A PHASE 3 RANDOMIZED WITHDRAWAL, DOUBLE-BLIND, PLACEBO-CONTROLLED, MULTI-CENTER STUDY INVESTIGATING THE EFFICACY AND SAFETY OF PF-04965842 IN SUBJECTS AGED 12 YEARS AND OVER, WITH MODERATE TO SEVERE ATOPIC DERMATITIS WITH THE OPTION OF RESCUE TREATMENT IN FLARING SUBJECTS
Phase: PHASE3
Conditions: Dermatitis, Dermatitis, Atopic, Eczema, Skin Diseases, Skin Diseases, Genetic, Genetic Diseases, Inborn, Skin Diseases, Eczematous, Hypersensitivity, Hypersensitivity, Immediate, Immune System Diseases
Sponsor: Pfizer

P F- 0 4 9 6 5 8 4 2
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A P H A S E 3 R A N D O MI Z E D WI T H D R A W A L, D O U B L E -B LI N D, 
P L A C E B O -C O N T R O L L E D, M U L TI- C E N T E R S T U D Y I N V E S TI G A TI N G T H E 
E F FI C A C Y A N D S A F E T Y O F P F -0 4 9 6 5 8 4 2 I N S U B J E C T S A G E D 1 2 Y E A R S A N D 
O V E R, WI T H M O D E R A T E T O S E V E R E A T O PI C D E R M A TI TI S WI T H T H E 
O P TI O N O F R E S C U E T R E A T M E N T I N F L A RI N G S U B J E C T S
I n vesti g ati o n al Pr o d uct N u m ber:
P F - 0 4 9 6 5 8 4 2
I n vesti g ati o n al Pr o d uct N a me:
N ot a p plica ble ( N/ A)
U nite d St ates ( U S) I n vesti g ati o n al Ne w 
Dr u g (I N D) N u m ber:
E ur o pe a n Cli nic al Tri als D at a b ase 
( E u dr a C T) N u m ber:
2 0 1 8 - 0 0 0 5 0 1- 2 3
Pr ot o c ol N u m ber:
B 7 4 5 1 0 1 4
P h ase:
3
T his d oc u me nt a n d acc o m pa n yi n g materials c o ntai n c o nfi de ntial i nf or mati o n bel o n gi n g t o Pfizer.  E xce pt as 
ot her wise a gree d t o i n writi n g, b y acce pti n g or re vie wi n g t hese d oc u me nts, y o u a gree t o h ol d t his i nf or mati o n i n 
c o nfi de nce a n d n ot c o p y or discl ose it t o ot hers (e xce pt w here re q uire d b y a p plica ble la w) or use it f or 
u na ut h orize d p ur p oses.  I n t he e ve nt of a n y act ual or s us pecte d breac h of t his o bli gati o n, Pfizer m ust be 
pr o m ptl y n otifie d.
C CI

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D oc u me nt Hist or y
D oc u me nt
Ve rsi o n D ate
S u m m ar y of C h a n ges a n d R ati o n ale
A me n d me nt 5
2 8 Oct o ber 2 0 1 9
T he C ol u m bia S uici de Se verit y Rati n g 
Scale ( C -S S R S) will be a d mi nistere d t o all 
o n g oi n g s u bjects at all re mai ni n g 
sc he d ule d visits i n R u n I n a n d Bli n de d 
treat me nts, a n d Resc ue wee ks 0, 8, 1 2, 1 6, 
a n d u p t o a n d i ncl u di n g t he E n d of 
Treat me nt/ Earl y Ter mi nati o n ( E O T/ E T) 
a n d/ or t he E n d of St u d y ( E O S) visit t o 
ali g n wit h ne w cr oss - pr o gra m pr ocesses.  
T he secti o ns of t he pr ot oc ol affecte d
i ncl u de Sc he d ules of Acti vities a n d i n 
Secti o n 6.
E n d p oi nts were re w or de d f or clarity.
Re m o val of E Q - 5 D-5 L / E Q- 5 D-Y, 
F A CI T - F/ Pe ds-F A CI T -F, a n d S F -3 6, ac ute
patie nt -re p orte d o utc o me ( P R O) e n d p oi nts
fr o m sec o n dar y o bjecti ves t o ali g n wit h t he 
Statistical A nal y sis Pla n.
A d mi nistrati ve c ha n ges a n d clarificati o n s
ha ve bee n ma de i n vari o us secti o ns of t he 
pr ot oc ol t hat are n ot c o nsi dere d s u bsta ntial 
b y  Pfizer beca use t here was n o i m pact t o 
t he safety of t he t rial partici pa nts, t he sc o pe 
of t he trial, or t he scie ntific i nter pretati o n 
of t he st u d y . T hese c ha n ges i n clu de:

A d mi nistrati o n of t he last d ose of 
o pe n -la bel r u n-i n peri o d st u d y  dr u g 
( 2 0 0 m g Q D) at t he Wee k 1 2 visit 
( Secti o ns 5 a n d 6);

Initiati n g a d mi nistrati o n of ra n d o mize d 
bli n de d t reat me nt o n t he da y after t he 
Wee k
1 2 visit ( Secti o ns 5 a n d 6);

A d mi nistrati o n of t he first d ose of 
o pe n -la bel Resc ue treat me nt at t he start 
of flare ( Secti o n 5);

A d diti o nal bl o o d c ollecti o n at t he 

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c urre nt P K sa m ple ti me p oi nt f or 
a nal ys is of P F-0 4 9 6 5 8 4 2 meta b olites
( Secti o ns 1, 2 , a n d 7);

U p date a n d clarificati o n of was h o ut 
peri o d f or C Y P 2 C 9 a n d C Y P 2 C 1 9 
i n d ucers ( A p pe n di x 3).
A me n d me nt 4
2 7 N o ve m ber 2 0 1 8
F or Tai wa n o nl y:
Si milar t o C hi na, ot her c o u ntries i n Asia, 
s uc h as Tai wa n, ha ve a hi g h pre vale nce of 
he patitis B s urface a nti ge n ( H Bs A g) 
ne gati ve, he patitis B c ore a nti b o d y  
( H BcA b ) p ositi ve, a n d he patitis B s urface 
a nti b o d y ( H Bs A b) p ositi ve ser ol o g y.  
T heref ore, Tai wa n will a d o pt t he sa me 
c ha n ges as t h ose pr o p ose d f or C hi na i n 
A me n d me nt 3 t o m o nit or t he ris k of 
he patitis B reacti vati o n.
T he f oll o wi n g 
secti o ns of t he pr ot oc ol are affecte d:
Sc he d ule of Acti vities, Secti o ns 4, 6, a n d 7, 
as a p plica ble.
A me n d me nt 3
1 2 Se pte m ber 2 0 1 8
T he f oll o wi n g c ha n ges , re q ueste d b y a n 
E t hics C o m mittee i n C hi na f or st u dy 
B 7 4 5 1 0 1 3, are bei n g a p plie d t o t he 
P F -0 4 9 6 5 8 4 2 pr o gra m.  
T hese c ha n ges are i n effect for C hi na o nl y :
S u bjects w h o are he patitis B s urface 
a nti ge n (H Bs A g ) ne gati ve, he patitis B c ore 
a nti b o d y (H Bc A b ) p ositi ve, a n d he patitis B
s urface a nti b o dy ( H Bs A b ) p ositi ve at 
Scree ni n g will ha ve refle x testi n g f or 
he patitis B vir us de o x yri b o n uclei c aci d 
(H B V D N A ). S u bjects w h o ha ve H B V 
D N A a b o ve t he l o wer li mit of 
q ua ntificati o n ( L L Q) will be e xcl u de d.  
S u bjects w h o are H B V D N A ne gati ve or 
bel o w L L Q ma y  e nr oll b ut will ha ve H B V 
D N A testi n g re peate d at Wee ks
1 2, 2 8, 4 0, 
5 2, Resc ue Wee k 1 2, a n d earl y ter mi nati o n 
fr o m st u d y d uri n g a n y treat me nt peri o d. 

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A si n gle H B V D N A test res ult a b o ve t he 
L L Q re q uires i m me diate a n d per ma ne nt 
disc o nti n uati o n fr o m treat me nt. 
T he f oll o wi n g secti o ns of t he pr ot oc ol are 
affecte d:
Sc he d ule of Acti vities , Secti o ns 4, 6, a nd 7 ,
as a p plica ble.
A me n d me nt 2
2 3 J ul y 2 0 1 8
S u m mar y a n d Secti o n 1 :

U p date d Bac k gr o u n d a n d Rati o nale 
te xt t o ali g n acr oss t he J A K 1 pr o gra m.
S u m mar y  a n d Secti o n 2:

Clarifie d t he pri mar y  a n d sec o n dar y 
o bjecti ves a n d e n d p oi nts.

A d diti o n of Ke y  Sec o n dar y e nd p oi nt.
S u m mar y  a n d Secti o ns 1, 3 a n d/ or 4 :

Clarifie d St u d y  desi g n.

Clarifie d i nf or me d c o nse nt 
re q uir me nts.

F or clarit y , defi ne d me dicate d t o pical 
t hera py as a t o pical pr o d uct t hat 
c o ntai ns a n acti ve p har mace utical 
i n gre die nt i n dicate d f or t he treat me nt of
A D (irres pecti ve of w het her it is a n 
o ver -t he-c o u nter [ O T C] or prescri be d 
pr o d uct).
S u m mar y  a n d/ or Secti o n 9 :

Clarifie d per -pr ot oc ol a nal y sis set 
maj or de viati o ns.

Clarifie d w or di n g/ gr o u p defi niti o ns a n d 
ot her clarificati o n of e n d p oi nts.

A d diti o n of Ke y  Seco n dar y  e n d p oi nt. 

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Secti o n s 3, 5, 6, 7 a n d Sc he d ule of 
Acti vities ( As A p plica ble): 

A d de d g ui da nce f or t he te m p orar y  
i nterr u pti o n t o d osi n g.

A d de d L y m p h oc y te S u bset t o t he 
Cli nical L a b orat or y tests t o s u p p ort 
a d diti o nal a nal ys is.
Sc he d ule of Acti vities, Se cti o ns 6 a n d 7:

Clarif y i n g t hat s u bjects in re gi o ns
a b o ve a l o w ris k f or t u berc ul osis 
(e g, > 1 0/ 1 0 0, 0 0 0 pre vale nce) will 
ha ve T B test re peate d after o ne ye ar of 
treat me nt e x p os ure.

A d de d Ast h ma Q uesti o n naire as a 
P R O a n d re m o ve d it as a safet y 
assess me nt.
S ecti o n 7.8 Patie nt Re p orte d O utc o mes:

Clarifie d pr ocess f or c ollecti o n of 
Patie nt Re p orte d O utc o me data.
Secti o ns 1 1. 1, 1 1. 2, 1 2. 3 u p date d wit h ne w 
Gl o bal Data Pr otecti o n Re g ulati o n 
la n g ua ge t o ali g n wit h re q uire me nt f or 
i ncl usi o n of rece ntly p u blis he d E u ro pea n 
U ni o n ( E U) Data Pri vac y la n g ua ge a n d 
le gislati o n. 
A p pe n di x 3 Pr o hi bite d C o nc o mita nt 
Me dicati o ns u p date d t o re d uce n u m ber of 
pr o hi bite d me dicati o ns base d o n c urre nt 
u n dersta n di n g of meta b olis m, a n d t o 
pr o vi de clarit y ar o u n d was h -o ut peri o ds .
A p pe n d i x 4 u p date d t o ali g n wit h ne w 
Te m p orar y  Interr u pti o n of D osi n g 
la n g ua ge a n d clarif y disc o nti n uati o n 
criteria.  
A me n d me nt 1
2 0 J u ne 2 0 1 8
T he f oll o wi n g re visi o ns were ma de base d 

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o n V H P fee d bac k:
Clarifie d i n Sc he d ule of Acti vities 
Wee k
5 2 (f o ot n ote ii) a n d i n Secti o n 7. 3. 4 
t hat f oll o wi n g o ne ye ar of t otal e x p os ure t o 
st u d y dr u g si nce t he last t u berc ul osis ( T B) 
test, all s u bjects i n re gi o ns a b o ve a 
l o w-ris k f or T B (ie, > 1 0/ 1 0 0, 0 0 0 
pre vale nce) will u n der g o T B testi n g. 
Clarifie d i n Sc he d ule of Acti vities f o ot n ote 
h h a n d i n Secti o n 4. 2 E xcl usi o n Criteria 
# 1 8 t hat a c hest X -ra y is re q uire d u nless 
pre vi o usl y  perf or me d a n d d oc u me nte d 
wit hi n 1 2 wee ks pri or t o St u d y  D a y 1.
Re vise d Pr ot oc ol S u m mar y , Sc he d ule of 
Acti vities, Secti o n 3 a n d Secti o n 6. 3. 1 t o 
i n dicate t hat n o n-res p o nders at Wee k 1 2 
ma y  r oll o ver o nt o St u d y B 7 4 5 1 0 1 5 
pr o vi di n g t he y  re mai n eli gi ble.
Clarifie d i n t he Pr ot oc ol S u m mar y  a n d i n 
Secti o n 9. 1 t hat base d o n pri or data, a b o ut 
4 4 % of s u bjects w o ul d meet t he 
pr ot oc ol - defi ne d criteria t o be a res p o n der 
at W ee k 1 2, a p pr o xi matel y  1 3 7 0 s u bjects 
w o ul d nee d t o e nter t he o pe n la bel r u n -i n 
peri o d t o e ns ure t hat 6 0 0 s u bjects are 
a vaila ble f or ra n d o mizati o n. 
Secti o n 3 was re vise d t o i n dicate t hat all 
s u bjects w h o ha ve starte d was h-o ut of A D 
treat me nt i n t he scree ni ng peri o d will be 
all o we d t o e nter t he r u n-i n a n d treat me nt 
peri o ds pr o vi di n g all i ncl usi o n criteria a n d 
n o ne of t he e xcl usi o n criteria are met. 
Secti o n 4. 1 clarifie d I ncl usi o n Criteria # 3 
a n d Secti o n 7. 8. 1 t o i n dicate t he pr urit us 
N R S se verit y  sc ore will be use d o n t he da y  
of baseli ne visit t o deter mi ne m o derate t o 
se vere A D ( n ot t he fre q ue nc y of pr urit us 
sc ore). 
Secti o n 4. 2 re vise d E xcl usi o n Criteria t o 
a d d Criteria # 2 3 - k n o w n h y perse nsiti vit y  

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t o P F-0 4 9 6 5 8 4 2 or a n y st u d y  dr u g 
e xci pie nts.
Clarifie d Sec ti o n 4. 3 t o i n dicate 
ra n d o mizati o n is stratifie d b y a ge cate g or y, 
ie < 1 8 years a n d 1 8 ye ars.
Clarifie d i n Secti o n 5. 3 t hat i n vesti gat or is 
res p o nsi ble f or brea ki n g t he bli n d f or 
safety reas o ns w here k n o wle d ge of 
treat me nt is esse ntial.
Clarifie d i n Secti o n 5. 9. 1 t hat l o w d ose 
acet yl  salic ylic aci d (1 0 0 m g Q D) is 
per mitte d f or t he p ur p ose of car di o vasc ular 
pr o p h y la xis. 
Secti o n 6. 1 re vise d t o i n dicate t hat s u bjects 
n ot meeti n g e nr oll me nt criteria (scree n 
fail ures) s h o ul d be c o ntacte d q uic kly t o 
res u me/i nitiate A D treat me nts.
Ori gi nal pr ot oc ol
2 6 Fe br uar y  2 0 1 8
N ot a p plica ble ( N/ A)
T his a me n d me nt i nc or p orates all re visi o ns t o date, i ncl u di n g a me n d me nts ma de at t he 
re q uest of c o u ntr y healt h a ut h orities a n d i nstit uti o nal re vie w b oar ds (IR Bs)/et hics c o m mittees
( E Cs). 

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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 ................................................................................................................... 1 3
LI S T O F FI G U R E S ................................................................................................................. 1 4
A P P E N DI C E S ......................................................................................................................... 1 4
P R O T O C O L  S U M M A R Y....................................................................................................... 1 5
S C H E D U L E O F A C TI VI TI E S F O R R U N -I N A N D B LI ND E D T R E A T M E N T S ................ 2 4
S C H E D U L E O F A C TI VI TI E S F O R R E S C U E T R E A T M E N T – F L A R E A T 
S C H E D U L E D O R U N S C H E D U L E D VI SI T ..................................................................... 3 2
1. I N T R O D U C TI O N ............................................................................................................... 3 6
1. 1. Mec ha nis m of Acti o n/I n di cati o n............................................................................. 3 6
1. 2. Bac k gr o u n d a n d Rati o nale ...................................................................................... 3 7
1. 2. 1. Dr u g De vel o p me nt a n d Rati o nale ..............................................................3 7
1. 2. 2. At o pic Der matitis ........................................................................................ 3 7
1. 2. 3. N o n -Cli nical a n d P hase 1 Data ................................................................... 4 0
1. 2. 4. P hase 2 b i n A D ( B 7 4 5 1 0 0 6) ....................................................................... 4 0
1. 3. S u m mar y  of P F-0 4 9 6 5 8 4 2 Cli nical P har mac o ki netics ........................................... 4 1
1. 4. P o p ulati o n P har mac o ki netics .................................................................................. 4 2
1. 5. S u m mar y  of Be nefits a n d Ris ks.............................................................................. 4 2
1. 6. D ose Selecti o n Rati o nale ........................................................................................ 4 2
2. S T U D Y O BJ E C TI V E S A N D E N D P OI N T S ....................................................................... 4 3
3. S T U D Y D E SI G N ................................................................................................................. 4 6
4. S U BJ E C T E LI GI BI LI T Y C RI T E R IA................................................................................. 4 9
4. 1. I ncl usi o n Criteria ..................................................................................................... 4 9
4. 2. E xcl usi o n Criteria ....................................................................................................5 1
4. 3. Ra n d o mi zati o n Criteria ........................................................................................... 5 6
4. 4. L ifest yle Re q uire me nts ........................................................................................... 5 6
4. 4. 1. C o ntrace pti o n ..............................................................................................5 7
4. 4. 2. Vacci ne a n d E x p os ure t o I nfecti o ns G ui deli nes ......................................... 5 9
4. 4. 2. 1. S u bject S pecific Rec o m me n dati o ns .......................................... 5 9
4. 4. 2. 2. G ui da nce Re gar di n g H o use h ol d C o ntact Vacci ne -Relate d 
E x p os ure ............................................................................................5 9
4. 4. 3. S ur ger y ........................................................................................................ 5 9
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4. 5. S p o ns or’s Q ualifie d Me dical Pers o n nel ..................................................................6 0
5. S T U D Y T R E A T M E N T S .....................................................................................................6 0
5. 1. All ocati o n t o Treat me nt ................................ ..........................................................6 1
5. 2. Resc ue Treat me nt ....................................................................................................6 1
5. 2. 1. G ui deli nes f or T o pical Resc ue Treat me nt ..................................................6 2
5. 3. Brea ki n g t he Bli n d ..................................................................................................6 3
5. 4 . S u bject C o m plia nce .................................................................................................6 3
5. 5. I n vesti gati o nal Pr o d uct S u p plies .............................................................................6 4
5. 5. 1. D osa ge F or m(s) a n d Pac ka gi n g ..................................................................6 4
5. 5. 2. Pre parati o n a n d Dis pe nsi n g ........................................................................6 4
5. 6. A d mi nistrati o n .........................................................................................................6 4
5. 7. I n vesti gati o nal Pr o d uct St ora ge ..............................................................................6 6
5. 8. I n vesti gati o nal Pr o d uct Acc o u nta bilit y................................ ...................................6 7
5. 8. 1. Destr ucti o n of I n vesti gati o nal Pr o d uct S u p plies........................................ 6 7
5. 9. C o nc o mita nt Treat me nt(s) .......................................................................................6 7
5. 9. 1. Per mitte d C o nc o mita nt Me dicati o ns.......................................................... 6 8
5. 9. 2. Pr o hi bite d M e dicati o ns a n d Treat me nts .....................................................6 8
6. S T U D Y P R O C E D U R E S................................ .....................................................................6 9
6. 1. Visit 1, Scree ni n g ....................................................................................................7 0
6. 2. R u n -In I n d ucti o n Treat me nt Peri o d ................................ ........................................7 2
6. 2. 1. Visit 2, Da y  1/ Wee k 0 ( Baseli ne)...............................................................7 2
6. 2. 2. Visit 3, Da y  8/ Wee k 1 (1 da y ).................................................................. 7 4
6. 2. 3. Visit 4, Da y  1 5/ Wee k 2 (1 da y )................................................................ 7 4
6. 2. 4. Visit 5, Da y  2 9/ Wee k 4 (2 da y s) ..............................................................7 5
6. 2. 5. Visit 6, Da y  4 3/ Wee k 6 (3 da y s) ..............................................................7 6
6. 2. 6. Visit 7, Da y  5 7/ Wee k 8 (3 da y s) ..............................................................7 7
6. 3. D o u ble- Bli n d Mai nte na nc e Treat me nt Peri o d ........................................................7 8
6. 3. 1. Visit 8, Da y  8 5/ Wee k 1 2 (3 da y s) Ra n d o mizati o n i nt o Mai nte na nce 
Treat me nt .........................................................................................................7 8
6. 3. 2. Visit 9, Da y  1 1 3/ Wee k 1 6 (3 da y s) ..........................................................8 0
6. 3. 3. Visit 1 0, Da y  1 9 7/ Wee k 2 8 (7 da y s) ........................................................8 1
6. 3. 4. Visit 1 1, Da y  2 8 1/ Wee k 4 0 (7 da y s) ........................................................8 2

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6. 3. 5. Visit 1 2, Da y  3 6 5/ Wee k 5 2 (3 da y s) E n d of Treat me nt ( E O T) or 
Earl y Ter mi nati o n ( E T) .................................................................................... 8 3
6. 4. F oll o w -u p Visit ....................................................................................................... 8 5
6. 4. 1. Visit 1 3, 4 Wee ks P ost E n d of Treat me nt/ Earl y  Ter mi nati o n - E n d of 
St u d y  ( ± 3 d a y s) ................................................................................................ 8 5
6. 5. Resc ue Treat me nt Peri o d ......................................................................................... 8 6
6. 5. 1. Resc ue Treat me nt - Flare Occ urri n g at a n U n pla n ne d Visit ( Resc ue 
Visit 1, Da y 1/ Wee k 0 ( 3 da y s)) .................................................................... 8 6
6. 5. 2. Resc ue Treat me nt – Visit 2, Da y  8/ Wee k 1 (1 da y )................................. 8 8
6. 5. 3. Resc ue Treat me nt – Visit 3, Da y  1 5/ Wee k 2 (1 da y )...............................8 8
6. 5. 4. Resc ue Treat me nt – Visit 4, Da y  2 9/ Wee k 4 (2 da y s) ............................. 8 9
6. 5. 5. Resc ue Treat me nt – Visit 5, Da y  4 3/ Wee k 6 (3 da y s) ............................. 9 0
6. 5. 6. Resc ue Treat me nt – Visit 6, Da y  5 7/Wee k 8 ( 3 da y s) ............................. 9 1
6. 5. 7. Resc ue Treat me nt - Visit 7, Da y  8 5/ Wee k 1 2 (3 da y s) E n d of 
Treat me nt ( E O T)/ Earl y Ter mi nati o n ( E T) .......................................................9 2
6. 5. 8. Resc ue Treat me nt - Visit 8, F oll o w - u p Visit a n d E n d of St u d y  
( ± 3 d a y s) .......................................................................................................... 9 4
6. 6. S u bject Wit h dra wal ................................................................................................. 9 5
7. A S S E S S M E N T S .................................................................................................................. 9 6
7. 1. Pre g na nc y  Testi n g................................................................................................... 9 7
7. 3. Safet y Assess me nts ................................................................................................. 9 9
7. 3. 1. V itals Si g ns................................................................................................. 9 9
7. 3. 2. Me dical Hist or y , P h ysical E xa mi nati o n, Hei ght, a n d Wei g ht .................... 9 9
7. 3. 3. C hest X -Ra y ..............................................................................................1 0 0
7. 3. 4. T u berc u l osis Testi n g................................................................................. 1 0 0
7 .3 . 5. Electr ocar di o gra m..................................................................................... 1 0 1
7. 3. 6. S pecial Safet y Assess me nt ....................................................................... 1 0 1
7. 4. S ki n T y pe Assess me nt .......................................................................................... 1 0 2
7. 5. A ssess me nt of S uici dal Ideati o n a n d Be ha vi or ..................................................... 1 0 2
7. 5. 1. C ol u m bia S uici de Se verit y  Rati n g Scale ( C-S S R S) .................................1 0 2
7. 5. 2. S uici dal Be ha vi ors Q uesti o n naire -Re vise d ( S B Q -R) ............................... 1 0 2
C CI

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7. 5. 3. Patie nt Healt h Q uesti o n naire – 8 ite ms ( P H Q - 8) ..................................... 1 0 2
7 . 6. Clin ical La b orat or y Tests......................................................................................1 0 3
7. 6. 1. Bl o o d V ol u me ...........................................................................................1 0 3
7. 6. 2. L a b orat or y Tests.......................................................................................1 0 3
7. 6. 2. 1. He patitis Testi n g ................................ .....................................1 0 5
7. 6. 2. 2. Varicella Z oster Vir us ( V Z V) I g G A nti b o d y ( A b) Testi n g ....1 0 5
7. 6. 2. 3. Baseli ne Viral Sc ree n ..............................................................1 0 6
7. 7. Efficac y  Assess me nts............................................................................................1 0 6
7. 7. 1. Rater Q ualificati o ns.................................................................................. 1 0 6
7. 7. 2. I n vesti gat or’s Gl o bal Assess me nt (I G A) ..................................................1 0 6
7. 7. 3. Ecze ma Area a n d Se verit y  In de x ( E A SI) .................................................1 0 7
7. 7. 3. 1. B o d y S urface A rea – Eff icac y ( B S A Efficac y)....................... 1 1 0
7. 7. 4. Sc ori n g At o pic Der matitis ( S C O R A D) ....................................................1 1 0
7. 8. Patie nt- Re p orte d O utc o mes ( P R Os) ......................................................................1 1 1
7. 8. 1. Pr urit us N u merical Rati n g Scale ( N R S)................................................... 1 1 2
7. 8. 2. Patie nt Gl o bal Assess me nt ( Pt G A)........................................................... 1 1 2
7. 8. 3. E ur o Q ol Q ualit y  of Life 5-Di me nsi o n 5 -Le vel Scale ( E Q - 5 D-5 L ) 
a n d E ur o Q ol Q ualit y of Life 5 - Di me nsi o n Y o ut h Scale ( E Q-5 D - Y i n 
select c o u ntries) .............................................................................................1 1 3
7. 8. 4. Der mat ol o g y  Life Q ualit y In d e x ( D L QI) a n d C hil dre n’s 
Der mat ol o g y  Life Q ualit y In de x ( C D L QI )....................................................1 1 3
7. 8. 5. Patie nt- Orie nte d Ecze ma Meas ure ( P O E M) .............................................1 1 3
7. 8. 6. H os pit al A n xiet y  a n d De pressi o n Scale ( H A D S).....................................1 1 3
7. 8. 7. Pr urit us a n d S y m pt o ms Assess me nt f or At o pic Der matitis ( P S A A D) .....1 1 4
7. 8. 8. S h ort F o r m-3 6 Healt h S ur ve y , Versi o n 2, Ac ute ( S F-3 6 v 2, Ac ute) ........1 1 4
7. 8. 9. F A CI T Fati g ue Scale ( F A CI T -F) a n d Pe diatric F A CI T -F 
( Pe ds-F A CI T -F) .............................................................................................1 1 4
7. 8. 1 0. Ast h ma C o ntr ol....................................................................................... 1 1 4
7. 9. P har m ac o ki netics ..................................................................................................1 1 5
7. 9. 1. Plas ma f or A nal ys is of P F-0 4 9 6 5 8 4 2 a n d Meta b olites ............................1 1 5
7. 9. 2. S hi p me nt of P har mac o ki netic Sa m ples ....................................................1 1 6
8. A D V E R S E E V E N T R E P O R TI N G ....................................................................................1 1 6
8. 1. R e q uire me nts .........................................................................................................1 1 6

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8. 1. 1. A d diti o nal Details o n Rec or di n g A d verse E ve nts o n t he C R F .................1 1 7
8. 1. 2. Eliciti n g A d verse E ve nt I nf or ma ti o n........................................................1 1 7
8. 1. 3. Wit h dra wal fr o m t he St u d y D ue t o A d verse E ve nts (see als o t he 
S u bject Wit h dra wal secti o n) ..........................................................................1 1 7
8. 1. 4. Ti me Peri o d f or C ollec tin g A E/ S A E I nf or mati o n ....................................1 1 8
8. 1. 4. 1. Re p orti n g S A Es t o Pfizer Safet y .............................................1 1 8
8. 1. 4. 2. Rec or di n g N o n -seri o us A Es a n d S A Es o n t he CR F ...............1 1 8
8. 1. 5. Ca usalit y  Assess me nt ...............................................................................1 1 8
8. 1. 6. S p o ns or’s Re p orti n g Re q uire me nts t o Re g ulat or y  A ut h orities................1 1 9
8. 2. Defi niti o ns................................ .............................................................................1 1 9
8. 2. 1. A d verse E ve nts .........................................................................................1 1 9
8. 2. 2. A b n or mal Test Fi n di n gs ...........................................................................1 2 0
8. 2. 3. Seri o us A d verse E ve nts ............................................................................1 2 0
8. 2. 4. H os pitalizati o n ..........................................................................................1 2 1
8. 3. Se verit y  Assess me nt ..............................................................................................1 2 2
8. 4. S pecial Sit uati o ns ..................................................................................................1 2 2
8. 4. 1. Pr ot oc ol- S pecifie d Seri o us A d verse E ve nts............................................. 1 2 2
8. 4. 2. P ote ntial Cases of Dr u g -I n d uce d Li ver I nj ur y..........................................1 2 2
8. 4. 3. E x p os ure t o t he I n vesti gati o nal Pr o d uct D uri n g Pre g na nc y  or 
Breastfee di n g, a n d Occ u pati o nal E x p os ure ...................................................1 2 4
8. 4. 3. 1. E x p os ure D uri n g Pre g na nc y ....................................................1 2 4
8. 4. 3. 2. E x p os ure D uri n g Breastfee di n g ..............................................1 2 5
8. 4 .3. 3. Occ u pati o nal E x p os ure ...........................................................1 2 5
8. 4. 4. Me dicati o n Err ors .....................................................................................1 2 6
8. 4. 4. 1. Me dicati o n Err ors ....................................................................1 2 6
9. D A T A A N A L Y SI S/ S T A TI S TI C A L  M E T H O D S.............................................................1 2 7
9. 1. Sa m ple Size Deter mi nati o n ...................................................................................1 2 7
9. 2. Efficac y  A nalys is ..................................................................................................1 2 7
9. 2. 1. A nal y sis Sets.............................................................................................1 2 7
9. 2. 2. Testi n g Pr oce d ure f or M ulti ple C o m paris o ns........................................... 1 2 8
9. 2. 3. A nal y sis of t he Pri mar y a n d Ke y Sec o n dar y E n d p oi nts...........................1 2 8
9. 2. 4. A nal y sis of Sec o n dar y E n d p oi nts.............................................................1 2 8
9. 3. Safet y A nal ys is......................................................................................................1 2 9

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9. 4. A nal y sis of P har mac o ki netic E n d p oi nts ...............................................................1 3 0
9. 5. E xter nal Data M o nit ori n g C o m mittee................................ ...................................1 3 0
9. 6. Safet y A dj u dicati o n C o m mittees ..........................................................................1 3 0
1 0. Q U A LI T Y C O N T R O L  A N D Q U A LI T Y A S S U R A N C E............................................... 1 3 1
1 1. D A T A H A N D LI N G A N D R E C O R D K E E PI N G ...........................................................1 3 1
1 1. 1. Case Re p ort F or ms ( C R F)/ Data C ollecti o n T o ols ( D C Ts)/ Electr o nic Data 
Rec or d ......................................................................................................................1 3 1
1 1. 2. Rec or d Rete nti o n................................................................................................. 1 3 2
1 2. E T HI C S ............................................................................................................................1 3 2
1 2. 1. I nstit uti o nal Re vie w B oar d/ Et hics C o m mittee ....................................................1 3 2
1 2 .2 . Et hical C o n d uct of t he St u d y ..............................................................................1 3 3
1 2. 3. S u bject I nf or mati o n a n d C o nse nt ........................................................................1 3 3
1 2. 4. Re p orti n g of Safet y I ss ues a n d Seri o us Breac hes o f t he Pr ot oc ol or I C H 
G C P .........................................................................................................................1 3 4
1 3. D E FI NI TI O N O F E N D O F T RI A L .................................................................................1 3 5
1 3. 1. E n d of Trial i n All Partici pati n g C o u ntries .........................................................1 3 5
1 4. S P O N S O R DI S C O N TI N U A TI O N C RI T E RI A ..............................................................1 3 5
1 5. P U B LI C A TI O N O F S T U D Y R E S U L T S ........................................................................1 3 5
1 5. 1 . C o m m u nicati o n of Res ults b y  Pfizer ..................................................................1 3 5
1 5. 2. P u blicati o ns b y  In vesti gat ors ..............................................................................1 3 6
1 6. R E F E R E N C E S ................................................................................................................1 3 8
L I S T O F T A B L E S
Ta ble 1.
O bjecti ves a n d E n d p oi nts .....................................................................................4 3
Ta ble 2.
I n vesti gati o nal Pr o d uct A d mi nistrati o n ................................................................6 5
Ta ble 3.
I n vesti gat or’s Gl o bal Assess me nt (I G A) Sc ore..................................................1 0 7
Ta ble 4.
Cli nical Si g n Se verit y  Sc ori n g Criteria f or t he Ecze ma Area a n d Se verity 
I n dex ( E A SI ).......................................................................................................1 0 8
Ta ble 5.
Ha n d pri nt Deter mi nati o n of B o d y S urface Area ( B S A) .....................................1 0 9
Ta ble 6.
Ecze ma Area a n d Se verit y I n de x ( E A SI) Area Sc ore Criteria...........................1 0 9
Ta ble 7.
Ecze ma Area a n d Se verit y I n de x ( E A SI) B o dy Re gi o n Wei g hti n g ...................1 0 9

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LI S T O F FI G U R E S
Fi g ure 1.
St u d y  Desi g n Sc he matic.......................................................................................4 7
A P P E N DI C E S
A p pe n di x 1. A b bre viati o ns ....................................................................................................1 4 2
A p pe n di x 2. Dia g n ostic Criteria f or At o pic Der matitis......................................................... 1 4 6
A p pe n di x 3. Pr o hi bite d C o nc o mita nt Me dicati o ns ................................................................1 4 7
A p pe n di x 4. G ui deli nes f or M o nit ori n g a n d Disc o nti n uati o n............................................... 1 4 9
A p pe n di x 5. Fitz patric k S ki n T y pe........................................................................................ 1 5 1
A p p en di x 6. Pr urit us Se verit y a n d Fre q ue nc y  ( Pr urit us N R S)..............................................1 5 2
A p pe n di x 7. Patie nt Gl o bal Assess me nt ( Pt G A) ...................................................................1 5 3
A p pe n di x 8. E ur o pea n Q u alit y of Life 5-Di me nsi o n 5 -Le vel Scale ( E Q -5 D -5 L ) a n d 
E ur o pea n Q ualit y  of Li fe 5-Di me nsi o n Y o ut h Scale ( E Q -5 D -Y i n select 
c o u ntries) ............................................................................................................1 5 4
A p pe n di x 9. Der mat ol o g y Life Q ualit y I n de x ( D L QI) a n d Ch il dre n’s Der mat ol o g y Life 
Q ualit y  In de x ( C D L QI ) ...................................................................................... 1 5 8
A p pe n di x 1 0. Patie nt- Orie nte d Ecze ma Meas ure ( P O E M) ...................................................1 6 1
A p pe n di x 1 1. H os pital A n x iet y a n d De pressi o n Scale ( H A D S) ...........................................1 6 2
A p pe n di x 1 2. Pr uri t us a n d S ym pt o ms Assess me nt f or At o pic Der matitis ( P S A A D; 
P S A A D S y m pt o m Diar y) ...................................................................................1 6 4
A p pe n di x 1 3. S h ort F or m -3 6 Versi o n 2 ( S F -3 6 v 2) ...............................................................1 6 8
A p pe n di x 1 4. F u ncti o nal Assess me nt of C hr o nic Ill ness T hera p y Fati g ue Scale 
( F A CI T-F) ...........................................................................................................1 7 4
A p pe n di x 1 5. C ol u m bia Se verit y  S uici de Rati n g Scale ( C-S S R S) f or Scree ni n g a n d 
Baseli ne Visits ....................................................................................................1 7 6
A p pe n di x 1 6. C ol u m bia Se verit y  S uici de Rati n g Scale ( C-S S R S) Si nce L ast Visit .............1 7 9
A p pe n di x 1 7. S uici de Be ha vi ors Q uesti o n naire – Re vise d ( S B Q -R) ....................................1 8 1
A p pe n di x 1 8. Patie nt Healt h Q uesti o n naire – 8 ite ms ( P H Q - 8)............................................1 8 2
A p pe n di x 1 9. Ast h ma C o ntr ol Q uesti o n naire ( A C Q) ............................................................1 8 3

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P R O T O C O L S U M M A R Y
B ac k gr o u n d a n d R ati o n ale:
At o pic der matitis ( A D), als o k n o w n as at o pic ecze ma, is a c o m m o n, c hr o nic, i nfla m mat or y
s ki n dis or der c haracterize d b y fla k y s ki n lesi o ns, i nte nse pr urit us, a n d a ge neral deteri orati o n
i n q ualit y of life.  O ver t he past 5 0 years, A D has bec o me m ore pre vale nt, es peciall y i n 
i n d ustrialize d, te m perate c o u ntries s uch as t h e U nite d St ates ( U S). 1 ,2  A D is o ne of t he m ost 
c om m o n, c hr o nic, rela psi n g c hil d h o o d der mat oses, i m pacti n g 1 5 -3 0 % of all c hil dre n i n t he 
U S a n d ma n y  ha ve disease t hat p ersists i nt o a d ult h o o d wit h a lifeti me pre vale nce of t h ose 
affecte d be yo n d c hil d h o o d re p orte d t o be 3 4 %. 8  Earlier re p orts i n dicate d t hat, i n u p t o 
7 0 % of cases, t he disease greatl y i m pr o ves or res ol ves b y  late c hil d h o o d, h o we ver m ore 
rece nt fi n di n gs s u g gest t hat disease acti vit y re mai ns ma nifest f or a pr ol o n ge d peri o d of ti me.  
Base d o n a t otal of 7 1 5 7 patie nts e nr olle d i n t he Pe diatric Ecze ma Electi ve Re gistr y  ( P E E R) 
st u d y, c o m prisi n g a t otal of 2 2, 5 5 0 pers o n - years, it was c o ncl u de d t hat sy m pt o ms ass ociate d 
wit h A D see m t o persist well i nt o t he sec o n d deca de of life a n d li kel y l o n ger. 3  At e ver y  a ge, 
m ore t ha n 8 0 % of P E E R st u d y  s u bjects ha d sy m pt o ms of A D a n d / or were usi n g me dicati o n 
t o treat t heir A D.
Of t he c urre ntl y a vaila ble t hera pies, n o ne offers a c ure; t heref ore, t he mai n ai ms of e xisti n g 
treat me nts are t o re d uce t he occ urre nce of ac ute flares, t o i ncrease t he ti me bet wee n rela pses, 
a n d to re d uce pr urit us a n d t he res ulti n g slee p dist ur ba nce. 5 ,6
N o n - me dicate d t o pical t hera pies i ncl u de e m ollie nts.  Me dicate d t o pical t hera pies f or 
m o derate t o se vere A D i ncl u de t o pical c ortic oster oi ds ( T C S ) (eg, beta met has o ne, cl o betas ol,
fl u oci n o ni de), t o pical calci ne uri n i n hi bit ors (T CI ) (e g, pi mecr oli m us, tacroli m us), a n d c oal 
tar pre parati o ns.  T C S are li mite d i n ter ms of t he treat me nt d urati o n (e g, c ortic oster oi d use is 
li mite d t o 2 t o 4 wee ks) a n d t he b o d y re gi o n of treat me nt, d ue t o c o nsiste nt s ki n t o xicities, as 
well as ha vi n g ris ks ass ociate d wit h t heir b r oa d i m m u n os u p pressi ve acti o ns. T CI  ha ve a 
li mite d r ole as a sec o n d-li ne treat me nt, d ue t o t heir li mitati o ns i n t he d urati o n a n d t he b o dy 
re gi o n of treat me nt, i n hi biti o n of t u m or s ur veilla nce i n t he s ki n, a n d safet y c o ncer ns wit h 
mali g na ncies.
C risa b or ole was a p pr o ve d as a t o pical me dicate d treat me nt i n Dece m ber 2 0 1 6 
b y  t he F o o d a n d Dr u g A d mi nistrati o n ( F D A ) f or use i n patie nts wit h mil d t o m o derate A D.  
A d diti o nal treat me nts ge nerall y reser ve d f or se vere A D i ncl u de p h ot ot hera p y (e g, ultra vi olet 
A li g ht [ U V A] wit h or wit h o ut ps orale n, ultra vi olet B li g ht [ U V B] narr o w ba n d or 
br oa d ba n d) a n d s ys te mic a ge nts (e g, c ortic oster oi ds, c ycl os p ori ne, rec o m bi na nt interfer o n 
ga m ma (I F N -), m yc o p he n olate m ofetil, met h otre xate [ M T X], azat hi o pri ne, i ntra ve n o us
i mm u n o gl o b uli n). 7
T here are a li mite d n u m ber of a p pr o ve d s ys te mic treat me nts a vaila ble f or m o derate t o se ve re 
A D, a n d, i n t he U nite d States of A meri ca ( U S A ), t he o nl y a p pr o ve d sys te mic dr u gs are 
c ortic oster oi ds a n d d u pil u ma b. D u pil u ma b , a n i njecta ble h u ma n m o n ocl o nal a nti b o d y 
tar geti n g i nterle u ki n (I L) -4 a n d - 1 3, was a p pr o ve d b y  t he F D A i n Marc h 2 0 1 7 a n d rece i ve d 
ma r keti n g a ut h orizati o n i n E ur o pe i n Se pte m ber 2 0 1 7, f or t he treat me nt of m o derate t o 
se vere A D. Treat me nt wit h s y ste mic c ortic oster oi ds has k n o w n a n d well d oc u me nte d 
a d verse effects. Treat me nt wit h d u pil u ma b has t he ris k of i njecti o n site reacti o ns , allergi c 
reacti o ns, e ye a n d e yeli d i nfla m mati o ns a n d c ol d s ores.  A n ot her li mitati o n of d u pil u ma b is 

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t he p ossi bilit y f or t he de vel o p me nt of a nti dr u g a nti b o dies, w hic h ma y res ult i n l oss of 
efficac y o ver ti me a n d t he de vel o p me nt of safety c o ncer ns s uc h as ser u m sic k ness-li ke 
reacti o ns. F urt her m ore, d u pil u ma b is deli vere d via s u bc uta ne o us i njecti o n, w hic h ma y  n ot 
be a met h o d of a d mi nistrati o n t olerate d well b y all patie nts.  D uri n g a 1 -ye ar, ra n d o mize d, 
d o u ble -bli n de d st u d y  wit h d u pil u ma b, i n t he d u pil u ma b 3 0 0 m g ev er y  2 wee ks ( mar kete d 
mai nte na nce d ose) pl us T C S gr o u p, t he esti mate d differe nce fr o m place b o of t he I n vesti gat or 
Gl o bal Assess me nt ( I G A) res p o nse rate a n d t he 7 5 % i m pr o ve me nt res p o nse rate i n t he 
Ecze ma Area a n d Se verit y I n de x (E A SI - 7 5) were 2 6 % a n d 4 6%, res pecti vel y.  T he pla ce b o 
res p o nse rate f or I G A a n d EA SI -7 5 was 1 2 % a n d 2 3 %. T he de vel o p me nt of p ote ntial 
treat ments wit h f urt her i m pr o ve me nts i n efficac y re mai ns desira ble. I n E ur o pe, c ycl os p ori ne 
is a p pr o ve d f or use i n patie nts wit h se vere AD w he n s yste mic t hera p y is re q uire d.  
C y cl os p ori ne use is ass ociate d wit h se veral u n desira ble si de effects a n d d ue t o its narr o w 
t hera pe utic i n de x, occasi o nal t hera pe utic dr u g m o nit ori n g is rec o m me n de d.  K n o w n a d verse 
effects i ncl u de i nfecti o ns, re nal t o xi cit y, h e pat ot o xicit y, s ki n mali gna ncies, l y m p h o ma a n d 
ot her mali g na ncies.
T he pre d o mi na nt u n met me dical nee d t he n is f or a n oral t hera p y wit h a n acce pta ble safet y 
pr ofile, f or l o n g-ter m use, w hic h is effecti ve f or m o derate t o se vere A D. Patie nts wit h 
m o d erate to se vere A D re q uire ot her s yste mic treat me nt o pti o ns be yo n d t h ose w hic h are 
c urre ntl y a p pr o ve d. P F -0 4 9 6 5 8 4 2 is a n oral ta blet, pr o vi di n g a m ore c o n ve nie nt r o ute of 
a d mi nistrati o n c o m pare d wit h t he s u bc uta ne o us i njecti o n re q uire d f or d u pil u ma b a n d s o it 
d o es n ot ha ve t he p ote ntial ris k of i njecti o n site reacti o ns.  T he l o n ger half- life of d u pil u ma b 
als o mea ns t hat it ma y ta ke a relati vel y l o n g peri o d of ti me f or s o me u n desira ble 
p har mac o d y n a mic effects (e g, treat me nt -relate d a d verse e ve nt [ A E]) t o s ubsi de after its 
disc o nti n uati o n . I n t his res pect, t he be nefit of a s h orter half-life wit h a ge nts s uc h as 
P F -0 4 9 6 5 8 4 2 is t hat a n A E ma y  p ote ntiall y res ol ve m ore ra pi dl y t ha n is t he case wit h 
d u pil u ma b.  U nli ke d u pil u ma b, P F -0 4 9 6 5 8 4 2 is a s mall m olec ule a n d t here is n o a ntici pate d 
i m m u n oge nicit y f or P F -0 4 9 6 5 8 4 2, a n d s o it is u nli kel y  t o ge nerate a nti dr u g a nti b o dies.
K e y c yt o ki nes i m plicate d i n t he pat h o p h ysi ol o g y of A D i ncl u de I L- 4, I L- 5, I L- 1 3, I L- 3 1,
a n d I F N -, re q uire Ja n us ki nase 1 (J A K 1) f or si g nal tra ns d ucti on ; t his s u g gests t hat selecti ve
J A K 1 i n hi bit ors t hat m o d ulate t he acti vit y of t hese c yt o ki nes re prese nt a c o m pelli n g
a p pr oac h t o t he treat me nt of i nfla m mat or y s ki n diseases s uc h as A D. 7
P F - 0 4 9 6 5 8 4 2 is a n orall y b ioa vaila ble s mall m olec ule t hat selecti vel y i n hi bits J A K 1 b y
bl oc ki n g t he a de n osi ne tri p h os p hate ( A T P) bi n di n g site. P F -0 4 9 6 5 8 4 2 has a hi g h de gree of
selecti vit y i n vitr o a gai nst ot her ki nases: 2 8-f ol d selecti vit y o ver Ja n us ki nase 2 (J A K 2), 
> 3 4 0 -f ol d o ver Ja n us ki nase 3 (J A K 3) a n d 4 3- f ol d o ver t yr osi ne ki nase 2 ( T Y K 2), as well as 
a g o o d selecti vit y pr ofile o ver t he br oa der ra n ge of h u ma n ki nases. T he selecti ve i n hi biti o n 
of J A K 1 will lea d t o m o d ulati o n of m ulti ple c y t o ki ne pat h wa ys i n v ol ve d i n t he 
pat h o p h ys i ol o g y of A D, i ncl u di n g I L-4, I L-5, I L -1 3, I L -3 1 a n d I F N -.  Data fr o m a P hase 2 b 
pr o of of c o nce pt ( P O C) st u d y  ( B 7 4 5 1 0 0 6) t hat e val uate d s u bjects wit h m o derate t o se vere 
A D ha ve s h o w n p ositi ve efficac y, as well as a n acce pta ble safet y pr ofile, s ufficie n t t o s u p p ort 
f urt her cli nical de vel o p me nt i n a lar ger P hase 3 pr o gra m.  St u d y  B 7 4 5 1 0 1 4 will i n vesti gate 
t he ti me t o l oss of res p o nse t o P F- 0 4 9 6 5 8 4 2 i n s u bjects wit h m o derate t o se vere A D 
f oll o wi n g a cli nical res p o nse t o o pe n-la bel i n d ucti o n treat ment wit h P F- 0 4 9 6 5 8 4 2.  S u bjects 

P F- 0 4 9 6 5 8 4 2
B 7 4 5 1 0 1 4
Fi nal P r otoc ol A me n d me nt 5, 2 8 Oct o ber 2 0 1 9
P FI Z E R C O N FI D E N TI A L
Pa ge 1 7
w h o e x perie nce a l oss of res p o nse de n ote d as flare ( per pr ot oc ol defi niti o n) will recei ve 
resc ue treat me nt wit h P F-0 4 9 6 5 8 4 2 i n c o m bi nati o n wit h t o pical t hera p y per sta n dar d of care . 
O bjecti ves a n d E n d p oi nts 
Pri m ar y O bjecti v e:

T o e va l uate a n d c o m pare t he mai nte na nce of effect of t w o d oses of P F-0 4 9 6 5 8 4 2 
( 2 0 0 m g a n d 1 0 0 m g o nce dail y  [ Q D]) a n d place b o i n s u bjects a ge d 1 2 a n d a b o ve 
wit h m o derate t o se vere at o pic der matitis w h o res p o n d t o a n i nitial o pe n- la bel r u n-i n 
treat me nt of 2 0 0 m g P F -0 4 9 6 5 8 4 2 Q D.
Sec o n d ar y O bjecti ves:

T o e val uate a n d c o m pare t he effect of P F -0 4 9 6 5 8 4 2 o n a d diti o nal efficac y  e n d p oi nts 
a n d patie nt -re p orte d o utc o mes o ver ti me i n s u bjects a ge d 1 2 years a n d ol der wit h 
m o derate t o se vere at o pic der matitis.

T o asse ss t he efficac y of o pe n-la bel resc ue treat me nt c o nsisti n g of 2 0 0 m g  
P F - 0 4 9 6 5 8 4 2 i n c o m bi nati o n wit h t o pical t hera p y per sta n dar d of care i n cases of 
flare ( per pr ot oc ol defi niti o n).
S afet y O bjecti ve:

T o ass ess t he safet y a n d t olera bilit y of P F -0 4 9 6 5 8 4 2 d ur i n g o pen- la bel a n d 
d o u ble -bli n d treat me nt i n s u bjects a ge d 1 2 a n d o ver wit h m o derate t o se vere A D.
P h ar m ac o ki netic O bjecti ve: 

T o e val uate t he p har mac o ki netics ( P K) of P F -0 4 9 6 5 8 4 2 a n d its meta b olites i n 
s u bjects a ge d 1 2 ye ars a n d ol der wit h m o derate t o se v ere at opic der matitis f oll o wi n g 
1 2 wee ks of mai nte na nce treat me nt.
 
 
Pri m ar y E n d p oi nt
1.
L oss of res p o nse re q uiri n g resc ue treat me nt will be e val uate d a n d c o m pare d a m o n g
gr o u p s d uri n g t he bli n de d treat me nt peri o d.  L oss of res p o nse is de n ote d as flare a n d 
is defi ne d as a l oss of at least 5 0 % of t he Ecze ma Area a n d Se verit y I n de x ( E A SI) 
res p o nse at Wee k 1 2 a n d a n I n vestigat or’s Gl o bal Assess me nt (I G A) sc ore of 2 or 
hi g her.
C CI

P F- 0 4 9 6 5 8 4 2
B 7 4 5 1 0 1 4
Fi nal P r otoc ol A me n d me nt 5, 2 8 Oct o ber 2 0 1 9
P FI Z E R C O N FI D E N TI A L
Pa ge 1 8
Ke y Se c o n d ar y E n d p oi nt
1.
L oss of res p o nse base d o n a n I G A sc ore of 2 or hi g her.
Sec o n d ar y E n d p oi nts
Cli nic al Effic ac y Assess me nts:
1.
Res p o nse base d o n t he I G A (sc ore of 0 or 1 a n d a re d ucti o n of ≥2 p oi nts) at all 
sc he d ule d ti me p oi nts. 
2.
Res p o nse base d o n E A SI t otal sc ore ( E A SI-5 0, E A SI -7 5, E A SI -9 0, a n d E A SI -1 0 0) at 
all sc he d ule d ti me p oi nts.
3.
Res p o nse base d o n ac hie vi n g 4 p oi nt i m pr o ve me nt i n t he se verit y  of pr urit us 
N u merical Rati n g Scale ( N R S) fr o m baseli ne at all sc he d ule d ti me p oi nts.
4.
Perce nt c ha n ge fr o m baseli ne i n perce nt B o d y S urface Area ( B S A) at all sc he d ule d 
ti me p oi nts.
5.
Perce nt c ha n ge fr o m baseli ne i n S C O Ri n g At o pic Der matitis ( S C O R A D) s u bjecti ve 
asses s me nts of itc h a n d slee p l oss at all sc he d ule d ti me p oi nts. 
6.
Res p o nse base d o n ac hie vi n g a 5 0 % a n d 7 5 % i m pr o ve me nt i n S C O R A D 
( S C O R A D-5 0, S C O R A D -7 5) fr o m baseli ne at all sc he d ule d ti me p oi nts.
Cli nic al Effic ac y Assess me nts i n S u bjects Re q uiri n g Resc ue Tre at me nt:
1.
Res p o nse base d o n t he I G A at t he e n d of resc ue t hera py. 
2.
Res p o nse base d o n t he E A SI  t otal sc ore at t he e n d of resc ue t hera p y. 
3.
Res p o nse base d o n ac hie vi n g 4 p oi nt i m pr o ve me nt i n t he se verit y  of pr urit us 
N u merical Rati n g Scale ( N R S) at t he e n d of r esc ue t hera p y relati ve t o t he start of 
resc ue t hera py baseli ne va l ue.
4.
Perce nt c ha n ge i n perce nt B o d y S urface Area ( B S A) at t he e n d of resc ue t hera p y 
relati ve t o t he start of resc ue t hera py baseli ne val ue .
5.
Perce nt c ha n ge i n S C O R A D s u bjecti ve assess me nts of itc h a n d slee p l oss at t he e n d 
of resc ue t hera p y rela ti ve t o t he start of resc ue t hera p y baseli ne val ue .
6.
Res p o nse base d o n ac hie vi n g a 5 0 % a n d 7 5 % i m pr o ve me nt i n S C O R A D 
( S C O R A D-5 0, S C O R A D- 7 5) at t he e n d of resc ue t hera p y relati ve t o t he start of 
resc ue thera p y baseli ne val ue .

