Clinical trial NCT04033367
Conditions: Atopic Dermatitis
Sponsor: Sanofi
Start date: 2019-08-22; Completion date: 2021-10-06
Enrollment: 188 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
Primary Objective:

To evaluate the effect of dupilumab on sleep quality in adult participants with moderate to severe atopic dermatitis (AD).

Secondary Objectives:

To evaluate the effect of dupilumab on objective and subjective quantitative sleep parameters, AD related outcomes, and daytime consequences of sleep deprivation.

To continue to assess the safety and tolerability throughout the study.

Detailed description:
Duration per participant was up to 28 weeks.

Arms: arm 1: Participants received dupilumab 600 milligrams (mg) (loading dose) injection subcutaneously (SC) on Day 1 followed by dupilumab 300 mg injection SC every 2 weeks (q2w) up to Week 10 in the double-blind (DB) period of 12 weeks. After completion of DB period, participants entered in the open-label extension (OLE) period (Week 12 to 24) and continued to receive dupilumab 300 mg injection SC q2w from Week 12 up to Week 22. arm 2: Participants received placebo matching to dupilumab injection SC on Day 1 then followed by placebo injection SC q2w up to Week 10 in the DB period of 12 weeks. After completion of DB period, participants entered in the OLE period (Week 12 to 24) and received dupilumab 600 mg (loading dose) at Week 12 followed by dupilumab 300 mg injection SC q2w up to Week 22.
Interventions: intervention 1: Dupilumab intervention 2: Placebo
Intervention descriptions: intervention 1: Pharmaceutical form: solution for injection Route of administration: subcutaneous intervention 2: Pharmaceutical form: solution for injection Route of administration: subcutaneous

Protocol documents:
Prot_000.pdf: 
 
 
 
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 . 
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 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 . 
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 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 . 
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 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  
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 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   
 
 
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 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. 
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 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 
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 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. 
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 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  
 
 
 
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 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, 
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 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 . 
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 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.  
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 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 
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 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 
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 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 
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 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 
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 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.  
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 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.  
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 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. 
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 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. 
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 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. 
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 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 
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 6  
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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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 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 
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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 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). 
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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 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 ). 
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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 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 ). 
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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 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 
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L P S 1 5 4 9 7  
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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 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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P a g e 5 3  
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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P a g e 5 4  
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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P a g e 5 7  
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


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 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 . 
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 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. 
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 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.  
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 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. 
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 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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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 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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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 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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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 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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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 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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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 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. 
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 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).  
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 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.  
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 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.  
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 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. 
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 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 
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 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

SAP_001.pdf: 
C o nfi de ntial  
S a n ofi gr o u p
N C T 0 4 0 3 3 3 6 7 
D u pil u m a b - L P S 1 5 4 9 7 
A r a n d o mize d d o u ble- bli n d pl ace b o-c o ntr olle d st u d y e v al u ati n g t he effect 
of d u pil u m a b o n slee p i n a d ult p atie nts wit h m o der ate t o se vere at o pic 
der m atitis 
3 0 J U L 2 0 2 1 
Fi nal Statistical A nal ysis Pla n 
Versi o n 2. 0 
Pre pare d b y:  


Sa n ofi Gr o u p  
 
Fi nal Statistical A nal ysis Pla n, Versi o n 2. 0  
 
D u pil u ma b - L P S 1 5 4 9 7  
 
Date Iss ue d: 3 0J U L 2 0 2 1  
 
  
 
 
 II 
T A B L E O F C O N T E N T S  
LI S T O F T A B L E S  ....................................................................................................................... V  
LI S T O F FI G U R E S  ..................................................................................................................... V  
LI S T O F A B B R E VI A TI O N S  ..................................................................................................... V  
1.  
I N T R O D U C TI O N............................................................................................................. 1  
2.  
S T U D Y O B J E C TI V E S, E N D P OI N T S A N D E S TI M A N D S ......................................... 1  
3.  
I N V E S TI G A TI O N A L P L A N .......................................................................................... 6  
3. 1.  O V E R A L L S T U D Y D E SI G N A N D P L A N  .................................................................................. 6  
3. 2.  S T U D Y E N D P OI N T S  ............................................................................................................. 7  
3. 3.  T R E A T M E N T S  ...................................................................................................................... 7  
3. 4.  D O S E A DJ U S T M E N T / MO DI FI C A TI O N S  ................................................................................. 8  
4.  
G E N E R A L S T A TI S TI C A L C O N SI D E R A TI O N S  ....................................................... 8  
4. 1.  S A M P L E S I Z E ...................................................................................................................... 8  
4. 2.  R A N D O MI Z A TI O N , S T R A TI FI C A TI O N , A N D B LI N DI N G  .......................................................... 8  
4. 3.  A N A L Y SI S S E T S  .................................................................................................................. 9  
4. 3. 1.  
Scree ne d A n alysis Set  ................................................................................................. 9  
4. 3. 2.  
I nte nt-t o-Tre at (I T T) A n alysis Set  ............................................................................... 9  
4. 3. 3.  
M o difie d I T T ( mI T T) A n alysis Set ............................................................................... 9  
4. 3. 4.  
O L E A n alysis Set ......................................................................................................... 9  
4. 3. 5.  
P S G  A n alysis Set  ......................................................................................................... 9  
4. 3. 6.  
S afety A n alysis Set  ...................................................................................................... 9  
4. 3. 7.  
A n alysis set wit h o ut tri al i m p act ( disr u pti o n) d ue t o C O VI D -1 9  ............................... 9  
4. 3. 8.  
A n alysis set wit h tri al i m p act ( disr u pti o n) d ue t o C O VI D -1 9  .................................... 9  
4. 4.  R E P O R TI N G C O N V E N TI O N S  ............................................................................................... 1 0  
4. 4. 1.  
Tre at me nt l a bels ........................................................................................................ 1 0  
4. 4. 2.  
Visit n a mi n g C o nve nti o ns  ......................................................................................... 1 0  
4. 4. 3.  
Visit Wi n d o ws ............................................................................................................ 1 0  
4. 4. 4.  
U nsc he d ule d Visits  .................................................................................................... 1 0  
4. 4. 5.  
Dis pl ay of D at a S u m m ary a n d A n alysis  ................................................................... 1 0  
4. 4. 6.  
B aseli ne, st u dy d ay a n d d ur ati o n deriv ati o ns  ........................................................... 1 1  
4. 4. 7.  
C h a n ge fr o m b aseli ne a n d Perce nt c h a n ge fr o m b aseli ne  ....................................... 1 2  
4. 5.  IN T E R C U R R E N T E V E N T T Y P E S  .......................................................................................... 1 2  
5.  
P A TI E N T DI S P O SI TI O N .............................................................................................. 1 2  
5. 1.  D I S P O SI TI O N ..................................................................................................................... 1 2  
5. 2.  P R O T O C O L D E VI A TI O N S  ................................................................................................... 1 4  
6.  
D E M O G R A P HI C S A N D B A S E LI N E C H A R A C T E RI S TI C S  .................................. 1 5  
6. 1.  D E M O G R A P HI C S  ................................................................................................................ 1 5  
6. 2.  B A S E LI N E D I S E A S E C H A R A C T E RI S TI C S  ............................................................................. 1 5  
6. 2. 1.  
Slee p c h ar acteristics a n d slee p rel ate d i m p air me nt at b aseli ne  ............................... 1 5  
6. 2. 2.  
A D a n d ass oci ate d dise ase c h ar acteristics at b ase li ne ............................................ 1 6  
6. 2. 3.  
He alt h ec o n o mic e n d p oi nts at b aseli ne  .................................................................... 1 7  


Sa n ofi Gr o u p  
 
Fi nal Statistical A nal ysis Pla n, Versi o n 2. 0  
 
D u pil u ma b - L P S 1 5 4 9 7  
 
Date Iss ue d: 3 0J U L 2 0 2 1  
 
  
 
  III 
6. 3.  A L C O H O L , T O B A C C O A N D C A F F EI N E U S A G E  .................................................................... 1 7  
6. 4.  M E DI C A L H I S T O R Y ........................................................................................................... 1 7  
6. 4. 1.  
Ge ner al Me di c al Hist ory  .......................................................................................... 1 7  
6. 4. 2.  
Dise ase -S pecific Hist ory  ........................................................................................... 1 7  
6. 5.  IN C L U SI O N A N D E X C L U SI O N C RI T E RI A  ............................................................................. 1 7  
6. 6.  O T H E R B A C K G R O U N D IN F O R M A TI O N  ............................................................................... 1 7  
7.  
T R E A T M E N T S A N D M E DI C A TI O N S  ....................................................................... 1 8  
7. 1.  P RI O R A N D C O N C O MI T A N T M E DI C A TI O N S  ........................................................................ 1 8  
7. 1. 1.  
Pri or Me dic ati o ns  ..................................................................................................... 1 8  
7. 1. 2.  
C o nc o mit a nt Me dic ati o ns  ......................................................................................... 1 8  
7. 1. 3.  
P ost -tre at me nt me dic ati o ns ...................................................................................... 1 8  
7. 2.  S T U D Y T R E A T M E N T S  ........................................................................................................ 1 8  
7. 2. 1.  
Exte nt of Ex p os ure  .................................................................................................... 1 8  
7. 2. 2.  
T re at me nt C o m pli a nce a n d M o dific ati o ns................................................................ 1 9  
8.  
E F FI C A C Y A N A L Y SI S  ................................................................................................. 2 0  
8. 1.  P RI M A R Y E F FI C A C Y E N D P OI N T  ......................................................................................... 2 0  
8. 1. 1.  
Pri m ary A n alysis  ....................................................................................................... 2 1  
8. 1. 2.  
Ass u m pti o n Testi n g  ................................................................................................... 2 2  
8. 1. 3.  
Missi n g D at a H a n dli n g  ............................................................................................. 2 2  
8. 1. 4.  
S u b gr o u p A n alysis  .................................................................................................... 2 2  
8. 1. 5.  
Se nsitivity A n alysis .................................................................................................... 2 2  
8. 1. 6.  
S u p ple me nt ary A n alyses  ........................................................................................... 2 2  
8. 1. 7.  
I m p act of C ovi d-1 9 P a n d e mic  .................................................................................. 2 2  
8. 2.  S E C O N D A R Y A N D E X P L O R A T O R Y E F FI C A C Y E N D P OI N T  ................................................... 2 3  
8. 2. 1.  
Acti gr a p hy d at a  ......................................................................................................... 2 3  
8. 2. 2.  
Slee p di ary  ................................................................................................................ 2 3  
8. 2. 3.  
Slee p Q u ality N R S  ..................................................................................................... 2 3  
8. 2. 4.  
Pe ak Pr urit us N R S  .................................................................................................... 2 3  
8. 2. 5.  
Ski n P ai n N R S  ........................................................................................................... 2 4  
8. 2. 6.  
Ski n Se nsitivity t o T o uc h N R S  ................................................................................... 2 4  
8. 2. 7.  
Ski n B ur n N R S ........................................................................................................... 2 4  
8. 2. 8.  
Ecze m a Are a S everity I n dex ( E A SI)  .......................................................................... 2 5  
8. 2. 9.  
P atie nt orie nte d ecze m a me as ure ( P O E M)  ............................................................... 2 6  
8. 2. 1 0.  
P R O MI S Slee p Rel ate d I m p air me nt S h ort F or m 8 a  .............................................. 2 6  
8. 2. 1 1.  
E p w ort h Slee pi ness Sc ale ( E S S)  ............................................................................ 2 6  
8. 2. 1 2.  
Der m at ol o gy Life Q u ality I n dex ( D L QI)  ............................................................... 2 6  
8. 2. 1 3.  
S C O Ri n g of At o pic Der m atitis ( S C O R A D)  ........................................................... 2 7  
8. 2. 1 4.  
J u ni per Ast h m a C o ntr ol Q uesti o n n aire ( A C Q -5)  .................................................. 2 7  
8. 2. 1 5.  
Aller gic R hi nitis Vis u al A n al o g Sc ale ( A R -V A S)  ................................................... 2 7  
8. 2. 1 6.  
Psyc h o m ot or Vi gil a nce T est ( P V T)  ....................................................................... 2 7  
8. 2. 1 7.  
Ne ur oc o g nitive Test ( A ut o m ate d Ne ur o psyc h ol o gi c al Assess me nt Metrics 
[ A N A M]) 2 8  
8. 2. 1 8.  
P olys o m n o gr a p hy ( P S G)  ....................................................................................... 2 8  
8. 2. 1 9.  
W ork Pr o d uctivity a n d A ctivity I m p air me n t Q u esti o n n aire: At o pic Der m atitis 
( W P AI-A D)  ............................................................................................................................. 2 8  


Sa n ofi Gr o u p  
 
Fi nal Statistical A nal ysis Pla n, Versi o n 2. 0  
 
D u pil u ma b - L P S 1 5 4 9 7  
 
Date Iss ue d: 3 0J U L 2 0 2 1  
 
  
 
  I V 
8. 2. 2 0.  
D ays misse d fr o m sc h o ol or fr o m w ork d ue t o A D  ................................................ 2 8  
8. 2. 2 1.  
H os pit al A nxiety a n d De pressi o n Sc ale ( H A D S)  ................................................... 2 9  
8. 2. 2 2.  
Rel ati o ns hi p bet wee n v ari a bles rel ati n g t o slee p dist ur b a nces a n d o bjective a n d 
s u bjective p ar a met ers ass oci ate d wit h A D............................................................................. 2 9  
8. 2. 2 3.  
M ulti plicity iss ues  .................................................................................................. 3 0  
9.  
S A F E T Y A N A L Y SI S ...................................................................................................... 3 0  
9. 1.  A D V E R S E E V E N T S  ............................................................................................................. 3 1  
9. 1. 1.  
I nci de nce of A dvers e Eve nts ..................................................................................... 3 2  
9. 1. 2.  
Rel ati o ns hi p of A dverse Eve nts t o St u dy Dr u g  ......................................................... 3 3  
9. 1. 3.  
Severity of A dverse Eve nt .......................................................................................... 3 3  
9. 1. 4.  
Seri o us A dverse Eve nts  ............................................................................................. 3 3  
9. 1. 5.  
A dverse Eve nts Le a di n g t o Per m a ne nt Tre at me nt Disc o nti n u ati o n  ......................... 3 3  
9. 1. 6.  
A dverse Eve nts Le a di n g t o St u dy Disc o nti n u ati o n  ................................................... 3 3  
9. 1. 7.  
A dverse Eve nts of S peci al I nterest ( A E SI)  ................................................................ 3 3  
9. 1. 8.  
A dverse Eve nts Le a di n g t o De at h  ............................................................................. 3 4  
9. 1. 9.  
De at h  ......................................................................................................................... 3 4  
9. 2.  C LI NI C A L L A B O R A T O R Y E V A L U A TI O N S  ........................................................................... 3 4  
9. 3.  V I T A L S I G N M E A S U R E M E N T S  ........................................................................................... 3 4  
9. 4.  P H Y SI C A L E X A MI N A TI O N  ................................................................................................. 3 5  
9. 5.  E L E C T R O C A R DI O G R A M  ..................................................................................................... 3 5  
9. 6.  O T H E R  S A F E T Y D A T A  ....................................................................................................... 3 5  
1 0.  
P H A R M A C O KI N E TI C S  ............................................................................................... 3 5  
1 1.  
P H A R M A C O D Y N A MI C S ............................................................................................. 3 5  
1 2.  
I N T E RI M A N A L Y SI S  ................................................................................................... 3 5  
1 3.  
C H A N G E S I N T H E P L A N N E D A N A L Y SI S  .............................................................. 3 6  
1 4.  
R E F E R E N C E S  ................................................................................................................ 3 6  
1 5.  
A P P E N DI C E S  ................................................................................................................. 3 8  
1 5. 1.  
S U M M A R Y O F S T A TI S TI C A L A N A L Y S E S  ......................................................................... 3 9  
1 5. 2.  
S C H E D U L E O F S T U D Y P R O C E D U R E S  .............................................................................. 4 1  
1 5. 3.  
M I S SI N G E F FI C A C Y D A T A  ............................................................................................. 4 6  
1 5. 3. 1.  
H a n dli n g of missi n g d at a a n d d at a w h ose i nter pret ati o ns h ave c h a n ge d  ............. 4 6  
1 5. 3. 2.  
H a n dli n g of missi n g d at a f or P atie nt -Re p orte d O utc o mes ( P R O S)  ...................... 4 6  
1 5. 3. 3.  
H a n dli n g of missi n g d at a f or Cli nici a n Re p orte d O utc o mes ( C LI N R O S) ............. 4 7  
1 5. 4.  
M I S SI N G S A F E T Y D A T A  ................................................................................................. 4 7  
1 5. 4. 1.  
H a n dli n g of missi n g a ge  ........................................................................................ 4 8  
1 5. 4. 2.  
H a n dli n g of c o m p ut ati o n of tre at me nt d ur ati o n if i nvesti g ati o n al me dici n al 
pr o d uct e n d of tre at me nt d ate is missi n g  ............................................................................... 4 8  
1 5. 4. 3.  
H a n dli n g of me dic ati o n missi n g/ p arti al d ates ....................................................... 4 8  
1 5. 4. 4.  
H a n dli n g of a dverse eve nts wit h missi n g or p arti al d ate/ti me of o nset ................. 4 8  
1 5. 4. 5.  
H a n dli n g of a dverse eve nts w he n d ate a n d ti me of first i nvesti g ati o n al me dici n al 
pr o d uct a d mi nistr ati o n is missi n g  .......................................................................................... 4 8  


Sa n ofi Gr o u p  
 
Fi nal Statistical A nal ysis Pla n, Versi o n 2. 0  
 
D u pil u ma b - L P S 1 5 4 9 7  
 
Date Iss ue d: 3 0J U L 2 0 2 1  
 
  
 
 
 V  
1 5. 4. 6 . 
H a n dli n g of missi n g assess me nt of rel ati o ns hi p of a dverse eve nts t o 
i nvesti g ati o n al me dici n al pr o d uct .......................................................................................... 4 8  
1 5. 4. 7.  
H a n dli n g of missi n g severity/ gr a des of a dverse eve nts  ......................................... 4 8  
1 5. 4. 8.  
H a n dli n g of p ote nti ally cli nic ally si g nific a nt a b n or m alities  ................................. 4 9  
1 5. 5.  
V I SI T W
I N D O W S ............................................................................................................ 4 9  
1 5. 6.  
S E A R C H C RI T E RI A F O R A E SI  ........................................................................................ 5 1  
1 5 . 7. 
P O T E N TI A L L Y C LI NI C A L L Y S I G NI FI C A N T A B N O R M A LI TI E S ( P C S A) C RI T E RI A  .............. 5 3  
1 5. 8.  
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) ...................................................................... 5 3  
1 5. 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) ........................................................... 6 0  
1 5. 9. 1.  
Cli nici a n Assess me nts ............................................................................................ 6 0  
1 5. 9 . 2. 
Ce nter Assiste d Assess me nts  ................................................................................. 6 1  
1 5. 1 0.  
O BJ E C TI V E A S S E S S M E N T S  .......................................................................................... 6 3  
1 5. 1 1.  
R E S C U E A N D P R O HI BI T E D M E DI C A TI O N S . .................................................................. 6 3  
L I S T O F T A B L E S 
Ta ble 3. 1. 1 - O bjecti ves a n d e n d p oi nts  ............................................................................................ 1  
Ta ble 3. 1. 2 S u m mar y of pri mar y esti ma n ds f or m ai n o bjecti ves  ................................................... 4  
Ta ble 4. 4. 1 Treat me nt la bels  ......................................................................................................... 1 0  
Ta ble 4. 5. 1 I nterc urre nt E ve nt T y pes  ........................................................................................... 1 2  
Ta ble 5. 2. 1 Ra n d o mizati o n a n d dr u g dis pe nsi n g irre g ularities  .................................................... 1 4  
Ta ble 1 5. 5. 1 A nal yses wi n d o w defi niti o n  .................................................................................... 4 9  
Ta ble 1 5. 6. 1 Searc h Criteria f or A E SI  .......................................................................................... 5 1  
Ta ble 1 5. 7. 1 P ote ntiall y Cli nicall y Si g nifica nt A b n or malities Criteria  ........................................ 5 3  
Ta ble 1 5. 8. 1 P R O MI S Slee p -Relat e d I m pair me nt c o n versi o n ta ble  ............................................ 5 4  
Ta ble 1 5. 9. 1 Rec o m me n de d usa ge of res ults i n t he a nal yses f or all c o m bi n ati o ns  ...................... 6 1  
LI S T O F FI G U R E S  
Fi g ure 3 -1 St u d y Pla n  ..................................................................................................................... 7  
L I S T O F A B B R E VI A TI O N S 
A C Q -5  
Ast h ma C o ntr ol Q uesti o n naire  
A D  
At o pic Der matitis  
A E  
A d verse E v e nt  
A E SI  
A d verse E v e nt of S pecial I nterest  
A N A M  
A ut o mate d Ne ur o ps y c h ol o gical Assess me nt Metri cs  
A N C O V A  A nal ysis of C o varia nce  
A R -V A S  
Aller gic R hi nitis -Vis ual A nal o g Scale  
A T C  
A nat o mical T hera pe utic C he mical  
B C P  
B usi ness C o nti n uit y Pla n  
B S A  
B o d y S urface Area  
CI  
C o nfi de nce I nter val  
C LI N R O  
Cli nicia n -Re p orte d O utc o me  
D P B  
Diast olic Bl o o d Press ure  
D L QI  
Der mat ol o g y Life Q u alit y I n d e x  
E A SI  
Ecze ma Area  Se verit y I n de x  
e C R F 
Electr o nic Case Re p ort F or m  


Sa n ofi Gr o u p  
 
Fi nal Statistical A nal ysis Pla n, Versi o n 2. 0  
 
D u pil u ma b - L P S 1 5 4 9 7  
 
Date Iss ue d: 3 0J U L 2 0 2 1  
 
  
 
  VI  
E S S  
E p w ort h Slee pi ness Scal e  
H A D S  
H os pital A n xiet y a n d De pressi o n Scale  
H L T  
Hi g h Le vel Ter m  
H L G T  
Hi g h Le vel Gr o u p T er m  
H R  
Heart Rate  
Ic E v 
I nterc urre nt E ve nt  
I C H 
I nter nati o nal C o nfere nce o n Har m o nisati o n 
I C F 
I nf or me d C o nse nt F or m 
I G A 
I n v esti gat or’s Gl o bal Ass ess me nt 
I M P 
I n v esti gati o nal Me dici nal Pr o d uct 
I T T 
inte nt -t o-treat 
L L T  
L o wer Le v el Ter m  
M A R  
Missi n g At Ra n d o m  
Me d D R A
 
Me dical Dicti o nar y f or R e g ulat or y A cti vities  
MI  
M ulti ple I m p utati o n  
M M R M  
Mi xe d M o del f or Re peate d Meas ures  
NI M P  
N o n -I n vesti gati o nal Me dici nal Pr o d uct  
N R S  
N u merical Rati n g Scale  
O L E  
O pe n -La b el E xte nsi o n  
P C S A  
P ote ntiall y Cli nicall y Si g nifica nt A b n or malities  
P O E M  
Patie nt Orie nte d Ecze ma Meas ure  
P R O  
Patie nt -Re p orte d O utc o me  
P R O MI S  
Patie nt -Re p orte d O utc o mes Meas ure m e nt I nf or mati o n S yste m  
P S G  
P ol ys o m n o gra p h y  
P T  
Preferre d Ter m  
P V T  
Ps yc h o m ot or Vi gila nce Test  
Q 1  
First Q uartile  
Q 2 W  
E ver y 2 Wee ks  
Q 3  
T hir d Q uartile  
R O W  
Rest o f W orl d 
Q o L  
Q ualit y of Life  
S A E  
S eri o us A d verse E v e nt  
S B P  
S yst olic Bl o o d Press ure  
S C O R A D  
S C O Ri n g At o pic Der matitis  
S D  
Sta n dar d De viati o n  
S E  
Slee p Efficie n c y  
S O C  
S yste m Or ga n Class  
S O L  
Slee p O nset Late n c y  
T E A E  
T reat me nt-E mer ge nt A d verse E ve nts  
T S T  
T otal Slee p Ti me  
V A S  
Vis ual A nal o g Scale  
W A S O  
Wa ke After Slee p O nset  
W N R G  
Was hi n gt o n Ne ur o ps y c h ol o g y Researc h Gr o u p, L L C  
W O C F  
W orst O bser vati o n Carri e d F or war d  
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 -At o pic Der matitis  
W H O -D D  
W orl d Healt h Or ga niz ati o n -Dr u g Dicti o nar y  


Sa n ofi Gr o u p  
 
Fi nal Statistical A nal ysis Pla n, Versi o n 2. 0  
 
D u pil u ma b - L P S 1 5 4 9 7  
 
Date Iss ue d: 3 0J U L 2 0 2 1  
 
  
 
 
 1  
 
D oc u me nt Hist or y –  C h a n ges c o m p are d t o pre vi o us versi o n of S A P  
 
Versi o n  
D ate  
C h a n ges  
Fi nal 1. 0  
0 4 M A Y 2 0 2 1  
I nitiati o n 
Fi nal 2. 0  
3 0J U L 2 0 2 1  
•  
S u b gr o u p a nal ysis base d o n Disease D urati o n has bee n 
re m o ve d as disease o nset is n ot c ollecte d 
•  
Baseli ne defi niti o n f or dail y assess me nts has bee n u p date d t o 
i ncl u de o ne patie nt w h o c o m plete d baseli ne assess me nt fr o m 
-1 3 t o -7 i nstea d of -6 t o Da y 0.  
•  
F or t he res p o n der a nal ysis o n E A SI, t he a nal ysis m o del has 
bee n c ha n ge d fr o m G E N M O D t o G LI M MI X.  
•  
P R O MI S missi n g ite m sc ore i m p utati o n r ule has bee n 
u p date d  
•  
A d de d s o me details f or retest a p pr oac h of Ps yc h o m ot or 
Vi gila nce Test.  
•  
Slee p diar y ill o gical data ha n dli n g r ules has bee n a d de d as a n 
S A P a d de n d u m.  
 
1.  I ntr o d ucti o n 
T his d oc u me nt pr o vi des t he det aile d statistical met h o d ol o g y f or t he a nal ysis of data fr o m t he Sa n ofi Gr o u p 
st u d y L P S 1 5 4 9 7. T he ta ble, listi n g a n d fi g ure s hells s u p p orti n g t he statistical a nal ysis pla n ( S A P) ca n be 
f o u n d i n a se parate S A P s hell d oc u me nt. 
 
T he a nal yses descri be d herei n are base d o n t he cli nical trial pr ot oc ol  (A me n d me nt 2), V ersi o n 1. 0, date d 
o n 7 t h A pril 2 0 2 0.  A n y  c ha n ges  or re visi o ns  t o t he pla n ne d a nal ysis descri be d i n t his d oc u me nt will be ma de 
pri or t o data base l oc k . 
2.  St u d y O bj e cti v e s , E n d p oi nt s  a n d E sti m a n d s  
T he st u d y o bjecti ves a n d c orres p o n di n g e n d p oi nts are s h o w n i n t h e Ta ble 3. 1 .1 . 
 
