecti o n t o ol se nt b y o ver ni g ht mail or c o urier 
ser vice. 
 I nitial n otificati o n via tel e p h o ne d oes n ot re place t he nee d f or t he I n v esti gat or t o c o mplete 
a n d si g n t he S A E C R F p a ges wit hi n t he desi g nate d re p orti n g ti me fra m es.  
 C o ntacts f or S A E re p orti n g ca n be f o u n d i n St u d y Refere n ce M a n ual.  
1 0. 4  
A P P E N DI X 4: C O N T R A C E P TI V E G UI D A N C E A N D C O L L E C TI O N O F  P R E G N A N C Y 
I N F O R M A TI O N  
D E FI NI TI O N S:  
W o m a n of c hil d be ari n g p ote nti al ( W O C B P)  
A w o ma n is c o nsi dere d fertile f oll o wi n g m e narc h e a n d u ntil bec o mi n g p ost me n o pa usal u nless 
per ma ne ntl y sterile (see bel o w).  
W o me n i n t he f oll o wi n g c ate g ori es are n ot c o nsi dere d W O C B P  
1.  Pre me narc hal  
2.  Pre me n o pa usal f e male wit h 1 of t he f oll o wi n g:  
- 
D oc u me nte d h ysterect o m y  
- 
D oc u me nte d bilateral sal pi n gect o m y  
- 
D oc u me nte d bilateral o o p h orect o m y  
N ote: D oc u me ntati o n ca n c o me fr o m t he site pers o n nel’s: re vie w of t he partici pa nt’s 
me dical rec or ds, me dic al e x a mi nati o n, or me dical hist or y i nter vie w.  
3.  P ost me n o pa usal fe male  
- 
A p ost me n o pa usal state is defi ne d as n o me ns es f or 1 2 m o nt hs wit h o ut a n alter nati ve  
me dical ca us e. A hi g h F S H le vel i n t he p ost me n o pa usal ra n ge ma y be u se d t o c o nfir m 
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V er si o n n u m b er: 1  
 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al  
P a g e 7 4  
a p ost me n o pa usal state i n w o me n n ot usi n g h or m o nal c o ntrace pti o n or h or m o nal 
re place me nt t hera p y ( H R T). H o we v er, i n t he a bs e nce of 1 2 m o nt hs of a me n orr hea, a 
si n gle F S H meas ur e me nt is i ns ufficie nt.  
- 
Fe males o n H R T a n d w h ose me n o pa usal stat us  is i n d o u bt will be re q uire d t o use 1 of 
t he n o n-estr o ge n h or m o nal hi g hl y effecti ve c o ntrace pti o n met h o ds if t he y wis h t o 
c o nti n ue t heir H R T d uri n g t he st u d y. Ot her wise, t he y m ust disc o nti n ue H R T t o all o w 
c o nfir mati o n of p ost me n o pa usal stat us bef ore st u d y e nr oll me nt.  
C O N T R A C E P TI O N G UI D A N C E  
Fe m ale p artici p a nts  
Fe male p artici pa nts of c hil d beari n g p ot e ntial are eli gi ble t o partici pate if t h e y a gree t o use a 
hi g hl y effecti ve m et h o d of c o ntrace pti o n c o nsiste ntl y a n d c orrectl y as descri be d i n Ta ble  6 . 
I n a d diti o n, W O C B P m ust refrai n fr o m d o nati n g o va f or t he d urati o n of t h e st u d y a n d f or 
1 2  wee ks after t he last d ose of st u d y i nter ve nti o n.  
T a bl e  6  - Hi g hl y eff e cti v e c o ntr a c e pti v e m et h o d s   
Hi g hl y eff e cti v e c o ntr a c e pti v e m et h o d s t h at ar e u s er d e p e n d e nt a  
F ail ur e r at e of < 1 % p er y e ar w h e n u s e d c o n si st e ntl y a n d c orr e ctl y.  
C o m bi n e d ( estr o g e n a n d pr o g est o g e n c o nt ai ni n g) h or m o n al c o ntr ac e pti o n ass oci at e d wit h i n hi biti o n of ov ul ati o n b  
 
Or al  
 
I ntr av a gi n al  
 
Tr a ns d er m al  
Pr o g est o g e n o nly h or m o n al c o ntr ac e pti o n ass oci at e d wit h i n hi biti o n of ov ul ati o n  
 
Or al  
 
I nj ect a bl e 
Hi g hl y eff e cti v e m et h o d s t h at ar e u s er i n d e p e n d e nt a 
I m pl a nt a bl e pr o g est o g e n o nly h or m o n al c o ntr ac e pti o n ass oci at e d wit h i n hi biti o n of ov ul ati o nb 
 
I ntr a ut eri n e d evic e (I U D) 
 
I ntr a ut eri n e h or m o n e-r el e asi n g syst e m (I U S) 
 
Bil at er al t u b al occl usi o n  
V a s e ct o mi z e d p art n er  
A v as ect o miz e d p art n er is a hi g hly eff ectiv e c o ntr ac e pti o n m et h o d pr ovi d e d t h at t h e p art n er is t h e s ol e m al e s ex u al p art n er o f 
t h e W O C B P a n d t h e a bs e nc e of s p er m h as b e e n c o nfir m e d. If n ot, a n a d diti o n al hi g hly eff ectiv e m et h o d of c o ntr ac e pti o n 
s h o ul d b e us e d. 
V V- C LI N- 0 5 5 0 3 9 6 4. 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol 0 2  
L P S 1 5 4 9 7  
7 -A pr -2 0 2 0  
V er si o n n u m b er: 1  
 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al  
P a g e 7 5  
S e x u al a b sti n e n c e  
S ex u al a bsti n e nc e is c o nsi d er e d a hi g hly eff ectiv e m et h o d o nly if d efi n e d as r efr ai ni n g fr o m h et er os e x u al i nt erc o urs e d uri n g t h e 
e ntir e p eri o d of risk ass oci at e d wit h t h e st u dy i nt erv e nti o n. T h e r eli a bility of s ex u al a bsti n e nc e n e e ds t o b e ev al u at e d i n r el ati o n 
t o t h e d ur ati o n of t h e st u dy a n d t h e pr ef err e d a n d us u al lif estyl e of t h e p artici p a nt. 
N O T E S:  
a  Ty pic al us e f ail ure rat es m ay diff er fr o m t h os e w h e n us e d c o nsist e ntly a n d c orrectly. Us e s h o ul d b e c o nsist e nt wit h l oc al r e g ul ati o ns 
re gardi n g t h e us e of c o ntrac e ptiv e m et h o ds f or p artici p a nts p artici p ati n g i n cli nic al st u di es.  
b  Hor m o nal c o ntr ac e pti o n m a y b e s usc e pti bl e t o i nt er acti o n wit h t h e st u dy i nt erv e nti o n, w hic h m ay r e d uc e t h e effic acy of t h e c o ntr ac e ptiv e 
m et h od. I n t his c as e, 2 hi g hly eff ectiv e m et h o ds of c o ntrac e pti o n s h o ul d b e utiliz e d d uri n g t h e i nt erv e nti o n p eri o d a n d f or at l e ast [ X, 
c orres po n di n g t o ti m e n e e d e d t o eli mi n at e st u dy i nt erv e nti o n pl us 3 0 d ays f or st u dy i nt erv e nti o ns wit h g e n ot oxic p ot e nti al] aft er t h e l ast 
d os e of st u dy i nt erv e nti o n . 
 