P F- 0 4 9 6 5 8 4 2
B 7 4 5 1 0 1 4
Fi nal P r otoc ol A me n d me nt 5, 2 8 Oct o ber 2 0 1 9
P FI Z E R C O N FI D E N TI A L
Pa ge 1 9
P atie nt -Re p orte d O utc o mes i n All S u bjects:
1.
Res p o nse base d o n ac hie vi n g Pt G A sc ore of clear ( 0) or al m ost clear ( 1); a n d a 
re d ucti o n fr o m baseli ne of ≥2 p oi nts at all sc he d ule d ti me p oi nts (a m o n g s u bjects 
wit h a sc ore ≥2 at baseli ne) .
2.
C ha n ge fr o m baseli ne i n Der mat ol o g y  Life Q ualit y In de x ( D L QI) or C hil dre n’s 
D L QI ( C D L QI) at all sc he d ule d ti me p oi nts. 
3.
C ha n ge fr o m baseli ne i n H os pital A n xiet y  De pressi o n Scale ( H A D S) at all sc he d ule d 
ti me p oi nts.
4.
C ha n ge fr o m baseli ne i n Patie nt Orie nte d Ecze ma Meas ure ( P O E M) at all sc he d ule d 
ti me p oi nts.
5.
C ha n ge fr o m baseli ne i n t he Pr urit us a n d S y m pt o ms Assess me nt i n At o pic Der matitis 
( P S A A D) at all sc he d ule d ti me p oi n ts.
S afet y E n d p oi nts:
1.
I nci de nce of treat me nt e mer ge nt a d verse e ve nts.
2.
I nci de nce of Seri o us A d verse E ve nts ( S A E)s a n d A d verse E ve nts ( A E)s lea di n g t o 
disc o nti n uati o n.
3.
I nci de nce of cli nical a b n or malities a n d c ha n ge fr o m baseli ne i n cli nical la b orat or y  
val ues , electr ocar di o gra m ( E C G) meas ure me nts a n d vital si g ns.
P h ar m ac o ki netic E n d p oi nt:
1.
P o p ul ati o n P K c haracterizati o n i n s u bjects a ge d 1 2 ye ars ol d a n d a b o ve wit h 
m o derate t o se vere at o pic der matitis. 
 
C CI

P F- 0 4 9 6 5 8 4 2
B 7 4 5 1 0 1 4
Fi nal P r otoc ol A me n d me nt 5, 2 8 Oct o ber 2 0 1 9
P FI Z E R C O N FI D E N TI A L
Pa ge 2 0
St u d y Desi g n
T his is a ra n d o mize d, res p o n der-e nric he d, d o u ble- bli n d, place b o -c o ntr olle d , P hase 3 
wit h dra wal trial t o e val uate t he efficac y  a n d safet y of P F-0 4 9 6 5 8 4 2 m o n ot hera p y i n s u bjects 
a ge d 1 2 ye ars a n d ol der wit h m o derate t o se vere A D as defi ne d per t he i ncl usi o n criteria a n d 
a b o d y wei g ht 4 0 k g.  A d olesce nt s u bjects bel o w t he le gal a g e of maj orit y (legal 
a d ult h o o d), i n t he s u bject’s c o u ntr y  ca n o nl y e nr oll i n t his st u d y if i nstr ucte d b y t he s p o ns or 
a n d a p pr o ve d b y t he c o u ntr y’s re g ulat or y/ healt h a ut h orit y.  If t hese a p pr o vals ha ve n ot bee n 
gra nte d, o nl y s u bjects t he le gal a ge of maj ority (le ga l a d ulth o o d), i n t he s u bject’s c o u ntr y
are all o we d t o e nr oll.  F or s u bjects y o u n ger t ha n t his, t heir le gall y acce pta ble 
re prese ntati ve/pare nt(s) or le gal g uar dia n pr o vi de writte n c o nse nt a n d mi n or c hil dre n pr o vi de 
asse nt, acc or di n g t o l ocal re g ul ati o ns a n d r ules re gar di n g a bilit y t o gi ve asse nt a n d c o nse nt.  
After pr o vi di n g i nf or me d c o nse nt, s u bjects are assesse d f or st u d y eli gi bilit y at t he scree ni n g 
visit.  D uri n g t he scree ni n g peri o d, treat me nts f or A D are was he d o ut, as a p plica ble, 
acc or di n g t o eli gi bil it y re quire me nts.  -A baseli ne ( Da y 1) visit occ urs wit hi n 2 8 da y s after 
t he scree ni n g visit. 
S u bjects ma y  be re-scree ne d o nce if t he y fail t he scree ni n g e val uati o n f or reas o ns relate d t o 
i nci de ntal tra nsit or y c o n diti o ns.  S u bjects f or w h o m scree n fail ure is relate d t o faili n g t he 
dise ase se verit y (i ncl u di n g e xte nt of disease) i ncl usi o n criteri o n a n d w h o s u bse q ue ntl y 
e x perie nce w orse ni n g A D, w hic h i n t he i n vesti gat or’s j u d ge me nt w o ul d ma ke t he m eli gi ble 
f or partici pati o n, ma y be c o nsi dere d f or re-scree ni n g.  S uc h cases s h o ul d be disc usse d wit h 
t he Pfizer Me dical M o nit or ( or desi g nee) t o deter mi ne if re-scree ni n g is a p pr o priate.
T he trial c o nsists of a n o pe n -la bel r u n-in peri o d t o deter mi ne res p o n der stat us t o a n i nitial 
i n d ucti o n treat me nt wit h P F-0 4 9 6 5 8 4 2 ( 2 0 0 m g , Q D), a ra n d o mize d, place b o-c o ntr olle d, 
d o u ble -bli n de d P F - 0 4 9 6 5 8 4 2 mai nte na nce treat me nt peri o d, a n d a 4- wee k u ntreate d 
f oll o w-u p safet y peri o d.  S u bjects w h o meet t he pr ot oc ol defi niti o n of flare d uri n g bli n de d 
treat me nt e nter a n o pe n-label resc ue treat me nt peri o d.
E nr olle d s u bjects i nitiate t he 1 2 -wee k, o pe n -la bel r u n-i n peri o d t o i de ntif y res p o n ders w h o 
ha ve a p ositi ve cli nical res p o nse t o i n d ucti o n treat ment wit h 2 0 0 m g P F -0 4 9 6 5 8 4 2 Q D.  
Res p o n der criteri a are defi ne d as a) ac hie vi n g a n I G A of clear ( 0) or al m ost clear ( 1) ( o n a 
5 - p oi nt scale), b) a re d ucti o n fr o m I G A baseli ne of 2 p oi nts, a n d c) reac hi n g a n E A SI - 7 5 
res p o nse c o m pare d t o baseli ne.  Baseli ne is defi ne d as t he I G A sc ore a n d E A SI sc ore 
o btai ne d pri or t o d osi n g o n Da y 1.  S u bjects meeti n g all of t he res p o n der criteria ma y  be 
eli gi ble f or ra n d o mizati o n. 
S u bjects w h o d o n ot reac h t he res p o nse t hres h ol d r e q uire d f or ra n d o mizati o n are declare d 
n o n -res p o n ders after c o m pleti o n of t he o pe n la bel r u n -i n peri o d.  N o n-res p o n ders are not 
eli gi ble f or ra n d o mizati o n i n t he B 7 4 5 1 0 1 4 st u d y , b ut ma y c h o ose t o e nr oll i nt o t he 
P F -0 4 9 6 5 8 4 2 L o n g Ter m E xte nsi o n ( L T E) st u d y  B 7 4 5 1 0 1 5 pr o vi di n g t he y  re mai n eli gi ble; 
ot h er wise t he y are per ma ne ntl y disc o nti n ue d fr o m treat me nt a n d e nter t he 4-wee k u ntr eate d 
f oll o w- u p peri o d i n B 7 4 5 1 0 1 4.

P F- 0 4 9 6 5 8 4 2
B 7 4 5 1 0 1 4
Fi nal P r otoc ol A me n d me nt 5, 2 8 Oct o ber 2 0 1 9
P FI Z E R C O N FI D E N TI A L
Pa ge 2 1
S u bjects wit h a p ositi ve cli nical res p o nse t o P F- 0 4 9 6 5 8 4 2 i n d ucti o n treat me nt at t he e n d of 
t he 1 2 -wee k o pe n -la bel r u n-i n peri o d e nter a 4 0 wee k, d o u ble -bli n d, mai nte na nce treat me nt 
peri o d i n w hic h t he y are ra n d o mize d i n t o 1 of 3 treat me nt ar ms i n a 1: 1: 1 rati o: 
1.
1 0 0 m g P F -0 4 9 6 5 8 4 2 Q D;
2.
2 0 0 m g P F -0 4 9 6 5 8 4 2 Q D; 
3.
Place b o.
Ra n d o mizati o n is stratifie d b y  a ge cate g or y, ie, < 1 8 years a n d 1 8 ye ars.  Eli gi ble s u bjects 
m ust ha ve a d oc u me nte d hist or y  of i na de q uate res p o nse wit h t o pical A D me dicati o ns or ha ve 
re q uire d sys te mic t hera pies f or c o ntr ol of t heir disease.
Me dicate d t o pic al a n d/ or s yste mic sta n dar d of care t hera pies are n ot all o we d d uri n g t he 
o pe n -la bel r u n-i n a n d bli n de d treat me nt peri o ds. Me dicate d t o pical t hera p y is defi ne d as a 
t o pical pr o d uct t hat c o ntai ns a n acti ve p har mace utical i n gre die nt i n dicate d f or t he treat me nt 
of A D (irres pecti ve of w het her it is a vaila ble as a n o ver- t he-c o u nter [ O T C] or prescri pti o n 
o nl y  pr o d uct).
F oll o wi n g c o m pleti o n of 4 0 wee ks of bli n de d tr eat me nt, all s u bjects are assesse d f or 
eli gi bilit y t o e nter t he P F-0 4 9 6 5 8 4 2 L T E st u d y  B 7 4 5 1 0 15.  If a s u bject disc o nti n ues 
pre mat urel y or is n ot eli gi ble or willi n g t o parti ci pate i n B 7 4 5 1 0 1 5, t he n t he s u bject e nters 
t he 4- wee k u ntreate d f oll o w-u p peri o d i n B 7 4 5 1 0 1 4.
D uri n g t he bli n de d treat me nt peri o d, s u bjects meeti n g t he pr ot oc ol defi niti o n of fl are e nter 
a n o pe n-la bel resc ue peri o d d uri n g w hic h t he y recei ve a n ot her 1 2-wee k c o urse of 2 0 0 m g  
P F - 0 4 9 6 5 8 4 2 Q D wit h t o pical t hera py per l ocal sta n dar d of care ( S O C).  I n t his st u d y, flare 
re q uiri n g resc ue treat me nt is defi ne d as a l oss of at least 5 0 % o f t he E A SI res p o nse at 
Wee k
1 2 a n d a n I G A sc ore of 2 or hi g her.  F or e xa m ple, if a s u bject has a t otal E A SI sc ore of 
4 0 at baseli ne a n d a sc ore of 1 0 at Wee k 1 2 (a c hie vi n g E A SI- 7 5 t o be a res p o n der at 
ra n d o mizati o n), t he E A SI res p o nse is -3 0.  T o meet t he defi niti o n of flare, t he t otal E A SI  
sc ore f or t his s u bject w o ul d ha ve t o g o u p by at least 1 5 ( 5 0 % of -3 0) fr o m Wee k 1 2, w hic h 
c o m p utes t o a t otal E A SI sc ore of at least 2 5, t his i n a d diti o n t o a n IG A sc ore of 2.
After c o m pleti n g t he f ull 1 2- wee k resc ue p eri o d, s u bjects ma y e nter t he L T E st u d y 
B 7 4 5 1 0 1 5, if eli gi ble.  S u bjects disc o nt i n ui n g earl y fr o m treat me nt or w h o are ot her wise 
i neli gi ble f or t he L T E st u d y e nter t he 4 wee k u ntreate d f oll o w - u p peri o d i n B 7 4 5 1 0 1 4.
A n i n vesti gat or ca n te m p oraril y i nterr u pt d osi n g f or u p t o a ma xi m u m of 2 8 c o nsec uti ve da ys 
f or a s u bject, f or safety rea s o ns or w hile m o nit ori n g a b n or mal la b orat or y tests if t he 
i n vesti gat or j u d ges t hat t his is necessar y. T he i n vesti gat or s h o ul d use t heir j u d ge me nt wit h 
re gar d t o u nsc he d ule d visits/la b orat or y/cli nical assess me nts re q uire d t o m o nit or t he s u bject 
d uri n g t his ti me-fra me. If wit hi n t his ti mefra me t he i n vesti gat or j u d ges t hat it is safe t o 
restart d osi n g, t he n t he s u bject ma y  restart i n vesti gati o nal pr o d uct. If t he i n vesti gat or j u dges 
t hat it is n ot safe t o restart d osi n g wit hi n t his ti mefra me t he n t he s u bject m ust be per ma ne ntl y 
disc o nti n ue d fr o m treat me nt, ha ve a n E n d of Treat me nt visit a n d e nter t he 4 -wee k f oll o w - u p 

P F- 0 4 9 6 5 8 4 2
B 7 4 5 1 0 1 4
Fi nal P r otoc ol A me n d me nt 5, 2 8 Oct o ber 2 0 1 9
P FI Z E R C O N FI D E N TI A L
Pa ge 2 2
peri o d.  D oses n ot ta ke n f or t he reas o ns me nti o ne d a b o ve d o n ot c o nstit ute pr ot oc ol 
de viati o ns or me dicati o n err ors a n d s h o ul d n ot be c o nsi dere d d osi n g err ors, b ut s h o ul d be 
n ote d i n t he d osi n g l o g wit h t he reas o n f or re d uce d d r u g c o ns u m pti o n clearl y descri be d. 
La b orat or y  tests are perf or me d t hr o u g h o ut t his st u d y as detaile d i n t he Sc he d ule of Acti vities . 
I n vesti gat ors f oll o w t he i nstr ucti o ns f or m ore fre q ue nt m o nit ori n g i n A p pe n di x 4 if t he 
s pecifie d la b orat or y val ues reac h t he liste d t hres h ol ds.
T he t otal st u d y  d urati o n if a s u bject d oes n ot flare is 5 2 wee ks ( 1 2 wee ks o pe n -la bel 
in d ucti o n treat me nt + 4 0 wee ks bli n de d mai nte na nce treat me nt).  T he p ote ntial ma xi m u m
st u d y d urati o n is 6 4 wee ks.  T his w o ul d o nl y  be ac hie ve d if a s u bject flare d o n t he last da y of 
t he mai nte na nce treat me nt peri o d ( 5 2 wee ks + 1 2 wee ks resc ue).  If s u bjects d o n ot i nte n d t o 
e nr oll i n t he LT E st u d y , t he a b o ve d urati o ns are e xte n de d b y + 4 w e e ks of a n u ntreate d
f oll o w-u p safet y peri o d.
A t otal of a p pr o xi matel y  1 3 7 0 s u bjects will be e nr olle d fr o m a p pr o xi matel y 2 1 8 sites l ocate d 
gl o ball y.
St u d y Tre at me nts
All e nr o lle d s u bjects recei ve 1 2 wee ks of 2 0 0 m g  P F- 0 4 9 6 5 8 4 2 Q D d uri n g t he o pe n-la bel 
r u n-in i n d ucti o n peri o d.   At t he e n d of t he 1 2 wee ks, s u bjects res p o n di n g t o treat me nt as 
descri be d a b o ve are ra n d o mize d t o recei ve d o u ble- bli n d mai nte na nce treat me nt wit h 1 0 0 m g
P F -0 4 9 6 5 8 4 2 Q D, 2 0 0 m g  P F- 0 4 9 6 5 8 4 2 Q D, or place b o ( 1: 1: 1 ra n d o mizati o n rati o) f or 
4 0 -wee ks.  I n t he eve nt of flare d uri n g bli n de d treat me nt, s u bjects e nter a 1 2 -wee k o pe n -la bel 
resc ue peri o d a n d recei ve 2 0 0 m g P F -0 4 9 6 5 8 4 2 Q D wit h c o nc o mita nt t o pical t hera p y  per 
S O C.
St atistic al Met h o ds
T he statistical o bjecti ve of t he st u d y  is t o c haracterize t he l oss of res p o nse wit h eac h 
ra n d o mize d gr o u p after ac hie vi n g res p o nse at Wee k 1 2 f oll o wi n g o pe n-la bel treat me nt wit h 
2 0 0 m g P F - 0 4 9 6 5 8 4 2 Q D.
A t otal of 6 0 0 s u bjects wit h 2 0 0 recei vi n g 1 0 0 m g P F -0 4 9 6 5 8 4 2 Q D, 2 0 0 recei vi n g 2 0 0 m g  
P F -0 4 9 6 5 8 4 2 Q D, a n d 2 0 0 recei vi n g plac e b o ( 1: 1: 1 ra n d o mizati o n rati o) will pr o vi de 
9 4 % p o wer t o detect a rati o of me dia n ti me t o flare of at least 1. 5 ti mes bet wee n eit her d ose 
of P F - 0 4 9 6 5 8 4 2 ( 1 0 0 m g or 2 0 0 m g) a n d place b o.  T he T y pe I err or rate is ass u me d t o be 
5 % ( 2-si de d).  Ass u mi n g base d o n pri or data, t hat a b o ut 4 4 % of s u bjects w o ul d meet t he 
pr ot oc ol -defi ne d criteria t o be a res p o n der at Wee k 1 2, a p pr o xi matel y  1 3 7 0 s u bjects w o ul d 
nee d t o e nter t he o pe n la bel r u n- i n peri o d of t he st u d y t o e ns ure t hat 6 0 0 s u bjects are 
a vaila ble f or ra n d o mi zati o n. 
T here are si x ke y  h yp ot heses t o be teste d f or eac h pair wise c o m paris o n bet wee n t w o 
P F -0 4 9 6 5 8 4 2 d oses ( 2 0 0 m g Q D a n d 1 0 0 m g Q D) a n d place b o, f or t he pri mar y  a n d ke y 
sec o n dar y e n d p oi nts.  F or t hese hy p ot heses, t he fa mil y wise T y pe-I err or rate will b e str o n gl y 
c o ntr olle d at 5 % usi n g a se q ue ntial, gate kee pi n g pr oce d ure. 

P F- 0 4 9 6 5 8 4 2
B 7 4 5 1 0 1 4
Fi nal P r otoc ol A me n d me nt 5, 2 8 Oct o ber 2 0 1 9
P FI Z E R C O N FI D E N TI A L
Pa ge 2 3
F or a nal y sis of t he pri mar y a n d ke y sec o n dar y e n d p oi nt s, a c o m bi nati o n of gra p hical a n d 
a nal yt ical met h o ds will be use d.  T he ti me (i n wee ks) t o pr ot oc ol -defi ne d flare will be use d 
t o e val uate t he pri mar y e n d p oi nt w hile t he ti me (i n wee ks) t o ac hie ve a n I G A sc ore of 
2 will be use d f or t he ke y sec o n dar y  e n d p oi nt.  S u bjects w h o d o n ot rep ort a n e ve nt 
( pr ot oc ol-defi ne d flare or I G A 2) or disc o nti n ue t he st u d y  d uri n g t he d o u ble-bli n d 
ra n do mize d peri o d will ha ve t heir ti me t o e ve nt ce ns ore d at t heir last k n o w n visit i n t his 
peri o d.  Ka pla n -Meier c ur ves will be use d t o dis pla y  t he ti me t o e ve nt a n d re p ort t he me dia n 
ti me t o e ve nt a m o n g t he t hree ra n d o mize d treat me nt gr o u ps .  T he l o g-ra n k test will be use d 
t o c o m pare t hese c ur ves.  Pr o p orti o ns of s u bjects wit h an e ve nt a n d c o nfi de nce i nter vals will 
als o be re p orte d b y ra n d o mize d treat me nt gr o u p.
I n ge neral, bi nar y e n d p oi nts will be a nal yze d usi n g t he ( C oc hra n -Ma ntel -Hae nszel ) test 
a dj uste d b y  ra n d o mizati o n strata (a ge gr o u ps) a n d baseli ne disease se verit y.   T he differe nce 
bet wee n treat me nt gr o u ps i n t he pr o p orti o n of s u bjects ac hie vi n g a res p o n se al o n g wit h its 
9 5 % c o nfi de nce i nter val ( usi n g t he n or mal a p pr o xi mati o n f or t he d iffere nce i n bi no mial 
pr o p orti o ns) will be re p orte d. 
I n ge neral, f or c o nti n u o us e n d p oi nts, a mi xe d -effect m o del wit h re peate d meas ures ( M M R M) 
will be use d.  T his m o del will i ncl u de t he fact ors (fi xe d effects) f or treat me nt gr o u p, 
ra n d o mizati o n strata (a ge gr o u ps) a n d bas eli ne disease se verit y , visit, treat me nt-b y -visit 
i nteracti o n, a n d rele va nt baseli ne val ue.  Wit hi n t he fra me w or k of M M R M, differe nces 
bet wee n gr o u ps will be teste d usi n g esti mates fr o m t he M M R M m o del.
All s u bjects w h o recei ve i n vesti gati o n al pr o d uct (safe t y p o p ulati o n) will be i ncl u de d i n t he 
safety a nal yses.  All t he safet y data will be s u m marize d descri pti vel y t hr o u g h a p pr o priate 
data ta b ulati o ns, descri pti ve statistics, cate g orical s u m maries, a n d gra p hical prese ntati o ns.

P F- 0 4 9 6 5 8 4 2
B 7 4 5 1 0 1 4
Fi nal P r otoc ol A me n d me nt 5, 2 8 Oct o ber 2 0 1 9
P FI Z E R C O N FI D E N TI A L
Pa ge 2 4
S C H E D U L E O F A C T I VI TI E S F O R R U N-I N AN D B LI N D E D T R E A T M E N T S
T he sc he d ule of acti vities ta ble pr o vi des a n o ver vie w of t he pr ot oc ol visits a n d pr oce d ures.  Refer t o t he S T U D Y P R O C E D U R E S a n d 
A S S E S S M E N T S secti o ns of t he pr ot oc ol f or detaile d i nf or mati o n o n eac h pr oce d ure a n d assess me nt re q uire d f or c o m plia nce wit h t he 
pr ot oc ol. 
T he i n vesti gat or ma y  sc he d ule visits ( u n pla n ne d visits) i n a d diti o n t o t h ose liste d o n t he sc he d ule of acti vities ta ble, i n or der t o 
c o n d uct e val uati o ns or assess me nts re q uire d t o pr otect t he well -bei n g of t he s u bject.
Visit I de ntifier
D a y -2 8 a
Sc ree ni n g
D a y 1
Wee k 0
B aseli ne
D a y 8
Wee k 1
C all
D a y 1 5
Wee k 2
D a y 2 9
Wee k 4
D a y 4 3
Wee k 6
C all
D a y 5 7
Wee k 8
D a y 8 5
Wee k 1 2 
R a n d o mize
Res p o n ders
D a y 1 1 3 b
Wee k 1 6
D a y 
1 9 7 b
Wee k 
2 8
D a y 2 8 1 b
Wee k 4 0
D a y 3 6 5 b
Wee k 5 2 
E O T/ E T
E O S,
F oll o w -u p
Wee k 5 6/
4 Wee ks 
p ost E T
Visit 1
Visit 2
Visit 3
Visit 4
Visit 5
Visit 6
Visit 7
Visit 8  
Visi t 9
Visit 1 0
Visit 1 1
Visit 1 2
Visit 1 3
Visit Wi n d o w
N o ne
N o ne
1 D a y 1 D a y 2 D a ys 3 D a ys 3 D a ys
3 D a ys
3 D a ys 7 D a ys
7 D a ys
3 D a ys
3 D a ys
E nr oll me nt Pr oce d ure
I nf or me d c o nse ntc
X
Re gister s u bject usi n g I R T 
s yste m
X
I ncl usi o n/ E xcl usi o n Criteria
X
X
X
C -S S R S d
X
X
X
X
X
X
X
X
X
S B Q -R d
X
P H Q -8 d
X
De m o gra p hics, Me dical 
Hi st or y, T o bacc o a n d Alc o h ol 
Hist or y, At o pic Der matitis 
Disease Hist or y e
X
Re vie w Pri or/ C o nc o mita nt 
Me dicati o ns & Tre at me nts
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X
Dis pe nse e -Diar y a n d i nstr uct 
s u bjects o n use
X
Pr o vi de Patie nt E mer ge nc y 
C o ntact Car d
X
Me dic al Pr oce d ures
C o m plete P h ysical E xa m f
X
X
X
X
Tar gete d P h ysical E xa m f
X
X
X
X
X
X
X
Vital Si g ns g
X
X
X
X
X
X
X
X
X
X
X
Wei g ht/ Hei g ht
d d
X
X
X
X

P F- 0 4 9 6 5 8 4 2
B 7 4 5 1 0 1 4
Fi nal P r otoc ol A me n d me nt 5, 2 8 Oct o ber 2 0 1 9
P FI Z E R C O N FI D E N TI A L
Pa ge 2 5
Visit I de ntifier
D a y -2 8 a
Sc ree ni n g
D a y 1
Wee k 0
B aseli ne
D a y 8
Wee k 1
C all
D a y 1 5
Wee k 2
D a y 2 9
Wee k 4
D a y 4 3
Wee k 6
C all
D a y 5 7
Wee k 8
D a y 8 5
Wee k 1 2 
R a n d o mize
Res p o n ders
D a y 1 1 3 b
Wee k 1 6
D a y 
1 9 7 b
Wee k 
2 8
D a y 2 8 1 b
Wee k 4 0
D a y 3 6 5 b
Wee k 5 2 
E O T/ E T
E O S,
F oll o w -u p
Wee k 5 6/
4 Wee ks 
p ost E T
Visit 1
Visit 2
Visit 3
Visit 4
Visit 5
Visit 6
Visit 7
Visit 8  
Visi t 9
Visit 1 0
Visit 1 1
Visit 1 2
Visit 1 3
Visit Wi n d o w
N o ne
N o ne
1 D a y 1 D a y 2 D a ys 3 D a ys 3 D a ys
3 D a ys
3 D a ys 7 D a ys
7 D a ys
3 D a ys
3 D a ys
E C G ( 1 2 -lea d)k k
X
X
X
X
X
X
X
X
X
X
X
L a b or at or y Assess me nts h
He mat ol o g y i
X
X
X
X
X
X
X
X
X
X
X
C oa g ulati o n Pa nel j
X
X
X
X
X
X
X
X
X
X
X
Ser u m c he mistr y k
X
X
X
X
X
X
X
X
X
X
X
Uri nal ysis l
X
X
X
X
X
X
X
X
X
X
X
Li pi d Pa nel m
X
X
X
X
X
Ser u m F S H ( p ost -me n o pa usal) 
or Pre g na nc y Test n
X
Uri ne Pre g na nc y Test 
(c o n d ucte d at st u d y site)o
X
X  
X
X  
X  
X  
X  
X  
X  
X
HI V Testi n g q
X
He patitis B S urface A nti ge n 
( H Bs A g), He patitis B 
S urface A nti b o d y ( H Bs A b), 
He patitis B C ore A nti b o d y 
( H Bc A b), He patitis C 
A nti b o d y ( H C V A b), 
He patitis C Viral R N A ( H C V 
R N A) r
X
H B V D N A testi n g f or C hi na
a n d Tai wa n jj
X
X
X  
X  
X
Varic ella Z oster Vir us ( V Z V 
I g G A b) (a d olesce nts o nl y, if 
a p plica ble) s
X
T u berc ul osis Test t
X
X ii
C hest X -ra yh h
X
X ii
C CI

P F- 0 4 9 6 5 8 4 2
B 7 4 5 1 0 1 4
Fi nal P r otoc ol A me n d me nt 5, 2 8 Oct o ber 2 0 1 9
P FI Z E R C O N FI D E N TI A L
Pa ge 2 6
Visit I de ntifier
D a y -2 8 a
Sc ree ni n g
D a y 1
Wee k 0
B aseli ne
D a y 8
Wee k 1
C all
D a y 1 5
Wee k 2
D a y 2 9
Wee k 4
D a y 4 3
Wee k 6
C all
D a y 5 7
Wee k 8
D a y 8 5
Wee k 1 2 
R a n d o mize
Res p o n ders
D a y 1 1 3 b
Wee k 1 6
D a y 
1 9 7 b
Wee k 
2 8
D a y 2 8 1 b
Wee k 4 0
D a y 3 6 5 b
Wee k 5 2 
E O T/ E T
E O S,
F oll o w -u p
Wee k 5 6/
4 Wee ks 
p ost E T
Visit 1
Visit 2
Visit 3
Visit 4
Visit 5
Visit 6
Visit 7
Visit 8  
Visi t 9
Visit 1 0
Visit 1 1
Visit 1 2
Visit 1 3
Visit Wi n d o w
N o ne
N o ne
1 D a y 1 D a y 2 D a ys 3 D a ys 3 D a ys
3 D a ys
3 D a ys 7 D a ys
7 D a ys
3 D a ys
3 D a ys
P h ar m ac o ki netic 
P har mac o ki netic Bl o o d 
Sa m pli n g ( P ost -d ose) u
X
Tri al Tre at me nt 
Ra n d o mizati o n 
X
Dr u g Dis pe nsi n g
X
X
X
X
X
X
X
I n vesti gati o nal Pr o d uct 
Acc o u nta bilit y 
X  
X
X  
X  
X  
X  
X  
X
I n vesti gati o nal Treat me nt 
A d mi nistrati o n v
X -------------------------------------------------------------------------------------------------------------------------- X
Re vie w e Diar y t o assess 
c o m pleti o n
X  
X  
X  
X  
X  
X  
X  
X  
X  
X
Assess eli gi bilit y f or 
B 7 4 5 1 0 1 5 w
X
X
Cli nic al Assess me nts 
Fitz patric k S ki n T y pe 
Assess m e nt
X
I n vesti gat or’s Gl o bal 
Assess me nt (I G A)
X  
X
X  
X
X  
X  
X  
X  
X  
X  
X
S C O Ri n g At o pic Der matitis 
( S C O R A D)
X  
X
X  
X
X  
X  
X  
X  
X  
X  
X
Ecze ma Area a n d Se verit y 
I n de x ( E A SI)
X  
X
X  
X
X  
X  
X  
X  
X  
X  
X
T otal B o d y S urface Area 
( B S A fr o m E A SI) 
X  
X
X  
X
X  
X  
X  
X  
X  
X  
X
P atie nt -re p orte d O utc o me 
Pr urit us N u merical Rati n g 
Scale -e Diar y ( N R S) x
X ---------X  
X ---------------------X  
X
X  
X  
X  
X  
X  
X  
X
Patie nt Gl o bal Assess me nt 
( Pt G A)
X
X  
X
X  
X  
X  
X  
X  
X  
X
Der mat ol o g y Life Q ualit y 
I n de x ( D L QI or C D L QI)y
X
X  
X
X  
X  
X  
X  
X  
X  
X

P F- 0 4 9 6 5 8 4 2
B 7 4 5 1 0 1 4
Fi nal P r otoc ol A me n d me nt 5, 2 8 Oct o ber 2 0 1 9
P FI Z E R C O N FI D E N TI A L
Pa ge 2 7
Visit I de ntifier
D a y -2 8 a
Sc ree ni n g
D a y 1
Wee k 0
B aseli ne
D a y 8
Wee k 1
C all
D a y 1 5
Wee k 2
D a y 2 9
Wee k 4
D a y 4 3
Wee k 6
C all
D a y 5 7
Wee k 8
D a y 8 5
Wee k 1 2 
R a n d o mize
Res p o n ders
D a y 1 1 3 b
Wee k 1 6
D a y 
1 9 7 b
Wee k 
2 8
D a y 2 8 1 b
Wee k 4 0
D a y 3 6 5 b
Wee k 5 2 
E O T/ E T
E O S,
F oll o w -u p
Wee k 5 6/
4 Wee ks 
p ost E T
Visit 1
Visit 2
Visit 3
Visit 4
Visit 5
Visit 6
Visit 7
Visit 8  
Visi t 9
Visit 1 0
Visit 1 1
Visit 1 2
Visit 1 3
Visit Wi n d o w
N o ne
N o ne
1 D a y 1 D a y 2 D a ys 3 D a ys 3 D a ys
3 D a ys
3 D a ys 7 D a ys
7 D a ys
3 D a ys
3 D a ys
Patie nt -Orie nte d Ecze ma 
Meas ure ( P O E M)
X
X  
X
X  
X  
X  
X  
X  
X  
X
H os pital A n xiet y a n d 
De pressi o n Scale ( H A D S)
X
X  
X
X  
X  
X  
X  
X  
X  
X
Pr u rit us a n d S y m pt o ms 
Assess me nt f or At o pic 
Der matitis - e Diar y ( P S A A D) z
X ---------X  
X ----------------------------------------------------------------------------------------------------------------------------------------X
E Q -5 D -5 L (a d ults) or 
E Q -5 D -Y (a ges 1 2 -1 7 years) aa
X
X  
X
X  
X  
X  
X  
X  
X  
X
S F -3 6 v 2, Ac ute b b (a d ults)
X
X
X
X
F A CI T -F (a d ults) or 
Pe ds -F A CI T -F ( a ges 1 2-1 7 
years )c c
X
X
X  
X
Ast h ma C o ntr ol Q uesti o n naire 
( A C Q) f or all s u bjects wit h a 
pri or dia g n osis of ast h ma 
X
X
X  
X
S af et y
Seri o us a n d n o n -seri o us 
a d verse e ve nt m o nit ori n g
X  
 
 
 
 
 
 
 
 
 
 
 

X
Assess f or prese nce of flare ee
X
X
X
X
C o ntrace pti o n C hec k ff
X
X
X
X
X
X
X
X
X
X
X
X
X
Ser u m Sa m ple f or Baseli ne 
Viral Scree n g g
X

P F- 0 4 9 6 5 8 4 2
B 7 4 5 1 0 1 4
Fi nal P r otoc ol A me n d me nt 5, 2 8 Oct o ber 2 0 1 9
P FI Z E R C O N FI D E N TI A L
Pa ge 2 8
A b bre viati o ns: A C Q = Ast h ma C o ntr ol Q uesti o n naire; B S A = b o d y s urface area; C D L QI = C hil dre n’s Der mat ol o g y Lif e Q ualit y I n de x ; C-S S R S = C ol u m bia 
S uici de Se verit y Rati n g Scale; D L QI = Der m at ol o g y Life Q ualit y I n de x; E A SI = Ecze m a Area a n d Se verit y I n de x ; E C G = electr ocar di o gra m; E O S = E n d of 
St u d y; E O T = E n d of Treat me nt; E T = earl y ter mi nati o n; E Q -5 D -5 L  = E ur o Q ol Q ualit y of Life 5-Di me nsi o n 5 -Le vel Scale; E Q -5 D -Y = E ur o Q ol Q ualit y of Life 
5- Di me nsi o n, Y o ut h Scale; F A CI T -F = F u ncti o nal Assess me nt of C hr o nic Ill ness T hera p y Fati g ue Scale; F S H = f ollicle sti m ulati n g h or m o ne; 
G G T = ga m ma -gl uta m yl tra nsferase; H A D S = H os pit al A n xiet y a n d De pressi o n Scale ; H Bs A g = he patitis B s urfac e a nti ge n; H Bs A b = he pati tis B s urface 
a nti b o d y; H Bc A b = he patitis B c ore a nti b o d y; H B V D N A = he patitis B vir us de o x yri b o n ucleic aci d; H C V A b = he patitis C a nti b o d y; H C V R N A = He patitis C 
Viral R N A; He p B = He pati tis B; HI V = h u ma n i m m u n o deficie nc y vir us; H S V -1 = her pes si m ple x vir us t y pe 1; H S V 2 = her pes si m ple x vir us t y pe 2; 
I G A = I n vesti gat or’s Gl o bal Assess me nt; I g E = I m m u n o gl o b uli n E; I R T = I nteracti ve Res p o nse S yste m; L D H = Lactate de h y dr o ge nase; L L Q = l o w er li mit of 
q ua ntificati o n; M C H = mea n c or p usc u lar he m o gl o bi n; M C H C = mea n c or p usc ular he m o gl o bi n c o nce ntrati o n; M C V = mea n c or p usc ular v ol u me; N K = Nat ural 
Killer; N R S = n u merical rati n g scale; Pe ds -F A CI T -F = Pe diatric F u ncti o nal Assess me nt of C hr o nic Ill nes s T hera p y Fati g ue Scale; P H Q-8 = Patie nt Hea lt h 
Q uesti o n naire 8 ite ms ; P O E M = Patie nt -Orie nte d Ecze ma Meas ure ; P S A A D = Pr urit us a n d S y m pt o ms Assess me nt f or At o pic Der matitis; Pt G A = Patie nt Gl o bal 
Assess me nt; R B C = Re d bl o o d cell; R N A = Ri b o n uc leic aci d; S B Q-R = S uici de Be ha vi ors Q uesti o n naire -Re vise d; S C O R A D = S C O Ri n g At o pic Der matitis; 
S F -3 6 v 2 = S h ort F or m -3 6 Healt h S ur ve y Versi o n 2; V Z V = varicella z oster vir us; V Z V I g G A b = varicella z oster vir us i m m u n o gl o b uli n G a nti b o d y.
a.
D a y  relati ve t o start of st u d y treat me nt ( Da y 1).
b.
Fr o m  Da y 8 6 t hr o u g h Da y 3 6 5, if t he s u bject flares as defi ne d b y pr ot oc ol, be gi n resc ue treat me nt peri o d.  See Sc he d ule of Acti vities f or Resc ue Treat me nt . 
c.
O btai n writte n i nf or me d c o nse nt; f or s u bjects a ge d u n der t he le gal a ge of maj orit y (le gal a d ult h o o d) i n t he s u bject’s c o u ntr y, o btai n writte n i nf or me d c o nse nt 
fr o m le gall y acce pta ble re prese ntati ve/pare nt(s) or le gal g uar dia n, a n d i nf or me d asse nt fr o m t he patie nt (if a ge a p pr o priate acc or di n g t o l ocal reg ulati o ns).
d.
Site staff is t o a d mi nister t he C -S S R S, S B Q -R a n d P H Q -8 t o all s u bjects at scree ni n g a n d sc ore i m me diatel y.  S u bjects w h o ha ve rece nt or acti ve s uici dal 
i deati o n or be ha vi or or cli nicall y si g nifica nt de pressi o n will be e xcl u de d fr o m t he st u d y or disc o nti n ue d fr o m t he st u d y per Se cti o n 4. 2 , Secti o n 7. 5. 1 , 
Secti o n 7. 5. 2 a n d Secti o n 7. 5. 3 .  S u bjects meeti n g e xcl usi o nar y res ults o n t he C- S S R S, S B Q -R a n d P H Q -8 s h o ul d be e xcl u de d fr o m partici pati o n; it is 
rec o m me n de d t he s u bject’s pri mar y care p h ysicia n ( P C P) s h o ul d be i nf or me d, a n d t he s u bject referre d t o a me ntal healt h pr ofessi o nal, eit her b y t he P C P or 
t he i n vesti gat or acc or di n g t o t heir us ual practice.  P ost -scree ni n g, if t here are “ yes” a ns wers o n ite ms 4, 5 or o n a n y be ha vi oral q uestio n of t he Si nce Last 
Visit C -S S R S a ris k assess me nt b y a q ualifie d me ntal healt h pr o fessi o nal (M H P ) s h o ul d be d o ne t o deter mi ne w het her it is safe f or t he s u bject t o c o nti n ue t o 
partici pate i n t he trial.
e.
At o pic Der matitis Disease Hist or y i ncl u des c ollecti o n of details of A D: A D dia g n osis a n d d urati o n, t he use of t o pical treat me nts, s yste m ic treat me nts an d 
ot her treat me nts f or A D. 
f.
C o m plete p h ysical e xa mi nati o ns m ust be perf or me d b y t he i n vesti gat or, s u b i n vesti gat or or a q ualifie d healt h pr ofessi o nal per l ocal g ui deli nes.   C o m plete 
p h ysical e xa mi nati o ns c o nsist of assess me nts of ge neral a p peara nce; s ki n; hea d, e yes, ears, n ose a n d t hr oat ( H E E N T); m o ut h, heart; l u n gs; breast ( o pti o nal); 
a b d o me n; e xter nal ge nitalia ( o pti o nal); e xtre mities; ne ur ol o gic f u ncti o n; a n d l y m p h n o de s.  Tar gete d p h ysical e xa mi nati o ns m ust be perf or me d b y t he 
i n vesti gat or, s u b-i n vesti gat or or a q ualifie d healt h pr ofessi o nal per l ocal g ui deli nes a n d s h o ul d i ncl u de s ki n, heart, l u n gs, a n d a b d o me n a n d e xa mi nati o n of 
b o d y s yste ms w here t here are s y m pt o m c o m p lai nts b y t he s u bject.
g.
Vital Si g ns i ncl u de sitti n g bl o o d press ure, p ulse, res pirat or y rate, a n d te m perat ure meas ure d after at least 5 mi n utes of rest. 
h.
La b orat or y tests wit h a b n or mal res ults ( per Secti o n 6. 1 a n d Secti o n 7. 6. 2 ) ma y be re peate d o nce d uri n g t he scree ni n g peri o d; t he last val ue will be use d t o 
deter mi ne eli gi bilit y.

P F- 0 4 9 6 5 8 4 2
B 7 4 5 1 0 1 4
Fi nal P r otoc ol A me n d me nt 5, 2 8 Oct o ber 2 0 1 9
P FI Z E R C O N FI D E N TI A L
Pa ge 2 9
i.
H e m at ol o g y i ncl u des: He m o gl o bi n, he mat ocrit, re d bl o o d cell c o u nt a n d i n dices ( M C H, M C H C, M C V, R B C M or p h ol o g y), w hite bl o o d cells, ne utr o p hils 
( %, a bs ol ute), l y m p h oc ytes ( %, a bs ol ute), m o n oc ytes ( %, a bs ol ute), e osi n o p hils ( %, a bs ol ute), bas o p hils ( %, a bs ol ute), platel ets, retic ul oc yte c o u nt, 
ly m p h oc yte s u bse ts a n d mar kers ( T otal T cells [ C D 3 +], C D 4 + T cells [ C D 3 + C D 4 +], C D 8 + T cells [ C D 3 + C D 8 +], N K cells [ C D 3 - C D 1 6 + C D 5 6 +], 
B cells [ C D 3-C D 1 9 +) . 
j.
C oa g ulati o n pa nel i ncl u des: Acti vate d Partial T hr o m b o plasti n Ti me ( AP T T), Pr ot hr o m bi n Ti me/I nter nati o n al N or malize d Rati o ( P T/I N R).
k.
Ser u m c he mistr y i ncl u des: bl o o d urea nitr o ge n ( B U N), ser u m creati ni ne, creati ne p h os p h o ki nase, gl uc ose, Ca + +, Na +, K +, Cl -, t otal C O 2, as partate 
a mi n otra nsferase ( A S T), ala ni ne a mi n otra nsferase ( A L T), ga m ma-gl uta m yl tra nsfera se ( G G T), t otal, i n direct a n d direct bilir u bi n, al kali ne p h os p hatase, 
lactate de h y dro ge nase, uric aci d, al b u mi n a n d t otal pr otei n.
l.
Uri nal ysis i ncl u des: p H, Gl uc ose ( q ualitati ve), Pr otei n ( q ualitati ve), Bl o o d ( q ualitati ve ), Ket o nes, Nitrites, Le u k oc yte esterase, Micr osc o py a n d/ or c ult ure 
( perf or me d as a p pr o priate). 
m.
Li pi d Pa nel i ncl u des: t otal c h olester ol, l o w -de nsit y li p o pr otei n (L D L), hi g h -de nsit y li p o pr otei n ( H D L), a n d tri gl yceri des.  A mi ni m u m of 8-h o ur fasti n g is 
re q uire d f or li pi d pr ofile e val uati o n at D a y 1, Wee k 4, Wee k
1 2, Wee k 5 2 a n d E O S visits.
n.
Ser u m pre g na nc y testi n g at scree ni n g is re q uire d f or w o me n of c hil d beari n g p ote ntial i ncl u di n g a d olesce nts a ge d 1 2 years a n d ol der re gar dless of w het her 
t he y ha ve e x perie nce d me narc he.  F ollicle sti m ulati n g h or m o ne ( F S H) test t o be perf or me d at Scree ni n g t o c o nfir m p ost me n o pa usal stat us i n fe male s u bjects 
w h o ha ve bee n a me n orr heic f or at least 1 2 c o nsec uti ve m o nt hs.
o.
Uri ne pre g na nc y test m ust be perf or me d at e ver y site visit pri or t o d osi n g wit h t he i n vesti gat i o nal pr o d uct f or fe male s u bjects of c hil d beari n g p ote ntial 
i ncl u di n g a d olesce nts a ge d 1 2 years a n d ol der re gar dless of w het her t he y ha ve e x perie nce d me narc he.
 
q.
S u bjects testi n g p ositi ve f or HI V will be scree n-faile d. 
r.
H Bs A b refle x testi n g will be perf or me d o nl y if H Bs A g ne gati ve b ut H Bc A b p ositi ve.  S u bj ects w h o are p ositi ve f or H C V A b a n d H C V R N A will be
scree n-faile d. 
s.
V Z V I g G a nti b o d y testi n g is re q uire d t o c o nfir m eli g i bilit y i n a d olesce nt s u bjects w h o ha ve n ot recei ve d at least o ne d ose of a varicella vacci ne.
t.
A d oc u me nte d T B test perf or me d wit hi n 1 2 we e ks pri or t o Da y 1 is acce pta ble.   S u bjects wit h a hist or y of t u berc ul osis ma y n ot re q uire T B testi n g as per t he 
pr ot o c ol e xcl usi o n criteria i n Secti o n 4. 2 .  Perf or m T B test pr oce d ure usi n g t he Q ua nti F E R O N-T B G ol d I n T u be Tes t ( or P urifie d Pr otei n Deri vati ve).  A 
ne gati ve P P D test ca n be s u bs tit ute d f or t he Q ua nti F E R O N-T B G ol d I n -T u be test o nl y if t he ce ntral la b orat or y is u na ble t o perf or m t he 
Q ua nti F E R O N -T B G ol d I n -T u be test or ca n n ot deter mi ne t he res ults t o be p ositi ve or ne gati ve a n d t he Pfizer Me dical M o nit or a p pr o ves it o n a 
case-b y -case basis.  I n a d diti o n t o pr ot oc ol re q uire d T B testi n g, sites s h o ul d f oll o w t heir l ocal sta n dar ds f or T B stat us deter mi nati o n, w hic h ma y i ncl u de 
c hest X -r a y.  See Secti o n 7. 3. 4 . 
u.
A P K bl o o d sa m ple will be c ollecte d at 2. 0 h o urs ( 3 0 mi n) p ost d ose of o pe n -la bel st u d y dr u g ( 2 0 0 m g) at t he Wee k 1 2 visit.  F or Earl y Ter mi nati o n ( E T) 
visits, if t he s u bject disc o nti n u es bef ore Wee k 4 , d o n ot c ollect a P K sa m ple.  If t he E T visit occ urs at or after Wee k 4 a n d bef ore Wee k 1 2, c ollect a P K 
sa m ple o nl y if t he s u bject ta kes t he i n vesti gati o nal pr o d uct at t he site visit.
C CI

P F- 0 4 9 6 5 8 4 2
B 7 4 5 1 0 1 4
Fi nal P r otoc ol A me n d me nt 5, 2 8 Oct o ber 2 0 1 9
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Pa ge 3 0
v.
S u bjects s h o ul d ta ke t he me dicati o n fr o m st u d y Da ys 1 t o 3 6 5.  S u bjects will be e nc o ura ge d t o ta ke t he me dicati o n i n t he m or ni n g w he ne ver p ossi ble; 
h o we ver, at st u d y visit da ys, s u bjects are t o be i nstr ucte d t o refrai n fr o m d osi n g at h o me a n d are t o ta ke t he d ose i n t he cl i nic.  I nstr uct s u bjects re gar di n g 
pr o per st ora ge c o n diti o ns f or i n vesti gati o nal pr o d uct o n Da y 1. 
w.
S u bjects w h o are n o n res p o n ders b ut c o m plete t he 1 2 wee k r u n- i n treat me nt a n d s u bjects w h o are re p o n ders at E O T will be assesse d f or eli gi bilit y f or 
partici pati o n i n l o n g -ter m e xte nsi o n st u d y B7 4 5 1 0 1 5 as n ote d i n Secti o n 6. 3. 5 . 
x.
Pr urit us N u merical Rati n g Scale ( N R S) will be assesse d usi n g a n e Diar y dail y d uri n g t he scree ni n g peri o d a n d fr o m St u d y Da y 1 t o 1 5.  After Da y 1 5, t he 
Pr uri t us N R S will be c o mplete d o nl y o n st u d y visit da ys i n t he e Diar y.  At t he Scree ni n g v isit, site staff will dis pe nse t he electr o nic ta blet (e P R O de vice ) a n d 
re vie w i nstr ucti o ns f or c o m pleti o n of t he s u bject e Diar y f or t he N R S.  At e ver y visit, t he st u d y c o or di nat or will revie w t he e Diar y f or c o m plete ness a n d 
c o u nsel t he s u bject o n h o w t o co m p lete t he ite ms i n t he dail y e Diar y, if nee de d. 
y.
D L QI will be c o m plete d b y a d ult s u bjects o nl y.  A d olesce nts 1 2 -1 7 years of a ge will c o m plete t he C D L QI i nstea d.
z.
Pr urit us a n d S y m pt o ms Assess me nt f or At o pic Der matitis ( P S A A D) will be c o n d ucte d ( o nl y i n sel ecte d c o u ntries) t o assess t he se verit y a n d fre q ue nc y of 
pr urit us, s y m pt o ms a n d slee p c ollecte d dail y i n a s u bject e -diar y d uri n g t he scree ni n g peri o d a n d fr o m Da y 1 t hr o u g h t he E n d of St u d y  visit ( See 
Secti o n 7. 8. 7 ).  At t he Scree ni n g visit, site staff will dis pe nse t he e P R O de vice a n d re view i nstr ucti o ns f or c o m plet i o n of t he s u bject e Diar y f or t he P S A A D 
q uesti o n naire.  S u bjec ts will be as ke d t o rec or d t heir assess me nt i n t heir e Diar y o nce a day bef ore ta ki n g t he i n vesti gati o nal pr o d uct.  At e ver y visit, t he 
st u d y c o or di nat or will re view t he e Diar y f or c o m plete ness an d c o u nsel t he s u bject o n h o w t o c o m plete t he ite ms i n t he dail y e Diar y, if nee de d.
aa.
T he E ur o Q ol Q ualit y of Life 5 -Di me nsi o n 5 -Le ve l Scale ( E Q -5 D -5 L) will be c o m plete d b y a d ult s u bjects o nl y.  A d olesce nts 1 2 -1 7 y ears of a ge will 
c o m plete t he E ur o Q ol Q ualit y of Life 5 -Di me nsi o n, Y o ut h Scale ( E Q -5 D -Y) i n select c o u ntries.
b b. S F -3 6 v 2 will be c o m plete d b y a d ult s u bjects o nl y.  A d olesce nts 1 2 -1 7 y ears of a ge will n ot c o m plete t his assess me nt.
cc.
F A CI T -F will be c o m plete d b y a d ult s u bjects o nl y.  A d olesce nts 1 2 -1 7 y ears of a ge will c o m plete t he Pe ds -F A CI T -F i nstea d .
d d. Hei g ht is n ot re q uire d at t he baseli ne visit.  O nl y a d olesce nts ( 1 2 t o < 1 8 years o ld) re q uire re peate d hei g ht meas ure me nt at scree ni n g, Wee k 1 2, a n d E O T/ E T 
visits.  A d ults re q uire o ne hei g ht meas ure me nt at t h e scree ni n g visit.
ee.
Assess f or t he e mer ge nce of flare defi ne d as a l oss of at least 5 0 % of t he E A SI res p o nse at Wee k 1 2 a n d a n I G A o f 2 or hi g her.
ff.
T he c o ntrace pti o n c hec k is a n o p p ort u nit y t o c o nfir m t hat c o ntrace pti o n, if assi g ne d, is use d c o nsiste ntl y a n d c orrectl y.  It als o facilitates c o nti n ual 
reassess me nt of c hil d-beari n g p ote ntial i n w o me n.  T his all o ws f or i m ple me nti n g necessa ry c ha n ges t o c o ntrace pti o n; f or e xa m ple, i n vesti gat ors ma y nee d t o 
e ns ure alter nati ve c o ntrace pti ve met h o ds if ne w c o nc o mita nt disease c o ntrai n dicates a selecte d met h o d of c o ntrace pti o n, or if a s u bject is de m o nstra bl y n o 
l o n ger of c hil d-beari n g stat us (a s per pr ot oc ol) t he n t he y will n o l o n ger re q uire c o ntrace pti o n.  C o nti n ual reassess me nt of c o ntrace pti ve nee ds is i m perati ve.
g g. A ser u m sa m ple will be c ollecte d at baseli ne b ut a nal yze d o nl y if t he s u bject has s us pecte d varicella or her pes z oster.  I n t hat e v e nt, t he sa m ple w o ul d be 
a nal yze d f or H S V -1, H S V -2 a n d V Z V.
h h. C hest X -r a y or ot her a p pr o priate dia g n ostic i ma ge (ie, C T or M RI) ma y be perf or me d u p t o 1 2 we e ks pri or t o St u d y Da y 1.  C hest X- r a ys ( p osteri or-a nteri or 
a n d lateral vie ws) are re q uire d f or a d ult s a n d rec o m me n de d f or a d olesce nts as per l ocal g ui deli nes a n d sta n dar d of care.  Official rea di n g m ust be l ocate d a n d 
a vaila ble i n t he s o urce d oc u me ntati o n.
ii.
F oll o w i n g o ne year of t otal e x p os ure t o st u d y dr u g si nce t he last T B test, all s u bjects i n re gi o ns w hic h are a b o ve a l o w -ris k f or T u berc ul osis 
(ie, > 1 0/ 1 0 0, 0 0 0 pre vale nce) will u n der g o t u berc ul osis ( T B) testi n g.  A c hest X -ra y will be perf or me d t o ai d i n T B stat us deter m i nati o n f or all a d ults a n d 
rec o m me n de d f or a d olesce nts acc or di n g t o l ocal g ui deli nes a n d sta n dar d of care i n c o u ntries wit h a hi g h i nci de nce rate of T B. 

P F- 0 4 9 6 5 8 4 2
B 7 4 5 1 0 1 4
Fi nal P r otoc ol A me n d me nt 5, 2 8 Oct o ber 2 0 1 9
P FI Z E R C O N FI D E N TI A L
Pa ge 3 1
jj.
I n C hi na a n d Tai wa n o nl y : S u bjects w h o are H Bs A g ne gati ve, H Bc A b p ositi ve, a n d H Bs A b p ositi ve at Scre e ni n g will ha ve refle x testi n g f or He patitis B 
Vir us ( H B V ) D N A. S u bjects w h o ha ve H B V D N A a b o ve t he l o w er li mit of q ua ntificati o n ( L L Q) will be e xcl u de d.  S u bjects w h o are H B V D N A ne gati ve 
or bel o w  L L Q ma y e nr oll b ut will ha ve H B V D N A testi n g re peate d at Wee ks
1 2, 2 8, 4 0 , 5 2, a n d earl y ter mi nati o n fr o m st u d y d uri n g a n y treat me nt peri o d. 
A si n gle p ositi ve H B V D N A test res ult a b o ve t he L L Q f or a s u bject re q uires i m me diate a n d per ma ne nt disc o nti n uati o n fr o m treat me nt.  Refer t o 
Secti o n 7. 6. 2. 1 .
k k. A si n gle 1 2 -Lea d E C G will be perf or m e d at scree ni n g a n d at all ot her pla n ne d o n -site visits a n d i nter prete d b y a ce ntral rea der.  Cli nicall y si g nifica nt or 
e xcl usi o nar y E C G fi n di n gs at t he scree ni n g or base li ne visits will re q uire scree n fail ure.