Ta ble 3. 1 .1 - O bjecti ves a n d e n d p oi nts  
O bjecti ve s 
E n d p oi nt s 
Pri m ar y  
•  
T o e val uate t he effect of 
d u pil u ma b  o n slee p q ualit y i n 
a d ult patie nts wit h m o derate 
t o se vere at o pic der matitis 
( A D) 
•  
Perce nta ge c ha n ge fr o m baseli ne t o wee k 1 2 i n slee p 
q ualit y n u merical rati n g scale ( N R S)  
Sec o n d ar y  
•  
T o e val uate t he effect of 
d u pil u ma b  o n o bjecti ve a n d 
s u bjecti ve q ua ntitati ve  slee p 
para meters, A D -relate d 
o utc o mes, a n d t he da yti me 
•  
C ha n ge fr o m baseli ne t o wee k 1 2 i n slee p efficie nc y 
( S E) base d o n acti gra p h y data 
•  
C ha n ge fr o m baseli ne t o wee k 1 2 i n t otal slee p ti me 
( T S T) base d o n acti gra p h y data 
•  
C ha n ge fr o m baseli ne t o wee k 1 2 i n wa ke after slee p 
o nset ( W A S O) base d o n acti gra p h y data  


Sa n ofi Gr o u p  
 
Fi nal Statistical A nal ysis Pla n, Versi o n 2. 0  
 
D u pil u ma b - L P S 1 5 4 9 7  
 
Date Iss ue d: 3 0J U L 2 0 2 1  
 
  
 
 
 2  
c o nse q ue nces of slee p 
de pri vati o n  
•  
C ha n ge fr o m baseli ne t o wee k 1 2 i n slee p o nset 
late nc y ( S O L) base d o n acti gra p h y data  
•  
Perce nt c ha n ge fr o m baseli ne t o wee k 1 2 i n Pr urit us 
N R S  
•  
C ha n ge fr o m baseli ne t o wee k 1 2 i n S C O Ri n g At o pic 
Der matitis ( S C O R A D) t otal sc ore  
•  
C ha n ge fr o m baseli ne t o wee k 1 2 i n S C O R A D slee p 
V is ual A nal o g S cale ( V A S) 
•  
E A SI 5 0 (re d ucti o n of E cze ma A rea Se verit y I n de x 
[ E ASI ] sc ore b y ≥5 0 % fr o m ba seli ne) at wee k 1 2 
•  
E A SI 7 5 (re d ucti o n of E A SI sc ore b y ≥7 5 % fr o m 
baseli ne) at wee k 1 2  
•  
E A SI 9 0 (re d ucti o n of E A SI sc ore b y ≥9 0 % fr o m 
baseli ne) at wee k 1 2.  
•  
C ha n ge fr o m baseli ne t o wee k 1 2 i n Patie nt Orie nte d 
Ecze ma Meas ure ( P O E M) t otal sc ore  
•  
C ha n ge fr o m baseli ne t o wee k 1 2 i n Der mat ol o g y 
Life Q ualit y I n de x ( D L QI) t otal sc ore  
•  
C ha n ge fr o m baseli ne t o wee k 1 2 i n 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 ) Slee p Relate d I m pair me nt S F 8a T otal 
Sc ore  
 
 
•  
T o c o nti n ue t o  assess  safet y 
a n d t olera bilit y of d u pil u ma b  
t hr o u g h o ut t he st u d y 
•  
I nci de nce of a d verse e ve nts t hr o u g h wee k 1 2 
•  
I nci de nce of a d verse e ve nts t hr o u g h wee k 2 4 
Ot her E x pl or at or y  
•  
T o f urt her e val uate t he effect 
of d u pil u ma b  o n o bjecti ve 
a n d s u bjecti ve slee p 
para meters, A D -relate d 
o utc o mes a n d da yti me 
c o nse q ue nces of slee p 
de pri vati o n  
•  
Perce nt c ha n ge fr o m baseli ne i n slee p q ualit y N R S t o 
wee k 1, 2, 4 a n d 8  
•  
Perce nt c ha n ge fr o m baseli ne i n pr urit us N R S t o wee k 
1, 2, 4 a n d 8  
•  
C ha n ge fr o m baseli ne i n S E  base d o n acti gra p h y t o 
wee k 1, 2, 4 a n d 8  
•  
C ha n ge fr o m baseli ne i n W A S O base d o n acti gra p h y 
t o wee k 1, 2, 4 a n d 8 
•  
C ha n ge fr o m baseli ne i n T S T base d o n acti gra p h y t o 
wee k 1, 2, 4 a n d 8  
•  
C ha n ge fr o m baseli ne i n S O L  base d o n acti gra p h y t o  
wee k 1, 2, 4 a n d 8  
•  
C ha n ge fr o m baseli ne i n S C O R A D t otal sc ore a n d 
slee p V A S t o wee k 1, 2, 4 a n d 8 
•  
E A SI 5 0 , E A SI 7 5 a n d E A SI 9 0 at wee ks 1, 2, 4 a n d 8  
•  
C ha n ge fr o m baseli ne t o wee k 1 2 i n 
p ol ys o m n o gra p h y ( P S G)  meas ures of S E , T S T, 
W A S O a n d S O L  
•  
C ha n ge fr o m baseli ne t o wee ks 1, 2, 4 a n d 8 i n 
P R O MI S Slee p Relate d I m pair me nt S F 8a t otal sc ore  
•  
C ha n ge fr o m baseli ne t o wee ks 1, 2, 4, 8 a n d 1 2 i n 
s ki n pai n N R S 


Sa n ofi Gr o u p  
 
Fi nal Statistical A nal ysis Pla n, Versi o n 2. 0  
 
D u pil u ma b - L P S 1 5 4 9 7  
 
Date Iss ue d: 3 0J U L 2 0 2 1  
 
  
 
 
 3  
•  
C ha n ge fr o m baseli ne t o wee ks 1, 2, 4, 8 a n d 1 2 i n 
s ki n se nsiti vit y t o t o uc h N R S 
•  
C ha n ge fr o m baseli ne t o we e ks 1, 2, 4, 8 a n d 1 2 i n 
s ki n b ur n N R S 
•  
C ha n ge fr o m baseli ne i n S O L, T S T, n u m ber of 
a wa ke ni n gs, W A S O, S E  a n d h o w reste d t he 
partici pa nt felt w he n getti n g u p at wee k 1, 2, 4, 8 a n d 
1 2 base d o n slee p diar y  
•  
C ha n ge fr o m baseli ne t o wee k 4 a n d 1 2 i n E p w ort h 
Slee pi ness Scale ( E S S)  
•  
C ha n ge fr o m baseli ne t o wee k 1 2 i n ps yc h o m ot or 
vi gila nce test ( P V T)  
•  
C ha n ge fr o m baseli ne t o wee k 1 2 i n R u n ni n g 
Me m or y, Mat he matical Pr ocessi n g a n d Pr oce d ural 
Reacti o n Ti me sc ores base d o n t he ne ur oc o g niti ve test 
( A ut o mate d Ne ur o ps yc h ol o gical Assess me nt metrics 
[ A N A M]) 
•  
W or k pr o d ucti vit y a n d acti vit y i m pair me nt –  At o pic 
Der matitis versi o n ( W P AI -A D) ass ociate d q uesti o ns 
c ha n ge fr o m baseli ne t o wee ks 4, 8 a n d 1 2  
•  
Misse d sc h o ol/ w or k da ys  fr o m baseli ne t o wee k 1 2  
 
 
•  
T o e val uate t he relati o ns hi p 
bet wee n slee p dist ur ba nce 
a n d ot her o bjecti ve a n d 
s u bjecti ve para meters 
ass ociate d wit h A D 
•  
Relati o ns hi p bet wee n varia bles relati n g t o slee p 
dist ur ba nces (e g, T S T, W A S O) a n d o bjecti ve a n d 
s u bjecti ve para meters ass ociate d wit h A D (e g, E A SI, 
S C O R A D, pr urit us N R S, D L QI, s ki n pai n N R S, s ki n 
b ur n N R S a n d se nsiti vit y t o t o uc h N R S)  
 
 
•  
T o e val uate t he effect of 
d u pil u ma b  i n c o m or bi d 
c o n diti o ns 
•  
C ha n ge fr o m baseli ne t o wee k 1 2 i n A C Q -5 a m o n g 
t h ose w h o re p orte d ast h ma at baseli ne 
•  
C ha n ge fr o m baseli ne t o w ee k 1 2 Aller gic R hi nitis -
Vis ual A nal o g Scale ( A R -V A S) a m o n g t h ose w h o 
re p orte d aller gic r hi nitis at baseli ne 
•  
C ha n ge fr o m baseli ne t o wee ks 4 a n d 1 2 i n H os pital 
A n xiet y a n d De pressi o n Scale ( H A D S )-a n xiet y a n d 
H A D S -de pressi o n sc ores  
 
 
•  
T o e val uate t he effect of 
d u pil u ma b  o n i n di vi d ual 
q ua ntitati ve a n d n o n -slee p 
relate d e n d p oi nts ass ociate d 
wit h A D at Wee k 2 4  
•  
C ha n ge or perce nt c ha n ge (as use d i n a nal yses of 
wee k 1 2 data) fr o m baseli ne t o wee k 2 4 f or pri mar y 
a n d sec o n dar y e n d p oi nts  
•  
C ha n ge or perce nt c ha n ge (as use d i n a nal yses of 
wee k 1 2 data) fr o m wee k 1 2 t o wee k 2 4 f or pri mar y 
a n d sec o n dar y e n d p oi nts  
 


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Fi nal Statistical A nal ysis Pla n, Versi o n 2. 0  
 
D u pil u ma b - L P S 1 5 4 9 7  
 
Date Iss ue d: 3 0J U L 2 0 2 1  
 
  
 
 
 4  
Ta ble 3. 1 .2  S u m mar y of pri mar y esti ma n d s f or mai n o bjecti ves  
E n d p oi nt 
C ate g or y  
(esti m a n d) 
Esti m a n ds  
 
E n d p oi nt(s) a 
P o p ul ati o n  
I nterc urre nt e ve nt(s) h a n dli n g  str ate g y 
P o p ul ati o n -le vel s u m m ar y 
( A n al ysis a n d missi n g d at a 
h a n dli n g)  
 
Pri m ar y o bjecti ve: T o e val uate t he effect of d u pil u ma b  o n slee p q ualit y i n a d ult patie nts wit h m o derate t o se vere at o pic der matitis ( A D).  
 
Pri mar y e n d p oi nt  
Perce nta ge 
c ha n ge fr o m 
baseli ne t o 
Wee k 1 2 i n 
slee p q ualit y 
N R S  
I T T 
•  
Disc o nti n uati o n  or i nterr u pti o n  of st u d y treat me nt d ue t o 
C o vi d -1 9 pa n de mic, off -treat me nt data will be set as 
missi n g  (h y p ot hetical  strate g y). T he assess me nts after 
patie nts res u me treat me nt will be use d.  
•  
Disc o nti n uati o n or i nterr u pti o n of st u d y treat me nt n ot d ue t o 
C o vi d -1 9 pa n de mic, all data c ollecte d f oll o wi n g sc he d ule 
after t he treat me nt disc o nti n uati o n will be use d i n t he 
a nal ysis (treat me nt p olic y strate g y).  
•  
Ta ki n g resc ue me dicati o ns  b pri or t o Wee k 1 2: data will be 
set t o missi n g val ues after t he me dicati o n usa ge 
( h y p ot hetical strate g y) 
•  
Ta ki n g pr o hi bite d me dicati o ns  b t hat affect slee p: All slee p 
relate d assess me nts (slee p N R S, S C O Ri n g s u bjecti ve slee p 
l oss sc ores, P R O MI S slee p dist ur ba nce s h ort f or m 8a 
i n di vi d ual q uesti o n sc ores, ES S, acti gra p h y data) o n t hat 
c orres p o n di n g ni g ht will be set t o missi n g  ( h y p ot hetical 
strate g y) 
•  
Ta ki n g pr o hi bite d me dicati o ns  b t hat affect A D, data will be 
set t o missi n g val ues after t he me dicati o n usa ge 
( h y p ot hetical strate g y) 
A  mi xe d effect m o del f or 
re peate d meas ures ( M M R M) 
u n der t he missi n g at ra n d o m 
( M A R) fra me w or k will be 
use d . T he M M R M will 
i ncl u de treat me nt, baseli ne 
val ue, ra n d o miz ati o n strat u m, 
visits ( u p t o wee k 1 2), 
treat me nt b y visit i nteracti o n, 
a n d baseli ne slee p q ualit y 
N R S b y visit i nteracti o n ter ms 
all as fi xe d effects.  
Ra n d o mizati o n strat u m, 
treat me nt a n d visits will be 
c o nsi dere d as cate g orical 
para meters.  N o e x plicit 
i m putati o n will be d o ne f or 
missi n g data.  
 
Sec o n d ar y o bjecti ve: T o e val uate t he effect of d u pil u ma b  o n o bjecti ve  a n d s u bjecti ve q ua ntitati ve slee p para meters, A D  relate d o utc o mes, a n d 
da yti me c o nse q ue nces of  slee p de pri vati o n. 
 


Sa n ofi Gr o u p  
Fi nal Statistical A nal ysis Pla n, Versi o n 2. 0  
D u pil u ma b - L P S 1 5 4 9 7  
Date Iss ue d: 3 0J U L 2 0 2 1  
 5  
E n d p oi nt 
C ate g or y  
(esti m a n d) 
Esti m a n ds  
E n d p oi nt(s) a 
P o p ul ati o n  
I nterc urre nt e ve nt(s) h a n dli n g  str ate g y 
P o p ul ati o n -le vel s u m m ar y 
( A n al ysis a n d missi n g d at a 
h a n dli n g)  
Sec o n dar y e n d p oi nt 
(treat me nt p olic y 
strate g y/ h y p ot hetical 
strate g y) 
C ha n ge or 
perce nt 
c ha n ge fr o m 
baseli ne i n 
Slee p a n d 
A D relate d  
o u tc o mes 
I T T 
Sa me as t he pri mar y e n d p oi nt  
T he sa me M M R M wit h t he 
baseli ne val ues c orres p o n di n g 
t o t he o utc o me varia bles. 
a  A d diti o nal  ke y  sec o n dar y e n d p oi nts are n ot i ncl u de d i n t his ta ble b ut w o ul d be ha n dle d wit h a si milar strate g y as t he e n d p oi nt t y pe (ie c o nt i n u o us, 
bi nar y , ti me-t o-e ve nt) at ot her wee ks . T he ke y sec o n dar y e n d p oi nts are liste d i n Secti o n 8. 2. 2 3 . 
b  Selecte d pr o hi bite d me dicati o ns a n d/ or resc ue me dicati o ns are liste d i n  Secti o n  1 5. 1 1 . 


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Fi nal Statistical A nal ysis Pla n, Versi o n 2. 0  
 
D u pil u ma b - L P S 1 5 4 9 7  
 
Date Iss ue d: 3 0J U L 2 0 2 1  
 
  
 
 
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3.  I n vesti g ati o n al Pl a n 
3. 1.  O ver all St u d y Desi g n a n d Pl a n  
T his is a P hase I V, pr os pecti ve, 2: 1 ra n d o mize d, m ulti nati o nal, m ultice nter 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 derat e t o se vere A D. 
 
A p pr o xi matel y 2 0 1 partici 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 e val 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 plete t he d o u ble -bli n d p orti o n (t o wee k 1 2) of t he st u d y.  
 
T he st u d y will c o m prise of:  
•  
Scree ni n g Peri o d 1 ( Da y -2 8 t o -8): Patie nts will be e val uate d acc or di n g t o i ncl usi o n a n d e xcl usi o n 
criteria 
•  
Scree ni n g Peri o d 2 ( Da y -7 t o -1; pre -baseli ne assess me nts): eli gi ble patie 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 k i 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 he 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 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 ble -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 pe n -la bel 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 ve acti ve treat me nt f or 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 2 8 wee ks.  A patie nt is c o nsi dere d t o ha ve c o m plete 
t he st u d y if he/s he has c o m plete d all p hases of t he st u d y i ncl u di n g t he last sc he d ule d visit s h o w n i n t he 
Sc he d ules of Acti vities (see A p pe n di x 1 5. 2 ). 
 
 


Sa n ofi Gr o u p  
 
Fi nal Statistical A nal ysis Pla n, Versi o n 2. 0  
 
D u pil u ma b - L P S 1 5 4 9 7  
 
Date Iss ue d: 3 0J U L 2 0 2 1  
 
  
 
 
 7  
Fi g ure 3 -1  St u d y Pla n  
 
P S G s u b -st u d y: of t he 2 0 1 partici pa nts, a p pr o xi matel 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 a P S G s u b -st u d y at selecte d U S sites . Eac h patie nt w h o partici pates 
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 ; 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 Wee 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 partici pati n g slee p ce nters a n d a vaila bilit y f or 
o ver ni g ht sta y.  
3. 2.  St u d y E n d p oi nts  
T he st u d y o bjecti ves a n d c orres p o n di n g e n d p oi nts are s h o w n i n t he  Ta ble 3. 1 .1 . 
3. 3.  Tre at me nts   
T he d ose selecte 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 vere A D f or 
D u pi xe nt i n U S, E U, a n d all ot her c o u ntries t hat t his st u d y will be c o n d ucte d.  
 
Patie nts will recei ve eit her;  
•  
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 oa di n g d ose), 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 ver y t w o wee ks ( Q 2 W) u ntil wee 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 otect t he bli n d w hile patie nts i n place b o  ar m  recei ve t heir 
l oa di n g d ose), f oll o we d b y 1 3 0 0 m g d u 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 place b o f or d u pil u ma b  ( 2 x 2 m L place b o i njecti o ns) o n Da y 1 (ie, t he l oa di n g d ose), 
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 d u pil u ma b  i njecti o ns Q 2 W wit h last i njecti o n at wee k 2 2. 
N o n -i n vesti g ati o n al me dic al pr o d ucts 
Starti n g o n Da y -7 , all patie nts are re q uire d t o u n der g o bac k gr o u n d treat me nt wit h me di u m -p ote nc y t o pical 
c ortic oster oi ds ( T C S) [i.e., n o n -i n vesti gati o nal me dical pr o d ucts ( NI M P)]. 


Sa n ofi Gr o u p  
 
Fi nal Statistical A nal ysis Pla n, Versi o n 2. 0  
 
D u pil u ma b - L P S 1 5 4 9 7  
 
Date Iss ue d: 3 0J U L 2 0 2 1  
 
  
 
 
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3. 4.  D ose A dj ust me nt/ M o dific ati o ns  
D ose m o dificati o n of d u pil u ma b  f or a n i n di vi d ual patie nt is n ot all o we d. 
4.  Ge ner al St atistic al C o nsi der ati o ns  
4. 1.  S a m ple Size  
T he sa m ple size calc ulati o ns were base d o n t he s u bset of patie nts w h o re p orte d ≥5 u nits 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 slee 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) 
data was use d as a basis f or t he sa m ple size 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 viati o n) esti mate f or t he s u bset of patie nts me nti o ne d a b o ve was 3 7 % f or t he % c ha n ge fr o m baseli ne t o 
wee k 1 2. Gi ve n t he u ncertai nt y i n t h e varia bilit y fr o m t his varia ble t o t he N R S wee kl y a vera ge slee p sc ore, 
t he a b o ve varia 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 slee 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) patie 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 nce of 2 5 % (effect size, Δ/ σ = 0. 5 7) f or t he 
perce nt c ha 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  N e 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 utes differe nce bet wee n treat me nts:  ( 2: 1 all ocati o n rati o; 
al p ha = 0. 0 5, 2 -si de d), ass u mi n g t he sa me 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 nee de d t o pr o vi de 9 0 % p o wer. F urt her m ore, t he pr o p ose d sa m ple size 
w o ul d ha ve > 9 0 % p o wer t o detect a differe nce of 1 0 % f or c ha n ge fr o m baseli ne i n acti gra p h y base d slee p 
efficie nc y, ass u mi n g a varia bilit y of 1 1 % (al p ha = 0. 0 5, 2 -si de d). T he varia bilit y esti mate was base d o n f or 
acti gra p h y base d slee p efficie nc y at wee k 4, i nflate d b y 5 0 % t o acc o u nt f or p ossi ble i ncrease 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 data use d f or acti gra p h y para meters are li mite d.  
 
All o wi n g f or 2 0 % 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 olle d i n t he st u d y. 
 
C o nsi deri n g t he u ncertai nt y of t he varia bilit y of t he pri mar y e n d p oi nt, w he n data are a vaila 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  c o m pleti n g Wee k 1 2 , t he varia bilit y will be assesse d i n a bli n de d 
ma n ner,  a n d t he sa m ple size will be re -esti mate d. If t he re -esti mate d sa m ple size is hi g her t ha n t he ori gi nal  
esti mate, t he sa m ple size ma y be i ncrease d acc or di n gl y, n ot t o e xcee d a t otal of 1 5 0 a d diti o nal  patie nts.  
 
Si nce t his a nal y sis 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 nal ysis. 
4. 2.  R a n d o miz ati o n, Str atific ati o n, a n d Bli n di n g  
Ra n d o mizati o n will be stratifie d b y: P S G (re gar dless of ge o gra p hic l ocati o n), n o n -P S G U S, n o n -P S G 
E ur o pe a n d n o n -P S G rest of w orl d ( R O W).   
 
A partici pa nt w h o has bee n all ocate d t o a ra n d o mize d i nter ve nti o n re gar dless 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 nteracti ve res p o nse tec h n ol o g y (I R T) will be 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. 
 


Sa n ofi Gr o u p  
 
Fi nal Statistical A nal ysis Pla n, Versi o n 2. 0  
 
D u pil u ma b - L P S 1 5 4 9 7  
 
Date Iss ue d: 3 0J U L 2 0 2 1  
 
  
 
 
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4. 3.  A n al ysis Sets  
Patie nts e x p ose d t o I M P bef ore or  wit h o ut bei n g ra n d o mize d will n ot be c o nsi dere d ra n d o mize d a n d will 
n ot be i ncl u de d i n a n y a nal ysis set  a n d will be re p orte d i n listi n g s u n der a treat me nt gr o u p na me d “ n ot 
ra n d o mize d b ut treate d”. H o we ver, if t hese patie nts e x perie nce d a n y safet y e ve nt, t he y w o ul d be 
d oc u me nte d se paratel y i n t he cli nical st u d y re p ort.  
 
Patie nts ra n d o mize d b ut n ot treate d will b e i ncl u de d i n a n y efficac y a nal yses a n d  will be re p orte d i n listi n g s 
u n der a treat me nt gr o u p na me d “ra n d o mize d b ut n ot treate d”. T hese patie nts will be a nal yze d f or efficac y 
a nal yses acc or di n g t o t he treat me nt gr o u p t o w hic h t he y are all ocate d t o b y t he I R T.  
4. 3. 1.  Scree ne d  A n al ysis Set  
T he Scree ne d  a nal ysis set i ncl u des all partici pa nts w h o si g n t he i nf or me d c o nse nt f or m (I C F).  
4. 3. 2.  I nte nt-t o-Tre at (I T T)  A n al ysis Set  
T he Inte nt -t o-T reat a nal ysis set  (I T T) c o nsists of ra n d o mize d patie nts  ( patie nts wit h a treat me nt kit n u m ber 
all ocate d a n d rec or de d i n t he I R T data base, re gar dless of w het her t he treat me nt kit was use d or n ot) . 
4. 3. 3.  M o difie d I T T ( mI T T) A n al ysis Set  
T he m o difie d I T T a nal ysis set ( mI T T) c o nsists of I T T patie nts w h o ha d a baseli ne a n d at least o ne p ost -
baseli ne meas ure me nt.  
4. 3. 4.  O L E A n al ysis Set  
T he O pe n -La bel E xte nsi o n ( O L E ) a nal ysis set c o nsists of  I T T patie nts w h o c o m plete d t he d o u ble -bli n d 
treat me nt, e ntere d t he o pe n la bel e xte nsi o n peri o d a n d t o o k at least o ne d ose d uri n g t he O L E peri o d.  
4. 3. 5.  P S G A n al ysis Set  
T he P S G a nal ysis set c o nsists of I T T patie nts w h o partici pate d i n t he P S G s u b-st u d y a n d ha ve b ot h baseli ne 
a n d at least o ne p ost -baseli ne P S G assess me nt.  
4. 3. 6.  S afet y  A n al ysis Set  
T he S afet y a nal ysis set i ncl u des all ra n d o mize d patie nts w h o act uall y recei ve d at least 1 d ose or partial d ose 
of t he I M P , a nal yze d acc or di n g t o t he treat me nt act uall y recei ve d. 
 
Ra n d o mize d patie nts f or w h o m it is u nclear w het her t he st u d y me dicati o n was ta ke n will be i ncl u de d i n t he 
safet y a nal ysis set as ra n d o mize d. 
 
F or patie nts recei vi n g m ore t ha n o ne I M P ( place b o a n d d u pil u ma b ) d uri n g t he st u d y, t he act ual treat me nt  
gr o u p f or as treate d a nal ysis will be t he d u pil u ma b  gr o u p.  
4. 3. 7.  A n al ysis set wit h o ut tri al i m p act ( disr u pti o n) d ue t o C O VI D -1 9  
T he a nal ysis set wit h o ut trial i m pact ( disr u pti o n) d ue t o C O VI D -1 9 i ncl u des a n y patie nt:  
- 
wit h o ut a n y critical or maj or pr ot oc ol de viati o n relate d t o C O VI D -1 9  
- 
a n d w h o di d n ot per ma ne ntl y disc o nti n ue treat me nt d ue t o C O VI D -1 9  
- 
a n d w h o di d n ot per ma ne ntl y disc o nti n ue st u d y d ue t o C O VI D -1 9  
4. 3. 8.  A n al ysis set wit h tri al i m p act ( disr u pti o n) d ue t o C O VI D -1 9  
T he a nal ysis set wit h trial i m pact ( disr u pti o n) d ue t o  C O VI D -1 9 i ncl u des a n y patie nt:  
- 
wit h a n y critical or maj or pr ot oc ol de viati o n relate d t o C O VI D -1 9  


Sa n ofi Gr o u p  
 
Fi nal Statistical A nal ysis Pla n, Versi o n 2. 0  
 
D u pil u ma b - L P S 1 5 4 9 7  
 
Date Iss ue d: 3 0J U L 2 0 2 1  
 
  
 
  1 0  
- 
or w h o per ma ne ntl y disc o nti n ue d treat me nt d ue t o C O VI D -1 9  
- 
or w h o per ma ne ntl y disc o nti n ue d st u d y d ue t o C O VI D -1 9  
 
Critical or maj or pr ot oc ol de viati o ns relate d t o C O VI D -1 9 will be re vie we d a n d fi nalize d bef ore data base 
l oc k. 
4. 4.  Re p orti n g C o n ve nti o ns  
Statistical a nal ysis will be perf or me d usi n g S A S ® Versi o n 9. 4 or hi g her.  
 
Sta n dar dize d a n d vali date d S A S macr os fr o m P P D will be use d t o set -u p ta ble,  listi n g, fi g ure ( T L F) f or mats 
( hea ders/f o oters a n d ta b ulati o n f or mat) a n d ta b ulate t he s u m maries. All ta bles a n d listi n gs will be 
i n de pe n de ntl y vali date d usi n g d o u ble pr o gra m mi n g; all fi g ures will be i n de pe n de ntl y vali date d ma n uall y. 
4. 4. 1.  Tre at me nt l a bels  
T he f oll o wi n g treat me nt la bels will be use d i n t he Ta bles, Fi g ures a n d Listi n gs. W here a p plica ble, i n t he 
listi n g,  
•  
patie nts w h o are ra n d o mize d b ut n ot treate d will be prese nte d i n a “ Ra n d o mize d, n ot  treate d” 
c ol u m n/ b y -li ne state me nt, w hic h will be prese nte d pri or a n y ot her treat me nt gr o u p, 
•  
p atie nts  w h o are n ot ra n d o mize d b ut treate d will be prese nte d i n a “ N ot ra n d o mize d, treate d” 
c ol u m n/ b y li ne state me nt, w hic h will be prese nte d pri or a n y ot her trea t me nt gr o u p. 
 
Ta ble 4. 4 .1  Treat me nt la bels  
Tre at me nt or der  
Tre at me nt gr o u p  
Tre at me nt L a bel  
1  
N ot ra n d o mize d, treate d  
N ot ra n d o mize d, treate d  
2  
Ra n d o mize d, n ot treate d  
Ra n d o mize d, n ot treate d  
3  
Place b o  
Place b o  
4  
D u pil u ma b  3 0 0 m g q 2 w  
D u pil u ma b  3 0 0 m g q 2 w  
5  
T otal  
T otal  
 
4. 4. 2.  Visit n a mi n g C o n ve nti o ns  
T he electr o nic Case Re p ort F or m (e C R F ) visit la bel will be use d t o classif y t he assess me nts.  
4. 4. 3.  Visit Wi n d o ws  
T he visit wi n d o ws as defi ne d i n  Secti o n 1 5. 5  will be a p plie d t o all e n d p oi nts . 
4. 4. 4.  U nsc he d ule d Visits  
U nsc he d ule d visit meas ure me nts will be use d i n t he a nal ysis o n efficac y varia bles a n d will be i ncl u de d i n 
t he b y-visit s u m maries f or t he safet y varia bles if t he y are re-all ocate d t o sc he d ule d visits  acc or di n g t o t he 
visit wi n d o w defi niti o ns i n S ecti o n 1 5. 5 . 
4. 4. 5.  Dis pl a y of D at a S u m m ar y a n d A n al ysis  
C o nti n u o us varia bles will be s u m marize d usi n g descri pti ve statistics, i ncl u di n g t he f oll o wi n g: sa m ple size 
( n), mea n, sta n dar d de viati o n ( S D), me dia n, first q uartile ( Q 1), t hir d q uartile ( Q 3), mi ni m u m a n d ma xi m u m 
f or eac h treat me nt gr o u p. 
 


Sa n ofi Gr o u p  
 
Fi nal Statistical A nal ysis Pla n, Versi o n 2. 0  
 
D u pil u ma b - L P S 1 5 4 9 7  
 
Date Iss ue d: 3 0J U L 2 0 2 1  
 
  
 
  1 1  
All mea n , Q 1, Q 3  a n d me dia n val ues will be f or matte d t o o ne m ore deci mal place t ha n t he meas ure d val ue. 
S D  val ues will be f or matte d t o t w o m ore deci mal places t ha n t he meas ure d val ue. Mi ni m u m a n d ma xi m u m 
will be f or matte d t o t he sa me n u m ber of deci mal  places  as t he meas ur e d val ue. 
 
9 5 % c o nfi de nce i nter vals ( C Is) will be t w o-si de d a n d dis pla ye d t o t he sa me le vel of precisi o n as t he statistic 
t he y relate t o. If a n esti mate or a CI is n ot esti ma ble, it will be prese nte d as ‘N E ’. If neit her a n esti mate, n or 
its CI are esti ma ble, it will be prese nte d as si m pl y ‘N E ’, n ot dis pla yi n g ‘N E ’ t wice. 
 
T he p -val ues will be t w o -si de d a n d will be r o u n de d t o t hree deci mal places. If a p-val ue is less t ha n 0. 0 0 1 
it will be re p orte d as ‘ < 0. 0 0 1’. If a p-val ue is greater t ha n 0. 9 9 9 it will be r e p orte d as ‘ > 0. 9 9 9’.  
 