P R E G N A N C Y T E S TI N G:  
 W O C B P s h o ul d o nl y b e i ncl u de d after a c o nfir me d me nstr ual peri o d a n d a ne gati ve hi g hl y 
se nsiti ve uri ne pre g n a nc y test.  
 Sta n dar d uri ne p re g na nc y testi n g will be perf or m e d f or W O C B P partici pa nts t hr o u g h o ut 
t he st u d y (s ee st u d y S O A Secti o n  1. 3 ). 
 Pre g n a nc y testi n g will als o be perf or me d w he n e v er a me nstr ual c ycle is misse d or w he n 
pre g na nc y is ot her wis e s us pecte d.  
C O L L E C TI O N O F P R E G N A N C Y I N F O R M A TI O N:  
M ale p artici p a nts wit h p art ners w h o bec o me pre g n a nt  
 T he I n vesti gat or will atte m pt t o c ollect pre g na nc y i nf or mati o n o n a n y male partici pa nt’s 
fe male part ner w h o b ec o mes pre g na nt w hile t he male partici pa nt is i n t his st u d y. T his 
a p plies o nl y t o male p artici pa nts w h o re cei ve st u d y i nter ve nti o n. 
 After o btai ni n g t he necessar y si g n e d i nf or me d c o nse nt fr o m t he pre g n a nt fe male part ner 
directl y, t h e I n vesti gat or will rec or d pre g na nc y i nf or mati o n o n t he a p pr o pri ate  f or m a n d 
s u b mit it t o t he S p o ns or wit hi n 2 4 h o urs  of lear ni n g of t he part ner’s pre g n a nc y. T he 
fe male part ner will als o b e f oll o we d t o deter mi ne t he o utc o me of t he pre g na nc y. 
I nf or mati o n o n t he stat us of t he m ot her a n d c hil d will be f or war de d t o t he S p o ns or. 
Ge nerall y, t he f oll o w -u p will be n o l o n ger t h a n 6 t o 8  wee ks f oll o wi n g t he esti mate d 
deli ver y date. A n y t er mi nati o n of t he pre g n a nc y will be re p orte d re gar dless of fetal stat us 
( prese n ce or a bse nce of a n o malies) or i n dicati o n f or t he pr oce d ure.  
Fe m ale p artici p a nts w h o bec o me pre g n a nt  
 T he I n vesti gat or will c oll ect pre g n a nc y i nf or m ati o n o n a n y fe male p artici pa nt w h o 
bec o mes pre g na nt w hile partici pati n g i n t his st u d y. I nf or mati o n will be rec or de d o n t he 
a p pr o priate f or m a n d s u b mitte d t o t he S p o ns or wit hi n  2 4 h o urs  of lear ni n g of a 
partici pa nt's pre g n a nc y. T he partici pa nt will be f oll o we d t o deter mi ne t he o utc o me of t he 
pre g na nc y. T he I n v esti gat or will c ollect f oll o w -u p i nf or mati o n o n t he partici pa nt a n d t he 
ne o nate a n d t h e i nf or mati o n will be f or war de d t o t he S p o ns or. Ge nerall y, f oll o w-u p will 
V V- C LI N- 0 5 5 0 3 9 6 4. 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol 0 2  
L P S 1 5 4 9 7  
7 -A pr -2 0 2 0  
V er si o n n u m b er: 1  
 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al  
P a g e 7 6  
n ot be re q uire d f or l o n ger t ha n 6 t o 8 wee ks b e y o n d t he esti mate d deli ver y date. A n y 
ter mi nati o n of pre g na n c y will be re p orte d, re gar dless of fetal stat us ( prese n ce or a bs e nce 
of a n o malies) or i n dicati o n f or t he pr oce d ure.  
 A n y pre g na n c y c o m plicati o n or electi ve ter mi nati o n of a pre g n a nc y will be re p orte d as a n 
A E or S A E. A s p o nta ne o us a b orti o n is al wa ys c o nsi dere d t o be a n S A E a n d will be 
re p orte d as s uc h. A n y p ost-st u d y pre g n a nc y relate d S A E c o nsi dere d reas o n a bl y relate d t o 
t he st u d y i nter ve nti o n b y t he I n v esti gat or will be re p orte d t o t he S p o ns or as descri be d i n 
Secti o n  8. 3. 5 . W hile t he I n v esti gat or is n ot o bli gate d t o acti vel y s ee k t his i nf or mati o n i n 
f or mer st u d y partici pa nts, he or s he ma y lear n of a n S A E t hr o u g h s p o nta n e o us re p orti n g.  
 A n y fe male p artici pa nt w h o bec o mes pre g na nt w hile partici pati n g i n t he st u d y will 
disc o nti n ue st u d y i nter ve nti o n  a n d be wit h dra w n fr o m t he st u d y . 
1 0. 5  
A P P E N DI X 5 : D E FI NI TI O N O F A N A P H Y L A XI S    
“ A na p h yla xis is a seri o us aller gic reacti o n t hat is ra pi d i n o nset a n d ma y ca use deat h." 
Cli nical criteria f or di a g n osi n g a na p h yl a xis  
 
1 0. 6  
A P P E N DI X 6 : C O U N T R Y -S P E CI FI C R E Q UI R E M E N T S   
N ot a p pl ica ble. 
1 0. 7  
A P P E N DI X 7 : AB B R E VI A TI O N S   
 
A A S M:  
A merica n A ca d e m y of Slee p Me dici ne  
A C Q:  
ast h ma c o ntr ol q uesti o n naire  
A D:  
at o pic der matitis  
A D Rs : 
a d verse dr u g reacti o ns  
A E : 
a d verse e ve nts  
A E SI:  
a d verse e ve nt of s p ecial i nterest  
V V- C LI N- 0 5 5 0 3 9 6 4. 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol 0 2  
L P S 1 5 4 9 7  
7 -A pr -2 0 2 0  
V er si o n n u m b er: 1  
 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al  
P a g e 7 7  
A N A M:  
a ut o mate d ne ur o ps yc h ol o gical assess me nt metrics  
A R -V A S:  
aller gic r hi nitis -vis ual a n al o g scale  
A Z A:  
azat hi o pri ne 
B S A:  
b o d y s urface area  
CI O M S:  
C o u ncil f or I nter nat i o nal Or ga nizati o ns of Me dical Scie nces 
C R Fs:  
case re p ort f or ms  
Cs A:  
s yste mic c ycl os p ori ne A 
D T P:  
Direct T o Patie nt  
E A SI:  
ecze ma area s e verit 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  
F S H:  
f ollicle sti m ulati n g h or m o ne 
G S O : 
Gl o bal safe t y officer 
H A D S:  
h os pital a n xiet y a n d d e pressi o n scale  
H b A 1c:  
he m o gl o bi n A 1c  
I B: 
I n v esti gat or's Br oc h ure 
I C F: 
i nf or me d c o nse nt f or m 
I E C: 
I n d e pe n de nt Et hics C o m mitees 
I g-4 : 
i m m u n o gl u b uli n-G 4  
I G A: 
I n v esti gat or's gl o bal assess me nt 
I L 4 R α: 
I L-4 rece pt or al p ha  
I L 4 R α/γ c: 
I L-4 si g n ali n g vi a t he T y pe I rece pt or  
I L-1 3 : 
i nterle u ki n-1 3  
I L-4 : 
i nterle u ki n-4  
I L-4 R α/I L -1 3 R α : I L-4 a n d I L -1 3 si g nali n g t hr o u g h t he T y p e II rece pt or  
I M P: 
i n vesti gati o nal me dici nal pr o d uct 
I R B: 
I nstit uti o nal Re vie w B oar ds 
I R T: 
I nteracti ve res p o nse t ec h n ol o g y 
I V R S: 
I nteracti ve V oice Res p o nse S yste m 
I W R S: 
I nteracti ve We b Res p o nse S yste m 
J A K: 
J a n us Ki nase 
M M F:  
m yc o p h e n olate m ofetil  
M M R M : 
mi x e d m o del effect m o del  
M T X:  
met h otre x ate  
NI M P:  
n o ni n vesti gati o nal me dici nal pr o d uct  
PI : 
Prescri bi n g I nf or m ati o n  
P S G:  
p ol ys o m n o gra p h y  
P V T:  
ps yc h o m ot or vi gila nce test  
Q 2 W:  
e ver y 2 w ee ks  
Q o L : 
q ualit y of life  
Q W : 
e ver y w ee k  
S C : 
s u bc uta ne o usl y 
S C O R A D : 
S C O Ri n g at o pic der matitis  
S o A:  
Sc he d ule of A cti vities  
S O L:  
slee p o nset late nc y 
V V- C LI N- 0 5 5 0 3 9 6 4. 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol 0 2  
L P S 1 5 4 9 7  
7 -A pr -2 0 2 0  
V er si o n n u m b er: 1  
 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al  
P a g e 7 8  
T CI:  
T o pical Calci ne uri n I n hi bit or  
T C S : 
t o pical c ortic oster oi ds 
T h 2 : 
T -hel per T y p e -2  
T S T:  
t otal slee p ti me 
V A S:  
vis ual a nal o g s cale  
W A S O:  
wa ke after slee p o nset  
W P AI -A D:  
w or k pr o d ucti vit y a n d acti vit y i m pair me nt q u esti o n naire f or at o pic der matitis  
 