P F- 0 4 9 6 5 8 4 2
B 7 4 5 1 0 1 4
Fi nal P r otoc ol A me n d me nt 5, 2 8 Oct o ber 2 0 1 9
P FI Z E R C O N FI D E N TI A L
Pa ge 3 2
S C H E D U L E O F A C TI VI TI E S F O R R E S C U E T R E A T M E N T – F L A R E A T S C H E D U L E D O R U N S C H E D U L E D VI SI T
Visit I de ntifier
D a y 1
Wee k 0
D a y 8
Wee k 1
C all
D a y 1 5
Wee k 2
D a y 2 9
Wee k 4
D a y 4 3
Wee k 6
C all
D a y 5 7
Wee k 8
D a y 8 5
E O T/ E T
Wee k 1 2
E O S, F oll o w -u p
Wee k 1 6/
4 Wee ks p ost E T
Resc ue
Visit 1
Resc ue
Visit 2
Resc ue
Visi t 3
Resc ue
Visit 4
Resc ue
Visit 5
Resc ue
Visit 6
Resc ue
Visit 7
Resc ue
Visit 8
Visit Wi n d o w
3 D a ys
1 D a y
1 D a y
2 D a ys
3 D a ys
3 D a ys
3 D a ys
3 D a ys
E nr oll me nt Pr oc e d ure
R e vie w Pri or/ C o nc o mita nt 
Me dicati o ns & Treat me nts
X
X
X
X
X
X
X
X
Me d ic al Pr oce d ures
Tar gete d P h ysical E xa m a
X
X
X
X
X
C o m plete P h ysical E xa m a
X
Vital Si g ns b
X
X
X
X
X
X
Wei g ht/ Hei g ht
q
X
X
E C G ( 1 2 -lea d)
X
X
X
X
X
X
T u berc ul osis Test r
X
L a b or at or y Assess me nts 
He mat ol o g y c
X
X
X
X
X
X
C oa g ulati o n Pa nel d
X
X
X
X
X
X
Ser u m c he mistr y e
X
X
X
X
X
X
Uri nal ysis f
X
X
X
X
X
X
Li pi d Pa nel h
X
X
X
X
Uri ne Pre g na nc y Test 
(c o n d ucte d at st u d y site)i
X
X
X
X
X
X
H B V D N A testi n g f or C hi na
a n d Tai wa n s
X
Tri al Tre at me nt 
Dr u g Dis pe nsi n g
X
X
X
I n vesti gati o nal Pr o d uct 
Acc o u nta bilit y 
X
X
X
X
X
I n vesti gati o nal Treat me nt 
A d mi nistrati o n j
X ----------------------------------------------------------------------------------------------------------------------X
C CI

P F- 0 4 9 6 5 8 4 2
B 7 4 5 1 0 1 4
Fi nal P r otoc ol A me n d me nt 5, 2 8 Oct o ber 2 0 1 9
P FI Z E R C O N FI D E N TI A L
Pa ge 3 3
Visit I de ntifier
D a y 1
Wee k 0
D a y 8
Wee k 1
C all
D a y 1 5
Wee k 2
D a y 2 9
Wee k 4
D a y 4 3
Wee k 6
C all
D a y 5 7
Wee k 8
D a y 8 5
E O T/ E T
Wee k 1 2
E O S, F oll o w -u p
Wee k 1 6/
4 Wee ks p ost E T
Resc ue
Visit 1
Resc ue
Visit 2
Resc ue
Visi t 3
Resc ue
Visit 4
Resc ue
Visit 5
Resc ue
Visit 6
Resc ue
Visit 7
Resc ue
Visit 8
Visit Wi n d o w
3 D a ys
1 D a y
1 D a y
2 D a ys
3 D a ys
3 D a ys
3 D a ys
3 D a ys
Re vie w e Diar y t o assess 
c o m pleti o n
X
X
X
X
X
X
X
X
Assess eli gi bilit y f or 
B 7 4 5 1 0 1 5 k
X
Cli nic al Assess me nt s
I n vesti gat or’s Gl o bal 
Assess me nt (I G A) 
X
X
X
X
X
X
S C O Ri n g At o pic Der m atitis 
( S C O R A D)
X
X
X
X
X
X
Ecze ma Area a n d Se verit y 
I n de x ( E A SI)
X
X
X
X
X
X
T otal B o d y S urface Area ( B S A 
fr o m E A SI) 
X
X
X
X
X
X
P atie nt -re p orte d O utc o me 
Pr urit us N u m erical Rati n g 
Scale -e Diar y ( N R S) l
X-------------------------------------- X
X
X
X
X
Patie nt Gl o bal Assess me nt 
( Pt G A)
X
X
X
X
X
X
Der mat ol o g y Life Q ualit y 
I n de x ( D L QI or C D L QI)m
X
X
X
X
X
X
Patie nt -Orie nte d Ecze ma 
Meas ure ( P O E M)
X
X
X
X
X
X
H os pital A n xiet y a n d 
De pressi o n Scale ( H A D S)
X
X
X
X
X
X
Pr urit us a n d S y m pt o ms 
Assess me nt f or At o pic 
Der matitis - e Diar y ( P S A A D) l
X ----------------------------------------------------------------------------------------------------------------------------------------------X
E Q -5 D -5 L (a d ults) or 
E Q -5 D -Y (a ges 1 2 -1 7 years) n
X
X
X
X
X
X
S F -3 6 v 2, Ac ute o (ad ults)
X
X
X
F A CI T -F (a d ults) or 
Pe ds -F A CI T - Fp (a ges 1 2- 1 7 
years o nl y )
X
X
X

P F- 0 4 9 6 5 8 4 2
B 7 4 5 1 0 1 4
Fi nal P r otoc ol A me n d me nt 5, 2 8 Oct o ber 2 0 1 9
P FI Z E R C O N FI D E N TI A L
Pa ge 3 4
Visit I de ntifier
D a y 1
Wee k 0
D a y 8
Wee k 1
C all
D a y 1 5
Wee k 2
D a y 2 9
Wee k 4
D a y 4 3
Wee k 6
C all
D a y 5 7
Wee k 8
D a y 8 5
E O T/ E T
Wee k 1 2
E O S, F oll o w -u p
Wee k 1 6/
4 Wee ks p ost E T
Resc ue
Visit 1
Resc ue
Visit 2
Resc ue
Visi t 3
Resc ue
Visit 4
Resc ue
Visit 5
Resc ue
Visit 6
Resc ue
Visit 7
Resc ue
Visit 8
Visit Wi n d o w
3 D a ys
1 D a y
1 D a y
2 D a ys
3 D a ys
3 D a ys
3 D a ys
3 D a ys
Ast h ma C o ntr ol Q uesti o n naire 
( A C Q) for all s u bjects wit h a 
pri or dia g n osis of ast h ma
X
X
X
S afet y
C -S S R S t
X
X
X
X
Seri o us a n d n o n -seri o us 
a d verse e ve nt m o nit ori n g
X 






X
C o ntrace pti o n C hec k
X
X
X
X
X
X
X
X
a.
C o m plete p h ysical e xa mi na ti o ns m ust be perf or me d b y t he i n vesti gat or, s u b i n vesti gat or or a q ualifie d healt h pr ofessi o nal per l ocal g ui deli nes.  C o m plete p h ysical 
e xa mi nati o ns c o nsist of assess me nts of ge neral a p peara nce; s ki n; hea d, e yes, ears, n ose a n d t hr oat ( H E E N T); m o ut h, heart; l u n gs; breast ( o pti o nal); a b d o me n; e xter nal 
ge nitalia ( o pti o nal); e xtre mities; ne ur ol o gic f u ncti o n; a n d l y m p h n o des.  Tar gete d p h ysical e xa mi nati o ns m ust be perf or me d b y t he i n vesti gat or, s u b -i n vesti gat or or a q ualifie d 
healt h pr ofessi o nal per l ocal g ui deli nes a n d s h o ul d i ncl u de s ki n, heart, l u n gs, a n d a b d o me n a n d e xa mi n ati o n of b o d y s yste ms w here t here are s y m pt o m c o m plai nts b y t he 
s u bject.
b.
Vital Si g ns i ncl u de sitti n g bl o o d press ure, p ulse, res pirat or y rate, a n d te m perat ure meas ure d aft er at least 5 mi n utes of rest.
c.
He mat ol o g y i ncl u des: He m o gl o bi n, he mat ocrit, re d bl o o d cells, w hite bl o o d cells, ne utr o p hils ( %, a bs ol ute), l y m p h oc ytes ( %, a bs ol ute), m o n oc ytes ( %, a bs ol ute), e osi n o p hils 
( %, a bs ol ute), bas o p hils ( %, a bs ol ute), platelets, retic ul oc yte c o u nt, R B C I n dices ( M C H, M C H C, M C V, R B C M or p h ol o g y), l y m p h oc yte s u bsets a n d mar kers ( T otal 
T cells [ C D 3 +], C D 4 + T cells [ C D 3 + C D 4 +], C D 8 + T cells [ C D 3 + C D 8 +], N K cells [ C D 3 -C D 1 6 + C D 5 6 +], B cells [ C D 3 -C D 1 9 +) .
d.
C oa g ulati o n pa nel i ncl u des: Acti vate d P artial T hr o m b o pl asti n Ti me ( A P T T), Pr ot hr o m bi n Ti me/I nter nati o nal N or malize d Rati o ( P T/I N R).
e.
Ser u m c he mistr y i ncl u des: bl o o d urea nitr o ge n ( B U N), ser u m creati ni ne, creati ne p h os p h o ki nase, gl uc ose, Ca + +, Na +, K +, Cl -, t otal C O 2, as partate a mi n otra nsferase (A S T), 
ala ni ne a mi n otra nsferase ( A L T), ga m ma-gl uta m yl tra nsferase ( G G T), t otal, i n dire ct a n d direct bilir u bi n, al kali ne p h os p hatase, lactate de h y dr o ge nase, uric aci d, al b u mi n a n d 
t otal pr otei n.
f.
Uri nal ysis i ncl u des: p H, Gl uc ose ( q ualitati ve), Pr otei n ( q ualit ati ve), Bl o o d ( q ualitati ve), Ket o ne s, Nitrites, Le u k oc yte esterase, Micr osc o p y a n d/ or c ult ure (perf or me d as 
a p pr o priate).
 
.
h.
Li pi d Pa nel i ncl u des: t otal c h olester ol, l o w -de n sit y li p o pr otei n (L D L), hi g h - de nsit y li p o pr otei n ( H D L), a n d tri gl yceri des.  A mi ni m u m of 8-h o ur fasti n g is re q uire d f or li pi d 
pr ofile e val uati o n at t he f oll o wi n g Resc ue Vi sits: Da y 1, Week 4, Wee k 1 2 a n d E O S visits.
i.
Uri ne pre g na nc y test m ust be perf or me d a t e ver y site visit pri or t o d osi n g wit h t he i n vesti gati o nal pr o d uct f or fe male s u bjects of c hil d beari n g p ote ntial i ncl u di n g a d o lesce nts 
a ge d 1 2 years a n d ol der re gar dless of w het her t he y ha ve e x perie nce d me narc he.
j.
S u bjects s h o ul d ta ke t he me dicati o n fr o m st u d y Da ys 1 t o 8 5 of t he resc ue treat me nt.  S u bjects will be e nc o ura ge d t o ta ke t he me dicati o n i n t he m or ni n g w he ne ver p ossi ble; 
h o we ver, at st u d y visit da ys, s u bjects are t o be i nstr ucted t o refrai n fr o m d osi n g at h o me a n d are t o ta ke t he d ose i n t he cli ni c.
C CI

P F- 0 4 9 6 5 8 4 2
B 7 4 5 1 0 1 4
Fi nal P r otoc ol A me n d me nt 5, 2 8 Oct o ber 2 0 1 9
P FI Z E R C O N FI D E N TI A L
Pa ge 3 5
k.
S u bjects w h o c o m plete E O T will be assesse d f or eli gi bilit y f or partici pati o n i n l o n g -ter m e xte nsi o n st u d y B 7 4 5 1 0 1 5 as n ote d i n Secti o n 6. 5. 7 . 
l.
Pr urit us N u merical Rati n g Scal e ( N R S) will be assesse d usi n g a n e Diar y, a n d will be c ollecte d dail y i n t he e Diar y fr o m St u d y D a ys 1- 1 5 d uri n g t he resc ue treat me nt a n d t he n 
o nl y o n st u d y visit da ys at t he i n vesti gati ve site t hereafter.  P S A A D will be c o m plete d dail y (i n selecte d c o u ntri es) i n t he e Diar y fr o m D a y 1 t hr o u g h t he E n d of St u d y ( E O S) 
visit d uri n g resc ue treat me nt.  At e ver y visit, t he st u d y c o or di nat or will re vie w t he e Diar y f or c o m plete ness a n d c o u nsel t he s u bject o n h o w t o c o m plete t he ite ms i n t he dail y 
e Diar y, if nee de d.
m.
D L QI will be c o m plete d b y a d ult s u bjects o nl y.  A d olesce nts 1 2 -1 7 years of a ge will c o m plete t he C D L QI i nstea d .
n.
T he E ur o Q ol Q ualit y of Life 5 -Di me nsi o n 5 -Le vel Scale ( E Q -5 D -5 L) will be c o m plete d b y a d ult s u bjects o nl y.  A d olesce nts 1 2 -1 7 ye ars of a ge will c o m plete t he E ur o Q ol 
Q ualit y of Life 5 - Di me nsi o n, Y o ut h Scale ( E Q-5 D -Y) i n select c o u ntries.
o.
S F - 3 6 v 2 will be c o m plete d b y a d ult s u bjects o nl y.  A d olesce nts 1 2-1 7 years of a ge will n ot c o m p lete t his assess me nt.
p.
F A CI T -F will be c o m plete d b y a d ult s u bjects o nl y .  A d olesce nts 1 2-1 7 years of a ge will c o m plete t he Pe ds- F A CI T -F i nstea d.
q.
C ollect wei g ht f or all s u bjects a n d hei g ht f or a d olesce nts o nl y ( 1 2 t o < 1 8 years ol d).
r.
F oll o wi n g o ne year of t ot al e x p os ure t o st u d y dr u g si nce t he last T B test, all s u bjects i n re g io ns w hic h are a b o ve a l o w -ris k f or T u berc ul osis (ie, > 1 0/ 1 0 0, 0 0 0 pre vale nce) will 
u n der g o t u berc ul osis ( T B) testi n g.  A c hest X-ra y will be perf or me d t o ai d i n T B stat us deter mi nati o n f o r all a d ults, a n d rec o m me n de d f or a d olesce nts acc or di n g t o l ocal 
g ui d eli nes a n d sta n dar d of care i n c o u ntries wit h a hi g h i nci de nce rate of T B. 
s.
I n C hi na a n d Tai wa n o nl y : F or s u bjects w h o ha d H B V D N A testi n g at Scree ni n g , H B V D N A testi n g is re peate d at Resc ue Wee k 1 2 or at a n earl y ter mi nati o n visit . A si n gle
p ositi ve H B V D N A test res ult a b o ve t he L L Q f or a s u bject re q uires i m me diate a n d per ma ne nt disc o nti n uati o n fr o m trea t me nt.  Refer t o Secti o n 7. 6. 2. 1 .
t.
P ost -scree ni n g, if t here are “ yes” a ns wers o n ite ms 4, 5 or o n a n y be ha vi oral q uesti o n of t he Si nce Last Visit C -S S R S a ris k assess me nt b y a q ualifie d me ntal healt h 
pr ofessi o nal ( M H P) s h o ul d be d o ne t o deter mi ne w het her it is sa fe f or t he s u bject t o c o nti n ue t o partici pate i n t he trial.

P F- 0 4 9 6 5 8 4 2
B 7 4 5 1 0 1 4
Fi nal P r otoc ol A me n d me nt 5, 2 8 Oct o ber 2 0 1 9
P FI Z E R C O N FI D E N TI A L
Pa ge 3 6
1. I N T R O D U C TI O N
1. 1. Mec h a nis m o f Acti o n/I n dic ati o n
P F - 0 4 9 6 5 8 4 2 is a Ja n us ki nase 1 (J A K 1) i n hi bit or t hat is bei n g i n vesti gate d as a treat me nt f or 
patie nts wit h At o pic Der matitis ( A D). 
T he Ja n us ki nase (J A K) fa mil y, i ncl u din g J A K 1, J A K 2, J A K 3 a n d t y r osi ne ki nase 2 ( T Y K 2), 
is a gr o u p of c yt o plas mic t y r osi ne ki nases t hat me diate si g nal tra ns d ucti o n via i nteracti o ns 
wit h T y pe 1 a n d T y pe 2 c y t o ki ne rece pt ors critical f or le u k oc yte acti vati o n, pr oliferati o n, 
s ur vi val a n d f u ncti o n.  C yt o ki ne rece pt ors de m o nstrate restricte d ass ociati o n wit h J AK s s uc h 
t hat differe nt rece pt ors or rece pt or classes prefere ntiall y utilize a gi ve n J A K di mer or tri mer 
c o m bi nati o n t o tra ns d uce t heir si g nal.  J A K 1 pairs wit h J A K 3 t o me d iate -c o m m o n c yt o ki ne 
si g nali n g a n d als o wit h J A K 2 or T Y K 2 t o tra ns mit t he si g nals of a d diti o nal c yt o ki nes 
i m p orta nt i n i nfla m mati o n a n d i m m u ne res p o nses i ncl u di n g i nterle u ki n (I L) - 4, - 5, - 6, - 1 3,
- 2 1, - 3 1, i nterfer o n ga m ma (I F N-), a n d i nterfer o n al p ha (I F N-).  J A K 2 h o m o di mers are 
critical f or t he si g nali n g of he mat o p oietic c y t o ki nes an d h or m o nes i ncl u di n g er y t hr o p oieti n 
( E P O), t hr o m b o p oieti n ( T P O), I L-3, gra n ul oc y te-macr o p ha ge c ol o n y- sti m ulati n g fact or 
( G M-C S F) a n d pr olacti n. 
K e y c yt o ki nes i m plicated i n t he pat h o p h ys i olo g y of A D i ncl u de I L- 4, I L- 5, I L- 1 3, I L- 3 1,
a n d I F N -, re q uire J A K1 f or si g nal tra ns d ucti o n; t his s u g gests t hat selecti ve J A K 1 i n hi bit ors 
t hat m o d ulate t he acti vit y of t hese c yt o ki nes re prese nt a c o m pelli n g a p pr oac h t o t he 
treat me nt of i nfla m mat or y s ki n diseases s uc h as A D.7
I L-1 2 a n d I L - 2 3 are de pe n de nt o n T Y K 2 a n d J A K 2 f or tra ns mitti n g t heir si g nals.  F oll o wi n g 
c yt o ki ne acti vatio n, rece pt or -ass ociate d J A Ks are p h os p h or y late d a n d i n t ur n p h os p h or ylate 
s pecific sites o n t he rece pt or i ntracell ular d o mai n.  P h os p h or ylati o n of s pecific sites o n t he 
i ntracell ular d o mai n of t he rece pt or all o ws f or t he recr uit me nt of si g nal tra ns d ucers an d 
acti vat ors of tra nscri pti o n ( S T A Ts) t hat ca n s u bse q ue ntl y  be p h os p h or y late d b y  J A Ks.  
P h os p h or y late d S T A T m olec ules are release d fr o m t he rece pt or, tra nsl ocate t o t he n ucle us 
w here t he y  bi n d t o s pecific sites o n t he de o x yri b o n ucleic aci d ( D N A) a n d re g ulate ge ne 
tra nscri pti o n. 
P F -0 4 9 6 5 8 4 2 is a n orall y bi oa vaila ble s mall m olec ule that selecti vel y i n hi bits J A K 1 b y  
bl oc ki n g t he A T P bi n di n g site.  P F- 0 4 9 6 5 8 4 2 has a hi g h de gree of selecti vit y  i n vitr o a gai nst 
ot her ki nases: 2 8 -f ol d selecti vit y o ver J A K 2, > 3 4 0-f ol d o ver J A K 3 a n d 4 3-f ol d o ver T Y K 2, 
as well as a g o o d selecti vit y pr ofile o v er t he br oa der ra n ge of h u ma n ki nases. T he selecti ve 
i n hi biti o n of J A K1 will lea d t o m o d ulati o n of m ulti ple c yt o ki ne pat h wa ys i n v ol ve d i n t he 
pat h o p h y si ol o g y of A D, i ncl u di n g I L-4, I L-5, I L -1 3, I L -3 1 a n d I F N -.  Data fr o m a P hase 2 b 
pr o of of c o nce pt ( P O C) st u d y ( B 7 4 5 1 0 0 6) t hat e val uate d s u bjects wit h m o derate t o se vere 
A D ha v e s h o w n p ositi ve efficac y, as well as a n acce pta ble safety pr ofile, s ufficie nt t o s u p p ort 
f urt her cli nical de vel o p me nt i n a lar ger P hase 3 pr o gra m.  St u d y B 7 4 5 1 0 1 4 will i n vesti gate 
t he ti me t o l oss of res p o nse t o P F-0 4 9 6 5 8 4 2 i n s u bjects wit h m o derate t o s evere A D 
f oll o wi n g a cli nical res p o nse t o o pe n-la bel i n d ucti o n treat me nt wit h P F-0 4 9 6 5 8 4 2.  S u bjects 
w h o e x perie nce a l oss of res p o nse de n ote d as flare ( per pr ot oc ol def i niti o n) will recei ve 
resc ue treat me nt wit h P F-0 4 9 6 5 8 4 2 i n c o m bi nati o n wit h t o pical t he ra p y per sta n dar d of care.

P F- 0 4 9 6 5 8 4 2
B 7 4 5 1 0 1 4
Fi nal P r otoc ol A me n d me nt 5, 2 8 Oct o ber 2 0 1 9
P FI Z E R C O N FI D E N TI A L
Pa ge 3 7
1. 2. B ac k gr o u n d a n d R ati o n ale
1. 2. 1. Dr u g De vel o p me nt a n d R ati o n ale
P F - 0 4 9 6 5 8 4 2 is bei n g devel o pe d as a n oral treat me nt f or patie nts wit h m o derate t o se ve re 
A D base d o n i ts mec ha nis m of acti o n, a n d t he cli nical res ults o btai ne d i n P hase 1 a n d
P hase 2 st u dies.  T he cli nical de vel o p me nt pr o gra m f or P F -0 4 9 6 5 8 4 2 i ncl u des healt h y  
v ol u nteers, s u bjects wit h ps oriasis a n d s u bjects wit h A D. 
A d diti o nal i nf or mati o n f or t his c o m p o u n d ma y  be f o u n d i n t he si n gle refere nce safety 
d oc u me nt ( S R S D), w hic h f or t his st u d y is t he I n vesti gat or’s Br oc h ure (I B). 
1. 2. 2. At o pic Der m atitis
At o pic der matitis, als o k n o w n as at o pic ecze ma, is a c o m m o n, c hr o nic, i nfla m mat or y s ki n 
dis or der c har acterize d b y flak y  s ki n lesi o ns, i nte nse pr urit us, a n d a ge neral deteri orati o n i n 
q uali ty of life.  O ver t he past 5 0 ye ars, A D has bec o me m ore pre vale nt, e s pecially i n 
i n d ustrialize d, te m perate c o u ntries s uc h as t he U S.1 ,2  A D is o ne of t he m ost c o m m o n,
c hr o nic, rela psi n g c hil d h o o d der mat oses, i m pacti n g 1 5 -3 0 % of all c hil dre n i n t he U S a n d 
ma n y  ha ve disease t hat persists i nt o a d ult h o o d wit h a lifeti me pre vale nce of t h o se affecte d 
be y o n d c hil d h o o d re p orte d t o be 3 4 %.8  Earlier re p orts i n dicate d t hat, i n u p t o 7 0 % of cases, 
t he disease greatly i m pr o ves or res ol ves b y l ate c hil d h o o d, h o we ver m ore rece nt fi n di n gs 
s u g gest t hat disease acti vit y remai ns ma nifest f or a pr ol o n ge d peri o d of ti me.  Base d o n a 
t otal of 7 1 5 7 patie nts e nr olle d i n t he Pe diatric Ecze ma Electi ve Re gistr y  ( P E E R) st u d y, 
c o m prisi n g a t otal of 2 2, 5 5 0 pers o n -ye ars, it was c o ncl u de d t hat s y m pt o ms ass ociate d wit h 
A D see m t o persist well i nt o t he sec o n d deca de of life a n d li kel y  l o n ger.3  At e ver y  a ge, m ore 
t ha n 8 0 % of P E E R st u d y s u bjects ha d sy m pt o ms of A D a n d/ or were usi n g me dicati o n t o treat 
t heir A D.  5 9 % of 8 3 3 A D patie nts w h o were a ge d 2 0 ye ars or ol der w he n t he y visite d t he 
cli nic a n d were 4 5 ye ars or older w he n t he y  c o m plete d a f oll o w u p q uesti o n naire, re p orte d 
t hat t he y ha d persiste nt A D at s o me ti me d uri n g t he last 1 2 m o nt hs. 9  
T he maj o rit y of st u dies c o n d ucte d acr oss m ulti ple a ge gr o u ps s u g gest a c o nti n ued decrease i n 
pre vale nce wit h ol der a ge. 1 0  A d ult- o nset A D d oes als o occ ur, t h o u g h it is less c o m m o n.  T he 
pre vale nce of A D i n a d ults is esti mate d t o be 1 0%. 1 1  Rece n t st u dies ha ve i n dicate d t hat 
a d ults wit h A D are m ore li kel y  t o s m o ke ci garettes, dri n k alc o h ol, a n d ha ve a se de ntar y 
lifest yle, p ote ntially ass ociate d wit h i ncrease d c o m or bi dities, s uc h as ast h ma a n d 
car di o vasc ular disease. 1 2
Alt h o u g h great stri des ha ve bee n ma de i n u n dersta n di n g t he ca uses, t he c o m ple x 
pat h o p h y si ol o g y of A D is still n ot c o m pletel y u n derst o o d.  It has bee n esta blis he d t hat t he 
pat h o p h y si ol o g y of A D i ncl u des a defecti ve s ki n barrier f u ncti o n, aller gic res p o nses, 
defecti ve a nti micr o bial i m m u ne defe nse, a n d a ge netic pre dis p ositi o n.  T he pre d o mi na nt 
s ym pt o m of A D, pr urit us a n d t he res ulti n g scratc hi n g, t y picall y s ets off a n a m plificati o n 
c ycle of at o pic s ki n i nfla m mati o n.  Acti vati o n of T l ym p h oc y tes, de n dritic cells, 
macr o p ha ges , kerati n oc ytes, mast cells, a n d e osi n o p hils res ults i n a release of n u mer o us 
pr o -i nfla m mat or y c yt o ki nes a n d c he m o ki nes.  T his a m plificatio n c y cle s ustai ns t he 
i nfla m mat or y res p o nses c haracteristic of t he A D lesi o ns.1 3

P F- 0 4 9 6 5 8 4 2
B 7 4 5 1 0 1 4
Fi nal P r otoc ol A me n d me nt 5, 2 8 Oct o ber 2 0 1 9
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Pa ge 3 8
Ac ute A D lesi o ns ha ve bee n ass ociate d wit h t he T y p e 2 hel per T cell ( T H 2) p he n ot ype, 
s h o wi n g d o mi na nce of I L- 4, - 5, -1 3, a n d - 3 1 secreti o n.1 3 ,1 4 ,7  Rece nt researc h s h o we d t hat a 
s mall i ncrease of T ype 1 hel per T cell ( T H 1)-ass ociate d ge nes has bee n als o detecte d i n ac ute 
p hase. 1 5
W hile I L - 4-pr o d uci n g T H 2 cells ma y  dri ve t he de vel o p me nt of at o pic s ki n lesi o ns, c hr o nic 
lesi o ns s h o w eit her t he c oe xiste nce of b ot h I L- 4-pr o d uci n g T H 2 a n d I F N--pr o d uci n g T H 1 
cells or T H 1 d o mi na nce. 1 3  T his c oe xiste nce of T H 2 a n d T H 1 res p o nses or T H 1 d o mi na nce 
is m ore li kel y t o be t he u n derl yi n g i m m u n o pat h ol o g y i n a d ult patie nts w h o ha ve ha d A D 
c hr o nicall y or i nter mitte ntl y  si nce c hil d h o o d.  Rece nt e vi de nce als o s u p p orts I L-3 1’s r ol e i n 
pr urit us a n d i nfla m mati o n i n A D. 1 4 ,7  
N o n - me dicate d t o pical t hera pies i ncl u de e m ollie nts.  Me dicate d t o pical t hera pies f or 
m o derate t o se vere A D i ncl u de T C S (e g, beta met has o ne, cl o betas ol, fl uoci n o ni de), T CI 
(e g, pi mecr oli m us, tacr oli m us), a n d c oal tar pre parati o ns.  T C S are li mite d i n ter ms of t he 
treat me nt d urati o n (e g, c ortic oster oi d use is li mite d t o 2 t o 4 wee ks) a n d t he b o d y re gi o n of 
treat me nt, d ue t o c o nsiste nt s ki n t o xicities, as well as ha vi n g ris ks ass ociate d wit h t heir br oa d 
i m m u n os u p pressi ve acti o ns. T CI  ha ve a li mite d r ole as a sec o n d li ne treat me nt, d ue t o t heir 
li mitati o ns i n ter ms of t he d urati o n of treat me nt a n d t he b o d y re gi o n of treat me nt, i n hi biti o n 
of t u m or s ur veilla nce i n t he s ki n, a n d safet y c o ncer ns wit h mali g na ncies.  Crisa b or ole was 
a p pro ve d as a me dicate d t o pical treat me nt i n Dece m ber 2 0 1 6 b y  t he F D A f or use i n patie nts 
wit h mil d t o m o derate A D.   A d diti o nal treat me nts ge nerall y reser ve d f or se vere A D i ncl u de 
p h ot ot her a p y (e g, ultra vi olet A li g ht [ U V A] wit h or wit h o ut ps orale n, ultra vi olet B li g ht 
[ U V B] narr o w ba n d or br oa d ba n d) a n d sys te mic a ge nts (e g, c ortic oster oi ds, c ycl os p ori ne, 
rec o m bi na nt I F N-, myc o p he n olate m ofetil, met h otre xate [ M T X], azat hi o pri ne, i ntra ve n o us 
i m m u n o gl o b uli n).4  Of t he curre ntl y  a vaila ble t hera pies, n o ne offers a c ure; t heref ore, t he 
mai n ai ms of e xisti n g treat me nts are t o re d uce t he occ urre nce of ac ute flares , t o i ncrease t he 
ti me betwee n rela pses, r e d uce pr urit us a n d t he res ulti n g slee p dist ur ba nce. 5 ,6
T here are a li mite d n u m ber of a p pr o ve d s ys te mic treat me nts f or m o derate t o se vere A D, a n d 
i n t he U S A, t he o nl y a p pr o ve d s ys te mic dr u gs are c ortic oster oi ds a n d d u pil u ma b.
D u pil u ma b, an i njecta ble h u m a n m o n ocl o nal a nti b o d y tar geti n g i nterle u ki n (I L) -4 a n d - 1 3,
was a p pr o ve d b y t he F D A i n Marc h 2 0 1 7 a n d recei ve d mar keti n g a ut h orizati o n i n E ur o pe i n 
Se pte m ber 2 0 1 7, f o r t he treat me nt of m o derate t o se vere A D. Treat me nt wit h s y ste mic 
c ortic oster oi ds has k n o w n a n d well d oc u me nte d a d verse effects. Treat me nt wit h d u pil u ma b 
has t he ris k of i njecti o n site reacti o ns, aller gic reacti o ns, e y e a n d e yeli d i nfla m mati o ns an d 
c ol d s ores.  A n ot her li mitati o n of d u pil u ma b is t he p ossi bilit y f or de vel o p ment of a nti dr u g 
a nti b o dies, w hic h ma y res ult i n l oss of efficac y o ver ti me a n d t he de vel o p me nt of safety 
c o ncer ns s uc h as ser u m sic k ness -li ke reacti o ns. F urt her m ore, d u pil u ma b is deli vere d via 
s u bc uta ne o us i njecti o n, w hic h ma y n ot be a met h o d of a d mi nistrati o n t olerate d well by all 
patie nts. 

P F- 0 4 9 6 5 8 4 2
B 7 4 5 1 0 1 4
Fi nal P r otoc ol A me n d me nt 5, 2 8 Oct o ber 2 0 1 9
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Pa ge 3 9
D uri n g a 1 -ye ar, ra n d o mize d, d o u ble -bli n de d st u d y  wit h d u pil u ma b, i n t he d u pil u ma b 
3 0 0 m g e ver y  2 wee ks ( mar kete d mai nte na nce d ose ) pl us TC S gr o u p , t he esti mate d 
differe nce fr o m place b o of t he I G A res p o nse rate a n d E A SI- 7 5 res p o nse rate were 2 6 % a n d 
4 6 %, res pecti vel y .  T he place b o res p o nse rate f or I G A a n d E A SI-7 5 was 1 2 % a n d 2 3 %, 
res pecti vely.  T he de vel o p me nt of p ote ntial treat me nt s wit h furt her i m pr o ve me nts t o efficac y  
re mai ns desira ble.
I n E ur o pe, c ycl os p ori ne is ap pr o ve d f or use i n patie nts wit h se vere A D w he n s y ste mic 
t hera py is re q uire d.  C ycl os p ori ne use is ass ociate d wit h se veral u n desira ble si de effects a n d 
d ue t o its narr o w t hera p e utic i nde x, occasi o nal t hera pe utic dr u g m o nit ori n g is rec o m me n de d.  
K n o w n a d ve rse effects i ncl u de i nfecti o ns, re nal t o xicit y, he pat ot o xicit y, s ki n mali g na ncies, 
l ym p h o ma a n d ot her mali g na ncies.
T he pre d o mi na nt u n met me dical nee d t he n is f or a n ora l t hera py wit h a n acce pta ble safet y  
pr ofile, f or l o n g-ter m use, w hic h is effecti ve f or m o derate t o se vere A D. Patie nts wit h 
m o derate t o se vere A D re q uire ot her s ys te mic treat me nt o pti o ns be yo n d t h ose w hic h are 
c urre ntl y a p pr o ve d.
C urre ntl y  a vaila ble t herapies f or t he treat me nt of A D ha ve m ulti ple li mitati o ns.  T he 
me dicate d t o pical t hera pie s ha ve dra w bac ks relate d t o t he d urati o n of use d ue t o t he p ote ntial 
f or l ocal a n d sys te mic si de effects (e g, c ortic oster oi d use is li mite d t o 2 t o 4 wee ks) a n d t o 
t he bo d y  re gio ns of u se (e g, mi d-hi g h p ote nc y  c ortic oster oi ds are n ot a p pr o ve d f or use o n t he
face a n d/ or i ntertri gi n o us areas).  F or A D patie nts n ot res p o n di n g t o me dicate d t o pical 
t hera pies a n d p h ot ot hera p y, o n- a n d off -la bel use of s yste mic a ge nts, w hic h i ncl u de oral 
c orticoster oi ds or oral i m m u n os u p pressa nts, re mai n t he last via ble treat me nt o pti o n.  
S y ste mic t hera p y o pti o ns are ass ociate d wit h p ote ntiall y se vere a d verse effects a n d re q uire 
caref ul m o nit ori n g.  T he ris k of t o xicit y a n d si de effects re mai n a c o ncer n w he n s ys te mic 
a ge nts are use d.  F or t hese reas o ns t he use of t hese a ge nts is li m ite d t o s h ort c o urses or 
i nter mitte nt t hera p y. 
P F - 0 4 9 6 5 8 4 2 is a n oral ta blet, a m ore c o n ve nie nt r o ute of a d mi nistrati o n c o m pare d wit h 
s u bc uta ne o us i njecti o n re q uire d for d u pil u ma b a n d s o it d oes n ot ha ve t he p ote ntial ris k of 
i njecti o n site reacti o ns. T h e l o n ger half -life of d u pil u ma b als o mea ns t hat it ma y ta ke a 
relati vely l o n g peri o d of ti me f or s o me u n desira ble p har mac o d y n a mic effects 
(e g, treat me nt-relate d a d verse e ve nt [ A E]) t o s u bsi de after its disc o nti n uati o n.  I n t his res pect, 
t he be nefit of a sh orter half- life wit h a ge nts s uc h as P F-0 4 9 6 5 8 4 2 is t hat a n A E ma y  
p ote ntiall y  res ol ve m ore ra pi dl y t ha n is t he case wit h d u pil u ma b.  U nli ke d u pil u ma b, 
P F - 0 4 9 6 5 8 4 2 is a s mall m olec ule an d t here is n o a ntici pate d i m m u n o ge nicit y  f or 
P F -0 4 9 6 5 8 4 2, a n d s o it is u nli kel y  t o ge nerate a nti dr u g a nti b o dies.  
As me nti o ne d a b o ve, a variet y of pr o -i nfla m mat or y c yt o ki nes s uc h as I L-4, I L -1 3, I L - 2 2, 
I L-3 1 a n d I F N -, ha ve bee n s u g geste d t o ha ve a r ole i n t he pat h o ge nesis of A D.  Ma ny of 
t hese pat h o ge nic c yt o ki nes use t he JA K 1 f or si g nali n g.  T heref ore, J A K 1 is a n attracti ve 
t hera pe utic tar get f or A D as a n i n n o vati ve oral t hera pe utic a ge nt.

P F- 0 4 9 6 5 8 4 2
B 7 4 5 1 0 1 4
Fi nal P r otoc ol A me n d me nt 5, 2 8 Oct o ber 2 0 1 9
P FI Z E R C O N FI D E N TI A L
Pa ge 4 0
1. 2. 3. N o n - Cli nic al a n d P h ase 1 D at a 
Data fr o m n o ncli n ical a n d P hase 1 pr o gra ms s u p p orts t he pla n ne d cli nical trials wit h 
P F -0 4 9 6 5 8 4 2 a n d f ur ther i nf or mati o n is i n t he c urre nt versi o n of t he I n vesti gat or’s Br oc h ure 
(I B).
1. 2. 4. P h ase 2 b i n A D ( B 7 4 5 1 0 0 6) 
B 7 4 5 1 0 0 6 was a P hase 2 b pr o of - of-c o nce pt trial i n a d u lts (a ges 1 8 -7 5) wit h m o d erate t o 
se vere A D i n vesti gati n g d oses of 1 0, 3 0, 1 0 0, a n d 2 0 0 m g P F - 0 4 96 5 8 4 2 or place b o ta ke n 
o nce dail y ( Q D) f or u p t o 1 2 wee ks.  T he pri mar y  e n d p oi nt i n t his st u d y was t he pr o p orti o n 
of s u bjects ac hie vi n g a n I G A sc ore of clear ( 0), or al m ost clear ( 1), a n d a 2- p oi nt 
i m pr o ve me nt fr o m baseli ne at Wee k 1 2.  T he baseli ne was d efi ne d as t he I G A sc ore o n 
D a y 1 pre -d ose. 
At Wee k 1 2, I G A res p o nse rates of P F -0 4 9 6 5 8 4 2 1 0 0 m g a n d 2 0 0 m g  d ose gr o u ps were 
si g nifica ntly greater t ha n place b o i n patients wit h m o derat e t o se vere A D.  T he I G A res p o nse 
rates of t he 2 0 0 m g  a n d 1 0 0 m g gr o u ps were 4 4. 5 % a n d 2 7. 8 %, res pecti vel y.  T he I G A 
res p o nse rate i n t he place b o gr o u p was 6. 3 % a n d t he esti mate d differe nces fr o m place b o i n 
t he 2 0 0 m g a n d 1 0 0 m g  gro u ps were 3 8. 2 % ( P = 0. 0 0 3 2 ) a n d 2 1. 5 % ( P = 0. 0 1 8 4), res pecti vel y.  
T he perce nt c ha n ge fr o m baseli ne ( % C ha n ge fr o m baseli ne ( C F B)) i n E A SI  sc ores at 
Wee k
1 2 were si g nifica ntl y  hi g her f or b ot h t he 2 0 0 m g a n d 1 0 0 m g  gr o u ps c o m pare d t o 
place b o.  T he esti mate d pe rce nt c han ge fr o m baseli n e i n E A SI sc ore was -3 5. 2 % i n t he 
place b o gr o u p, -8 2. 5 7 % i n t he 2 0 0 m g g r o u p a n d -5 9. 0 4 % i n t he 1 0 0 m g gr o u p.  At 
Wee k
1 2, t he pr o p orti o n of s u bjects ac hie vi n g E A SI -7 5 res p o nse was 1 5. 6 % i n t he place b o 
gr o u p, 6 3. 7 % i n t he 2 0 0 m g gr o u p a n d 4 1. 6 % i n t he 1 0 0 m g gr o u p.  T he differe nce fr o m 
place b o was 4 1. 8 % ( P = < 0. 0 0 0 1) f or t he 2 0 0 m g  gr o u p a n d 2 6. 0 % ( P = 0. 0 0 4 3) i n t he 1 0 0 m g 
gr o u p.  At Da y 1 5, t he pr o p orti o n of res p o nse base d o n ac hie vi n g at least 4 p oi nts 
i m pr o ve me nt i n t he se verit y of Pr urit us N u merical Rati n g Scale ( N R S) fr o m baseli ne 
( Pr urit us N R S 4) of P F -0 4 9 6 5 8 4 2 1 0 0 m g a n d 2 0 0 m g d ose gr o u ps was greater t ha n place b o.  
T he esti mate d pr o p orti o n of Pr urit us N R S 4 res p o nses at Da y 1 5 were 6 9. 8 %, 4 1. 1 % a n d 
1 5. 7 % f or 2 0 0 m g , 1 0 0 m g a n d p lace b o gro u ps, res pecti ve l y.
P F -0 4 9 6 5 8 4 2 de m o nstrate d a ra pi d o nset of acti o n.  I n t he 2 0 0 m g g ro u p, I G A a n d E A SI 
sc ores i m pr o ve d u ntil W ee k 4 a n d W ee k 6, res pecti vel y , a n d mai ntai ne d t heir effect t hr o u g h 
1 2 wee ks of treat me nt.  Res p o nse rates at Wee k
1 2 f or t he 1 0 m g  a n d 3 0 m g g r o u ps were n ot 
si g nifica ntly differe nt fr o m place b o.  A ke y differe ntiati n g feat ure f or t his J A K 1 i n hi bit or 
was ra pi d res ol uti o n of itc h ass ociate d wit h A D.  Si g nifica nt se parati o n fr o m place b o was 
ac hie ve d f or t he Pr urit us N R S sc ore as ear l y as 2 d a y s after i nitiati o n of treat me nt f or t he 
2 0 0 m g d ose gr o u p.
O verall, t he res u lts de m o nstrate d d ose-de pe n de nt i ncreases i n res p o nses at Wee k 1 2 f or ke y  
efficac y e n d p oi nts (I G A, E A SI a n d pr urit us N R S sc ore).

P F- 0 4 9 6 5 8 4 2
B 7 4 5 1 0 1 4
Fi nal P r otoc ol A me n d me nt 5, 2 8 Oct o ber 2 0 1 9
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Pa ge 4 1
P F - 0 4 9 6 5 8 4 2 a p peare d generall y safe a n d well t olerate d i n t his st u d y .  O verall, a d verse 
e ve nts ( A Es) a n d seri o us a d verse e ve nts ( S A Es) were n u merically hi g her i n s u bjects 
recei vi n g P F-0 4 9 6 5 8 4 2 c o m pare d t o place b o, b ut di d n ot a p pear t o i ncrease wit h d ose.  T he 
m ost c o m m o n A Es we re i n t he i nfectio ns a n d i nfestat i o ns, s ki n a n d s u bc uta ne o us tiss ue 
dis or ders a n d gastr oi ntesti nal dis or d ers s ys te m or ga n class, a n d t he maj orit y of t he A Es were 
mil d.  T here were 2 cases of her pes z oster, o ne i n t he 1 0 m g gr o u p ( n ot treat me nt relate d), 
a nd o ne i n t he 3 0 m g gr o u p (treat me nt relate d).  T here were d ose -de pe n de nt decreases i n 
platelet c o u nts o b ser ve d i n t he st u d y, w hic h platea ue d at Wee k 4.  F urt her details of t he 
cli nical P hase 2 de vel o p me nt pr o gra m ca n be f o u n d i n t he I B.
1. 3. S u m m ar y of P F - 0 4 9 6 58 4 2 Cli nic al P h ar m ac o ki netics 
P F -0 4 9 6 5 8 4 2 was ra pi dl y  a bs or be d f oll o wi n g si n gle d ose oral s ol uti o n/s us pensi o n 
a d mi nistrati o n o ver t he d ose ra n ge 3 m g  t o 2 0 0 m g  wit h ti me t o ma xi m u m a bs or pti o n ( Tma x ) 
ra n gi n g bet wee n 0. 5 5 t o 0. 7 7 h o urs ( B 7 4 5 1 0 0 1).  Me dia n Tma x at d oses of 4 0 0 m g a n d 
8 0 0 m g were 1. 5 a n d 3. 9 h o urs, res pecti vel y , w hic h i n dicate d t he sl o wer a bs orp ti o n 
c o m pare d t o l o wer d oses.  P F - 0 4 9 6 5 8 4 2 s h o we d a m o n o p hasic decli ne at d ose < 1 0 0 m g  wit h 
bi p hasic pr ofiles at d oses 1 0 0 m g.  O bser ve d pea k plas ma P F- 0 4 9 6 5 8 4 2 c o nce n trati o ns 
( Cma x ) f oll o wi n g t he si n gle-d ose a d mi nistrati o n ge nerall y i ncrease d i n pr o p ort io n t o t he d ose 
fr o m 3 m g t o 8 0 0 m g .  I n c o ntrast, b ot h area u n der t he plas ma c o nce ntrati o n-ti me c ur ve fr o m 
ti me zer o e xtra p olate d t o i nfi nit y ( A U Ci nf) a n d area u n der t h e plas ma c o nce nt rati o n ti me 
pr ofile fr o m ti me zer o t o t he last q ua ntifia ble c o nce ntrati o n ( A U C last) were d ose pr o p orti o nal 
i n t he ra n ge of 3 m g  t o 2 0 0 m g, w hile a greater t ha n pr o p orti o nal i ncrease was o bser ve d at 
d oses of 4 0 0 a n d 8 0 0 m g. T he arit h metic m ea n ter mi nal p hase half-life (t½ ) was 1. 9 t o 
4. 9 h o urs.
F oll o wi n g o nce dail y ( Q D) a d mi n istrati o n o ver t he d ose ra n ge 3 0 m g  t o 4 0 0 m g a n d 1 0 0 m g  
a n d 2 0 0 m g t wice a da y ( BI D) f or 1 0 d a y s, me dia n Tma x ra n ge d bet wee n 0. 5 0 t o 0. 7 7 h o urs 
( B 7 4 5 1 00 1).  After attai n me nt of C ma x , the dis p ositi o n of P F -0 4 9 6 5 8 4 2 was c o nsiste nt wit h 
t hat o bser ve d f oll o win g si n gle - d ose a d mi nistrati o n, s h o wi n g a bi p hasic decli ne f oll o wi n g all 
b ut t he l o west d ose a n d a n arit h metic mea n ter mi nal p hase t ½ bet wee n 2. 8 t o 5. 0 h o urs.  
Alt h o u g h C ma x ge nerall y  increase d i n pr o p orti o n t o t he d ose u p t o 1 0 0 m g gi ve n t wice dail y 
( BI D), it i ncrease d m ore t ha n t he d ose i ncrease d at 4 0 0 m g Q D a n d 2 0 0 m g BI D.  T he sa me 
tre n d was als o o bser ve d f or area u n der t he plas ma c o nce ntrati o n-ti me c ur ve ( A U C ta u) o ver 
t he d osi n g i nter val (ta u = 1 2 or 2 4 h o urs).  T he o bser ve d acc u m ulati o n rati o ( R ac) fo ll o wi n g 
2 0 0 m g BI D was 2. 0 a n d 2. 5 f or A U C ta u a n d C ma x , res pecti vely.  R ac was 1. 1 t o 1. 5 at ot her 
d oses.  T heref ore, t he res ults s h o we d t hat dr u g c o nc e ntrati o n acc u m ul ati o n is mi ni mal after 
re peate d oral a d mi nistrati o n at l o wer d oses c o nsiste nt wit h t he p re dicti o n fr o m t½ .  Uri nar y 
rec o ver y of P F-0 4 9 6 5 8 4 2 was l o w, wit h < 5 % of t he d ose rec o vere d u nc ha n ge d i n uri ne 
acr oss all d oses a n d re gi me ns i n all c o h orts.
At a si n gle 8 0 0 m g d ose, t h e ge o metric mea n perce nt c oefficie nt of variati o n ( % C V) C ma x
( n g/ m L) was si milar i n Wester n ( n = 5; 3 8 1 9 ( 2 6)) a n d Ja pa nese s u bjects ( n = 1 0; 3 6 6 0 ( 4 8)).  
H o we ver, ge o metric mea n A U C i nf ( n g * hr/ m L) was 2 6 % hi g her i n Wester n s u bjects ( n = 5; 
2 7 5 4 0 ( 3 5)) t ha n t hat o bser ve d i n Ja pa nese s u bjects ( n = 9; 2 1 8 6 0 ( 4 3)) ( B 7 4 5 1 0 0 1).  
Ge o metric m ea n ( % C V) C ma x a n d A U C ta u f oll o wi n g m ulti ple-d ose a d mi nistrati o n of 

P F- 0 4 9 6 5 8 4 2
B 7 4 5 1 0 1 4
Fi nal P r otoc ol A me n d me nt 5, 2 8 Oct o ber 2 0 1 9
P FI Z E R C O N FI D E N TI A L
Pa ge 4 2
2 0 0 m g BI D were 1 7 % a n d 5 6 % hi g her, res pecti vel y , i n t he Wester n s u bjects ( n = 5) t han i n 
Ja pa nese s u bjects ( n = 6). 
C o -a d mi nistrati o n of 4 0 0 m g ( 4 x 1 0 0 m g) of t he ta blet wit h f o o d res ulte d i n e q ui vale nt 
ge o metric mea n A U C i nf bet wee n faste d a n d fe d c o n diti o ns a n d a s mall mea n decrease 
( < 5 %) i n Cma x .  T he ma g nit u de of decrease i n Cma x was n ot c o nsi dere d t o be cli nicall y  
i mp orta nt.  O verall, P F - 0 4 9 6 5 8 4 2 ca n be a d mi nistere d wit h or wit h o ut f o o d.
Plas ma pr ofili n g fr o m t he [ 1 4C] P F -0 4 9 6 5 8 4 2 h u ma n mass bala nce st u d y  ( B 7 4 5 1 0 0 8) 
i n dicate d pare nt as t he m ost pre vale nt circ ulati ng s pecies ( 2 6 %), wit h 3 maj or a n d m ore p olar 
m o n o -h y dr o x y late d meta b olites i de ntifie d: P F - 0 6 4 71 6 5 8 ( 3 -h y dr o x y pr o p yl , 1 1 %), 
P F - 07 0 5 5 0 8 7 ( 2 -h y dr o x y pr o p y l, 1 2 %), a n d P F-0 7 0 5 4 8 7 4 ( p y rr oli di n o ne p yri mi di ne, 1 4 %).
1. 4. P o p ul ati o n P h ar m ac o ki netics
P o p ulati o n p har mac o ki netic ( P K) a nal ysis was c o n d ucte d b y p o oli n g data fr o m t w o P hase 1 
st u dies ( B 7 4 5 1 0 0 1, first-i n-h u ma n st u d y , a n d B 7 4 5 1 0 0 4, relati ve bi oa vaila bilit y st u d y) i n 
healt h y  s u bjects a n d t he pr o of- of-c o nce pt st u d y ( B 7 4 5 1 0 0 6) i n A D patie nts.  Baseli ne b o d y
wei g ht, race, a ge a n d se x were teste d as c o vari ates o n cleara nce a n d di d n ot a p pear t o i m pact 
t he P K of P F- 0 4 9 6 5 8 4 2. 
1. 5. S u m m ar y of Be nef its a n d Ris ks
T here was cli nicall y mea ni n gf ul be nefit de m o nstrate d i n t he P hase 2 b Pr o of of C o nce pt st u d y  
i n a d ult patie nts wit h m o derate t o se vere A D.  T he p ote ntial ris ks of treat me nt i ncl u de t h ose 
t hat were n ote d i n P hase 2 b a n d/ or t h ose base d o n t he p h ar mac ol o g y of J A K i n hi bit ors a n d 
i ncl u de viral reacti vati o n, seri o us a n d o p p ort u nistic i nfecti o ns, he mat o p oietic effects
(i ncl u di n g re d uce d platelet c o u nt), a n d mali g nan c y  a n d i m m u n o proliferati ve dis or ders. 
F urt her i nf or mati o n is a vaila ble i n t he I n vesti g at or’s Br oc h ure (I B).  A p pr o priate ris k 
e val uati o n a n d miti gati o n strate gies ha ve bee n i nc or p orate d i nt o t his pr ot oc ol.
O verall, t here is a fa v ora ble be nefit -ris k pr ofile t o s u p p ort t he c o nti n ue d de vel o p me nt i nt o 
P hase 3 of P F -0 4 9 6 5 8 4 2 i n t he treat me nt of patie nts, 1 2 years of a ge a n d ol der, wit h A D f or 
b ot h t he 1 0 0 m g a n d 2 0 0 m g d ose.
1. 6. D ose Selecti o n R ati o n ale
D ose selecti o n f or P hase 3 was base d o n efficac y  a n d safet y of P F - 0 4 9 6 5 8 4 2 fro m a 
d ose -ra n gi n g P hase 2 b st u d y , B 7 4 5 1 0 0 6 t hat e val uate d a 2 0-f ol d d ose ra n ge ( 1 0 m g t o 
2 0 0 m g Q D) i n a d ult s u bjects wit h A D.  T he 2 0 0 m g Q D d ose as a m o n ot hera p y  is e x pecte d 
t o pr o vi de efficac y si milar t o t hat of c urre ntl y a p pr o ve d s yste mic treat me nts (eg c y cl os p ori ne, 
s yste mic c ortic oster oi ds a n d d u pil u ma b) i n m o derate t o se vere A D, base d o n d ose-res p o nse 
m o deli n g of I G A res p o nse i n t he P hase 2 st u d y , a n d was t heref ore selecte d as t he hi g h dose 
f or e val uati o n i n P hase 3 st u dies.  A d diti o n all y, a d ose of 1 0 0 m g Q D was als o selecte d f or 
P hase 3 e val uati o n. T he 1 0 0 m g d ose is e x pecte d t o differe ntiate fr o m t he hi g her d ose i n 
ter ms of e x pecte d efficac y, safety a n d s ys te mic e x p os ure.  B ot h 1 0 0 m g a n d 2 0 0 m g Q D 

P F- 0 4 9 6 5 8 4 2
B 7 4 5 1 0 1 4
Fi nal P r otoc ol A me n d me nt 5, 2 8 Oct o ber 2 0 1 9
P FI Z E R C O N FI D E N TI A L
Pa ge 4 3
d oses de m o nstrate d acce pta ble saf et y a n d t olera bi lit y i n t he P hase 2 st u d y .  F urt her details 
are a vaila ble i n t he I B. 
Si nce b o d y  wei g ht di d n ot a p pear t o be a si g nifica nt deter mi na nt of P K acr oss t he wei g ht 
ra n ge e val uate d i n t he P hase 2 b st u d y, a d olesce nts a ge d 1 2 ye ars a n d ol der wei g hin g 4 0 k g or 
m ore will be a d mi nistere d t he sa me d ose as t he a d ults (ie, 1 0 0 m g Q D a n d 2 0 0 m g Q D.)  
(See Secti o n 1. 3 P o p ulati o n P har mac o ki netics) .  T he P K efficac y  a n d safet y data c ollecte d i n 
a dolesce nts wil l be m o n it ore d peri o dicall y b y a n e xter nal data m o nit ori n g c o m mittee 
( E-D M C ) t o e ns ure acce pta ble be nefit ris k f or t his patie nt p o p ulati o n.
 