Cate g orical a n d or di nal data will be s u m marize d usi n g t he c o u nts a n d perce nta ge s. W he n c o u nt data are 
prese nte d, t he perce nt will be s u p presse d w he n t he c o u nt is zer o i n or der t o dra w atte nti o n t o t he n o n -zer o 
c o u nts. A r o w de n ote d ‘ Missi n g” will be i ncl u de d i n c o u nt ta b ulati o ns f or de m o gra p hics, baseli ne 
c haracteristics a n d c o m plia n ce t o acc o u nt f or missi n g val ues. N o perce nta ges will be dis pla ye d o n t he 
‘ Missi n g’ r o ws a n d t he perce nta ges o n t he ot her r o ws will be base d o n t he n u m ber of n o n -missi n g 
o bser vati o ns. U nless ot her wise s pecifie d, t he de n o mi nat or f or all ot her perce nta ges wi ll be t he n u m ber of 
s u bjects i n t hat treat me nt wit hi n t he s pecific a nal ysis set of i nterest. All perce nta ges will be r o u n de d t o o ne 
deci mal place. T he n u m ber a n d perce nta ge of res p o nses will be prese nte d i n t he f or m x x ( x x. x), w here t he 
perce nta ge is i n t h e pare nt heses. W he n  t he n u merat or is e q ual t o t he de n o mi nat or, t he perce nta ge s h o ul d be 
prese nte d as ( 1 0 0) i nstea d of ( 1 0 0. 0).  
 
All listi n gs will be s orte d f or prese ntati o n i n or der of assi g ne d treat me nt ar m, st u d y ce nter  n u m ber , patie nt 
n u m ber a n d date of  pr oce d ure or e ve nt.  
 
4. 4. 6.  B aseli ne , st u d y d a y a n d d ur ati o n deri v ati o ns 
T he baseli ne val ue of efficac y para meters is defi ne d as t he last a vaila ble vali d ( n o n -missi n g) val ue o n or 
pri or t o  ra n d o mizati o n a n d pri or t o t he first d ose of st u d y me dicati o n e xce pt as n ote d bel o w.  
•  
F or assess me nts t o be c o m plete d dail y d uri n g t he wee k pri or t o baseli ne visit (e. g., slee p N R S, 
acti gra p h y para meters, slee p diar y, etc.), t heir baseli ne val ue will be t he a vera ge of 7 c o nti n u o us -
da y s of assess me nts ( or at least 5 da ys if data f or 7 da ys were n ot a vaila ble) pri or t o t he Visit 1 
Wee k  0 baseli ne  visit  b ut after t he Scree ni n g visit.   
•  
P ol ys o m n o gra p hic data c ollecte d at t he accli mati o n ni g ht ( Da y -2) will n ot be use d.  
 
T he baseli ne val ue of safet y para meters is defi ne d as t he last a vaila ble vali d ( n o n-missi n g) val ue pri or t o 
t he first d ose of i n vesti gati o nal me dici nal pr o d uct (I M P).  
 
If m ulti ple vali d val ues of a varia ble (efficac y or safet y) e xist wit hi n a sa me da y a n d ti me is n ot a vaila ble, 
t he sc he d ule d val ue will be use d. If n o sc he d ule d val ue is a vaila ble, t he n t he a vera ge will be selecte d. 
 
B aseli ne safet y a n d efficac y res ults are prese nte d i n t he safet y a n d efficac y a nal yses . 
 
T he refere nce da y ( de n ote d as Da y 1) f or t he calc ulati o n of e xte nt of e x p os ure a n d st u d y da y f or A E listi n gs 
will be t he da y of t he first a d mi nistrati o n of I M P:  
•  
E xte nt of e x p os ure (see Secti o n 7. 2. 1 ) 
•  
St u d y da y f or A E listi n g: A E o nset date –  first a d mi nistrati o n date of I M P + 1 
 
T he refere nce da y ( de n ote d as Da y 1) f or t he calc ulati o n of st u d y da y of efficac y assess me nts will be t he 
ra n d o mizati o n date. 


Sa n ofi Gr o u p  
 
Fi nal Statistical A nal ysis Pla n, Versi o n 2. 0  
 
D u pil u ma b - L P S 1 5 4 9 7  
 
Date Iss ue d: 3 0J U L 2 0 2 1  
 
  
 
  1 2  
•  
F or visit pri or t o ra n d o mizati o n,  st u d y da y = assess me nt date –  ra n d o mizati o n date. 
•  
F or visit at or after ra n d o mizati o n, st u d y da y = assess me nt date –  ra n d o mizati o n date + 1. 
 
I nter vals t hat are prese nte d i n wee ks will be tra nsf or me d fr o m da ys t o wee ks b y usi n g ( wit h o ut r o u n di n g) 
t he f ollo wi n g c o n versi o n f or m ula:  
W E E K S = D A Y S / 7  
 
I nter vals t hat are prese nte d i n m o nt hs will be tra nsf or me d fr o m da ys t o m o nt hs b y usi n g ( wit h o ut r o u n di n g) 
t he f oll o wi n g c o n versi o n f or m ula: 
M O N T H S = D A Y S / 3 0 .4 3 7 5  
 
T he last o n -treat me nt val ue of safet y para meters is t he fi nal meas ure me nt assessed d uri n g t he treat me nt 
e p oc h ( d o u ble-bli n d treat me nt peri o d a n d O L E peri o d res pecti vel y) , re gar dless of t he i ntr o d ucti o n of resc ue 
t hera p y, i ncl u di n g meas ure me nts at u nsc he d ule d visits. 
4. 4. 7.  C h a n ge fr o m b aseli ne a n d Perce nt c h a n ge fr o m b aseli ne  
C ha n ge fr o m baseli ne is defi ne d as: C ha n ge fr o m baseli ne = Val ue at s pecific ti me p oi nt –  Baseli ne val ue  
 
Perce nt c ha n ge fr o m baseli ne is defi ne d as:  
P erc e nt  c h a n g e fr o m b as eli n e (% ) = V al u e  at  s p ecific ti m e p oi nt −B as eli n e  v al u e  
B as eli n e  v al u e
× 1 0 0 %  
4. 5.  I nterc urre nt E ve nt T y pes 
Ta ble 4. 5 .1  s pecifies t he t y pes of I nterc urre nt e ve nts (Ic E vs), a n d ass ociate d la bels, use d t o defi ne t he 
esti ma n ds. 
 
Ta ble 4. 5 .1  I nterc urre nt E ve nt T y pes  
L a bel  
I nterc urre nt E ve nt T y pe  
Ic E v 1 ( disc o nti n uati o n or i nterr u pti o n of st u d y 
treat me nt d ue t o C o vi d-1 9)  
Treat me nt disc o nti n uati o n  or i nterr u pti o n  d ue t o 
C o vi d -1 9  
Ic E v 2 ( disc o nti n uati o n or i nterr u pti o n of st u d y 
treat me nt n ot d ue t o C o vi d -1 9  
Treat me nt disc o nti n uati o n or i nterr u pti o n n ot d ue 
to  C o vi d -1 9  
Ic E v3  ( Resc ue Me ds) 
Use of resc ue me dicati o ns  
Ic E v4  (Pr o hi bite d Me ds)  
Use of pr o hi bite d me dicati o ns  
5.  P atie nt  Dis p ositi o n  
5. 1.  Dis p ositi o n  
T he patie nt dis p ositi o n will be s u m marize d f or t he I T T a nal ysis set  b y treat me nt gr o u p a n d o verall usi n g 
n u m ber a n d perce nta ge . T his secti o n descri bes patie nt dis p ositi o n f or b ot h patie nt st u d y stat us a n d t he 
patie nt a nal ysis sets. 
 
F or patie nt st u d y stat u s, t he n u m ber a n d perce nta ge  of patie nts i n t he f oll o wi n g cate g ories will be prese nte d:  
•  
S cree ne d patie nts 
•  
Scree n fail ure patie nts  
•  
Patie nts treate d wit h o ut bei n g ra n d o mize d  
•  
Ra n d o mize d patie nts  
•  
Ra n d o mize d b ut n ot treate d patie nts  


Sa n ofi Gr o u p  
 
Fi nal Statistical A nal ysis Pla n, Versi o n 2. 0  
 
D u pil u ma b - L P S 1 5 4 9 7  
 
Date Iss ue d: 3 0J U L 2 0 2 1  
 
  
 
  1 3  
•  
Ra n d o mize d a n d treate d patie nts  
•  
Patie nts w h o ha ve c o m plete d treat me nt d uri n g t he d o u ble-bli n d treat me nt peri o d  
•  
Patie nts w h o di d n ot c o m plete treat me nt d uri n g t he d o u ble-bli n d treat me nt peri o d a n d t he mai n 
reas o n f or treat me nt disc o nti n uati o n. Relati o ns hi p wit h C O VI D-1 9 will be re p ort e d f or “ A d v erse 
E v ent ” a n d “ Ot her” reas o ns will be s u m marize d t o o.  
•  
Patie nts w h o disc o nti n ue d  t he st u d y d uri n g t he d o u ble -bli n d treat me nt peri o d a n d t he mai n reas o n 
f or st u d y disc o nti n uati o n. Relati o ns hi p wit h C O VI D-1 9 will be re p orte d f or “ A d v erse E vent ” a n d 
“ Ot her” reas o ns will be s u m marize d t o o.  
•  
Patie nts w h o e ntere d i nt o o pe n -la bel e xte nsi o n treat me nt peri o d ( O L E)  
•  
Patie nts w h o di d n ot c o m plete treat me nt d uri n g t he O L E treat me nt peri o d a n d t he mai n reas o n f or 
treat me nt disc o nti n uati o n. Relati o ns hi p wit h C O VI D -1 9 will be re p orte d f or “ A d v erse E vent ” a n d 
“ Ot her” reas o ns will be s u m marize d t o o.  
•  
Patie nts w h o c o m plete d st u d y  
•  
Patie nts w h o disc o nti n ue d  t he st u d y d uri n g t he O L E treat me nt peri o d a n d t he mai n reas o n f or st u d y 
disc o nti n uati o n . Relati o ns hi p wit h C O VID -1 9 will be re p orte d f or “ A d v erse E v ent ” a n d “ Ot her” 
reas o ns will be s u m marize d t o o. 
•  
Patie nts w h o ha d resc ue me dicati o ns  (see Secti o n 1 5. 1 1 ) 
o  Patie nts w h o ha ve c o m pl ete d t he d o u ble -bli n d treat me nt peri o d a n d ha d resc ue me dicati o ns  
o  Patie nts w h o di d n ot c o m plete t he d o u ble -bli n d treat me nt peri o d a n d ha d resc ue 
me dicati o ns  
•  
Fi nal St u d y Stat us  
 
F or scree ne d, scree n fail ure, a n d patie nts treate d wit h o ut bei n g ra n d o mize d, perce nta ges will be calc ulate d 
usi n g t he n u m ber of scree ne d patie nts as t he de n o mi nat or f or o verall o nl y. All ot her cate g ories of patie nts 
will be prese nte d b y treat me nt gr o u p a n d  f or o verall a n d t he perce nta ges will be calc ulate d usi n g t he n u m ber 
of ra n d o mize d patie nts wit hi n eac h treat me nt gr o u p a n d o verall,  as de n o mi nat or.  Reas o ns f or treat me nt 
disc o nti n uati o n will be s u p plie d i n ta bles gi vi n g n u m ber a n d perce nta ge  b y treat me nt gr o u p.  
 
If a p plica ble, patie nts treate d b ut n ot c o nsi dere d as ra n d o mize d, a n d patie nts ra n d o mize d b ut n ot treate d 
will be i de ntifie d a n d descri be d i n se parate listi n gs.  
Listi n gs of patie nts wit h per ma ne nt treat me nt disc o nti n uati o n, patie nts wit h pre mat ure e n d of st u d y will be 
pr o vi de d.  
 
A d diti o nall y, a s u m mar y of all t he a nal ysis sets f or safet y a n d efficac y ( Efficac y [I T T, m -I T T, O L E, a n d 
P S G] ,  Safet y , a nal ysis set wit h o ut trial i m pact ( disr u pti o n) d ue t o C O VI D-1 9 a n d a nal ysis set wit h trial 
i m pact ( disr u pti o n) d ue t o C O VI D 1 9) will be s u m marize d f or t he I T T a nal ysis set  b y  treat me nt gr o u p a n d 
o verall usi n g n u m ber a n d perce nta ge .  
 
A listi n g of patie nts e xcl u de d fr o m a nal ysis sets will be pr o vi de d.  Patie nts wit h per ma ne nt treat me nt 
disc o nti n uati o n, patie nts wit h pre mat ure e n d of st u d y  will be i de ntifie d a n d descri be d i n se parate listi n gs.  
 
T he reas o ns f or bei n g i n t he a nal ysis set wit h trial i m pact ( disr u pti o n) d ue t o C O VI D-1 9 will b e s u m marize d 
f or t he m o difie d I T T a nal ysis set  b y treat me nt gr o u p a n d o verall usi n g n u m ber a n d perce nta ge .  
 
A listi n g of patie nts e xcl u de d fr o m t he a nal ysis set wit h o ut trial i m pact ( disr u pti o n) d ue t o C O VI D -1 9 will 
be pr o vi de d.  
 
T he dis p ositi o n of scree ne d patie nts, scree n fail ure patie nts, ra n d o mize d a n d n ot treate d patie nts, 
ra n d o mize d patie nts, ra n d o mize d a n d treate d patie nts b y c o u ntr y  a n d site will be s u m marize d f or t he 
scree ne d a nal ysis set  b y  treat me nt gr o u p a n d o verall usi n g n u m ber a n d perce nta ge . 


Sa n ofi Gr o u p  
 
Fi nal Statistical A nal ysis Pla n, Versi o n 2. 0  
 
D u pil u ma b - L P S 1 5 4 9 7  
 
Date Iss ue d: 3 0J U L 2 0 2 1  
 
  
 
  1 4  
 
A s u m mar y ta ble t o s h o w patie nt dis p ositi o n b y visit acc or di n g t o trial i m pact ( disr u pti o n) d ue t o C O VI D -
1 9 ( visit n ot d o ne, visit partiall y d o ne o n site, visit partiall y d o ne b y p h o ne a n d visit d o ne b ut dela ye d) will 
be pr o vi de d. A s u m mar y ta ble t o s h o w t he patie nt dis p ositi o n b y visit acc or di n g t o  trial i m pact ( disr u pti o n) 
d ue t o C O VI D -1 9 b y c o u ntr y a n d site will be pr o vi de d t o o.  
5. 2.  Pr ot oc ol D e vi ati o ns  
All  critical or  maj or  pr ot oc ol  de viati o ns i ncl u di n g ra n d o mizati o n a n d dr u g -dis pe nsi n g irre g ularities will be 
s u m marize d acc or di n g t o C O VI D -1 9 i m pact (i.e. de viati o ns relate d t o C O VI D -1 9 pa n de mic a n d de viati o ns 
n ot relate d t o C O VI D -1 9 p a n de mic)  f or t he I T T a nal ysis set  b y treat me nt gr o u p  a n d o verall usi n g n u m ber 
a n d perce nta ge. 
 
A  listi n g of patie nts wit h at least o ne critical or maj or pr ot oc ol de viati o ns will be pr o vi de d.  
 
Ra n d o mizati o n a n d dr u g -dis pe nsi n g irre g ularities occ ur w he ne ver:  
1.  A ra n d o mizati o n is n ot i n acc or da nce wit h t he pr ot o c ol-defi ne d ra n d o mizati o n met h o d, s uc h as a) 
a n i neli gi ble patie nt is ra n d o mize d, b) a patie nt is ra n d o mize d base d o n a n i nc orrect strat u m, c) a 
patie nt is ra n d o mize d t wice, or d) i n a d y na mic ra n d o mizati o n sc he me t he treat me nt assi g n me nt is, 
i n fact, n ot ra n d o m, d ue t o a c o m p uter pr o gra m err or. 
 
O R  
 
2.  A patie nt is dis pe nse d a n I M P kit n ot all ocate d b y t he pr ot oc ol -defi ne d ra n d o mizati o n, s uc h as a) 
a patie nt at a n y ti me i n t he st u d y is dis pe nse d a differe nt treat me nt kit t ha n as ra n d o mize d ( w hic h 
ma y or ma y n ot c o ntai n t he c orrect -as-ra n d o mize d I M P), or b) a n o n-ra n d o mize d patie nt is treate d 
wit h I M P reser ve d f or ra n d o mize d patie nts.  
Ra n d o mizati o n a n d dr u g -dis pe nsi n g irre g ularities will be m o nit ore d t hr o u g h o ut t he st u d y a n d re vie we d o n 
a n o n g oi n g basis.  
 
All ra n d o mizati o n a n d dr u g -dis pe nsi n g irre g ularities will be d oc u me nte d i n t he cli nical st u d y re p ort.  If t he 
n u m ber of irre g ularities is lar ge e n o u g h t o ma ke a ta b ular s u m mar y usef ul, t he critical or maj or irre g ularities 
will be cate g orize d a n d s u m marize d f or t he I T T a nal ysis set b y treat me nt gr o u p a n d o verall usi n g n u m ber 
a n d perce nta ge . N o n-ra n d o mize d, treate d patie nts will be descri be d se paratel y. 
 
A listi n g of patie nts wit h at least o ne critical or maj or pr ot oc ol de viati o ns relate d t o ra n d o mizati o n a n d 
dr u g -dis pe nsi n g irre g ularities will be pr o vi de d.  
 
Ra n d o mizati o n a n d dr u g -dis pe nsi n g irre g ularities t o be pr os pecti vel y i de ntifie d i ncl u de b ut are n ot li mite d 
t o: 
 
Ta ble 5. 2 .1  Ra n d o mizati o n a n d dr u g dis pe nsi n g irre g ularities  
R a n d o miz ati o n a n d dr u g all oc ati o n irre g ul arities  
•  
Kit dis pe nsati o n wit h o ut I R T tra nsacti o n  
•  
Err o ne o us kit dis pe nsati o n  
•  
Kit n ot a vaila ble  
•  
Ra n d o mizati o n b y err or  
•  
Patie nt ra n d o mize d t wice  
•  
Stratificati o n err or  


Sa n ofi Gr o u p  
 
Fi nal Statistical A nal ysis Pla n, Versi o n 2. 0  
 
D u pil u ma b - L P S 1 5 4 9 7  
 
Date Iss ue d: 3 0J U L 2 0 2 1  
 
  
 
  1 5  
•  
O pe n -la bel kit dis pe nse d i nstea d of d o u ble-bli n d kit at 
Wee k 1 2  
List of ra n d o mizati o n a n d dr u g -dis pe nsi n g irre g ularities will be pr o vi de d b y S A N O FI.  
6.  De m o gr a p hics a n d B aseli ne C h ar acteristics  
T he de m o gra p hics , patie nt c haracteristics  a n d baseli ne disease c haracteristics will be s u m marize d usi n g  t he 
I T T a n d P S G a nal ysis set s b y treat me nt gr o u p a n d o verall  usi n g descri pti ve statistics or usi n g n u m ber a n d 
perce nta ge . P -val ues o n t he treat me nt differe nce f or t he de m o gra p hic a n d baseli ne c haracteristics data will 
n ot be calc ulate d. I n ge neral, n o s pecific descri pti o n of t he safet y para meters will be pr o vi de d at baseli ne. 
If rele va nt, t he baseli ne val ues will be descri be d al o n g wit h eac h safet y/efficac y a nal ysis. 
6. 1.  De m o gr a p hics  
T he f oll o wi n g de m o gra p hics a n d patie nt c haracteristics will be s u m marize d b y treat me nt gr o u p a n d 
o verall:  
•  
A ge ( years),  
•  
A ge cate g ories ( ≥1 8 t o < 4 0, ≥4 0 t o < 6 5, ≥6 5),  
•  
Ge n der ( Male, Fe male)  
•  
Et h nicit y ( His pa nic or Lati n o, N ot His pa nic or Lati n o, N ot  Re p orte d, U n k n o w n),  
•  
Race  ( A merica n I n dia n or Alas ka Nati ve, Asia n, Blac k or Africa n A merica n, Nati ve Ha waiia n or 
Ot her Pacific Isla n der, M ulti ple, W hite, N ot Re p orte d, U n k n o w n),  
•  
B aseli ne b o d y wei g ht ( k g) wit h gr o u pi n g ( < 7 0, ≥7 0 t o < 1 0 0, ≥1 0 0),  
•  
Baseli ne h ei g ht (c m), 
•  
Baseli ne  b o d y mass i n de x ( B MI) ( k g/ m²) deri ve d as: ( Wei g ht i n k g)/( Hei g ht i n meters)²,  
•  
Baseli ne B MI cate g ories ( < 1 5, ≥1 5 t o < 2 5, ≥2 5 t o < 3 0, ≥3 0)  
•  
Re gi o n ( U S [P S G, n o n -P S G ], E ur o pe a n d R O W) 
•  
Alc o h ol ha bits at scree ni n g ( Ne ver, Occasi o nal, At Least Dail y, At Least Wee kl y, At Least 
M o nt hl y)  
6. 2.  B aseli ne Dise ase C h ar acteristi cs  
T he f oll o wi n g baseli ne disease c haracteristics will be s u m marize d b y treat me nt gr o u p a n d o verall:  
6. 2. 1.  Slee p c h ar acteristics a n d slee p rel ate d i m p air me nt at b aseli ne  
•  
Rescale d Slee p q ualit y N R S *  
•  
S C O R A D s u bjecti ve slee p l oss sc ore  (slee p V A S) 
•  
P R O MI S slee p dist ur ba nce s h ort f or m 8a ra w a n d T-sc ores  
•  
Acti gra p h y  
o  Slee p o nset late nc y ( S O L) *  
o  Wa ke after slee p o nset ( W A S O) *  
o  T otal Slee p Ti me ( T S T) *  
o  Slee p efficie nc y ( S E) *  
•  
Slee p diar y  
o  S O L *  
o  T S T *  
o  W A S O *  
o  S E *  
o  N u m ber of a wa ke ni n gs *  
o  H o w reste d  t he partici pa nt felt w he n getti n g u p ( N R S) * 


Sa n ofi Gr o u p  
 
Fi nal Statistical A nal ysis Pla n, Versi o n 2. 0  
 
D u pil u ma b - L P S 1 5 4 9 7  
 
Date Iss ue d: 3 0J U L 2 0 2 1  
 
  
 
  1 6  
•  
E S S sc ore, a n d t he cate g ories as defi ne d b y  
o  L o wer N or mal Da yti me Slee pi ness ( 0 -5)  
o  Hi g her N or mal Da yti me Slee pi ness ( 6 -1 0)  
o  Mil d E xcessi ve Da yti me Slee pi ness ( 1 1 -1 2)  
o  M o derate E xcessi ve Da yti me Slee pi ness ( 1 3 -1 5)  
o  Se vere E xcessi ve Da yti me Slee pi ness ( 1 6 -2 4)  
•  
P V T  ( O utc o me metrics fr o m data tra nsfer) 
o  T otal err ors  
o  N u m ber of la pses  
o  Mea n reci pr ocal res p o nse ti me ( mea n 1/ R T)  
o  Mea n fastest res p o nse ti me  ( Fastest 1 0 % R T) 
o  Mea n sl o west reci pr ocal res p o nse ti me ( Sl o west 1 0 % R T)  
•  
A N A M: r u n ni n g me m or y, mat he matical pr ocessi n g, pr oce d ural reacti o n ti me  
o  Mea n res p o nse ti me  
o  Perce nta ge of c orrect res p o nse  
o  T hr o u g h p ut  
•  
P ol ys o m n o gra p h y i n t he P S G a nal ysis set  ( defi ne d i n 4. 3. 5 ) 
o  S O L  
o  W A S O  
o  T S T  
o  S E  
o  L o n gest slee p e pis o de  
o  Sta ges of slee p  
o  Ar o usal i n de x  
 
* a vera ge val ue of t he  assess me nt re p orte d d uri n g t he wee k pri or t o baseli ne visit  
6. 2. 2.  A D a n d ass oci ate d dise ase c h ar acteristics at b aseli ne  
•  
I n vesti gat or’s Gl o bal Assess me nt (I G A) sc ore 
o  Clear ( 0)  
o  Al m ost clear ( 1)  
o  Mil d disease ( 2)  
o  M o derate disease ( 3)  
o  Se vere disease ( 4)  
•  
B o d y S urface  Area ( B S A) I n v ol ve me nt of A D  
•  
E A SI t otal sc ore 
•  
S C O R A D o verall sc ore  
•  
Pea k pr urit us N R S *  
•  
S ki n pai n N R S *  
•  
S ki n se nsiti vit y t o t o uc h N R S *  
•  
S ki n b ur n N R S *  
•  
P O E M sc ore a n d cate g ories as defi ne d b y  
o  Clear or al m ost clear ( 0 -2)  
o  Mil d ecze ma ( 3 -7)  
o  M o derate ecze ma ( 8-1 6)  
o  Se vere ecze ma ( 1 7 -2 4)  
o  Ver y se vere ecze ma ( 2 5 -2 8)  
•  
D L QI t otal sc ore  
•  
H A D S -A n xiet y sc ore, H A D S -De pressi o n sc ore  


Sa n ofi Gr o u p  
 
Fi nal Statistical A nal ysis Pla n, Versi o n 2. 0  
 
D u pil u ma b - L P S 1 5 4 9 7  
 
Date Iss ue d: 3 0J U L 2 0 2 1  
 
  
 
  1 7  
•  
A C Q -5 t otal sc ore  
•  
A R -V A S sc ore  
6. 2. 3.  He alt h ec o n o mic e n d p oi nts at b aseli ne  
•  
W P AI -A D: c urre ntl y e m pl o ye d stat us ( yes/ n o); n u m ber of h o urs misse d d ue t o A D ( o nl y if 
e m pl o ye d); n u m ber of h o urs misse d d ue t o ot her reas o ns ( o nl y if e m pl o ye d); n u m ber of h o urs 
act uall y w or ke d ( o nl y if e m pl o ye d); N R S of at o pic der matitis affecte d pr o d ucti vit y w hile 
w or ki n g ( o nl y if e m pl o ye d) a n d N R S of at o pic der matitis affecte d a bilit y t o d o re g ular dail y 
acti vities, ot her t ha n w or k at j o b  
•  
Da y misse d fr o m sc h o ol or fr o m w or k d ue t o A D : patie nts w h o were e m pl o ye d or e nr olle d i n 
sc h o ol were as ke d t o re p ort t he n u m ber of sic k lea ve/ misse d sc h o ol da ys d ue t o A D fr o m eac h 
assess me nt si nce t he last st u d y visit, se paratel y f or e m pl o y me nt/sc h o ol stat us b y f ull ti me a n d 
part ti me  
6. 3.  Alc o h ol, T o b acc o a n d C affei ne Us a ge  
T he f oll o wi n g alc o h ol, t o bacc o a n d Caffei ne ha bit s will be s u m marize d b y treat me nt gr o u p a n d o verall: 
•  
Alc o h ol c o ns u m pti o n: a m o u nt ( glass) per da y a n d per visit  
•  
Caffei ne c o ns u m pti o n: a m o u nt  (c u p) per da y a n d per visit 
•  
T o bacc o c o ns u m pti o n: a m o u nt (ci garette) per da y a n d per visit  
 
T he t o bacc o a n d caffei ne data are o nl y c ollecte d f or P S G patie nts.  
6. 4.  Me dic al Hist or y  
6. 4. 1.  Ge ner al Me dic al Hist or y  
Me dical ( or s ur gical) hist or y i ncl u des all t he rele va nt me dical ( or s ur gical) hist or y d uri n g t he lifeti me of 
t he patie nt. 
 
Me dical a n d s ur gical hist or y will be c o de d t o “l o wer le vel ter m ( L L T)”, “ preferre d ter m ( P T)”, “ hi g h le vel 
ter m ( H L T)”, “ hi g h le vel gr o u p ter m ( H L G T)”, a n d ass ociate d pri mar y “s yste m or ga n class ( S O C)” usi n g 
t he versi o n of Me dical Dicti o nar y f or Re g ulat or y Acti vities ( Me d D R A) i n effect at Sa n ofi at t he ti me of 
eac h data base l oc k.  
 
T he n u m ber a n d perce nta ge of s u bjects wit h a n y me dical hist or y will be s u m marize d b y treat me nt gr o u p 
a n d o verall a n d f or eac h S O C. S O C will be s orte d i n desce n di n g or der of fre q ue nc y base d o n t he t otal of 
all treat me nt gr o u ps.  
6. 4. 2.  Dise ase -S pecific Hist or y  
N ot a p plica ble.  
6. 5.  I ncl usi o n a n d E xcl usi o n Criteri a 
I ncl usi o n a n d e xcl usi o n criteria will be prese nte d f or t he scree ne d a nal ysis set f or eac h treat me nt gr o u p a n d 
o verall usi n g n u m ber a n d  perce nta ge.  
6. 6.  Ot her B ac k gr o u n d I nf or m ati o n  
N ot a p plica ble.  


Sa n ofi Gr o u p  
 
Fi nal Statistical A nal ysis Pla n, Versi o n 2. 0  
 
D u pil u ma b - L P S 1 5 4 9 7  
 
Date Iss ue d: 3 0J U L 2 0 2 1  
 
  
 
  1 8  
7.  Tre at me nts a n d Me dic ati o ns  
7. 1.  Pri or a n d C o nc o mit a nt Me dic ati o ns  
T he pri or a n d c o nc o mita nt me dicati o ns will be prese nte d f or t he I T T a nal ysis set  f or eac h treat me nt gr o u p 
a n d o verall usi n g n u m ber a n d perce nta ge . N o statistical test f or t he bet wee n-gr o u p differe nce will be 
perf or me d.  
 
All me dicati o ns will be c o de d usi n g t he W orl d Healt h Or ga nizati o n -Dr u g Dicti o nar y ( W H O -D D) usi n g t he 
versi o n i n effect at Sa n ofi at t he ti me of eac h data base l oc k.  
 