1 0. 8  
A P P E N DI X 8   A C TI G R A P H Y   
Acti gra p h y is a n o bjecti ve a n d c o n v e nie nt met h o d f or ass essi n g q ua ntitati v e slee p para meters i n 
m ulti ple slee p relate d c o n diti o ns. I n t his st u d y a m ost a d va nce d a n d acce pta bl e b y t h e re g ulat or y 
a ut h orities de vice will be selecte d. A t h or o u g h re vie w of t he e xisti n g literat ure re v eale d relia ble 
a n d vali date d de vi ces s uc h as Acti watc h S pectr u m ( P hili ps/ Res pir o nics, M urr ys ville, P A).  
Wrist acti gra p h y is a t ec h ni q ue f or meas uri n g m o v e me nt of a li m b o ver a n e xte n de d rec or di n g 
peri o d ( da ys t o w ee ks). T he si g nals ge nerate d b y wrist m o ve me nt are s e nse d b y a ti n y 
micr oc o m p uter c o nt ai ne d wit hi n t he watc h a n d tr a nslate d i nt o acti vit y c o u nts. Al g orit h ms ha ve 
bee n de v el o pe d t o tra nslate t hese acti vit y c o u nts or “e p oc hs” ( or “ p eri o ds”) t hat c orres p o n d t o 
ti mes w he n a pers o n is li kel y t o be aslee p or wa k e. Acti gra p h y pr o vi des t he a bilit y t o esti mate 
slee p d urati o n, slee p p atter ns (i ncl u di n g ti mi n g of slee p a n d na p pi n g) a n d dist ur be d slee p 
(a wa k e ni n gs d uri n g t he slee p peri o d) m or e acc uratel y t ha n q uesti o n naire. It is easier t o use t ha n 
ot her a p pr oac hes s u c h as p ol ys o m n o gra p h y.  
Act i gra p h y is bei n g perf or me d i n t his st u d y t o pr o vi de relia ble esti mates of t he d urati o n, ti mi n g 
a n d patter ns of sle e p i n st u d y partici pa nts.  
T he e q ui p me nt t hat will be use d f or t his st u d y, t he Acti watc h S pectr u m ® (fr o m P hili ps 
Res pir o nics, I nc .) is a s m all de vice t hat will be w or n o n t he n o n -d o mi na nt wrist. T he Acti watc h 
S pectr u m ® c o ntai ns a s oli d -state piez oelectric acceler o meter (se nsiti ve t o 0. 0 2 5 G a n d a b o ve), 
lit hi u m batter y, micr o pr o cess or, n o n v olatile 1 M B of me m or y, a n d ass o ciat e d circ uitr y. T h e 
orie n tati o n a n d se nsiti vit y of t he acceler o meter are o pti mize d f or hi g hl y effecti ve sle e p/ wa ke 
i nfere n ce fr o m wrist acti vit y, w hic h has b ee n pre vi o usl y vali date d. 
T he de vice is d esi g n e d t o be c o m pact, li g ht wei g ht, water pr o of, a n d t o detect m o ve me nt, ti me “ off 
the wrist” a n d e n vir o n m e ntal li g ht. After t h e watc h data are sc ore d b y a sel ecte d e x pert ce nter, a 
n u m ber of s u m mar y me as ure me nts will be ge nerate d f or eac h partici pa nt, i ncl u di n g: a vera ge 
slee p d urati o n a n d slee p efficie n c y ( perce nta ge of ti me i n be d s pe nt  aslee p). 
D uri n g t h e be gi n ni n g of t he st u d y t he patie nts will be s h o w n h o w t o use t he slee p watc h. T h e 
partici pa nt will be i nstr ucte d t o wear t he wat c h o n t he n o n -d o mi na nt wrist f or 7  da ys  2 4 h o ur 
peri o ds ( mi ni m u m of 5 ni g hts, i ncl u di n g at least 1 wee ke n d/ n o n -w or k da y p eri o d). T he watc h will 
be w or n 7 e v e ni n gs of slee p bef ore eac h cli nical visit. T he partici pa nt als o will be i nstr ucte d o n 
V V- C LI N- 0 5 5 0 3 9 6 4. 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol 0 2  
L P S 1 5 4 9 7  
7 -A pr -2 0 2 0  
V er si o n n u m b er: 1  
 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al  
P a g e 7 9  
c o m pleti n g a di ar y c o n c urre ntl y  (see Secti o n  1 0. 9 , A p pe n di x 9). T his will pr o vi de a “ b ac k u p” i n 
case t here are q uesti o ns a b o ut t he rec or di n g.  
Ste ps t o pr ocess acti gra p h y  dat a  a n d se n d t he m t o t he Rea di n g C e nter are d escri be d i n det ail i n a  
Site C o or di nat or Ma n ual.  
A n acti gra p h l o g s h o ul d be mai ntai ne d at t he cli ni c s o t hat t he l ocati o ns of t he Acti watc h de vices 
are k n o w n at all ti mes. A serial n u m ber ( E X. A 0 1 7 8 5) f or eac h Acti watc h ca n be f o u n d o n t he 
bac ksi de of eac h Acti wat c h. T his s h o ul d  be use d as t he Acti watc h I D.  
Q U A LI T Y A S S U R A N C E F O R T H E A C TI W A T C H  
Eac h researc h pers o n nel c har ge d wit h t he res p o nsi bilit y of i nitializi n g, d o w nl oa di n g or a n y ot her 
ha n dli n g of t he Acti watc h will be re q uire d t o meet perf or ma nce sta n d ar ds t hat i n dicate a n 
u n dersta n di n g of t he A cti watc h’s batter y life, use of c o m m u nicati o ns d oc k a n d s oft ware, a n d 
e x plai ni n g t he Acti watc h a n d slee p diar y c o m pleti o n t o t he partici pa nt. O nl y pers o n nel w h o meet 
t hese sta n dar ds will be certifie d a n d a p pr o ve d t o h a n dle t he Acti watc h de vi ces a n d i nstr uct t he 
partici pa nts.  
Pers o n nel will be re q uir e d t o atte n d a trai ni n g sessi o n, or u n der g o l ocal trai ni n g b y a certifie d 
tec h nicia n. 
Trai ni n g will c o nsist of:  
1.  O ver vie w of Acti gra p h y O perati o ns Ma n ual, i ncl u di n g detaile d us e of Acti watc h, t he 
s oft ware, a n d t he c o m m u nicati o ns d oc k 
2.  Ha n ds o n trai ni n g f or i nitializi n g a n d d o w nl oa di n g/sa vi n g of files  
3.  O ver vie w of Acti ware S pectr u m ® S oft ware Ma n ual  
C E R TI FI C A TI O N  
Eac h staff me m ber h a n dli n g t he Acti watc h de vi ces nee ds t o s uccessf ull y c o m plete 
3  i nitializati o ns, d o w nl oa di n g, file c h ec ki n g, a n d t he sa vi n g t o t he assi g n e d f ol der.  
V V- C LI N- 0 5 5 0 3 9 6 4. 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol 0 2  
L P S 1 5 4 9 7  
7 -A pr -2 0 2 0  
V er si o n n u m b er: 1  
 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al  
P a g e 8 0  
1 0. 9  
A P P E N DI X 9 : C LI NI CI A N -R E P O R T E D O U T C O M E S ( C LI N R O S) A N D P A TI E N T -
R E P O R T E D O U T C O M E S ( P R O S)   
1.  I G A (c o m plete d b y I n vesti g at or at scree ni n g a n d b aseli ne visits o nl y)  
I G A Scale 
 