 
 
 
 
2. S T U D Y O B J E C TI V E S A N D E N D P OI N T S
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 pr o vi de d i n Ta ble 1. 
T a ble 1.
O bjecti ves a n d E n d p oi nts
Pri m ar y O bjecti ve:
Pri m ar y E n d p oi nt:

T o e val uate a n d c o m pare 
t he mai nte na nce of effect of 
t wo d oses of P F -0 4 9 6 5 8 4 2 
( 2 0 0 m g a n d 1 0 0 m g o nce
dail y ( Q D)) a n d place b o i n 
s u bjects a ge d 1 2 a n d a b o ve 
wit h m o derate t o se vere 
at o pic der matitis w h o 
res p o n d t o i nitial o pe n-la bel 
r u n-i n treat me nt of 2 0 0 m g 
P F -0 4 9 6 5 8 4 2 Q D.
1.
L oss of res p o nse re q uiri n g resc ue treat me nt will be e val uate d a n d 
c o m pare d a mo n g gr o u ps d uri n g t he bli n de d treat me nt peri o d.  L oss 
of res p o nse is de n ote d as flare a n d is defi ne d as a l oss of at least 
5 0 % of t he Ecze ma Area a n d Se verit y I n de x ( E A SI) re s p o nse at 
Wee k
1 2 a n d a n I n vesti gat or’s Gl o bal Assess me nt (I G A) sc ore of 
2 o r hi g her.
C CI

P F- 0 4 9 6 5 8 4 2
B 7 4 5 1 0 1 4
Fi nal P r otoc ol A me n d me nt 5, 2 8 Oct o ber 2 0 1 9
P FI Z E R C O N FI D E N TI A L
Pa ge 4 4
S ec o n d ar y O bjecti ves:
Sec o n d ar y E n d p oi nts:

T o e val uate a n d c o m pare 
t he effect of P F-0 4 9 6 5 8 4 2 
o n a d diti o nal efficac y 
e n d p oi nts a n d 
patie nt -re p orte d o utc o mes 
o ver ti me i n s u bjects a ge d 
1 2 years a n d ol der w it h 
m o derate t o se vere at o pic 
der matitis;

T o assess the efficac y of 
o pe n la bel resc ue treat me nt 
c o nsisti n g of 2 0 0 m g 
P F -0 4 9 6 5 8 4 2 i n 
c o m bi nati o n wit h t o pical 
t hera p y per sta n dar d of care 
i n cases of flare ( per 
pr ot oc ol def i niti o n). 
K e y Sec o n d ar y E n d p oi nt
1.
L oss of res p o nse base d o n a n I G A sc ore of 2 or hi g her.
Cli nic al Effic ac y Assess me nts:
1.
Res p o nse base d o n t he I G A (sc ore of 0 or 1 a n d a re d ucti o n of 
≥2 p oi nts ) at all sc he d ule d ti me p oi nts. 
2.
Res p o nse base d o n E A SI t otal sc o re ( E A SI-5 0, E A SI -7 5, E A SI -9 0, 
a n d E A SI -1 0 0) at all sc he d ule d ti me p oi nts.
3.
Res p o nse bas ed o n ac hie vi n g ≥4 p oi nt i m pr o ve me nt i n t he se verit y 
of pr urit us N u merical Rati n g Scale ( N R S) fr o m baseli ne at all 
sc he d ule d ti me p oi nts.
4.
Perce nt c ha n ge fr o m baseli ne i n perce nt B o d y  S urface Area ( B S A) at 
all sc he d ule d ti me p oi nts.
5.
Perce nt c ha n ge fr o m baseli ne i n S C O Ri n g At o pic Der matitis 
( S C O R A D) s u bjecti ve assess me nts of itc h a n d slee p l oss at all 
sc he d ule d ti me p oi nts. 
6.
Res p o nse base d o n ac hie vi n g a 5 0 % a n d 7 5 % i mpr o ve me nt i n 
S C O R A D ( S C O R A D -5 0, S C O R A D -7 5) fr o m baseli ne a t all 
sc he d ule d ti me p oi nts.
Cli n ic al Effic ac y Assess me nts i n S u bjects Re q uiri n g Resc ue 
Tre at m e nt:
1.
Res p o nse base d o n t he I G A at t he e n d of resc ue t hera p y. 
2.
Res p o nse ba se d o n t he E A SI t otal sc ore at t he e n d of resc ue t hera p y. 
3.
Res p o nse base d o n ac hie vi n g ≥4 p oi nt i m pr o ve me nt i n t he se verit y 
of pr urit us N u merical Rati n g Scale ( N R S) at t he e n d of resc ue 
t hera p y relati ve t o t he start of resc ue t hera p y baseli ne val ue .
4.
Perce nt c ha n ge i n perce nt B o d y S urface Area ( B S A) at t he e n d of 
resc ue t hera p y relati ve t o t he start of resc ue t hera p y baseli ne val ue .
5.
Perce nt c ha n ge i n S C O R A D s u bjecti ve assess me nts of itc h a n d slee p 
l oss at t he e n d of resc ue t hera p y relati ve t o t he start of resc ue t hera p y
baseli ne val ue .
6.
Res p o nse base d o n ac hie vi n g a 5 0 % a n d 7 5 % i mpr o ve me nt i n 
S C O R A D ( S C O R A D -5 0, S C O R A D -7 5) at t he e n d of resc ue t hera p y 
relati ve t o t he start of resc ue t hera p y baseli ne val ue .
P atie nt -Re p orte d O u tc o mes i n All Su bjects :
1.
Res p o nse base d o n ac hie vi n g Pt G A sc ore of clear ( 0) or al m ost clear 

P F- 0 4 9 6 5 8 4 2
B 7 4 5 1 0 1 4
Fi nal P r otoc ol A me n d me nt 5, 2 8 Oct o ber 2 0 1 9
P FI Z E R C O N FI D E N TI A L
Pa ge 4 5
(1); a n d a re d ucti o n fr o m baseli ne of ≥2 p oi nts at all sc he d ule d ti me 
p oi nts ( a mo n g s u bjects wit h a sc ore ≥2 at baseli ne) .
2.
C ha n ge fr o m ba seli ne i n Der mat ol o g y Life Q ualit y I n de x ( D L QI) or 
C hil dre n’s D L QI ( C D L QI) at all sc he d ule d ti me p oi nts. 
3.
C ha n ge fr o m ba seli ne i n H os pital A n xiet y De pressi o n Scale 
( H A D S) at all sc he d ule d ti me p oi nts.
4.
C ha n ge fr o m baseli ne i n Patie nt Orie nte d Ecze m a Meas ure ( P O E M) 
at all sc he d ule d ti me p oi nts.
5.
C ha n ge fr o m baseli ne i n t he Pr urit us a n d S y m pt o ms Assess me nt i n 
At o pic Der matitis ( P S A A D) at all sc he d ule d ti me p oi nts.
S afet y O bjecti ve:
S afet y E n d p oi nts:

T o assess t he safet y a n d 
t olera bilit y of P F-0 4 9 6 5 8 4 2 
d uri n g o pe n la bel a n d 
d o u ble bli n d treat me nt i n 
s u bjects a ged 1 2 a n d o ver 
w it h m o derate t o se vere 
A D.

I nci de nce of treat me nt em er ge nt a d verse e ve nts.

I nci de nce of Seri o us A d verse E ve nts ( S A E)s a n d A d verse E ve nts 
( A E)s lea di n g t o disc o nti n uati o n.

T he i nci de nce of cli nical a b n or malities a n d c ha n ge fr o m baseli ne i n 
cli nical la b orat or y val ues, electr ocar di o gra m ( E C G) meas ure me nts, 
a nd vital si g ns.
P h ar m ac o ki netic O bjecti ve:
P h ar m ac o ki netic E n d p oi nt :

T o e val uate t he P K of 
P F -0 4 9 6 5 8 4 2 a n d its 
meta b olites i n s u bjects a ge d 
1 2 years a n d ol der w it h 
m o derate t o se vere at o pic
der matitis f ol l o wi n g 
1 2 we e ks of m ai nte n a nce
treat me nt.
1.
P o p ulati o n P K c haracterizati o n i n s u bjects a ge d 1 2 years ol d a n d 
a b o ve wit h m o derate t o se vere at o pic der matitis.
 
 
 
 
 
 
  
 
A D = At o p ic der matitis; A E = A d verse E ve nt; B S A = B o d y S urface Area; C D L QI = C hil dre n’s Der mat ol o g y 
Life Q ualit y I n de x; D L QI = D er m at ol o g y Life Q ualit y I n de x; E A SI = Ecze ma Area a n d Se verit y I n de x; 
E C G = Electr ocar di o gra m; H A D S = H os pital A n xiet y a n d De pressi o n Sca le; I G A = I n vesti gat or’s Gl o bal 
Assess me nt ; N R S = pr urit us n u merical rati n g scale; P K = p har m ac o ki netics; S C O R A D = Sc ori n g At o pic 
Der m atitis; P O E M = Patie nt -Orie nte d Ecze ma Meas ure ; Pt G A = Patie nt Gl o bal Assess me nt; P S A A D
= Pr urit us a n d S y m pt o ms Assess me nt f or At o pic Der matitis; Q D = O nce Dail y; S A E = Seri o us A d verse 
E ve nt.
C CI
C CI

P F- 0 4 9 6 5 8 4 2
B 7 4 5 1 0 1 4
Fi nal P r otoc ol A me n d me nt 5, 2 8 Oct o ber 2 0 1 9
P FI Z E R C O N FI D E N TI A L
Pa ge 4 6
3. S T U D Y D E SI G N
T his is a ra n d o mize d, res p o n der-e nric he d, d o u ble- bli n d, place b o -c o ntr olle d, P hase 3 
wit h dra wal tria l t o e val uate the efficac y  a n d safet y of P F-0 4 9 6 5 8 4 2 m o n o t hera py i n s u bje cts 
a ge d 1 2 ye ars a n d ol der wit h c hr o nic m o derate t o se vere A D as defi ne d per t he i ncl usi o n 
criteria a n d a b o d y wei g ht 4 0 k g.  A d olesce nt s u bjects bel o w t he le gal a ge of maj orit y  (legal 
a d ult h o o d) i n t he s u bject’s c o u ntr y ca n be e nr oll i n t his st u d y if i nstr ucte d b y t he s p o ns or a n d 
a p pr o ve d b y t he c o u ntr y ’s re g ulat or y/ healt h a ut h orit y.  If t hese a p pr o vals ha ve n ot bee n 
gra nte d, o nl y s u bjects t he le gal a ge of maj ority (le gal a d ult h o o d) i n t he s u bje ct’s c o u ntr y
are all o we d t o e nr oll.  F or s u bjects y o u n ger tha n t his, t heir le gall y acce pta ble 
re prese ntati ve/pare nt(s) or le gal g uar dia n pr o vi de writte n c o nse nt a n d mi n or c hil dre n pr o vi de 
asse nt, acc or di n g t o l ocal re g ulati o ns a n d r ules re ga r di n g a bilit y to gi ve asse nt a n d c o nse nt.   
After pr o vi di n g i nf or me d c o nse n t, s u bjects are assesse d f or st u dy eli gi bilit y at t he scree ni n g 
visit.  D uri n g t he scree ni n g peri o d, treat me nts f or A D are was he d - o ut, as a p plica ble, 
acc or di n g t o eli gi bilit y re q uireme nts.  A baseli ne ( Da y 1) visit is t o occ ur wit hi n 2 8 da y s 
after the scr e e ni n g visit. 
S u bjects ma y  be re-scree ne d o nce if t he y fail t he scree ni n g e val uati o ns f or reas o ns relate d t o 
i nci de ntal tra nsit or y c o n diti o ns.  S u bjects f or w h o m scree n fail ure is relate d t o faili n g t he 
dis ease se verit y (i ncl u di n g e xte nt of disease) i ncl usi o n criteri o n a n d w h o s u bse q ue ntl y 
e x perie nce w orse ni n g A D, w hic h i n t he i n vesti gat or’s j u d ge me nt w o ul d ma ke t he m eli gi ble 
f or partici pati o n, ma y be c o nsi dere d f or re-scree ni n g.  S uc h cases s h o ul d be disc usse d wit h 
t he Pfizer Me dical M o nit or y ( or desi g nee) t o deter mi ne if re-scree ni n g is a p pr o priate.
T he trial c o nsists of a n o pe n -la bel r u n-i n peri o d t o deter mi ne res p o n der stat us t o a n i nitial 
i n d ucti o n treat me nt wit h 2 0 0 m g P F-0 4 9 6 5 8 4 2 Q D, a ra n d o mize d, plac e b o-c o ntr olle d,
d o u ble -bli n de d P F -0 4 9 6 5 8 4 2 mai nte n a nce treat me nt peri o d, a n d a 4 wee k u ntreate d 
f oll o w-u p safet y peri o d.  S u bjects w h o meet t he pr ot oc ol defi niti o n of flare d uri n g bli n de d 
treat me nt e nter a n o pe n-la bel resc ue treat me nt peri o d.  A st u d y desig n sc he matic is prese nte d 
i n Fi g ure 1 . 

P F- 0 4 9 6 5 8 4 2
B 7 4 5 1 0 1 4
Fi nal P r otoc ol A me n d me nt 5, 2 8 Oct o ber 2 0 1 9
P FI Z E R C O N FI D E N TI A L
Pa ge 4 7
Fi g ure 1 .
St u d y Desi g n Sc he m atic
E nr olle d s u bjects i nitiate t he 1 2 -wee k, o pe n -la bel r u n-i n peri o d t o i de ntif y res p o n ders w h o 
ha ve a p os iti ve cli nical res p o nse t o i n d ucti o n treat me nt wi t h 2 0 0 m g P F -0 4 9 6 5 8 4 2 Q D.  
Res p o n der criteri a are defi ne d as a) ac hie vi n g a n I G A of clear ( 0) or al m ost clear ( 1) ( o n a 
5 - p oi nt scale), b) a re d ucti o n fr o m I G A baseli ne of 2 p oi nts, a n d c) reac hi n g a n E A SI - 7 5 
res p o nse c o m pare d t o baseli ne.  Baseli ne is defi ne d as t he I G A sc ore a n d E A SI sc ore 
o btai ne d pri or t o d osi n g o n Da y  1.  S u bjects meeti n g all res p o n der criteria ma y be eli gi ble f or 
ra n d o mizati o n.  S u bjects w h o d o n ot reac h t he res p o nse t hres h ol d re q uire d f or ra n d o mizati o n 
are declare d n o n-res p o nders after c o m pleti o n of t he o pe n la bel r u n- i n peri o d. 
N o n -res p o n ders are n ot eli gi ble f or ra n d o mizati o n i n t his st u d y b ut ma y ch o ose t o e nr oll i nt o 
t he P F-0 4 9 6 5 8 4 2 L o n g Ter m E xte nsi o n ( L T E) st u d y  B 7 4 5 1 0 1 5 pr o vi din g t he y  re mai n 
eli gi ble; ot her wise, t he y are per mane ntl y disc o nti n ue d fr o m treat me nt a n d e nter t he 4 -wee k 
u ntreate d f oll o w -u p peri o d i n t his st u d y .
Res p o n ders at t he e n d o f t he 1 2-wee k o pe n -la bel r u n-i n peri o d e nter t he 4 0 wee k, 
d o u ble - bli n d, mai nte na nce treat me nt peri o d i n w hic h t he y are ra n d o mize d i nt o 1 of 
3 treat me nt ar ms i n a 1: 1: 1 rati o: 
1.
1 0 0 m g P F -0 4 9 6 5 8 4 2 Q D;
2.
2 0 0 m g P F -0 4 9 6 5 8 4 2 Q D; 
3.
Place b o.

P F- 0 4 9 6 5 8 4 2
B 7 4 5 1 0 1 4
Fi nal P r otoc ol A me n d me nt 5, 2 8 Oct o ber 2 0 1 9
P FI Z E R C O N FI D E N TI A L
Pa ge 4 8
All s u bjects w h o ha ve s tarte d was h-o ut of A D treat me nt i n t he scree ni n g peri o d will be 
all o we d t o e nter t he r u n-i n a n d treat me nt peri o ds pr o vi di n g all i ncl usio n criteria a n d n o ne of 
t he e xcl usi o n criteria are met. Ra n d o mizati o n is stratifie d b y a ge cate g or y, ie , < 1 8 years a n d 
1 8 ye ars.  Eli gi ble s u bjects m ust ha ve a d oc u me nte d hist or y  of i na de q uate res p o nse wit h 
t o pical A D me dicati o ns or ha ve re q uire d s yste mic t hera pies f or c o ntr ol of t heir disease. 
Me dicate d t o pical a n d/ or s y ste mic sta n dar d of care t hera pies are n ot all o we d d uri n g t he 
o pe n -la bel r u n-i n a n d bli n de d treat me nt peri o ds. 
Me dicate d t o pical t hera p y is defi ne d as a 
t o pical pr o d uct t hat c o ntai ns a n acti ve p har mace utical i n gre die nt i n dicate d f or t he treat me nt 
of A D (irres pecti ve of w het her it is a n o ver -t he-c o u nter [ O T C ] or prescri pti o n o nl y pr o d uct).
F oll o wi n g c o m pleti o n of t he 4 0 -wee ks of bli n de d tre at me nt, all s u bjects are assesse d f or 
eli gibilit y  to e nter t he P F -0 4 9 6 5 8 4 2 L T E st u d y  B 7 4 5 1 0 1 5.  If a s u bject disc o nti n ues 
pre mat urel y or is n ot eli gi ble/ willi n g t o partici p ate i n B 7 4 5 1 0 1 5, t he n t he s u bject e nters t he 
4 - wee k u ntreate d f oll o w-u p peri o d.
D uri n g t he bli n de d treat me nt peri o d, s u bjects m eeti n g the pr ot oc ol defi niti o n of fl are e nter 
a n o pe n-la bel resc ue peri o d d uri n g w hic h t he y recei ve a n ot her 1 2-wee k c o urse of 2 0 0 m g  
P F - 0 4 9 6 5 8 4 2 Q D wit h t o pical t hera py per l ocal sta n dar d of care ( S O C).  I n t his s t u d y, flare 
re q uiri n g resc ue treat me nt is defi ne d as a l oss of at least 5 0 % of t he E A SI res p o nse at 
Wee k
1 2 a n d a n I G A sc ore of 2 or hi g her.  F or e xa m ple, if a s u bject h as a t otal E A SI sc ore of 
4 0 at baseli ne a n d a sc ore of 1 0 at Wee k 1 2 (ac hie vi n g E A SI - 7 5 t o be a res p o n der at 
ra n d o mizati o n), t he EA SI res p o nse is - 3 0.  T o meet t he defi niti o n of flare, t he t otal E A SI  
sc ore f or t his s u bject w o ul d ha ve t o g o u p by at least 15 ( 5 0 % of -3 0) fr o m Wee k 1 2, w hic h 
c o m p utes t o a t otal E A SI sc ore of at least 2 5, t his i n a d diti o n t o a n IG A sc ore of 2. 
After c o m pleti n g t he 1 2 -wee k resc ue peri o d, s u bjects ma y  e nter t he L T E st u d y B 7 4 5 1 0 1 5, if 
eli gi ble.  S u bjects disc o nti n ui n g earl y fr om treat me nt, or w h o are ot her wise i neli gi ble f or t he 
L T E st u d y e nter a 4 wee k f oll o w - u p peri o d i n B 7 4 5 1 0 1 4.
A n i n vesti gat or ca n te m p orari ly i nterr u pt d osi n g f or u p t o a ma xi m u m of 2 8 c o nsec uti ve da ys 
f or a s u bject, f or safety reas o ns or w hile m o nit ori n g a b n or mal la b orat or y  tests if t he 
i n vesti gat or j u d ges t hat t his is necessar y. T he i n vesti gat or s h o ul d use t heir j u d ge me nt wit h 
re gard t o u n sc he d ule d visits/la b orat or y/cli nical assess me nts re q uire d t o m o nit or t he s u bject 
d uri n g t his ti me- fra me. If wit hi n t his ti mefra me t he i n vesti gat or j u d ges t hat it is safe t o 
restart d osi n g, t he n t he s u bject m a y  restart i n vesti gati o nal pr o d uct. If the i n ve sti gat or j u d ges 
t hat it is n ot safe t o restart d osi n g wit hi n t his ti mefra me t he n t he s u bject m ust be per ma ne ntly 
disc o n ti n ue d fr o m treat me nt, ha ve a n E n d of Treat me nt visit a n d e nter t he 4-wee k f oll o w - u p 
pe ri o d.  D oses n ot ta ke n f or t he reas o ns me nti o ne d ab o ve d o n ot c o nstit ute pr ot oc ol 
de viati o ns or me dicati o n err ors a n d s h o ul d n ot be c o nsi dere d d osi n g err ors, b ut s h o ul d be 
n ote d i n t he d osi n g l o g wit h t he reas o n f or re d uce d dr u g c o ns u m pti o n clearl y  descri be d.
La b orat or y  tests are perf or me d t hr o u g h out t his st u d y as detaile d i n t he Sc he d ule of Acti vities
a n d i n vesti gat ors will f oll o w t he i n str ucti o ns f or m ore fre q ue nt m o nit ori n g i n A p pe n di x 4 if 
t he s pecifie d la b orat or y val ues reac h t he liste d th res h ol ds.

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B 7 4 5 1 0 1 4
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P FI Z E R C O N FI D E N TI A L
Pa ge 4 9
T he t otal st u d y  d urati o n if a s u bject d oes n ot flare is 5 2 wee ks ( 1 2 wee ks o pe n -la bel 
treat me nt + 4 0 wee ks bli n de d treat me nt).  T he ma xi m u m st u d y  d urati o n is u p t o 6 4 wee ks.  
T his w o ul d o nl y  be achie ve d if a s u bject flare d o n t he last da y  of t he mai nte na nce treat me nt 
peri o d ( 5 2 wee ks + 1 2 wee ks resc ue) .  If s u bjects d o n ot i nte n d t o e nr oll i n t he L T E st u d y, t he 
a b o ve d urati o ns are e xte n de d b y  + 4 wee ks of a n u ntreate d f oll o w -u p peri o d.  A t otal of 
a ppr o xi matel y  1 3 7 0 s u bjects will be e nr olle d fr o m a pp r o xi matel y 2 1 8 sites l ocate d gl o ball y. 
4. S U B J E C T E LI GI BI LI T Y C RI T E RI A
T his st u d y  ca n f ulfill its o bjecti ves o nl y if a p pr o priate s u bjects are e nr olle d.  T he f oll o wi n g 
eli gi bilit y criteria are desi g ne d t o select s u bjects f or w h o m partici pati o n i n t he st u d y is
c o nsi dere d a p pr o priate.  All rele va nt me dical a n d n o n m e dical c o n diti o ns s h o ul d be ta ke n i nt o 
c o nsi derati o n w he n deci di n g w het her a partic ular s u bject is s uita ble f or t his pr ot oc ol. 
S u bject eli gi bilit y  s ho ul d be re vie we d a n d d oc u me nte d b y  a n a p pr opriate m e m ber of t he 
i n vesti gat or’s st u dy tea m (t hat is lice nse d t o practice me dici ne i n t he state/ pr o vi nce or 
c o u ntr y w here t he st u d y is bei n g c o n d ucte d or by a n ot her healt hcare practiti o ner as per mitte d 
b y  l ocal la w) bef ore s u bjects are i ncl u de d i n t he st u d y.  Initial s u bject eli gi bilit y  m ust be 
c o nfir me d a n d d oc u me nte d pri or t o s u bjects recei vi n g a d ose of i n vesti gati o nal pr o d uct (I P). 
4. 1. I ncl usi o n Criteri a
S u bjects m ust meet all of t he f oll o wi n g i ncl usi o n criteri a t o be eli gi ble f or e nr oll me nt i nt o t he 
stu d y :
1.
E v ide nce of a pers o nall y  si g ne d a n d date d i nf or me d c o nse nt d oc u me nt i n dicati n g t hat 
t he s u bject, or his/ her le gall y acce pta ble re prese ntati ve/pare nt(s) or le gal g uar dia n if a 
mi n or, ha ve bee n i nf or me d of all perti ne nt as pects of t he st u d y . 
2.
Male or fe male s u b jects of 1 2 ye ars of a ge or ol der, at t he ti me of i nf or me d c o nse nt 
a n d b o d y wei g ht 4 0 k g.  A d olesce nt s u bjects bel o w t he le gal a ge of maj orit y  (le gal 
a d ult h o o d) i n t he s u bject’s c o u ntr y  will o nl y be e nr olle d i n t his st u d y if i nstr ucte d b y 
t he s p o ns or a n d a p pr o ve d b y t he c o u ntr y’s re g ulat or y/ healt h a ut h orit y. If t hese 
a p pr o vals ha ve n ot bee n gra nte d, o nl y s u bjects t he le gal a ge of maj ority (le gal 
a d ult h o o d) i n t he s u bject’s c o u ntr y  will be e nr olle d.
3.
Meet
all t he f oll o wi n g at o pic der matitis criter ia:

Cli n ical dia g n osis of c hr o nic at o pic der matitis (als o k n o w n as at o pic ecze ma) f or 
at least 1 ye ar pri or t o Da y 1 a n d has c o nfir me d at o pic der matitis at t he scree ni n g 
a n d baseli ne visits acc or di n g t o Ha nifi n a n d Raj ka criteria of A D 4 3 (see 
A p pe n di x 2 ).

D oc u me nte d rece nt hist or y  ( wit hi n 6 m o nt hs bef ore t he scree ni n g v isit) of 
i na de q uate res p o nse t o treat me nt wit h me dicate d to pical t hera p y f or A D f or at 
least 4 wee ks, or w h o ha ve re q uire d s y ste mic t hera pies f or c o ntr ol of t heir 
disease.

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N O T E: Me dicate d t o pical t hera p y is defi ne d as a t o pical pr o d uct t hat c o ntai ns a n 
acti ve p har mace utical i n gre die nt i n dicate d f or t he treat me nt of A D (irres pecti ve of 
w het her it is a n o ve r-t he-c ou nter [ O T C] or prescri pti o n o nl y pr o d uct).

M o derate t o se vere A D (affecte d B S A 1 0 %, I G A 3, E A SI  1 6 a n d pr urit us 
N R S se verit y  4 o n t he da y  of t he baseli ne visit).
4.
Willi n g a n d a ble t o c o m pl y  wit h sc he d ule d visits, treat me nt pla n, la b orat or y tests a n d 
ot h er st u d y pr oce d ures.
5.
Fe male s u bjects w h o are of c hil d- beari n g p ote ntial ( w hic h i ncl u des a d olesce nts a ge d 
1 2 ye ars a n d ol der re gar dless of w het her t h e y  ha ve e x perie nce d me narc he) m ust n ot 
be i nte n di n g t o be c o me pre g na nt, c urre ntl y pre g na nt, or lacta ti n g.  T he f oll o wi n g 
c o n diti o ns a p pl y:
a.
Fe male s u bjects of c hil d beari n g p ote ntial m ust ha ve a c o nfir me d ne gati ve 
pre g na nc y  test pri or t o treat me nt wit h i n vesti gati o nal pr o d uct;
b.
Fe male s u bjects of c hil d beari n g p ote n tial m ust a gree t o use a hi g hly effecti ve 
m et h o d of c o ntrace pti o n (as per Secti o n 4. 4. 1 ) f or t he d urati o n of t he acti ve 
treat me nt peri o d a n d f or at least 2 8 d a y s after t he last d ose of i n vesti gati o nal 
pr o d uct.
N O T E: Se x ual a bsti ne nce, d efi ne d as c o m pletely a n d persiste ntl y refrai ni n g fr o m all 
heter ose x ual i nterc o urse (i ncl u di n g d uri n g t he e ntire peri o d of ris k ass ociate d wit h 
st u d y treat me nts) ma y o b viate t he nee d f or c o ntrace pti o n O N L Y if t his is t he 
preferre d a n d us ual lifest y le of t he s u bject. 
6.
Fe male s u bjects of n o n -c hil d beari n g p ote ntial m ust meet at least 1 of t he f oll o wi n g 
criteria: 

Ha ve u n der g o ne a d oc u me nte d h y sterect o m y a n d/ or bilateral o o p h orect o m y;

Ha ve me dicall y  c o nfir me d o varia n fail ure; or

Ac hie ve d p ost me n o pa usal stat us, d efi ne d as f oll o ws: cessati o n of re g ular me nses 
f or at least 1 2 c o nsec uti ve m o nt hs wit h n o alter nati ve pat h ol o gical or 
p h y si ol o gical ca use a n d ha ve a ser u m f ollicle-sti m ulati n g h or m o ne ( F S H) le vel 
c o nfir mi n g t he p ost me n o pa usal state.
All ot her fe male s u bjec ts (i nclu di n g fe male s u bjects wit h t u bal li gati o ns) are 
c o nsi dere d t o be of c hil d beari n g p ote ntial.
7.
M ust a gree t o a v oi d pr ol o n ge d e x p os ure t o t he s u n a n d n ot t o use ta n ni n g b o ot hs, s u n 
la m ps or ot her ultra vi olet li g ht s o urces d uri n g t he st u d y.

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4. 2. E xcl usi o n Cr iteri a
S u bjects wit h a n y of t he f oll o wi n g c haracteristics/c o n diti o ns will n ot be i ncl u de d i n t he 
st u d y:
1.
Ot her ac ute or c hr o nic me dical or ps yc hi atric c o n diti o n i ncl u di n g rece nt ( wit hi n t he 
past y ear) or acti ve s ui ci dal i deati o n or be ha vi or or la b orat or y  a bn or mali ty t hat ma y 
i ncrease t he ris k ass ociate d wit h st u d y partici pati o n or i n vesti gati o nal pr o d uct 
a d mi nistrati o n or ma y i nterfere wit h t he i nter pretati o n of st u d y res ults a n d, i n t he 
j u d g me nt of t he i n vesti gat or, w o ul d ma ke t he s u bject i na p pr o priate f or e ntr y in t o t his 
st u d y.
2.
A n y  psyc hiatric c o n diti o n i ncl u di n g rece nt or acti ve s uici dal i deat i o n or be ha vi or t hat 
meets a n y of t he f oll o wi n g criteria: 

S uici dal i deati o n ass ociate d wit h act ual i nte nt a n d a met h o d or pla n i n t he past 
ye ar: “ Yes” a ns wers o n items 4 or 5 of t he C ol u m bia s uici de se verit y rati n g scale 
( C-S S R S) ( A p pe n di x 1 5 );

Pre vi o us hist or y  of s uici dal be ha vi ors i n t he past 5 years: “ Yes” a ns wer (f or 
e ve nts t hat occ urre d i n t he past 5 years) t o a n y of the s uic idal be ha vi or ite ms of 
t he C-S S R S;

A n y  lifeti me hist or y of seri o us or rec urre nt s uici dal be ha vi or;

S uici dal be ha vi ors q uesti o n naire – re vise d ( S B Q-R) t otal sc ore 8 ( A p pe n di x 1 7 );

Cli nicall y  si g nifica nt de pressi o n: patie nt health q uesti o n naire – 8 ite ms ( P H Q -8) 
t otal sc ore 1 5 ( A p pe n di x 1 8 );

T he prese nce of a n y c urre nt maj or ps yc hiatric dis or der t hat is n ot e x plicitl y 
per mitte d i n t he i ncl usi o n/e xcl usi o n criteria;

I n t he o pi ni o n of t he i n vesti gat or or P fizer ( or desi g nee) e xcl usi o n is re q uire d.
3.
A c urre nt or past me dical hist or y  of c o n diti o ns ass ociate d wit h t hr o m b oc yt o pe nia, 
c oa g ul o pat h y or platelet d ysf u ncti o n.
4.
Recei vi n g a nti -c oa g ula nts or me dicati o ns kn o w n t o ca use t hr o m b oc y t o pe nia ( u nless 
c o nsi dere d safe t o st o p a n d was h o ut f o r t he d urati o n of t he st u d y).
5.
C urre ntl y  ha ve acti ve f or ms of ot her i nfla m mat or y s ki n diseases, ie, n ot A D or ha ve 
e vi de nce of s ki n c o n diti o ns (e g, ps oriasis, se b orr heic der matitis , L u p us) at t he ti me of 
D a y 1 t hat w o ul d i nterfere wit h e val uati o n of at o pic der matitis or res p o nse t o 
treat me nt.

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6.
Vacci nate d or e x p ose d t o a li ve or atte n uate d vacci ne wit hi n t he 6 wee ks pri or t o t he 
first d ose of i n vesti gati o nal pr o d uct, or is e x pecte d t o be vacci nate d or t o ha ve 
h o use h ol d e x p os ure t o t h ese vacci nes d uri n g treat ment or d uri n g t he 6 wee ks 
f oll o wi n g disc o nti n uati o n of i n vesti gati o nal pr o d uct.
7.
A d olesce nt s u bjects 1 2 t o < 1 8 ye ars ol d wit h o ut d oc u me nte d e vi de nce of ha vi n g 
recei ve d at least o ne d ose of t he varicel la vacci ne i n c o u ntries w here t he vacci ne is 
a p pr o ve d a n d sta n dar d of care or t h ose w h o d o n ot ha ve e vi de nce of pri or e x p os ure t o 
varicella z oster vir us ( V Z V) base d o n ser ol o gical testi n g (ie, varicella z oster vir us 
i m m u n o gl o b uli n G a ntib o d y  [ V Z V I g G A b]) at scree ni n g.
8.
S u bjects w h o ha ve recei ve d pri or treat me nt wit h a n y J A K i n hi bit ors.
9.
Partici pati o n i n ot her st u dies i n v ol vi n g i n vesti gati o nal dr u g(s) 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 st u d y e ntr y a n d/ or d uri n g 
st u dy partici pati o n.
N ote: A n y  i n vesti gati o nal or e x peri me ntal t hera py ta ke n or pr oce d ure perf or me d f or 
A D, ps oriasis, ps oriatic art hritis or r he u mat oi d art hritis i n t he pre vi o us 1 ye ar s h o ul d 
be disc usse d wit h t he Pfizer Me dical M o nit or ( or desi g nee).  S u bjec ts ca n n ot 
partici pate i n st u die s of ot her i n vesti gati o nal or e x peri me ntal t hera pies or pr oce d ures 
at a n y ti me d uri n g t heir partici pati o n i n t his st u d y .
1 0. Ha ve recei ve d a n y of t he f oll o wi n g treat me nt re gi me ns s pecifie d i n t he ti mefra mes 
o ut li ne d bel o w:
Wit hi n
1 ye ar of first d ose of i n vest igati o nal pr o d uct:

Pri or treat me nt wit h n o n B cell -s pecific ly m p h oc yte de pleti n g a ge nts/t hera pies 
(e g, ale mt uz u ma b [ C A M P A T H ], al k ylati n g a ge nts [e g, c ycl o p h os p ha mi de or 
c hl ora m b ucil], t otal l ym p h oi d irra di ati o n, etc.).  S u bj ects w h o ha ve recei ve d 
rit u xi mab or ot her selecti v e B l y m p h oc y te de pleti n g a ge nts (i ncl u di n g 
e x peri me ntal a ge nts) are eli gi ble if t he y  ha ve n ot recei ve d s uc h t hera p y f or at 
least 1 ye ar pri or t o st u d y baseli ne a n d ha ve n or mal cl uster of differe ntiati o n ( C D ) 
1 9/ 2 0 + c o u nts b y  fl u oresce nce-acti vate d cell s or ti n g ( F A C S) a nal ysis.
Wit hi n 1 2 wee ks of first d ose of i n vesti gati o nal pr o d uct:

Ot her bi ol o gics: wit hi n 1 2 wee ks of first d ose of i n vesti gati o nal pr o d uct or 
5 half -li ves (if k n o w n), w hic h e ver is l o n ger.
Wit hi n 6 wee ks of first d ose of i nv esti gati o nal pr o d uct:

Use of d u pil u ma b.

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Wit hi n 4
wee ks of first d ose of i n vesti gati o nal pr o d uct: 

Use of oral i m m u n os u p pressi ve dr u gs (e g, c ycl os p ori n A [ Cs A], azat hi o pri ne, 
met h otre xate, s y ste mic c ortic oster oi ds, m yc o p he n olate-m ofetil, I F N -) wit hi n 
4 we eks of first d ose of i n vesti gati o nal pr o d uct or wit hi n 5 half -li ves (if k n o w n), 
w hic he ver is l o n ger; 

P h ot ot hera p y  narr o w ba n d U V B (N B -U V B) or br oa d ba n d p h ot ot hera p y;

Re g ular use ( m ore t ha n 2 visits per wee k) of a ta n ni n g b o o t h/ parl or;

Her bal me dicati o ns wi t h u n k n o w n pr o perties or k n o w n be neficial effects f or A D.
Wit hi n 1 wee k of first d ose of i n vesti gati o nal pr o d uct:

A nti- platelet dr u gs. 
N ote: l o w d ose acet y l salic ylic aci d (1 0 0 m g  Q D) is per mitte d, f or the p ur p ose of 
car di o vasc ular pr o p h yl a xis, at t he d iscreti o n of t he i n vesti gat or.
Wit hi n 7 2 h o urs of first d ose of i n vesti gati o nal pr o d uct:

T o pical treat me nts t hat c o ul d affect at o pic der matitis (e g, c ortic oster oi ds, 
calci ne uri n i n hi bit ors, tars, a nti bi otic crea ms, t o pical a n ti hista mi nes);
N ote: C ortic os teroi d i n halers a n d i ntra nasal s pra ys are all o we d f or sta ble ast h ma 
a n d/ or aller gic r hi nitis patie nts.
1 1. Ha ve a hist or y  of a n y ly m p h o pr oliferati ve dis or der s uc h as E pstei n Barr Vir us ( E B V) 
relate d ly m p h o pr olife rati ve dis or der, hist or y of l y m p h o ma, le u ke mia, or si g ns or 
s ym pt o ms s u g gesti ve of c urre nt l y m p hatic or l y m p h oi d disease.
1 2. I nfecti o n Hist or y:
a.
Ha ve a hist or y  of s yste mic i nfecti o n re q uiri n g h os pitalizati o n, pare nteral 
a nti micr o bial t hera p y, or as ot her wise j u d ge d cli nicall y  sig nifica nt b y t he 
i n vesti gat or wi t hi n 6 m o nt hs pri or t o Da y 1.
b.
Ha ve acti ve c hr o nic or ac ute s ki n i nfecti o n re q uiri n g treat me nt wit h s y ste mic 
a nti bi otics, a nti virals, a nti parasitics, a nti pr ot oz oals, or a ntif u n gals wit hi n 2 wee ks 
pri or t o D a y 1 , or s u perficial s ki n i nfecti o ns wit hi n 1 we e k pri or t o Da y 1.
c.
A s u bject k n o w n t o be i nfecte d wit h H u ma n I m m u n o deficie nc y Vir us ( HI V), 
He patitis B, or He patitis C ( Secti o n 7. 6. 2 ).

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F or C hi n a a n d T ai w a n o nl y :
S u bjects w h o are he patitis B s u rface a nti ge n (H Bs A g ) ne gati ve, he patitis B c ore 
a nti b o d y (H Bc A b ) p ositi ve, a n d he patitis B s urface a nti b o d y  (H Bs A b ) p ositi ve at 
Scree ni n g will ha ve refle x testi n g f or h e patitis B vir us ( H B V ) D N A. S u bjects
w h o ha ve H B V D N A a b o ve t he l o wer li mit of q ua ntif icati o n ( L L Q) will be
e xcl u de d.  S u bjects w h o are H B V D N A ne gati ve or bel o w L L Q ma y  e nr oll b ut 
will ha ve H B V D N A tes ti n g re peate d at Wee ks 1 2, 2 8, 4 0, 5 2 , Resc ue Wee k
1 2 , 
a n d earl y ter mi nati o n fr o m st u d y  d uri n g a ny treat me nt peri o d .
d.
Ha ve a hist or y  (si n gle e pis o de) of disse mi nate d her pes z oster or disse mi nate d 
her pes si m ple x, or a rec urre nt ( m ore t ha n o ne e pis o de of) l ocalize d, der mat o mal 
her pes z oster.
1 3. Ha ve a hist or y  of alc o h ol or s u bsta nce a b use wit hi n 6 m o nt hs pri or t o Da y 1 t hat i n 
t he o pi ni o n of t he i n vesti gat or will precl u de partici pati o n i n t he st u d y .
1 4. A Scree ni n g 1 2 -lea d E C G t hat de m o nstrates cli nicall y si g nifica nt a b n or malities 
re q uiri n g treat me nt (e g, ac ute m yocar dial i nfarcti o n, seri o us tac h y - or 
br a d y- arr h yt h mias) or t hat are i n dicati ve of seri o us u n derl y i n g heart disease 
(e g, car di o m yo pat h y , maj or c o n ge nital heart disease, l o w v olta ge i n all lea ds, 
W olff - Par ki ns o n-W hite s y n dr o me) or criteria ass ociate d wit h Q wa ve i nter val 
( Q T)/ Fri dericia-c orrecte d Q wa ve ( Q Tc F) a b n o r malities i ncl u di n g:

A mar ke d p rol o n gati o n of Q Tc F i nter val ( > 4 5 0 millisec o n ds [ ms]) o n t he 
scree ni n g E C G;

A hist or y  of a d ditio nal ris k fact ors f or T orsa de de P oi ntes ( T d P) (e g, heart fail ure, 
h y p o kale mia, fa mil y hist or y of L o n g Q T S y n dr o me);

Use of c o nc o m ita nt me dicati o ns t hat pr ol o n g the Q T/ Q Tc F i nter val.
1 5. Ha ve a k n o w n i m m u n o deficie nc y  dis or der or a first-de gree relati ve wit h a here ditar y  
i m m u n o deficie nc y.
1 6. Ha ve a n y m ali g na ncies or ha ve a hist or y of mali g na ncies wit h t he e xce pti o n of 
a de quatel y treate d or e xcise d n o n -metastatic basal cel l or s q ua m o us cell ca ncer of t he 
s ki n, or cer vical carci n o ma i n sit u.
1 7. Re q uire treat me nt wit h pr o hi bite d c o nc o mita nt me dicati o n(s) ( Secti o n 5. 9. 2 a n d 
A p pe n di x 3 ) or ha ve recei ve d a pr o hi bite d c o nc o mita nt me dicati o n wit hi n t he 
s pecifie d ti me fra me pri or t o t he first d ose of st u d y me dicati o n.
1 8. Ha ve e vi de nce of acti ve or late nt or i na de q uate l y treate d i nfecti o n wit h 
M y c o bacteri u m t u berc ul os is ( T B) as e vi de nce d b y a ny of t he f oll o wi n g:

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
A p ositi ve Q ua nti F E R O N -T B G ol d ( Q F T -G) I n -T u be test or p ositi ve 
Ma nt o u x/ P urifie d Pr otei n Deri vati ve ( P P D) t u berc uli n s ki n test perf or me d at or 
wit hi n t he 1 2 we e ks pri or t o Da y 1.

It is rec o m me n de d t hat s u bjects wit h a hist or y of Bacille Cal mette G uéri n ( B C G) 
vacci nati o n be teste d wit h t he Q F T -G test si nce t he Ma nt o u x/ P P D t u berc uli n s ki n 
test ma y be p ositi ve d ue t o vacci nati o n.  See Secti o n 7. 3. 4 f or re q uire me nts f or 
Ma nt o u x/ P P D t u berc uli n s ki n testi n g. 

A ne gati ve Q F T -G or Ma nt o u x/ P P D t u berc uli n s ki n test is re q uire d u nless t he 
s u bject has pre vi o usly recei ve d a d oc u me nte d a de q uate c o urse of t hera p y f or 
eit her late nt ( 9 m o nt hs of is o niazi d i n a l ocal e w here rates of pri mar y  m ulti-dr u g 
T B resista nce are < 5 % or a n acce pta ble alter nati ve re gi me n) or acti ve (acce pta ble 
m ulti -dr u g re gi me n) T B i nfecti o n.  If t he c urre nt i nci de nce rates of m ulti-dr u g 
resista nt T B i nfecti o n i n the l ocale are u na vaila ble, a n a d e q uate treat me nt re gi me n 
s h o ul d be defi ne d as t he re gi me n rec o m me n de d b y t he healt h mi nistr y or e x pert 
pa nel i n t he l ocale;

C hest ra di o gra p h ( or c hest C o m p ute d T o m o gra p h y ( C T) sca n, if a vaila ble) ta ke n 
at scree ni n g wit h c ha nges s u g gesti ve of acti ve t u berc u l osis ( T B) i nfecti o n as 
deter mi ne d b y a q ualifie d ra di ol o gist.  A c hest X -ra y is re q uire d f or a d ults a n d 
rec o m me n de d f or a d olesce nts per l ocal sta n dar d/ g ui deli nes, u nless pre vi o usl y 
perf or me d a n d d oc u me nte d wit hi n 1 2 wee ks p ri or t o St u d y D a y 1.

A hist or y  of eit her u ntreate d or i na de q uatel y treate d late nt or acti ve T B i nfecti o n;

A s u bject w h o is c urre ntl y bei n g treate d f or acti ve T B i nfecti o n is t o be e xcl u d e d.
1 9. A N Y of t he f oll o wi n g a b n or malities i n cli nical la b orat or y tests at scree ni n g, as 
assesse d b y t he st u d y-s pecific la b orat or y a n d c o nfir me d b y a si n gle re peat, if dee me d 
necessar y :

A bs ol ute ne utr o p hil c o u nt of < 1. 2 x 1 0 9/ L ( < 1 2 0 0/ m m3);

He m o gl o bi n < 1 0. 0 g/ d L  or he mat ocrit < 3 0 %;

Platelet c o u nt of < 1 5 0 x 1 0 9/ L ( < 1 5 0, 0 0 0/ m m3);

A bs ol ute l y m p h oc y te c o u nt of < 0. 5 0 x 1 0 9 / L ( < 5 0 0/ m m3);

Esti mate d Creati ni ne Cleara nce < 4 0 m L / mi n base d o n t he a ge a p pr o priate 
calc ulati o n, or ser u m creati ni ne > 1. 5 ti mes t he u p per li mit of n or mal ( U L N);

As partate a mi n otra nsferase ( A S T) or ala ni ne a mi n otra nsferase ( A L T) val ues 
> 2 ti mes the U L N;

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
T otal bilir u bi n 1. 5 ti mes t he U L N; s u bjects wit h a hist or y of Gil bert's sy n dr o me 
ma y  ha ve a direct bilir u bi n meas ure d a n d w o ul d be eli gi ble f or this st u d y  
pr o vi de d t he direct bilir u bi n is U L N.
2 0. I n t he o pi ni o n of t h e i n vesti gat or or s p o ns or, ha ve a n y u nc o ntr olle d cli nicall y 
si g nifica nt la b orat or y a b n or malit y t hat w o ul d affect i nter pretati o n of st u dy data or t he 
s u bject’s partici pati o n i n t he st u d y.
2 1. Ha ve u n der g o ne si g nifica nt tra u ma or maj or s ur ger y wit hi n 1 m o nt h of t he first d ose 
of i n vesti gati o n al pr o d uct.
2 2. I n vesti gat or site staff me m bers directly i n v ol ve d i n t he c o n d uct of t he st u d y a n d t heir 
fa mil y me m bers, site staff me m bers ot her wise s u per vise d b y  t he i n vesti gat or, or 
s u bjects w h o are Pfizer e mpl o y ees, i ncl u di n g t heir fa mil y me m bers, directl y in v ol ve d 
i n t he c o n d uct of t he st u d y. 
2 3. Ha ve k n o w n h y p erse nsiti vit y t o P F-0 4 9 6 5 8 4 2 or t o a n y  of t he e xci pie nts of t he st u d y 
dr u g.
4. 3. R a n d o miz ati o n Criteri a 
S u bjects will be e nr olle d i nt o t he o pe n -la bel, r u n-i n peri o d of t he st u d y pr o vi de d t he y or t heir 
le gally acce pta ble re prese ntati ve /pare nt(s) or le gal g uar dia n if a mi n or, ha ve si g ne d a n 
i nf or me d c o nse nt d oc u me nt at scree ni n g t o partici pate i n t he st u d y, have u n der g o ne all 
scree ni n g pr oce d ures, a n d ha ve met all i ncl usi o n a n d n one of t he e xcl usi o n criteria f o r
partici pati o n i n t he st u d y  at Da y 1.  S u bjects w h o c o m plete t he r u n-i n peri o d a n d res p o n d t o 
o pe n -la bel treat me nt will be ra n d o mize d t o o ne of t hree treat me nt ar ms a n d e nter t he 
d o u ble -bli n d peri o d of t he trial (see Secti o n 3 ).  Ra n d o mizati o n is stratifie d b y a ge cate g or y, 
ie, < 1 8 years a n d 1 8 ye ars.  A c o m p uter- ge nerate d ra n d o mizati o n sc he d ule will be use d t o 
assi g n s u bjects t o t he treat me nt gr o u ps usi n g a n I nt eracti ve Res p o nse Tec h n ol o g y (IR T). 
4. 4. Lifest yle Re q uire me nts 
I n or der t o partici pate i n t he st u d y, s u bjects m ust be a ware of t he f oll o wi n g lifestyl e
g ui deli nes a n d restricti o ns t hat a p pl y d uri n g a n d after t he treat me nt peri o d.

O n st u d y  visit da ys: Da y 1, W ee ks 4, 1 2, 5 2 a n d E n d of St u d y ( E O S) a n d 
c orres p o n di n g visits if a s u bject e nters t he resc ue treat me nt peri o d, s u bjects m ust 
c o m pl y wit h fasti n g re q uire me nt f or at least 8 h o urs pri or t o t he visit.  Water a n d 
per mitte d n o n -st u d y me dicati o ns are all o we d (see Secti o n 5. 9. 1 ).

O n st u d y  visit da ys, s u bjects m ust n ot s m o ke or i n gest caffei ne d uri n g t he 3 0 mi n utes 
pri or t o bl o o d press ure a n d heart rate meas ure me nts.

O n st u d y  visit da ys, s u bjects m ust n ot ta ke t he d o se of i n vesti gatio nal pr o d uct u ntil 
i nstr ucte d t o d o s o b y t he i n vesti gat or or desi g nate d st u d y site staff.

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
O n st u d y  visit da ys, s h o weri n g or bat hi n g is per mitte d pri or t o atte n di n g t he st u d y 
visit, b ut s u bjects m ust n ot m oist urize or a p pl y  e m ollie nt.  N o n-me dicate d e m oll ie nt 
is all o we d after t he visit.  Disc o nti n ue a n d a v oi d usi n g certai n me dicati o ns a n d 
treat me nts (Secti o n 4. 2 , Secti o n 5. 9. 2 , a n d A p pe n di x 3 ).

A gree t o use o ne hi g hl y  effecti ve met h o d of c o ntrace pti o n (as s pecifie d i n 
Secti o n 4. 4. 1 , as a p plica ble.
4. 4. 1. C o ntr ace pti o n
T he c o ntrace pti o n c hec k is a n o p p ort u nit y t o c o nfir m t hat c o ntrace pti o n, if assi g ne d, is use d 
c o nsiste ntl y a n d c orrectl y.  It als o facilitates c o nti n ual reassess me nt of c hil d-beari n g p ote ntial 
i n w o me n.  T his all o ws f or i m ple me nti n g necessary c ha n ges t o c o ntrace pti o n; f or e xa m ple, 
i n vesti gat ors ma y nee d t o e ns ure alter nati ve c o ntrace pti ve met h o ds if ne w c o nc o mita nt 
disease c o ntrai n dicates a selecte d met h o d of c o ntrace pti o n, or if a s u bject is de m o nstra bl y  n o 
l o n ger of c hil d-beari n g stat us (as per pr ot oc ol) t he n t he y  will no l o n ger re q uire c o ntrace pti o n.  
C o nti n ual reassess me nt of c o ntrace pti ve nee ds is i m perati ve.
All fe male s u bjects w h o are of c hil d beari n g p ote ntial i ncl u di n g a d olesce nts a ge d 1 2 ye ars 
a n d ol der re gar dless o f w het her t he y ha ve e x perie nce d me narc he, w h o are, i n t he o pi ni o n of 
t he i n vesti gat or, se x uall y acti ve a n d at ris k f or pre g na nc y wit h t heir part ner(s) m ust a gree t o 
use a hi g hl y effecti ve met h o d of c o ntrace pti o n c o nsiste ntl y  a n d c orrectl y f or t he d urati o n of 
t he acti ve treatme nt peri o d a n d f or at least 2 8 d a y s after t he last d ose of i n vesti gati o nal 
pr o d uct. 
T he i n vesti gat or or his or her desi g nee, i n c o ns ultati o n wit h t he s u bject, will c o nfir m t hat t he 
s u bject has selecte d a n a p pr o priate met h o d of c o ntracepti o n f or t he i n di v id ual s u bject a n d her 
part ner f ro m t he per mitte d list of c o ntrace pti o n met h o ds (see bel o w) a n d will c o nfir m t hat t he 
s u bject has bee n i nstr ucte d i n its c o nsiste nt a n d c orrect use.  At ti me p oi nts i n dicate d i n t he 
Sc he d ule of A cti vities , t he i n vesti gat or or desi g nee will i nf or m t he s u bject of t he nee d t o use 
hi g hl y effecti ve c o ntrace pti o n c o nsiste ntl y  a n d c orrectly a n d d oc u me nt t he c o n versati o n a n d 
t he s u bject’s affir mati o n i n t he s u bject’s c hart (s u bjects nee ds t o affir m t hei r c o nsiste nt a n d 
c orrect use of at least 1 of t he selecte d met h o ds of c o ntrace pti o n).  I n a d diti o n, t he 
i n vesti gat or or desi g nee will i nstr uct t he s u bject t o call i m me diatel y if t he selecte d 
c o ntrace pti o n met h o d is disc o nti n ue d or if pre g na nc y  is k n o w n or s us pecte d i n t he s u bject or 
t he part ner. 
Hi g hl y effecti ve met h o ds of c o ntrace pti o n are t h ose t hat, al o ne or i n c o m bi nati o n, res ult i n a 
fail ure rate of less t ha n 1 % per ye ar w he n use d c o nsiste ntl y a n d c orrectl y (ie, perfect use) a n d 
i ncl u de t he f oll o wi n g:
1.
E sta blis he d use of h or m o nal meth o ds of c o ntrace pti o n ass ociate d wit h i n hi biti o n of 
o v ulati o n (e g, oral, i nserte d, i njecte d, i m pla nte d, tra ns der mal) pr o vi de d t he s u bject 
pla ns t o re mai n o n t he sa me treat me nt t hr o u g h o ut t he e ntire st u d y  an d has bee n usi n g 
t hat h or m o nal c o ntrace pti ve f or an a de q uate peri o d of ti me t o e ns ure effecti ve ness.
2.
C orrectl y place d c o p per -c o ntai ni n g i ntra uteri ne de vice (I U D). 

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3.
Male c o n d o m or fe male c o n d o m use d WI T H a se parate s per mici de pr o d uct (ie, f oa m, 
gel, fil m, crea m, or s u p p osit o r y).  F or c o u ntries w here s per mici de is n ot a vaila ble or 
c o n d o m pl us s per mici de is n ot acce pte d as hi g hl y effecti ve c o ntrace pti o n, t his o pti o n 
is n ot a p pr o priate.
4.
Male sterilizati o n wit h a bse nce of s per m i n t he p ost- vasect o m y ejac ulate. 
N ote: Vasect o mize d p art ner is a hi g hl y effecti ve b irt h c o ntr ol met h o d pr o vi de d t hat 
part ner is t he s ole se x ual part ner of t he w o ma n of c hil d beari n g p ote ntial ( W O C B P) 
trial partici pa nt a n d t hat t he vasect o mize d part ner has recei ve d me dical assess me nt of 
the s ur gical s uccess .
5.
Bilateral t u bal li gati o n/ bilat eral sal pi n gect o m y or bilateral t u bal occl usi ve pr oce d ure 
( pr o vi de d t hat occl usi o n has bee n c o nfir me d i n acc or da nce wit h t he de vice’s la bel).
N O T E: Se x ual a bsti ne nce, defi ne d as c o m pletel y a n d persiste ntl y refrai ni n g fr o m all 
heter ose x ual i nterc o urse (i nc lu di n g d uri n g t he e ntire peri o d of ris k ass ociate d wit h t he st u d y  
treat me nts) ma y o b viate t he nee d f or c o ntrace pti o n O N L Y if t his is t he preferre d a n d us ual 
lifest yle of t he s u bject. 
T he c o ntrace pti o n c hec k is a n o p p ort u nit y to c o nfir m t hat c o ntrace pti o n, if assi g ne d, is use d 
c o nsiste ntl y a n d c orrectl y. 
F or c o u ntries i n t he E U:
Hi g hl y effecti ve met h o ds of c o ntrace pti o n are t h ose t hat, al o ne or i n c o m bi nati o n, res ult i n a 
fail ure rate of less t ha n 1 % per ye ar w he n use d c o nsis tentl y  a n d c orrectl y (ie, perfect use) a n d 
i ncl u de t he f oll o wi n g:
1.
Esta blis he d use of h or m o nal met h o ds of c o ntrace pti o n ass ociate d wit h i n hi biti o n of 
o v ulati o n (e g, oral, i nserte d, i njecte d, i m pla nte d, tra ns der mal) pr o vi de d t he s u bject 
pl a ns t o re mai n o n t he sa me treat me nt t hr o u g h o ut t he e ntire st u d y a n d has bee n usi n g 
t hat h or m o nal c o ntrace pti ve f or a n a de q uate peri o d of ti me t o e ns ure effecti ve ness.
2.
C orrectl y place d c o p per -c o ntai ni n g i ntra uteri ne de vice (I U D).
3.
Male sterilizati o n wit h a bs e nce of s per m i n t he p ost -vasect o m y ejac ulate.
N ot e: Vasect o mize d part ner is a hi g hl y effecti ve birt h c o ntr ol met h o d pr o vi de d t hat 
part ner is t he s ole se x ual part ner of t he W O C B P trial partici pa nt a n d t hat t he 
vasect o mize d part ner has recei ve d me dical asse ss me nt of t he s urgi cal s uccess.
4.
Bilateral t u bal li g ati o n/ bilateral sal pi n gect o m y or bilateral t u bal occl usi ve pr oce d ure 
( pr o vi de d t hat occl usi o n has bee n c o nfir me d i n acc or da nce wit h t he de vice’s la bel).