Me dica ti o ns will be s u m marize d b y treat me nt gr o u p acc or di n g t o t he W H O-D D, c o nsi deri n g t he first di git 
of t he a nat o mic cate g or y ( A T C) class (a nat o mic cate g or y) a n d t he first 3 di gits of t he A T C class (t hera pe utic 
cate g or y). All A T C c o des c orres p o n di n g t o a me dic ati o n will be s u m marize d, a n d patie nts will be c o u nte d 
o nce i n eac h A T C cate g or y (a nat o mic or t hera pe utic) li n ke d t o t he me dicati o n. T heref ore, patie nts ma y be 
c o u nte d se veral ti mes f or t he sa me me dicati o n.  
 
T he s u m maries f or pri or, c o nc o mita nt , a n d p ost -treat me nt me dicati o ns will be s orte d b y decreasi n g 
fre q ue nc y of A T C f oll o we d b y all ot her t hera pe utic classes base d o n t he i nci de nce in t he d u pil u ma b  
treat me nt gr o u p. I n case of e q ual fre q ue nc y re gar di n g A T Cs, al p ha betical or der will be use d. 
 
F or t he p ur p ose of i ncl usi o n i n pri or a n d/ or c o nc o mita nt me dicati o n ta bles, i nc o m plete me dicati o n start a n d 
st o p dates will be i m p ute d as descri be d i n secti o n 1 5. 4. 3 . 
7. 1. 1.  Pri or Me dic ati o ns  
Pri or me dicati o ns are t h ose t he patie nt be ga n  pri or t o first I M P i nta ke. Pri or me dicati o ns ca n be 
disc o nti n ue d bef ore first treat me nt a d mi nistrati o n or ca n be o n g oi n g d uri n g  t he treat me nt p hase. 
7. 1. 2.  C o nc o mit a nt Me dic ati o ns  
C o nc o mita nt me dicati o ns are a n y treat me nts recei ve d b y t he patie nt c o nc o mita ntl y t o t he I M P, starti n g 
fr o m t he 1st a d mi nistrati o n of I M P t o t he date of last a d mi nistrati o n + 1 4 da ys  ( b o u n dar y n ot i ncl u de d). A 
gi ve n me dicati o n ca n be classifie d b ot h as a pri or me dicati o n a n d as a c o nc o mita nt me dicati o n.  
7. 1. 3.  P ost -tre at me nt me dic ati o ns 
P ost -treat me nt me dicati o ns are t h ose t he patie nt t o o k (c o nti n ue d or i nitiate d) i n t he peri o d r u n ni n g fr o m 
t he 1 4t h da y after t he last a d mi nistrati o n of I M P u p t o t he e n d of t he st u d y.  
7. 2.  St u d y Tre at me nts  
T he e xte nt of I M P e x p os ure a n d c o m plia nce will be assesse d a n d s u m marize d  se paratel y wit hi n t he d o u ble-
bli n d treat me nt peri o d , t he O L E peri o d (f or c o m plia nce o nly)  a n d o verall  peri o d  (c o m bi ne d d o u ble -bli n d 
a n d O L E peri o ds) b y act ual treat me nt  gr o u p  a n d o verall usi n g t he safet y a nal ysis set a n d a nal ysis set wit h 
trial i m pact ( disr u pti o n) d ue t o C O VI D-1 9 . 
7. 2. 1.  E xte nt of E x p os ure  
T he e xte nt of I M P e x p os ure will be assesse d b y t he d urati o n of I M P e x p os ure.  
 
D urati o n of I M P e x p os ure is defi ne d as last I M P a d mi nistrati o n d ose date –  first I M P a d mi nistrati o n d ose 
date + 1 4 da ys , re gar dless of u n pla n ne d i nter mitte nt disc o nti n uati o ns. 
 


Sa n ofi Gr o u p  
 
Fi nal Statistical A nal ysis Pla n, Versi o n 2. 0  
 
D u pil u ma b - L P S 1 5 4 9 7  
 
Date Iss ue d: 3 0J U L 2 0 2 1  
 
  
 
  1 9  
D urati o n of I M P  e x p os ure will be s u m marize d descri pti vel y as a q ua ntitati ve varia ble ( n u m ber, mea n,  S D, 
me dia n,  Q 1, Q 3, mi ni m u m a n d ma xi m u m). I n a d diti o n, d urati o n of I M P e x p os ure will als o be s u m marize d 
cate g oricall y b y n u m bers a n d perce nta ges f or eac h of t he f oll o wi n g cate g ories a n d c u m ulati vel y acc or di n g 
t o t hese cate g ories: 
•  
> 0 a n d ≤2 wee ks  
•  
> 2 a n d ≤4 wee ks  
•  
> 4 a n d ≤8 wee ks  
•  
> 8 a n d ≤1 2 wee ks  
•  
> 1 2 a n d ≤1 6 wee ks  
•  
> 1 6 a n d ≤2 0 wee ks  
•  
> 2 0 a n d ≤2 4 wee ks  
•  
> 2 4 wee ks  
 
A d diti o nall y, t he c u m ulati ve d urati o n of I M P e x p os ure will be pr o vi de d, defi ne d as t he s u m of d urati o n of 
I M P e x p os ure f or all patie nts, a n d will be e x presse d i n patie nt years. 
7. 2. 2.  Tre at me nt C o m pli a nce a n d M o dific ati o ns  
A gi v e n a d mi nistrati o n will be c o nsi dere d n o n -c o m plia nt if t he patie nt di d n ot ta ke t he pla n ne d d ose of 
treat me nt as re q uire d b y pr ot oc ol (i.e. a s yri n ge n ot f ull y i njecte d is c o nsi dere d as a n o n -c o m plia nt 
a d mi nistrati o n) . N o i m p utati o n will be ma de f or missi n g or i nc o m plete data.  
Perce nta ge of c o m plia nce f or a patie nt will be defi ne d as t he n u m ber of a d mi nistrati o ns t hat t he patie nt was 
c o m plia nt ( pla n ne d d ose f ull y i njecte d) di vi de d b y t he t otal n u m ber of a d mi nistrati o ns t hat t he patie nt was 
pla n ne d t o ta ke d uri n g eac h of treat me nt peri o d (fr o m t he first t o t he last date of I M P a d mi nistrati o n wit hi n 
eac h peri o d). 
Perce nta g e of c o m plia n ce ( %) = [
T ot al n u m b er of c o m pli a nt i nj ecti o ns d uri n g s p ecific tr e at m e nt p eri o d
N u m b er of pl a n n e d i nj ecti o ns d uri n g s p ecifi c tr e at m e nt p eri o d
] × 1 0 0 %  
L oa di n g d oses f or t he sa me patie nt will be c o u nte d as 1.  
Perce nta ge of c o m plia nce a n d perce nta ge of i njecti o ns wit h c o m plia nce t o t he I M P a d mi nistrati o n will be 
s u m marize d descri pti vel y as q ua ntitati ve varia bles ( n u m ber, mea n, S D, m e dia n, Q 1, Q 3, mi ni m u m a n d 
ma xi m u m) se paratel y f or eac h treat me nt peri o d ( d o u ble -bli n d treat me nt peri o d a n d O L E) a n d o verall. I n 
a d diti o n, t he perce nta ge of c o m plia nce will be prese nte d b y t he s pecific ra n ges f or eac h treat me nt gr o u p:  
•  
< 8 0 %  
•  
≥8 0 % t o < 1 2 0 %  
•  
≥1 2 0 %  
 
A n o ver d ose (acci de ntal or i nte nti o nal) wit h t he I M P is a n e ve nt s us pecte d b y t he I n vesti gat or or 
s p o nta ne o usl y n otifie d b y t he partici pa nt a n d defi ne d as at least 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. Cases of s y m pt o matic o ver d oses will c o nstit ute 
A E SIs a n d will be liste d as s uc h. M ore ge nerall y, d osi n g irre g ularities will be liste d i n Secti o n 5. 2 . 
 
D o se m o dificati 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 a n d t heref ore n o s u m mar y of d ose 
m o dificati o ns will be pr o vi de d.  D r u g-dis pe nsi n g irre g ularities  are i ncl u de d as part of t he pr ot oc ol 
de viati o ns s u m mar y ( Secti o n 5. 2 ). 


Sa n ofi Gr o u p  
 
Fi nal Statistical A nal ysis Pla n, Versi o n 2. 0  
 
D u pil u ma b - L P S 1 5 4 9 7  
 
Date Iss ue d: 3 0J U L 2 0 2 1  
 
  
 
  2 0  
8.  Effic ac y A n al ysis  
Efficac y a nal yses will be perf or me d o n t he m I T T a nal ysis set, O L E a nal ysis set or P S G a nal ysis set 
de pe n di n g o n t he efficac y e n d p oi nts. 
 
Patie nts will be a nal yze d f or efficac y acc or di n g t o t he treat me nt gr o u p t o w hic h t he y are all ocate d b y t he 
I R T acc or di n g t o t he ra n d o mizati o n sc he d ule at t he ra n d o mizati o n visit (as ra n d o mize d), irres pecti ve of t he 
treat me nt act uall y recei ve d. 
 
F or t he a nal ysis of pri mar y o bjecti ve i n t he d o u ble -bli n d treat me nt peri o d,  
•  
T he n ull statistical h y p ot hesis teste d is t hat t he re is n o treat me nt differe nce bet wee n  d u pil u ma b  a n d 
place b o  o n slee p q ualit y N R S  i n a d ult patie nts wit h m o derate t o se vere A D a n d slee p dist ur ba nce. 
•  
t he alter nati ve statistical h y p ot hesis teste d is t hat t here is a treat me nt differe nce bet wee n d u pil u ma b  
a n d place b o o n slee p q ualit y N R S  i n a d ult patie nts wit h m o derate t o se vere A D a n d slee p 
dist ur ba nce.  
 
N ote t hat d ue t o t he s mall sa m ple size i n t he P S G a nal ysis set, n o statistical testi n g will be c o n d ucte d f or 
P S G relate d e n d p oi nts. S u m mar y statistics wit h 9 5 % CI b y treat me nt gr o u p will be pr o vi de d.  
 
Statistical testi n g will be o nl y be c o n d ucte d o n res ults f or t he d o u ble -bli n d treat me nt peri o d. Statistical 
testi n g will n ot be c o n d ucte d f or t he assess me nts c o m plete d d uri n g O L E peri o d. All relate d e n d p oi nts will 
be s u m marize d.  
 
All efficac y meas ur e me nts c ollecte d d uri n g t he st u d y wi ll be c o nsi dere d f or a nal yses, i ncl u di n g t h ose 
o btai ne d after I M P disc o nti n uati o n.  
 
All dail y assess me nts (e. g., slee p q ualit y N R S, acti gra p h y para meters, slee p diar y, etc.) will be a nal yze d as 
wee kl y a vera ges f or t he wee k i m me diatel y prece di n g t he st u d y visit.  
 
Li ne p l ots f or c ha n ge fr o m baseli ne or perce nt c ha n ge fr o m baseli ne will be prese nte d b y treat me nt gr o u p , 
dis pla yi n g t he mea n, me dia n, Q 1 a n d Q 3  at eac h visit. T hese pl ots will be pr o vi de d f or t he pri mar y a n d all 
sec o n dar y c o nti n u o us e n d p oi nts. 
Bar pl ots f or perce nta ge of patie nts wit h E A SI 5 0, E A SI 7 5 a n d E A SI 9 0 will be prese nte d b y treat me nt 
gr o u p , dis pla yi n g t he perce nta ge of E A SI res p o n ders at eac h visit.  
8. 1.  Pri m ar y Effic ac y E n d p oi nt  
T he slee p q ualit y scale was use d t o assess t he q ualit y of t he p artici pa nt’s pre vi o us ni g ht s’ slee p, c ollecte d 
o n a 1 1 -p oi nt scale ( 0 t o 1 0) i n w hic h 0 i n dicate d w orst p ossi ble slee p w hile 1 0 t he best p ossi ble slee p. T he 
pri mar y efficac y e n d p oi nt perce nta ge c ha n ge fr o m baseli ne will be calc ulate d base d o n t he rescale d val ues 
w here eac h assess me nt ( of t he a vera ge o ver t he wee k prece di n g t he st u d y visit) will be rescale d as ( 1 0 
mi n us t he o bser ve d val ue) s uc h t hat 0 i n dicate d t he best p ossi ble slee p a n d 1 0 i n dicate d t he w orst p ossi ble 
slee p base d o n t he rescale d val ue. T his is d o ne i n or der t o ha ve c o nsiste nt i nter pretati o ns o n perce nt 
i m pr o ve me nt bet wee n scales (e.g. Pea k pr urit us N R S).  
 
Rescale d slee p q ualit y N R S = 1 0 mi n us o bser ve d slee p q ualit y N R S.  
Perce nt c ha n ge fr o m baseli ne ( %) = [
W e e k  1 2  r e s c al e d  sl e e p  N R S  −r e s c al e d  sl e e p  N R S  b a s eli n e  v al u e
r e s c al e d  sl e e p  N R S  b a s eli n e  v al u e
] × 1 0 0  
T heref ore, a ne gati ve perce nt c ha n ge fr o m baseli ne will i n dicate a n i m pr o ve me nt. 


Sa n ofi Gr o u p  
 
Fi nal Statistical A nal ysis Pla n, Versi o n 2. 0  
 
D u pil u ma b - L P S 1 5 4 9 7  
 
Date Iss ue d: 3 0J U L 2 0 2 1  
 
  
 
  2 1  
8. 1. 1.  Pri m ar y A n al ysis  
 
Perce nta ge c ha n ge fr o m baseli ne i n slee p q ualit y N R S will be  a nal yze d usi n g a M M R M u n der t he M A R 
fra me w or k. T he M M R M m o del will i ncl u de treat me nt ( d u pil u ma b , p lace b o), baseli ne val ue of slee p q ualit y 
N R S, ra n d o mizati o n strat u m (re gi o n), visits ( u p t o wee k 1 2), treat me nt b y visit i nteracti o n, a n d baseli ne 
slee p q ualit y N R S b y visit i nteracti o n ter ms all as fi xe d effects. A n u nstr uct ure d c orrelati o n matri x will be 
use d t o m o del t he wit hi n -patie nt err ors. T he Ke n war d -R o ger a p pr o xi mati o n ( d df m = kr ) will be use d t o 
esti mate t he de n o mi nat or of de grees of free d o m. P ara meters will be esti mate d usi n g restricte d ma xi m u m  
li keli h o o d met h o d wit h t he Ne wt o n-Ra p hs o n al g orit h m. L S mea n differe nce bet wee n t he d u pil u ma b  a n d 
p lace b o gr o u p, t he c orres p o n di n g 9 5 % CI of t he differe nces a n d 2 -si de d n o mi nal p -val ues will be pr o vi de d.  
T he pri mar y p -val ue is at Wee k 1 2. A n y ot her p -val ues s h o ul d be treate d as s u g gesti ve f or p ossi ble f urt her 
st u d y as t he st u d y is n ot p o were d f or t hese tests. 
 
If t he n u m ber of patie nts i n t he P S G-s u b st u d y is less t ha n 5 0 % of pla n ne d, P S G-strata will be p o ole d wit h 
t he n o n-P S G strata i n t he U S a n d t he n t here will be o nl y 3 strata: U S ( c o m bi ne d n o n -P S G a n d P S G ), E ur o pe 
a n d R O W. 
If t he M M R M m o del fails t o ac hie ve c o n ver ge nce d ue t o c o m ple xit y of m o del s pecificati o n, differe nt 
c o varia nce str uct ures w ill be use d acc or di n g t o t he f oll o wi n g or der till c o n ver ge nce is ac hie ve d: 
1.  U nstr uct ure d c orrelati o n ( U N)  
2.  Heter o ge ne o us T oe plitz ( T O E P H)  
3.  H o m o ge ne o us T oe plitz ( T O E P)  
4.  First -Or der A ut ore gressi ve [ A R( 1)]  
5.  C o m p o u n d S y m metr y ( C S)  
 
M M R M m o del will be b uilt wit h t he  f oll o wi n g sa m ple S A S c o de t o e val uate t he treat me nt effect t hr o u g h 
wee k 1 2:  
pr oc mi xe d data = a d qs met h o d = re ml;  
w here para mc d e q ‘slee p q ualit y N R S’ a n d a visit n ge 2 a n d a visit n le 6 a n d I T T F L e q 
“ Y”; 
class us u bji d strat u m trt 0 1 p n a visit n;  
m o del pctc h g = base trt 0 1 p n strat u m a visit n trt 0 1 p n *a visit n base *a visit n / s ol uti o n d df m 
= kr;  
re peate d a visit n / t y pe = u n s u bject = us u bji d; 
ls mea ns trt 0 1 p n *a visit n / cl; 
/ *c o ntrast “D u pil u ma b  vs Place b o at Wee k 1 Visit 2”  
trt 0 1 p n -1 1 trt 0 1 p n *a visit n -1 0 0 0 0 1 0 0 0 0;  
c o ntrast “ D u pil u ma b  vs Place b o at Wee k 2 Visit 3”  
trt 0 1 p n -1 1 trt 0 1 p n *a visit n 0 -1 0 0 0 0 1 0 0 0;  
c o ntrast “ D u pil u ma b  vs Place b o at Wee k 4 Visit 4”  
trt 0 1 p n -1 1 trt 0 1 p n *a visit n 0 0 -1 0 0 0 0 1 0 0;  
c o ntrast “ D u pi l u ma b vs Place b o at Wee k 8 Visit 5”  
trt 0 1 p n -1 1 trt 0 1 p n *a visit n 0 0 0 -1 0 0 0 0 1 0; */  
 
 
c o ntrast “ D u pil u ma b  vs Place b o at Wee k 1 2 Visit 6”  
trt 0 1 p n -1 1 trt 0 1 p n *a visit n 0 0 0 0 -1 0 0 0 0 1;  
o ds o ut p ut diffs = diffs ls mea ns =ls mea ns; 
r u n; 
 
N ote t hat sa m p le c o de ass u mes t he a visit n f or visit 2 is 2 a n d a visit n f or visit 6 is 6, if t hat is n ot t he case, 
t he c o de s h o ul d be a dj uste d. T he c o ntrast state me nt ass u mes trt 0 1 p n f or place b o is l o wer t ha n t hat of 


Sa n ofi Gr o u p  
 
Fi nal Statistical A nal ysis Pla n, Versi o n 2. 0  
 
D u pil u ma b - L P S 1 5 4 9 7  
 
Date Iss ue d: 3 0J U L 2 0 2 1  
 
  
 
  2 2  
d u pil u ma b . T he sa m ple c o ntrast state me nt f or ot her ti me p oi nt e xce pt wee k 1 2 is pr o vi de d as well i n t he 
c o m me nt, w hic h c o ul d be use d f or c o m paris o ns at ot her visits.  
8. 1. 2.  Ass u m pti o n Testi n g  
N o ass u m pti o n testi n g will be perf or me d.  
8. 1. 3.  Missi n g D at a H a n dli n g  
N o i m p utati o n will be ma de f or t he missi n g val ues f or t he pri mar y a p pr oac h.  
8. 1. 4.  S u b gr o u p  A n al ysis  
T he pri mar y e n d p oi nt will be s u m marize d usi n g t he f oll o wi n g s u b gr o u ps:  
•  
A ge cate g ories ( ≥1 8 t o < 4 0, ≥4 0 t o < 6 5, ≥6 5),  
•  
Ge n der ( Male, Fe male)  
•  
Baseli ne B o d y wei g ht at scree ni n g ( k g) wit h gr o u pi n g ( < 7 0, ≥7 0 t o < 1 0 0, ≥1 0 0),  
•  
Re gi o n ( U S [ n o n -P S G a n d P S G], E ur o pe a n d R O W).  
•  
Baseli ne I G A ( m o derate [I G A = 3] a n d se vere [I G A = 4]) 
•  
Baseli ne m o derate t o se vere E A SI ( ≤2 1, > 2 1 ) 
•  
Baseli ne se vere E A SI ( < 2 5, ≥2 5)  
•  
Baseli ne S C O R A D ( ≤5 0, > 5 0)  
•  
Baseli ne pea k pr urit us N R S ( < 7, ≥7)  
•  
Pre vi o us use of s yste mic i m m u n os u p pressa nts f or A D ( Yes, N o)  
 
List of c o de d ter ms f or s yste mic i m m u n os u p pressa nts  ( me dicati o ns) use d f or A D will be pr o vi de d b y 
S A N O FI.  
 
Res ults will  als o be ill ustrate d wit h f orest pl ots.  
8. 1. 5.  Se nsiti vit y A n al ysis  
If a s pecific wee kl y a vera ge f or t he slee p q ualit y N R S was deri ve d usi n g 3 or less assess me nts, s uc h 
assess me nts will be set t o missi n g i n a n y se nsiti vit y a nal ysis.  
8. 1. 6.  S u p ple me nt ar y A n al ys es 
N ot a p plica b le. 
8. 1. 7.  I m p act of C o vi d-1 9 P a n de mic  
D uri n g t he C o vi d -1 9 pa n de mic, a b usi ness c o nti n uit y pla n ( B C P)  was p ut i n place t o mi ni mize t he i m pact 
of t he cli nic visit i nterr u pti o n, e ns ure I M P treat me nt c o nti n uit y a n d data c ollecti o n. Direct t o patie nt 
deli ver y of I M P fr o m t he site(s) was ma de a vaila ble, h o me i njecti o n(s) were d o ne as pla n ne d per pr ot oc ol. 
I M P i nterr u pti o n d ue t o C o vi d-1 9 pa n de mic is t heref ore e x pecte d t o be mi ni m u m. Data c ollecti o n f or 
¨ P R Os are n ot e x pecte d t o be missi n g as t he y ca n be c o m plete d at patie nt’s h o me o n his/ her i Pa d. Site(s) 
ca n u p date/c orrect t he sc he d ule of c o m pleti o n if visit is resc he d ule d/ dela ye d –  u nless site staff ca n n ot access 
ve n d or platf or m t o u p date sc he d ule d dates.  
 
Missi n g data d ue t o C o vi d -1 9 pa n de mic is li kel y t o be missi n g at ra n d o m. T heref ore, t he pri mar y a nal ysis 
usi n g M M R M ca n a de q uatel y a d dress t his t y pe of missi n g data.  Patie nt dis p ositi o n b y visit acc or di n g t o 
trial i m pact ( disr u pti o n) d ue t o C O VI D-1 9 a n d b y c o u ntr y a n d site are alrea d y me nti o ne d i n secti o n 5. 1  of 
t his S A P.  


Sa n ofi Gr o u p  
 
Fi nal Statistical A nal ysis Pla n, Versi o n 2. 0  
 
D u pil u ma b - L P S 1 5 4 9 7  
 
Date Iss ue d: 3 0J U L 2 0 2 1  
 
  
 
  2 3  
8. 2.  Sec o n d ar y a n d E x pl or at or y Effic ac y E n d p oi nt  
T he sec o n dar y efficac y e n d p oi nts ass ociate d wit h “ C ha n ge fr o m baseli ne” a n d “ Perce nt c ha n ge fr o m 
baseli ne” d uri n g t he d o u ble -bli n d treat me nt peri o d will be a nal yze d usi n g t he sa me a p pr oac h as use d f or 
t he a nal ysis of t he pri mar y e n d p oi nt. 
Defi niti o ns of e n d p oi nts are i ncl u de d i n Secti o n s 1 5. 8 , 1 5. 9  a n d 1 5. 1 0 . 
8. 2. 1.  Acti gr a p h y d at a  
S E, T S T, W A S O a n d S O L, all base d o n acti gra p h y data,  will be s u m marize d at eac h p ost -baseli ne visit 
( Wee k 1, Wee k 2, Wee k 3, Wee k 4 , Wee k 8, Wee k 1 2 , Wee k 1 6, Wee k 2 0, a n d Wee k 2 4). 
 
I n a d diti o n, at eac h p ost-baseli ne visit  u ntil Wee k 1 2 , t he c ha n ge fr o m baseli ne will be m o delle d usi n g t he 
sa me M M R M m o del use d f or t he a nal ysis of t he pri mar y e n d p oi nt. L S mea n differe nces bet wee n t he 
d u pil u ma b  a n d place b o gr o u p, t he c orres p o n di n g 9 5 % CI of t he differe nces a n d t w o-si de d p-val u es will be 
pr o vi de d.  All p -val ues e xce pt f or Wee k 1 2 will be c o nsi dere d n o mi nal.  
 
C ha n ge fr o m baseli ne t o Wee k 2 4 a n d C ha n ge fr o m Wee k 1 2 t o Wee k 2 4 will be s u m marize d o n t he O L E 
a nal ysis set usi n g descri pti ve statistics  i n eac h treat me nt gr o u p (t h ose ori gi nall y ra n d o mize d t o i n t he 
d o u ble -bli n d st u d y treat me nt peri o d) . N o c o m parati ve statistical a nal yses will be d o ne.  
8. 2. 2.  Slee p di ar y  
S E, T S T, W A S O , S O L, n u m ber of a wa ke ni n gs a n d h o w reste d  t he partici pa nt felt w he n getti n g u p, all 
base d o n slee p diar y data, will be s u m marize d at eac h p ost -baseli ne visit ( Wee k 1, Wee k 2, Wee k 3, Wee k 
4, Wee k 8 , a n d Wee k 1 2). 
 
I n a d diti o n, at eac h p ost-baseli ne visit, t he c ha n ge fr o m baseli ne will be m o delle d usi n g t he sa me M M R M 
m o del use d f or t he a nal ysis of t he pri mar y e n d p oi nt. L S mea n differe nces bet wee n t he d u pil u ma b  a n d 
place b o gr o u p, t he c orres p o n di n g 9 5 % CI of t he differe nces a n d t w o -si de d p-val ues will be pr o vi de d.  All 
p -val ues e xce pt f or Wee k 1 2 will be c o nsi dere d n o mi nal.  
8. 2. 3.  Slee p Q u alit y N R S  
Rescale d s lee p Q ualit y N R S (see secti o n 8. 1 ) will be s u m marize d at eac h p ost -baseli ne visit ( Wee k 1, Wee k 
2, Wee k 3, Wee k 4 , Wee k 8 , Wee k 1 6, Wee k 2 0, a n d Wee k 2 4 ) 
 
I n a d diti o n, at eac h p ost-baseli ne visit  u ntil Wee k 1 2 , t he perce nt c ha n ge fr o m baseli ne will be m o delle d 
usi n g t he  sa me M M R M m o del use d f or t he a nal ysis of t he pri mar y e n d p oi nt. L S mea n differe nces bet wee n 
t he d u pil u ma b  a n d place b o gr o u p, t he c orres p o n di n g 9 5 % CI of t he differe nces  a n d t w o-si de d p-val ues will 
be pr o vi de d.  All p -val ues e xce pt f or Wee k 1 2 will be c o nsi dere d n o mi nal.  
 
Perce nt c ha n ge fr o m baseli ne t o Wee k 2 4 a n d perce nt c ha n ge fr o m Wee k 1 2 t o Wee k 2 4 will be s u m marize d 
o n t he O L E a nal ysis set usi n g descri pti ve statistics i n eac h treat me nt gr o u p (t h ose ori gi nall y ra n d o mize d t o 
i n t he d o u ble-bli n d st u d y treat me nt peri o d). N o c o m parati ve statistical a nal yses will be d o ne.  
8. 2. 4.  Pe a k Pr urit us N R S  
Pea k pr urit us N R S  will be s u m marize d at eac h p ost -baseli ne visit ( Wee k 1, Wee k 2, Wee k 3, Wee k 4, Wee k 
8 , Wee k 1 2 , Wee k 1 6, Wee k 2 0, a n d Wee k 2 4). Dail y res ults f or eac h da y of Wee k 1 will als o be  pr o vi de d.  
 
I n a d diti o n, at eac h p ost-baseli ne visit  u ntil Wee k 1 2 , t he perce nt c ha n ge fr o m baseli ne will be m o delle d 
usi n g t he sa me M M R M m o del use d f or t he a nal ysis of t he pri mar y e n d p oi nt. L S mea n differe nces bet wee n 


Sa n ofi Gr o u p  
 
Fi nal Statistical A nal ysis Pla n, Versi o n 2. 0  
 
D u pil u ma b - L P S 1 5 4 9 7  
 
Date Iss ue d: 3 0J U L 2 0 2 1  
 
  
 
  2 4  
t he d u pil u ma b  a n d place b o gr o u p, t he c orres p o n di n g 9 5 % CI of t he differe nces a n d t w o-si de d p-val ues will 
be pr o vi de d.  All p -val ues e xce pt f or Wee k 1 2 will be c o nsi dere d n o mi nal.  
 
Perce nt c ha n ge fr o m baseli ne t o Wee k 2 4 a n d perce nt c ha n ge fr o m Wee k 1 2 t o Wee k 2 4 will be s u m marize d 
o n t he O L E a nal ysis set usi n g descri pti ve statistics  i n eac h treat me nt gr o u p (t h ose ori gi nall y ra n d o mize d t o 
i n t he d o u ble-bli n d st u d y treat me nt peri o d). N o c o m parati ve statistical a nal yses will be d o ne.  
 
Ti me s t o pr urit us i m pr o ve me nt are defi ne d as : 
1.  Ti me t o ac hie vi n g ≥3 p oi nts i m pr o ve me nt i n N R S [ Ti me fra m e: Baseli ne till Wee k 4 ] 
2.  Ti me t o ac hie vi n g ≥4 p oi nts i m pr o ve me nt i n N R S [ Ti me fra me: Baseli ne till Wee k 4 ] 
 
T he ti me varia ble will be t he first da y of ac hie vi n g ≥x p oi nts i m pr o ve me nt, a n d if t hat was n ot ac hie ve d 
d uri n g t he first 4 wee ks ( w here dail y asses s me nts were d o ne ), it will be ce ns ore d at 2 8 da ys. Alt h o u g h t he 
ti me varia ble is c o u nti n g t he n u m ber of da ys, t he baseli ne will still be t he wee kl y a vera ge at Visit 1 si nce 
t hat is t he i ncl usi o n criteria a n d better re prese nts t he patie nt pr urit us at baseline. T he baseli ne date will be 
t he date of  Visit 1.  Patie nts w h o disc o nti n ue d f or a n y reas o n wit hi n t he first 4 wee ks will be ce ns ore d at t he 
ti me of disc o nti n uati o n. 
 