V V- C LI N- 0 5 5 0 3 9 6 4. 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol 0 2  
L P S 1 5 4 9 7  
7 -A pr -2 0 2 0  
V er si o n n u m b er: 1  
 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al  
P a g e 8 1  
2.  B o d y S urf ace Are a of At o pic d er m atitis I n v ol ve me nt ( B S A) (c o m pl ete d b y 
I n vesti g at or at scree ni n g a n d b aseli ne visits o nl y) 
Deri ve d fr o m “ Meas ure me nt of i n v ol ve d s urface area i n p atie nts wit h ps oriasis”, b y B. Ra msa y 
a n d C. M. La wre n ce. Britis h J o ur nal of Der mat ol o g y ( 1 9 9 1) 1 2 4, 5 6 5 -5 7 0. C o p yri g ht © 1 9 9 1 T he 
Ne wcastle u p o n T y ne H os pitals N H S F o u n dati o n Tr ust  
Re pr o d uce d wit h per missi o n of T he Ne wcastle u p o n T y ne H os pitals N H S F o u n dati o n Tr ust  
 
 
 
V V- C LI N- 0 5 5 0 3 9 6 4. 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol 0 2  
L P S 1 5 4 9 7  
7 -A pr -2 0 2 0  
V er si o n n u m b er: 1  
 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al  
P a g e 8 2  
3.  E A SI ( Refere nce f or t h e I n vesti g at or ) 
E A SI s cale  
 
 
 
 
V V- C LI N- 0 5 5 0 3 9 6 4. 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol 0 2  
L P S 1 5 4 9 7  
7 -A pr -2 0 2 0  
V er si o n n u m b er: 1  
 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al  
P a g e 8 3  
 
 
 
 
V V- C LI N- 0 5 5 0 3 9 6 4. 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol 0 2  
L P S 1 5 4 9 7  
7 -A pr -2 0 2 0  
V er si o n n u m b er: 1  
 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al  
P a g e 8 4  
 
 
 
 
V V- C LI N- 0 5 5 0 3 9 6 4. 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol 0 2  
L P S 1 5 4 9 7  
7 -A pr -2 0 2 0  
V er si o n n u m b er: 1  
 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al  
P a g e 8 5  
 
V V- C LI N- 0 5 5 0 3 9 6 4. 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol 0 2  
L P S 1 5 4 9 7  
7 -A pr -2 0 2 0  
V er si o n n u m b er: 1  
 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al  
P a g e 8 6  
 
V V- C LI N- 0 5 5 0 3 9 6 4. 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol 0 2  
L P S 1 5 4 9 7  
7 -A pr -2 0 2 0  
V er si o n n u m b er: 1  
 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al  
P a g e 8 7  
 
 
 
 
V V- C LI N- 0 5 5 0 3 9 6 4. 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol 0 2  
L P S 1 5 4 9 7  
7 -A pr -2 0 2 0  
V er si o n n u m b er: 1  
 
Pr o p ert y of t h e S a n ofi Gr o u p - stri ctl y c o nfi d e nti al  
P a g e 8 8  
 
 
 
V V- C LI N- 0 5 5 0 3 9 6 4. 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol 0 2  
L P S 1 5 4 9 7  
7 -A pr -2 0 2 0  
V er si o n n u m b er: 1  
 
 
Pr o p ert y of t h e S a n ofi gr o u p - stri ctl y c o nfi d e nti al  
P a g e 8 9  
 
 
 
.
V V- C LI N- 0 5 5 0 3 9 6 4. 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol 0 2  
L P S 1 5 4 9 7  
7 -A pr -2 0 2 0  
V er si o n n u m b er: 1  
 
 
Pr o p ert y of t h e S a n ofi gr o u p - stri ctl y c o nfi d e nti al  
P a g e 9 1  
 
5.  Slee p Q u alit y N R S (c o m plete d b y p atie nts)  
I nstr ucti o ns: Ple as e c o m plete t he f oll o wi n g q uesti o n u p o n a w a ke ni n g f or t he d a y.  
Select t he n u m ber t h at best descri be t he q u alit y of y o ur slee p l ast ni g ht.  
0  
1  
2  
3  
4  
5  
6  
7  
8  
9  
1 0  
W orst  
p ossi ble 
slee p 
 
Best  
p ossi ble 
slee p 
 
6.  At o pic der m atitis Slee p Di ar y (c o m plete d b y p atie nts)  
I nstr ucti o ns: 
Ple as e c o m plete t he f oll o wi n g q uesti o ns u p o n a w a ke ni n g f or t he d a y.  
1 a. A p pr o xi matel y w hat ti me di d y o u start tr yi n g t o fall aslee p last ni g ht? 
[ E nter ti me: X X: X X P M/ A M] 
 
1 b. A p pr o xi matel y w hat ti me di d y o u fall asle e p last ni g ht?  
[ E nter ti me: X X: X X P M/ A M] 
 
2 . A p pr o xi matel y h o w ma n y ti mes di d y o u wa k e u p last ni g ht ( n ot i ncl u di n g w he n y o u w o ke 
u p f or t he da y t o da y)? Rec or d “ 0” if y o u d o n ot re me m ber wa ki n g u p last ni g ht.  
[ E nter n u m ber of ti mes: X X] 
 
3 . C o nsi deri n g all t he ti mes y o u w o ke u p last ni g ht, h o w m uc h ti me were y o u a wa ke i n t otal?      
Rec or d “ 0 ” if y o u d o n ot re me m ber wa ki n g u p last ni g ht.  
[ E nter t otal a m o u nt of ti me a wa k e: X X h o urs a n d/ or X X mi n utes] 
 
V V- C LI N- 0 5 5 0 3 9 6 4. 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol 0 2  
L P S 1 5 4 9 7  
7 -A pr -2 0 2 0  
V er si o n n u m b er: 1  
 
 
Pr o p ert y of t h e S a n ofi gr o u p - stri ctl y c o nfi d e nti al  
P a g e 9 2  
 
4 . At w hat ti me di d y o u wa ke u p f or t he da y t o da y?  
[ E nter ti me: X X: X X P M/ A M] 
 
5 . Select t he n u m ber t hat best descri bes h o w reste d y o u felt w he n y o u g ot u p f or t he da y t o da y. 
0  
1  
2  
3  
4  
5  
6  
7  
8  
9  
1 0  
N ot at 
all 
reste d 
 