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N O T E: Se x ual a bsti ne nce, defi ne d as c o m pletel y a n d persiste ntl y refrai ni n g fr o m all 
heter ose x ual i nter co urse (i ncl u di n g d uri n g t he e ntire peri o d of ris k ass ociate d wit h t he st u d y  
treat me nts) ma y o b viate t he nee d f or c o ntrace pti o n O N L Y if t his is t he preferre d a n d us ual 
lifest yle of t he s u bject.
4. 4. 2. V acci ne a n d E x p os ure t o I nfec tio ns G ui deli nes
4. 4. 2. 1. S u bject S pecific Rec o m me n d ati o ns
It is rec o m me n de d t hat all s u bjects s h o ul d be u p-t o-date wit h res pect t o sta n dar d of care 
vacci nati o ns (as defi ne d b y  t heir c o u ntr y healt h mi nistr y) or A D g ui deli nes.  Vacci nati o n of 
s u bjects wit h li ve atten u ate d vacci nes is pr o hi bite d wit h i n t he 6 wee ks pri or t o first d ose of 
i n vesti gati o nal pr o d uct.  A d olesce nt s u bjects wit h o ut d oc u me nte d e vi de nce of ha vi n g 
recei ve d at least o ne d ose of t he varicella vacci ne or t h ose w h o are wit h o ut e vi de nce of 
pre vi o us va ricella z oster e x p os ure as c o nfir m e d b y V Z V I g G A b ser ol o gical testi n g are 
e xcl u de d.
4. 4. 2. 2. G ui d a nce Re g ar di n g H o use h ol d C o nt act V acci ne - Rel ate d E x p os ure
C urre nt r o uti ne h o use h ol d c o ntact wit h c hil dre n a n d ot hers w h o ha ve bee n vacci nate d wit h a 
li ve atte n uate d va cci ne ma y p ose a ris k d uri n g treatme nt a n d f or 6 wee ks f oll o wi n g 
c o m pleti o n of t he st u d y.  S o me of t hese vacci nes i ncl u de varicella (“c hic ke n p o x”) vacci ne, 
oral p oli o vacci ne, a n d t he i ntra nasal fl u vacci ne.  F oll o wi n g vacci nati o n wit h li ve atte n uate d 
vacc i nes, t he vir us ma y be s he d i n b od il y fl ui ds, i ncl u di n g st o ol, a n d t here is a p ote ntial ris k 
t hat t he vir us ma y be tra ns mitte d.  Ge neral g ui deli nes f or i m m u n os u p presse d s u bjects 
s u g gest t hat e x p os ure (t hr o u g h r o uti ne c o ntact) s h o ul d be a v oi de d f oll o wi n g vacci nati o n ( of 
ot hers) wit h t hese v acci nes f or t he state d ti me peri o d:
a.
Varicella or atte n uate d t y p h oi d fe ver vacci nati o n f or 4 wee ks f oll o wi n g vacci nati o n.
b.
Oral p oli o vacci nati o n f or 6 wee ks f oll o wi n g vacci nati o n.
c.
Atte n uate d r ota vir us vacci ne f or 1 0 d a y s f ollo wi n g vacci nati o n.
d.
Fl u Mist (i ntra nasal fl u vacci ne) f or 1 wee k f oll o wi n g vacci nati o n.
S u bjects s h o ul d a v oi d e x p os ure t o vacci nate d or i nfecte d pers o ns a n d c o ntact t he i n vesti gat or 
pr o m ptl y s h o ul d t he y  de vel o p si g ns or sy m pt o ms of i nfect i o ns.
4. 4. 3. S ur ger y
D uri n g t he st u d y , n o electi ve s ur gery s h o ul d occ ur wit h o ut first c o ns ulti n g wit h t he Pfizer 
Me dical M o nit or or desi g nee.  Prefera bl y, electi ve s ur ger y  s h o ul d occ ur bef ore t he st u d y or 
be dela y e d u ntil partici pati o n i n t he st u d y is c o m plete d.
T he Pf izer Me dical M o nit or or desi g nee s h o ul d be n o tifie d if a s u bject re q uires s ur ger y 
(i ncl u di n g de ntal s ur ger y) d uri n g t he st u d y t o deter mi ne w het her t he s u bject s h o ul d 
disc o nti n ue fr o m t he st u d y a n d/ or disc o nti n ue i n vesti gati o nal pr o d uct pri or t o t he s ur gica l 
pr oce d ure. I n ge neral, pla n ne d s ur gical pr oce d ures s h o ul d n ot be perf or me d u nless t he 

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i n vesti gati o nal pr o d uct has bee n disc o nti n ue d f or at least 2 8 d a y s ( u nless ot her wise a d vise d 
b y  t he Pfizer Me dical M o nit or or desi g nee).  T he Pfizer Me dical M o nit or or desi g nee s h o ul d 
be n otifie d as s o o n as p ossi ble if a s u bject u n der g oes a s ur gical pr oce d ure wit h o ut first 
i nf or mi n g t he st u dy staff.
4. 5. S p o ns or’s Q u alifie d Me dic al Pers o n nel
T he c o ntact i nf or mati o n f or t he s p o ns or's a p pr o priatel y  q ualifie d me dical perso n nel f or t he 
st u d y is d oc u me nte d i n t he st u d y c o ntact list l ocate d i n t he c o or di nat or’s ma n ual a n d i n t he 
st u d y p ortal.
T o facilitate access t o a p pr o priatel y q ualifie d me dical pers o n nel o n st u d y- relate d me dical 
q uesti o ns or pr o ble ms, s u bjects are pr o vi de d wit h a c o ntact car d.  T he c o ntact car d c o ntai ns, 
at a mi ni m u m, pr ot oc ol a n d i n vesti gati o nal pr o d uct i de ntifiers, s u bject st u d y  n u m bers, 
c o ntact i nf or mati o n f or t he i n vesti gat or site, a n d c o ntact details f or a c o ntact ce nter i n t he 
e ve nt t hat t he i n vesti gat or site staff ca n not be reac he d t o pr o vi de a d vice o n a me dical 
q uesti o n or pr o ble m ori gi nati n g fr o m a n ot her healt hcare pr ofessi o nal n ot i n v ol ve d i n t he 
s u bject’s partici pati o n i n t he st u d y.  T he c o ntact n u m ber ca n als o be use d b y i n vesti gat or 
staff if t hey are see ki n g a d vice o n me dical q uesti o ns or pr o bl ems; h o we ver, it s h o ul d be use d 
o nl y  i n t he e ve nt t hat t he esta blis he d c o m m u nicati o n pat h wa ys bet wee n t he i n vesti gat or site 
a n d t he st u d y tea m are n ot a vaila ble.  It is t heref ore i nte n de d t o a u g me nt, b ut n ot re place, t he 
establis he d c o m m u nicati o n pat h wa y s b et wee n t he i n vesti gat or site a n d t he st u d y tea m f or 
a d vice o n me dical q uesti o ns or pr o ble ms t hat ma y arise d uri n g t he st u d y.  T he c o ntact 
n u m ber is n ot i nte n de d f or use b y t he s u bject directl y , a n d if a s ubject , t heir le gally 
acce pta ble re prese ntati ve /par e nt(s) or le gal g uar dia n calls t hat n u m ber, he or s he will be 
directe d bac k t o t he i n vesti gat or site.
5. S T U D Y T R E A T M E N T S 
F or t his st u d y , t he i n vesti gati o nal pr o d ucts are P F-0 4 9 6 5 8 4 2 a n d place b o.  E nr olle d s u bjects
recei ve 1 2 w ee ks i n d ucti o n treat me nt of 2 0 0 m g  P F-0 4 9 6 5 8 4 2 Q D d uri n g a n o pe n -la bel 
r u n-i n peri o d.  At t he e n d of t he 1 2 wee ks, s u bjects res p o n di n g t o treat me nt as descri be d i n 
Secti o n 3 are ra n d o mize d i nt o t he d o u ble- bli n d e d, mai nte nance treat me nt peri o d d uri n g 
w hi ch t he y  recei ve 2 0 0 m g P F-0 4 9 6 5 8 4 2 Q D, 1 0 0 m g P F -0 4 9 6 5 8 4 2 Q D, or place b o 
( 1: 1: 1 ra n d o mizati o n rati o) f or 4 0-wee ks.  T he last d ose of o pe n la bel r u n- i n treat me nt 
( 2 0 0 m g) is a d mi nistere d at t he Wee k 1 2 visit ; s u bjects i nitiate a d mi nistrati o n of ra n d o mize d 
b li n de d treat me nt t he da y after t he Wee k 1 2 visit.   I n t he e ve nt of l oss of res p o nse d uri n g 
bli n de d treat me nt de n ote d as flare, defi ne d as a l oss of at least 5 0 % of t he E A SI  res p o nse at 
Wee k
1 2 a n d a n I G A sc ore of 2 or hi g her, s u bjects will e nter a 1 2- wee k op e n -la bel resc ue 
peri o d a n d recei ve 2 0 0 m g P F -0 4 9 6 5 8 4 2 Q D wit h c o nc o mita nt t o pical t hera p y  per S O C.
A n i n vesti gat or ca n te m p oraril y i nterr u pt d osi n g f or u p t o a ma xi m u m of 2 8 c o nsec uti ve da ys 
f or a s u bject f or safety reas o ns or w hile m o nit ori n g a b n or mal l ab orat or y  tests if t he 
i n vesti gat or j u d ges t hat t his is necessar y (A p pe n di x 4 ). T he i n vesti gat or s h o ul d use t heir 
j u d ge me nt wit h re gar d t o u nsc he d ule d visits/la b orat or y /cli nical assess me nts re q uire d t o 
m o nit or t he s u bject d uri n g t his ti me -fra me. If wit hi n t his ti mefra me t he i n vesti gat or j u d ges 
t hat it is safe t o restart d osi n g, t he n t he s u bject ma y restart i n vesti gati o nal pr o d uct. If t he 

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i n vesti gat or j u d ges t hat it is n ot safe t o restart d osi n g wit hi n t his ti mefra me, t he n t he s u bject 
m ust be per ma ne ntl y disc o nti n ue d fr o m treat me nt, ha ve a n E n d of Treat me nt visit a n d e nter 
t he 4-wee k f oll o w -u p peri o d.  D oses n ot ta ke n f or t he reas o ns me nti o ne d a b o ve d o n ot 
c o nstit ute pr ot oc ol de viati o ns or me dicat i o n err ors a n d s h o ul d n ot be c on si dere d d osi n g 
err ors, b ut s h o ul d be n ote d i n t he d osi n g l o g wit h t he reas o n f or re d uce d dr u g c o ns u m pti o n 
clearl y descri be d.
F or t he p ur p oses of t h is st u d y, a n d per I nter nati o nal C o nfere nce o n Har m o nisati on (I C H) 
g ui deli nes, i n vesti gati o nal pr o d uct is define d as a p har mace utical f or m of a n acti ve 
i n gre die nt or place b o bei n g teste d or use d as a refere nce/c o m parat or i n a cli nical trial, 
i ncl u di n g a pr od uct wit h a mar keti n g a ut h orizati o n w he n use d or asse m ble d (f or m ulate d or 
pac ka ge d) i n a wa y  differe nt fr o m the a p pr o ve d f or m, or w he n use d f or a n u na p pr o ve d 
i n dicati o n, or w he n use d t o gai n f urt her i nf or mati o n a b o ut a n a p pr o ve d use (IC H E 6 1. 3 3). 
5. 1. All oc at i o n t o Tre at me nt
All ocati o n of s u bjects t o treat me nt gr o u p s will pr ocee d t hr ou g h t he use of a n I nteracti ve 
Re s p o nse Tec h n ol o g y (I R T) s yste m.  T he site pers o n nel (st u d y c o or di nat or or s pecifie d 
desi g nee) will be re q uire d t o e nter or select i nf or mati o n i ncl u di n g b ut n ot li mi te d t o t he 
user’s i de ntificati o n (I D) a n d pass w or d, pr ot oc ol n u m ber, t he s u bject n u m ber a n d t he date of 
birt h of t he s u bject.  T he site pers o n nel will t he n be pr o vi de d wit h a treat me nt assi g n me nt 
a n d dis pe nsa ble u nit ( D U) or c o ntai ner n u m ber w he n i n vesti ga ti o nal pr o d uct is bei n g 
s u p plie d via t he I RT.  T he I R T s ys t em will pr o vi de a c o nfir mati o n r ep ort c o ntai ni n g t he 
s u bject n u m ber a n d D U or c o ntai ner n u m ber assi g ne d.  T he c o nfir mati o n re p ort m ust be 
st ore d i n t he site’s files. 
T here is a 2 4 h o ur a da y , 3 6 5 da y s a year I R T hel p des k a vaila ble f or a n y  q uesti o ns or issues.  
T he st u d y  s pecific I R T refere nce ma n ual will pr o vi de t he c o ntact i nf or mati o n a n d f urt her 
details o n t he use of t he I R T. 
N ote: T he I R T is t he s o urce of t he s u bject n u m ber.  T he I R T s y ste m will pr o vi de t he s u bject 
n u m ber at t he e n d of t he first I R T s u bject tra nsacti o n.
5. 2. Resc ue Tre at me nt
S u bjects will be i nstr ucte d t o c o ntact t he site if t he y e x perie nce a si g nifica nt w orse ni n g of 
t heir at o pic der matitis, s uc h as a rec urre nce of pr urit us, d uri n g t he d o u ble-bli n d treat me nt 
peri o d.  Site staff will deter mi ne if t he s u bject s h o ul d ret ur n to t he site f or a n u nsc he d ule d 
(see Secti o n 6. 5. 1 ) or re g ularl y sc he d ule d visit (see Secti o n 6. 3 ). S u bject will be re mi n de d 
n ot t o ta ke st u d y dr u g o n t he da y of t he site visit.  At t he visit (re g ular or u n pla n ne d) t he 
s u bject will be assesse d f or flare, defi ne d as a l oss of at least 5 0 % of t he E A SI  res p o nse at 
Wee k
1 2 a n d a n I G A of 2 or hi g her.  S u bjec ts w h o meet t he defi niti o n of flare are t o recei ve 
resc ue treat me nt t hat da y a n d e nter a n o pe n -la bel resc ue peri o d d uri n g w hic h t he y recei ve 
1 2 -wee ks of 2 0 0 m g P F -0 4 9 6 5 8 4 2 Q D wit h c o nc o mita nt t o pical t hera p y per S O C.  See 
S ecti o n 5. 2. 1 f or g ui da nce o n t o pical t hera pies. 

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After c o m pleti n g t he resc ue peri o d, s u bjects ar e all o we d t o e nter t he L T E st u d y  B 7 4 5 1 0 1 5, if 
eli gi ble.  If a s u bject disc o nti n ues pre mat urel y or is n ot eli gi b le or willi n g t o partici pate i n 
B 7 4 5 1 0 1 5, t he n t he s u bject e nters t he 4- wee k, u ntreate d f oll o w- u p safety peri o d.  Refer t o 
Sc he d ule of Acti vities f or Resc ue Treat me nt .
S u bjects n ot meeti n g t he defi niti o n of flare will c o n ti n ue o n t heir bli nde d treat me nt.  
P h y sicia ns ma y co nti n ue t o cli nicall y  e val uate f or flare usi n g t he E A SI a n d I G A assess me nts 
at t heir discreti o n.
5. 2. 1. G ui deli nes f or T o pic al Resc ue Tre at me nt
Starti n g o n Da y  1 of resc ue treat me nt, all s u bjects will i nitiate t opical treat me nt a n d c o nti n ue 
a t o pical re gi me n as lo n g as nee de d d uri n g t he resc ue peri o d.  T hree classes of treat me nt 
re gi me ns, s pecificall y, t o pical c ortic oster oi ds, t o pical calci ne uri n i n hi bit ors, a n d a 
p h os p h o diesterase i n hi bit or 4 ( P D E -4) i n hi bit or, a re all o we d al o ne or i n c o m bi nati o n d uri n g 
t he rescu e peri o d.  I n vesti gat ors are t o use t hese t hree treat me nt classes acc or di n g t o t heir 
us ual practice . 
Rec o m me n de d t o pical treat me nts c o ul d i ncl u de:
T o pic al C ortic oster oi ds:
T o pical c ortic oster oi ds ( T C S) ca n be use d acc or di n g t o t he i n vesti gat or’s us ual practice.  T he 
f oll o wi n g use of T C S is s u g geste d f or t his st u d y:

A p pl y  me di u m p ote nc y T CS (e g, 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) o nce dail y t o areas wit h acti ve lesi o ns.

After lesi o ns are u n der c o ntr ol (clear or al m ost clear), treat o nce dail y f or 7 da ys, 
t he n st o p;

If lesi o ns ret ur n d uri n g t he rescue peri o d, res u me treat me nt wit h me di u m p ote nc y  
T C S, b ut use t he a p pr oac h descri be d a b o ve u p o n lesi o n res ol uti o n.

L o w p o te nc y T C S (ie, h y droc ortis o ne 1 % crea m) ca n be use d o nce dail y  o n areas of 
t hi n s ki n (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, etc.).

Hi g h or s u per -hi g h p ote nc y  T C S ma y be use d f or lesi o ns persisti n g or w orse ni n g 
u n der o nce dai l y treat me nt wit h me di u m p ote nc y T C S, u nless hi g her p ote nc y  T C S 
are c o nsi dere d u nsafe.
S u bject s h o ul d be m o nit ore d 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 T C S 
treat me nt as necessar y.  T C S treat me nt is n ot e x pecte d t o last l o n ger t ha n 4 wee ks.

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Ot her T o pic al Tre at me nts:
T he use of t o pical calci n e uri n i n hi bit ors (e g, tacr oli m us, pi mecr oli m us) or a 
p h os p h o diesterase 4 ( P D E -4) i n hi bit or (crisa b or ole) ca n be use d acc or di n g t o l ocall y  
a p pr o ve d la bel at t he i n vesti gat or’s discreti o n base d o n pri or res p o nse or i nt olera nce t o t hese 
me dicati o ns. 
I n cases w here t he desire d t o pical treat me nt re gi me n differs si g nifica ntl y  fr o m t he a b o ve 
g ui deli nes, t he Pfizer me dical m o nit or s h o ul d be c o ntacte d f or g ui da nce.
5. 3. Bre a ki n g t he Bli n d
I n vesti gat ors, s u bjects a n d t he s p o ns or st u d y tea m will be bli n de d as t o treat me nt gr o u p.  At 
all ti mes, treat me nt a n d ra n d o mizati o n i nf or mati o n will be ke pt c o nfi de nt ial a n d will n ot be 
release d t o t he i n vesti gat or, t he st u d y staff, or t he s p o ns or’s st u d y tea m u ntil f oll o wi n g t he 
c o nclusi o n of t he st u d y , wit h t he e xce pti o n descri be d i n t his secti o n. 
At t he i nitiati o n of t he st u d y , t he st u d y site will be i nstr ucte d o n pr oce d ures f or brea ki n g t he 
bli n d.  Bli n di n g c o des s h o ul d o nl y  be br o ke n i n e mer ge nc y sit uati o ns f or reas o ns of s u bject 
safety.  T he i n vest i gat or is res p o nsi ble f or a n d m ay brea k t he bli n d f or safet y  reas o ns w here 
t he k n o wle d ge of act ual treat me nt is esse ntial f or f urt her ma na ge me nt of t he s u bject.  T he 
met h o d will be a n electr o nic pr ocess.  W he n t he bli n d f or a s u bject has bee n br o ke n, t he 
reas o n m ust be f ull y d oc u me nte d an d e ntere d o n t he Case Re p ort F or m ( C R F).  W he ne ver 
p ossi ble, t he i n vesti gat or s h o ul d c o ntact Pfizer bef ore brea ki n g t he bli n d.  If t he bli n d is 
br o ke n, t he i n vesti gat or s h o ul d pr o m ptl y i nf or m t he Pfizer C li nicia n or Me dical M o nit or.  
T he s u bject f or w h o m t he bli n d has bee n br o ke n will be disc o nti n ue d fr o m t he st u d y a n d 
u n der g o t he early t er mi nati o n ( E T) pr oce d ures. 
5. 4. S u bject C o m pli a nce
F or self -a d mi nistrati o n of t he i n vesti gati o nal pr o d uct at h o me, ti me of d ose will be ca pt ur e d 
a n d c o m plete d b y t he s u bject .  S u bjects will be iss ue d a n electr o nic d osi n g diar y  (e Diar y) a n d 
will be e d ucate d t o rec or d t he ti me of dail y d osi n g o nce t he y ha ve ta ke n t he i n vesti gati o nal 
pr o d uct.   W he n i n vesti gati o nal pr o d uct is a d ministere d at t he res earc h facilit y, it will be 
a d min istere d u n der t he s u per visi o n of st u d y pers o n nel.
C o m plia nce wit h t he d osi n g of i n vesti gati o nal pr o d uct will be m o nit ore d a n d verifie d b y 
dele gate d site pers o n nel t hr o u g h a c o m bi nati o n of t he acc o u nti n g of u n use d i n vesti gati o nal 
pr o d uct ret ur ne d b y t he s u b ject at t he st u d y visits, re vie w of t he d osi n g diar y, a n d disc ussi o n 
wit h t he s u bject w hic h will be d oc u me nte d i n t he s o urce d oc u me nts. 
S u bjects s h o ul d ta ke t he i n vesti gati o nal pr o d uct fr o m st u d y  Da y 1 u n til i nstr ucte d ot her wise 
b y  t he site staff (e g, tem p orar y  i nterr u pti o n t o d osi n g).  I n vesti gati o nal pr o d uct s h o ul d be 
ta ke n i n t he m or ni n g w he ne ver it is p ossi ble; h o we ver at st u d y visit da ys, s u bjects are t o be 
i nstr ucte d t o refrai n fr o m d osi n g at h o me, an d are t o ta ke t he d ose i n t he cli nic.  S u bjects 
s ho ul d be i nstr ucte d t hat if a d ose is i na d verte ntl y misse d t he n it s h o ul d be ta ke n as s o o n as 
re me m bere d, b ut n ot wit hi n 1 2 h o urs of t he ne xt sc he d ule d d ose. T he s u bject s h o ul d e nter a 
dail y  rec or d i n t heir e Diar y e ver y ti me t he y ta ke a d ose of i n vesti gatio nal pr o d uct.

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T he f oll o wi n g c o m plia nce cases will be c o nsi dere d me dic ati o n err ors a n d will be disc usse d 
wit h t he s p o ns or f or p ossi ble wit h dra wal fr o m t he st u d y :

S u bjects i nterr u pti n g i n vesti gati o nal pr o d uct f or m ore t ha n 4 c o nsec uti ve da y s or f or a 
t otal o f m ore t ha n 7 d a y s bet wee n visits;

S u bjects a d mi ni steri n g > 8 ta blets i n o ne da y or a d mi nisteri n g 4 ta blets/ da y f or 
4 c o nsec uti ve da ys;

S u bjects w h o ha ve a n o verall c o m plia nce of < 8 0 % or > 1 2 0 % bet wee n visi ts 
A n y  de viati o n fr o m pr ot oc ol s pecifie d d osi n g s ho ul d be rec or de d as a pr ot oc ol de viati o n a n d 
t he in vesti gat or or desi g nee is t o c o u nsel t he s u bject , le gall y acce pta ble 
re prese ntati ve/pare nt(s) or le gal g uar dia n (if a p plica ble) a n d e ns ure ste ps are ta ke n t o 
i m pr o ve c o m pliance.  I n a d diti o n, if t he c o m plia nce de viati o n reac hes t he t hres h ol ds defi ne d 
a b o ve it s h o ul d als o be rec or de d as a me dicati o n err or (see Secti o n 8. 4. 4 ).
N ote: te m p orar y  i nterr u pti o n t o d osi n g per i n vesti gat or j u d ge me nt, as d escri be d i n 
A p pe n di x 4 , will n ot be c o nsi dere d a pr ot oc ol de viati o n or me dicati o n err or.
5. 5. I n vesti g ati o n al Pr o d uct S u p plies
5. 5. 1. D os a ge F or m(s) a n d P ac k a gi n g
P F -0 4 9 6 5 8 4 2 will be pr o vi de d as 1 0 0 m g ta blets f or oral a d mi nistrati o n d uri n g t he 
o pe n -la bel r u n i n a d mi nistrati o n of 2 0 0 m g P F -0 4 9 6 5 8 4 2 Q D. 
Bli n de d P F -0 4 9 6 5 8 4 2 a n d place b o will be pr o vi de d as 1 0 0 m g ta blets f or oral a d mi nistrati o n.  
T he 1 0 0 m g ta blets a n d t heir place b os will be s u p plie d i n se parate b ottles a n d la bele d 
acc or di n g t o l ocal re g ulat or y re quire me nts.
W he n recei ve d b y t he p har mac y , P F-0 4 9 6 5 8 4 2 a n d place b o will be i n c o ntai ners t hat will 
s ufficie ntl y bli n d all site staff t o c o nte nt wit hi n t he b ottles (ie, acti ve vers us place b o).
5. 5. 2. Pre p ar ati o n a n d Dis pe nsi n g
T he i n vesti gat io nal pr o d uct s h o ul d be dis pe nse d usi n g a dr u g ma na ge me nt s y ste m at eac h 
dis pe nsi n g visit.  A q ualifie d staff me m ber will dis pe nse t he i n vesti gati o nal pr o d uct via 
u ni q ue c o ntai ner n u m bers i n b ottles pr o vi de d, i n q ua ntities a p pr o priate f or t he st u d y  visit 
sche d ule.  T he s u bject/ca re gi ver s h o ul d be i nstr ucte d t o mai ntai n t he pr o d uct i n t he b ottles 
pr o vi de d t hr o u g h o ut t he c o urse of d osi n g a n d ret ur n t he b ottles t o t he site at t he ne xt st u d y  
visit. 
5. 6. A d mi nistr ati o n
D uri n g t he o pe n -la bel i n d ucti o n treat me nt a n d resc ue treat me nt peri o ds, s u bjects will recei ve 
2 0 0 m g P F -0 4 9 6 5 8 4 2 dail y .  T w o ( 2) b ottles of i n vesti gati o nal pr o d uct will be dis pe nse d t o 
t he s u bject at eac h dis pe nsi n g visit a n d t he s u bject gi ve n clear d osi n g i nstr ucti o ns t o ta ke o ne 
ta blet fr o m eac h b ottle, o nce dail y, prefera b l y i n t he m or ni n g at a p pr o xi matel y t he sa me ti me 

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of da y .  S u bjects s h o ul d ta ke t he i n vesti gati o nal pr o d uct orall y o nce a da y f or u p t o 1 2 wee ks, 
h o we ver, f or st u d y visit da ys, s u bjec ts are t o be i nstr ucte d t o refrai n fr o m d osi n g at h o me, 
a n d are t o ta ke t he d ose i n t he cli nic o n site visit da ys. 
D uri n g bli n de d treat me nt, s u bjects will be dis pe nse d t w o ( 2) b ottles at eac h dis pe nsi n g visit 
a n d gi ve n clear d osi n g i nstr ucti o ns t o ta ke o n e ta blet fr o m eac h b ottle, o nce dail y , prefera bly 
in t he m or ni n g, at a p pr o xi matel y  t he sa me ti me of da y.  S u bjects s h o ul d ta ke t he 
i n vesti gati o nal pr o d uct orall y o nce a da y f or u p t o 4 0 wee ks, h o we ver, f or st u d y  visit da ys, 
s u bjects are t o be i nstr ucte d t o refrai n fr o m d osi ng at h o me, a n d are t o ta ke t he d ose i n t he 
cli nic o n si te visit da ys.
Refer t o Ta ble 2 f or treat me nt a d mi nistrati o n a n d dis pe nsi n g of i n vesti gati o nal pr o d uct.
T a ble 2.
I n vesti g ati o n al Pr od uct A d mi nistr ati o n
Tre at m e nt Assi g n me nt
D uri n g O p e n-l a bel R u n-I n a n d 
Resc ue Tre at me nt - Q D D osi n g
D uri n g Bli n de d Tre at me nt
Q D D osi n g *
1 0 0 m g Q D
N ot a p plica ble
B ottle A 1 0 0 m g - 1 ta blet
B ottle B Place b o - 1 ta blet
2 0 0 m g Q D
B ottle A 1 0 0 m g - 1 ta blet
B ottle B 1 0 0 m g - 1 ta blet
B ottle A 1 0 0 m g - 1 ta bl et
B ottle B 1 0 0 m g - 1 ta blet
Place b o
N ot a p plica ble
B ottle A Place b o - 1 ta blet
B ottle B Place b o - 1 ta blet
* B ottle A a n d B desi g nati o ns are use d f or e xa m ple p ur p oses o nl y.
S u bjects will s wall o w t he i n v esti gati o nal pr o d uct w h ole, a n d will n ot ma ni p ulate or c he w t he 
me dicati o n pri or t o s wall o wi n g.  I n vesti gati o nal pr o d uct ma y  be ta ke n wit h or wit h o ut f o o d, 
ot her t ha n o n st u d y  visit da ys w here fasti n g is re q uire d. 
A n i n vesti gat or ca n te m p oraril y i nterr u pt d osi n g f or u p t o a ma xi m u m of 2 8 c o nsec uti ve da ys
f or a s u bject, f or safety reas o ns or w hile m o nit ori n g a b n or mal la b orat or y  tests if t he 
i n vesti gat or j u d ges t hat t his is necessar y (A p pe n di x 4 ).  T he i n vesti gat or s h o ul d use t heir 
j u d ge me nt wit h re gar d t o u nsc he d ule d visits/la b o rat or y/cli nical assess me nts re q uire d t o 
m o nit or t he s u bject d uri n g t his ti me- fra me. If wit hi n t his ti mefra me t he i n vesti gat or j u d ges 
t hat it is safe t o restart d osi n g, t he n t he s u bject ma y restart i n vestigati o nal pr o d uct. If t he 
i n vesti gat or j u d ges t hat it is n ot safe t o restart d osi n g wit hi n t his ti mefra me t he n t he s u bject 
m ust be per ma ne ntl y disc o nti n ue d f r o m treat me nt, ha ve a n E n d of Treat me nt visit a n d e nter 
t he 4-wee k f oll o w -u p peri o d.  D oses n ot ta k e n f or t he reas o ns me nti o ne d a b o ve d o n ot 
c o nstit u te pr ot oc ol de viati o ns or me dicati o n err ors a n d s h o ul d n ot be c o nsi dere d d osi n g 
err ors, b ut s h o ul d be n ote d i n t he d osi n g l o g wit h t he reas o n f or re d uce d dr u g c o ns u m pti o n 
clearl y descri be d. 
A g ui da nce d oc u me nt wit h detaile d d osi n g i nstr ucti o ns a n d i n vesti g ati ve pr o d uct (IP) st ora ge 
i nstr ucti o n will als o be pr o vi de d t o s u bjects t o s u p p ort at-h o me d osi n g.

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5. 7. I n vesti g ati o n al Pr o d uct St or a ge 
T he i n vesti gat or or a n a p pr o ve d re prese ntati ve, e g, p har macist, will e ns ure t hat all 
i n vesti gati o nal pr o d ucts are st ore d in a sec ure d area wit h c o ntr olle d access u n der re q uire d 
st ora ge c o n diti o ns 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. 
I n vesti gati o nal pr o d uct s h o ul d be st ore d i n t heir ori gi nal c o ntai ner a n d i n acc or da nce wit h t he 
la bels.  See t he I n vesti gati o nal Pr o d uct Ma n ual (I P Ma n ual) f or st ora ge c o n diti o ns of t he 
pr o d uct.
A n y  st ora ge c o n diti o ns state d i n the S R S D will be s u perse de d b y t he st ora ge c o n diti o ns 
state d o n t he pr o d uct la bel.
Site s y ste ms m ust be ca pa ble of meas uri n g a n d d oc u me nti n g (f or e xa m p le, via a l o g), at a 
mi ni m u m, dail y  mi ni m u m a n d ma xi m u m te m perat ures f or all site st ora ge l ocati o ns (as 
a pplica ble, i ncl u di n g fr oze n, refri gerate d, a n d/ or r o o m- te m perat ure pr o d ucts).  T his s h o ul d 
be ca pt ur e d fr o m t he ti me of i n vesti gati o nal pr o d uct recei p t t hr o u g h o ut t he st u d y.  E ve n f or 
c o nti n u o us-m o nit ori n g s y ste ms, a l o g or site pr oce d ure t hat e ns ures acti ve e val uati o n f or 
e xc ursi o ns s h o ul d be a vaila ble.  T he i nte nt is t o e ns ure t hat t he mi ni m u m a n d ma xi m u m 
te m perat ure is c hec ke d eac h b usi ness da y  t o c onfir m t hat n o e xc ursi o n occ urre d si nce t he last 
e val uati o n a n d t o pr o vi de t he site wit h t he ca pa bilit y  t o st ore or vie w t he mi ni m u m/ ma xi m u m 
te m perat ure f or all n o n-w or ki n g da y s u p o n ret ur n t o n or mal o peratio ns.  T he o perati o n of t he 
te m perat ure m o nit ori n g d e vice a n d st ora ge u nit (f or e xa m ple, refri gerat or), as a p plica ble, 
s h o ul d be re g ularly i ns pecte d t o e ns ure t h e y are mai ntai ne d i n w or ki n g or der. 
A n y  e xc ursi o ns fr o m t he pr o d uct la bel st ora ge c o n diti o ns s ho ul d be re p orte d t o Pfizer u p o n 
disc o ver y .  T he site s h o ul d acti vel y p urs ue o pti o ns f or ret ur ni n g t he pr o d uct t o t he st ora ge 
c o n diti o ns descri be d i n t he la beli n g, as s o o n as p ossi ble.  De viati o ns f r o m t he st ora ge 
re q uire me nts, i ncl u di n g a n y acti o ns ta ke n, m ust be d oc u me nte d a n d re p orte d t o Pfizer. 
O nce a n e xc ursi o n is i de ntifie d, t he i n vesti gati o nal pr o d uct m ust be q uara nti ne d a n d n ot use d 
u ntil Pfizer pr o vi des d oc u me ntati o n of per missi o n t o use t h e i n vesti gati o nal pr o d uct.  It will 
n ot be c o nsi dere d a pr o t oc ol de viati o n if Pfizer a p pr o ves t he use of t he in vesti gati o nal 
pr o d uct after t he te m perat ure e xc ursi o n.  Use of t he i n vesti gati o nal pr o d uct pri or t o Pfizer 
a p pr o val will be c o nsi dere d a pr ot oc ol de viati o n.   S pecific details re gar di n g i nf or mati o n t he 
site s h o ul d re p ort f or eac h e xc ursi o n will be pr o vi de d t o t he site i n t he IP Ma n ual. 
Recei pt of materials, d o or o pe ni n g a n d cl osi n g, a n d ot her r o uti ne ha n dli n g o perati o ns w here 
t he pr o d ucts are briefl y o ut of t he te m perat ure ra n ge descri be d i n t he la beli n g are n ot 
c o nsi dere d exc ursi o ns.
Site staff will i nst r uct s u bjects o n t he pr o per st ora ge re q uire me nts f or ta ke h o me 
i n vesti gati o nal pr o d ucts. 

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5. 8. I n vesti g ati o n al Pr o d uct Acc o u nt a bilit y 
T he i n vesti gat or site m ust mai ntai n a de q uate rec or ds d oc u me nti n g t he recei pt, use, l oss, or 
ot h er dis p ositi o n of t he i n vesti gati o nal pr o d uct s u p plies.  All i n vesti gati o nal pr o d ucts will be 
acc o u nte d f or usi n g a dr u g acc o u nta bilit y f or m/rec or d.  T o e ns ure a de q uate rec or ds, all dr u g 
s u p plies will be acc o u nte d f or i n t he dr u g acc o u nta bilit y i n ve nt or y for ms as i nstr ucte d b y  
Pfizer a n d will be m o nit ore d b y  t he acc o u nti n g of u n use d i n vesti gati o nal pr o d uct ret ur ne d by 
t he s u bjects.  At t he e n d of t he cli nical trial, all dr u g s u p plies u nall ocate d or u n use d b y t he 
s u bjects m ust be ret ur ne d t o Pfizer or its a pp oi nte d a ge nt, or destr o ye d i n a n a p pr o ve d 
ma n ner u nless ot her wise a ut h orize d b y  Pfizer.  I n eit her case, t he f or ms m ust i de ntif y t he 
i n vesti gati o nal pr o d uct, i ncl u di n g batc h or c o de n u m bers, a n d acc o u nt f or its dis p ositi o n o n a 
s u bject-b y -s u bject basis, incl u di n g s pecific dates a n d q ua n tities. 
All b ottles of i n vesti gati o nal pr o d uct m ust be br o u g ht bac k t o t he site at e ver y visit f or 
i ns pecti o n b y t he site staff a n d all b ottles/ un use d i n vesti gati o nal pr o d uct m ust be ret ur ne d t o 
t he i n vesti gat or by t he s u bj ect at t he rele va nt visit(s).
5. 8. 1. Destr ucti o n of I n vesti g ati o n al Pr o d uct S u p plies 
T he s p o ns or or desi g nee will pr o vi de g ui da nce o n t he destr ucti o n of u n use d i n vesti gati o nal 
pr o d uct (e g, at t he site).  If destr ucti o n is a ut h orize d t o ta ke place at t he i n vesti g at or site, t he 
i n vesti gat or m ust e ns ure t hat t he materials are destr o y e d i n c o m plia nce wit h a p plica ble 
e n vir o n me ntal re g ulati o ns, i nstit uti o nal p olic y , a n d a n y s pecial i nstr ucti ons pr o vi de d b y  
Pfizer, a n d all destr ucti o n m ust be a de q uate l y d oc u me nte d.
F or all b ottles ret ur ne d t o t he i n v esti gat or by t he s u bject, t he i n vesti gat or will mai ntai n t he 
ret ur ne d s u p ply u ntil destr ucti o n is a ut h orize d.  Pfizer will pr o vi de i nstr ucti o ns as t o t he 
dis p ositi o n of a n y  u n use d i n vesti gati o nal pr o d uct.
5. 9. C o nc o mit a nt Tre at me n t(s)
S u bjects m ust c o nti n ue t o av oi d use of me dicati o ns t hat ha ve bee n was he d - o ut pri or t o 
e nr oll me nt a n d will a bstai n fr o m all c o nc o mita nt me dicati o ns as descri be d i n Secti o n 4. 2 a n d 
A p pe n di x 3 o f t he pr ot oc ol.  Me dicati o ns t hat are ta ke n i n t he Scree ni n g/ Was h o ut peri o d 
(after i nf or me d c o nse nt is o btai ne d a n d bef ore t he first d ose of i n vesti gati o nal pr o d uct o n 
D a y 1) will be d oc u me nte d as pri or me dicati o ns.  Me dicat i o ns ta ke n after t he first d ose of 
i n vesti gati o nal pr o d uct o n Da y 1 has bee n a d mi nistere d will be d oc u me nte d as c o nc o mita nt 
me dicati o ns.  All c o nc o mita nt me dicati o ns ta ke n d uri n g t he st u d y m ust be rec or de d i n st u d y 
rec or ds wit h i n dicati on (if At o pic Der mat itis), refere nce t o a ny ass ocia te d a d verse e ve nt, 
d ose, a n d start a n d st o p dates of a d mi nistrati o n.  S u bjects will be q uerie d a b o ut c o nc o mita nt 
me dicati o n (i ncl u di n g t o pical me dicati o ns a n d treat me nts, o ver -t he-c o u nter a n d prescri pti o n 
m e dicati o ns a n d treat me nts, a n d vacci nati o ns) at each st u d y  visit.  A n y ne w c o nc o mita nt 
me dicati o ns or d ose c ha n ges t o c urre nt c o nc o mi ta nt me dicati o ns s h o ul d be e val uate d f or 
p ote ntial ne w or w orse ni n g a d verse e ve nts. 
Me dicate d t o pical t hera pies ie, a t o pical pr o d uct t hat c ontai ns a n acti ve p har mace utical
i n gre die nt i n dicate d f or t he treat me nt of A D (irres pecti ve of w het her it is a n o ver-t he-c o u nter 
[ O T C] or prescri pti o n o nl y pr o d uct), are o nl y per mitte d i n t his trial d uri n g t he resc ue peri o d. 

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5. 9. 1. Per mitte d C o nc o mit a nt Me dic ati o ns
T he f oll o wi n g c o nc o mita nt A D t hera pies are per mitte d d uri n g t he st u d y:

Oral a nti hista mi nes; 

T o pical n o n -me dica te d e m ollie nt. 
T he f oll o wi n g c o nc o mita nt me dicati o ns are per mitte d d uri n g t he st u d y:

C ortic oster oi d i n halers a n d i ntra nasa l s pra ys are all o wed f or sta ble ast h ma a n d/ or 
allergic r hi nitis patie nts;

O p ht hal mic c ortic oster oi ds are all o we d f or patie nts recei vi n g a sta ble d ose t o treat 
r hi n oc o nj u nti vitis;

L o w d ose acet yl  salic ylic aci d (1 0 0 m g  Q D) is per mitte d, f or t he p ur p ose of 
car di o vasc ular pr o p h y la xis, at t he discreti o n of th e in vesti gat or ;

Aceta mi n o p he n/ paraceta m ol ma y  be use d i nter mitte ntl y ( n ot t o e xcee d 1 g/ da y ); 

Vita mi n a n d mi neral s u p ple me nts of sta n dar d p ote nc y are all o we d i n a m o u nts n ot 
k n o w n t o be ass ociate d wit h a d v erse effects (s uc h as h yper -vita mi n osis).
F or t he p ur p oses of t his pr ot oc ol, dietar y  s u p ple me nts are defi ne d as vita mi ns, mi nerals, an d 
p urifie d f o o d s u bsta nces.  Vita mi ns, mi nerals a n d p urifie d f o o d s u bsta nces are all o we d i n 
a m o u nts n ot k n o w n t o be ass oci ate d wit h a d verse e ffects (s uc h as hy p er-vita mi n os is).
U nless a pr o hi bite d me dicati o n or treat me nt, s u bjects ma y  be a d mi nistere d a n y ot her 
me dicati o ns necessar y  f or t he treat me nt of c o nc o mita nt me dical dis or ders as dee me d 
necessar y  b y t he treati n g p h ysician.  F oll o wi n g Da y 1 , a d diti o n of c o nc o mita nt me dicati o ns 
or a n y c ha n ge i n t he d osa ge s h o ul d be li mite d t o t h ose c o nsi dere d me dicall y esse ntial.
A s u bject w h o is recei vi n g a per mitte d c o nc o mita nt me dicati o n f or a n y reas o n m ust be o n a 
l ocall y- a p pr o ve d me dicati o n a n d d ose, a n d t his m ust be d oc u me nte d i n t he C R F.  S u bjects 
are n ot all o we d a n y ot her i n vesti gati o nal dr u gs or treat me nts d uri n g t he st u d y . 
S u bjects s h o ul d re p ort a n y  c ha n ges t o per mitte d me dicati o ns d uri n g t he st u d y t o t he 
i n vesti gat or as s o o n as the y  occ ur.  Me dicati o n c ha n ges m ust be d oc u me nte d in t he s u bject’s 
rec or d a n d C R F.
5. 9. 2. Pr o hi bite d Me dic ati o ns a n d Tre at me nts
S u bjects are re q uire d t o disc o nti n ue a n d a v oi d usi n g certai n me dicati o ns a n d treat me nts (see 
Secti o n 4. 2 , I ncl usi o n Criteria a n d E xcl usi o n Cr iteria, a n d A p pe n di x 3 ).  S u bjects s h o ul d be 
i nstr ucte d at eac h visit t o c o ntact t he st u dy site i n vesti ga t or pr o m ptl y if t here are a ny 
i nte n de d c ha n ges or ad diti o ns t o c o nc o mita nt me dicati o ns. 

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All me dicati o ns a n d treat me nts t hat c o ul d affect at o pic der matitis m ust be disc o nti n ue d 
e xce pt oral a nti hista mi nes.  D ue t o t he p ote ntial t o affect at o pic der matitis w it h ultra vi olet 
li ght e x p os ure, s u bjects m ust als o a v oi d pr ol o n ge d e x p os ure t o t he s u n a n d n ot t o use ta n ni n g 
b o ot hs, s u n la m ps or ot her ultra vi olet li g ht s o urces d uri n g t he st u d y. 
S u bjects w h o recei ve d pri or treat me nt wit h J A K i n hi bit ors are t o be e xcl u d e d fr o m t he st u d y. 
Her bal me dicati o ns wit h u n k n o w n pr o perties or k n o w n be neficial effects f or A D m ust be 
disc o nti n ue d at lea st 4 wee ks bef ore t he first d ose of i n vesti gati o nal pr o d uct. 
Restricti o ns o n certai n vacci nati o ns are descri be d i n S ecti o n 4. 4. 2 .
T he Pfizer st u d y tea m is t o be n otifie d of a n y  pr o hi bite d me dicati o ns ta ke n d uri n g t he st u d y.  
After c o ns ulti n g wit h t he Me dical M o nit or, t he i n vesti gat or will ma ke a j u d ge me nt o n t he 
o n g oi n g e li gi bilit y of a ny s u bject wit h pr o hi bite d me dicati o n use d uri n g t he st u d y. 
6. S T U D Y P R O C E D U R E S 
Refer t o t he Sc he d ule of Acti vities f or a detaile d list of st u d y pr oce d ures as t he y s h o ul d be 
c o n d ucte d at eac h res pecti ve visit. 
D ue t o p ossi ble ne e d f or P P D testi n g a n d c hest ra d i o gra p h, scree ni n g pr oce d ures ma y be 
perf or me d o ver m ore t ha n 1 visit i n t he 2 8 da y s pri or t o t he Da y 1 visit. 
Visit wi n d o ws are base d o n t he Da y 1 Baseli ne visit ( Visit 2).  T o ass ure c o nsiste nc y  a n d 
re duce varia bilit y , all st u d y visits s h o ul d occ ur i n the m or ni n g w h e ne ver p ossi ble.  O n da y s 
of st u d y  visits, s u bjects will recei ve t heir d ose at t he cli nic d uri n g t he visit. 
S u bjects are re q uire d t o fast f or at least 8 h o urs pri or t o all visits t hat i ncl u de li pi d pr ofile 
pa ne l testi n g ( Da y 1, Wee k 4, Wee k 1 2, Wee k 5 2, E O S a n d Resc ue Da y 1, Resc ue Wee k 4, 
Resc ue Wee k 1 2).  D uri n g t he fasti n g peri o d, s u bjects s h o ul d refrai n fr o m all f o o d a n d 
li q ui ds ( water a n d per mitte d n o n-st u d y me dicati o ns are all o we d). 
Uri ne pre g na nc y  test must be perf or me d at e ver y  visit, be gi n ni n g wi t h Da y 1 t hr o u g h E O S 
pri or t o d osi n g wit h t he i n vesti gati o nal pr o d uct f or fe male s u bjects of c hil d beari n g p ote ntial 
i ncl u di n g a d olesce nts a ge d 1 2 ye ars a n d ol der re gar dless of w het her t he y  ha ve e x perie nce d 
me nar c he. 
Pri or t o atte n di n g a st u d y visit, s u bje cts are all o we d t o s h o wer a n d bat he b ut s h o ul d n ot 
m oist urize or a p pl y  e m ollie nt. 
E C Gs will be i nter prete d b y  a ce ntral rea der.
I n t he e ve nt of a s us pecte d o p p ort u nistic i nfecti o n, eff ort s h oul d be ma de t o i de n tif y t he 
pat h o ge n utilizi n g la b o rat or y or ot her met h o ds a p pr o priate t o t he cli nical sit uati o n. 

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I n case of a s us pecte d viral s ki n i nfecti o n (e g, her pes z oster a n d her pes si m ple x) or ecze ma 
her petic u m, a s peci me n f or viral D N A s h o ul d be o btai ne d f or c o nfir m ati o n.  Details f or s uc h 
c ollecti o n will be pr o vi de d i n t he la b orat or y ma n ual. 
F or s u bjects wit h a past hist or y  of oral or ge nital H S V a n d a prese ntati o n c o nsiste nt t o pri or 
i nfecti o ns, a sa m ple ma y be o btai ne d at t he discreti o n of t he i n vesti gat or. 
Refe r t o A p pe n di x 4 f or g ui deli nes o n s u bject safet y m o nit ori n g a n d disc o nti n uati o n. 
6. 1. Visit 1, Scree ni n g
S u bjects will be scree ne d ( Visit 1) wit hi n 2 8 da y s pri or t o a d mi nistrati o n of t he 
i n vesti gati o nal pr o d uct t o co nfir m t hat t he y  meet t he s u bject selecti o n criteria f or t he st u d y.  
T he i n vesti gat or ( or a n a p pr o priate dele gate at t he i n vesti gat or site) will o btai n i nf or me d 
c o nse nt fr o m eac h s u bject, le gally acce pta ble re prese ntati ve /pare nt(s) or l eg al g uar dia n (a n d 
asse nt fr o m t he s u bject, as a p pro priate), i n acc or da nce wit h t he pr oce d ures descri be d i n t he 
S u bj ect Inf or mati o n a n d C o nse nt i n Secti o n 1 2. 3 . 
S u bjects n ot meeti n g e nr oll me nt criteria (scree n fail ures) f or a n y reas o n s h o ul d be c o ntacte d 
q uic kl y  t o res u me/i nitiate A D treat me nts. 
If t he Ma nt o u x P P D t u berc uli n s ki n test is gi ve n, t he s u bject m ust ret ur n bet wee n 
4 8 - 7 2 h o urs p ost -i njecti o n f or i n d urati o n e valuati o n.
Scree ni n g la b orat or y  tests wit h a b n or mal res ults ma y be re peate d o nce t o c o nfir m a b n or mal 
res ults; t he last val ue will be use d t o deter mi ne eli gi bilit y.  If res ults ret ur n t o n or mal wit hi n 
t he 4-wee k scree ni n g peri o d, t he s u bject ma y  e nter t he st u dy. 
T he f oll o wi n g pr oce d ures wi ll be c o m plete d: 

O btai n writte n i nf or me d c o nse nt; f or s u bjects u n der t he le gal a ge of maj orit y  (le gal 
a d ult h o o d) i n t he s u bject’s c o u ntr y , o btai n writte n i nf or me d c o nse nt fr o m le gall y 
acce pta ble re prese nta ti ve/pare n t(s) or le gal g uar dia n a n d i nf or me d asse n t fr o m t he 
patie nt (if a ge a p pr o priate acc or di n g t o l ocal re g ulati o ns);

Re gister s u bject usi n g t he I R T s ys te m;

C ollect de m o gra p h y;

A d mi nister a n d sc ore t he C -S S R S, S B Q -R a n d P H Q -8.  S u bjects meeti n g a n y  of t he 
criteria s peci fie d i n E xcl usi o n Criteri o n 2 will be i neli gi ble f or partici pati o n; i t is 
rec o m me n de d t he s u bject’s pri mar y care p hys icia n ( P C P) s h o ul d be i nf or me d, a n d t he 
s u bject referre d t o a me ntal healt h pr ofessi o nal , eit her by t he P C P or t he i n vesti gat or 
acc or di n g to t heir us ual practice ;

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
C o m plete me dical hist or y, i ncl u di n g hist or y  of alc o h ol a n d t o bacc o use.  S m o ki n g 
stat us a n d a vera ge wee kl y alc o h ol c o ns u m pti o n ( u nits/ wee k) will als o be c ollecte d, 
w here a u nit c o nt ai ns 1 2 g of p ure a lc o h ol, a n a m o u nt e q ui vale nt t o t hat c o ntai ne d i n 
5 oz/ 1 5 0 ml (a glass) of wi ne, 1 2 oz/ 3 6 0 ml of beer, or 1. 5 oz/ 4 5 ml of 9 0 pr o of 
( 4 5 % alc o h ol b y v ol u me) of s pirits;

C o m plete A D disease hist or y  i ncl u des c ollecti o n of details of A D: A D dia g n osis a n d 
d urati o n, t he use of t o pical treat me n ts, sys te mic treat me nts a n d ot her treat me nts f or 
A D;

O btai n c o m plete me dicati o n hist or y  of all prescri pti o n or n o n prescri pti o n dr u gs, a n d 
dietar y  a n d her bal s u p ple me nts ta ke n wit hin 2 8 da ys pri or t o t he pla n ne d first d ose, 
e x ce pt as n ote d bel o w: 
T he f oll o wi n g ti mefra me pri or t o t he pla n ne d first d ose m ust be use d f or c ollecti o n of 
t he f oll o wi n g C urre nt/ Pri or Me dicati o ns:

1 ye ar: Pre vi o us t o pical treat me nts use d f or A D;

A n y  pre vi o us hist or y of s yste mic treat me nt f or A D;

A n y  pre vi o us hist or y of i nt olera nce/aller g y t o a ny dr u g, re gar dless of i n dicati o n;

O btai n vital si g ns i ncl u di n g p ulse rate, bl o o d press ure, res pirat or y  rate a n d oral or 
t ym pa nic te m perat ure (after at least 5 mi n utes of rest);

O btai n wei g ht a n d hei g ht of all s u b jects;

Perf or m a si n gle 1 2 -lea d electr ocar di o gra m ( E C G).  Cli nicall y  si g nifica nt or 
e xcl usi o nar y E C G fi n di n gs re q uire scree n fail ure;

C o n d uct c o m plete p h y sical e xa mi nati o n;

Dis pe nse electr o nic patie nt re p orte d o utc o me (e P R O) ha n d hel d de v ice a n d i nstr uct 
s ubject i n h o w t o use t he de vice. I nstr uct t he s u bject t o be gi n daily c o m pleti o n of t he 
P S A A D (i n selecte d c o u ntries) a n d pr urit us N R S q uesti o n naire; 

Pr urit us N R S will be c ollecte d dail y i n a s u bject e Diar y  d urin g t he scree ni n g peri o d 
a nd fr o m Da y 1 t o 1 5 a n d t he n o n st u d y visit da ys; 

P S A A D will be c ollecte d dail y  i n a s u bject e Diar y d uri n g t he scree ni n g peri o d a n d 
fr o m Da y 1 t hr o u g h t he E n d of St u d y  visit, i n selecte d c o u ntries; 

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
C hest X -ra y or ot her a p pr o priate dia g n ostic i ma ge (ie, c o m p uterize d t o m o gra p h y  
[ C T] or ma g netic res o na nce im a gi n g [ M RI]) ma y be perf or me d u p t o 1 2 wee ks pri or 
t o St u d y D a y 1.   C hest X -ra ys ( p osteri or-a nteri or a n d lateral vie ws) are re q uire d f or 
a d ults a n d rec o m me n de d f or a d olesce nts as per l ocal g ui deli nes a n d s ta n dar d of care.  
Official rea di n g m ust be l ocate d a n d a vaila ble i n t he s o urce d oc u me ntati o n;

O btai n sa m ples f or la b orat or y testi n g: ser u m c he mistr y , he mat ol o g y (i ncl u di n g 
c oa g ulati o n pa nel, re d bl o o d cell ( R B C) a n d w hite bl o o d ce ll ( W B C) i n dices, a n d 
l ym p h oc y te s u bsets a n d mar kers), uri nal ys is, ser u m F S H ( p ost-me n o pa usal w o me n) 
or ser u m pre g na nc y  test ( w o me n of c hil d beari n g p ote ntial i ncl u di n g a d olesce nts a ge d 
1 2 ye ars a n d ol der re gar dless of w het her t he y  ha ve e x perie nce d me narc he), HI V, 
he patitis B s urfac e a nti ge n ( H Bs A g), he patitis B c ore a nti b o d y  ( H Bc Ab ), he patitis B 
s urface a nti b o dy ( H Bs A b), he patitis C viral a nti b o d y  ( H C V A b), he patitis C viral 
ri b o n ucleic aci d ( H C V R N A) (see Secti o n 7. 6. 2. 1 ), V Z V I g G a nti b o dy testi n g f or 
a d olesce nt s u bject s w h o ha ve n ot recei ve d at least o ne d ose of a varicella vacci ne, 
a nd baseli ne viral scree n sa m ple . F or C hi na a n d Tai wa n o nl y : S u bjects w h o are 
H Bs A g ne gati ve , H Bc A b p ositi ve , a n d H Bs A b p ositi ve will ha ve refle x testi n g f or
H B V D N A.