T he me dia n ti me t o pr urit us i m pr o ve me nt a n d pr o p orti o n of patie nts ac hie vi n g ≥x p oi nts i m pr o ve me nt at 
Wee k 1, Wee k 2, Wee k 3, a n d at Wee k 4 al o n g wit h t he c orres p o n di n g 9 5 % CI will be calc ulate d usi n g 
Ka pla n Meier met h o d . 
 
A s u m mar y wit h t he n u m ber of patie nts ac hie vi n g t he pr urit us i m pr o ve me nt, t he n u m ber of ce ns ore d 
patie nts, t he me dia n ti me , rates at Wee k 1, Wee k 2, Wee k 3, a n d Wee k 4  al o n g wit h t he c orres p o n di n g 9 5 % 
CI will be pr o vi de d.  Ka pla n -Meier c ur ves will be pr o vi de d t o o.  
8. 2. 5.  S ki n P ai n N R S  
S ki n Pai n N R S will be s u m marize d at eac h p ost -baseli ne visit ( Wee k 1, Wee k 2, Wee k 3,  Wee k 4, Wee k 
8 , a n d Wee k 1 2).  Dail y res ults f or eac h da y of Wee k  1  will als o be pr o vi de d.  
 
I n a d diti o n, at eac h p ost-baseli ne visit, t he c ha n ge fr o m baseli ne will be m o delle d usi n g t he  sa me M M R M 
m o del use d f or t he a nal ysis of t he pri mar y e n d p oi nt. L S mea n dif fere nces bet wee n t he d u pil u ma b  a n d 
place b o gr o u p, t he c orres p o n di n g 9 5 % CI of t he differe nces a n d t w o -si de d p-val ues will be pr o vi de d.  All 
p -val ues e xce pt f or Wee k 1 2 will be c o nsi dere d n o mi nal.  
8. 2. 6.  S ki n Se nsiti vit y t o T o uc h N R S  
S ki n Se nsiti vit y t o T o uc h N R S w ill be s u m marize d at eac h p ost-baseli ne visit ( Wee k 1, Wee k 2, Wee k 3, 
Wee k 4, Wee k 8 , a n d Wee k 1 2).  
 
I n a d diti o n, at eac h p ost-baseli ne visit, t he c ha n ge fr o m baseli ne will be m o delle d usi n g t he sa me M M R M 
m o del use d f or t he a nal ysis of t he pri mar y e n d p oi nt. L S mea n differe nces bet wee n t he d u pil u ma b  a n d 
place b o gr o u p, t he c orres p o n di n g 9 5 % CI of t he differ e nces  a n d t w o -si de d p-val ues will be pr o vi de d.  All 
p -val ues e xce pt f or Wee k 1 2 will be c o nsi dere d n o mi nal.  
8. 2. 7.  S ki n B ur n N R S  
S ki n B ur n N R S will be s u m marize d at eac h p ost -baseli ne visit ( Wee k 1, Wee k 2,  Wee k 3,  Wee k 4, Wee k 
8 , a n d Wee k 1 2).  
 
I n a d diti o n, at eac h p ost -baseli ne visit, t he c ha n ge fr o m baseli ne will be m o delle d usi n g t he sa me M M R M 
m o del use d f or t he a nal ysis of t he pri mar y e n d p oi nt. L S mea n differe nces bet wee n t he d u pil u ma b  a n d 


Sa n ofi Gr o u p  
 
Fi nal Statistical A nal ysis Pla n, Versi o n 2. 0  
 
D u pil u ma b - L P S 1 5 4 9 7  
 
Date Iss ue d: 3 0J U L 2 0 2 1  
 
  
 
  2 5  
place b o gr o u p, t he c orres p o n di n g 9 5 % CI of t he differe nces a n d t w o -si ded p -val ues will be pr o vi de d.  All 
p -val ues e xce pt f or Wee k 1 2 will be c o nsi dere d n o mi nal.  
8. 2. 8.  Ecze m a Are a Se v erit y I n de x ( E A SI)  
 
 
T he E A SI t otal sc ore a n d perce nt c ha n ge fr o m baseli ne i n E A SI t otal sc ore will be s u m marize d at eac h 
p ost -baseli ne visit. A t eac h post -baseli ne visit u ntil Wee k 1 2, t he perce nt c ha n ge fr o m baseli ne  i n E A SI 
t otal sc ore will be m o delle d usi n g t he sa me M M R M m o del use d f or t he a nal ysis of t he pri mar y e n d p oi nt. 
L S mea n differe nces bet wee n t he d u pil u ma b  a n d place b o gr o u p, t he c orres p o n di n g 9 5 % CI of t he 
differe nces a n d t w o -si de d p-val ues will be pr o vi de d. All p -val ues e xce pt  f or Wee k 1 2 will be c o nsi dere d 
n o mi nal.  
 
I n a d diti o n, t he res p o n der bi nar y varia bles E A SI 5 0, E A SI 7 5 a n d E A SI 9 0 i n dicati n g w het her t he patie nt 
ac hie ve d at least 5 0 %, 7 5 % a n d 9 0 % i m pr o ve me nt (re d ucti o n), res pecti vel y, will be s u m marize d a n d 
m o delle d. T he n u m ber a n d perce nta ge of patie nts wit h E A SI 5 0, E A SI 7 5 a n d E A SI 9 0 will be prese nte d f or 
eac h p ost -baseli ne visit ( Wee k 1, Wee k 2, Wee k 4, Wee k 8, Wee k 1 2, Wee k 1 6, Wee k 2 0 a n d Wee k 2 4) 
al o n gsi de t he n u m ber of patie nts e val uate d at t hat visits. T he perce nta ge f or eac h res p o n der varia ble will 
be deri ve d base d o n t he n u m ber of patie nts w h o are e val ua ble at t he visit.  
 
M ore o ver, at eac h p ost -baseli ne visit u ntil 
Wee k 1 2, t he res p o n der varia bles (E A SI 5 0 , E A SI 7 5 a n d 
E A SI 9 0) will be m o delle d usi n g Ge neralize d Li near Mi xe d M o del ( G L M M) . T he ter ms i ncl u de d will be 
t he sa me as t h ose i n t he M M R M m o del use d f or t he a nal ysis of t he pri mar y e n d p oi nt. T he m o del will be 
fitte d usi n g P R O C G LI M MI X ass u mi n g a bi n o mial distri b uti o n a n d l o git li n k. T he esti mate d i nci de nce  rate 
f or eac h treat me nt gr o u p  a n d t he c orres p o n di n g 9 5 % CI of t he esti mate d i nci de nce  rates will be pr o vi de d . 
T he o d ds rati os a n d t he c orres p o n di n g 9 5 % CI of t he o d ds rati o  wit h  t w o-si de d p-val ue will be pr o vi de d.  
All p -val ues e xce pt f or Wee k 1 2 will be c o nsi dere d n o mi nal. 
 
T he G LI M MI X pr oce d ure f or m o delli n g t he bi n o mial res p o n der varia bles will be base d o n  t he f oll o wi n g 
sa m ple S A S c o de t o e val uate t he treat me nt effect t hr o u g h wee k 1 2: 
 
 
p r oc gli m mi x data = a dcc;  
 
 
w here para mc d e q “ E A SI 5 0” a n d a visit n g e 2 a n d a visit n le 6 a n d I T T F L =” Y”;  
 
 
class us u bji d strat u m  a visit n trt 0 1 p n(ref =’ x’);  
* * ‘ x’ s h o ul d be c o de f or t he place b o gr o u p  * *  
m o del res p (e ve nt =’ 1’) = base trt 0 1 p n strat u m a visit n a visit n *trt 0 1 p n base *a visit n / 
dist = bi n o mial li n k =l o git s ol uti o n d df m = kr;  
ra n d o m _resi d ual _ / s u bject = us u bji d t y pe = U N; * * t y pe ca n als o c ha n ge here as i n mi xe d 
t o T O E P H, T O E P, A R( 1) or C S t o ac hie ve c o n ver ge nce . * * 
ls mea ns trt 0 1 p n *a visit n / p diff  ili n k O R C L;  
 
r u n; 
 
N ote t hat sa m ple c o de ass u mes t hat t he rele va nt p ost-baseli ne visits u ntil Wee k 1 2 are c o de d bet wee n 2 a n d 
6 i ncl usi ve, if t hat is n ot t he case, t he c o de s h o ul d be a dj uste d.  
 
If t he G L M M m o de l fails t o ac hie ve c o n ver ge nce (e ve n wit h si m pler c o varia nce str uct ures), t he res p o n der 
varia ble s will be a nal yze d usi n g a l o gistic re gressi o n m o del , se paratel y at eac h assess me nt ti me p oi nt 
t hr o u g h Wee k 1 2. T he l o gistic re gressi o n m o del will i ncl u de treat me nt ( d u pil u ma b , p lace b o) as fi xe d effect , 
a n d will i ncl u de baseli ne val ue of E A SI , ra n d o mizati o n strat u m (re gi o n) as fi xe d effect c o variat es. A 
s u m mar y ta ble will prese nt the esti mate d i nci de nce f or eac h treat me nt gr o u p a n d c orres p o n di n g 9 5 % 


Sa n ofi Gr o u p  
 
Fi nal Statistical A nal ysis Pla n, Versi o n 2. 0  
 
D u pil u ma b - L P S 1 5 4 9 7  
 
Date Iss ue d: 3 0J U L 2 0 2 1  
 
  
 
  2 6  
c o nfi de nce i nter val ( CI); als o, t he o d ds rati o, c orres p o n di n g 9 5 % CI a n d p-val ue f or t he treat me nt differe nce 
bet wee n t he d u pil u ma b  a n d place b o gr o u p . A n esti mate of t he o d ds rati o a n d a CI a b o ve 1 is a n i n dicati o n 
t hat y o u are m ore li kel y t o be a res p o n der o n t he acti ve treat me nt gr o u p rat her t ha n place b o. 
 
If t he l o gistic re gressi o n m o del fails t o ac hie ve c o n ver ge nce at a p ost -baseli ne visit, t he Cl o p per Pears o n 
9 5 %  CI of t he i nci de nce rate (e x presse d i n perce nta ge) a n d t he 9 5 % CI of t he differe nce i n i nci de nce rate 
bet wee n treat me nt gr o u p a n d place b o (i.e. treat me nt –  place b o) a n d p-val ue will be prese nte d. T he 9 5 %  CI 
f or t he differe nce bet wee n d u pil u ma b  a n d place b o  will be base d o n t he C oc hra n -Ma ntel -Hae nszel ( C M H) 
test a dj uste d b y t he ra n d o mizati o n strat u m, at t he p ost-baseli ne ti me p oi nt. 
8. 2. 9.  P atie nt orie nte d ecze m a me as ure ( P O E M)  
T he P O E M t otal sc ore will be s u m marize d at eac h p ost -baseli ne visit ( Wee k 4 , Wee k 1 2 , a nd Wee k 2 4 ). 
 
I n a d diti o n, at eac h p ost-baseli ne visit  u ntil Wee k 1 2 , t he c ha n ge fr o m baseli ne will be m o delle d usi n g t he 
sa me M M R M m o del use d f or t he a nal ysis of t he pri mar y e n d p oi nt. L S mea n differe nce s bet wee n t he 
d u pil u ma b  a n d place b o gr o u p, t he c orres p o n di n g 9 5 % CI of t he differe nces  a n d t w o-si de d p-val ues will be 
pr o vi de d.  All p -val ues e xce pt f or Wee k 1 2 will be c o nsi dere d n o mi nal.  
 
C ha n ge fr o m baseli ne t o Wee k 2 4 a n d C ha n ge fr o m Wee k 1 2 t o Wee k 2 4 will be s u m marize d  o n t he O L E 
a nal ysis set usi n g descri pti ve statistics i n eac h treat me nt gr o u p (t h ose ori gi nall y ra n d o mize d t o i n t he 
d o u ble -bli n d st u d y treat me nt peri o d). N o c o m parati ve statistical a nal yses will be d o ne.  
8. 2. 1 0.  P R O MI S Slee p Rel ate d I m p air me nt S h ort F or m 8 a  
T he P R O MI S Slee p Relate d I m pair me nt S F 8a t otal ra w a n d T-sc ores w ill be s u m marize d at eac h p ost-
baseli ne visit ( Wee k 1, Wee k 2, Wee k 4, Wee k 8 , Wee k 1 2 , Wee k 1 6, Wee k 2 0, a n d Wee k 2 4). T -sc ore 
calc ulati o n is defi ne d i n  Ta ble 1 5. 8 .1 . 
 
I n a d diti o n, at eac h p ost-baseli ne visit  u ntil Wee k 1 2 , t he c ha n ge fr o m baseli ne f or ra w sc ore a n d T-sc ore 
will be m o delle d usi n g t he sa me M M R M m o del use d f or t he a nal ysis of t he pri mar y e n d p oi nt. L S mea n 
differe nces bet wee n t he d u pil u ma b  a n d place b o gr o u p, t he c orres p o n di n g 9 5 % CI of t he differe nces  a n d 
t w o-si de d p-val ues will be pr o vi de d.  All p -val ues e xce pt f or Wee k 1 2 will be c o nsi dere d n o mi nal.  
 
C ha n ge fr o m baseli ne t o Wee k 2 4 a n d C ha n ge fr o m Wee k 1 2 t o Wee k 2 4 will be s u m marize d  o n t he O L E 
a nal ysis set usi n g descri pti ve statistics i n eac h treat me nt gr o u p (t h ose ori gi nall y ra n d o mize d t o i n t he 
d o u ble -bli n d st u d y treat me nt peri o d). N o c o m parati ve statistical a nal yses will be d o ne.  
8. 2. 1 1.  E p w ort h Slee pi ness Sc ale ( E S S)  
T he E S S will be s u m marize d at eac h p ost -baseli ne visit ( Wee k 4 , Wee k 1 2 , a n d Wee k 2 4). 
 
I n a d diti o n, at eac h p ost-baseli ne visit, t he c ha n ge fr o m baseli ne will be m o delle d usi n g t he sa me M M R M 
m o del use d f or t he a nal ysis of t he pri mar y e n d p oi nt. L S mea n differe nces bet wee n t he d u pil u ma b  a n d 
place b o gr o u p, t he c orres p o n di n g 9 5 % CI of t he differ e nces  a n d t w o -si de d p-val ues will be pr o vi de d.  All 
p -val ues e xce pt f or Wee k 1 2 will be c o nsi dere d n o mi nal.  
8. 2. 1 2.  Der m at ol o g y Life Q u alit y I n de x ( D L QI)  
T he D L QI  will be s u m marize d at eac h p ost -baseli ne visit ( Wee k 4 , Wee k 1 2 , a n d Wee k 2 4 ). 
 
I n a d diti o n, at eac h post -baseli ne visit  u ntil Wee k 1 2 , t he c ha n ge fr o m baseli ne will be m o delle d usi n g t he 
sa me M M R M m o del use d f or t he a nal ysis of t he pri mar y e n d p oi nt. L S mea n differe nces bet wee n t he 


Sa n ofi Gr o u p  
 
Fi nal Statistical A nal ysis Pla n, Versi o n 2. 0  
 
D u pil u ma b - L P S 1 5 4 9 7  
 
Date Iss ue d: 3 0J U L 2 0 2 1  
 
  
 
  2 7  
d u pil u ma b  a n d place b o gr o u p, t he c orres p o n di n g 9 5 % CI of t he differe nces a nd t w o -si de d p-val ues will be 
pr o vi de d.  All p -val ues e xce pt f or Wee k 1 2 will be c o nsi dere d n o mi nal.  
 
C ha n ge fr o m baseli ne t o Wee k 2 4 a n d C ha n ge fr o m Wee k 1 2 t o Wee k 2 4 will be s u m marize d  o n t he O L E 
a nal ysis set usi n g descri pti ve statistics i n eac h treat me nt gr o u p (t h ose ori gi nall y ra n d o mize d t o i n t he 
d o u ble -bli n d st u d y treat me nt peri o d). N o c o m parati ve statistical a nal yses will be d o ne.  
8. 2. 1 3.  S C O Ri n g of At o pic Der m atitis ( S C O R A D)  
T he S C O R A D t otal sc ore a n d slee p V A S will be s u m marize d at eac h p ost baseli ne visit ( Wee k 1, Wee k 2, 
Wee k 4, Wee k 8 , Wee k 1 2 , Wee k 1 6, Wee k 2 0, a n d Wee k 2 4). 
 
I n a d diti o n, at eac h p ost-baseli ne visit  u ntil Wee k 1 2 , t he c ha n ge fr o m baseli ne will be m o delle d usi n g t he 
sa me M M R M m o del use d f or t he a nal ysis of t he pri mar y e n d p oi nt. L S mea n differe nces bet wee n t he 
d u pil u ma b  a n d place b o gr o u p, t he c orres p o n di n g 9 5 % CI of t he differe nces a n d t w o-si de d p-val ues will be 
pr o vi de d.  All p -val ues e xce pt f or Wee k 1 2 will be c o nsi dere d n o mi nal.  
 
C ha n ge fr o m baseli ne t o Wee k 2 4 a n d C ha n ge fr o m We e k 1 2 t o Wee k 2 4 will be s u m marize d  o n t he O L E 
a nal ysis set usi n g descri pti ve statistics i n eac h treat me nt gr o u p (t h ose ori gi nall y ra n d o mize d t o i n t he 
d o u ble -bli n d st u d y treat me nt peri o d). N o c o m parati ve statistical a nal yses will be d o ne.  
8. 2. 1 4.  J u ni per Ast h m a C o ntr ol Q uesti o n n aire  ( A C Q-5)  
T he A C Q -5 gl o bal sc ore will be s u m marize d at eac h p ost -baseli ne visit (Wee k 1 2  a n d Wee k 2 4). 
 
I n a d diti o n, t he c ha n ge fr o m baseli ne at Wee k 1 2  will be m o delle d usi n g t he sa me M M R M m o del use d f or 
t he a nal ysis of t he pri mar y e n d p oi nt. L S mea n differe nce bet wee n t he d u pil u ma b  a n d place b o gr o u p, t he 
c orres p o n di n g 9 5 % CI of t he differe nce a n d t w o-si de d p-val ue will be pr o vi de d.  All p -val ues e xce pt f or 
Wee k 1 2 will be c o nsi dere d n o mi nal.  
8. 2. 1 5.  Aller gic R hi nitis Vis u al A n al o g Sc ale ( A R -V A S)  
T he A R -V A S sc ore will be s u m marize d at eac h p ost -baseli ne visit (Wee k 1 2  a n d Wee k 2 4) . 
 
I n a d diti o n, at eac h p ost-baseli ne visit  u ntil Wee k 1 2 , t he c ha n ge fr o m baseli ne will be m o delle d usi n g t he 
sa me M M R M m o del use d f or t he a nal ysis of t he pri mar y e n d p oi nt. L S mea n differe nce bet wee n t he 
d u pil u ma b  a n d place b o gr o u p, t he c orres p o n di n g 9 5 % CI of t he differe nce a n d t w o-si de d p-val ues will be 
pr o vi de d.  All p -val ues e xce pt f or Wee k 1 2 will be c o nsi dere d n o mi nal. 
8. 2. 1 6.  Ps yc h o m ot or Vi gil a nce Test ( P V T)  
T he P V T varia bles, t otal err ors, n u m ber of la pses, mea n reci pr ocal res p o nse ti me, mea n fastest res p o nse 
ti me, a n d mea n sl o west reci pr ocal res p o nse ti me will be s u m marize d at eac h p ost-baseli ne visit ( Wee k 1 2 
a n d Wee k 2 4). 
 
I n a d diti o n, at eac h p ost-baseli ne visit u ntil Wee k 1 2, t he c ha n ge fr o m baseli ne will be m o delle d usi n g t he 
sa me M M R M m o del use d f or t he a nal ysis of t he pri mar y e n d p oi nt. L S mea n differe nce bet wee n t he 
d u pil u ma b  a n d place b o gr o u p, t he c orres p o n di n g 9 5 % CI of t he differe nce a n d t w o-si de d p-val ues will be 
pr o vi de d.  All p -val ues e xce pt f or Wee k 1 2 will be c o nsi dere d n o mi nal.  
 
F or tests t hat i n dicate “ Faile d Q C: clear n o n -c o m plia nce”, t he tests a n d t he ass ociate d metrics will be 
e xcl u de d fr om t he a nal yses si nce t he res ults are j u d ge d t o be pr oce d urall y n o n -c o m plia nt rat her t ha n d ue t o 
ps yc h o m ot or i m pair me nt. If t he differe nce i n t he pr o p orti o n of “ Faile d Q C: clear n o n -c o m plia nce” tests 


Sa n ofi Gr o u p  
 
Fi nal Statistical A nal ysis Pla n, Versi o n 2. 0  
 
D u pil u ma b - L P S 1 5 4 9 7  
 
Date Iss ue d: 3 0J U L 2 0 2 1  
 
  
 
  2 8  
bet wee n t he treat me nts is m ore t ha n 2 0 %, a n e x pl orat or y a nal ysis of t he s u m maries me nti o ne d a b o ve will 
be re peate d b y i ncl u di n g t hese tests.  
8. 2. 1 7.  Ne ur oc o g niti ve Test  ( A ut o m ate d Ne ur o ps yc h ol o gic al Assess m e nt 
Metri cs 
[ A N A M]) 
T he A N A M varia bles, m ea n res p o nse ti me  f or all res p o nses, perce nta ge of c orrect res p o nse a n d t hr o u g h p ut  
will be s u m marize d at eac h p ost -baseli ne visit ( Wee k 1 2 a n d Wee k 2 4) a n d f or eac h of t he t hree s u btests.  
 
I n a d diti o n, at eac h p ost-baseli ne visit u ntil Wee k 1 2, t he c ha n ge fr o m baseli ne will be m o delle d usi n g t he 
sa me M M R M m o del us e d f or t he a nal ysis of t he pri mar y e n d p oi nt. L S mea n differe nce bet wee n t he 
d u pil u ma b  a n d place b o gr o u p, t he c orres p o n di n g 9 5 % CI of t he differe nce a n d t w o-si de d p-val ues will be 
pr o vi de d.  All p -val ues e xce pt f or Wee k 1 2 will be c o nsi dere d n o mi nal.  
 
F or te sts wit h vali dit y fla g as “I n vali d”, t he tests a n d t he ass ociate d metrics will be e xcl u de d fr o m t he 
A N A M data a nal ysis. If t he differe nce i n pr o p orti o n of “i n vali d” tests bet wee n t he treat me nts is m ore t ha n 
2 0 %, a n e x pl orat or y a nal ysis of t he s u m maries me n ti o ne d a b o ve will be re peate d b y i ncl u di n g t hese tests. 
8. 2. 1 8.  P ol ys o m n o gr a p h y ( P S G)  
S E, T S T, W A S O, a n d S O L, all base d o n P S G  meas ures , will be s u m marize d at p ost-baseli ne visit (Wee k 
1 2)  o n t he P S G a nal ysis set. 
8. 2. 1 9.  W or k 
Pr o d ucti vit y 
a n d 
Acti vit y 
I m p air me nt 
Q uesti o n n aire: 
At o pic 
Der m atitis ( W P AI -A D)  
T he n u m ber a n d perce nta ge of patie nts c urre ntl y e m pl o ye d ( yes/ n o)  will be prese nte d f or eac h p ost -baseli ne 
visit ( Wee k 4, Wee k 8 , Wee k 1 2 , a n d Wee k 2 4) al o n gsi de t he n u m ber of patie nts e val uate d at t hat visits  
If e m pl o ye d, t he n u m ber of h o urs misse d d ue t o A D  i n t he past wee k, n u m ber of h o urs misse d d ue t o ot her 
reas o ns i n t he past wee k, n u m ber of h o urs act uall y w or ke d i n t he past wee k, N R S of at o pic der matitis 
affecti n g pr o d ucti vit y w hile w or ki n g  i n t he past wee k  a n d N R S of at o pic der matitis affecti n g t he a bilit y t o 
d o re g ular dail y acti vities ot her t ha n w or k at a j o b  i n t he past wee k will be s u m marize d at eac h p ost -baseli ne 
visit ( Wee k 4, Wee k 8, Wee k 1 2, a n d Wee k 2 4). 
 
I n a d diti o n, at eac h p ost-baseli n e visit u ntil Wee k 1 2, t he c ha n ge fr o m baseli ne will be m o delle d usi n g t he 
sa me M M R M m o del use d f or t he a nal ysis of t he pri mar y e n d p oi nt. L S mea n differe nce bet wee n t he 
d u pil u ma b  a n d place b o gr o u p, t he c orres p o n di n g 9 5 % CI of t he differe nce a n d t w o-si de d p-val ues will be 
pr o vi de d.  All p -val ues e xce pt f or Wee k 1 2 will be c o nsi dere d n o mi nal.  
8. 2. 2 0.  D a ys misse d fr o m sc h o ol or fr o m w or k d ue t o A D  
T he Da ys misse d fr o m sc h o ol or fr o m w or k will  be s u m marize d at eac h p ost -baseli ne visit ( Wee k 4, Wee k 
8, Wee k 1 2, Wee k 1 6, Wee k 2 0 , a n d Wee k 2 4). 
 
T he t otal n u m ber of da ys of sic k lea ve o ver 1 2 wee ks will be a nal yze d usi n g a ne gati ve bi n o mial m o del, 
w here da ys of sic k lea ve t hr o u g h wee k 1 2 will be t h e res p o nse varia ble, t he i n de pe n de nt varia bles will be 
t he treat me nt gr o u p a n d re gi o n, a n d t he l o g tra nsf or mati o n of d urati o n of e m pl o y me nt t hr o u g h wee k 1 2 
will be use d as t he offset varia ble. N o missi n g data will be i m p ute d.  
Sa m ple c o de f or ne gati ve bi n o m ial m o del: 
pr oc ge n m o d data = da ys _ misse d;  
class trt 0 1 p n re gi o n;  


Sa n ofi Gr o u p  
 
Fi nal Statistical A nal ysis Pla n, Versi o n 2. 0  
 
D u pil u ma b - L P S 1 5 4 9 7  
 
Date Iss ue d: 3 0J U L 2 0 2 1  
 
  
 
  2 9  
m o del a val = trt 0 1 p n re gi o n/ dist = ne g bi n li n k =l o g offset =l o g d ur;  
            ls mea ns trt 0 1 p n / p diff cl e x p; 
            o ds o ut p ut ls mea ndiffs = diffs ls mea ns =ls mea ns;  
r u n; 
 
T he d urati o n of e m pl o y me nt t hr o u g h wee k 1 2, da ys of sic k lea ve t hr o u g h wee k 1 2 a n d e m pl o y me nt 
d urati o n a dj uste d sic k lea ve da ys per 1 2 wee ks will be s u m marize d f or eac h treat me nt gr o u p usi n g 
descri pti ve statistics.  
8. 2. 2 1.  H os pit al A n xiet y a n d De pressi o n Sc ale ( H A D S)  
T he H A D S -a n xiet y a n d H A D S -de pressi o n sc ores  will be s u m marize d at eac h p ost -baseli ne visit ( Wee k 4, 
Wee k 1 2 , a n d Wee k 2 4). 
 
I n a d diti o n, at eac h p ost-baseli ne visit u ntil Wee k 1 2, t he c ha n ge fr o m baseli ne will be m o delle d usi n g t he 
sa me M M R M m o del use d f or t he a nal ysis of t he pri mar y e n d p oi nt. L S mea n differe nce bet wee n t he 
d u pil u ma b  a n d place b o gr o u p, t he c orres p o n di n g 9 5 % CI of t he differe nce  a n d t w o-si de d p-val ues will be 
pr o vi de d . All p -val ues e xce pt f or Wee k 1 2 will be c o nsi dere d n o mi nal.  
8. 2. 2 2.  Rel ati o ns hi p bet wee n v ari a bles rel ati n g t o sle e p dist ur b a nces a n d o bjecti v e 
a n d s u bjecti ve p ar a meters ass oci ate d wit h A D.  
Relati o ns hi p bet wee n varia bles (c ha n ge fr o m baseli ne a n d perce nt c ha n ge fr o m baseli ne) relati n g t o slee p 
dist ur ba nces a n d o bjecti ve a n d s u bjecti ve para meters ass ociate d wit h A D will be e x pl ore d. Pears o n 
c orrelati o n c oefficie nt  a n d p -val ue will be pr o vi de d b y visit.  F or t he P S G s u bset, S pear ma n c orrelati o n 
c oefficie nt a n d p -val ue will be pr o vi de d b y visit.  
Varia bles relati n g t o slee p dist ur ba nces i ncl u de:  
•  
Slee p q ualit y N R S  
•  
S E, T S T, W A S O, a n d S O L base d o n acti gra p h y data  
•  
S E, T S T,  W A S O, a n d S O L base d o n slee p diar y data  
•  
S C O R A D slee p V A S  
•  
P R O MI S Slee p Relate d I m pair me nt S F 8a t otal sc ore  
•  
S E, T S T, W A S O, a n d S O L  base d o n t he P S G data  
•  
P V T varia bles:  t otal err ors, n u m ber of la pses, mea n reci pr ocal res p o nse ti me, mea n fastest res p o nse 
ti me, a n d mea n sl o west reci pr ocal res p o nse ti me 
•  
A N A M varia bles: mea n res p o nse ti me, perce nta ge of c orrect res p o nse a n d t hr o u g h p ut f or r u n ni n g 
me m or y, mat he matical pr ocess i n g a n d pr oce d ural reacti o n ti me. 
 