Ver y 
well 
reste d 
 
 
7.  Pe a k Pr urit us N R S (c o m plete d b y p atie nts) 
 
8.  S ki n P ai n N R S (c o m plete d b y p atie nts)  
T hi n k a b o ut all t he areas of y o ur s ki n wit h ecze ma. H o w w o ul d y o u rate y o ur s ki n pai n  at 
its w orst i n t he past 2 4 h o urs?  
0  
1  
2  
3  
4  
5  
6  
7  
8  
6  
1 0  
N o  
 
 
 
 
 
 
 
 
 
W o rst 
p ai n  
 
 
 
 
 
 
 
 
 
p ai n  
 
 
 
 
 
 
 
 
 
 
p o ssib l e 
V V- C LI N- 0 5 5 0 3 9 6 4. 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol 0 2  
L P S 1 5 4 9 7  
7 -A pr -2 0 2 0  
V er si o n n u m b er: 1  
 
 
Pr o p ert y of t h e S a n ofi gr o u p - stri ctl y c o nfi d e nti al  
P a g e 9 3  
 
9.  S ki n B ur n N R S (c o m plete d b y p atie nts)  
T hi n k a b o ut all t he areas of y o ur s ki n wit h ecze ma. H o w m uc h di d y o ur s ki n b ur n at its 
w orst i n t he past 2 4 h o urs?  
0  
1  
2  
3  
4  
5  
6  
7  
8  
9  
1 0  
N ot                                                                                                                 Ver y  
at all                                                                                                               m uc h  
 
1 0.  S ki n Se nsiti vit y t o t o uc h N R S (c o m plete d b y p atie nts)  
T hi n k a b o ut all t he areas of y o ur s ki n wit h ecze ma. H o w se nsiti ve was y o ur s ki n at its w orst 
i n t he past 2 4 h o urs?  
0  
1  
2  
3  
4  
5  
6  
7  
8  
9  
1 0  
N or mal   
 
 
 
 
 
 
 
E xtre mel y se nsiti ve  
 
 
V V- C LI N- 0 5 5 0 3 9 6 4. 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol 0 2  
L P S 1 5 4 9 7  
7 -A pr -2 0 2 0  
V er si o n n u m b er: 1  
 
Pr o p ert y of t h e S a n ofi gr o u p - stri ctl y c o nfi d e nti al  
P a g e 9 7  
 
V V- C LI N- 0 5 5 0 3 9 6 4. 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol 0 2  
L P S 1 5 4 9 7  
7 -A pr -2 0 2 0  
V er si o n n u m b er: 1  
 
 
Pr o p ert y of t h e S a n ofi gr o u p - stri ctl y c o nfi d e nti al  
P a g e 9 9  
 
1 5.  H A D S (c o m plete d b y p atie nts)  
V V- C LI N- 0 5 5 0 3 9 6 4. 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol 0 2  
L P S 1 5 4 9 7  
7 -A pr -2 0 2 0  
V er si o n n u m b er: 1  
 
 
Pr o p ert y of t h e S a n ofi gr o u p - stri ctl y c o nfi d e nti al  
P a g e 1 0 1  
 
V V- C LI N- 0 5 5 0 3 9 6 4. 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol 0 2  
L P S 1 5 4 9 7  
7 -A pr -2 0 2 0  
V er si o n n u m b er: 1  
 
 
Pr o p ert y of t h e S a n ofi gr o u p - stri ctl y c o nfi d e nti al  
P a g e 1 0 3  
 
1 8.  W or k Pr o d ucti vit y a n d Acti vit y I m p air me nt Q uest i o n n aire f or A D ( W P AI-A D) 
(c o m plete d b y p atie nts) 
 
V V- C LI N- 0 5 5 0 3 9 6 4. 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol 0 2  
L P S 1 5 4 9 7  
7 -A pr -2 0 2 0  
V er si o n n u m b er: 1  
Pr o p ert y of t h e S a n ofi gr o u p - stri ctl y c o nfi d e nti al  
P a g e 1 0 4  
 
 
 
V V- C LI N- 0 5 5 0 3 9 6 4. 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol 0 2  
L P S 1 5 4 9 7  
7 -A pr -2 0 2 0  
V er si o n n u m b er: 1  
 
 
Pr o p ert y of t h e S a n ofi gr o u p - stri ctl y c o nfi d e nti al  
P a g e 1 0 5  
 
1 9.  W or k/ Sc h o ol D a ys Misse d  
V V- C LI N- 0 5 5 0 3 9 6 4. 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol 0 2  
L P S 1 5 4 9 7  
7 -A pr -2 0 2 0  
V er si o n n u m b er: 1  
 
Pr o p ert y of t h e S a n ofi gr o u p - stri ctl y c o nfi d e nti al  
P a g e 1 0 6  
 
1 0. 1 0  A P P E N DI X 1 0 : P O L Y S O M N O G R A P H Y ( PS G) S U B -S T U D Y   
1.  I ntr o d u cti o n 
Patie nts wit h A D are k n o w n t o ha ve si g nifica nt slee p dis or ders d ue t o s cratc hi n g a n d p er ha ps  
ot her A D relate d pat h o p h ysi ol o g y.  T he o verall o bjecti ve of  t he c urre nt st u d y is t o e val uat e t he 
slee p q ualit y of t hese A D patie nts treate d wit h d u pil u ma b, usi n g slee p diar y a n d acti gra p h y, 
a n d ot her patie nt r e p orte d assess me nts.  
Wit hi n t his st u d y a P S G s u b -st u d y is pla n ne d f or a p pr o xi matel y 3 0 patie nts. 
P ol ys o m n o gra p h y  is a m ulti-para metric test use d i n t he st u d y of slee p (e g, bi o p h ysi ol o gical 
c ha n ges t hat occ ur d uri n g slee p) a n d it is a sta n dar d dia g n ostic t o ol i n slee p me dici ne. 
P ol ys o m n o gra p h y  is t y pi call y p erf or me d at ni g ht, us uall y i n a cli nic. Slee p para meters t hat are 
c o m m o nl y o btai ne d d uri n g a P S G pr o ce d ure will be c ollecte d f or t his st u d y, mai nl y i ncl u di n g 
slee p o nset late nc y ( S O L), wa ke after sl ee p o nset ( W A S O), t otal slee p ti me ( T S T), l o n gest 
slee p e pis o de, sta ges of slee p, slee p efficie n c y a n d ar o usal i n de x.   
T he o bjecti ve of t h e P S G s u b -st u d y is t o e val uat e t he a b o ve sle e p para meters wit h a m ore 
o bjecti ve assess me nt t o ol t o pr o vi de a d diti o nal r o b ust data i n s u p p ort of t he diar y a n d 
acti gra p h y e v al uati o ns.  
2.  Patie nts  
Of t he 2 0 1 partici p a nts, a p pr o xi matel y 3 0  c o nse nti n g patie nts ( a p pr o xi matel y 2 0 d u pil u ma b 
a n d 1 0 place b o p atie nts) will partici pate i n t his P S G s u b -st u d y.  
Base d o n e x pert i n p ut, re vie w of t he li mite d literat ure a n d o perati o nal f easi b ilit y it is deci de d 
t hat a sa m ple siz e of 3 0 patie nts c o ul d be s uffici e nt t o gat her relia ble P S G data t o re prese nt t he 
w h ole st u d y gr o u p. T he P S G data fr o m t his gr o u p will n ot be use d i n statistical c o m paris o ns 
bet wee n d u pil u ma b a n d place b o t heref ore n o st atistical c o nsi derati o ns t o o k place i n de ci di n g 
t he s u b gr o u p siz e. Ce nters selecte d f or t he P S G s u b-st u d y are e x perts i n slee p researc h a n d 
ha ve a m ple e x perie nce wit h re gar d t o P S G pr oce d ures a n d dat a c ollecti o n/s c ori n g. S electi o n 
of patie nts f or t he P S G s u b -st u d y will be bas e d o n pr o xi mit y ( w here patie nts li ve) t o 
partici pati n g sl ee p ce nters a n d a vaila bilit y f or se v eral o ver ni g ht sta ys at t he ce nters per st u d y 
pr ot oc ol . 
3.  Sc he d ule  
a)  At  Scree ni n g 2 Visit (D a y -7), patie nts will be as k e d t o kee p a re g ular slee p/ wa ke 
sc he d ule t hr o u g h Da y -1 ( 2 n d P S G ni g ht ) wit h a p pr o xi matel y 3 0  t o 6 0  mi n utes  
de viati o n fr o m t heir us ual be d ti me. T he us ual be dti me  “ Bas eli ne” will be c h ose n b y 
t he patie nt a n d s h o ul d reflect t heir ha bit ual sc he d ule. T his slee p/ wa ke s c he d ule will be 
m o nit ore d usi n g t he slee p d iar y, w hic h will be gi n o n Scree ni n g 2 . Patie nts will be 
re mi n de d (re mi n der call/te xt) t hat t he baseli ne st u d y visit s h o ul d be sc he d ul e d  at least 
o ne wee k after tra vel f or t h ose patie nts w h o tra vel e d acr oss m ore t ha n 1 ti me z o ne i n 
or der t o rec or d n or mal slee p/ wa k e c ycl e . 
b)  Be gi n ni n g o n St u d y d a y 7 7 ( 1 wee k b ef ore t he Pri mar y E n d p oi nt Visit, Visit 6) a n d 
c o nti n ui n g u ntil after t he  t hir d P S G ni g ht, patie nts will kee p a re g ul ar slee p/ wa ke 
V V- C LI N- 0 5 5 0 3 9 6 4. 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol 0 2  
L P S 1 5 4 9 7  
7 -A pr -2 0 2 0  
V er si o n n u m b er: 1  
 