Q ua nti F E R O N – T B G ol d test ( u nless perf or me d wit hi n 1 2 wee ks of Da y 1).  If 
Ma nt o u x P P D t u berc uli n s ki n test is perf or me d, t he s u bject m ust ret ur n bet wee n 
4 8 - 7 2 h o urs p ost -i njecti o n f or e val uati o n of i n d urati o n (see Secti o n 7. 3. 4 f or f urt her 
details o n T B testi n g);

C o n d uct cli nical e val uati o ns i ncl u di n g I G A, S C O R A D, E A SI  a n d B S A (calc ulate d i n 
t he E A SI);

Assess nee d f or c o ntrace pti o n a n d a d here nce t o a p plica ble life styl e re q uire me nts 
(Secti o n 4. 4 ).  Esta blis h willi n g ness a n d a bility t o c o m pl y wit h lifest yl e re q uire me nts 
g oi n g f or war d i n t he st u d y;

Re vie w I ncl usi o n a n d E xcl usi o n criteria f or s u bject eli gi b ilit y;

Assess f or o cc urre nce of A d verse E ve nts: T h e a d verse e ve nt a n d S A E re p orti n g 
peri o d starts wit h t he si g ni n g of t he i nf or me d c o nse nt d oc u me nt;

If s u bject is eli gi ble f or c o nti n ue d partici pati o n, pr o vi de s u bject wit h patie nt 
e mer ge nc y c o ntact car d.
6. 2. R u n-I n I n d ucti o n Tre a t me nt Peri o d
6. 2. 1. Visit 2, D a y 1/ Wee k 0 ( B aseli ne)
A d mi nister a n d sc ore t he Si nce Last Visit C -S S R S.  S u bjects meeti n g a n y of t he criteria 
s pecifie d i n Secti o n 7. 5. 1 will be i neli gi ble f or partici p ati o n; a ris k assess me nt b y a qualifie d 
me ntal hea lt h pr ofessi o nal (M H P ) s h o ul d be d o ne t o deter mi ne w het her it is safe f or t he 
s u bject t o c o nti n ue t o partici pate i n t he trial.

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
A d mi nister patie nt -re p orte d o utc o me ( P R O)s i ncl u di n g: Pt G A, D L QI ( or C D L QI), 
P O E M, H A D S, E Q - 5 D-5 L  ( or E Q-5 D -Y i n select c o u ntries), S F-3 6 v 2, Ac ute a n d 
F A CI T -F ( or Pe ds -F A CI T -F).  S F -3 6 v 2 will be c o m plete d b y  a d ult s u bjects o nl y; 

A d olesce nts 1 2 -1 7 y ears of a ge will n ot c o m plete t he S F -3 6 v 2.  A d olesce nts 1 2- 1 7 
ye ars of a ge will c o m ple te t he C D L QI i nstead of t he D L Q I, t he E Q-5 D- Y i n s elect 
c o u ntries i nstea d of t he E Q - 5 D-5 L  a n d Pe ds-F A CI T -F i nstea d of t he F A CI T -F;

Re vie w P S A A D dail y  c o m pleti o n (i n selecte d c o u ntries) a n d pr urit us N R S dail y 
c o m pleti o n i n t he e Diar y.  Re vie w e Diar y pr oce d ures wit h s u bject as necessar y ;

Re vie w a n y c ha n ges i n t he s u bject’s pri or a n d c o nc o mita nt me dicati o ns a n d treat me nt 
i nf or mati o n;

A d mi nister Ast h ma C o ntr ol Q uesti o n naire ( A C Q) test f or all s u bjects wit h a pri or 
dia g n osis of ast h ma;

O btai n pre -d ose vital si g n s i ncl u di n g p ulse rate, bl o o d p ress ure, res pirat ory rate a n d 
oral or t y m pa nic te m perat ure (after at least 5 mi n utes of rest);

O btai n wei g ht ( hei g ht n ot re q uire d);

Perf or m a si n gle 1 2 -lea d E C G pri or t o d osi n g wit h i n vesti gati o nal pr o d uct.  Cli nicall y 
si g nifica nt or e xcl usi o nar y E C G fi n di n g s re q uire scree n fail ure;

C o n d uct c o m plete p h y sical e xa mi nati o n; 

C o n d uct cli nical e val uati o ns i ncl u di n g Fitz patric k S ki n T y pe Assess me nt, I G A, 
S C O R A D, E A SI  a n d B S A (calc ulate d i n t he E A SI);

O btai n fasti n g sa m ples f or la b or at or y testi n g: ser um c he mistr y , he mat ol o g y 
(i ncl u di n g c oa g ulati o n, R B C/ W B C In dices, a n d l y m p h oc yte s u bsets a n d mar kers), 
li pi d pr ofile, a n d uri nalys is; 
 

Uri ne pre g na nc y  test (fe male s u bjects of c hil d beari n g p otential i ncl u d i ng a d olesce nts 
a ged 1 2 y ears a n d ol der re gar dless of w het her t he y  ha ve e x perie nce d me narc he).  A 
ne gati ve uri ne pre g na nc y test m ust be o btai ne d pri or t o d osi n g wit h t he 
i n vesti gati o nal pr o d uct; 

C ollect sa m ple f or viral s ur v eilla nce: Her pes sim ple x vir us ( HS V) H S V- 1, H S V - 2 
a n d V ZV; 

Assess nee d f or c o ntrace pti o n a n d a d here nce t o a p plica ble lifest yl e re q uire me nts 
(Secti o n 4. 4 ).  Esta blis h willi n g ness a n d a bilit y t o c o m pl y wit h lifestyl e re q uire m e nts 
g oi n g f or war d i n t he st u d y;
C CI

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
Re vie w of I ncl usi o n/ E xcl usi o n Criteria;

If s u bject c o nti n ues t o meet all I ncl usi o n/ E xcl usi o n criteria, officially e nr oll s u bject 
i nt o t he st u d y;

Dis pe nse i n vesti gati o nal pr o d uct t o t he s u bject ;

A d mi nister first d ose of i n ve sti gati o nal pr o d uct t o s u bject;

Assess a n d rec or d a n y A d verse E ve nts si nce t he last visit. 
6. 2. 2. Visit 3, D a y 8/ Wee k 1 ( 1 d a y)

Call s u bject a n d c o nfir m c o m plia nce wit h dail y c o m pleti o n of pr urit us N R S a n d 
P S A A D (i n selecte d c o u nt ries); 

Ver ball y c o nfir m s u bjec t has bee n c o m plia n t wit h st u d y d osi n g a n d e ntr y i n t he 
e Diar y.  Re vie w e Diar y pr oce d ures wit h s u bject as necessar y;

Re vie w a n y c ha n ges i n t he s u bject’s c o nc o mita nt me dicati o ns a n d treat me nt 
i nf or mati o n;

Assess nee d f or c o ntr ace pti o n a n d a d here nce t o a p pli cable lifest yl e re quire me nts 
(Secti o n 4. 4 ).  Esta blis h willi n g ness a n d a bilit y t o c o m pl y wit h lifestyl e re q uire me nts 
g oi n g f or war d i n t he st u d y;

Assess a n d rec or d a n y A d verse E ve nts si nce t he last visit.
6. 2. 3. Visit 4, D a y 1 5/ Wee k 2 ( 1 d a y)

A d mi nister P R Os i ncl u di n g: Pt G A, D L QI ( or C D L QI), P O E M, H A D S a n d 
E Q - 5 D-5 L  ( or E Q 5 D-Y i n selec t c o u ntries);

A d olesce nts 1 2 -1 7 y ears of a ge will c o m plete t he C D L QI  i nstea d of t he D L QI a n d t he 
E Q - 5 D- Y i n select c o u ntries i nstea d of t he E Q - 5 D-5 L ;

Re vie w dail y P S A A D c o m pleti o n (i n selecte d c o u ntries) a n d dail y pr urit us N R S 
c o m pleti o n i n t he e Diar y.  In str uct s u bject t hat pr urit us N R S will n o w be c o m plete d 
o nl y  at site visits, b ut t he P S A A D will still be c o m p lete d dail y i n t he e Diar y.  Re vie w 
e Diar y pr oce d ures wit h s u bject as necessar y;

Re vie w a n y c ha n ges i n t he s u bject’s c o nc o mita nt me dicati o ns a n d treat me nt 
i nf or mati o n;

O btai n vital si g ns i ncl u di n g p ulse rate, bl o o d press ure, res pirat or y  rate a n d oral or 
t ym pa nic te m per ature (after at lea st 5 mi n utes of rest);

Perf or m a si n gle 1 2 -lea d E C G;

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
C o n d uct a tar gete d p h ys ical e xa m;

C o n d uct cl i nical e val uati o ns i ncl u di n g I G A, S C O R A D, E A SI a n d B S A (calc ulate d i n 
t he E A SI);

O btai n sa m ples f or la b orat or y t esti n g: ser u m c he mistr y, he matol o g y  (i ncl u di n g 
c oa g ulati o n, R B C/ W B C i n dices, l ym p h oc y te s u bsets a n d mar kers) a n d uri nal ysis;

Uri ne pre g na nc y  test (fe male s u bjects of c hil d beari n g p ote ntial i ncl u di n g a d olesce nts 
a ge d 1 2 ye ars a n d ol der re gar dless of w het her t he y  ha ve e x perie nce d me narc he).  A 
ne gati ve u ri ne pre g na nc y test m ust be o btai ne d pri or t o d osi n g wit h t he 
i n vesti gati o nal pr o d uct;

Assess nee d f or c o ntrace pti o n a n d a d here nce t o a p plica ble lifest yl e re q uire me nts 
(Sect i o n 4. 4 ).  Esta blis h willi n g ness a n d a bilit y t o c o m pl y wit h lifestyl e re q uire me nts 
g oi n g f or war d i n t he st u d y;

Re vie w e Diar y  t o assess c o m pleti o n;

Perf or m dr u g acc o u nta bilit y  pr oce d ures;

A d mi nister i n vesti gati o nal pr o d uct t o t he s u bject;

Assess a n d rec or d a n y A d verse E ve nts s i nce t he last visit.
6. 2. 4. Visi t 5, D a y 2 9/ Wee k 4 (2 d a ys)

A d mi nister P R Os i ncl u di n g: Pt G A, D L QI ( or C D L QI), P O E M, H A D S a n d 
E Q - 5 D-5 L  ( or E Q-5 D -Y i n select c o u ntries);

A d olesce nts 1 2 -1 7 y ears of a ge will c o m plete t he C D LQI  i nstea d of t he D L QI a nd t he 
E Q - 5 D- Y i n select c o u ntries i nstea d of t he E Q - 5 D-5 L ;

Re vie w P S A A D dail y  c o m pleti o n (i n selecte d c o u ntries) a n d pr uritis N R S c o m pleti o n 
f or t his visit i n t he e Diar y;

Perf or m a si n gle 1 2 -lea d E C G;

Re vie w a n y c ha n ges i n t he s u bject’s c o nc omita nt me dic ati o ns a n d treat me nts 
i nf or mati o n;

O btai n vi tal si g ns i ncl u di n g p ulse rate, bl o o d press ure, res pirat or y rate a n d oral or 
t ym pa nic te m perat ure (after at least 5 mi n utes of rest);

C o n d uct tar gete d p h ys ical e xa mi nati o n;

P F- 0 4 9 6 5 8 4 2
B 7 4 5 1 0 1 4
Fi nal P r otoc ol A me n d me nt 5, 2 8 Oct o ber 2 0 1 9
P FI Z E R C O N FI D E N TI A L
Pa ge 7 6

C o n d uct cli nical e val uati o n s i ncl u di n g I GA, S C O R A D, E A SI  an d B S A (calc ulate d i n 
t he E A SI);

O btai n fasti n g sa m ples f or la b orat or y  testi n g: ser u m c he mistr y, he mat ol o g y 
(i ncl u di n g c oa g ulati o n pa nel, R B C/ W B C i n dices, l ym p h y c yte s u bsets a n d mar kers), 
li pi d pr ofile a n d uri nal ys is; 

Uri ne pre g na nc y  test (fe male s u bjects of c hil d beari n g p ote ntia l i ncl u di n g a d olesce nts 
a ge d 1 2 ye ars a n d ol der re gar dless of w het her t he y  ha ve e x perie nce d me narc he).  A 
ne gati ve uri ne pre g na nc y test m ust be o btai ne d pri or t o d osi n g wit h t he 
i n vesti gati o nal pr o d uct; 

Assess n eed f or c o ntrace pti o n a n d a d here nce t o a p pli ca ble lifest yl e re q uire me nts 
(Secti o n 4. 4 ).  Esta blis h willi n g ness a n d a bility t o c o m pl y wit h lifest yl e re q uire me nts 
g oi n g f or war d i n t he st u d y;

Re vi e w e Diar y t o assess c o m pleti o n;

Perf or m dr u g acc o u nta bilit y  pr oce d ures;

A d mi nister i n vesti gati o nal pr o d uct t o t he s u bject;

Dis pe nse i n vesti gati o nal pr o d uct t o t he s u bject;

Assess a n d rec or d a n y A d verse E ve nts si nce t he last v isit.
6. 2. 5. Visit 6, D a y 4 3/ Wee k 6 ( 3 d a ys)

Call s u bjec t a n d c o nfir m c o m plia nce wit h daily c o m pleti o n of P S A A D (i n selecte d 
c o u ntries);

Ver ball y c o nfir m s u bject has bee n c o m plia nt wit h st u d y  d osi n g a n d e ntr y i n t he 
e Diar y.  Re vie w e Diar y pr oce d ures wit h s u bject as necessar y;  

Re vie w a n y c ha n g es i n t he s u bject ’s c o nc o mita nt me dicati o ns a n d treat me nt 
i nf or mati o n;

Assess nee d f or c o ntrace pti o n a n d a d here nce t o a p plica ble lifest yl e re q uire me nts 
(Secti o n 4. 4 ).  Esta blis h willi n g ness a n d a bilit y t o c o m pl y wit h lifest yl e re q uire me nts 
g oi n g f or war d i n t he st u d y;

Assess a n d rec or d a n y A d verse E ve nts si nce t he last visit.

P F- 0 4 9 6 5 8 4 2
B 7 4 5 1 0 1 4
Fi nal P r otoc ol A me n d me nt 5, 2 8 Oct o ber 2 0 1 9
P FI Z E R C O N FI D E N TI A L
Pa ge 7 7
6. 2. 6. Visit 7, D a y 5 7/ Wee k 8 ( 3 d a ys)

A d mi nister a n d sc ore t he Si nce Last Visi t C-S S R S.  F or s u bj ects meeti n g an y  of t he 
criteria s pecifie d i n Secti o n 7. 5. 1 a ris k assess me nt b y a q ualifie d M H P s h o ul d be 
d o ne t o deter mi ne w het her it is safe f or t he s u bject t o c o nti n ue t o partici pate i n t h e 
trial;

A d m i nister P R Os i ncl u di n g: Pt G A, D L QI ( or C D L QI), P O E M, H A D S a n d 
E Q - 5 D-5 L  ( or E Q-5 D -Y i n select c o u ntries);

A d olesce nts 1 2 -1 7 y ears of a ge will c o m plete t he C D L QI  i nstea d of t he D L QI a n d t he 
E Q - 5 D- Y i n select c o u ntries i nstea d of t he E Q- 5 D-5 L ;

Re v ie w P S A A D dail y c o mpleti o n (i n selecte d c o u ntries) a n d pr uritis N R S c o m pleti o n 
f or t his visit i n t he e Diar y; 

Re vie w a n y c ha n ges i n t he s u bject’s c o nc o mita nt me dicati o ns a n d treat me nts 
i nf or mati o n;

O btai n vital si g ns i ncl u di n g p ulse rate, bl o o d press ure, r es pirat or y rate a n d oral or 
t ym pa nic te m perat ure ( after at least 5 mi n utes of rest);

Perf or m a si n gle 1 2 -lea d E C G;

C o n d uct tar gete d p h ys ical e xa mi nati o n;

C o n d uct cli nical e val uati o ns i ncl u di n g I G A, S C O R A D, E A SI  a n d B S A (calc ulate d i n 
t he E A SI);

O btai n sa m p les f or la b orator y  testi n g: ser u m c he mistr y, he matol o g y  (i ncl u di n g 
c oa g ulati o n pa nel, R B C/ W B C I n dices, l y m p h oc y te s u bsets a n d mar kers) a n d 
uri nal y sis; 

Uri ne pre g na nc y  test (fe male s u bjects of c hil d beari n g p ote ntial i ncl u di n g a d olesce nts 
a ge d 1 2 ye ars a n d ol der re gar d less of w het her t he y ha ve e x perie nce d me narc he) .  A 
ne gati ve uri ne pre g na nc y test m ust be o btai ne d pri or t o d osi n g wit h t he 
i n vesti gati o nal pr o d uct; 

Assess nee d f or c o ntrace pti o n a n d a d here nce t o a p plica ble lifest yl e re q uire me nts 
(Secti o n 4. 4 ).  Esta blis h willi n g ness a n d a bility t o c o m pl y wit h lifest yl e re q uire me nts 
g oi n g f or war d i n t he st u d y;

Re vie w e Diar y  t o assess c o m pleti o n;

Perf or m dr u g acc o u nta bilit y  pr oce d ures;

A d mi nister i n v esti gati o nal pr o d uct t o t he s u bject;

P F- 0 4 9 6 5 8 4 2
B 7 4 5 1 0 1 4
Fi nal P r otoc ol A me n d me nt 5, 2 8 Oct o ber 2 0 1 9
P FI Z E R C O N FI D E N TI A L
Pa ge 7 8

Dis pe nse i n ve sti gati o nal pr o d uct t o t he s u bject;

Assess a n d rec or d a n y A d verse E ve nts si nce t he last visit.
6. 3. D o u ble - Bli n d M ai nte n a nce Tre at me nt Peri o d
6. 3. 1. Visit 8, D a y 8 5/ Wee k 1 2 ( 3 d a ys) R a n d o miz ati o n i nt o M a i nte n a nce Tre at me nt

A d mi ni ster a nd sc ore t he Si nce Last Visit C -S S R S.  F or s u bjects meeti n g a n y  of t he 
criteria s pecifie d i n Secti o n 7. 5. 1 a ris k assess me nt b y a q ualifie d M H P s h o ul d be 
d o ne t o deter mi ne w het her it is safe f o r t he s u bject t o c onti n ue t o partici pate i n t he 
trial;

A d mi nister P R Os i ncl u di n g: Pt G A, D L QI ( or C D L QI), P O E M, H A D S, E Q -5 D- 5 L  
( or E Q- 5 D-Y i n select c o u ntries), S F -3 6 v 2, Ac ute a n d F A CI T -F ( or Pe ds -F A CI T- F).  
S F -3 6 v 2 will be c o m plete d b y  a d ult s u bjects onl y ;

A d olesce nts 1 2 - 1 7 ye ars of a ge will n ot c o m plete t he S F-3 6 v 2.  A d olesce nts
1 2- 1 7 ye ars of a ge will c o m plete t he C D L QI i nstea d of t he D L QI, t he E Q - 5 D- Y i n 
select c o u ntries i nstea d of t he E Q - 5 D-5 L  a n d Pe ds-F A CI T -F i nstea d of t he F A CI T -F;

Re vie w P S A A D d ail y c o m pleti o n (i n sel ecte d c o u ntries) a n d pr urit us N R S 
c o m pleti o n f or t his visit i n t he e Diar y; 

O btai n wei g ht f or all s u bjects a n d hei g ht f or a d olesce nts o nl y  ( 1 2 t o < 1 8 ye ars ol d);

O btai n vital si g ns i ncl u di n g p ulse rate, bl o o d press ure, res pirat or y rate an d oral or 
t ym pa nic te m perat ure (after at least 5 mi n utes of rest);

Perf or m a si n gle 1 2 -lea d electr ocar di o gra m ( E C G);

C o n d uct c o m plete p h y sical e xa mi nati o n;

C o n d uct cli nical e val uati o ns i ncl u di n g I G A, S C O R A D, E A SI  a n d B S A (calc ulate d i n 
t he E A SI);

O bta i n fasti n g sa m ples f or la b orat or y testi n g: ser u m c he mistr y, he mat ol o g y 
(i ncl u di n g c oa g ulati o n pa nel, R B C/ W B C I ndices, l ym p h oc y te s u bsets a n d mar kers), 
li pi d pr ofile, a n d uri nalys is; 
 

F or C hi na a n d Tai wa n o nl y : F or s u bjects w h o ha d H B V D N A testi n g at Scree ni n g, 
c ollect bl o o d sa m ple f or r e peat H B V D N A testi n g;
C CI

P F- 0 4 9 6 5 8 4 2
B 7 4 5 1 0 1 4
Fi nal P r otoc ol A me n d me nt 5, 2 8 Oct o ber 2 0 1 9
P FI Z E R C O N FI D E N TI A L
Pa ge 7 9

Uri ne pre g na nc y test (fe male s u bjects of c h il d beari n g p ote ntial i ncl u di n g a d olesce nts 
a ge d 1 2 ye ars a n d ol der re gar dless of w het her t he y  ha ve e x perie nce d me narc he).  A 
ne gati ve uri ne pre g na nc y test m ust be o btai ne d pri or t o d osi n g wit h t he 
i n vesti gati o nal pr o d uct; 

Deter mi ne if t he s u bject meets al l of t he res p o n der criteri a f or r a n d o miz ati o n :
a.
I GA of cl ear ( 0) or al m ost clear ( 1);
b.
A re d ucti o n i n I G A fr o m b aseli ne ( Da y 1) of 2 p oi nts or m ore, a n d 
c.
Reac hi n g a n E A SI- 7 5 res p o nse c o m pare d t o baseli ne ;

Re vie w of I ncl usi o n/ E xcl usi o n Cri teria;

Ra n d o mize s u bject if all res p o n der a n d i ncl usi o n criteria are met , an d n o ne of t he 
e xcl usi o n criteria are met; 

S u bjects n ot meeti n g t he res p o n der criteria re q uire d f or ra n d o mizati o n 
(ie, n o n -res p o n ders) are t o be disc o nti n ue d a n d e nter t he 4 - wee k foll o w - u p safety 
per i o d; or e nr oll i nt o t he P F-0 4 9 6 5 8 4 2 L o n g Ter m E xte nsi o n ( L TE) st u d y B 7 4 5 1 0 1 5 
pr o vi di n g t he y  re mai n eli gi ble;

A ssess nee d f or c o ntrace pti o n a n d a d here nce t o a p plica ble lifestyl e re q uire me nts 
(Secti o n 4. 4 ).  Esta blis h willi n g ness a n d a bility t o c o m pl y wit h lifest yl e re q uire me nts 
g oi n g f or war d i n t he st u d y;

Re vie w a n y c ha n ges i n t he s u bj ect’s c o nc o mita nt me dicati o ns a n d treat me nts 
i nf or mati o n;

Re vie w e Diar y  t o assess c o m pleti o n;

Perf or m dr u g acc o u n ta bilit y pr oce d ures;

A d mi nister last d ose of o pe n-la bel r u n-i n peri o d st u d y dr u g ( 2 0 0 m g) ;

O btai n a bl o o d sa m p le f or P K a nalys is at 2. 0 h o urs (3 0 mi n) p ost d ose of o pe n -la bel 
st u d y dr u g ( 2 0 0 m g ).  For Earl y Ter mi nati o n ( E T) visits, if t he s u bject disc o nti n ues 
bef ore Wee k 4, d o n ot c ollect a P K sa m ple.  If t h e ET visit occ urs at or after Wee k 4 
a n d bef ore Wee k
1 2, c ollect a P K sa m ple o nl y if t he s u bject ta kes t he i n vesti gati o nal 
pr o d uct at t he site vi sit;

Dis pe nse bli n d e d i n vesti gati o nal pr o d uct t o t he s u bject t o i nitiate ra n d o mize d 
treat me nt me dicati o n t he day after t he Wee k 1 2 visit; 

Assess a n d rec or d a n y  A d verse E ve nts si nce t he last visit;

P F- 0 4 9 6 5 8 4 2
B 7 4 5 1 0 1 4
Fi nal P r otoc ol A me n d me nt 5, 2 8 Oct o ber 2 0 1 9
P FI Z E R C O N FI D E N TI A L
Pa ge 8 0

A d mi nister A C Q test f or all s u bjects wit h a pri or dia g n osi s of ast h ma. 
6. 3. 2. Visit 9, D a y 1 1 3/ Wee k 1 6 ( 3 d a ys) 

A d mi nister a n d sc ore t he Si nce Last Visit C -S S R S.  F or s u bjec ts meeti n g a n y  of t he 
criteria s pecifie d i n Secti o n 7. 5. 1 a ris k assess me nt b y a q ualifie d M H P s h o uld be 
d o ne t o deter m i ne w het her it is safe f or t he s u bject t o c o ntin ue t o partici pate i n t he 
trial;

A d mi nister P R Os i ncl u di n g: Pt G A, D L QI ( or C D L QI), P O E M, H A D S a n d 
E Q - 5 D-5 L  ( or E Q-5 D -Y i n select c o u ntries); 

A d olesce nts 1 2 - 1 7 ye ars of a ge will c o m plete t he C D L QI  i nstea d of the D L QI a n d t he 
E Q - 5 D- Y i n select c o u ntries i nstea d of t he E Q- 5 D-5 L ;

Re vi e w P S A A D dail y c o m pleti o n (i n selecte d c o u ntries) a n d pr urit us N R S 
c o m pleti on f or t his visit i n t he e Diar y ; 

O btai n vital si g ns i ncl u di n g p ulse rate, bl o o d press ure , res pirat or y rate a n d oral or 
t ym pa nic te m perat ure (after at least 5 mi n utes of rest);

Perf or m a si n gle 1 2-lea d E C G;

C o n d uct tar gete d p h ys ical e xa mi nati o n;

O btai n sa m p les f or la b orat or y testi n g: ser u m c he mistr y, he mat ol o g y (i ncl u di n g 
c oa g ulati o n pa nel, R B C/ W B C I n dices, l y m p h o c y te s u bsets a n d mar kers) a n d 
uri nal y sis; 

Uri ne pre g na nc y  test (fe male s ubjects of c hil d beari n g p ote ntial i ncl u di n g a d olesce nts 
a ge d 1 2 ye ars a n d ol der re gar dless of w het her t he y  ha ve e x perie nce d me narc he).  A 
ne gati ve uri ne pre g na nc y test m ust be o btaine d pri or t o d osi n g wit h t he 
i n vesti gati o nal pr o d uct; 

C o n d uct cli nical e val uati o ns i ncl u di n g I G A, S C O R A D, E A SI  a n d B S A (calc ulate d i n 
t he E A SI);

Det er mi ne if t he s u bject e x perie nce d a flare, defi ne d as a l oss of at least 5 0 % of t he 
E A SI res p o nse at Wee k 1 2 a n d a n I G A of 2 or hi g her.  If flare, t he s u bject will e nter 
t he resc ue pe ri o d (see Secti o n 6. 5 );

Assess nee d f or c o ntrace pti o n a n d a d here nce t o a p plica ble lifestyl e re q uir e me nts 
(Secti o n 4. 4 ).  Esta blis h willi n g ness a n d a bilit y t o c o m pl y wit h lifest yl e re q uire me nts 
g oi n g f or w ar d i n t he st u d y;

Re vie w a n y c ha n ges i n t he s u bject’s c o nc o mita nt me dicati o ns a n d treat me nts 
i nf or mati o n;

P F- 0 4 9 6 5 8 4 2
B 7 4 5 1 0 1 4
Fi nal P r otoc ol A me n d me nt 5, 2 8 Oct o ber 2 0 1 9
P FI Z E R C O N FI D E N TI A L
Pa ge 8 1

R e vie w e Diar y t o assess c o m pleti o n;

Perf or m dr u g acc o u nta bilit y  pr oce d ures;

A d mi nister i n vesti gati o nal pr o d uct t o t he s u bject;

Dis pe nse i n vesti gati o nal pr o d uct t o t he s u bject;

Assess a n d rec or d a n y A d verse E ve nts si nce t he last visit.
6. 3. 3. Vis it 1 0, D a y 1 9 7/ Wee k 2 8 ( 7 d a ys) 

A d mi nister a n d sc ore t he Si nce Last Visit C -S S R S.  F or s u b jects meeti n g a n y of t he 
criteria s pecifie d i n Secti o n 7. 5. 1 a ris k assess me nt b y a q ualifie d M H P s h o ul d be 
d o ne t o det er mi ne w het her it i s safe f or t he s u bject t o c o ntin ue t o partici pate i n t he 
trial;

A d mi nist er P R Os i ncl u di n g: Pt G A, D L QI ( or C D L QI), P O E M, H A D S a n d 
E Q - 5 D-5 L  ( or E Q-5 D - Y i n select c o u ntries); 

A d olesce nts 1 2 - 1 7 ye ars of a ge will c o m plete t he C D L QI  i nstea d of t he D L QI a n d t he 
E Q - 5 D- Y i n select c o u ntries i nstea d of t he E Q- 5 D-5 L ;

R e vie w P S A A D dail y c o m pleti o n (i n selecte d c o u ntries) a n d pr urit us N R S 
c o m pleti o n f or t his visit i n t he e Diar y; 

O btai n vital si g ns i ncl u di n g p ulse rate, bl o o d press ure, res pirat or y  rate a n d oral or 
t ym p a nic te m perat ure (after at least 5 mi n utes of rest);

P erfor m a si n gle 1 2 -lea d E C G;

C o n d uct tar gete d p h ys ical e xa mi nati o n;

O btai n sa m ples f or la b orat o r y testi n g: ser u m c he mistr y, he mat ol o g y (i ncl u di n g 
c oa g ulati o n pa nel, R B C/ W B C i n dices, l y m p h oc y te s u bsets a n d mar kers) a n d 
uri nal y sis; 

F or C hi na a n d Tai wa n o nl y : For s u bjects w h o ha d H B V D N A testi n g at Scree ni n g, 
c ollect bl o o d sa m ple f or re peat H B V D N A testi n g; 

Uri ne pre g na nc y  test (fe male s u bjects of c hil d beari n g p ote ntial i ncl u di n g a d olesce nts 
a ge d 1 2 ye ars a n d ol der re gar dless of w het her t he y  ha ve e x perie nce d me narc he).  A 
ne gati ve uri ne pre g na nc y test m ust be o btai ne d pri or t o d osi n g wit h t he 
i n vesti gati o nal pr o d uct; 

C o n d uct cli nical e val uati o ns i ncl u di n g I G A, S C O R A D, E A SI  a n d B S A (calculate d i n 
t he E A SI);

P F- 0 4 9 6 5 8 4 2
B 7 4 5 1 0 1 4
Fi nal P r otoc ol A me n d me nt 5, 2 8 Oct o ber 2 0 1 9
P FI Z E R C O N FI D E N TI A L
Pa ge 8 2

Deter mi ne if t he s u bject e x perie nce d a flare, defi ne d as a l oss of at least 5 0 % of t he 
E A SI  res p o nse at Wee k 1 2 a n d a n I G A of 2 or hi g her.  If flar e, t he s u bject will e nter 
t he resc ue peri o d (see Secti o n 6. 5 );

Assess nee d f or c o ntrace pti o n a n d a d he re nce t o a p plica ble lifestyl e re q uire me nts 
(Secti o n 4. 4 ).  Esta blis h willi n g ness a n d a bility t o c o m pl y wit h lifest yl e re q uire me nts 
g oi n g f or war d i n t he st u d y;

Re vie w a n y c ha n ges i n t he s u bje ct’s c o nc o mita nt me dicati o ns a n d treat me nts 
i nf or mati o n;

Re vie w e Diar y  t o assess c o m pleti o n;

Pe rf or m dr u g acc o u nta bilit y pr oce d ures;

A d mi nister i n vesti gati o nal pr o d uct t o t he s u bject;

Dis pe nse i n vesti gati o nal pr o d uct t o t he s u bject;

Assess a n d rec or d a n y A d ve rse E ve nts si nce t he last visit.
6. 3. 4. Visit 1 1, D a y 2 8 1/ Wee k 4 0 ( 7 d a ys) 

A d mi nister a n d sc ore t he Si nce Last Visit C -S S R S.  F or s u bjects meeti n g a n y  of t he 
criteria s pecifie d i n Secti o n 7. 5. 1 a ris k assess me nt b y a q ualifie d M H P s h o ul d be 
d o ne t o deter mi ne w het her it is safe f or t he s u bject t o c o nti n ue t o partici pate i n t he 
trial;

A d mi nister P R Os i ncl u di n g: Pt G A, D L QI ( or C D L QI), P O E M, H A D S a n d 
E Q - 5 D-5 L  ( or E Q-5 D -Y i n select c o u ntries); 

A d oles ce nts 1 2-1 7 y ears of a ge will c o m plete t he C D LQI  i nstea d of t he D L QI a n d t he 
E Q - 5 D-Y i n select c o u ntries i nstea d o f t he E Q- 5 D-5 L ;

Re vie w P S A A D dail y c o m pleti o n (i n selecte d c o u ntries) a n d pr urit us N R S 
co m pleti o n f or t his visit i n t he e Diar y ; 

O btai n vital si g ns i ncl u di n g p ulse rate, bl o o d press ure, res pirat or y rate a n d oral or 
t ym pa nic te m perat ure (after at least 5 mi n utes of rest);

Perf or m a si n gle 1 2 -lea d E C G;

C o n d uct tar gete d p h ys ical e xa mi nati o n;

O bt ai n sa m ples f or la b orat or y  testi n g: ser u m c he mistr y, he matol o g y  (i ncl u di n g 
c oa g ulati o n pa nel, R B C/ W B C In dices, l y m p h oc y te s u bsets a n d mar kers) a n d 
uri nal y sis; 

P F- 0 4 9 6 5 8 4 2
B 7 4 5 1 0 1 4
Fi nal P r otoc ol A me n d me nt 5, 2 8 Oct o ber 2 0 1 9
P FI Z E R C O N FI D E N TI A L
Pa ge 8 3

F or C hi n a a n d Tai wa n o nl y : F or s u bjects w h o ha d H B V D N A testi n g at Scree ni n g, 
c ollect bl o o d sa m p le f or re peat H B V D N A testi n g;

Uri ne pre g na nc y  test (fe male s u bjects of c hil d beari n g p ote ntial i ncl u di n g a d olesce nts 
a ge d 1 2 ye ars a n d ol der re gar dless of w het her t he y ha ve e x perie nce d me narc he).  A 
ne gati ve uri ne pre g na nc y test m ust be o btai ne d pri or t o d osi n g wit h t he 
i n vesti gati o nal pr o d uct; 

C o n d uct cli n ical e val uati o ns i ncl u di n g I G A, S C O R A D, E A SI  a n d B S A (calc ulate d i n 
t he E A SI);

Deter mi ne if t he s u bject e x perie nce d a flare, defi ne d as a l oss of at least 5 0 % of t he 
E A SI  res p o nse at Wee k 1 2 a n d a n I G A of 2 or hi g her.  If flare, t he su bject will e nter 
t he rescue peri o d (see Secti o n 6. 5 );

Assess nee d f or c o ntrace pti o n a n d a d here nce t o a p plica ble lifest yl e re q uire me nts 
(Secti o n 4. 4 ).  Esta blis h willi n g ness a n d a bilit y t o c o m pl y wit h lifest yl e re q uire me nts 
g oi n g f or war d i n t he st u d y;

Re vie w a n y  c han ges i n t he s u bject’s c o nc o mita nt me dicati o ns a n d treat me nts 
i nf or mati o n;

Re vie w e Diar y  t o assess c o m pleti on;

Perf or m dr u g acc o u nta bilit y  pr oce d ures;

A d mi nister i n vesti gati o nal pr o d uct t o t he s u bject;

Dis pe nse i n vesti gati o nal pr o d uct t o t he s u bject;

Assess a n d rec or d a n y A d verse E ve nts si nce t he last visit.
6. 3. 5. Visit 1 2, D a y 3 6 5/ Wee k 5 2 ( 3 d a ys) E n d of Tre at me nt ( E O T) or E arl y 
Ter mi n ati o n ( E T)

A d mi nist er a n d sc ore t he Si nce Last Visit C- S S R S.  F or s u bjects meeti n g a n y  of t he 
criteria s pecifie d i n Secti o n 7. 5. 1 a ris k assess me nt b y a q ualifie d M H P s h o uld be 
d o ne t o deter m i ne w het her it is safe f or t he s u bject t o c o nti n ue t o partici pate i n t he 
trial;

A d mi nister P R Os i ncl u di n g: Pt G A, D L QI ( or C D L QI), P O E M, H A D S, E Q - 5 D- 5L 
( or E Q- 5 D-Y i n select c o u ntries), S F - 3 6 v 2, Ac ute a n d F A CI T-F ( or Pe ds -F A CI T- F).  
S F - 3 6v 2 will be c o m plete d b y  a d ult s u bjects onl y ; 

A d olesce nts 1 2 - 1 7 ye ars of a ge will n ot c o m plete t he S F -3 6 v 2.  A d olesce nts
1 2 - 1 7 ye ars of a ge will c o m plete t he C D L QI i nst ea d of t he D L QI, t he E Q - 5 D- Y i n 
select c o u ntries i nstea d of t he E Q- 5 D-5 L  a n d Pe ds-F A CI T - F i nstea d of t he F ACI T- F;

P F- 0 4 9 6 5 8 4 2
B 7 4 5 1 0 1 4
Fi nal P r otoc ol A me n d me nt 5, 2 8 Oct o ber 2 0 1 9
P FI Z E R C O N FI D E N TI A L
Pa ge 8 4

Re vie w P S A A D d ail y c o m pleti o n (i n selecte d c o u ntries) a n d pr urit us N R S 
c o m pleti o n f or t his visit i n t he e Diar y; 

O btai n wei g ht f or all s u bject s a n d hei g ht f or a d olesce nts o nl y ( 1 2 t o < 1 8 ye ars ol d);

O btai n vital si g ns i ncl u di n g p u lse rate, bl o o d press ure, res pirat or y rate a n d oral or 
t ym pa nic te m perat ure (after at least 5 mi n utes of rest);

Perf or m a si n gle 1 2 -lea d E C G; 

C o n d uct a c o m plete p h ys ical e xa mi nati o n;

C o n d uct cli nical e val uati o ns i ncl u di n g I G A, S C O R A D, E A SI  a n d B S A (calc ulate d i n 
t he E A SI);

Deter mi ne if t he su bject e x perie nce d a flare, defi ne d as a l oss of at least 5 0 % of t he 
E A SI  res p o nse at Wee k 1 2 a n d a n I G A of 2 or hi g her.  If flare, t he s u bject will e nter 
t he resc ue peri o d (Secti o n 6. 5 );

O bt ai n fasti n g sa m ples f or la b orat or y  testi n g: ser u m c he mistr y, he mat ol o g y 
(i ncl u di n g c oa g ulati o n pa nel, R B C/ W B C i n dices, l y m p h oc y te s u bsets a n d mar kers), 
lipi d pr ofile, a n d uri nal ys is; 
 

F o r C hi na a n d Tai w a n o n l y: F or s u bjects w h o ha d H B V D N A testi n g at Scree ni n g, 
c ollect bl o o d sa m ple f or re peat H B V D N A testi n g;

F oll o wi n g o ne year of t otal e x p os ure t o st u d y dr u g si nce t he last T B test, all s u bjects 
i n re gi o ns w hic h are a bo ve a l o w ris k f or T u berc ul osis (ie , > 1 0/ 1 0 0, 0 0 0 pre vale nce) 
will u n der g o t u berc ul osis ( T B) testi n g.  If s o, e ns ure testi n g is perf or me d as per 
Secti o n 7. 3. 4 .  A n e gati ve test res ult f or t u berc ul osis is re q uire d f or o n g oi n g 
eli gi bilit y f or st u d y partici pati o n;

Uri ne pre g na nc y  test (fe male s u bjects of c hil d beari n g p ote ntial i ncl u di n g a d olesce nts 
a ge d 1 2 ye ars a n d ol der re gar dless of w het her t he y ha ve e x perie nce d me narc he).  A 
ne gati ve uri ne pre g n a nc y test m ust be o btai ne d pri or t o d osi n g wit h t he 
i n vesti gati o nal pr o d uct; 

S u bjects w h o c o m plete d t he 4 0 w ee ks of bli n de d treat me nt wit h o ut e x perie nci n g flare 
will b e assesse d f or eli gi bilit y t o e nter L T E st u d y B 7 4 5 1 0 1 5.  S u bjects w h o are n ot 
eli gi ble or are n ot i nterested are t o c o nti n u e i n t he 4-wee k, u ntreate d safet y f oll o w- u p 
peri o d;

Assess nee d f or c o ntra ce pti o n a n d a d here nce t o a p plica ble lifest yl e re q uire me nts 
(Secti o n 4. 4 ).  Esta blis h willi n g ness a n d a b ilit y t o c o m pl y wit h lifesty le re q uire me nts 
g oi n g f or war d i n t he st u d y;
C CI

P F- 0 4 9 6 5 8 4 2
B 7 4 5 1 0 1 4
Fi nal P r otoc ol A me n d me nt 5, 2 8 Oct o ber 2 0 1 9
P FI Z E R C O N FI D E N TI A L
Pa ge 8 5

Re vie w a n y c ha n ges i n t he s u bject’s c o nc o mita nt me dicati o ns a n d treat me nts 
i nf or mati o n;

Re vie w e Diar y  t o assess c o m pleti o n;

Perf or m dr u g acc o u nta bilit y  pr oce d ures;

A d mi nister last d ose of i n vesti gati o nal p r o d uct as part of t he bli n de d mai nte na nce 
peri o d t o t he s u bject;

Assess a n d rec or d a n y A d verse E ve nts si nce t he last visit;

A d mi nister A C Q test f or all s u bjects wit h a pri or dia g n osis of ast h ma. 
6. 4. F oll o w -u p Visit
6. 4. 1. Visi t 1 3, 4 Wee ks P ost E n d of Tre at me nt / E arly Ter mi n ati o n - E n d of St u d y
( ±3 d a ys)

A d mi nister a n d sc ore t he Si nce Last Visit C -S S R S.  F or s u bjects meeti n g a n y  of t he 
criteria s pecifie d i n Secti o n 7. 5. 1 a ris k asses s me nt b y a q ualified M H P s h o ul d be 
d o ne t o deter mi ne w het her it is safe f or t he s u bject t o c o nti n ue t o partici pate i n t he 
trial;

A d mi nister P R Os i ncl u di n g: Pt G A, D L QI ( or C D L QI), P O E M, H A D S, E Q - 5 D-5 L  
( or E Q- 5 D-Y i n select c o u ntries), S F - 3 6 v 2, Ac ute a n d F A CI T-F ( or Pe ds -F A CI T- F ).  
S F -3 6 v 2 will be c o m plete d b y  a d ult s u bjects o nl y; 

A d olesce nts 1 2 -1 7 y ears of a ge will n ot c o m plete t he S F -3 6 v 2.  A d olesce nts
1 2 - 1 7 ye ars of a ge will c o m p lete t he C D L QI i nstea d of t he D L QI, t he E Q- 5 D- Y i n 
select c o u ntries i nstea d of t he E Q- 5 D-5 L  a n d Pe ds- F A CI T -F i nstea d of t he F A CI T -F; 

Re vie w P S A A D dail y  c o m pleti o n (i n selecte d c o u ntr ies) a n d pr urit us N R S 
c o m pleti o n f or t his visit i n t he e Diar y;

O btai n vital si g ns i ncl u di n g p ulse rate, bl o o d press ure, res pirat or y rate a n d oral or 
ty m pa nic te m perat ure (after at least 5 mi n utes of rest);

Perf or m a si n gle 1 2 -lea d E C G;

C o n d uct tar gete d p h ys ical e xa mi nati o n;

C o n d uct cli nical e val uati o ns i ncl u di n g I G A, S C O R A D, E A SI  a n d B S A (calc ulate d i n 
t he E A SI);

O btai n fasti n g sa m ples f or la b orat or y  testi n g: ser u m c hemistr y, he mat ol o g y 
(i ncl u di n g c oa g ulati o n pa nel, R B C/ W B C In dices, l y m p h oc y te s u bsets a n d mar kers), 
li pi d pr ofile, a n d uri nalys is; 

P F- 0 4 9 6 5 8 4 2
B 7 4 5 1 0 1 4
Fi nal P r otoc ol A me n d me nt 5, 2 8 Oct o ber 2 0 1 9
P FI Z E R C O N FI D E N TI A L
Pa ge 8 6

Uri ne pre g na nc y  test (fe male s u bjects of c hil d beari n g p ote ntial i ncl u di n g a d olesce nts 
a ge d 1 2 ye ars a n d ol der re gar dless of whet he r t he y ha ve e x perie nce d me narc he); 

Assess a d here nce t o c o ntrace pti o n a n d a p plica ble lifest y le re q uire me nts (Secti o n 4. 4 );

Re vie w a n y c ha n ges i n t he s u bject’s c o nc o mita nt m e dicati o ns a n d t reat me nts 
i nf or mati o n;

Assess a n d rec or d a n y A d verse E ve nts si nce t he last visit;

A d mi nister A C Q test f or all s u bjects wit h a pri or dia g n osis of ast h ma.
6. 5. Resc ue Tre at me nt Peri o d 
S u bjects will be i nstr ucte d t o c o ntact t he site if t he y e x per ie nce a si g nifica nt w orse ni n g of 
t heir at o pic der matitis, s uc h as a rec urre nce of pr urit us, d uri n g t he d o u ble-bli n d treat me nt 
peri o d.   Site staff will deter mi ne if t he s u bject s h o ul d ret ur n t o t he site f or a n u nsc he d ule d 
(see Secti o n 6. 5. 1 ) or re g ularl y sc he d ule d visit (see Secti o n 6. 3 ).  At t he visit (re g ular or 
u n pla n ne d) t he s u bject will be assesse d f or flare, defi ne d as a l oss of at least 5 0 % of t he 
E A SI  res p o nse at Wee k 1 2 a n d a n I G A sc ore of 2 or hi g her.  S u bjects w h o meet t he 
defi niti o n of flare are t o recei ve resc ue treat me nt a n d e nter a n o pe n -la bel resc ue peri o d 
d uri n g w hic h t he y  recei ve 1 2-wee ks of 2 0 0 m g  P F -0 4 9 6 5 8 4 2 Q D wit h c o nc o mita nt t o pical 
t hera py per S O C.  See Secti o n 5. 2. 1 f or g ui da nce o n t o pical t hera pies. 
After c o m ple ti n g t he resc ue peri o d, s u bjects are all o we d t o e nter t he L T E st u d y  B 7 4 5 1 0 1 5, if 
eli gi ble.  If a s u bject di sco nti n ues pre mat urel y or is n ot eli gi ble or willi n g t o partici pate i n 
B 7 4 5 1 0 1 5, t he n t he s u bject e nters t he 4 - wee k, u ntreate d f oll o w- u p safety peri o d.  Ref er t o 
Sc he d ule of Acti vities f or Resc ue Treat me nt . 
S u bjects n ot me eti n g t he defi niti o n of flare will c o nti n ue o n t heir bli n de d treat me nt.  
P h y sicia ns ma y c o nti n ue t o cli nicall y e val uate f or flare usi n g t he E A SI a nd I G A as sess me nts 
at t heir discreti o n. 
6. 5. 1. Resc ue Tre at me nt - Fl are Occ urri n g at a n U n pl a n n e d Visit ( Resc ue Vi sit 1, 
D a y 1/ Wee k 0 ( 3 d a ys) )

A d mi nister a n d sc ore t he Si nce Last Visit C -S S R S.  F or s u bjects meeti n g a n y  of t he 
criteria s pecifie d i n Secti o n 7. 5. 1 a ris k assess me nt b y a q ualifie d M H P s ho ul d b e 
d o ne t o deter m i ne w het her it is safe f or t he s u bject t o c o ntin ue t o partici pate i n t he 
trial;

A d mi nister P R Os i ncl u di n g: Pt G A, D L QI ( or C D L QI), P O E M, H A D S, E Q - 5 D- 5L 
( or E Q- 5 D-Y i n select c o u ntries), S F - 3 6 v 2, Ac ute a n d F A CI T-F ( or Pe ds -F A CI T- F).  
S F - 3 6 v 2 will be c o m plete d b y  a d ult s u bjects o nl y; 

A d olesce nts 1 2 - 1 7 ye ars of a ge will n ot c o m plete t he S F -3 6 v 2.  A d olesce nts
1 2 - 1 7 ye ars of a ge will c o m p lete t he C D L QI i nstea d of t he D L QI, t he E Q - 5 D- Y i n 
select c o u ntries i nstea d of t he E Q- 5 D-5 L  a n d Pe ds-F A C I T-F i nstea d of t he F A CI T- F;

P F- 0 4 9 6 5 8 4 2
B 7 4 5 1 0 1 4
Fi nal P r otoc ol A me n d me nt 5, 2 8 Oct o ber 2 0 1 9
P FI Z E R C O N FI D E N TI A L
Pa ge 8 7

Re vie w P S A A D dail y  c o m pleti o n (i n selecte d c o u ntr ies) a n d pr urit us N R S 
c o m pleti o n f or t his visit i n t he e Diar y.  I nstr uct the s u bject t hat t he pr uritis N R S 
c o m pleti o n will be c ollecte d dail y  i n t he e Diar y fr o m D a ys 1-1 5 d uri n g resc ue
treat me nt a n d the n o nl y o n st u d y  visit da ys at t he i n vesti gat or site t hereafter.  P S A A D 
will be c o m plete d dail y  (i n selecte d c o u ntries) i n t he e Diar y fr o m D a y 1 t hr o u g h t he 
E O S visit d uri n g resc ue treat me nt.  Re vie w e Diar y pr oce d ures wit h s u bject as
ne cess ar y;

O btai n wei g ht f or all s u bjects a n d hei g ht f or a d olesce nts o nl y  ( 1 2 t o < 1 8 ye ars ol d);

C o n d uct tar gete d p h ys ical e xa mi nati o n; 

O btai n vital s i g ns i ncl u di n g p ulse rate, bl o o d press ure, res pirat or y  rate a n d oral or 
t ym pa nic te m perat ure (after at l east 5 mi n utes of rest );

Perf or m a si n gle 1 2 -lea d E C G;

C o n d uct cli nical e val uati o ns i ncl u di n g I G A, S C O R A D, E A SI  a n d B S A (calc ulate d i n 
t he E A SI); 

O btai n fasti n g sa m ples f or la b orat or y  testi n g: ser u m c he mistr y, he mat ol o g y 
(i ncl u di n g c oa g ulati o n, R B C/ W B C In dic es, l ym p h oc y te s u bsets a n d mar kers), li pi d 
pr ofile, a n d uri nal ys is;
 

F oll o wi n g o ne year of t otal e x p os ure t o st u d y  dr u g si nce t he last T B test, all s u bjects 
i n re gi o ns w hic h are a b o ve a l o w ris k f or Tu be rc ul osis (ie, > 1 0/ 10 0, 0 0 0 pre vale nce) 
will u n der g o t u berc ul osis ( T B) testi n g.  If s o, e ns ure testi n g is perf or me d as per 
Secti o n 7. 3. 4 .  A ne gati ve test res ult f or t u berc ul osis is re q uire d f or o n g oi n g 
eli gi bilit y f or st u d y partici pati o n;

Uri ne pre g na nc y  test (fe male s u bjects of c hil d beari n g p ote ntial i ncl u di n g a d olesce nts 
a ge d 1 2 ye ars a n d ol der re gar dless of w het her t he y  ha ve e x perie nce d me narc he).  A 
ne gati ve uri ne pre g na nc y test m ust be o b taine d pri or t o d osi n g wit h t he 
i n vesti gati o nal pr o d uct;

Re vie w a n y c ha n ges i n t he s u bject’s pri or a n d c o nc o mita nt me dicati o ns a n d treat me nt 
i nf or mati o n; 

Assess nee d f or c o ntrace pti o n a n d a d here nce t o a p plica ble lifest yl e re q uire me nts 
(Secti o n 4. 4 ).  Esta blis h willi n g ness a n d a bility t o c o m pl y wit h lifest yl e re q uire me nts 
g oi n g f or war d i n t he st u d y;

Re vie w e Diar y t o assess c o m pleti o n;

Perf or m dr u g acc o u nta bilit y  pr oce d ures;
C CI

P F- 0 4 9 6 5 8 4 2
B 7 4 5 1 0 1 4
Fi nal P r otoc ol A me n d me nt 5, 2 8 Oct o ber 2 0 1 9
P FI Z E R C O N FI D E N TI A L
Pa ge 8 8

A d mi nister i n vesti gat i o nal pr o d uct t o t he s u bject;

Dis pe nse i n vesti gati o nal pr o d uct t o t he s u b ject;

Assess a n d rec or d a n y A d verse E ve nts si nce t he last visit;

A d mi nister A C Q test f or all s u bje cts wit h a pri or dia g n osis of ast h ma. 
6. 5. 2. Resc ue Tre at me nt – Visit 2, D a y 8/ Wee k 1 ( 1 d a y)

Ca ll s u bject a n d co nfir m c o m plia nce wit h dail y c o m pleti o n of pr urit us N R S a n d 
P S A A D (i n selecte d c o u ntries); 

Ver ball y c o nfir m s u bject has bee n c o m plia nt wit h st u d y  d osi n g a n d e ntr y i n t he 
e Diar y.  Re vie w e Diar y pr oce d ures wit h s u bject as necessar y;

Re vie w a n y  c ha n ges i n t he s u bject’s c o nc o mita nt me dicati o ns a n d treat me nt 
i nf or mati o n;

Assess nee d f or c o ntrace pti o n a n d a d here nce t o a p plica ble lifest yl e re q uire me nts 
(Secti o n 4. 4 ).  Esta blis h w illi n gness a n d a bilit y t o c o m pl y wit h lifestyl e re q uire me nts 
g oi n g f or war d i n t he st u d y;

Assess a n d rec or d a n y A d verse E ve nts si nce t he last visit .
6. 5. 3. Resc ue Tre at me nt – Visi t 3, D a y 1 5/ Wee k 2 (1 d a y)

A d mi nister P R Os i ncl u di n g: Pt G A, D L QI ( or C D L QI), P O E M, H A D S a nd 
E Q - 5 D-5 L  ( or EQ- 5 D -Y i n select c o u ntries);

A d olesce nts 1 2 -1 7 y ears of a ge will c o m plete t he C D L QI  i nstea d of t he D L QI a n d t he 
E Q - 5 D-Y i n select c o u ntries i nstea d o f t he E Q- 5 D-5 L ;

Re vie w dail y P S A A D c o m pleti o n (i n selecte d c o u ntries) a n d dail y pr ur it us N R S 
c o m pleti o n i n t he e Diar y; Instr uct s u bject t hat pr urit us N R S will n o w be c o m plete d 
o nl y  at site visits, b ut t he P S A A D will still be c o m plete d dail y i n t he e Diar y. Re vie w 
e Diar y pr oce d ures wit h s u bject as necessar y;

Re vie w a n y c ha n ges i n t he s u bje ct’s c onc o mita nt me dica ti o ns a n d treat me nt 
i nf or mati o n;

O btai n vital si g ns i ncl u di n g p ulse rate, bl o o d press ure, res pirat or y  rate a n d oral or 
t ym pa nic te m perat ure (after at least 5 mi n utes of rest);

Perf or m a si n gle 1 2 -lea d E C G;

C o n d uct a tar gete d p h ys ical e xam; 

P F- 0 4 9 6 5 8 4 2
B 7 4 5 1 0 1 4
Fi nal P r otoc ol A me n d me nt 5, 2 8 Oct o ber 2 0 1 9
P FI Z E R C O N FI D E N TI A L
Pa ge 8 9