Varia bles relati n g t o o bjecti ve a n d s u bjecti ve para meters ass ociate d wit h A D  i ncl u de: 
•  
S C O R A D t otal sc ore  
•  
E A SI t otal sc ore  
•  
P O E M t otal sc ore  
•  
D L QI t otal sc ore  
•  
Pea k pr urit us N R S  
 
T he c orrelati o ns  at baseli ne, Wee k 1 2 a n d c ha n ge fr o m baseli ne t o Wee k 1 2 will be a nal yze d b y gr o u p as 
defi ne d bel o w:  
 
•  
Gr o u p 1:  Slee p q ualit y N R S v ers us E A SI  t otal sc ore, S C O R A D t otal sc ore, P O E M  t otal sc ore, 
D L QI  t otal sc ore, a n d Pea k Pr urit us  N R S  


Sa n ofi Gr o u p  
 
Fi nal Statistical A nal ysis Pla n, Versi o n 2. 0  
 
D u pil u ma b - L P S 1 5 4 9 7  
 
Date Iss ue d: 3 0J U L 2 0 2 1  
 
  
 
  3 0  
•  
Gr o u p 2:  Slee p diar y v ers us Acti gra p h y (c orres p o n di n g meas ure, S E, T S T, W A S O, a n d S O L), 
P O E M t otal sc ore, SC O R A D t otal sc ore , P R O MI S Slee p Relate d I m pair me nt S F 8a t otal sc ore.  
•  
Gr o u p 3:  P S G v ers us Ac ti gra p h y (c orres p o n di n g meas ure), slee p diar y (c orres p o n di n g meas ure) 
o n t he s u bs et of P S G patie nts.  
•  
Gr o u p 4:  S lee p q ualit y N R S v ers us P V T varia bles, A N A M  varia bles , W P AI-A D v aria bles a n d da ys 
misse d fr o m sc h o ol or fr o m w or k.  
•  
Gr o u p 5:  Slee p q ualit y N R S v ers us  P V T  varia bles, A N A M varia bles , W P AI-A D v aria bles a n d da ys 
misse d fr o m sc h o ol or fr o m w or k f or Wee k 2 4,  a n d C h a n ge fr o m baseli ne t o Wee k 2 4  
 
F or acti gra p h y  a n d slee p diar y data, t he wee kl y a vera ges will be use d f or c orrelati o ns. A d di ti o nall y, f or 
Gr o u p 3, t he sa me da y assess me nt ( n ot t he a vera ge) will be use d. 
 
A d diti o nall y, relati o ns hi p bet wee n P S G a n d acti gra p h y data f or t he P S G a nal ysis set will be a nal yze d b y 
pr o vi d i n g scatter pl ots f or eac h of t he P S G para meters vers us t he c orres p o n di n g acti gra p h y para meters.  F or 
acti gra p h y data, t he sa me da y assess me nt ( n ot t he a vera ge) as t h ose of t he P S G data will be use d.  
8. 2. 2 3.  M ulti plicit y iss ues  
T he o verall t y pe -I err or rate will be c o ntr olle d at t he t w o-si de d 0. 0 5 le vel usi n g a se q ue ntial testi n g 
pr oce d ure. I n or der f or a n y sec o n dar y e n d p oi nts t o be eli gi ble f or bei n g declare d si g nifica nt , t he pri mar y 
e n d p oi nt m ust be si g nifica nt  at 0. 0 5 si g nifica nce le vel . T he sec o n dar y e n d p oi nts will be teste d f oll o wi n g 
t he hierarc hical testi n g pr oce d ure wit h a pre-s pecifie d or der, t hat is, i nfere ntial c o ncl usi o ns a b o ut s uccessi ve 
sec o n dar y e n d p oi nts re q uire statistical si g nifica nce at 0. 0 5 si g nifica nce le vel of t he pre vi o us o ne.  
T he f oll o wi n g ke y sec o n dar y e n d p oi nts will be i ncl u de d i n t he m ulti plicit y a dj ust me nt sc he me a n d teste d 
i n t he f oll o wi n g or der: 
1.  Perce nt c ha n ge fr o m baseli ne t o Wee k 1 2 i n pea k pr urit us N R S  
2.  C ha n ge fr o m baseli ne t o Wee k 1 2 i n S C O R A D t otal sc ore  
3.  C ha n g e fr o m baseli ne t o Wee k 1 2 i n S C O R A D slee p V A S  
4.  C ha n ge fr o m baseli ne t o Wee k 1 2 i n P R O MI S Slee p I m pair me nt S F 8a sc ore  
5.  C ha n ge fr o m baseli ne t o Wee k 1 2 i n T S T base d o n acti gra p h y data  
6.  C ha n ge fr o m baseli ne t o Wee k 1 2 i n S E base d o n acti gra p h y data  
7.  C ha n ge fr o m baseli ne t o Wee k 1 2 i n W A S O base d o n acti gra p h y data 
8.  C ha n ge fr o m baseli ne t o Wee k 1 2 i n S O L base d o n acti gra p h y data  
 
Eac h e n d p oi nt will be teste d at 0. 0 5 (t w o -si de d) le vel of si g nifica nce. If at a n y ste p t he n ull statistical 
h y p ot hesis of n o treat me nt differe nce is n ot rejecte d, t he e n d p oi nts liste d after t hat ste p will be re p orte d at 
n o mi nal le vel, ot her wise will be tec h nicall y eli gi ble f or bei n g declare d si g nifica nt. Re gar dless of eli gi bilit y 
f or bei n g declare d si g nifica nt, all e n d p oi nts ( n o n-ke y se c o n dar y a n d e x pl orat or y) will be teste d at 0. 0 5 
(t w o-si de d) le vel of si g nifica nce a n d re p orte d at n o mi nal le vel . 
9.  S afet y A n al ysis  
All safet y res ults will be s u m marize d se paratel y wit hi n t he  d o u ble -bli n d  treat me nt peri o d a n d t he o verall 
peri o d ( c o m bi ne d d o u b le-bli n d a n d O L E  peri o d s), usi n g  t he Safet y a nal ysis set b y act ual treat me nt gr o u p 
a n d o verall. 
 
T he o bser vati o n peri o ds i ncl u de:  
•  
T he pre -tre at me nt peri o d is defi ne d as t he ti me fr o m t he si g ne d i nf or me d c o nse nt date u p t o first 
a d mi nistrati o n of t he I M P.  
•  
T he r a n d o mize d o n -tre at me nt peri o d is defi ne d as t he ti me fr o m t he first a d mi nistrati o n of t he 
I M P ( o n Da y 1) t o t he last a d mi nistrati o n of t he I M P pri or t o Wee k 1 2 + 1 4 da ys if t he patie nt d oes 


Sa n ofi Gr o u p  
 
Fi nal Statistical A nal ysis Pla n, Versi o n 2. 0  
 
D u pil u ma b - L P S 1 5 4 9 7  
 
Date Iss ue d: 3 0J U L 2 0 2 1  
 
  
 
  3 1  
n ot e nter t he O L E peri o d, or u ntil pri or t o t he l oa di n g d ose at Wee k 1 2 if t he patie nt e nters t he O L E 
peri o d.  
•  
T he o pe n -l a bel e xte nsi o n o n-tre at me nt peri o d is defi ne d as t he ti me fr o m t he l oa di n g d ose at 
Wee k 1 2 t o t he last a d mi nistrati o n of t he I M P + 1 4 da ys.  
•  
T he tre at me nt-e mer ge nt a d verse e ve nt ( T E A E)  peri o d is defi ne d as t he ti me fr o m t he first 
a d mi nistrati o n of t he I M P ( o n Da y 1) t o t he last a d mi nistrati o n of t he I M P + 1 4 da ys  (b ot h 
ra n d o mize d o n-treat me nt an d o pe n -la bel e xte nsi o n o n-treat me nt peri o ds). 
9. 1.  A d verse E ve nts  
T he a d verse e ve nt o bser vati o n peri o ds i ncl u de:  
•  
Pre -tre at me nt a d verse e ve nts are a d verse e ve nts t hat de vel o pe d or w orse ne d or beca me seri o us 
fr o m t he si g ne d i nf or me d c o nse nt date u p t o t he first a d mi nistrati o n of t he I M P. 
•  
Tre at me nt -e mer ge nt a d verse e ve nts  are a d verse e ve nts t hat de vel o pe d or w orse ne d or beca me 
seri o us d uri n g t he T E A E peri o d. 
•  
P ost -tre at me nt a d verse e ve nts are a d verse e ve nts t hat de vel o pe d or w orse ne d or beca me seri o us 
after T E A E pe ri o d. 
 
T he pri mar y f oc us of a d verse e ve nt re p orti n g will be o n treat me nt -e mer ge nt a d verse e ve nts.  Pre -treat me nt 
a n d p ost -treat me nt a d verse e ve nts will be s u m marize d se paratel y. 
 
All a d verse eve nts will be c o de d t o a L L T, P T, H L T, H L G T, a n d ass ociate d pri mar y S O C usi n g t he versi o n 
of Me dical Dicti o nar y f or Re g ulat or y Acti vities ( Me d D R A) c urre ntl y i n effect at Sa n ofi at t he ti me of eac h 
data base l oc k.  
 
A d verse e ve nts will be rec or de d fr o m t he ti me of si g ne d i nf or me d c o nse nt u ntil t he e n d of t h e st u d y or t he 
res ol uti o n/sta bilizati o n of all S A E a n d A E SI. 
 
If a n a d verse e ve nt date/ti me of o nset ( occ urre nce, w orse ni n g, or bec o mi n g seri o us) is i nc o m plete, a n 
i m p utati o n al g orit h m will be use d t o classif y t he a d verse e ve nt as pre-treat me nt, treat me nt-e mer ge nt, or 
p ost -treat me nt. T he al g orit h m f or i m p uti n g date/ti me of o nset will be c o nser vati ve a n d will classif y a n 
a d verse e ve nt as treat me nt -e mer ge nt u nless t here is defi niti ve i nf or mati o n t o deter mi ne it is pre -treat me nt 
or p ost -treat me nt. Details o n classificati o n of a d verse e ve nts wit h missi n g or partial o nset dates are pr o vi de d 
i n Secti o n 1 5. 4. 4 . 
 
A d verse e ve nt will be s u m marize d b y pri mar y S O C, H L G T, H L T, a n d P T, s orte d i n al p ha betical or der f or 
eac h treat me nt gr o u p usi n g n u m ber  a n d perce nta ge of patie nts e x perie nci n g a n a d verse e ve n t. M ulti ple 
occ urre nces of t he sa me e ve nt i n t he sa me patie nt will be c o u nte d o nl y o nce i n t he ta bles wit hi n a treat me nt 
p hase. T he de n o mi nat or f or c o m p utati o n of perce nta ges is t he safet y a nal ysis set wit hi n eac h treat me nt 
gr o u p.  
 
S orti n g wit hi n ta bles e n s ures t he sa me prese ntati o n f or t he set of all a d verse e ve nts wit hi n t he o bser vati o n 
peri o d ( pre -treat me nt, treat me nt-e mer ge nt, a n d p ost -treat me nt). F or t hat p ur p ose, t he ta ble of all treat me nt-
e mer ge nt a d verse e ve nts prese nte d b y pri mar y S O C a n d P T (s orte d b y t he i nter nati o nall y a gree d S O C or der 
a n d decreasi n g fre q ue nc y of P Ts wit hi n S O Cs i n t he d u pil u ma b  gr o u p) will defi ne t he prese ntati o n or der 
f or all ot her s u m maries u nless ot her wise s pecifie d.  I n case of e q ual fre q ue nc y re gar di n g P Ts, al p ha betical 
or d er will be use d. 
 
O n t o p of t he a nal ysis pla n ne d bel o w, all T E A Es, all treat me nt -e mer ge nt S A Es, T E A Es lea di n g t o 
per ma ne nt treat me nt disc o nti n uati o n a n d T E A Es lea di n g t o deat hs will be s u m marize d b y treat me nt gr o u p 
a n d b y trial i m pact ( disr u pti o n) d ue t o C O VI D-1 9.  


Sa n ofi Gr o u p  
 
Fi nal Statistical A nal ysis Pla n, Versi o n 2. 0  
 
D u pil u ma b - L P S 1 5 4 9 7  
 
Date Iss ue d: 3 0J U L 2 0 2 1  
 
  
 
  3 2  
 
O ver vie w s u m mar ies of t he n u m ber a n d perce nta ges of patie nts wit hi n t he f oll o wi n g cate g ories will be 
pr o vi de d b y treat me nt gr o u p a n d o verall,  f or pre-treat me nt A Es, T E A Es d uri n g d o u ble -bli n d treat me nt 
peri o d , T E A Es d uri n g t he  st u d y, a n d p ost-treat me nt A Es. 
•  
A n y T E A E  
•  
A n y st u d y dr u g relate d  T E A E  
•  
A n y Se vere T E A E  
•  
A n y Seri o us T E A E  
•  
A n y T E A E lea di n g t o per ma ne nt treat me nt disc o nti n uati o n  
•  
A n y T E A E of s pecial i nterest  
•  
A n y Seri o us T E A E of s pecial i nterest  
•  
A n y T E A E lea di n g t o deat h  
 
T he o ver vie w s u m maries f or T E A Es d uri n g t he d o u ble -bli n d treat me nt peri o d a n d d uri n g t he o verall peri o d 
will be pr o vi de d o n  t he safet y a nal ysis set a n d t he a nal ysis set wit h trial i m pact ( disr u pti o n) d ue t o C O VI D-
1 9.  
 
I n di vi d ual listi n gs ( A Es, S A Es, A Es lea di n g t o per ma ne nt treat me nt disc o nti n uati o n, A Es lea di n g t o deat h, 
A E SI  a n d all A Es i n treate d patie nts b ut n ot c o nsi dere d as ra n d o mize d ) will be pr o vi de d t o s u p p ort t he 
s u m mar y ta bles base d o n t he safet y a nal ysis set. 
9. 1. 1.  I nci de nce of A d verse E ve nts  
T he f oll o wi n g T E A E s u m maries will be ge nerate d f or t he safet y a nal ysis set, f or eac h treat me nt gr o u p 
a n d o verall. 
•  
All T E A Es prese nte d b y pri mar y S O C  a n d P T, s h o wi n g t he n u m ber  a n d perce nta ge of patie nts 
wit h at least 1 T E A E, s orte d b y i nter nati o nall y a gree d or der of pri mar y S O C  a n d b y decreasi n g 
i nci de nce o f P Ts wit hi n eac h S O C i n t he d u pil u ma b gr o u p. T his s orti n g will be a p plie d t o all 
ot her s u m maries, u nless ot her wise s pecifie d.  
•  
All T E A Es prese nte d b y pri mar y S O C, H L G T, H L T, a n d P T, s h o wi n g t he n u m ber a n d 
perce nta ge  of patie nts wit h at least 1 T E A E, s orte d b y i nter nati o nall y a gree d or der of pri mar y 
S O C. T he ot her le vels ( H L G T, H L T, P T) will be prese nte d i n al p ha betical or der  
•  
All p re-treat me nt A E prese nte d b y pri mar y S O C a n d P T, s h o wi n g n u m ber a n d perce nta ge  of 
patie nts wit h at least 1 T E A E, s orte d b y i nter nati o nall y a gree d or der of pri mar y S O C a n d b y 
decreasi n g i nci de nce of P Ts wit hi n eac h S O C i n t he d u pil u ma b  gr o u p.  
•  
All treat me nt -e mer ge nt C O VI D -1 9 relate d a d verse e ve nt s prese nte d b y pri mar y S O C a n d P T, 
s h o wi n g n u m ber a n d perce nta ge of patie nts wit h at least 1 treat me nt -e mer ge nt C O VI D -1 9 relate d 
A E, s orte d b y i nter nati o nall y a gree d or der of pri mar y S O C a n d b y decreasi n g i nci de nce of  P Ts 
wit hi n eac h S O C i n t he d u pil u ma b  gr o u p.  
•  
All p ost -treat me nt A E prese nte d b y pri mar y S O C a n d P T, s h o wi n g n u m ber a n d perce nta ge  of 
patie nts wit h at least 1 T E A E, s orte d b y i nter nati o nall y a gree d or der of pri mar y S O C a n d b y 
decreasi n g i nci de nce of P Ts wit hi n eac h S O C i n t he d u pil u ma b  gr o u p.  
•  
C o m m o n T E A Es ( P Ts wit h a n i nci de nce ≥ 5 % i n a n y treat me nt gr o u p) b y pri mar y S O C, H L G T, 
H L T, a n d P T, s orte d b y i nter nati o nall y a gree d or der of S O Cs. T he ot her le vels ( H L G T, H L T, P T) 
will be prese nte d i n al p ha betic or der.  
 
Searc h criteria f or C O VI D -1 9 relate d A E will be pr o vi de d b y S A N O FI.  


Sa n ofi Gr o u p  
 
Fi nal Statistical A nal ysis Pla n, Versi o n 2. 0  
 
D u pil u ma b - L P S 1 5 4 9 7  
 
Date Iss ue d: 3 0J U L 2 0 2 1  
 
  
 
  3 3  
9. 1. 2.  Rel ati o ns hi p of A d verse E ve nts t o St u d y Dr u g  
T he f oll o wi n g T E A E s u m maries will be ge nerate d f or t he safet y a nal ysis set , f or eac h treat me nt gr o u p 
a n d o verall. 
•  
All T E A Es b y  relati o ns hi p, prese nte d b y pri mar y S O C, H L G T, H L T a n d P T, s h o wi n g t he n u m ber 
a n d perce nta ge  of patie nts wit h at least 1 T E A E, s orte d b y i nter nati o nall y a gree d or der of pri mar y 
S O C. T he ot her le vels ( H L G T, H L T a n d P T) will be prese nte d i n al p ha betical or der  
9. 1. 3.  Se verit y of A d verse E ve nt  
T he f oll o wi n g T E A E s u m maries will be ge nerate d f or t he safet y a nal ysis set , f or eac h treat me nt gr o u p 
a n d o verall. 
•  
All T E A Es b y ma xi mal se verit y, prese nte d b y pri mar y S O C a n d P T, s h o wi n g t he n u m ber a n d 
perce nta ge  of patie nts wit h at least 1 T E A E b y se verit y (i.e., mil d, m o derate, se vere) . 
9. 1. 4.  Seri o us A d verse E ve nts  
T he f oll o wi n g T E A E s u m maries will be ge nerate d f or t he safet y a nal ysis set , f or eac h treat me nt gr o u p 
a n d o verall. 
•  
All seri o us T E A Es prese nte d b y pri mar y S O C, H L G T, H L T a n d P T, s h o wi n g t he n u m ber a n d 
perce nta ge  of patie nts wit h at least 1 seri o us T E A E, s orte d b y i nter nati o nall y a gree d or der of 
pri mar y S O C. T he ot her le vels ( H L G T, H L T a n d P T) will be prese nte d i n al p ha b etical or der .  
•  
All seri o us T E A Es b y  relati o ns hi p, prese nte d b y pri mar y S O C, H L G T, H L T a n d P T, s h o wi n g t he 
n u m ber a n d perce nta ge  of patie nts wit h at least 1 T E A E, s orte d b y i nter nati o nall y a gree d or der of 
pri mar y S O C. T he ot her le vels ( H L G T, H L T a n d P T) wil l be prese nte d i n al p ha betical or der 
9. 1. 5.  A d verse E ve nts Le a di n g t o Per m a ne nt Tre at m e nt Disc o nti n u ati o n  
T he f oll o wi n g T E A E s u m maries will be ge nerate d f or t he safet y a nal ysis set , f or eac h treat me nt gr o u p 
a n d o verall. 
•  
All T E A Es lea di n g t o per ma ne nt treat me nt disc o nti n uati o n, prese nte d b y pri mar y S O C, H L G T, 
H L T a n d P T, s h o wi n g t he n u m ber a n d perce nta ge  of patie nts wit h at least 1 seri o us T E A E, s orte d 
b y i nter nati o nall y a gree d or der of pri mar y S O C. T he ot her le vels ( H L G T,  H L T a n d P T) will be 
prese nte d i n al p ha betical or der  
9. 1. 6.  A d verse E ve nts Le a di n g t o St u d y Disc o nti n u ati o n  
N ot a p plica ble  
9. 1. 7.  A d verse E ve nt s of S peci al I nterest ( A E SI)  
As defi ne d i n A p pe n di x 1 5. 6 , A d verse E ve nts of S pecial I nterest ( A E SI) i ncl u de: 
•  
A na p h yla xis  
•  
S yste mic or se vere h y perse nsiti vit y reacti o ns  
•  
Mali g na nc y (e xce 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 bas al 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  
•  
Pre g na nc y occ urri n g i n a fe male patie nt or i n a fe male part ner of male patie nt a d mi nistere d 
I M P/ NI M P 
•  
S y m pt o m atic o ver d ose of I M P/ NI M P  
 


Sa n ofi Gr o u p  
 
Fi nal Statistical A nal ysis Pla n, Versi o n 2. 0  
 
D u pil u ma b - L P S 1 5 4 9 7  
 
Date Iss ue d: 3 0J U L 2 0 2 1  
 
  
 
  3 4  
T he f oll o wi n g T E A E s u m maries will be ge nerate d f or t he safet y a nal ysis set , f or eac h treat me nt gr o u p 
a n d o verall. 
•  
All T E A Es of S pecial I nterest, prese nte d b y pri mar y S O C, H L G T, H L T a n d P T, s h o wi n g t he 
n u m ber a n d perce nta ge  of pat ie nts wit h at least 1 seri o us T E A E, s orte d b y i nter nati o nall y a gree d 
or der of pri mar y S O C. T he ot her le vels ( H L G T, H L T a n d P T) will be prese nte d i n al p ha betical 
or der  
•  
All seri o us T E A Es of S pecial I nterest, prese nte d b y pri mar y S O C, H L G T, H L T a n d P T, s h o wi n g 
t he n u m ber a n d perce nta ge  of patie nts wit h at least 1 seri o us T E A E, s orte d b y i nter nati o nall y 
a gree d or der of pri mar y S O C. T he ot her le vels ( H L G T, H L T a n d P T) will be prese nte d i n 
al p ha betical or der  
9. 1. 8.  A d verse E ve nts Le a di n g t o De at h  
T he f oll o wi n g T E A E s u m m aries will be ge nerate d f or t he safet y a nal ysis set , f or eac h treat me nt gr o u p 
a n d o verall. 
•  
All T E A Es lea di n g t o deat h ( deat h as a n o utc o me o n t he e C R F f or m “ A d verse E ve nt” as re p orte d 
b y I n vesti gat or), prese nte d b y pri mar y S O C, H L G T, H L T a n d P T, s h o wi n g t h e n u m ber a n d 
perce nta ge  of patie nts wit h at least 1 seri o us T E A E, s orte d b y i nter nati o nall y a gree d or der of 
pri mar y S O C. T he ot her le vels ( H L G T, H L T a n d P T) will be prese nte d i n al p ha betical or der  
9. 1. 9.  De at h  
T he f oll o wi n g s u m maries of deat hs will be ge nerate d f or t he safet y a nal ysis set , f or eac h treat me nt gr o u p 
a n d o verall.  
•  
N u m ber a n d perce nta ge  of patie nts w h o die d d uri n g t he o verall  peri o d  a n d ca use of deat h b y 
st u d y peri o d. 
•  
N u m ber a n d perce nta ge  of n o n -ra n d o mize d patie nts or ra n d o mize d b ut n ot treate d patie nts w h o 
die d.  
 
A listi n g of all patie nts w h o die d d uri n g t he st u d y will be pr o vi de d.  
9. 2.  Cli nic al L a b or at or y E v al u ati o ns  
Uri ne h u ma n c h ori o nic g o na d otr o pi n pre g na nc y test (as nee de d f or w o me n of c hil d beari n g p ote ntial) will 
be perf or me d b y t he l ocal la b orat or y, at desi g nate d visits. N o ot her la b orat or y tests are pla n ne d i n pr ot oc ol.  
A d diti o nal tests ma y be perf or me d at a n y ti me d uri n g t he st u d y as deter mi ne d necessar y b y t he I n vesti gat or 
or re q uire d b y l ocal re g ulati o ns; a n y cli nicall y si g nifica nt a b n or mal la b val ues will be i ncl u de d i n t he 
a d verse e ve nt a nal yses.  
N o la b orat or y varia bles will be s u m marize d f or t his st u d y.  
9. 3.  Vit al Si g n Me as ure me nts  
Vital si g ns i ncl u di n g hei g ht, wei g ht, heart rate ( H R), sitti n g s yst olic ( S B P) a n d diast olic bl o o d press ure 
( D B P), te m perat ure a n d res pirati o n rate, will be c ollecte d at scree ni n g visit a n d all s u bse q ue nt visits bef ore 
i njecti o n a n d at 3 0 mi n utes (± 1 0 mi n utes) p ost -i njecti o n. 
  
T he vital si g n res ults will be s u m marize d f or t he safet y a nal ysis set  b y treat me nt gr o u p usi n g descri pti ve 
statistics a n d f or eac h visit or st u d y assess me nt ( baseli ne, eac h -p ost -baseli ne ti me p oi nt, last o n -treat me nt 
val ue).  
 


Sa n ofi Gr o u p  
 
Fi nal Statistical A nal ysis Pla n, Versi o n 2. 0  
 
D u pil u ma b - L P S 1 5 4 9 7  
 
Date Iss ue d: 3 0J U L 2 0 2 1  
 
  
 
  3 5  
T he P ote ntiall y Cli nicall y Si g nifica nt A b n or malities ( P C S A) at a n y ti me d uri n g t he T E A E peri o d will be 
s u m marize d f or t he safet y a nal ysis set  b y treat me nt gr o u p a n d o verall, usi n g n u m ber a n d perce nta ge . T he 
P C S As are pr o vi de d i n  Secti o n  1 5. 7 . 
 
All meas ure me nts c ollecte d d uri n g t he T E A E peri o d, i ncl u di n g val ues fr o m u nsc he d ule d visits, will be 
c o nsi dere d f or t he P C S A s u m maries. T he s u m maries will i ncl u de patie nts i n t he safet y a nal ysis set  w h o 
ha ve at least 1 assess me nt perf or me d d uri n g t he T E A E peri o d. W he n a P C S A defi niti o n i n v ol ves a c ha n ge 
fr o m baseli ne val ue, patie nts m ust als o ha ve a baseli ne val ue t o be i ncl u de d i n t he s u m maries. 
 
A listi n g of patie nts wit h at least 1 p ost -baseli ne P C S A will be pr o vi de d a n d will dis pla y t he patie nt’s pr ofile 
o ver ti me of all vital si g n para meters.  
 
I n di vi d ual data listi n gs will i ncl u de t he f oll o wi n g fla gs: 
•  
Baseli ne val ues will be fla g ge d “ B”,  
•  
Para meter val ues reac hi n g a P C S A li mit will be fla g ge d ( +, or - de pe n di n g of t he directi o n).  
9. 4.  P h ysic al E x a m i n ati o n 
T here will be a p h ysical e xa mi nati o n at baseli ne visit t o e xa 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 n t’s me dical hist or y. T he y will i ncl u de a n assess me nt of hea d, heart, l u n g, 
a b d o me n, m usc ul os keletal, s ki n a n d ne ur ol o gical. Res ults ( n or mal, a b n or mal or n ot d o ne) fr o m t he 
assess me nt will be re p orte d. All de viati o ns fr o m n or mal will be rec or de d, i ncl u di n g t h ose attri b uta ble t o 
t he patie nt’s disease. 
A n y ne w or w orse ni n g fi n di n g will be re p orte d as a ne w a d verse e ve nt.  
 
T he n u m ber a n d perce nta ge  of patie nts wit h a b n or mal p h ysical e xa ms at baseli ne will be s u m marize d f or 
t he safet y a nal ysis set  b y treat me nt gr o u p a n d o verall. 
 
9. 5.  Electr oc a r di o gr a m  
N ot a p plica ble.  
9. 6.  Ot her S afet y D at a  
N ot a p plica ble.  
1 0.  P h ar m ac o ki netics  
P har mac o ki netic para meters are n ot e val uate d i n t his st u d y.  
1 1.  P h ar m ac o d y n a mics  
P har mac o d y na mic para meters are n ot e val uate d i n t his st u d y.  
1 2.  I nteri m A n al ysis 
After all patie nts ha ve 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 efficac y data will 
be a nal yze 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 de d. 
 