Pr o p ert y of t h e S a n ofi gr o u p - stri ctl y c o nfi d e nti al  
P a g e 1 0 7  
sc he d ule wit h a p pr o xi matel y 3 0  t o 6 0 mi n utes de viati o n fr o m t heir sc he d ul e c h ose n f or 
t he Bas eli ne slee p sc h e d ule. D uri n g t his re mi n der call/te xt patie nts will be as ke d if 
t he y pla n t o tr a vel a cr oss m ore t ha n o ne ti me z o ne i n t he ne xt 7 da ys. If yes, t heir P S G 
a n d t he acc o m pa n yi n g site visit ( visit 6 ) s h o ul d be resc he d ul e d s o t hat t here will be a 
mi ni m u m of 7 da ys bet w ee n s uc h tr a vel a n d t he P S G. T he  slee p/ wa k e sc he d ule will be 
m o nit ore d us i n g slee p di ar y, w hich will be gi n o n Scree ni n g 2 a n d c o nti n ue p ast 
Visit  6. P ol ys o m n o gra p h y  s h o ul d occ ur at least o ne wee k after tra vel f or t h ose patie nts 
w h o tra vele d acr oss m or e t ha n 1 ti me z o ne . 
4.  Pr oce d ures  
Bef ore a n y P S G pr o ce d ure s, t he site s h o ul d calc ul ate t he mea n of t he slee p q ualit y N R S a n d 
t he mea n of pea k pr urit us N R S c o m plete d f or 5 da ys b y t he patie nt, t o  c o nfir m t hat i ncl usi o n 
criteria 7 a n d 8 are met.  
A)  Da y of a d missi o n  
a)  T he slee p ce nter staff will  d oc u me nt all caffei ne, t o bacc o, alc o h ol, a n d pres cri pti o n  or 
o ver t he c o u nter me dic ati o ns ta ke n si nce a wa ke ni n g.  
b)  Patie nts t o bri n g slee p di ar y (i Pa d) pr o vi d e d b y t he s p o ns or t o t he slee p ce nter. T his 
will be re vie we d b y st u d y staff.  
c)  Patie nt s t o arri ve at slee p ce nter a p pr o xi matel y 3  h o urs bef ore t heir c h os e n slee p ti me.  
d)  Patie nts will wear acti w atc h w he n arri vi n g i n t he cli nic . 
e)  Slee p ce nter will d o cli nical a d missi o n per t heir S O Ps.  
f) Slee p ce nter will a d mi nister electr o des per A merica n Aca d e m y of Slee p Me dici ne 
(A A S M ) criteria f or a cli nical slee p rec or di n g, i ncl u di n g electr oe nce p hal o gra m , 
electr o ocul o gra p h y , el ectr o m y o gra p h y, E C G, electr o des f or m o nit ori n g l e g 
m o ve me nts, airfl o w se ns ors a n d Res pirat or y I n d u cta nce Plet h ys m o gra p h y se ns ors f or 
m o nit ori n g breat hi n g a n d O 2 sat urati o n. Cali brati o ns per S O P f or t he slee p ce nter. 
g)  Slee p ce nter will be gi n sl ee p rec or di n g ~ 3 0 mi n utes pri or t o eac h i n di vi d ual patie nt’s 
c h ose n slee p ti me.  
h)  Slee p ce nter will be gi n a vi de o rec or di n g ~ 3 0 mi n utes pri or t o eac h i n di vi d ual 
patie nt’s c h ose n slee p ti me.  
B)  Ne xt da y  (a n d t he t hir d P S G ni g ht) 
a)  Slee p rec or di n g will e n d after eac h i n di vi d ual pati e nt’s nat ural  wa ke ti me.  
b)  Vi de o rec or di n g will e n d after eac h i n di vi d ual pati e nt’s nat ural  wa ke ti me.  
c)  Patie nts will c o nti n ue t o wear acti watc h a n d c o m plete all patie nt re p ort e d o utc o mes i n 
t heir i Pa d u p o n a wa ke ni n g f or t he da y. 
d)  Patie nts a n d st u d y site will c o m plete t he re mai ni n g st u d y rel ate d assess me nts as per 
t he sc he d ule of acti vities. 
V V- C LI N- 0 5 5 0 3 9 6 4. 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol 0 2  
L P S 1 5 4 9 7  
7 -A pr -2 0 2 0  
V er si o n n u m b er: 1  
 