C o n d uct cli nica l e val uati o ns i ncl u di n g I G A, S C O R A D, E A SI a n d B S A (calc ulate d i n 
t he E A SI);

O btai n sa m ples f or la b orat or y testi n g: ser u m c he mistr y , he mat ol o g y (i ncl udi n g 
c oa g ulati o n, R B C/ W B C i n dices, l ym p h oc y te s u bsets a n d mar kers) a n d uri nal ysis;

F o ll owi n g o ne year of t o tal e x p os ure t o st u d y dr u g si nce t he last T B test, all s u bjects 
i n re gi o ns w hic h are a b o ve a l o w ris k f or T u berc ul osis (ie, > 1 0/ 1 0 0, 0 0 0 pre vale nce) 
will u n der g o t u berc ul osis ( T B) testi n g.  If s o, e ns ure testi n g is perf or me d as per 
Secti o n 7. 3. 4 .  A ne g ati ve test res ult f or t u berc ul osis is re q uire d f or o n g oi n g 
eli gi bilit y f or st u d y partici pati o n;

Uri ne pre g na nc y  test (fe male s u bjects of c hil d beari n g p ote ntial i ncl u di n g a d olescents
a ge d 1 2 ye ars an d ol der re gar dless of w het her t he y  ha ve e x perie nce d me narc he).  A 
ne gati ve uri ne pre g na nc y test m ust be o btai ne d pri or t o d osi n g wit h t he 
i n vesti gati o nal pr o d uct;

Assess nee d f or c o ntrace pti o n a n d a d here nce t o a p plica ble lifest yl e req ui re me nts 
(Secti o n 4. 4 ).  Esta blis h willi n g ness a n d a bilit y t o c o m pl y wit h lifestyl e re q uire me nts 
g oi n g f or war d i n t he st u d y ;

Re vie w e Diar y  t o assess c o m pleti o n;

Perf or m dr u g acc o u nta bilit y  proce d ur es;

A d mi nister i n vesti gati o nal pr o d uct t o t he s u bject;

Assess a n d rec or d a n y A d verse E ve nts si nce t he last visit.
6. 5. 4. Resc ue Tre at me nt – Visit 4, D a y 2 9/ Wee k 4 ( 2 d a ys)

A d mi nister P R Os i ncl u di n g: Pt G A, D L QI ( or C D L QI), P O E M, H A D S a n d 
E Q - 5 D-5 L  ( or E Q-5 D -Y i n s elect c o u ntries) ; 

A d olesce nts 1 2 -1 7 y ears of a ge will c o m plete t he C D L QI  i nstea d of t he D L QI a n d t he 
E Q - 5 D- Y i n select c o u ntries i nstea d of t he E Q- 5 D-5 L ;

Re vie w P S A A D dail y c o m pleti o n (i n selecte d c o u ntr ies) a n d pr urit us N R S 
c o m pleti o n f or t his visi t in t he e Diar y .  Re vie w e Diar y pr oce d ures wit h s u bject as 
necessar y ;

Re vie w a n y c ha n ges i n t he s u bject’s pri or a n d c o nc o mita nt me dicati o ns a n d treat me nt 
i nf or mati o n;

O bta i n vital si g ns i ncl u di n g p ulse rate, bl o o d press ure, res pirat or y rate a n d oral or 
t ym pa n ic te m perat ure (after at least 5 mi n utes of rest);

P F- 0 4 9 6 5 8 4 2
B 7 4 5 1 0 1 4
Fi nal P r otoc ol A me n d me nt 5, 2 8 Oct o ber 2 0 1 9
P FI Z E R C O N FI D E N TI A L
Pa ge 9 0

Perf or m a si n gle 1 2 -lea d electr ocar di o gra m ( E C G);

C o n d uct tar gete d p hys ical e xa mi nati o n;

C o n d uct cli nical e val uati o ns i ncl u di n g I G A, S C O R A D, E A SI a n d B S A (calc ulate d i n 
t he E A SI);

O btai n fasti n g sa m ples f or la b orat or y testi ng: ser u m c he mistr y , he mat ol o g y 
(i ncl u di n g c oa g ulati o n pa ne, R B C/ W B C i n dices, l y m p h oc yte s ubsets a n d mar kers), 
li pi d pr ofile a n d uri nalys is;

F oll o wi n g o ne y ear of t otal e x p os ure t o st u d y dr u g si nce t he last T B test, all s u bjects 
i n re gi o ns whic h are a b o ve a l o w ris k f or T u berc ul osis (ie, > 1 0/ 1 0 0, 0 0 0 pre vale nce) 
will u n der g o t u berc ul osis ( T B) testi n g.  If s o, e ns ure testi n g is perf or me d as per 
Secti o n 7. 3. 4 .  A ne gati ve test result f or t u berc ul osis is re q uire d f or o n g oi n g 
eli gi bilit y f or st u d y partici pati o n;

Uri ne pre g na nc y  test (fe male s u bjects of c hil d beari n g p ote ntial i ncl u di n g a d olesce nts 
a ge d 1 2 ye ars a n d ol der re gar dless of w het her t he y  ha ve e x perie nce d me narc he).  A 
ne g ative uri ne pre g na nc y test m ust be o btai ne d pri or t o d osi n g wit h t he 
i n vesti gati o nal pr o d uct;

Assess nee d f or c o ntrace pti o n a n d a d here nce t o a p plica ble lifest yl e re q uire ments 
(Secti o n 4. 4 ).  Esta blish willi n g ness a n d a bilit y t o c o m pl y wit h lifest yl e re q uire me nts 
g oi n g f or war d i n t he st u d y;

Re vie w e Diar y  t o assess c o m pleti o n;

Perf or m dr u g acc o u nta bilit y  pr oce d ures;

A d mi nister i n vesti gati o nal pr o d uct t o t he s u bject;

Dis pe nse i n vesti gati o nal pr o d uct to t he s u bject;

Asse ss a n d rec or d a ny A d verse E ve nts si nce t he last visit.
6. 5. 5. Resc ue Tre at me nt – Visit 5, D a y 4 3/ Wee k 6 ( 3 d a ys)

Call s u bject a n d c o nfir m c o m plia nce wit h d ail y c o m pleti o n of P S A A D (i n selecte d 
c o u ntries);

Ver ball y c o nf ir m s u bject has bee n co m p liant wit h st u d y  d osi n g a n d e ntr y i n t he 
e Diar y.  Re vie w e Diar y pr oce d ures wit h s u bject as necessar y;  

Re vie w a n y c ha n ges i n t he s u bject’s c o nc o mita nt me dicati o ns a n d treat me nt 
i nf or mati o n;

P F- 0 4 9 6 5 8 4 2
B 7 4 5 1 0 1 4
Fi nal P r otoc ol A me n d me nt 5, 2 8 Oct o ber 2 0 1 9
P FI Z E R C O N FI D E N TI A L
Pa ge 9 1

Assess nee d f or c o ntrace pti o n a n d a d here nce t o a p plica ble life sty le re q uire me nts 
(Secti o n 4. 4 ).  Esta blis h willi n g ness a n d a bility t o c o m pl y wit h lifestyl e re q uire me nts 
g oi n g f or war d i n t he st u d y;

Assess a n d rec or d a n y A d verse E ve nts si nce t he l ast visit.
6. 5. 6. Resc u e Tre at me nt – Visit 6, D a y 5 7/ Wee k 8 ( 3 d a ys)

A d mi nister a n d sc ore t he Si nce Last Visit C -S S R S.  F or s u bjects meeti n g a n y  of t he 
criteria s pecifie d i n Secti o n 7. 5. 1 a ris k assess me nt b y a q ualifie d M H P s h o ul d be 
d o ne t o deter mi ne w het her it is safe f or t he s u bject t o c o nti n ue t o partici pate i n t he 
trial;

A d mi nister P R Os i ncl u di n g: Pt G A, D L QI ( or C D L QI), P O E M, H A D S a n d 
E Q - 5 D-5 L  ( or E Q-5 D -Y i n select c o u ntries); 

A d olesce nt s 1 2- 1 7 ye ars of a ge w ill c o m plete t he C DL Q I i nstea d of t he D L QI a n d t he 
E Q - 5 D- Y i n select c o u ntries i nstea d of t he E Q- 5 D-5 L ;

Re vie w P S A A D dail y c o m pleti o n (i n selecte d c o u ntr ies) a n d pr u ritus N R S 
c o m pleti o n f or t his visit i n t he e Diar y.  Re vie w e Diar y pr oce d ures wit h s u bject a s 
necessar y ;

Re vie w a n y c ha n ges i n t he s u bject’s pri or a n d c o nc o mita nt me dicati o ns a n d treat me nt 
i nf or mati o n;

O btai n vital si g ns i ncl u di n g p ulse rate, bl o o d press ure , res pirat or y rate a n d oral or 
t ym pa nic te m perat ure (after at least 5 mi n ute s of rest);

Per f or m a si n gle 1 2-lea d E C G;

C o n d uct tar gete d p h ys ical e xa mi nati o n;

C o n d uct cli nical e val uati o ns i ncl u di n g I G A, S C O R A D, E A SI  a n d B S A (calc ulate d i n 
t he E A SI);

O btai n s a m ples f or la b orat or y testi n g: ser u m c he mistr y, he mat ol o g y (i ncl u di n g
c oa g ul ati o n pa nel, R B C/ W B C i n dices, l y m p h oc y te s u bsets a n d mar kers) a n d 
uri nal y sis; 

F oll o wi n g o ne year of t otal e x p os ure t o st u d y dr u g si nce t he last T B test, all s u bjects 
i n re gi o ns w hic h are a b o ve a l o w ris k f or T u berc ul osis (ie, > 1 0/ 1 0 0, 0 0 0 pre vale nce ) 
will u n der g o t u berc u l osis ( T B) testi n g.  If s o, e ns ure testi n g is perf or me d as per 
Secti o n 7. 3. 4 .  A ne gati ve test res ult f or t u berc ul osis is re q uire d f or o n g oi n g 
eli gi bilit y f or st u d y partici pati o n;

P F- 0 4 9 6 5 8 4 2
B 7 4 5 1 0 1 4
Fi nal P r otoc ol A me n d me nt 5, 2 8 Oct o ber 2 0 1 9
P FI Z E R C O N FI D E N TI A L
Pa ge 9 2

Uri ne pre g na n c y test (fe male s u bjects of c hil d beari n g p ote ntial i ncl u di n g a d olesce nts 
a ge d 1 2 ye ars a n d ol der re gar dless of w het her t he y ha ve e x perie nce d me narc he).  A 
ne gati ve uri n e pre g na nc y test m ust be o btai ne d pri or t o d osi n g wit h t he 
i n vestigati o na l pr o d uct;

Asse ss nee d f or c o ntrace pti o n a n d a d here nce t o a p plica ble lifest yl e re q uire me nts 
(Secti o n 4. 4 ).  Esta blis h willi n g ness a n d a bility t o c o m pl y wit h lifest yl e re q uire me nts 
g oi n g f or war d i n t he st u d y;

Re vie w e Diar y  t o assess c o m pleti o n;

Perf or m dr u g acc o u nta bilit y  pr oce d ures;

A d mi nister i n vesti gati o nal pr o d uct t o t he s u bject;

Dis pe nse i n vesti gati o nal pr o d uct t o t he s u bject;

Assess a n d rec or d a n y A d verse E ve nts si nce t he last visit.
6. 5. 7. Resc ue Tre at me nt - Vi sit 7, D a y 8 5/ Wee k 1 2 ( 3 d a ys) E n d of Tre at me nt 
( E O T)/ E arl y Ter mi n ati o n ( E T)

A d mi nister a n d sc ore t he Si nce Last Visit C -S S R S.  F or s u bjects meeti n g a n y  of t he 
criteri a s pecifie d i n Secti o n 7. 5. 1 a ris k assess m e nt b y a q ualifie d M H P s h o ul d be 
d o ne t o deter mi ne w het her it is safe f or t he s u bject t o c o nti n ue t o partici pate i n t he 
trial;

A d mi nister P R Os i ncl u di n g: Pt G A, D L QI ( or C D L QI), P O E M, H A D S, E Q - 5 D-5 L  
( or E Q- 5 D-Y i n se lect c o untries), S F - 3 6 v 2, Ac ute a n d F A CI T-F ( or Pe ds -F A CI T- F ).  
S F -3 6 v 2 will be c o m plete d b y  a d ult s u bjects o nl y; 

A d olesce nts 1 2 -1 7 y ears of a ge will n ot c o m plete t he S F -3 6 v 2.  A d olesce nts
1 2 - 1 7 ye ars of a ge will c o m p lete t he C D L QI i nstea d of t he D L QI, t he E Q - 5 D- Y i n 
select c o u ntries i nstea d of t he E Q- 5 D-5 L  a n d Pe ds-F A CI T -F i nstea d of t he F A CI T -F;

Re vie w P S A A D dail y  c o m pleti o n (i n selecte d c o u ntries) a n d pr urit us N R S 
c o m pleti o n f or t his visit i n t he e Diar y.  Re vie w e Diar y pr oce d ures wit h s u bject as 
necessa r y;

Re v ie w a ny c ha n ges i n t he s u bject’s c o nc o mita nt me dicat i o ns a n d treat me nts 
i nf or mati o n;

O btai n wei g ht f or all s u bjects a n d hei g ht f or a d olesce nts o nl y  ( 1 2 t o < 1 8 years ol d);

O btai n vital si g ns i ncl u di n g p ulse rate, bl o o d press ure, res pirat or y rate a n d oral or
t ym pa nic te m perat ure (after at l east 5 mi n utes of r est);

P F- 0 4 9 6 5 8 4 2
B 7 4 5 1 0 1 4
Fi nal P r otoc ol A me n d me nt 5, 2 8 Oct o ber 2 0 1 9
P FI Z E R C O N FI D E N TI A L
Pa ge 9 3

Perf or m a si n gle 1 2 -lea d E C G;

C o n d uct a c o m plete p h ys ical e xa mi nati o n;

C o n d uct cli nical e val uati o ns i ncl u di n g I G A, S C O R A D, E A SI  a n d B S A (calc ulate d i n 
t he E A SI);

O btai n fasti n g sa m ples f or l a b orat or y testi n g: ser u m c he mistr y, he mat ol o g y  
(i ncl u di n g c oa g ulati o n pa nel, R B C/ W B C i n dices, l ym p h oc y te s u bsets a n d mar kers), 
li pi d pr ofile, a n d uri nalys is; 

F or C hi na a n d Tai wa n o nl y : F or s u bjects w h o ha d H BV D N A testi n g at Scree ni n g, 
c ollect bl o o d sa m pl e f or repeat H B V D N A testi n g;

F oll o wi n g o ne y ear of t otal ex p os ure t o st u d y  dr u g si nce t he last T B test, all s u bjects 
i n re gi o ns w hic h are a b o ve a l o w ris k f or T u berc ul osis (ie, > 1 0/ 1 0 0, 0 0 0 pre vale nce) 
will u n der g o t u berc ul osis ( T B) testi n g.  If s o, e ns ure testi n g is perf or me d as per 
Secti o n 7. 3. 4 .  A ne gat i ve test res ult f or t u berc ul osis is re q uire d f or o n g oi n g 
eli gi bilit y f or st u d y partici pati o n;
 

Uri ne pre g na nc y  test (fe male s u bjects of c hil d beari n g p ote ntial i ncl u di n g a d olesce nts 
a ge d 1 2 ye ars a n d ol der re gar dless of w het her t he y ha ve e x perie nce d me narc he);

Assess nee d f or c o ntrace pti o n a n d a d here nce t o a p pl ica ble lifestyl e re q uire me nts 
(Secti o n 4. 4 ).  Esta blis h willi n g ness a n d a bility t o c o m pl y wit h lifest yl e re q uire me nts 
g oi n g f or war d i n t he st u d y ;

If t he s u bject c o m plete d t he 1 2 wee ks of resc ue treat me nt t he y  will be assesse d f or 
eligi bilit y  t o e nter L T E st u d y B 7 4 5 10 1 5.  S u bjects w h o are n ot eli gi ble or u n willi n g 
t o partici pate are t o c o nti n ue i n t he 4- wee k, u ntreate d safety f oll o w - up peri o d;

Re vie w e Diar y  t o assess c o m pleti o n;

Pe rf or m dr u g acc o u nta bilit y pr oce d ures;

A d mi niste r last dose of i n vesti gati o nal pr o d uct as part of t he resc ue treat me nt peri o d 
t o t he s u bject;

Assess a n d rec or d a n y A d verse E ve nts si nce t he last visit;

A d mi nister A C Q test f or all s u bjects wit h a pri or dia g n o sis of ast h ma. 
C CI

P F- 0 4 9 6 5 8 4 2
B 7 4 5 1 0 1 4
Fi nal P r otoc ol A me n d me nt 5, 2 8 Oct o ber 2 0 1 9
P FI Z E R C O N FI D E N TI A L
Pa ge 9 4
6. 5. 8. Resc ue Tre at me nt - Visit 8, F ol l o w-u p V isit a n d E n d of St u d y ( ±3 d a ys)

A d mi nister a n d sc or e t he Si nce Last Visit C -S S R S.  F or s u bjects meeti n g a n y  of t he 
criteria s pecifie d i n Secti o n 7. 5. 1 a risk assess me nt b y  a q ualifie d M H P s h o ul d be 
d o ne t o deter mi ne w het her it is safe f or t he s u bject t o c o ntin ue t o partici pate i n t he 
trial;

A d mi nister P R Os i ncl u di n g: Pt G A, D L QI ( or C D L QI), P O E M, H A D S, E Q - 5 D-5 L  
( or E Q- 5 D-Y i n select c o u ntries), S F -3 6 v 2, Ac ute a n d F A CI T -F ( or Pe ds -F A CI T- F ).  
S F - 3 6v 2 will be c o m plete d b y  a d ult s u bjects o nl y; 

A d ol esce nts 1 2 -1 7 y ears of a ge will n ot c o m plete t he S F -3 6 v 2.  A d olesce nts
1 2 - 1 7 ye ars of a ge will c o m plete t he C D L QI i nstea d of t he D L QI, t he E Q- 5 D- Y i n 
select c o u ntries i nstea d of t he E Q- 5 D-5 L  a n d Pe ds-F A CI T -F i nstea d of t he F A CI T -F; 

Re vie w P S A A D dail y  c o m pleti o n (i n selecte d c o u ntries) a n d pr urit us N R S 
co m pleti o n f or t his visit i n t he e Diar y ;

Re vie w a n y c ha n ges i n t he s u bject’s c o nc o mita nt me dicati o ns a n d treat me nts 
i nf ormati o n;

O btai n vital si g ns i ncl u di n g p ulse rate, bl o o d press ure, res pirat or y  rate a n d oral or 
t ym pa nic te m perat ure (after at least 5 mi n utes of rest);

Perf or m a si n gle 1 2 -lea d E C G;

C o n d uct a tar gete d p h ys ical e xa mi nati o n;

C o n d uct cli nical e val uati o ns i ncl u di n g I G A, S C O R A D, E A SI  a n d BS A (calc u late d i n 
t he E A SI);

O btai n fasti n g sa m ples f or la b orat or y  testi n g: ser u m c he mistr y, he mat ol o g y
(i ncl u di n g c oa g ulati o n pa nel, R B C/ W B C i n dices, l y m p h oc yte s u bsets a n d mar kers), 
li pi d pr ofile, a n d uri nalys is; 

F oll o wi n g o n e year of t otal e x p os ure t o st u d y dr ug si nce t he last T B test, all s u bjects 
i n re gi o ns w hic h are a b o ve a l o w ris k f or T u berc ul osis (ie, > 1 0/ 1 0 0, 0 0 0 pre vale nce) 
will u n der g o t u berc ul osis ( T B) testi n g.  If s o, e ns ure testi n g is perf or me d as per 
Secti o n 7. 3. 4 .  A ne gati ve test res u lt f or t u berc ul osis is re q uire d f or o n g oi n g 
eli gi bilit y f or st u d y partici pati o n;

Uri ne pre g na nc y  test (fe male s u bjects of c hil d beari n g p ote ntial i ncl u di n g a d olesce nts 
a ge d 1 2 ye ars a n d ol der re gar dless of whet her t he y  ha ve e x perie nce d me narc he); 

Assess a d here nce t o c o ntrace pti o n a n d a p plica ble lifest y le re q uire me nts (Secti o n 4. 4 );  

Re vie w e Diar y  t o assess c om pleti o n;

P F- 0 4 9 6 5 8 4 2
B 7 4 5 1 0 1 4
Fi nal P r otoc ol A me n d me nt 5, 2 8 Oct o ber 2 0 1 9
P FI Z E R C O N FI D E N TI A L
Pa ge 9 5

As sess a n d rec or d a n y A d ver se E ve nts si nce t he last visit;

A d mi nister A C Q test f or all s u bjects wit h a pri or dia g n osis of ast h ma .
6. 6. S u bject Wit h dr a w al
O n g oi n g s afet y c o ncer n at t he ti me of s u bject wit h dr a w al fr o m t he st u d y :
If a s u bject has a cli nicall y si g nifica nt, treat me nt-e mer ge nt, a b n or malit y at t he ti me of 
wit h dra wal fr o m t he st u d y, t he Pfizer Me dical M o nit or ( or desi g nee) s h o ul d be n otifie d a n d 
e ver y eff ort s h o ul d be ma de t o arra n ge f oll o w-u p e val uati o ns at a p pr o priate i nter vals t o 
d oc u me nt t he c o urse of t he a b n or mality.  All a b n or mal la b orat or y  e ve nts of cli nical 
si g nifica nce s h o ul d be f oll o we d u ntil t he la borat or y val ues ha ve ret ur ne d t o n or mal or 
baseli ne le vels or are dee me d cli nicall y  sta ble.  F oll o w-u p f or a b n or mal la b orat or y  fi n di n gs 
a nd a d verse e v e nts b y t he i n vestigat or is re q uire d u ntil t he e ve nt or its se q uelae res ol ve or 
sta bilize at a le vel acce pta ble t o t he i n vesti gat or, a n d Pfizer c o nc urs wit h t hat assess me nt.  
Refer t o A p pe n di x 4 f or G ui deli nes f or Mo nit ori n g a n d Disc o nti n uati o n. 
Wit h d r a w al of c o nse nt :
S u bjects ( le gall y acce pta ble re prese ntati ve/pare nt(s) or le gal g uar dia n, as a p plica ble) w h o 
re q uest t o disc o nti n ue recei pt of st u d y treat me nt will re mai n i n t he st u d y.  If t his re q uest 
occ urs at a sc he d ule d visit, a n e n d of treat me n t visit s h o ul d be perf orme d a n d t he s u bject 
s h o ul d e nter i nt o t he f oll o w-u p peri o d, wit h a n e n d of st u d y  visit sc he d ule d f or 4 wee ks after 
t he e n d of treat me nt visit.  If t he re q uest occ urs o utsi de of a sc he d ule d visit (e g, via tele p h o ne
c o ntact) t he s u bje ct s h oul d be sc he d ule d t o ret ur n t o site f or a n e n d of treat me nt visit wit hi n 
o ne wee k after t heir last d ose, a n d t he s u bject s h o ul d e nter i nt o t he f oll o w -u p peri o d, wit h a n 
e n d of st u d y visit sc he d ule d f or 4 wee ks after t he e n d of treatme nt visit. 
T he o n l y e xce pti o n t o t his is w he n a s u bject ( le gall y acce pta ble re prese ntati ve/pare nt(s) or 
le gal g uar dia n, as a p plica ble) s pecificall y wit h dra ws c o nse nt f or a n y f urt her c o ntact wit h hi m 
or her or pers o ns pre vi o usl y  a ut h orize d b y t he s u bject t o pr o vi de t his i nfor mati o n.  S u bjects 
(le gall y acce pta ble re prese ntati ve/pare nt(s) or le gal g uar dia n, as a p plica ble) s h o ul d n otif y t he 
i n vesti gat or i n writi n g of t he decisi o n t o wit h dra w c o nse nt fr o m f ut ure f oll o w-u p, w he ne ver 
p ossi ble.  T he w it h dra wal of c o nse nt s h o ul d be e x plaine d i n detail i n t he me dical rec or ds b y 
t he i n vesti gat or, as t o w het her t he wit h dra wal is o nl y fr o m f urt her recei pt of i n vesti gati o nal 
pr o d uct or als o fr o m st u d y pr oce d ures a n d/ or p osttreat me nt st u d y  f oll o w-u p, a n d e nte re d o n 
t he ap pr o priate C R F p a ge.  I n t he e ve nt t hat vital stat us ( w het her t he s u bject is ali ve or dea d) 
is bei n g meas ure d, p u blicl y a vaila ble i nf or mati o n s h o ul d be use d t o deter mi ne vital stat us 
o nl y  as a p pr o priately directe d i n acc or da nce wit h l ocal la w.
L ost t o f oll o w -u p: 
All reas o na ble ef f orts m ust be ma de t o l ocate s u bjects t o deter mi ne a n d re p ort t heir o n g oi n g 
stat us.  T his i ncl u des f oll o w-u p wit h pers o ns a ut h orize d b y  t he s u bject as n ote d a b o ve.  L ost 
t o f oll o w-u p is defi ne d b y  t he i na bility t o reac h t he s u bject after a mi ni m u m of 2 d oc u me nte d 
p h o ne c alls, fa xes, or e - mails as well as lac k of res p o nse by t he s u bject t o 1 re gistere d mail 

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letter.  All atte m pts s h o ul d be d oc u me nte d i n t he s u bject’s me dical rec or ds.  If it is 
deter mi ne d t hat t he s u bject h as die d, t he site will use loca ll y per missi ble met h ods t o o btai n 
t he date a n d ca use of deat h.  If t he i n vesti gat or’s use of a t hir d-part y re prese ntati ve t o assist 
i n t he f oll o w-u p p orti o n of t he st u d y  has bee n i ncl u de d i n t he s u bject’s (le gall y acce pta ble 
re prese ntative/ pare nt(s) or le gal g uar dia n, as a p plica ble) i nf or me d c o nse nt, t he n t he 
i n vesti gat or ma y use a s p o ns or-retai ne d t hir d-part y  re prese ntati ve t o assist site staff wit h 
o btai ni n g t he s u bject’s c o ntact i nf or mati o n or ot her p u blic vital stat us data necessar y  t o 
c o m plete t he f oll o w- u p p orti o n of t he st u d y.  T he site staff a n d re prese ntati ve will c o ns ult 
p u blicl y  a vaila ble s o urces, s uc h as p u blic healt h re gistries a n d data bases, i n or der t o o btai n 
u p date d c o ntact i nf or mati o n.  If, after all atte m pts, t he s u bject re mai ns l ost t o f oll o w- u p, t he n 
t he last-k n o w n -ali ve date as deter mi ne d b y t he i n vesti gat or s h o ul d be re p orte d a n d 
d oc u me nte d i n t he s u bject’s me dical rec or ds.
S u bjects ma y wit h dra w fr o m t he st u d y  at a n y ti me at t heir o w n re q uest, or t he y m a y be 
wit h dra w n at a n y ti me at t he discre ti o n of t he i n vesti gat or or s p o ns or f or safet y  (see als o t he 
Wit h dra wal Fr o m t he St u d y  D ue t o A d verse E ve nts secti o n) or be ha vi oral reas o ns, or t he 
i na bilit y of t he s u bject t o c om pl y  wit h t he pr ot oc ol -re q uire d sc he dule of st u d y  visits or 
pr oce d ures at a gi ve n st u d y site.  S u bjects t hat disc o nti n ue st u d y  treat me nt will re mai n i n t he 
st u d y a n d m ust ha ve t heir e n d of treat me nt visit wit hi n 1 wee k after t heir last d ose, a n d will 
t he n e nter t he 4 wee k f oll o w u p p erio d wit h a n E n d of St u d y visit 4 wee ks after E n d of 
Treat me nt visit.  See A p pe n di x 4 f or G ui deli nes f or M o nit ori n g a n d Disc o nti n uati o n. 
If a s u bject d oes n ot ret ur n f or a sc he d ule d visit, e ver y eff ort s h o ul d be ma de t o c o ntact t he 
s ubject.  All atte m pts t o c o ntact t he s u bject a n d i nf or mati o n recei ve d d uri n g c o ntact atte m pts 
m ust be d oc u me nte d i n t he s u bject’s me dical rec or d.  I n a n y circ u msta nce, e ver y  eff ort 
s h o ul d be ma de t o d oc u me nt su bject o utc o me, if p oss i ble.  T he i n vesti gat or sh o ul d i n q uire 
a b o ut t he reas o n f or wit h dra wal, re q uest t hat t he s u bject ret ur n all u n use d i n vesti gati o nal 
pr o d uct(s), re q uest t hat t he s u bject ret ur n f or a fi nal visit, if a p plica ble, a n d f oll o w u p wit h 
t he su bject re ga r di n g a ny u n res ol ve d A Es.
If t he s u bj ect wit h dra ws fr o m t he st u d y , a n d als o wit h dra ws c o nse nt f or discl os ure of f ut ure 
i nf or mati o n, n o f urt her e val uati o ns s h o ul d be perf or me d, a n d n o a d diti o nal data s h o ul d be 
c ollecte d.  T he s p o ns or ma y  retai n an d c o nti n ue t o use a ny data c ollecte d b ef ore s uch 
wit h dra wal of c o nse nt.
7. A S S E S S M E N T S
E ver y  eff ort s h o ul d be ma de t o e ns ure t hat t he pr ot oc ol-re q uire d tests a n d pr oce d ures are 
c o m plete d as descri be d.  H o we ver, it is a ntici pate d t hat fr o m ti me t o ti me t here m a y  be 
circu msta nces o u tsi de of t he c o ntr ol of the i n vesti gat or t hat ma y  ma ke it u nfeasi ble t o 
perf or m t he test.  I n t hese cases t he i n vesti gat or will ta ke all ste ps necessar y t o e ns ure t he 
safety a n d well -bei n g of t he s u bject.  W he n a pr ot oc ol -re q uire d test ca n n ot be perf or me d, t he 
i n vesti gat or will d oc u me nt t he reas o n f or t his a n d a n y  c orrecti ve a n d pre ve nti ve acti o ns t hat 
he or s he has ta ke n t o e ns ure t hat n or mal pr ocesses are a d here d t o as s o o n as p ossi ble.  T he 
st u d y tea m will be i nf or me d of t hese i ncide nts i n a ti mel y ma n ner.

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F or sa m ples b ei n g c oll ecte d a n d s hi p pe d, detaile d c ollecti o n, pr ocessi n g, st ora ge, a n d 
s hi p me nt i nstr ucti o ns a n d c o ntact i nf or mati o n will be pr o vi de d t o t he i n vesti gat or site pri or 
t o i nitiati o n of t he st u d y. 
7. 1. Pre g n a nc y Testi n g
F o r fe male s ubjects of c h il d beari n g p ote ntial i nclu di n g a d olesce nts a ge d 1 2 ye ars a n d ol der 
re gar dless of w het her t he y ha ve e x perie nce d me narc he, a ser u m pre g na nc y test wit h a 
se nsiti vit y of at least 2 5 mI U/ m L, will be perf or me d at scree ni n g.  A uri ne pre g na n c y  test 
wi t h a se nsitivit y  of at least 2 5 mI U/ m L, will be perf or me d at e ver y  site visit i ncl u di n g t he 
E n d of Treat me nt ( E O T) a n d f oll o w - u p visit t o c o nfir m t he s u bject has n ot bec o me pre g na nt 
d uri n g t he st u d y, a n d at t he f oll o w -u p visit. 
A ne gati ve pre g n a nc y test res ult is re quire d bef ore t he s ubject m a y  recei ve t he i n vesti gati o nal 
pr o d uct.  Pre g na nc y  tests will als o be d o ne w he ne ver 1 me nstr ual c y cle is misse d d uri n g t he 
acti ve treat me nt peri o d ( or w he n p ote ntial pre g na nc y  is ot her wise s us pecte d).  Pre g na nc y 
tests ma y  als o be re peate d if re q ueste d b y i nstit uti o nal re vie w b oar ds (IR Bs)/et hics 
c o m mittees ( E Cs) or if re q uire d b y l ocal re g ulati o ns. 
Uri ne pre g na nc y  tests m ust be se nsiti ve t o at least 2 5 mI U/ m L a n d will be c o n d ucte d wit h t he 
test kit pr o vi de d b y  t he ce ntral la b orat or y i n acc or da nce wi t h i nstr ucti o ns pr o vi de d i n its 
pac ka ge i nsert.  S u bjects w h o ha ve misse d a me nstr ual peri o d or w h o s h o w a n i n deter mi nate 
or p ositi ve res ult o n t he uri ne test ma y  n ot f urt her pr o gress i n t he st u dy u ntil pre g na nc y i s 
r ule d o ut usi n g f urt h er dia g n ostic testin g (e g , a ne gati ve q ua ntitati ve ser u m pre g na nc y  test 
c o n d ucte d at a certifie d la b orat or y).
I n t he case of a p ositi ve c o nfir me d pre g na nc y, t he s u bject will be wit h dra w n fr o m 
a d mi nistrati o n of i n vesti gati o nal pr o d uct b ut ma y re mai n i n t he st u d y u ntil c o m pleti o n of t he 
4 wee k u ntreate d f oll o w -u p peri o d.
 
 
 
 
 
 
  
 
 
C CI

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C CI

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7. 3. S afet y Assess me nts
Safet y  will be assesse d b y t he s p o nta ne o us re p ortin g of A Es, p h ys ical e xa mi nati o ns, vital 
si g ns a n d cli nical la b orat or y res ults i n all s u bjects w h o recei ve at least o ne d ose of t he 
i n vesti gati o nal pr o d uct.  U nsc he d ule d safety assess me nts ma y be perf or me d at a n y ti me 
d uri n g t he st u d y t o assess a n y percei ved safe t y c o ncer ns.  I n vesti gat ors a n d Pfizer Cli nicia ns 
( or desi g nees) will re vie w i n di vi d ual s u bject data t hr o u g h o ut t he c o n d uct of t he st u d y t o 
e ns ure s u bjects’ well -bei n g.
7. 3. 1. Vit als Si g ns
Vital si g ns (sitti n g bl o o d press ure, p ulse rate, res pirat or y rates an d te m perat ure) will be 
meas ure d after 5 mi n utes of rest as i n dicate d i n t he Sc he d ule of Acti vities . 
B o d y te m perat ure will be c ollecte d usi n g t he t y m pa nic or oral met h o ds a n d t he sa me met h o d 
s h o ul d be used c o nsiste ntl y  thr o u g h o ut t he st u d y. 
Bl o o d press ure ( B P) will be meas ure d usi n g a sta n dar d cali brate d bl o o d press ure meas uri n g 
de vice.  A B P de vice t hat uses m ulti ple c uff sizes base d o n t he ar m circ u mfere nce is t he 
re q uire d ty pe of de vice.  T he a p pr o pria te c uff size f or t he s u bj ect m ust be use d t o e ns ure 
acc urate meas ure me nt.  T he ar m circ u mfere nce at t he mi d p oi nt of t he le n gt h of t he u p per ar m 
s h o ul d be meas ure d t o deter mi ne t he a p pr o priate c uff size i n acc or da nce wit h t he 
s pecificati o ns of the B P meas ur i n g de vice.  T he s ame pr o perl y  size d a n d cali brate d bl o o d 
press ure c uff will be use d t o meas ure bl o o d press ure eac h ti me. 
S u bjects s h o ul d be seate d i n a c hair, bac k s u p p orte d, a n d ar ms bare d (free of restricti o ns s uc h 
as r olle d - u p slee ves, etc.) a n d s u p p orte d at heart level .  Meas ure me nts s h o ul d be ta ke n o n t he 
sa me ar m at eac h visit ( prefera bly n o n - d o mi na nt).  S u bjects s h o ul d refrai n fr o m s m o ki n g or 
i n gesti n g caffei ne d uri n g t he 3 0 mi n utes prece di n g t he meas ure me nts.  Meas ure me nts s h o ul d 
be gi n after at least 5 mi n utes of rest. 
H eart rate s h o ul d be meas ure d at a p pr o xi matel y  t he sa me ti me as B P f or a mi ni m u m of 
3 0 sec o n ds.  W he n t he ti mi n g of B P a n d p ulse ( heart) rate meas ure me nts c oi nci des wit h a 
bl o o d c ollecti o n or ot her st u d y  pr oce d ure, B P a nd p ulse ( hea rt) rate s h o ul d be o btai n e d first.
7. 3. 2. Me dic al H ist or y, P h ysic al E x a mi n ati o n, Hei g ht, a n d Wei g ht
C o m plete A D disease hist or y  i ncl u des c ollecti o n of details of A D at Scree ni n g: A D 
dia g n osis, t he use of t o pical treat me nts, s ys te mic treat me nts a n d ot her treat me nt s f or A D.  
Me dic al hist or y i n a d diti o n t o A D hist or y  i ncl u di n g disease d urati o n will be c ollecte d at 
scree ni n g.  Me dical hist or y als o i ncl u des hist or y of dr u g, alc o h ol a n d t o bacc o use.  S m o ki n g 
stat us a n d a vera ge wee kl y alc o h ol c o ns u m pti o n ( u nits/ wee k) will be c ollecte d, w he re a unit 
c o ntai ns 1 2 g o f p ure alc o h ol, a n a m o u nt e q ui vale nt t o t hat c o ntai ne d i n 5 oz/ 1 5 0 m L  (a 
glass) of wi ne, 1 2 oz/ 3 6 0 m L  of beer, or 1. 5 oz/ 4 5 m L  of 9 0 pr o of of s pirits.  Hei g ht a n d 
wei g ht will be meas ure d wit h o ut t he s u bject weari n g s h oes.  Hei g h t (i nc hes or ce nti meters) 
a nd wei g ht (l bs. or k g) will be meas ure d a n d rec or de d i n t he s o urce d oc u me nt at t he 
scree ni n g visit a n d at vari o us ti me p oi nts, see Sc he d ule of Acti vities .

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C o m plete p h y sical e xa mi nati o ns m ust be perf orme d b y t he i n vesti gat or, su b- i n vesti gat or or a 
q ualifie d healt h pr ofessi o nal per l ocal g ui deli nes.  C o m plete p h y sical e xa mi nati o ns c o nsist of 
assess me nts of ge neral a p peara nce; s ki n; hea d, e yes, ears, n ose a n d t hr oat ( H E E N T); m o ut h, 
hear t; l u n gs; breast ( opti o na l); a b d o me n; e xter nal ge nitalia ( o pti o nal); e xtre mities; ne ur ol o gic 
f u ncti o n; a n d l ym p h n o des.
Tar gete d p h ys ical e xa mi nati o ns m ust be perf or me d b y t he i n vesti gat or, s u b-i n vesti gat or or a 
q ualifie d healt h pr ofessi o nal pe r l ocal g ui deli nes a n d s h o ul d i ncl u de s ki n, heart, l u n gs, a n d 
a b d o me n a n d e xa mi nati o n of b o d y sys te ms w here t here are sy m pt o m c o m plai nts b y  t he 
s u bject. 
C o m plete a n d Tar gete d p h y sical e xa mi nati o ns are perf or me d at vari o us ti me p oi nts, see 
Sc he d ule of A ctivities .
7. 3. 3. C hest X -R a y
C hest ra di o gra p h ( p osteri or-a nteri or a n d lateral vie ws) are re q uire d f or a d ults a n d 
rec o m me n de d f or a d olesce nts (as per l ocal g ui deli nes a n d sta n dar d of care) or ot her 
a p pr o priate dia g n ostic i ma ge (ie, c o m p ute d t o m o g ra p hy [ C T] or mag ne tic res o na nce i ma gi n g
[ M RI]) wit h n o e vi de nce of c urre nt, acti ve T B or pre vi o us i nacti ve T B, ta ke n at scree ni n g or 
wit hi n 1 2 wee ks pri or t o St u d y  D a y 1 a n d rea d b y  a q ualifie d ra di ol o gist.  D oc u me ntati o n of 
t he official rea din g m ust be l ocate d a n d a vail a ble i n the s o urce d oc u me ntati o n.
7. 3. 4. T u berc ul osis Testi n g
At t he ti me of scree ni n g, all s u bjects will u n der g o t u berc ul osis ( T B) testi n g u nless perf or me d 
wit hi n 1 2 wee ks of Da y  1.  Q ua nti F E R O N-T B G ol d I n- T u be Test is t he preferre d testi n g 
met h o d.  If t he Q ua n ti FE R O N -T B G ol d I n -T u be test ca n n ot be perf or me d, or if t he res ults 
ca n n ot be deter mi ne d b y t he refere nce la b orat or y t o be eit her p ositi ve or ne gati ve, t he n 
s u bjects ma y be scree ne d usi n g t he P urifie d Pr otei n Deri vati ve ( P P D) Tu berc uli n S k i n Test 
( Ma nt o u x me t h o d) wit h a p pr o val of t he Pfizer Me dical M o nit or. 
I n a d diti o n t o T B testi n g as s pecifie d i n t his cli nical pr ot oc ol, a c hest X-r a y will be 
perf or me d t o ai d i n T B stat us deter mi nati o n f or all a d ults, a n d rec o m me n de d f or a d ole sce nts 
acc ordi n g t o l ocal g u i deli nes a n d sta n dar d of care a n d/ or i n c o u ntries wit h a hi g h i nci de nce 
rate of T B.  F oll o wi n g o ne year of t otal e x p os ure t o st u d y dr u g si nce t he last T B test, all 
s u bjects i n re gi o ns w hic h are a b o ve a l o w-ris k f or T u berc ul osis (ie, > 1 0/ 1 0 0, 0 0 0 i ncide nce ) 
will u n de r g o t u berc ul osis testi n g. 
Q ua nti F E R O N -T B G ol d I n- T u be is a n i n vitr o dia g n ostic test usi n g a pe pti de c oc ktail 
si m ulati n g E S A T-6, C F P - 1 0 a n d T B 7. 7 pr otei ns t o sti m ulate cells i n he pari nize d w h ole 
bl o o d.  Detecti o n of i nterfer o n-ga m ma b y  E nz y me - Li n ke d I m mu n os or be nt Assa y  ( E LI S A) is 
use d t o i de ntif y  i n vitr o res p o nses t o t hese pe pti de a nti ge ns t hat are ass ociate d wit h 
Myc o b acteri u m t u berc ul osis
i nfecti o n.  Q ua nti F E R O N-T B G ol d I n - T u be is a n i n direct test 
f or M. t u bercul o sis i nfecti o n (incl u di n g dis ease) a n d is i nte n de d f or use i n c o nj u ncti o n wit h 
ris k assess me nt, ra di o gra p h y a n d ot her me dical a n d dia g n ostic e val uati o ns.

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A bl o o d sa m ple (a p pr o xi matel y  3 m L ) will be c ollecte d at scree ni n g f or Q ua nti F E R O N-T B 
G ol d I n- T u be testi n g.  F oll o wi n g sa mple pr oc essi n g, the sa m ple will be s hi p pe d t o t he 
s p o ns or’s desi g nate d refere nce la b orat or y f or testi n g.  T he pr oce d ure f or pr ocessi n g a n d 
pre pari n g t he sa m ple f or s hi p me nt is descri be d f ull y  i n t he la b orat or y ma n ual, w hic h will be 
p r o vi de d t o i n vesti gat ors.
A ne g ati ve P P D test ca n be s u bstit ute d f or t he Q ua nti F E R O N-T B G ol d I n -T u be test o nl y  if 
t he ce ntral la b orat or y is u na ble t o perf or m t he Q ua nti F E R O N-T B G ol d I n-T u be test or 
ca n n ot deter mi ne t he res ults t o be p ositi ve or ne gati ve a n d t he Pfizer Me dical M o nit or 
a p pr o ves it, o n a case-b y -case basis.
P urifie d Pr otei n Deri v ati ve ( P P D) Test
If t he Q ua nti F E R O N-T B G ol d I n - T u be test ca n n ot be perf or me d, or if t he res ults ca n n ot be 
deter mi ne d t o be p ositi ve or ne gati ve, t he n s u bjects ma y  be s cree ne d usi n g t h e P urifie d 
P r otei n Deri vati ve ( P P D) T u berc uli n Test ( Ma nt o u x met h o d), wit h t he a p pr o val of t he Pfizer 
Me dical M o nit or. 
S u bjects m ust ha ve t he P P D test a d mi nistere d a n d e val uate d b y a healt h care pr ofessi o nal 
4 8 t o 7 2 h o urs later i n or de r to be eli gi ble f o r t he st u d y, u nless perf or me d a n d d oc u me nte d 
wit hi n t he last 3 m o nt hs.  T he test s h o ul d be perf or me d acc or di n g t o l ocal sta n dar ds wit h 
i n d urati o n of < 5 m m re q uire d f or i ncl usi o n.
7. 3. 5. Electr oc ar di o gr a m
Si n gle 1 2 -lea d E C Gs s h o ul d be c ollecte d at ti mes s pecifie d i n the Sc he d ule of Acti vities
usi n g a mac hi ne pr o vi de d b y  t he ce ntral rea der.  E C G rea di n gs will be perf or me d b y a ce ntral 
rea der.
All sc he d ule d E C Gs s h o ul d be perf or me d after t he s u bject has reste d q uietl y f or at least 
1 0 m i n utes i n a s u pi ne p ositi o n a n d pri or t o a n y bl o o d c ollecti o n. 
T he scree ni n g E C G val ues will ser ve as eac h s u bject’s baseli ne val ues.  S u bjects wit h 
cli nicall y si g nifica nt E C G a b n or malities at scree ni n g are t o be e xcl u de d fr o m t he st u d y. 
7. 3. 6. S peci al S afet y A ssessme nt
I n t he e ve nt of a s us pecte d o p p ort u nistic i nfecti o n, eff ort s h o ul d be ma de t o i de ntif y t he 
pat h o ge n utilizi n g la b orat or y  or ot her met h o ds a p pr o priate t o t he cli nical sit uati o n. 
I n case of a s us pecte d viral s ki n i nfecti o n (e g, her pes z oster or he r pes si m ple x), or ecze ma 
her petic u m, a s peci me n f or viral D N A ma y  be a nal yze d l ocall y f or c o nfir mati o n a n d res ults 
pr o vi de d t o t he a dj u dicati o n c o m mittee t o s u p p ort e val uati o n. 
F or s u bjects wit h a past hist or y  of oral or ge nital her pes si mple x vir us ( H S V) a n d a 
prese ntati o n c o nsiste nt t o pri or i nfecti o ns, f urt her la b orat or y  a nalys is ma y be perf or me d at 
t he discreti o n of t he i n vesti gat or. 

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7. 4. S ki n T y pe Assess me nt
As part of baseli ne c haracteristics, a s ki n t y pe assess me nt will be d o ne at t he Da y 1 visit 
usi n g t he Fitz patric k S ki n T y pe assess me nt ( Refer t o A p pe n di x 5 ).  T his is use d t o classif y a 
pers o n’s s ki n t y pe b y  t heir res p o nse t o s u n e x p os ure (ie, b ur ni n g or ta n ni n g).
7. 5. Assess me nt of S uici d al I de ati o n a n d Be h a v i or
S u bjects meeti n g e xcl usi o na r y res ults o n t he C-S S R S, S B Q -R a n d P H Q -8 s h o ul d be 
e xcl u de d fr o m partici pati o n; it is rec o m me n de d t he s u bject’s pri mar y  care p h ysicia n ( P C P) 
s h o ul d be i nf or me d, a n d t he s u bject referre d t o a me ntal healt h pr ofessi o nal, eit her by t he 
P C P or t he i n vesti gat or acc or din g t o t heir us ual practice.  S uc h s u bjects ma y  be rescree ne d, 
at a later date, if t he y were e val uate d a n d treate d as a p pr o priate, a n d t he re peat sc ores per mit 
i ncl usi o n.
7. 5. 1. C ol u m bi a S uici de Se verit y R ati n g Sc ale ( C -S S R S )
T he C ol u m bia S uic i de Se verity Rati n g S cale is a vali date d t o ol f or i n vesti gati ve staff t o use 
t o e val uate s uici dal i deati o n a n d be ha vi or (A p pe n di x 1 5 ).1 8  At t he scree ni n g visit, i f there 
are “ yes” ans wers o n it e ms 4 or 5 i n t he past y ear or o n a n y q uesti o n in t he s uici dal be ha vi or 
secti o n of t he C-S S R S i n t he past 5 ye ars, t he s u bject will n ot be i ncl u de d i n t he st u d y .  
Trai ne d site staff will a d mi nister t he C -S S R S t o all s u bjects at scree ni n g a n d score 
i m me diatel y t o assess t he s u bject’s eli gi bilit y base d o n t he a ns wers.
At p ost -baseli ne visits, if t here are “ y es” a ns wers o n ite ms 4, 5 or o n a n y  be ha vi oral q uesti o n 
of t he Si nce Last Visit C -S S R S ( A p pe n di x 1 6 ), a ris k asses s me nt b y a qualifie d M H P s h o ul d 
be d o ne t o deter mi ne w het her it is safe f or t he s u bject t o c o nti n ue t o partici pate i n t he trial.
S u bjects w h o ha ve rec urre nt s uici dal i deati o n a n d beh a vi or (SI B) d uri n g a cli nical trial 
s h o ul d be disc o nti nue d fr o m t he st u d y a n d treate d a p pr o priately.  If a st u dy s u bject e n d orses 
a 4 or 5 o n t he i deati o n s u bscale or a n y  be ha vi oral ite m of t he C-S S R S o n m ore t ha n 
2 occasi o ns a n d is c o nfir me d t o ha ve acti ve SI B o n b ot h occasi o ns b y a ris k assess me nt 
c o n d ucte d b y  a q ualifie d M H P,
t he n t he s ubject s h oul d be disc o nti n ue d fr o m t he st u d y  a n d 
treate d a p pr o priately.  T hese s u bjects s h o ul d be disc usse d wit h t he Pfizer Me dical M o nit or.
7. 5. 2. S uici d al Be h a vi ors Q uesti o n n aire - Re vise d ( S B Q-R)
T he S uici dal Be ha vi ors Q uesti o n naire- Re vise d ( A p pe n di x 1 7 ) is a patie nt-re p orte d 
q uesti o n naire c o nsisti n g of 4 ite ms t o assess s uici dal i deati o n, s uici de atte m pts, t hreat of 
s uici dal be ha vi or, a n d li keli h o o d of s uici dal be havi or.  At t he Scree ni n g Vi sit, if S B Q-R t ot al 
sc ore 8, t he s u bject wil l n ot be i ncl u de d i n t he st u d y.4 0  Site staff will a d mi nister t he S B Q -R 
t o all s u bjects at scree ni n g a n d sc ore i m me diatel y.
7. 5. 3. P atie nt He alt h Q uesti o n n aire – 8 ite ms ( P H Q - 8)
T he Patie nt Healt h Q uesti o n naire – 8 ite ms ( A p pe n di x 1 8 ) is a patie nt-re p orte d q uesti o n naire 
c o nsisti n g of 8 ite ms t o assess t he s u bject’s de pressi o n le vel.  At Scree nin g Visit, if P H Q - 8 
t otal sc ore 1 5, t he s u bject will n ot be i ncl u de d i n t he st u dy. 4 1  Site staff will a d mi nister t he 
P H Q -8 t o all s u bjects at scree ni n g a n d sc ore i m me diatel y .

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7. 6. Cli nic al L a b or at o r y Tests
7. 6. 1. Bl o o d V ol u me
T otal bl o o d sa m pli n g v ol u me esti mate d f or t his st u d y de pe n ds u p o n s u bject res p o nse:

T otal bl o o d v ol u me f o r n o n-resp o n ders c o m pleti n g 1 2 wee ks is a p pr o xi matel y  
1 1 3 mls;

T otal bl o o d v ol u me f or res p o n ders c o m pleti n g 5 2 wee ks is a p pr o xi ma tel y 1 6 6 mls;

Ma xi m u m t otal bl o o d v ol u me esti mate d f or a res p o n der t hat flares o n t he last da y  of 
the mai nte na nce peri o d a n d c o m pleti n g 6 4 wee ks is a p pr o xi matel y  1 9 8 mls. 
A n a d diti o nal 5 mls is a d de d t o t hese v ol u mes f or a d olesce nts re q uiri n g V Z V testi n g.
F urt her details r e gar di n g t he c ollecti o n, pr ocessi n g, st ora ge, a n d s hi p pi n g of t he bl o o d 
sa m ples will be pr o vi de d i n t he la b ma n ual.
7. 6. 2. L a b or at or y Tests
T he f oll o wi n g la b orat or y tests will be perf or me d at ti me p oi nts i de ntifie d i n t he Sc he d ule o f 
Acti vit ies.  U nsc he d ule d cli nical la bs ma y be o btai ne d at a ny ti me d uri n g t he st u d y t o assess 
a n y percei ve d safet y c o ncer ns at t he i n vesti gat or’s discreti o n.
Sa m ple c ollecti o n, la beli n g, st ora ge, a n d s hi p pi n g i nf or mati o n ca n be f o u n d i n t he la b orat or y 
m a n ual.  Al l la b orat or y tests wit h cli nicall y i m p orta nt c ha n ges fr o m baseli ne i dentifie d after 
a d mi nistrati o n of i n ves ti gati o nal pr o d uct will be f oll o we d u ntil t he val ue sta bilizes.
S u bjects m ust a bstai n fr o m all f o o d a n d dri n k (e xce pt wa ter a n d n o n-st u d y me dicati o ns ) f or 
a n 8-h o ur o ver ni g ht fast pri or t o la bs t hat i ncl u de t he li pi d pr ofile pa nel o n Da y 1, Wee k 4 , 
Wee k
1 2 , Wee k 5 2, a n d E O S f or s u bjects w h o c o m plete d o u ble - bli n d treat me nt.  F or 
s u bjects t hat e nter t he resc ue peri o d, fasti n g la bs are re q uire d at Resc ue Da y 1, Wee k 4, 
Wee k
1 2, a n d E O S.  All ot her la bs d o n ot re q uire fasti n g.