Sa n ofi Gr o u p  
 
Fi nal Statistical A nal ysis Pla n, Versi o n 2. 0  
 
D u pil u ma b - L P S 1 5 4 9 7  
 
Date Iss ue d: 3 0J U L 2 0 2 1  
 
  
 
  3 6  
O nce all patie nts c o m plete t he last visit p ost ra n d o mizati o n  (after O L E peri o d), 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 yze d.  
1 3.  C h a n ges i n t he Pl a n ne d A n al ysis  
T he c ha n ges fr o m t he pr ot oc ol ha ve are liste d bel o w:  
•  
P S G a nal ysis set  t o be use d f or t he a nal ysis of t he e n d p oi nt base d o n P S G meas ures 
•  
O L E a nal ysis set  t o be use d f or t he e x pl orat or y e n d p oi nts liste d bel o w: 
o  C ha n ge or perce nt c ha n ge (as use d i n a nal yses of wee k 1 2 data) fr o m baseli ne t o wee k 2 4 
f or pri mar y a n d sec o n dar y e n d p oi nts 
o  C ha n ge or perce nt c ha n ge (as use d i n a nal yses of wee k 1 2 data) fr o m wee k 1 2 t o wee k 2 4 
f or pri mar y a n d sec o n dar y e n d p oi nts  
•  
E A SI 9 0 a d de d t o t he a nal yses of E A SI sc ore. 
•  
I nterc urre nt e ve nts ha ve bee n a d de d f or t he pri mar y a n d ke y sec o n dar y e n d p oi nts i n or der t o ta ke 
i nt o c o nsi derati o n t he patie nts w h o disc o nti n ue d d ue t o C o vi d-1 9 pa n de mic, n ot  d ue t o c o vi d -1 9 
pa n de mic a n d  t h ose patie nts ta ki n g selecte d pr o hi bite d me dicati o ns a n d/ or resc ue me dicati o ns. 
•  
F or t he res p o n der a nal ysis  o n E A SI, C M H met h o d ha ve bee n c ha n ge d t o M M R M m o del as t he 
a nal ysis  first, t he n if t he M M R M m o del fails to ac hie ve c o n ver ge nce, t he l o gistic re gressi o n at 
eac h visit will be use d i n or der t o a d d baseli ne val ue as o ne of t he c o variates. If t he l o gistic 
re gressi o n m o del fails t o ac hie ve c o n ver ge nce, C M H met h o d will be use d. C ha n ge fr o m baseli ne 
of E A SI t otal sc ore will be m o delle d wit h a M M R M m o del.  
•  
S u b gr o u p a nal ysis base d o n Disease D urati o n has bee n re m o ve d as disease o nset is n ot c ollecte d  
•  
Baseli ne defi niti o n f or dail y assess me nts has bee n u p date d t o i ncl u de o ne patie nt w h o c o m plete d 
baseli ne assess me nt fr o m -1 3 t o -7 i nstea d of -6 t o Da y 0.  
•  
F or t he res p o n der a nal ysis o n E A SI, t he a nal ysis m o del has bee n c ha n ge d fr o m G E N M O D t o 
G LI M MI X.  
•  
A d de d s o me details f or retest a p pr oac h of Ps yc h o m ot or Vi gila nce Test.  
•  
Slee p diar y ill o gical data ha n dli n g r ule s has bee n a d de d as a n S A P a d de n d u m. 
1 4.  Refere nces  
Gittler J K, S he mer A, S u árez -Fari ñas M, F ue ntes -D uc ula n J, G ule wi cz 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 n s c haracterizes 
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 Dec; 1 3 0( 6): 1 3 4 4 -5 4.  
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, K ot h L L, Arr o n J R, Fa h y 
J V. T-hel per t y p e 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 as pt h ma. A m J Res pir 
Crit Care Me d 2 0 0 9 Se p 1; 1 8 0( 5): 3 8 8 -9 5  
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.  
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 n ce: fi n di n gs of t he Gl o bal B ur de n of Dis ease St u d y 2 0 1 0. La ncet 2 0 1 3 Mar 
2 3; 3 8 1( 9 8 7 1): 9 9 7 -1 0 2 0.  
Z u ber bier T, Orl o w SJ, Paller A S, Taie b A, Alle n R, Her na nz -Her m osa J M, et al. Patie nt 
pers pecti ves o n t he m a na ge me nt of at o pic der matitis. J Aller g y Cli n I m m u n ol 2 0 0 6 
J ul; 1 1 8( 1): 2 2 6-3 2.  


Sa n ofi Gr o u p  
 
Fi nal Statistical A nal ysis Pla n, Versi o n 2. 0  
 
D u pil u ma b - L P S 1 5 4 9 7  
 
Date Iss ue d: 3 0J U L 2 0 2 1  
 
  
 
  3 7  
Di n ges D F 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 n ce d ecre me nts d uri n g a wee k of slee p restricte d t o 4 -5 h o urs per ni g ht. Slee p 1 9 9 7, 2 0 
( 4): 2 6 7 -7 7  
Je o n C, Ya n D, Na k a 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 d el b) 
2 0 1 7; Se p; 7( 3): 3 4 9 -3 6 4  
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  
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  
Bas ner M, Di n ges, D F. Ma xi mizi 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 1-5 9 1.  
Wil ke n J A, Ka n e R, S ulli va n C L, Walli n M, Usis ki n J B, Q ui g M E, et al. T he utilit y  of 
c o m p uterize d n e 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 patie 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.  
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.  
Ha nifi n J M, T h urst o n M, O m ot o M, et al. T he ecze ma area a n d s e verit y i n d e x ( E A SI): 
assess me nt of relia bilit y  i n at o pic der matitis. E x p Der mat ol 2 0 0 1; 1 0( 1): 1 1-1 8.  
C har ma n C R, Ve n n AJ, a n d Willia ms, H C. T he patie nt -orie nte d ecze ma m eas ure. Arc h 
Der mat ol 2 0 0 4; 1 4 0: 1 5 1 3 -1 5 1 9.  
Ba d ia X, Mascar o J M, L oza n o R, et al. Meas uri n g healt h-rel ate d q ualit 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 se 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: 6 9 8-7 0 2.  
Zi g m o n d A S a n d S nait h R P. T he h os pital a n xiet y a n d de pressi o n scale. Acta Ps yc hiatr Sca n d 
1 9 8 3; 6 7: 3 6 1 -3 7 0.  
Herr ma n n C. I nt er nati o n al e x perie n ces wit h t he h os pital a n xiet y a n d de 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.  
Sa n ofi Data Vali dit y Verificati o n Pla n - L P S 1 5 4 9 7 _ D u pista d. Vista Life  Scie nces, I nc. 2 0 1 9  
Mic hael J. T h or p y , et al. A ra n d o mize d st u d y of s olria mfet ol f or e x cessi ve slee pi ness i n 
narc ole ps y.  A n n Ne ur ol . 2 0 1 9 Mar; 8 5( 3): 3 5 9– 3 7 0.  
Y u, La n & B u ysse, Da ni el & Ger mai n, A n ne & M o ul, D o u glas & St o ver, A n gela & D o d ds, 
Nat ha n & J o h nst o n, Kell y & Pil k o nis, Pa ul. ( 2 0 1 1). De vel o p me nt of S h ort F or ms fr o m t he 


Sa n ofi Gr o u p  
 
Fi nal Statistical A nal ysis Pla n, Versi o n 2. 0  
 
D u pil u ma b - L P S 1 5 4 9 7  
 
Date Iss ue d: 3 0J U L 2 0 2 1  
 
  
 
  3 8  
P R O MI S Slee p Dist ur ba nce a n d Slee p -Relate d I m pair me nt Ite m Ba n ks. Be ha vi oral slee p 
me dici ne. 1 0. 6 -2 4. 1 0. 1 0 8 0/ 1 5 4 0 2 0 0 2. 2 0 1 2. 6 3 6 2 6 6.  
F o gel ber g, D o nal d & Vitiell o, Mic hael & H off ma n, Jea n ne & Ba mer, Al yssa & A mt ma n n, 
Da g mar. ( 2 0 1 4). C o m paris o n of Self -Re p ort Slee p Meas ures f o r I n di vi d uals Wit h M ulti ple 
Scler osis a n d S pi nal C or d I nj ur y. Arc hi v es of p h ysical me dici ne a n d re ha bilitati o n. 9 6. 
1 0. 1 0 1 6/j.a p mr. 2 0 1 4. 1 0. 0 0 1.  
Bas ner, M. a n d D. Di n g es, Ma xi mizi 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  Ma y 1 . 3 4( 5): p. 5 8 1-5 9 1.  
Li m, J. L. a n d D. F. Di n ges, Slee p de pri vati o n a n d vi gila nt atte nti o n, i n M olec ular a n d 
Bi o p h ysical Mec ha nis ms of Ar o usal, Alert ness, a n d Atte nti o n. 2 0 0 8. p. 3 0 5 -3 2 2.  
D orria n, J., N. L. R o gers, a n d D. F. Di n g es, Ps yc h o m ot or vi gila nce perf or ma nce: Ne ur oc o g niti ve 
assa y se nsiti ve t o slee p l oss, i n Slee p de pri vati o n Cli nical iss ues, p har mac ol o g y, a n d slee p l oss 
effects, C. A. K us hi da, E dit or. 2 0 0 5, Marcel D e k k er: Ne w Y or k. p. 3 9 -7 0.  
D ora n, S. M., H. P. A. v. D o n ge n, a n d D. F. Di n ges, S ustai n e d atte nti o n perf or ma nce d uri n g slee p 
de pri vati o n: E vi de nce of state i nsta bilit y. Arc hi ves Italie n nes de Bi ol o gie, 2 0 0 1. 1 3 9: p. 2 5 3 -2 6 7.  
Bal ki n, T.J., et al., C o m parati ve utilit y of i nstr u me nts f or m o nit ori n g slee pi ness -relat e d 
perf or ma n ce d ecre me nts i n t he o perati o nal e n vir o n me nt. J o ur nal of Slee p Researc h, 2 0 0 4. 1 3: p. 
2 1 9 -2 2 7.  
 
 
1 5.  A p pe n dices  
 


Sa n ofi Gr o u p  
 
Fi nal Statistical A nal ysis Pla n, Versi o n 2. 0  
D u pil u ma b - L P S 1 5 4 9 7  
 
Date Iss ue d: 3 0J U L 2 0 2 1  
 
  
 
 
 3 9  
1 5. 1.  
S u m m ar y of St atistic al A n al yses  
 
E n d p oi nt  
A n alysis  
Set  
Pri m ary  
a n alysis  
S u p p ortive  
a n alysis  
S u b gr o u p  
a n alysis  
 
Esti m a n d s 
Pri m ary e n d p oi nt  
 
 
 
 
 
Slee p Q u ality N R S: t he perce nt c h a n ge 
fr o m b aseli ne t o week 1 2 
(d u pil u m a b , pl ace b o) 
m I T T 
M M R M, wit h o ut i m p ut ati o n 
of missi n g v al ues  
Se nsitivity  a n alysis:  
Set missi n g t o t h ose weeks wit h 3 
or less av ail a ble slee p N R S d at a. 
N o i m p ut ati o n will be m a de f or t he 
missi n g d at a. Usi n g t he s a me 
M M R M m o del  
Yes  
Yes  
Sec o n d ary e n d p oi nts  
 
 
 
 
 
C o nti n u o us v ari a bles  
m I T T 
S a me a p pr o ac h  as pri m ary 
e n d p oi nts 
N o  
N o  
Yes (f or 
key 
sec o n d ary 
e n d p oi nts 
o nly)  
Bi n ary v ari a bles  
m I T T 
C oc hr a n -M a ntel -H ae nszel  
test, defi ne missi n g as n o n-
res p o n der 
N o  
N o  
N o  
E x pl or at ory e n d p oi nts  
 
 
 
 
 
C o nti n u o us v ari a ble  
m I T T 
S a me a p pr o ac h  as pri m ary 
e n d p oi nts 
N o  
N o  
N o  
D ays m isse d fr o m sc h o ol or w ork t o 
week 1 2  
m I T T 
Ne g ative Bi n o mi al M o del  
N o  
N o  
N o  
P V T & A N A M  
m I T T 
S a me a p pr o ac h as pri m ary 
e n d p oi nt 
N o  
N o  
N o  


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Fi nal Statistical A nal ysis Pla n, Versi o n 2. 0  
D u pil u ma b - L P S 1 5 4 9 7  
 
Date Iss ue d: 3 0J U L 2 0 2 1  
 
  
 
 
 4 0  
E n d p oi nt  
A n alysis  
Set  
Pri m ary  
a n alysis  
S u p p ortive  
a n alysis  
S u b gr o u p  
a n alysis  
 
Esti m a n d s 
Bi n ary v ari a bles  
m I T T 
S a me a p pr o ac h  as 
sec o n d ary e n d p oi nts 
N o  
N o  
N o  
Slee p dist ur b a nces (e g, T S T, W A S O ) 
a n d p ar a meters ass oci ate d wit h A D 
(e g, E A SI, 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, se nsitivity t o t o uc h N R S) 
m I T T 
C orrel ati o n  
N o  
N o  
N o  
All effic acy a n d P atie nt -Re p ort 
O utc o me ( P R O) me as ures: fr o m week 
1 2 t o week 2 4 a n d fr o m b aseli ne t o 
week 2 4:  
will be a n alyze d se p ar ately f or t h ose 
ori gi n ally r a n d o mize d t o d u pil u m a b , 
a n d t h ose ori gi n ally r a n d o mize d t o 
pl ace b o ( a n d s witc he d t o d u pil u m a b  
d uri n g t he o pe n l a bel exte nsi o n)  
m I T T 
S u m m ary st ats o nly  
N o  
N o  
N o  
 


Sa n ofi Gr o u p  
 
Fi nal Statistical A nal ysis Pla n, Versi o n 2. 0  
D u pil u ma b - L P S 1 5 4 9 7  
 
Date Iss ue d: 3 0J U L 2 0 2 1  
 
  
 
 
 4 1  
1 5. 2.  
Sc he d ule of St u d y Pr oce d ures  
 
 


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Fi nal Statistical A nal ysis Pla n, Versi o n 2. 0  
D u pil u ma b - L P S 1 5 4 9 7  
 
Date Iss ue d: 3 0J U L 2 0 2 1  
 
  
 
 
 4 2  
 


Sa n ofi Gr o u p  
 
Fi nal Statistical A nal ysis Pla n, Versi o n 2. 0  
D u pil u ma b - L P S 1 5 4 9 7  
 
Date Iss ue d: 3 0J U L 2 0 2 1  
 
  
 
 
 4 3  
 


Sa n ofi Gr o u p  
 
Fi nal Statistical A nal ysis Pla n, Versi o n 2. 0  
D u pil u ma b - L P S 1 5 4 9 7  
 
Date Iss ue d: 3 0J U L 2 0 2 1  
 
  
 
 
 4 4  
 
 


Sa n ofi Gr o u p  
 
Fi nal Statistical A nal ysis Pla n, Versi o n 2. 0  
D u pil u ma b - L P S 1 5 4 9 7  
 
Date Iss ue d: 3 0J U L 2 0 2 1  
 
  
 
 
 4 5  
 
 
 


Sa n ofi Gr o u p  
 
Fi nal Statistical A nal ysis Pla n, Versi o n 2. 0  
D u pil u ma b - L P S 1 5 4 9 7  
 
Date Iss ue d: 3 0J U L 2 0 2 1  
 
  
 
 
 
4 6  
1 5. 3.  
Missi n g Effic ac y D at a  
1 5. 3. 1.  H a n dli n g of missi n g d at a a n d d at a w h ose i nter pret ati o ns h a ve c h a n ge d  
T he f oll o wi n g will be a p plie d t o all efficac y e n d p oi nts:  
•  
Patie nts will be e nc o ura ge d t o sta y i n t he st u d y if t he y disc o nti n ue t he I M P, e ve n d ue t o 
C o vi d -1 9 pa n de mic (Ic E v 1a n d Ic E v 2 ).  
o  If disc o nti n uati o n or i nterr u pti o n of st u d y treat me nt d ue t o C o vi d -1 9, off -treat me nt 
data will be set t o missi n g . T he assess me nts  after patie nts res u me treat me nt will be 
use d.  
o  If disc o nti n uati o n or i nterr u pti o n of st u d y treat me nt n ot d ue t o C o vi d -1 9,  all data 
c ollecte d f oll o wi n g sc he d ule after t he treat me nt disc o nti n uati o n will be use d i n t he 
a nal ysis . 
•  
Ta ki n g selecte d pr o hi bite d me dicati o ns t hat affect slee p ( Pr ot oc ol Secti o n 6. 5. 1), all slee p 
relate d assess me nts (slee p q ualit y N R S, S C O R A D slee p V A S a n d t otal sc ore, P R O MI S slee p 
i m pair me nt S F 8a t otal sc ore, E S S, a n d acti gra p h y data) o n t hat c orres p o n di n g ni g ht will be 
set t o missi n g . A D assess me nts will be i ncl u de d i n t he a nal yses. 
•  
Ta ki n g selecte d pr o hi bite d me dicati o ns t hat affect A D ( Pr ot oc ol Secti o n 6. 5. 1), all A D 
assess me nts will be set t o missi n g after t he me dicati o n usa ge.  
•  
Ta ki n g resc ue me dicati o ns f or A D (ie. t o c o ntr ol i nt olera ble A D s y m pt o ms) is all o we d. F or 
t he p ur p ose of efficac y a nal ysis, all A D assess me nts will be set t o missi n g after t he 
me dicati o n usa ge.  
•  
If a patie nt disc o nti n ue s fr o m treat me nt or fr o m t he st u d y, or is ta ki n g resc ue or selecte d 
pr o hi bite d m e dicati o ns,  t he patie nt will be c o u nte d as a n o n -res p o n der f or t he ti me p oi nts 
after disc o nti n uati o n or resc ue/ pr o hi bite d me dicati o n start f or all bi nar y e n d p oi nts. 
1 5. 3. 2.  H a n dli n g of missi n g d at a f or P atie nt -Re p orte d O utc o mes ( P R O S)  
Patie nt -Orie nte d Ecze ma Meas u re ( P O E M) 
•  
If o nl y o ne q uesti o n is left u na ns were d, t his is sc ore d  0 a n d t he sc ores are s u m me d a n d 
e x presse d as us ual o ut of a ma xi m u m of 2 8  
•  
If m ore t ha n o ne q uesti o n is left u na ns were d, t he q uesti o n naire is n ot sc ore d 
•  
If 2 or m ore res p o nse o pti o ns are selecte d f or a si n gle q uesti o n, t he res p o nse o pti o n wit h 
t he hi g hest sc ore will be rec or de d.  
P R O MI S Slee p Relate d I m pair me nt S F 8a T otal S c ore  
T he t otal sc ore  f or P R O MI S is t he s u m of 8 ite m sc ores.  
•  
F or a n y missi n g ite m sc ore at a s pecific ti me p oi nt, t he mea n of t he re mai ni n g n o n -missi n g 
ite m sc ores f or t hat patie nt at t his s pecific ti me p oi nt is use d t o i m p ute t he missi n g ite m 
sc ore(s). I n t hese cases, t he t otal sc ore is calc ulate d as t he s u m of t he  o bser ve d a n d t he 
i m p ute d ite m sc ores 
Der mat ol o g y Life Q u alit y i n de x ( D L QI)  


Sa n ofi Gr o u p  
 
Fi nal Statistical A nal ysis Pla n, Versi o n 2. 0  
D u pil u ma b - L P S 1 5 4 9 7  
 
Date Iss ue d: 3 0J U L 2 0 2 1  
 
  
 
 
 
4 7  
•  
If o nl y o ne q uesti o n is left u na ns were d, t his is sc ore d 0 a n d t he sc ores are s u m me d a n d 
e x presse d as us ual o ut of a ma xi m u m of 3 0  
•  
If 2 or m ore q uesti o ns are left u na ns were d, t he q uesti o n naire is n ot sc ore d  
•  
If 2 or m ore res p o nse o pti o ns are selecte d f or a si n gle q uesti o n, t he res p o nse o pti o n wit h 
t he hi g hest sc ore s h o ul d be rec or de d 
•  
Relate d t o q uesti o n 7:  
o  If q uesti o n 7 is a ns were d “yes ”, t his is sc ore d 3 
o  If q uesti o n 7 is a ns were d “n o ” b ut t he n eit her “a l ot” or “a little” is tic ke d, t his is 
t he n sc ore d 2 or 1 (res pecti vel y). 
o  If “ n ot rele va nt” is tic ke d, t his is sc ore d 0  
o  If q uesti o n 7 is a ns were d “ n o”, b ut t he sec o n d half is left i nc o m plete, t he sc ore will 
re mai n 0. 
J u ni per Ast h ma C o nt r ol Q uesti o n naire ( A C Q-5)  
•  
If o nl y o ne q uesti o n is left u na ns were d at a s pecific ti me p oi nt, 
o  If t he q uesti o n naire fr o m t he pre vi o us ti me p oi nt is c o m plete, it is i nter p olate d 
( pr o-rate d) usi n g t he c o m plete d q uesti o ns fr o m t he pre vi o us ti me p oi nt 
o  If t he q uesti o n naire fr o m t he pre vi o us ti me p oi nt is n ot c o m plete,  t he missi n g val ue 
will be i m p ute d as t he a vera ge of t he c o m plete d q uesti o ns wit hi n t he c urre nt visit.  
•  
If 2 or m ore q uesti o ns are left u na ns were d, t he gl o bal sc ore is i n vali d a n d is c o nsi dere d as 
missi n g  
H os pital A n xiet y a n d De pressi o n Scale  ( H A D S) 
•  
If o nl y o ne q uesti o n is left u na ns were d i n t he A n xiet y s u bscale (s u m of all t he A q uesti o ns) 
or De pressi o n s u bscale (s u m of all D q uesti o ns) at a s pecific ti me p oi nt, a sc ore ca n be 
c o m p ute d usi n g t he pers o n s pecific mea n of t he c orres p o n di n g s u bscale at t his s pe cific 
ti me p oi nt 
•  
If 2 or m ore q uesti o ns are left u na ns were d i n t he A n xiet y s u bscale or De pressi o n s u bscale, 
t he sc ore is i n vali d a n d is c o nsi dere d as missi n g i n t he c orres p o n di n g s u bscale. 
Ot her Patie nt -Re p orte d  O utc o mes  
F or all ot her q u esti o n nair es, if o n e or more q uesti o ns are left u n a ns were d, t he 
q uesti o n naire is n ot sc ore d.  
1 5. 3. 3.  H a n dli n g of missi n g d at a f or Cli nici a n Re p orte d O utc o mes  
( C LI N R O S) 
N o  i m p utati o n will be ma de f or missi n g or i nc o m plete data.  
1 5. 4.  
Missi n g S afet y D at a  
F or cate g orical varia bles, patie nts wit h missi n g data are n ot i ncl u de d i n calc ulati o ns of perce nta ges 
u nless ot her wise s pecifie d. W he n rele va nt, t he n u m ber of patie nts wit h missi n g data is prese nte d.  


Sa n ofi Gr o u p  
 
Fi nal Statistical A nal ysis Pla n, Versi o n 2. 0  
D u pil u ma b - L P S 1 5 4 9 7  
 
Date Iss ue d: 3 0J U L 2 0 2 1  
 
  
 
 
 
4 8  
1 5. 4. 1.  H a n dli n g of missi n g a ge  
If a ge is missi n g b ut year of birt h is c ollecte d, t he n a ge will be deri ve d as date of i nf or me d c o nse nt 
si g ne d mi n us year of birt h a n d J u ne 3 0 t h, kee pi n g t he i nte ger part of t he res ult.  
1 5. 4. 2.  H a n dli n g of c o m p ut ati o n of tre at me nt d ur ati o n if i n vesti g ati o n al 
me dici n al pr o d uct e n d of tre at me nt d ate is missi n g  
F or t he calc u lati o n of t he treat me nt d urati o n, t he date of t he last d ose of I M P is e q ual t o t he date of 
last a d mi nistrati o n re p orte d o n t he e-C R F “ Treat me nt stat us” pa ge.  If t his date is missi n g, t he last 
a vaila ble a d mi nistrati o n date i n t he “ E x p os ure” f or m will be us e d.  
 
T he last d ose i nta ke s h o ul d be clearl y i de ntifie d i n t he e C R F a n d s h o ul d n ot be a p pr o xi mate d b y t he 
last ret ur ne d pac ka ge date 
1 5. 4. 3.  H a n dli n g of me dic ati o n missi n g/ p arti al d ates  
N o i m p utati o n of me dicati o n start/e n d dates or ti mes will be perf or me d. If a m e dicati o n date or ti me 
is missi n g or partiall y missi n g a n d it ca n n ot be deter mi ne d w het her it was ta ke n pri or or 
c o nc o mita ntl y, it will be c o nsi dere d a pri or, c o nc o mita nt a n d p ost -treat me nt me dicati o n. 
1 5. 4. 4.  H a n dli n g of a d verse e v e nts wit h missi n g or p arti al d at e/ti me of o nset  
Missi n g or partial a d verse e ve nt o nset dates a n d ti mes will be i m p ute d s o t hat if t he partial a d verse 
e ve nt o nset date/ti me i nf or mati o n d oes n ot i n dicate t hat t he a d verse e ve nt starte d pri or t o treat me nt 
or after t he treat me nt -e mer ge nt a d verse e ve nt peri o d, t he a d verse e ve nt will be classifie d as 
treat me nt-e mer ge nt.  N o i m p utati o n of a d verse e ve nt e n d dates/ti mes will be perf or me d.  T hese data 
i m p utati o ns are f or cate g orizati o n p ur p ose o nl y a n d will n ot be use d i n listi n gs.  N o i m p utati o n is 
pla n ne d f or date/ti me of a d verse e ve nt res ol uti o n.  
1 5. 4. 5.  H a n dli n g of a d verse e v e nts w he n d ate a n d ti me of first i n vesti g ati o n al 
me dici n al pr o d uct a d mi nistr ati o n is missi n g  
W he n t he date a n d ti me of t he first I M P a d mi nistrati o n is missi n g, all a d verse e ve nts t ha t occ urre d 
o n or after t he da y of ra n d o mizati o n s h o ul d be c o nsi dere d as treat me nt -e mer ge nt a d verse e ve nts.  
T he e x p os ure d urati o n s h o ul d be ke pt as missi n g.  
T he last d ose i nta ke s h o ul d be clearl y i de ntifie d i n t he e C R F a n d s h o ul d n ot be a p pr o xi mate d b y t he  
last ret ur ne d pac ka ge date. 
1 5. 4. 6.  H a n dli n g of missi n g assess m e nt of rel ati o ns hi p of a d verse e v e nts t o 
i n vesti g ati o n al m e dici n al pr o d uct  
If t he assess me nt of t he relati o ns hi p t o I M P is missi n g, t he n t he relati o ns hi p t o I M P has t o be ass u me d 
a n d t he a d verse e ve n t c o nsi dere d as s uc h i n t he fre q ue nc y ta bles of p ossi bl y relate d a d verse e ve nts, 
b ut n o i m p utati o n s h o ul d be d o ne at t he data le vel.  
1 5. 4. 7.  H a n dli n g of missi n g se verit y/ gr a des of a d verse e ve nts  
If t he se verit y/ gra de is missi n g f or 1 of t he treat me nt-e mer ge nt occ urre nces of a n a d verse e ve nt, t he 
ma xi mal se verit y o n t he re mai ni n g occ urre nces will be c o nsi dere d.  If t he se verit y is missi n g f or all 
t he occ urre nces, a “ missi n g” cate g or y will be a d de d i n t he s u m mar y ta ble. 


Sa n ofi Gr o u p  
 
Fi nal Statistical A nal ysis Pla n, Versi o n 2. 0  
D u pil u ma b - L P S 1 5 4 9 7  
 
Date Iss ue d: 3 0J U L 2 0 2 1  
 
  
 
 
 
4 9  
1 5. 4. 8.  H a n dli n g of p ote nti all y cli nic all y si g nific a nt a b n or m alities  
If a patie nt has a missi n g baseli ne he will be gr o u pe d i n t he cate g or y “ n or mal/ missi n g at baseli ne.” 
 
F or P C S As wit h 2 c o n diti o ns, o ne base d o n a c ha n ge fr o m baseli ne val ue or a n or mal ra n ge a n d t he 
ot her o n a t hres h ol d val ue, wit h t he first c o n diti o n bei n g missi n g, t he P C S A will be base d o nl y o n 
t he sec o n d c o n diti o n. 
1 5. 5.  
Visit Wi n d o ws  
T he f oll o wi n g ste ps will deci de h o w t he sc he d ule d a n d/ or u nsc he d ule d visits will be use d i n t he 
a nal yses o n efficac y varia bles a n d t he b y -visit s u m maries f or safet y varia bles. 
Ste p 1: A sc he d ule d meas ure me nt ( descri be d i n A p pe n di x 1 5. 2 ) will be use d if it is a vaila ble; 
ot her wise, a n u nsc he d ule d meas ure me nt (i ncl u di n g t he e n d of treat me nt/st u d y visit f or t h ose 
pre mat urel y disc o nti n ue d) will be use d if it ha p pe ns t o be o n t he sa me date as t he date of t he 
sc he d ule d visit. 
Ste p 2: After Ste p 1, if t here is still n o meas ure me nt f or a gi ve n para meter at a sc he d ule d visit, t he 
a nal ysis wi n d o w bel o w ”[i n brac kets]”  will be a p plie d t o re -all ocate a p ost -baseli ne u nsc he d ule d 
meas ure me n t t o a sc he d ule d meas ure me nt. 
 