Pr o p ert y of t h e S a n ofi gr o u p - stri ctl y c o nfi d e nti al  
P a g e 1 0 8  
C)  Wit hi n 2  b usi ness da ys  
a)  Slee p ce nter will se n d t he E D F files  or ot her a gree d u p o n f or mat of  t he P S G 
rec or di n gs t o a bli n de d ce ntral rea der site w hic h will use A A S M criteria t o sc ore b y a 
re gistere d P S G tec h nici a n.  
- 
Re p orte d o utc o mes i ncl u de ( b ut n ot li mite d t o)  slee p o nset late nc y ( S O L), wa ke after 
slee p o nset ( W A S O), t otal slee p ti me ( T S T), l o n gest slee p e pis o de, sta ges of slee p, 
slee p effi cie nc y a n d ar o usal i n de x. 
b)  If a patie nt h as e vi de nce of a cli nical slee p dis or der as detecte d b y t he P S G, t he ce ntral 
rea di n g P S G cli nic will n otif y t he P S G site t he patie nt is fr o m, a n d t he P S G site will 
t he n n otif y t he p atie nt. T hat site will als o be res p o nsi ble f or re p orti n g t his as a n A E if 
rele va nt (i e, i n case of w orse ni n g of fre q ue n c y or se verit y of slee p dis or der as 
c o m pare d t o bas eli ne stat us) . T hese patie nts will c o nti n ue i n t he mai n st u d y u nless 
t heir c o n diti o n re q uires i m me diate atte nti o n or per ma ne nt  or te m p orar y 
disc o nti n uati o n of t he st u d y f or a n y safet y reas o n.   
1 0. 1 1  A P P E N DI X 1 1 : P R O T O C O L A M E N D M E N T HI S T O R Y   
T he Pr ot oc ol A me n d me nt S u m mar y of C ha n ges T a 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 bl e of C o nte nts ( T O C).  
C ha n ges i n pr ot oc ol a me n d me nt 1 ( date d 1 0 -Oct -2 0 1 9) are liste d bel o w.  
Pr ot o c ol a m e n d m e nt 1 s u m m ar y of c h a n g e s t a bl e  
S e cti o n # a n d N a m e  
D e s cri pti o n of C h a n g e  
Bri ef R ati o n al e  
Titl e p a g e  
St u dy acr o ny m “ D U PI S T A D” h as b e e n 
a d d e d  
T o b e c o nsist e nt wit h I nf or m e d C o ns e nt 
F or m  
1. 1 Sy n o psis: i nt erv e nti o n gr o u ps a n d 
d ur ati o n  
1. 3 Sc h e d ul e of Activiti es  
4. 1 Ov er all d esi g n  
A d d e d t h at scr e e ni n g c a n b e d o n e as a 
si n gl e visit, if pr ef err e d by t h e p ati e nt 
a n d t h e i nv esti g at or  
F or l o gistic al  r e as o ns, t o all o w f or s o m e 
fl exi bility 
1. 1  Sy n o psis: I nt erv e nti o n gr o u ps a n d 
d ur ati o n  
1. 3 Sc h e d ul e of Activiti es  
4. 1 Ov er all D esi g n  
8. 1. 1. 5 P olys o m n o gr a p hy (s u b -st u dy; 
c o n d uct e d by t h e tr ai n e d pr of essi o n al)  
A d d e d t h e w or d “pr ef er a bly” b et w e e n 2 
c o ns ec utiv e ov er ni g ht P S Gs 
Mi n or e dit t o a d d fl exi bility f or p ossi bly 
n o n -c o ns ec utiv e ni g hts, as f e asi bility 
s h o w e d it m ay n ot al w ays b e p ossi bl e t o 
h av e t h e ‘ accli m atiz ati o n’ visit a n d t h e 
act u al ass ess m e nt visit o n c o ns ec utiv e 
ni g hts.  
1. 1  Sy n o psis: I nt erv e nti o n gr o u ps a n d 
d ur ati o n  
4. 1 Ov er all D esi g n  
A d d e d “i n s el ect e d U S sit es” f or P S G  
Mi n or e dit t o m e nti o n t h at P S G s u b -
st u dy will b e c o n d uct e d i n U S sit es ( w as 
alr e a dy pl a n n e d, b ut n ot s p ecifi e d i n t h e 
ori gi n al pr ot oc ol).  
V V- C LI N- 0 5 5 0 3 9 6 4. 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol 0 2  
L P S 1 5 4 9 7  
7 -A pr -2 0 2 0  
V er si o n n u m b er: 1  
 
Pr o p ert y of t h e S a n ofi gr o u p - stri ctl y c o nfi d e nti al  
P a g e 1 0 9  
S e cti o n # a n d N a m e  
D e s cri pti o n of C h a n g e  
Bri ef R ati o n al e  
1. 1  Sy n o psis : St u dy I nt erv e nti o n D os e 
R e gi m e n  
6 St u dy I nt erv e nti o n T a bl e 2 Ov ervi e w 
of st u dy i nt erv e nti o ns a d mi nist er e d  
L a n g u a g e m o difi e d fr o m “l ast i nj ecti o n 
t hr o u g h w e ek  2 4” t o “l ast i nj ecti o n at 
w e ek  2 2”  
Alr e a dy pl a n n e d i n t h e ori gi n al pr ot oc ol; 
l a n g u a g e m o difi e d t o m ak e it m or e cl e ar 
t h at t h e l ast i nj ecti o n wit hi n t h e 2 4-w e ek 
tr e at m e nt p eri o d will b e at w e ek  2 2.  
1. 3 Sc h e d ul e of Activiti es  
+ 1 d ay a d d e d t o all ot h er visits p ost 
D ay  1  
T o c orr ect a mi n or err or i n t h e S o A. As 
Bas eli n e is at D ay 1, o n e d ay w as  
a d d e d t o all visits p ost D ay 1, t o k e e p 
ex actly 1  w e ek ( 7 d ays), or 2 w e eks ( 1 4 
d ays), or 4 w e eks ( 2 8 d ays) b et w e e n 
f urt h er c o ns ec utiv e visits. 
1. 3 Sc h e d ul e of Activiti es  
Psyc h o m ot or Vi gil a nc e t est ( P V T) a n d 
N e ur oc o g nitiv e t est ( Aut o m at e d 
Psyc h ol o gic al A ss ess m e nt M etrics-
A N A M) s plit i nt o 2 s e p ar at e li n es i n t h e 
S o A t a bl e.  
Mi n or (f or m atti n g) c h a n g e, f or cl arity.  
2. 3 B e n efit/ Risk Ass ess m e nt  
A d d e d s u m m ary of b e n efit a n d risk of 
d u pil u m a b tr e at m e nt  
T his s ecti o n w as r ei ns ert e d as p er E U 
H e alt h A ut h oriti es r e q u est. 
3. 0 O bj ectiv es a n d E n d p oi nts  
A d d e d s p ecific d et ails a b o ut pr oc e d ur al 
r e acti o n ti m e sc or e al o n g wit h r u n ni n g 
m e m ory a n d m at h e m atic al pr oc essi n g 
i n ex pl or at ory e n d p oi nt. 
C orr ect e d a n o missi o n fr o m t h e 
pr evi o us v ersi o n t o m atc h t h e cli nic al 
m e as ur e m e nts wit h t h e c orr es p o n di n g 
e n d p oi nts . 
5. 2 Excl usi o n crit eri a E 2 8  
C o ntr ac e pti o n p eri o d aft er t h e l ast d os e 
of st u dy dr u g c h a n g e d fr o m 1 2 0 d ays t o 
1 2 w e eks  
T his c h a n g e is d o n e t o c orr ect a n err or  
i n t h e ori gi n al pr ot oc ol a n d m ak e it 
c o nsist e nt wit h I B a n d I C F, a n d is als o 
b as e d o n d u pil u m a b h alf -lif e. 
9. 4. 1 Effic acy a n alysis  
T a bl e 4  Effic acy a n alys es  
M M R M d o es n ot e m pl oy f or m al 
i m p ut ati o n f or missi n g d at a; t h er ef or e n o 
i m p ut ati o ns f or missi n g v al u es will b e 
c arri e d o ut f or th e pri m ary a n alysis.  
T o c orr ect a n o missi o n as p er E U 
H e alt h A ut h oriti es r e q u est, t o cl arify h o w 
missi n g d at a will b e h a n dl e d. Mix e d 
M o d el R e p e at e d M e as ur es ( M M R M) will 
i m plicitly acc o u nt f or missi n g v al u es. 
9. 4. 1 Effic acy a n alysis  
T a bl e 4  Effic acy a n alys es  
A d d e d t h at f or m al st atistic al 
c o m p aris o ns will n ot b e p erf or m e d o n 
t h e P S G e n d p oi nts. 
N o c h a n g e i n t h e pl a n n e d st atistic al 
a n alysis, b ut cl arific ati o n a d d e d t o 
ex pl ai n t h at, du e t o t h e li mit e d s a m pl e 
siz e of t h e s u b-st u dy, t h e a n alys es will 
b e li mit e d t o pr ovi di n g s u m m ary 
st atistics f or t h e P S G  e n d p oi nts.  
S ecti o n 1 0. 4 A p p e n dix 4 C o ntr ac e ptiv e 
G ui d a nc e a n d C oll ecti o n of Pr e g n a ncy 
I nf or m ati o n 
R e m ov e d b ull et p oi nt st ati n g t h at 
a d diti o n al pr e g n a ncy t esti n g is n ot 
r e q uir e d d uri n g t h e st u dy p eri o d 
(tr e at m e nt as w ell as f oll o w-u p)  
C orr ect e d a mi n or err or i n t h e pr evi o us 
v ersi o n, t o m atc h wit h ass ess m e nts as 
p er S o A .  
S ecti o n 1 0. 1 0   
A p p e n dix 1 0  P olys o m n o gr a p hy ( P S G) 
s u b-st u dy 
A d d e d A p p e n dix f or p olys o m n o gr a p hy  
T h e P S G Ap p e n dix  is a d d e d i n t h e 
pr ot oc ol a m e n d m e nt t o pr ovi d e t h e 
d et ail e d d escri pti o n, pr oc e d ur e, a n d 
sc h e d ul e f or p olys o m n o gr a p hy, as 
r e q u est e d by E U H e alt h A ut h oriti es. 
I n a d diti o n, ot her mi n or e dit orial c ha n ges (e g, gra m matical, st ylistic, a n d mi n or t y p o gra p hi cal er r or c orrecti o ns) were 
i m ple me nte d t hr o u g h o ut t he pr ot oc ol. 
V V- C LI N- 0 5 5 0 3 9 6 4. 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol 0 2  
L P S 1 5 4 9 7  
7 -A pr -2 0 2 0  
V er si o n n u m b er: 1  
 
Pr o p ert y of t h e S a n ofi gr o u p - stri ctl y c o nfi d e nti al  
P a g e 1 1 0  
1 1  
R E F E R E N C E S   
 
1 . Gittler J K, S he mer A, S uárez -Fari ñas  M, F ue ntes -D uc ula n J, G ule wicz KJ, Wa n g C Q, et al. 
Pr o gressi ve acti vati o n of T( H) 2/ T( H) 2 2 c yt o ki nes a n d selecti ve e pi der mal pr otei ns 
c haracteriz es ac ute a n d c hr o nic at o pic der matitis. J Aller g y Cli n I m m u n ol. 2 0 1 2; 1 3 0( 6): 1 3 4 4 -
5 4.  
2 . W o o dr uff P G, M o dre k B, C h o y D F, Jia G, A b bas A R, Ell wa n ger A, et al. T -hel per t y pe 2 -
dri ve n i nfla m mati o n defi nes maj or s u b p h oe n ot y pes of ast h ma. A m J Res pir Crit Care Me d. 
2 0 0 9; 1 8 0( 5): 3 8 8 -9 5.  
3 . Bie ber T. Mec h a nis ms of disease: At o pic Der matitis. N E n gl J Me d. 2 0 0 8; 3 5 8: 1 4 8 3 -9 4.  
4 . M urra y CJ, Ric har ds M A, Ne wt o n J N, Fe nt o n K A, A n ders o n H R, At ki ns o n C, et al. U K 
healt h perf or ma nce: fi n di n gs of t he Gl o bal B ur de n of Disease St u d y 2 0 1 0. La n cet. 
2 0 1 3; 3 8 1( 9 8 7 1): 9 9 7 -1 0 2 0.  
5 . Sil ver ber g JI. Ass ociati o ns bet wee n at o pic d er matitis a n d ot her  dis or ders. 2 0 1 8; 7( F 1 0 0 0 
Fac ult y Re v): 3 0 3.  
6 . Di n ges D F, Pac k F, Willia ms K, Gille n K A, P o well J W, Ott G E, et al. C u m ulati ve slee pi ness, 
m o o d dist ur ba nce, a n d ps yc h o m ot or vi gila nce perf or ma nce  d ecre me nts d uri n g a wee k of slee p 
restricte d t o 4-5 h o urs p er ni g ht. Slee p. 1 9 9 7; 2 0( 4): 2 6 7 -7 7.  
7 . J e o n C, Ya n D, Na ka m ur a M, Se k h o n S, B h uta ni T, Lia o W. Fre q ue n c y a n d ma na ge me nt of 
slee p dist ur ba nce i n a d ults wit h at o pic der matitis. A s yste matic re vie w. Der mat ol T her. 
( Hei del b) 2 0 1 7; 7( 3): 3 4 9-6 4.  
8 . R uzic ka T, Mi hara R. A nti -i nterle u ki n-3 1 rece pt or A a nti b o d y f or at o pic d er matitis . N E n gl J 
Me d. 2 0 1 7; 3 7 6: 8 2 6.  
9 . C har ma n C R, Ve n n AJ, Willia ms, H C. T he patie nt -orie nte d ecze ma meas ure. Arc h Der mat ol. 
2 0 0 4; 1 4 0: 1 5 1 3 -1 9.  
1 0 . Ba dia X, M ascar o J M, L oza n o R. Meas uri n g h ealt h -relate d q u alit y of life i n patie nts wit h mil d 
t o m o derate ecze ma a n d ps oriasis: cli nical vali dit y, relia bilit y a n d s e nsiti vit y t o c ha n ge of t he 
D L QI. Br J Der mat ol. 1 9 9 9; 1 4 1( 4): 6 9 8 -7 0 2.  
1 1 . Zi g m o n d A S, S nait h R P. T he h os pital a n xiet y a n d de pressi o n scal e. Acta Ps yc hi atr Sca n d. 
1 9 8 3; 6 7: 3 6 1 -7 0.  
1 2 . Herr ma n n C. I nt er nati o n al e x perie nces wit h t he h os pital a n xiet y a n d d e pressi o n scale –  a 
re vie w of vali dati o n data a n d cli nical res ults. J Ps yc h os o m Res. 1 9 9 7; 4 2( 1): 1 7-4 1.  
1 3 . Bas ner M, Di n ges, D F. Ma xi mi zi n g se nsiti vit y of t he Ps yc h o m ot or Vi gila nce Test ( P V T) t o 
slee p l oss. Slee p. 2 0 1 1; 3 4: 5 8 1-9 1.  
V V- C LI N- 0 5 5 0 3 9 6 4. 0

A m e n d e d Cli ni c al Tri al Pr ot o c ol 0 2  
L P S 1 5 4 9 7  
7 -A pr -2 0 2 0  
V er si o n n u m b er: 1  
 
Pr o p ert y of t h e S a n ofi gr o u p - stri ctl y c o nfi d e nti al  
P a g e 1 1 1  
1 4 . Wil ke n J A, Ka ne R, S ulli va n C L, Walli n M, Usis ki n J B, Q ui g M E, et al. T h e utilit y of 
c o m p uteriz e d ne ur o ps yc h ol o gical assess me nt of c o g niti ve d ysf u ncti o n i n p atie nts wit h 
rela psi n g-re mitti n g m ulti ple scler osis. M ult Scler. 2 0 0 3; 9: 1 1 9-2 7.  
1 5 . Ree ves D L, Wi nter K P, Blei ber g J, Ka ne R L. A N A M ® ge n o gra m: Hist ori cal pers p ecti ves, 
descri pti o n, a n d c urre nt e n dea v ors. Arc h Cli n Ne ur o ps yc h ol. 2 0 0 7; 2 2 S: S 1 5 -S 3 8.  
 
 
V V- C LI N- 0 5 5 0 3 9 6 4. 0

Si g nat ure Pa ge f or V V- C LI N- 0 5 5 0 3 9 6 v 4. 0
l ps 1 5 4 9 7- 1 6- 1- 1-a me n de d- pr ot oc ol 0 2
A p pr o ve & e Si g n
A p pr o ve & e Si g n
V V- C LI N- 0 5 5 0 3 9 6 4. 0