Ta ble 1 5. 5 .1  A nal yses wi n d o w defi niti o n  
 
Sc he d ule d 
visit  
p ost b aseli ne  
 
T ar gete d  
st u d y 
d a y  
A n al ysis wi n d o w  
P S G  
Wei g h
t 
P V T, A N A M, 
A C Q -5 a n d 
A R -V A S  
All ot her e n d p oi nts/ p ar a meters  
Wee k 1 ( Visit 
2)  
7  
 
 
 
[ 1, 1 1] 
Wee k 2 ( Visit 
3)  
1 4  
 
 
 
[ 1 2, 2 1] 
Wee k 4 ( Visit 
4)  
2 8  
 
 
 
[ 2 2, 4 2] 
Wee k 8 ( Visit 
5)  
5 6  
 
 
 
[ 4 3, 7 0] 
Wee k 1 2 
( Visit 6) 
8 4  
[ 1, ~] 
 
[ 1, 1 2 6] 
> = 7 1 f or patie nts w h o di d n ot e nter 
O L E.  
[ 7 1, 1st d ose date of O L E[ f or 
patie nts e ntere d O L E.  
Wee k 1 6 
( Visit 7) 
1 1 2  
 
 
 
[ First d ose of O L E, 1 2 6] 
Wee k 2 0 
( Visit 8) 
1 4 0  
 
 
 
[ 1 2 7, 1 5 4] 


Sa n ofi Gr o u p  
 
Fi nal Statistical A nal ysis Pla n, Versi o n 2. 0  
D u pil u ma b - L P S 1 5 4 9 7  
 
Date Iss ue d: 3 0J U L 2 0 2 1  
 
  
 
 
 
5 0  
 
Sc he d ule d 
visit  
p ost b aseli ne  
 
T ar gete d  
st u d y 
d a y  
A n al ysis wi n d o w  
P S G  
Wei g h
t 
P V T, A N A M, 
A C Q -5 a n d 
A R -V A S  
All ot her e n d p oi nts/ p ar a meters  
Wee k 2 4 
( Visit 9) 
 
1 6 8  
 
[ 1, ~] 
[ 1 2 7, ~] 
[ 1 5 5, ~] 
St u d y da ys are calc ulate d fr o m t he da y of first a d mi nistrati o n of I M P; t he da y of first a d mi nistrati o n 
of I M P ( or t he da y of ra n d o mizati o n if n ot e x p ose d) is Da y 1.  
F or e n d p oi nts wit h dail y assess me nts  u ntil Wee k 4, Wee k 3 will be s u m marize d . Wee k 3 visit is 
assi g ne d t o rec or ds w hic h lie o n t he 7 da ys f oll o wi n g t he fi nal da y of Wee k 2.  If t h is 7 da y  
wi n d o w  o verla p s wit h alrea d y assi g ne d Wee k 4 rec or ds t he n Wee k 3 will ha ve a d urati o n of less 
t ha n 7 da ys. 
After a p pl yi n g t he a b o ve ti me wi n d o ws, if m ulti ple assess me nts are ass ociate d t o t he sa me ti me 
p oi nt, t he cl osest fr o m t he tar gete d st u d y da y will be use d. I n case of e q ualit y, t he last meas ure me nt 
will be use d. Re -all ocate d sc he d ule d visits (i.e., visit n u m bers) s h o ul d be se q ue ntial if or dere d b y 
t he date of meas ure me nt. 
After Ste p 2, if t here is still n o meas ure me nt f or a gi ve n para meter at a sc he d ule d visit, data is 
c o nsi dere d missi n g. 
F or e n d p oi nts w here meas ure me nts were o nl y sc he d ule d o nce f or p ost -baseli ne (e. g., wei g ht at 
wee k 2 4 a n d P S G at wee k 1 2), t he meas ure me nt t hat is cl osest t o t he tar get da y will be use d.  
 
 


Sa n ofi Gr o u p  
 
Fi nal Statistical A nal ysis Pla n, Versi o n 2. 0  
D u pil u ma b - L P S 1 5 4 9 7  
 
Date Iss ue d: 3 0J U L 2 0 2 1  
 
  
 
 
 
5 1  
1 5. 6.  
Se ar c h Criteri a f or A E SI  
Ta ble 1 5. 6 .1  Searc h Criteria f or A E SI  
A E SI  
Se arc h Criteri a  
A na p h yla xis  
S M Q: A na p h yla xis [ Narr o w]  
S yste mic or se vere h y perse nsiti vit y reacti o ns  
S M Q: H y perse nsiti vit y [ Narr o w]  
Mali g na nc y (e xce 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)  
S u b -S M Q ( 2 0 0 0 0 0 9 1) –  Mali g na nt or 
u ns pecifie d t u m ors  
Hel mi nt hic i nfecti o ns  
H L Ts of “ Hel mi nt hic i nfecti o ns N E C”  
S uici de -relate d e ve nts 
P Ts of  
•  
C o m plete d s uici de  
•  
S uici dal i deati o n  
•  
De pressi o n s uici dal  
•  
S uici dal be ha vi or  
•  
S uici de atte m pt  
A n y t y pe of c o nj u ncti vitis or ble p haritis 
(se vere or seri o us) 
 
1. Narr o w c o nj u ncti vitis is defi ne d as t he 
f oll o wi n g P Ts 
•  
C o nj u ncti vitis  
•  
C o nj u ncti vitis aller gic  
•  
C o nj u n cti vitis bacterial  
•  
C o nj u ncti vitis viral  
•  
At o pic Kerat oc o nj u ncti vitis  
 
2. Br oa d c o nj u ncti vitis is defi ne d as t he 
f oll o wi n g P Ts 
•  
C o nj u ncti vitis, C o nj u ncti vitis aller gic  
•  
C o nj u ncti vitis bacterial  
•  
C o nj u ncti vitis viral  
•  
At o pic Kerat oc o nj u ncti vitis  
•  
Ble p haritis  
•  
Dr y e ye  
•  
E ye irritati o n  
•  
E ye pr urit us  
•  
Lacri mati o n i ncrease d  
•  
E ye disc har ge  
•  
F orei g n b o d y se nsati o n i n e yes  
•  
P h ot o p h o bia, Xer o p ht hal mia  
•  
Oc ular h y perae mia  
•  
C o nj u ncti val h y perae mia  
 
3. C o nj u ncti vitis is defi ne d as t he f oll o wi n g 
P Ts  
•  
C o nj u ncti vitis  
•  
N o n -i nfecti ve c o nj u ncti vitis 


Sa n ofi Gr o u p  
 
Fi nal Statistical A nal ysis Pla n, Versi o n 2. 0  
D u pil u ma b - L P S 1 5 4 9 7  
 
Date Iss ue d: 3 0J U L 2 0 2 1  
 
  
 
 
 
5 2  
•  
C o nj u ncti vitis aller gic  
•  
C o nj u ncti vitis bacterial  
•  
C o nj u ncti vitis viral  
•  
E ye irritati o n  
•  
E ye i nfla m mati o n  
 
Keratitis  
P Ts of  
•  
Keratitis, Aller gic keratitis  
•  
Ulcerati ve keratitis  
•  
At o pic kerat oc o nj u ncti vitis  
•  
Her pes o p ht hal mic  
•  
O p ht hal mic her pes si m ple x  
Pre g na nc y occ urri n g i n a fe male patie nt or i n a 
fe male part ner of male patie nt a d mi nistere d 
I M P/ NI M P 
 
“ Pre g na nc y” or “ Part ner Pre g na nc y” c hec ke d 
i n e C R F f or m “ Pre g na nc y” 
S y m pt o matic o ver d os e of I M P/ NI M P 
 
“ O ver d ose of St u d y Treat me nt” or “ O ver d ose 
of NI M P” c hec ke d a n d “ S y m pt o matic 
o ver d ose” c hec ke d i n e C R F f or m “ O ver d ose”  
 
 
 


Sa n ofi Gr o u p  
 
Fi nal Statistical A nal ysis Pla n, Versi o n 2. 0  
D u pil u ma b - L P S 1 5 4 9 7  
 
Date Iss ue d: 3 0J U L 2 0 2 1  
 
  
 
 
 
5 3  
1 5. 7.  
P ote nti all y Cli nic all y Si g nific a nt A b n or m alities ( P C S A) Crit eri a  
Ta ble 1 5. 7 .1  P ote ntiall y Cli nicall y Si g nifica nt A b n or malities Criteria  
 
C RI T E RI A f or P O T E N TI A L L Y C LI NI C A L L Y SI G NI FI C A N T A B N O R M A LI TI E S  
f or p h ase 2/ 3 st u dies ( o nc ol o g y e xce pte d) 
( Fr o m B T D-0 0 9 5 3 6 M a y 2 1, 2 0 1 4)  
 
P ar a meter  
P C S A  
C o m me nts  
H R  
≤5 0 b p m a n d decrease fr o m baseli ne ≥2 0 
b p m  
≥1 2 0 b p m a n d i ncrease fr o m baseli ne ≥2 0 
b p m  
T o be a p plie d f or all p ositi o ns 
(i ncl u di n g missi n g) e xce pt 
S T A N DI N G.  
 
S B P  
≤9 5 m m H g a n d decrease fr o m baseli ne 
≥2 0 m m H g  
≥1 6 0 m m H g a n d i ncrease fr o m baseli ne 
≥2 0 m m H g  
T o be a p plie d f or all p ositi o ns 
(i ncl u di n g missi n g) e xce pt 
S T A N DI N G.  
 
D B P  
≤4 5 m m H g a n d decrease fr o m baseli ne ≥1 0 
m m H g  
≥1 1 0 m m H g a n d i ncrease fr o m baseli ne 
≥1 0 m m H g  
T o be a p plie d f or all p ositi o ns 
(i ncl u di n g missi n g) e xce pt 
S T A N DI N G.  
 
Wei g ht  
≥5 % i ncrease fr o m baseli ne 
≥5 % decrease fr o m baseli ne  
F D A Fe b 2 0 0 7  
 
1 5. 8.  
P atie nt -Re p orte d O utc o mes ( P R O S)  
Patie nt orie nte d ecze ma meas ure ( P O E M)  
T he P O E M is a 7 -ite m, vali date d q uesti o n naire use d i n cli nical practice a n d cli nical trials t o assess 
fre q ue nc 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, slee p l oss, blee di n g, a n d wee pi n g) base d o n fre q ue nc y d uri n g 
t he past wee k (ie, 0 = n o 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 yste m of 0 t o 2 8; t he t otal sc ore reflects disease -relate d se verit y. 
P O E M sc ore will be directl y pr o vi de d b y K O N E K S A.  
P R O MI S Slee p Relate d I m pair me nt S h ort F or m 8 a  
T he P R O MI S is a D S M -5, Le vel 2, slee p dist ur ba nce meas ure. T his st u d y uses t he 8 -ite m P R O MI S 
Slee p Relate d I m pair me nt S h ort F or m t hat assesses t he d o mai n of slee p relate 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.  


Sa n ofi Gr o u p  
 
Fi nal Statistical A nal ysis Pla n, Versi o n 2. 0  
D u pil u ma b - L P S 1 5 4 9 7  
 
Date Iss ue d: 3 0J U L 2 0 2 1  
 
  
 
 
 
5 4  
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 he 
past 7 da ys. Eac h ite m o n t he meas ure is rate 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 me nt.  
 
L ocate t he a p plica ble sc ore c o n versi o n i n  Ta ble 1 5. 8 .1 , a n d use t his ta ble t o tra nslate t he t otal ra w 
sc ore or i m p ute d t otal score i nt o a P R O MI S T -sc ore f or eac h partici pa nt. T he T-sc ore rescales t he 
ra w sc ore i nt o a sta n dar dize d sc ore wit h a mea n of 5 0 a n d a sta n dar d de viati o n of 1 0. T heref ore, a 
pers o n wit h a T -sc ore of 4 0 is o ne S D bel o w t he mea n. T he sta n dar dize d T-sc ore is rep orte d as t he 
fi nal sc ore f or eac h partici pa nt.  
 
Ta ble 1 5. 8 .1  P R O MI S Slee p -Relate d I m pair me nt c o n versi o n ta ble  
R a w Sc ore  
T -sc ore 
R a w Sc ore  
T -sc ore 
8  
3 0  
2 5  
6 0. 3  
9  
3 5. 1  
2 6  
6 1. 3  
1 0  
3 8. 7  
2 7  
6 2. 3  
1 1  
4 1. 4  
2 8  
6 3. 3  
1 2  
4 3. 6  
2 9  
6 4. 3  
1 3  
4 5. 5  
3 0  
6 5. 3  
1 4  
4 7. 3  
3 1  
6 6. 3  
1 5  
4 8. 9  
3 2  
6 7. 3  
1 6  
5 0. 3  
3 3  
6 8. 4  
1 7  
5 1. 6  
3 4  
6 8. 5  
1 8  
5 2. 9  
3 5  
7 0. 7  
1 9  
5 4  
3 6  
7 1. 9  
2 0  
5 5. 1  
3 7  
7 3. 3  
2 1  
5 6. 1  
3 8  
7 5  
2 2  
5 7. 2  
3 9  
7 6. 9  
2 3  
5 8. 2  
4 0  
8 0  
2 4  
5 9. 3  
 
 
 
P R O MI S sc ore will be directl y pr o vi de d b y K O N E K S A.  
E p w ort h Slee pi ness Scal e ( E S S)  
T he E S S is a self -a d mi nistere d q uesti o n naire wit h 8 q uesti o ns. Res p o n de nts are as ke 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 aslee p w hile 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 nall y, alt h o u g h n ot necessaril y e ver y 


Sa n ofi Gr o u p  
 
Fi nal Statistical A nal ysis Pla n, Versi o n 2. 0  
D u pil u ma b - L P S 1 5 4 9 7  
 
Date Iss ue d: 3 0J U L 2 0 2 1  
 
  
 
 
 
5 5  
da y. T he E S S sc ore (t he s u m of 8 ite m sc ores, 0 -3) ca n ra n ge fr o m 0 t o 2 4. T he hi g her t he E S S sc ore, 
t he hi g her t hat pers o n’s a vera ge slee p pr o pe nsit y i n dail y life, or t heir da yti me slee pi ness. 
 
E S S sc ore will be directl y pr o vi de d b y K O N E K S A.  
Slee p Q ualit y N R S  
T he Slee p Q ualit y 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 q ualit y of 
patie nt’s last ni g ht slee p. Patie nts w ill be as ke d t he f oll o wi n g q uesti o n: 
 
“ O n a scale of 0 t o 1 0, wit h 0 bei n g “ w orst p ossi ble slee p” a n d 1 0 bei n g t he “ best  p ossi ble slee p”, 
select t he n u m ber t hat best descri be t he q ualit y of y o ur slee p last ni g ht” 
 
Patie nts will c o m plete t he rati n g scale 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 basel i 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), t he n dail y d uri n g t he wee k bef ore eac h 
pla n ne d visit.  
 
Patie nt c h o oses a val ue fr o m 0 t o 1 0 i n t he o nl y q uesti o n of t he scale a n d t hat val ue is t he gl o bal 
sc ore of t he scale. 
Slee p Q ualit y  N R S sc ore will be directl y pr o vi de d b y K O N E K S A.  
Pea k Pr urit us 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 dail y recall peri o d. Patie nts will be as ke d t he f oll o wi n g q uesti o n:  
 
“ 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 ble ’ , 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 scal 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.  


Sa n ofi Gr o u p  
 
Fi nal Statistical A nal ysis Pla n, Versi o n 2. 0  
D u pil u ma b - L P S 1 5 4 9 7  
 
Date Iss ue d: 3 0J U L 2 0 2 1  
 
  
 
 
 
5 6  
 
Patie nt c h o oses a val ue fr o m 0 t o 1 0 i n t he o nl y q uesti o n of t he scale a n d t hat val ue is t he gl o bal 
sc ore of t he scale. 
Pea k Pr urit us N R S sc ore will be directl y pr o vi de d b y K O N E K S A.  
S ki n Pai n 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 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?” 
 
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 da ys pri or t o baseli ne 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 bef ore eac h pla n ne d visit.  
 
Patie nt c h o oses a val ue fr o m 0 t o 1 0 i n t he o nl y q uesti o n of t he scale a n d t hat val ue is t he gl o bal 
sc ore of t he scale. 
S ki n Pai n N R S sc ore will be directl y pr o vi de d b y K O N E K S A.  
S ki n Se nsiti vit y t o t o uc h 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?”  
 


Sa n ofi Gr o u p  
 
Fi nal Statistical A nal ysis Pla n, Versi o n 2. 0  
D u pil u ma b - L P S 1 5 4 9 7  
 
Date Iss ue d: 3 0J U L 2 0 2 1  
 
  
 
 
 
5 7  
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 da ys pri or t o baseli ne 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 bef ore eac h pla n ne d visit.  
 
Patie nt c h o oses a val ue fr o m 0 t o 1 0 i n t he o nl y  q uesti o n of t he scale a n d t hat val ue is t he gl o bal 
sc ore of t he scale. 
S ki n Se nsiti vit y t o T o uc h N R S sc ore will be directl y pr o vi de d b y K O N E K S A.  
S ki n B ur n 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 da ys pri or t o baseli ne 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 bef ore eac h pla n ne d visit.  
 
Patie nt c h o oses a v al ue fr o m 0 t o 1 0 i n t he o nl y q uesti o n of t he scale a n d t hat val ue is t he gl o bal 
sc ore of t he scale. 
S ki n B ur n N R S sc ore will be directl y pr o vi de d b y K O N E K S A.  
Slee p diar 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 hr o u g h visit 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 slee 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 be d i n t he m or ni n g. T he f oll o wi n g varia bles will be deri ve d fr o m slee p diar y:  
W A S O = Ti me a wa ke after i nitial slee p o nset b ut bef ore t he fi nal a wa ke ni n g  
 


Sa n ofi Gr o u p  
 
Fi nal Statistical A nal ysis Pla n, Versi o n 2. 0  
D u pil u ma b - L P S 1 5 4 9 7  
 
Date Iss ue d: 3 0J U L 2 0 2 1  
 
  
 
 
 
5 8  
T his is data c ollecte d fr o m Q uesti o n 3 of t he Slee p Diar y: “ 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?” 
T S T = Ti me of wa ki n g u p f or t he da y mi n us Ti me of falli n g slee p mi n us W A S O  
S O L = Ti me of falli n g slee p –  Ti me of tr yi n g t o fall slee p  
S E =
T S T
Ti m e  of  w a ki n g  u p  f or t h e d a y − Ti m e  of  tr yi n g t o f all sl e e p × 1 0 0 %  
 
Slee p diar y data will be directl y pr o vi de d b y K O N E K S A.  
 
D ue t o ill o gical data res p o nses t o t he Slee p diar y q uesti o n naires, a S A P a d de n d u m wit h data 
ha n dli n g r ules t o be a p plie d will be pr o vi de d i n a se parate d oc u me n t. 
 
Der mat ol o g y Life 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 use 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 ualit y of Life ( Q o L). T he f or mat is a si m ple 
res p o nse ( 0 t o 3 w here 0 is “ n ot at all’ a n d 3 is “ ver y m uc h”) t o 1 0 q uesti o ns, w hic h assess Q o L o ver 
t he past wee 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 he D L QI sc ore will be directl y pr o vi de d b y K O N E K S A.  
J u ni per Ast h ma C o ntr ol Q uesti o n naire ( A C Q -5 ) [a m o n g t h ose re p orti n g ast h mas at 
baseli ne ] 
T he 5 -q uesti o n versi o n of t he J u ni per ast h ma c o ntr ol q uesti o n naire ( A C Q) is a vali date d 
q uesti o n naire t o e val uate 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 ma, at Baseli ne ( Wee k 0), Wee k 1 2 a n d Wee k 2 4.  
Eac h q uesti o n is a 7 -p oi nt scale ( 0 = n o i m pair me nt t o 6 = ma xi m u m i m pair me nt). A gl o bal sc ore is 
calc ulate d: t he q uesti o ns are e q uall y wei g hte d, a n d t he A C Q -5 sc ore is t he mea n of t he 5 q uesti o ns 
a n d, t heref ore, bet wee n 0 (t otall y c o ntr olle d) a n d 6 (se verel y u nc o ntr olle d).  
O n t he 7 -p oi nt scale of t he A C Q -5, a c ha n ge or differe nce i n sc ore of 0. 5 is t he s mallest t hat ca n be 
c o nsi dere d cli nicall y i m p orta nt, c o rres p o n di n g t o t he 
Mi ni mal Cli nicall y I m p orta nt Differe nce 
( M CI D) defi ne d b y t he de vel o per. 
 
A C Q -5 sc ore will be directl y pr o vi de d b y K O N E K S A.  
Aller gic R hi nitis Vis ual A nal o g Scale ( A R -V A S) [a m o n g t h ose re p orti n g aller gic r hi nitis at 
baseli ne ] 
T he A R -V A S i s 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 gic 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:  


Sa n ofi Gr o u p  
 
Fi nal Statistical A nal ysis Pla n, Versi o n 2. 0  
D u pil u ma b - L P S 1 5 4 9 7  
 
Date Iss ue d: 3 0J U L 2 0 2 1  
 
  
 
 
 
5 9  
“ O verall 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 ne , Wee k 1 2 a n d Wee k 2 4 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 A R -V A S sc ore will be directl y pr o vi de d b y K O N E K S A.  
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: At o pic Der mat itis ( W P AI-A D)  
T he W P AI -A D is desi g ne 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 ure i m pair me nts i n w or k a n d acti vities o ver a 7-da y recall 
peri o d. T he W P AI -A D o utc o mes are e x presse d as i m pair me nt perce nta ges, wit h hi g her n u m bers 
i n dicati n g greater i m pair me nt a n d less pr o d ucti vit y. 
T he W P AI -A D q uesti o n naire will be directl y pr o vi de d b y K O N E K S A.  
Da ys m isse d fr o m sc 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 urr e 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.  
Ot her assess me nts will be perf or me d:  
•  
D urati o n of e m pl o y me nt t hr o u g h wee k 1 2 = s u m of all e m pl o y me nt i nter vals (s pecific 
assess me nt date  –  last assess me nt date) fr o m t he first visit till t he last assess me nt of 
e m pl o y me nt stat us o n or pri or t o wee k 1 2 + 1 da y.  F or t he first p ost -baseli ne assess me nt, if 
n o baseli ne assess me nt is rec or de d t he n ra n d o mizati o n date s h o ul d be use d as last assess me nt 
date.  D urati o n of e m pl o y me nt will be calc ulate d disre gar di n g f ull or partial e m pl o y me nt 
stat us.  
•  
Da ys of sic k lea ve t hr o u g h wee k 1 2 is t he s u m of all misse d w or k/sc h o ol da ys u p t o t he last 
assess me nt date o n or pri or t o wee k 1 2.  F or t he first p ost -baseli ne assess me nt, if n o baseli ne 
assess me nt is rec or de d a n d t he n u m ber of misse d da ys is hi g her t ha n i m p ute d e m pl o y me nt 
d ura ti o n t he n t he n u m ber of misse d da ys will be e q ual t o e m pl o y me nt d urati o n.  
•  
E m pl o y me nt d urati o n a dj uste d sic k lea ve days p er 1 2 wee ks will be use d f or treat me nt 
c o m paris o n. It is o nl y a p plie d f or patie nts w h o are f ull y or partiall y e m pl o ye d. If da ys of 
sic k lea ve t hr o u g h wee k 1 2 val ue is missi n g f or a s pecific assess me nt, t he le n gt h of t his 
assess me nt i nter val will be de d ucte d fr o m t he d urati o n of e m pl o y me nt t hr o u g h wee k 1 2.  
E m pl o y m e nt  d ur ati o n  a dj ust e d  sic k l e a v e d a ys  p er  1 2  w e e ks   
 =
D a ys  of  sic k l e a v e t hr o ug h  w e e k  1 2  
D ur ati o n  (i n d a ys ) of  e m pl o y m e nt  t hr o u g h w e e k  1 2  ∗1 2  w e e ks  (i n d a ys ) 
Da ys misse d  fr o m sc h o ol or fr o m w or k d ue t o A D will be directl y pr o vi de d b y K O N E K S A. 
 


Sa n ofi Gr o u p  
 
Fi nal Statistical A nal ysis Pla n, Versi o n 2. 0  
D u pil u ma b - L P S 1 5 4 9 7  
 
Date Iss ue d: 3 0J U L 2 0 2 1  
 
  
 
 
 
6 0  
H os pital A n xiet y a n d De pressi o n Scale ( H A D S)  
T he H A D S is a n i nstr u me nt f or assessi n g s y m pt o m s 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 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. 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 ble sc ores ra n ge fr o m 0 t o 2 1 f or eac h s u bscale.  
T he H A D S  sc ores will be directl y pr o vi de d b y K O N E K S A.  
1 5. 9.  
Cli nici a n -Re p orte d O utc o mes ( C LI N R O S)  
1 5. 9. 1.  Cli nici a n  Assess m e nt s 
 
S C O R i n g of At o pic Der matitis ( 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 vel 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. T here are 3 c o m p o ne nts t o t he 
assess me nt: 
•  
A = e xte nt or affecte d B S A  
•  
B = se verit y  
•  
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 e ac 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 verall S C O R A D calc ulati 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 xc oriati o n, s ki n 
t hic ke ni n g/lic he nificati o n, dr y ness) is assesse d usi n g t he f oll o wi n g scale: n o ne ( 0), mil d ( 1), 
m o derate ( 2), or se vere ( 3) (f or a ma 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 o r eac h s y m pt o m by t he 
patie nt or relati ve o n a vis ual a nal o g scale ( V A S, w here 0 is n o itc h ( or slee pless ness) a n d 1 0 is t he 
w orst i ma gi na ble itc h ( or slee pless ness), wit h a ma xi m u m p ossi ble sc ore of 2 0 (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.  
 
T he S C O R A D t otal sc ore, itc h a n d slee pless ness V A S w ill be directl y pr o vi de d b y K O N E K S A. 
Ecze ma Area a n d Se 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 disease 
c haracteristics (er yt he ma, t hic k ness [i n d urati o n, pa p ulati o n, a n d e de ma], scratc hi n g [e xc oriati o n], 
a n d lic he nificati o n) will eac h be assesse d f or se verit y b y t he i n vesti gat or or desi g nee o n a scale 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 b s, a n d c o n verte d t o a sc 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 %).  
F or eac h b o d y re gi o n ( hea d, tr u n k, u p per li m bs, a n d l o wer li m bs), E A S I sc ore = (s u m of t he f o ur 
A D disease c haracteristics sc ores) m ulti pl y (area of A D i n v ol ve me nt sc ore). T he t otal E A SI s ore  
is t he wei g hte d t otal of t he b o d y re gi o n E A SI sc ores usi n g t he wei g hts 1 0 % = hea d, 2 0 % = u p per 






Sa n ofi Gr o u p  
 
Fi nal Statistical A nal ysis Pla n, Versi o n 2. 0  
D u pil u ma b - L P S 1 5 4 9 7  
 
Date Iss ue d: 3 0J U L 2 0 2 1  
 
  
 
 
 
6 3  
T he tests i ncl u de d i n t he D u pista d St u d y batter y are n ot o verl y diffic ult. I n a d diti o n, t he y all i n v ol ve 
bi nar y res p o nse o pti o ns, t h us 5 0 % acc urac y w o ul d reflect c ha nce -le vel res p o n di n g. Tests wit h 
vali dit y fla g as “I n vali d” will  be e xcl u de d fr o m t he A N A M data a nal ysis.  If t he differe nce i n 
pr o p orti o n of “i n vali d” tests bet wee n t he treat me nts is m ore t ha n 2 0 %, a n e x pl orat or y a nal ysis of t he 
s u m maries i n secti o n 8. 2. 1 7  will be re peate d b y i ncl u di n g t hese tests.  
1 5. 1 0.  
O bjecti ve Assess m e nts  
Acti gra p h y data  
Wrist acti gra p h y is a tec h ni q ue f or meas uri n g m o ve 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 wee ks). T he si g nals ge nerate d b y wrist m o ve me nt are se nse d b y a ti n y micr oc o m p uter 
c o ntai ne d wit hi n t he watc h a n d tra 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 S E ). 
Eli gi ble 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 baseli 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 bef ore eac h pla n ne d visit.  
 
Acti gra p h y data sc ore will be directl y pr o vi de d b y K O N E K S A.  
 
P ol ys o m n o gra p h y ( P S G)  
P ol ys o m n o gra p h y is a m ulti -para metric tes t 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 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 S O L, 
W A S O , T S T, l o n gest slee p e pis o de, sta ges of slee p, S E 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. 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” a n d c ollect baseli ne data; t he n 1 o ver ni g ht P S G at wee k 1 2.  
 
P S G data will be directl y pr o vi de d b y S T A N F O R D.  
1 5. 1 1.  
Resc ue a n d P r o hi bite d Me dic ati o ns.  
Re sc ue me dicati o ns will be i de ntifie d b y selecti n g “resc ue t hera p y ” f or t he reas o n f or treat me nt i n 
“ Me dicati o ns” C R F pa ge.  
 
Treat me nt wit h f oll o wi n g c o nc 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 yste 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 kers, o pi oi ds, t he o p h ylli ne, cl o ni di ne, a nti de pressa nts or ot her 
me dicati o ns k n o w n t o i nterfere wit h slee p  a n d A D as deter mi ne d b y t he I n vesti 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 
•  
I n vesti gati o nal dr u gs 


Sa n ofi Gr o u p  
 
Fi nal Statistical A nal ysis Pla n, Versi o n 2. 0  
D u pil u ma b - L P S 1 5 4 9 7  
 
Date Iss ue d: 3 0J U L 2 0 2 1  
 
  
 
 
 
6 4  
•  
Hi g h -p ote nc y a n d s u per -p ote nt T C S, e xce pt w he n use d f or resc ue  
•  
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, Cs A, 
A Z A, M T X, M M F, J A K i n hi bit ors, etc.), e xce pt w he n use d f or resc ue  
 
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 use d t hr o u g h wee k 2 4:  
•  
Treat me nt wit h a li ve (atte n uate d) vacci ne  
•  
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, Cs A, A Z A, M T X, M M F, J A K i n hi bit ors, etc.)  
 
N ote: If a patie nt recei ves resc ue treat me nt wit h s yste mic c ortic oster oi ds or o t her s yste mic 
i m m u n os u p pressi ve dr u gs ( Cs A, 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 dee me d a p pr o priate b y t he I n vesti gat or a n d t he me 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 yste mic resc ue me dicati o n. 
 
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 be d/ b o ot h  
 
List of c o de d ter ms f or pr o hi bite d me dicati o ns will be pr o vi de d b y S A N O FI.