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L a b or at or y Tests
H e m at ol o g y
Ser u m C he mistr y
Uri n al ysis
Ot her
H e m o gl o bi n
H e m at ocrit
R B C i n dices
M C H
M C H C
M C V
R B C M or p h ol o g y
R B C c o u nt
Retic ul oc yte c o u nt
Platelet c o u nt
W B C c o u nt wit h differe ntial
T otal ne utr o p hils ( %, 
A bs)
E osi n o p hils ( %, A bs)
M o n oc yte s ( %, A bs)
Bas o p hils ( %, A bs )
L y m p h oc ytes ( %, A bs)
C oa g ulati o n Pa nel
Acti vate d Partial 
T hr o m b o plasti n Ti me 
Pr ot hr o m bi n 
Ti m e/I nter nati o nal 
N or malize d Rati o 
(P T/I N R)
B U N a n d Creati ni ne
Creati ne P h os p h o ki nase
Gl uc ose
Na +, K +, Cl - , Ca + +
T otal C O 2 ( Bicar b o nate )
A S T,  A L T
G G T
T otal, I n dir ect & Dir ect Bilir u bi n
Al kali n e p h os p hatase
Lactate de h y dr o ge nase 
Uric aci d
Al b u mi n
T otal pr otei n
Li pi d Pr ofile Pa nel f
T otal c h olester ol
L D L 
H D L
Tri gl yceri des
p H
Gl uc ose ( q ual)
Pr otei n ( q ual)
Bl o o d ( q ual)
Ket o nes
Nitrites
Le u k oc yte esterase
Micr osc o p y a n d/ or 
c ult ured
HI V a
H Bs A g a
H Bc A b a
H Bs A b b
H C V A b a
H C V R N A b
V Z V I g G A b g
Ser u m F S H 
( p ost-me n o pa usal w o me n) 
or Pre g na nc y Test a, c
Uri ne pre g na nc y test c
Q F T -G or P P D (if 
a p plica ble) e
H S V -1, H S V -2, V Z V 
L y m p h oc yte S u bsets 
( L y m p h oc yte Mar kers)
T otal T cells ( C D 3 +)
C D 4 + T cells ( C D 3 + C D 4 +)
C D 8 + T cells ( C D 3 + C D 8 +)
N K cells 
( C D 3-C D 1 6 + C D 5 6 +)
B cells ( C D 3-C D 1 9 +)
H B V D N A h
a
At Scree ni n g o nl y.
HI V testi n g will b e perf or me d f or all s u bjects.
b
H Bs A b refle x testi n g o nl y if H Bs A g ne gati ve b ut H Bc A b p ositi ve.  H C V R N A is refle x testi n g o nl y if 
H C V A b is p ositi ve.
c
Pre g na nc y testi n g f or w o me n of c hil d beari n g p ote ntial i ncl u di n g a d olesce nts a ge d 1 2 years a n d ol der 
re gar dless of w het her t he y ha ve e x perie nce d me narc he; ser u m F S H f or w o m e n w h o ha ve bee n a me n orr heic 
f or at least 1 2 c o nsec uti ve m o nt hs.
d
Micr osc o p y wit h c ult ure perf or me d as a p pr o priate. 
e
P P D res ults s h o ul d be rea d w it hi n 4 8 t o 7 2 h o urs . 
f
Li pi d Pr ofile Pa nel re q uires at least a n 8 h o ur fast.  Li pi d pr ofile pa nel will be c o m plete d a t Da y 1, Wee k 4, 
Wee k
1 2, We e k 5 2, a n d E O S, a n d will i ncl u de t otal c h olester ol, L D L, H D L, a n d tri gl yceri des.  F or s u bjects 
recei vi n g resc ue t hera p y, a li pi d pr ofile w ill be c o mplete d at resc ue Da y 1, Wee ks 4, 1 2 a n d E O S. 
g
O nl y f or a d olesce nts w h o d o n ot ha ve d oc u me ntati o n of at lea st o ne d ose of varicella vacci ne.
h
F or C hi na a n d Tai wa n o nl y : S u bjects w h o are H Bs A g ne gati ve, H Bc A b p ositi ve, a n d H Bs A b p ositi v e at 
Scree ni n g will ha ve refle x testi n g f or H B V D N A. S u bjects w h o ha ve H B V D N A a b o ve t he l o w er li mit of 
q ua ntificati o n ( L L Q) w ill be e xcl u de d.  S u bjects w h o are H B V D N A ne gati ve or bel o w  L L Q ma y e nr oll 
b ut will ha ve H B V D N A testi n g re peate d at Wee ks 1 2, 2 8, 4 0, 5 2, Resc ue W ee k 1 2, a n d earl y ter mi nati o n
fr o m st u d y d uri n g a n y treat me nt peri o d. 
Cli nical l y si g nifica nt a b n or mal fi n di n gs s h o ul d be rec or de d as A Es.  A b n or mal test res ults 
deter mi ne d t o be ca use d fr o m la b orat or y  err or s h o ul d n ot be re p orte d as A Es.  Cli nicall y 
si g nifica nt la b orat or y fi n di n gs at t he fi nal assess me nt s h o ul d be f oll o we d to res ol u ti o n or 
u ntil deter mi ne d b y  t he i n vesti gat or t o be sta bilize d.  Re peat tests ma y be i n dicate d t o 
esta blis h t his.  S u bjects w h o are p ositi ve f or HI V will be s cree n -faile d.  Refer t o A p pe n di x 4
f or G ui deli nes o n M o nit ori n g a n d Disc o nti n uati o n.

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7. 6. 2. 1. He p atitis Tes ti n g 
He p atitis B testi n g: H B s urface a nti ge n ( H Bs A g), H B c ore a nti b o d y ( H Bc A b), H B s urface 
a nti b o d y ( H Bs A b).
I nter pret ati o n of He p atitis B Testi n g Res ults:

H Bs A g ne gati ve a n d H Bc A b ne gati ve: S u bject is eli gi ble f or t he st u d y ;

H Bs A g p ositi ve a n d H Bc A b ne g ati ve: S u bject is e xcl u de d fr o m st u d y  partici pati o n;

H Bs A g ne gati ve a n d H Bc A b p ositi ve a n d H Bs A b p ositi ve: S u bject is eli gi ble f o r 
st u d y;

H Bs A g ne ga ti ve a n d H Bc A b p ositi ve a n d H Bs A b ne gati ve: S u bject is e xcl u de d fr o m 
st u d y partici pati o n.
F or C hi n a a n d T ai w a n o nl y : S u bjects w h o are H Bs A g ne gati ve, H Bc A b p ositi ve, 
a n d H Bs A b p ositi ve at Scree ni n g will ha ve refle x testi n g f or H B V D N A. S u bjects 
w h o ha ve H B V D N A a b o ve t he L L Q will be e xcl u de d.  S u bjects w h o are H B V D N A 
ne gati ve or bel o w L L Q ma y  e nr oll b ut will ha ve H B V D N A testi n g re peate d at 
Wee ks 1 2, 2 8, 4 0, 5 2, Resc ue Wee k
1 2, a n d earl y ter mi nati o n fr o m st u d y d uri n g a ny 
treat me nt peri od. 
A si n gle p o sitive H B V D N A test res ult a b o ve t he L L Q f or a s u bject re q uires 
i m me diate a n d per ma ne nt disc o nti n uati o n fr o m tre at me nt, an d t he Me dical M o nit or 
( or desi g nee) m ust be n otifie d. T he s u bject m ust be sc he d ule d f or a n E n d of 
Treat me nt visit/ Earl y Ter mi nati o n v isit, e nters t he e n d of treat me nt f oll o w u p peri o d, 
a n d m ust be sc he d ule d f or a n E n d of St u d y  visit. N o f urt her sc he d uled H B V D N A 
tests will be re q uire d f or a s u bject o nce a res ult a b o ve t he L L Q is esta blis he d f or t hat 
s u bject d uri n g a ny st u d y  i n t he pr o gra m.  F oll o w u p b y  t he i n vesti gat or is re q uire d as 
detaile d i n Secti o n 8. 1. 4. 1 . 
He p atitis C testi n g: He patitis C A nti b o d y  ( H C V A b), He patitis C Viral R N A ( H C V R N A 
f or c o nfir matio n of p ositi ve H C V A b res ult). 
I nter pret ati o n of He p atitis C Testi n g Res ults:

H C V A b p ositi ve a n d H C V R N A p ositi ve: S u bject i s e xcl u ded fr o m st u d y 
partici pati o n. 
7. 6. 2. 2. V aricell a Z ost er Vir us ( V Z V) I g G A nti b o d y ( A b) Testi n g
A d olesce nt s u bjects wit h o ut d oc u me nt e d e vi de nce of ha vi n g recei ve d at least a si n gle d ose of 
t he varicella vacci ne i n c o u ntries w here the varicella vacci ne is a p pr o ve d a n d sta n dar d of 
care will be teste d f or varicel la z oster vir us I g G A b as descri be d i n t he la b ma n ual.  S u bjects 
t hat lac k e vi de nce of pri or e x pos ure t o varicella z oster vir us base d o n ser ol o gical V Z V I g G 
A b testi n g are e xcl u de d.

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7. 6. 2. 3. B aseli ne Vir al Scree n 
A ser u m sa m ple will be c ollecte d at baseli ne b ut a nal yze d o nl y if t he s u bject has s us pecte d 
varicella or her pes z oster.  I n t hat e ve nt, t he sa m ple w o ul d be a nal y ze d f or H S V 1, H S V 2 a n d 
V Z V.  A d diti o nal sa m ple c ollecti o n i nstr uct i o ns will be pr o vi de d i n t he la b ma n ual (Sc he d ule
of Acti vities ).  T he retai ne d sa m ples will be destr o ye d u p o n s u bject c o m ple ti o n of t his st u d y 
or t he l o n g -ter m e xte nsi o n st u d y. 
7. 7. Effic ac y Assess me nts
7. 7. 1. R ater Q u alific ati o ns
Cli nical e val uati o ns of at o pic der matiti s will be perf or me d b y a n e x perie nce d a n d q ualifie d
der mat ol o gist ( b oar d certifie d or e q ui vale nt). A n e x perie nce d a n d q ualifie d 
n o n -der mat ol o gist p h y sicia n or e x perie nce d me dical pr ofessi o nal wit h e x perie nce i n t he
c o nd uct of der mat ol o g y cli nical trials ma y be per mitte d t o perf or m t he cli nical e val uati o ns of 
at o pic der matitis w he n desi g nate d b y t he pri mar y site I n vesti ga t or.  T he e val uat or m ust 
recei ve a n d d oc u me nt pr ot oc ol s pecific a n d a p plica ble efficac y assess me nt scales trai ni n g 
pri or t o perf o r mi n g t hese e val uati o ns.  T o ass ure c o nsiste nc y a n d re d uce v ari a bilit y, t he 
s a me e v al u at or m ust assess all der m at ol o gic al cli ni c al e v al u ati o ns f or a n y i n di vi d u al 
s u bject t hr o u g h o ut t he st u d y w he ne ver p ossi ble; a bac k-u p e x perie n ce d a n d q ualifie d, 
pr ot oc ol -trai ne d eval uat or will o nl y be all o we d a n d d oc u me nte d i n case of e mer ge n c y or
s pecial sit uati o ns w he n t he desi g nate d e val uat or is u na ble t o perf orm t he e val uati o n.
7. 7. 2. I n vesti g at or’s Gl o b al Assess me nt (I G A)
T he I G A of at o pic der mati tis is sc ore d o n a 5-p oi nt s cale ( 0- 4), reflecti n g a gl o bal 
c o nsi derati o n of er yt he ma, i n d urati o n an d scali n g.  T he cli nical e val uat or of at o pic der matitis
will perf or m a n as sess me nt of t he o verall se verity of at o pic der matitis a n d assi g n a n I G A 
sc ore a n d cate g or y as descri be d i n Ta ble 3 .  T he assess me nt will be a static e val uati o n 
wit h o ut re gar d t o t he sc ore at a pre vi o us visit.

P F- 0 4 9 6 5 8 4 2
B 7 4 5 1 0 1 4
Fi nal P r otoc ol A me n d me nt 5, 2 8 Oct o ber 2 0 1 9
P FI Z E R C O N FI D E N TI A L
Pa ge 1 0 7
T a ble 3.
I n vesti g at or’s Gl o b al Assess me nt (I G A) Sc ore
Sc ore
C ate g or y
Descri pti o n 
0
Clear
At o pic der matiti s is cleare d, e xce pt f or a n y resi d ual disc ol orati o n 
( p ost-i nfla m mat or y h y per pi g me ntati o n a n d/ or h y p o pi g me ntati o n).
1
Al m ost 
Cl ear
O verall, t he at o pic der matitis is n ot e ntirel y cleare d a n d re mai ni n g lesi o ns 
are li g ht pi n k ( n ot i ncl u di n g p ost i nfla m mat or y h y per pi g m e ntati o n) a n d/ or; 
ha ve barel y pal pa ble har d t hic ke ne d s ki n a n d/ or pa p ules a n d/ or; ha ve barel y 
perce pti ble lic he nificat i o n; e xc oriati o n a nd o ozi n g/cr usti n g are a bse nt.
2
Mil d
O verall, t he at o pic der matitis c o nsists of l esi o ns t hat are li g ht re d; wit h 
sli g ht, b ut defi nite har d t hic ke ne d s ki n a n d/ or pa p ules; wit h sli g ht, b ut 
defi nite li near or pic ke d scratc h mar ks or pe netr ati n g s urface i nj ur y; wit h 
sli g ht, b ut defi nite t hic ke ne d s ki n, fi ne s ki n mar ki n gs, a n d lic he n oi d scale; 
o ozi n g/cr us ti n g is a bse nt.
3
M o d erate
O verall, t he at o pic der matitis c o nsists of lesi o ns t hat are re d; wit h easil y 
pal pa ble m o derate har d t hic ke ne d s k i n a n d/ or pa p ules; wit h m o derate li near 
or pic ke d scratc h mar ks or pe netrati n g s urface i nj ur y; wit h m o derate 
t hic ke ne d s ki n, c oarse s ki n mar ki n gs, a n d c oarse lic he n oi d scale; wit h sli g ht 
o ozi n g/cr usti n g.
4
Se vere
O verall, t he at o pic der matitis c o nsists of lesi o ns t hat are d ee p, dar k re d; wit h 
se vere har d t hic ke ne d s ki n a n d/ or pa p ules; wit h se vere li near or pic ke d 
scratc h mar ks or pe netrati n g s urface i nj ur y; wit h se vere t hic ke ne d s ki n wit h 
ver y c oarse s ki n mar ki n gs a n d lic he n oi d scale; wit h m o derate t o se ve re 
o ozi n g/cr usti n g.
T he I G A will e xcl u de scal p, pal ms, a n d s oles fr o m t he assess me nt/sc ori n g.
7. 7. 3. Ecz e m a Are a a n d Se verit y I n de x ( E A SI)
T h e E A SI q ua ntifies t he se verit y of a s u bject’s at o pic der matitis base d o n b ot h se verit y of 
lesi o n cli nical si g ns a n d t he perce nt of B S A af fecte d.  E A SI is a c o m p osite sc ori n g by t he 
at o pic der matitis cli nical e val uat or o f t he de gree of er yt he ma, i nd urati o n/ pa p ulati o n, 
e xc oriati o n, a n d lic he nificati o n (eac h sc ore d se paratel y ) f or eac h of f o ur b o d y re gi o ns, wit h 
a dj ust me nt for t he perce nt of B S A i n v ol ve d f or eac h b o d y  re gi o n a n d f or t he pr o p orti o n of 
t he b o d y re gi o n t o t he w h ol e b o d y.
Lesi o n Se verit y b y Cli nic al Si g ns: T he basic c haracteristics of at o pic der matitis 
lesi o ns-er yt he ma, i n d urati o n/ pa p ulati o n, e xc oriati o n, a n d lic he nificati o n -pr o vi d e a mea ns f or 
assessi n g t he se verit y of lesi o ns.  Assess me nt of t hese f o ur mai n cl i nical si g ns is perf or me d 
separatel y  f or f o ur b o dy re gi o ns: hea d a n d nec k, u p per li m bs, tr u n k (i ncl u di n g a xillae a n d 
gr oi n) a n d l o wer li m bs (i ncl u di n g b utt oc ks).  A vera ge er y t he ma, i n d urati o n/ pa p ulati o n, 
e xc oriati o n, a n d lic he nificati o n are sc ore d f or eac h b o d y re gi o n acc or di n g t o a 4 p oi nt s cale: 
0 = a bse nt; 1 = mil d; 2 = m o derate; 3 = se vere.  M or p h ol o gic descri pt ors f or eac h cli nical 
si g n se verit y sc ore are s h o w n i n Ta ble 4 .

P F- 0 4 9 6 5 8 4 2
B 7 4 5 1 0 1 4
Fi nal P r otoc ol A me n d me nt 5, 2 8 Oct o ber 2 0 1 9
P FI Z E R C O N FI D E N TI A L
Pa ge 1 0 8
T a ble 4.  
Cli nic al Si g n Se verit y Sc ori n g Criteri a f or t he E cze m a Area a n d Se verit y 
I n de x ( E A SI)
Sc ore
Descri pti o n *
Er y t he ma ( E)
0
A bse nt
N o ne; ma y  ha ve resi d ual disc ol orati o n ( p ost-i nfla m mat or y 
h y per pi g m e ntati o n a n d/ or h yp o pi g me ntati o n).
1
Mil d
Li g ht pi n k t o li g ht re d
2
M o derate
Re d
3
Se vere
Dee p, dar k re d
In d urati o n / Pa p ulati o n (I)
0
A bse nt
N o ne
1
Mil d
Barel y pal pa ble t o sli g ht, b ut defi nite har d t hic ke ne d s ki n a n d/ or 
pa p ules
2
M o derate
Easil y  pal pa ble m o derate har d t hic ke ne d s ki n a n d/ or pa p ules
3
Se vere
Se vere har d t hic ke ne d s ki n a n d/ or pa p ules
E xc oriat i o n ( E x)
0
A bse nt
N o ne
1
Mil d
Sli g ht, b ut defi nite li near or pic ke d scratc h mar ks or pe netrati n g 
s urface i nj ur y
2
M o derate
M o derate li near or p ic ke d scratc h mar ks or pe netrati n g s urface 
i nj ur y
3
Se vere
Se vere li near or pic ke d scratc h mar ks or pe netrati n g s urfac e 
i nj ur y
Lic he nificati o n ( L)
0
A bse nt
N o ne
1
Mil d
Barel y perce pti ble t o sli g ht, b ut defi nite t hic ke ne d s ki n, fi ne ski n 
mar ki n gs, a n d l ic he n oi d scale
2
M o derate
M o derate t hic ke ne d s ki n, c oarse s ki n mar ki n gs, a n d c oar se 
lic he n oi d scale
3
Se vere
Se vere t hic ke ne d s ki n wit h ver y  c oarse s ki n mar ki n gs a n d 
lic he n oi d scale
T he E A SI will e xcl u de scal p, pal ms, a n d s oles fr o m t he assess me nt/sc ori n g.
Perce nt B S A wit h At o pic Der m atitis: T he n u m ber of ha n d pri nts of s ki n affli cte d wit h 
at o pic der matitis i n a b o d y re gi o n ca n be use d t o deter mi ne t he e xte nt ( %) t o w hic h a b o d y 
re gi o n is i n v ol ve d wit h at o pic der matitis (Ta ble 5 ).  W he n meas uri n g, t he ha n d pri nt u nit 
refers t o t he size of eac h i n di vi d ual s u bject’s ha n d wit h fi n gers i n a cl ose d p ositi o n.

P F- 0 4 9 6 5 8 4 2
B 7 4 5 1 0 1 4
Fi nal P r otoc ol A me n d me nt 5, 2 8 Oct o ber 2 0 1 9
P FI Z E R C O N FI D E N TI A L
Pa ge 1 0 9
T a ble 5.  
H a n d pri nt Deter mi n ati o n of B o d y S urf ace Are a ( B S A)
B o d y Re gi o n
T ot al N u m ber o f 
H a n d pri nts i n B o d y 
Re gi o n *
S urf ace Are a of B o d y 
Re gi o n E q ui v ale nt of O ne 
H a n d pri nt *
Hea d a n d Nec k
1 0
1 0 %
U p per Li m b s
2 0
5 %
Tr u n k (i ncl u di n g a xillae a n d 
gr oi n/ ge nitals)
3 0
3. 3 3 %
L o wer Li m bs (i ncl u di n g 
b utt oc ks)
4 0
2. 5 %
Ha n d pri nt re fers t o t he ha n d size of eac h i n di vi d ual s u bject.
* T he n u m ber of ha n d pri nts will be f or t he e ntire b o d y  re gi o n; t hese val ues will n ot be a dj uste d f or e xcl usi o n 
of scal p, pal ms, a n d s oles fr o m t he B S A assess me nt.
T he e xte nt ( %) t o w hic h eac h o f t he f o ur bo d y  re gi o ns is i n v ol ve d wit h at o pic der matitis is 
cate g orize d t o a n u merical Area Sc ore usi n g a n o n-l i near scali n g met h o d acc or din g t o t he
f oll o wi n g B S A sc ori n g criteria (Ta ble 6 ).
T a ble 6.
Ecze m a Are a a n d Se v erit y I n de x ( E A SI) Are a Sc ore Criteri a
Perce nt B S A wit h At o pic Der m atitis i n a B o d y Re gi o n
Are a Sc ore
0 %
0
> 0 - < 1 0 %
1
1 0 - < 3 0 %
2
3 0 - < 5 0 %
3
5 0 - < 7 0 %
4
7 0 - < 9 0 %
5
9 0 - 1 0 0 %
6
B o d y Re gi o n Wei g hti n g: Eac h b o d y re gi o n is wei g hte d acc or di n g t o its a p pr o xi mate 
perce nta ge of t he w h ole b o d y  (Ta ble 7 ).
T a ble 7. 
Ecze m a Are a a n d Se verit y I n de x ( E A SI) B o d y Re gi o n Wei g hti n g
B o d y Re gi o n
B o d y Re gi o n Wei g hti n g
Hea d a n d Nec k
0 . 1
U p per Li m bs
0. 2
Tr u n k (i ncl u di n g a xillae a n d 
gr oi n/ ge nitals)
0. 3
L o wer Li m bs (i ncl u di n g b utt oc k s)
0. 4
* N o a dj ust me nt f or b o d y re gi o ns e xcl u de d f or assess me nt
I n eac h b o dy re gi o n, t he s u m of t he Cli nical Si g ns Se verit y Sc ores f or er yt he ma, 
i n d urati o n/ pa p ulati o n, e xc oriati o n, a n d lic he nificati o n is m ulti plie d b y t he Area Sc ore a n d b y 
t he B o dy Re gi o n Wei g hti n g t o pr o vi de a b o d y re gi o n val ue, w hic h is t he n s u m me d acr oss all 
f o ur b o dy re gi o ns res ulti n g i n a n E A SI  sc ore as descri be d i n E q uati o n 3 .

P F- 0 4 9 6 5 8 4 2
B 7 4 5 1 0 1 4
Fi nal P r otoc ol A me n d me nt 5, 2 8 Oct o ber 2 0 1 9
P FI Z E R C O N FI D E N TI A L
Pa ge 1 1 0
E q u ati o n 3:
E A SI = 0. 1 A h( E h +I h + E x h + L h) + 0. 2 A u( E u +I u + E x U + L u) + 
0. 3 At( Et +It + E xt + L t) + 0. 4 Al( El +Il + E xl + Ll)
A = Area Sc ore; E = er y t hema; I = i n d urati o n/ pa p ulati o n; E x = e xc oriati o n; 
L = lic he nificati o n; h = hea d a n d nec k; u = u p per li m bs; t = tr u n k; l = l o wer li m bs
T he E A SI sc or e ca n var y i n i ncre me nts of 0. 1 a n d ra n ge fr o m 0. 0 t o 7 2. 0, wit h hi g her sc ores 
re prese nti n g greater se verit y of at o pic der matitis.
7. 7. 3. 1. B o d y S urf ace Are a – Effic ac y ( B S A Effic ac y)
B S A Efficac y  will be deri ve d fr o m t he s u m of t he B S A i n ha n d pri nts acr oss 4 b o d y  re gi o ns 
assesse d as part of t he E A SI  assess me nt (Ta ble 5 ).  Ha n d pri nt refers t o t hat of eac h 
i n di vi d ual s u bject f or t heir o w n meas ure me nt.  T he B S A Efficac y ra n ges fr o m 0 t o 
1 0 0 %, wit h hi g her val ues re prese nti n g gr eater se verit y of at o pic der matitis.  Si nce t he scal p, 
pal ms, a n d s oles will be e x cl u de d fr o m t he B S A ( Efficac y) assess me nt, t he ma xi m u m 
p ossi ble val ue will be less t ha n 1 0 0 %.
7. 7. 4. Sc ori n g At o pic Der m atitis ( S C O R A D)
S C O R A D is a vali date d sc or i n g i n de x f or at o pic der matitis, w hic h c o m bi nes e xte nt ( 0 -1 0 0), 
se verity ( 0 -1 8), a n d s u bjecti ve s y m pt o ms ( 0 - 2 0) base d o n pr urit us a n d slee p l oss, eac h sc ore d 
usi n g a vis ual a nal o g scale ( 0 -1 0). 
E xte nt ( A, m a xi m u m sc ore of 1 0 0 %)
T o deter mi ne e xte nt of A D, r ule of 9 is use d to calc ulate b o d y s urface area affecte d b y A D as 
a perce nta ge of t he w h ole b o d y  s urface area.  B o d y s urface area as perce nta ge of t otal b o d y 
s urface area f or eac h b o d y re gi o n is as f oll o ws:

Hea d a n d nec k 9 %; 

U p per li m bs 9 % eac h; 

L o wer l i m bs 1 8 % eac h; 

A nt eri or tr u n k 1 8 %; 

Bac k 1 8 %; 

1 % f or ge nitals. 
T he sc ore f or eac h b o d y re gi o n is ad de d u p t o deter mi ne t he B S A affecte d b y  A D ( A), w hic h 
has a p os si ble ma xi m u m sc ore of 1 0 0 %. 

P F- 0 4 9 6 5 8 4 2
B 7 4 5 1 0 1 4
Fi nal P r otoc ol A me n d me nt 5, 2 8 Oct o ber 2 0 1 9
P FI Z E R C O N FI D E N TI A L
Pa ge 1 1 1
Se verit y ( B, m a xi m u m sc ore of 1 8)
A re prese ntati ve area of A D is selecte d.  I n this area, t he se verit y of eac h of t he f oll o wi n g 
si g ns is assesse d as n o ne ( 0), mild ( 1), m o derate ( 2) or se ver e ( 3). 

E r yt he ma (re d de ni n g);

E de ma (s welli n g)/ pa p ulati o n;

O ozi n g/cr usti n g; 

E xc oriati o n (scratc h mar ks);

S ki n t hic ke ni n g (lic h e nificati o n); 

Xer o sis ( dr yness) (t his is assesse d i n a n area w here t here is n o i nfla m mati o n).
T he se verit y sc ores are a d de d t o ge t her t o gi ve ' B' ( ma xi m u m sc ore of 18).
S u bjecti ve S y m pt o ms ( C, m a xi m u m sc ore of 2 0)
S u bjecti ve s y m pt o ms, ie , itc h a n d slee p l oss, are eac h sc ored b y  t he s u bject or care gi ver 
usi n g a vis ual a nal o g scale ( V A S) w here “ 0” is n o itc h ( or n o slee p l oss) a n d “ 1 0” is t he 
w orst i ma gi na ble itc h ( or slee p l oss).  T he val ue f or eac h s h o ul d reflect t he a vera ge o n a 
1 0 p oi nt scale f or t he last 3 da y s/ ni g hts.  These sc ores are a d de d t o gi ve ' C' ( ma xi m u m sc ore 
of 2 0). 
S C O R A D T ot al Sc ore
T he S C O R A D f or a n i n di vi d ual is ca lc ulate d b y  t he f or m ula: A/ 5 + 7 B/ 2 + C (ca n ra n ge 
fr o m 0 t o 1 0 3). 
7. 8. P atie nt - Re p orte d O utc o mes ( P R Os)
S u bjects will c o m plete P R O s a n d A D cli nical assess me nts at t he cli nic i n t he or der t he y  are 
prese nte d i n t he electr o nic ta blet (e P R O de vice).  All P R Os a n d A D cli ni cal assess me nts 
s h o ul d be c o m plete d pri or t o ot her cli nical acti vities a n d i n vesti gat or pr o d uct a d mi nistrati o n.  
Res ul ts of cli nical assess me nt of A D s h o ul d n ot be s hare d wit h t he s u bject u ntil t he y  ha ve 
c o m plete d t heir P R Os. T he P R Os s h o ul d be c hec ke d f o r c o m plete ness b y t he st u d y site staff 
bef ore pr ocee di n g wit h ot her ste ps of t he cli nical visit pr oce d ures.  C o m plia nc e wit h 
sc he d ule d PR Os acti vities will be m o nit ore d.  Dele gate d site staff will o versee t he 
a d mi nistrati o n of P R Os at site visits t o e ns ure pr ot oc ol c o m plia nce.  S u bjects are gi ve n a 
ha n d hel d de vice t o c o m plete t he pr urit us N R S a n d P S A A D o n a dail y  basis.  Dele gate d site 
staff will re vie w c o m plia nce at eac h visit a n d c o u nsel as a p pr o priate.  If a s u bject has 
re peate d n on -c o m plia nce, t he s u bject s h o ul d be re -trai ne d o n t he de vice.  If a s u bject is 
u na ble t o c o m plete t he P R Os o n t he ha n d hel d de vice d ue t o d oc u me nte d diffic ult y  usi n g t he 
tec h n ol o gical de vices or ot her li mitati o n, t he s u bject will be per mitte d t o e nter or re mai n i n 

P F- 0 4 9 6 5 8 4 2
B 7 4 5 1 0 1 4
Fi nal P r otoc ol A me n d me nt 5, 2 8 Oct o ber 2 0 1 9
P FI Z E R C O N FI D E N TI A L
Pa ge 1 1 2
t he stu d y .  I n t he e ve nt of electr o nic malf u ncti o n, a re place me nt de vice will be s hi p pe d t o t he 
site. 
S o me e xa m ples of t he vali date d pa per versi o ns of Patie nt Re p orte d O utc o mes i nstr u me nts 
are i ncl u de d i n t he A p pe n dices of t his pr ot o c ol.  I n i nsta nces w here a n electr o n de vice is use d 
to c ollect t he P R O data, t he electr o nic versi o n ma y differ sli g htl y i n f or mat or w or di n g 
c o m pare d wit h t he pa per versi o n t o facilitate electr o nic i m ple me ntati o n. 
7. 8. 1. Pr urit us N u meric al R ati n g Sc ale ( N R S) 
Se verit y of Pr urit us
T he se ve rity of i tc h ( pr urit us) due t o at o pic der matitis will be assesse d usi n g t he pr urit us 
N u merical Rati n g Scale, a vali date d h oriz o ntal N R S ( A p pe n di x 6 ).4 4  S u bjects will be as ke d
t o assess t heir “ w orst itc hi n g d ue t o at o pic der matitis o ver t he past 2 4 h o urs” o n a n N R S 
a nc h ore d b y t he ter ms “ n o i tc h” ( 0) a n d “ w orst itc h i magi na ble” ( 1 0).  T his ite m will be 
a d mi nistere d t o all s u bjects.  S u bjects will e nter pr urit us N R S ass ess me nt int o a n e Diar y .  
Se verit y  of pr urit us sc ore as it is assesse d o n t he da y of t he baseli ne visit will be i ncl u de d i n 
t he e val uati o n of I ncl usi o n Crit eria 3 .
Fre q ue nc y of Pr urit us 
T he fre q ue nc y of itc h ( pr urit us) d ue t o a t o pic dermatitis will be assesse d usi n g a h oriz o ntal 
N R S ( A p pe n di x 6 ).  S u bjects will be as ke d t o assess fre q ue nc y of itc hi n g d ue t o at o pic 
der matitis o ver t he past 2 4 h o urs o n a n N R S a nc h ore d b y t he ter ms “ ne ve r/ n o itc hi n g” 
( 0) a n d “al wa ys/c o nsta nt itc hi n g” ( 1 0).  T his ite m will be a d mi nistere d t o all s u bjects.  
S u bjects will e nter pr u rit us N R S assess ment i nt o a n e Diar y .  Fre q ue nc y of pr urit us will n ot 
be i ncl u de d i n t he e val uati o n of I ncl usi o n Criteria 3 .
T he pr urit us N R S s h o ul d be c o m plete d as per Sc he d ule of Acti vities . 
7. 8. 2. P a tie nt Gl o b al Assess me nt ( Pt G A)
T he Pt G A as ks t he s u bject t o e val uate t he o verall c uta ne o us disease at t hat p oi nt i n ti me o n a 
si ngle -ite m, 5 -p oi nt scale ( A p pe n di x 7 ).  T he sa me cate g or y la bels use d i n t he I n vesti gat or’s 
Gl o bal Assess me nt will b e use d f or t he Patie nt Gl o bal Assess me nt, ie, “se vere ( 4)”, 
“ m o derate ( 3)”, “ mil d ( 2)”, “al m ost clear ( 1)”, a n d “clear ( 0)”.  T he Pt G A s h o ul d be 
c o m plete d as per Sc he d ule of Acti vities .  T his si n gle-ite m scale will be a d mi nistere d t o all 
s u bjects.

P F- 0 4 9 6 5 8 4 2
B 7 4 5 1 0 1 4
Fi nal P r otoc ol A me n d me nt 5, 2 8 Oct o ber 2 0 1 9
P FI Z E R C O N FI D E N TI A L
Pa ge 1 1 3
7. 8. 3. E ur o Q ol Q u alit y of Life 5- Di me nsi o n 5 -Le vel Sc ale ( E Q - 5 D-5 L) a n d E ur o Q ol 
Q u alit y of Life 5 -Di me ns i o n Y o ut h Sc ale ( E Q-5 D -Y i n select c o u ntries)
T he E Q -5 D is a vali date d, sta n dar dize d, ge neric i nstr u me nt t hat is t he m ost wi del y  use d 
pr efere nce-base d healt h -relate d q ualit y of life q uesti o n naire i n c ost-effecti ve ness an d healt h 
tec h n ol o gies assess me nt ( H TA) ( A p pe n di x 8 ).1 9 -2 2  Rece ntl y , a versi o n was de vel o pe d calle d 
E Q - 5 D-5 L  wit h 5 resp o nse le vels o n e ac h di me nsi o n c o m pare d t o t h e 3 res p o nse le vels i n t he 
E Q - 5 D-3 L .1 9 ,2 1 ,2 3 ,2 4 ,2 5 A versi o n of t he i nstr u me nt s pecific all y de vel o pe d a n d vali date d f or 
use b y  yo ut hs a ge 1 2 t hr o u g h 1 7 ye ars is calle d t he E Q- 5 D-Y a n d is o nl y a vaila ble i n select 
c o u ntries. 2 6 ,2 7 ,2 8
Meas ure me nt pr o perties of t he E Q- 5 D- 5 L  de m o nstrate d t o be a vali d versi o n of t he 3-le vel 
q uesti o n naire t hat i m pr o ve d meas ure ments b y  a d di n g discri mi nat or y p o wer, re d uci n g t he 
ceili n g, a n d esta blis hi n g c o n ver gent a n d k n o w n -gr o u ps vali dit y .2 1 ,2 0 ,2 3 ,2 5  B ot h t he E ur o Q ol 
E Q - 5 D-3 L  a n d E Q- 5D- 5 L  versi o ns are well-esta b lis he d i nstr u me nts use d t o meas ure healt h 
states a n d utilities i n vari o us diseases areas a n d assess m o bilit y, self-care, us ual acti vities, 
pai n/ d isc o mf ort, a n xiet y/ de pressi o n a n d healt h stat us usi n g a vis ual a nal o g ue scale 
( V A S).2 2 ,2 8  T he E Q - 5 D-3 L  was use d pre vi o usl y i n A D st u dies, i ncl u din g t he d u pil u ma b 
trials, t o meas ure utilities.2 9 -3 2
7. 8. 4. Der m at ol o g y Life Q u alit y I n de x ( D L QI) a n d C hil dre n’s Der m at ol o g y Life 
Q u alit y I n de x ( C D L QI)
T he D L QI is a vali da te d ge neral der mat o l o g y q uesti o n naire t hat c o nsists of 1 0 ite ms t o assess 
s u bject-re p orte d healt h-relate d q ualit y of life ( dail y acti vities, pers o nal relati o ns hi ps, 
s ym pt o ms a n d feeli n gs, leis ure, w or k a n d sc h o ol, a n d treat me nt) ( A p pe n di x 9 ).3 3  It has bee n 
e xte nsi vel y use d i n cli nical trials f o r A D.  T he D L QI is a ps yc h o metricall y vali d a n d relia ble 
i nstr u me nt t hat has bee n tra nslate d i nt o se veral la n g ua ges, a n d t he D LQI  t otal sc ores have 
bee n s h o w n t o be res p o nsi ve t o c ha n ge.  T he mi ni mall y  i m p orta nt differe nce f or t he D L QI 
has bee n esti mate d a s a 3 t o 5 p oi nt c ha n ge fr o m baseli ne.  A versi o n of t he i nstr u me nt 
s pecifically de vel o pe d a n d vali date d f or use b y a d olesce nts fr o m a ge 1 2 t o 1 7 is calle d t he 
C L D QI .3 4  T he D L QI  s h o ul d be c o m plete d as per Sc he d ule of Acti vities .
7. 8. 5. P atie nt - Orie nte d Ecze m a Me as ure ( P O E M)
T he P O E M is a vali date d 7 -ite m P R O meas ure use d t o assess t he i m pact of A D recalle d o ver 
t he past wee k ( A p pe n di x 1 0 ).  T his i nstr ume nt is a p pr o priate f or use b y s u bjects a ge d 1 2 a n d 
ol der. 3 5 ,3 6  T he P O E M s h o ul d be c o m plete d as per Sc he d ule of Acti vitie s.
7. 8. 6. 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 is a vali date d 1 4 -ite m P R O meas ure use d t o assess states of a n xiet y a n d 
d e pressi o n o ver t he past wee k ( A p pe n di x 1 1 ).  T he i nstr u me nt has bee n vali date d f or u se by 
a d olesce nts a ge d 1 2 a n d ol der.3 7  T he H A D S s h o ul d be c o m plete d as per S c he d ule of 
Acti vities .

P F- 0 4 9 6 5 8 4 2
B 7 4 5 1 0 1 4
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7. 8. 7. Pr urit us a n d S y m pt o ms Assess me nt f or At o pic Der m atitis ( P S A A D)
T he P S A A D is a da il y patie nt re p orte d sy m pt o m diar y .  T he preli mi nar y versi o n 
(A p pe n di x 1 2 ) is a 1 5-ite m q uesti o n naire t hat i ncl u des 1 1 ite ms de vel o pe d t o meas ure 
s ym pt o ms of at o pic der matitis, ca pt uri n g t h ose i de ntifie d b y patie nts t o be m ost i m p orta nt, 
base d o n a 2 4 -h o ur recall. A nal y sis of t he P S A A D will be base d s olely o n t hese 1 1 ite ms.  
F o ur a d diti o nal ite ms were a d de d f or e x pl orat or y an d ps y c h o metric vali dati o n p ur p oses 
( Slee p & Us ual Acti vities Q uesti o ns a n d Patie nt Gl o bal I m pressi o n of Se verit y  [ P GIS] a n d 
Patie nt Gl o bal I m pressi o n of C ha n ge Q uesti o ns [ P GI C]).   T he P S A A D is a n electr o nic P R O 
t hat was de vel o pe d t hr o u g h c o nce pt elicitati o n a n d c o g niti ve de briefi n g i n A D patie nts 
a ges 1 2 t o 6 7; t he q uesti o n naire utilize d i n B 7 4 5 1 0 0 6 as a n e x pl orat or y  e n d p oi nt will be 
i m ple me nted i n t his st u d y wit h a n y refi ne me nts a n d c ha n ges assesse d as a res ult of t he 
preli mi nar y  ps yc h o metric vali dati o n. All tec h nical d oc u me nts descri bi n g meas ure me nt 
pr o perties of t he P S A A D will be s u b mitte d as re q uire d t o t he Re g ulat or y A ge ncies u p o n 
fi nalizati o n.  T he P S A A D s h o ul d be c o m plete d b y s u bjects ( o nl y i n selecte d c o u ntries) as per 
Sc he d ule of Acti vities o n a n e Diar y . 
7. 8. 8. S h ort F or m -3 6 He alt h S ur ve y, Versi o n 2, Ac ute ( S F -3 6 v 2, Ac ute) 
T he S F -3 6 v 2 is a vali date d ge neric healt h stat us meas ure (A p pe n di x 1 3 ). It meas ures 
8 ge neral healt h d o mai ns: p h y sical f uncti o ni n g, r ole li mitati o ns d ue t o p h y sical healt h, b o dil y
pai n, ge neral healt h per ce pti o ns, vitalit y , social f u ncti o ni n g, r ole li mitati o ns d ue t o e m oti o nal
pr o ble ms, a n d me ntal healt h.  T hese d o mai ns ca n als o be s u m marize d as p h y sical a nd me ntal
c o m p o ne nt s u m mar y sc ores.  T he use of t his scale is restricte d t o a d ult s u bjects a n d n ot f or
a d olesce nts t o c o m plete. 3 8  S F -3 6 v 2 will be c o m plete d b y a d ult s u bjects o nl y.  A d olesce nts 
1 2 - 1 7 ye ars of a ge will n ot c o m plete t his assess me nt.
7. 8. 9. F A CI T F ati g ue Sc ale ( F A CI T -F) a n d Pe di atric F A CI T -F ( Pe ds -F A CI T - F)
T he F u ncti o nal Asse ss me nt of C hr o nic Ill ness T hera p y Fati g ue Scale ( F A CI T – F) is a 
vali date d s u bject c o m plete d q uesti o n naire c o nsisti n g of 1 3 ite ms t hat assess fati g ue.  
I nstr u ment sc ori n g yi el ds a ra n ge fr o m 0 t o 5 2, wit h hi g her sc ores re prese nti n g bette r o verall 
healt h stat us (less fati g ue ) (A p pe n di x 1 4 ).3 9  T he F A C T -F s h o ul d be c o m pl ete d as per
Sc he d ule of Acti vities .  F A CIT- F will b e c o m plete d b y a d ult s u bjects o nly.  A d olesce nts 
1 2 - 1 7 ye ars of a ge will c o m plete t he Pe diatric F A CI T- F ( Pe ds -F A CI T -F) i nstea d of t he 
F A CI T -F. 4 2
7. 8. 1 0. Ast h m a C o ntr ol
Ast h ma c o ntr ol f or all s u bjects wit h ast h ma s h o ul d be assesse d at ti mes s pecifie d i n t he 
Sc he d ule of Acti vities usi n g t he Ast h ma C o ntr ol Q uesti o n naire ( A C Q; A p pe n di x 1 9 ).  T he 
A C Q meas ures t he a de q uac y  of ast h ma c o ntr ol a n d c ha n ge i n ast h ma c o ntr ol w hic h occ urs 
eit her s p o nta ne o usl y or as a res ult of treat me nt.  T he A C Q has 5 q uesti o ns (t he t o p sc ori n g 
5 s ym pt o ms).  S u bjects are as ke d t o recall h o w t heir ast h ma has bee n d uri n g t he pre vi o us 
wee k a n d t o res p o n d t o t he s y m pt o m q uesti o ns o n a 7 -p oi nt scale ( 0 = n o i m pair me nt, 
6 = ma xi m u m i m pair me nt).  T he q uesti o ns are e q uall y wei g hte d a n d t he A C Q 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) an d 6 (se verel y 
u nc o ntr olle d). 1 6 ,1 7 ,4 5

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7. 9. P h ar m ac o ki netics
7. 9. 1. Pl as m a f or A n al ysis of P F -0 4 9 6 5 8 4 2 a n d Met a b olites
D uri n g t he st u d y, bl o o d sa m ples ( 8 m L ) t o pr o vi de mi ni m u m 3. 2 m L  of plas ma f or P K 
a nal ys is will be c ollecte d i nt o a p pr o priately l a bele d t u bes c o ntai ni n g di p otassi u m
et h yle ne dia mi netetraacetic aci d ( K2E D T A) f or meas ure me nt of plas ma c o nce ntrati o n of 
P F - 0 4 9 6 5 84 2 a n d its meta b olites P F -0 6 4 7 1 6 5 8, P F -0 7 0 5 5 0 8 7, a n d P F -0 7 0 5 4 8 7 4 at ti mes 
s pecifie d i n t he Sc he d ule of Acti viti es. T h e actual date a n d ti me ( 2 4 -h o ur cl oc k ti me) of 
eac h sa m ple will be rec or de d.
A bl o o d sa m ple f or P K a nal y sis will be c ollecte d at 2. 0 h o urs ( 3 0 mi n) p ost d ose at 
Wee k
1 2. 
All eff orts will be ma de t o o btai n t he P K sa m ple at t he e xact n o mi nal ti me re lati ve t o d osi n g.  
T he e xact ti m e of t he sa m ple c ollecti o n is t o be n ote d o n t he s o urce d oc u me nt a n d data 
c ollecti o n t o ol (e g, C R F).  A sa m ple o btai ne d o utsi de t he wi n d o ws s pecifi e d i n t he Sc he d ule 
of Acti viti es will be c o ns i dere d a prot oc ol de viati o n.   F o r E T visits, if t he s u bject 
disc o nti n ues bef ore Wee k 4 d o n ot c ollect t he P K sa m ple.  If t he E T visit occ urs after 
Wee k
4, c ollect t he P K sa m ple o nl y if t he s u bject ta kes t he i n vesti gati o nal pr o d uct at t he si te 
visit.

T he pl as ma will be st ore d i n a p pr o priately la bele d scre w -ca p pe d p ol y pr o p yle ne t u be 
at a p pr o xi matel y - 2 0C wit hi n 1 h o ur of c ollecti o n.

F urt her details re gar di n g t he c ollecti o n, pr ocessi n g, st ora ge a n d s hi p pi n g of t he bl o o d 
sam ples will be pr o vi de d i n t he la b ma n ual.

Sa m ples will be a nal y ze d us i n g a vali date d a nalyt ical met h o d i n c o m plia nce wit h 
Pfizer sta n dar d o perati n g pr oce d ures. 

T he P K sa m ple m ust be pr ocesse d a n d s hi p pe d as i n dicate d t o mai ntai n sa m ple 
i nte grity.  A n y de v iati o ns fr o m t he P K pr ocessi n g ste ps, i ncl u di n g a ny acti o ns ta ke n, 
m u st be d oc u me nte d a n d re p orte d t o t he s p o ns or.  O n a case-b y -case basis, t he 
s p o ns or ma y ma ke a deter mi nati o n as t o w het her sa m ple i nte grit y has bee n
c o m pr o mise d.  A n y sa m ple dee me d o utsi d e of esta blis he d sta b ilit y, or of q uesti o na ble 
i nte grit y, will be c o n si dere d a pr ot oc ol de viati o n.

As part of u n dersta n di n g t he P Ks of t he i n vesti gati o nal pr o d uct, sa m ples ma y be use d 
f or meta b olite i de ntificati o n a n d/ or e val uati o n of t he bi oa nalyt ical meth o d.  T hese 
data will be use d f or i nt er nal e x pl ora t or y p ur p oses a n d will n ot be i ncl u de d i n t he 
cli nical re p ort.

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7. 9. 2. S hi p me nt of P h ar m ac o ki netic S a m ples
T he ce ntral la b orat or y  will pr o vi de c ollecti o n materials a n d directio ns f or pac ka gi n g a n d 
s hi p me nt of sa m ples a n d will f or war d sa m ples t o t he c o ntract a nal yt ical la b orat or y.  Refer t o 
t he ce ntral la b ve n d or ma n ual f or f urt her i nf or mati o n.
8. A D V E R S E E V E N T R E P O R T I N G
8. 1. Re q uire me nts
T he ta ble bel o w s u m marizes t he re q uire me nts f or rec or di n g safet y e ve nts o n t he C R F a n d f or 
re p orti n g safet y e ve nts o n t he Cl i nical Trial ( C T) Seri o us A d verse E ve nt ( S A E) Re p ort F or m 
t o Pfizer Safet y.  T hese re q uire me nts are deli neate d f or 3 t ypes of e ve nts: ( 1) S A Es; 
( 2) n o n -seri o us a d verse e ve nts ( A Es); a n d ( 3) e x p os ure t o t he i n vesti gati o nal pr o d uct u n der 
st u dy d uri n g pre g na n c y or breastfee di n g, a n d occ u pati o nal e x p os ure. 
S afet y E ve nt
Rec or de d o n t he C R F
Re p orte d o n t he C T S A E 
Re p ort F or m t o Pfizer 
S afet y Wit hi n 2 4 H o urs of 
A w are ness
S A E
All
All
N o n -seri o us A E
All
N o ne
E x p os ure t o t he 
in vesti gati o nal pr o d uc t 
u n der st u d y  d uri n g 
pre g na nc y  or 
breastfee di n g , a n d 
occ u pati o nal e x p os ure
All (re gar dless of w het her 
ass ociate d wit h a n A E), 
e xce pt occ u pati o nal e x p os ure
E x p os ure d uri n g pre g na nc y , 
e x p os ure via breastfee di n g, 
occ u pati o nal e x p os ure 
(regar dless of w het her 
ass ociate d wit h an A E)
All o bser ve d or v ol u ntee re d e ve nts re gar dless of treat me nt gr o u p or s us pecte d ca usal 
relati o ns hi p t o t he i n vesti gati o nal pr o d uct(s) will be re p orte d as descri be d i n t he f oll o wi n g 
para gra p hs.
E ve nts liste d i n t he ta ble a b o ve t hat re q uire re p orti n g t o Pfizer Safet y o n t he C T S A E Re p ort 
F or m wit hi n 2 4 h o urs of a ware ness of t he e ve nt b y  t he i n vesti gat or are t o be re p orte d 
re g ar dless of w het her t he e ve nt is deter mi ne d b y t he i n ve sti g at or t o be rel ate d t o a n 
i n vesti g atio n al pr o d uct u n der st u d y .  In partic u lar, if t he S A E is fatal or life-t hreate ni n g, 
n oti ficati o n t o Pfizer Safet y m ust be ma de i m me diatel y, irres pecti ve of t he e xte nt of a vaila ble 
e ve nt i nf or mati o n.  T his ti me fra me als o a p plies t o a d diti o nal ne w (f oll o w -u p ) i nf or mati o n o n 
pre v i o usl y f or war de d re p orts.  In t he rare sit uati o n t hat t he i n vesti g at or d oes n ot bec o me 
i m me diatel y a ware of t he occ urre nce of a n e ve nt, t he i n vesti gat or m ust re p ort t he e ve nt 
wit hi n 2 4 h o urs afte r lear ni n g of it a n d d oc u me nt t he ti me of his/ her first a wareness of t he 
e ve nt.
F or eac h e ve nt, t he i n vesti g at or m ust p urs ue a n d o btai n a de q uate i nf or mati o n b ot h t o 
deter mi ne t he o utc o me a n d t o assess w het her it meets t he criteria f or classificati o n as a n S A E 
(see t he Seri o us A d verse E ve n ts secti o n bel o w).  I n a d diti o n, t he i n vesti gat or may be 

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re q ueste d by Pfizer Safet y t o o btai n s pecific f oll o w -u p i nf or mati o n i n a n e x pe dite d fas hi o n.  
T his i nf or mati o n is m ore detaile d t ha n t hat rec or de d o n t he C R F .  I n ge neral, t his will i ncl u de 
a descri pti o n of t he e ve nt i n s ufficie nt d etail t o all o w f or a c o m plete me dical assess me nt of 
t he case a n d i n de pe n de nt deter mi nati o n of p ossi ble ca usalit y.  A n y i nf or mati o n rele va nt t o 
t he e ve nt, s uc h as c o nc o mita nt me dicati o ns a nd ill nesses, m ust be pr o vi de d.  I n t h e case of a 
s u bject deat h, a s um mar y of a vaila ble a ut o ps y fi n di n gs m ust be s u b mitte d as s o o n as p ossi ble 
t o Pfizer Safet y.  A ny perti ne nt a d diti o nal i nf or mati o n m ust be re p orte d o n t he C T S A E 
Re p ort F or m; a d diti o nal s o u rce d oc u me nts (e g, medical rec or ds, C R F, la b orat or y  data) are t o 
be se nt t o Pfizer Safet y O N L Y u p o n re q uest.
A n y  cli nicall y si g nifica nt w orse ni n g of A D is c o nsi dere d a n A E re gar dless of meeti n g t he 
defi niti o n of flare. 
As part of o n g oi n g safet y re vie ws c o n d ucte d b y  t he s p o ns or, a ny n o n -seri ous A E t hat is 
deter mi ne d b y t he s p o ns or t o be serio us will be re p orte d b y  t he s p o ns or as a n S A E.  T o assist 
i n t he deter mi nati o n of case seri o us ness, f urt her i nf or mati o n ma y  be re q ueste d fr o m t he 
i n vesti gat or t o pr o vi de clarit y a n d u n dersta n di n g of t he e ve nt i n t he c o nte xt of t he cli nical 
st u d y.
8. 1. 1. A d diti o n a l Det ails o n Rec or di n g A d verse E ve nts o n t he C R F
All e ve nts detail e d i n t he ta ble a b o ve will be rec or de d o n t he A E pa ge(s) of t he C R F.  I t 
s h o ul d be n ote d t hat t he C T S AE Re p ort F or m f or re p orti n g of S A E i n f or mati o n is n ot t he 
sa me as t he A E pa ge of t he C R F.  W he n t he sa me data are c ollecte d, t he f or ms m ust be 
c o m plete d i n a c o nsiste nt ma n ner.  A Es s h o ul d be rec or de d usi n g c o ncise me dical 
ter mi n ol o g y a n d t he sa me A E ter m s h o ul d be use d o n b oth t he C R F a n d t he C T S A E Re p ort 
F or m f or re p ort i n g of S A E i nf or mati o n.
8. 1. 2. Eliciti n g A d verse E ve nt I nf or m ati o n
T he i n vesti gat or is t o re c or d o n t he C R F all directl y o bser ve d A Es a n d all A Es s p o nta ne o usl y 
re p orte d by t he st u d y s u bject , le gall y acce pta ble re prese ntati ve/ pare nt(s) or le gal g uar dia n, if 
a p plica ble.  I n a d diti o n, eac h st u d y s u bject, le gally acce pta ble re prese ntati ve/ pare nt(s) o r 
le gal g uar dia n, if a p plica ble, will be q uesti o ne d a b o ut t he occ urre nce of A Es i n a n o n-lea di n g 
ma n ner .
8. 1. 3. Wit h dr a w al fr o m t he
St u d y D ue t o A d verse E ve nts (see als o t he S u bject 
Wit h dr a w al
secti o n)
Wit h dra wal d ue t o A Es s h o ul d be disti n g uis he d fr o m wit h dra wal d ue t o ot her ca uses, 
acc or di n g t o t he defi niti o n of A E n ote d bel o w, a n d rec o r de d o n t he C R F. 
W he n a s u bject wit h dra ws fr o m t he st u d y  beca use of a n S A E, t he S A E m u st be rec or de d o n 
t he C R F a n d re p orte d, as a p pr o priate, o n t he C T S A E Re p ort F or m, i n acc or da nce wit h t he 
Re q uire me nts secti o n a b o ve.

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8. 1. 4. Ti me Peri o d f or C ollecti n g A E/ S A E I nf or m ati o n
T he ti me peri o d f or acti vel y  eliciti n g a n d c ollecti n g A Es a n d S A Es (“acti ve c ollecti o n 
peri o d”) f or eac h s u bject be gi ns fr o m t he ti me t he s u bject, le gall y acce pta ble 
re prese ntati ve/ pare nt(s) or le gal g uar dia n, if a p plica ble, pr o vi des i nf or m e d c o nse nt, w hic h is 
o bta i ne d bef ore t he s u bject’s partici pati o n in t he st u d y  (ie, bef ore u n der g oi n g a ny 
st u d y-relate d pr oce d ure a n d/ or recei vi n g i n vesti gati o nal pr o d uct), t hr o u g h a n d i ncl u di n g a 
mi ni m u m of 2 8 cale n dar da ys; e xce pt as i n dicate d bel o w after t he last a d mi nistrati o n of t he 
i n vesti gati o nal pr o d uct.
F or s u bje cts w h o are scree n fail ures, t he acti ve c ollecti o n peri o d e n ds w he n scree n fail ure 
stat us is deter mi ne d.
8. 1. 4. 1. Re p orti n g S A Es t o Pfizer S afet y
All S A Es occ urri n g i n a s u bject d uri n g t he acti ve c ol lecti o n peri o d are re p orte d t o Pfizer 
Safet y  o n t he C T S A E Re p ort F or m.
S A Es occ urri n g i n a s u bject after t he acti ve c ollecti o n peri o d has e n de d are re p orte d t o Pfizer 
Safet y  if t he i n vesti gat or bec o mes a ware of t he m; at a mi ni m u m, all S A Es t hat t he 
i n vesti gat or belie ves ha ve at l east a reas o na ble p oss i bilit y of bei n g relate d t o i n vesti gati o nal 
pr o d uct m ust be re p orte d t o Pfizer Safet y .
F oll o w u p b y  t he i n vesti gat or c o nti n ues t hr o u g h o ut a n d after t he acti ve c ollecti o n peri o d a n d 
u ntil t he e ve nt or its se q ue lae res ol ve or sta bilize at a le vel acce pta ble t o t he i n vesti gat or, a n d 
Pfizer c o nc urs wit h t hat assess me nt.
8. 1. 4. 2. Rec or di n g N o n -seri o us A Es a n d S A Es o n t he C R F
D uri n g t he acti ve c ollecti o n peri o d, b ot h n o n-seri o us A Es a n d S A Es are rec or de d o n t he 
C R F.
F oll o w - u p b y  t he i n vesti gat or ma y be re q uire d u ntil t he e ve nt or its se q uel ae res ol ve or 
sta bilize at a le vel acce pta ble t o t he i n vesti gat or, a n d Pfizer c o nc urs wit h t hat assess me nt.
8. 1. 5. C a us alit y Assess me nt
T he i n vesti gat or’s assess me nt of ca usali t y m ust be pr o vi de d for all A Es (seri o us a n d 
n o n -seri o us); t he i n vesti gat or m ust rec or d t he ca usal relati o ns hi p o n t he C R F, a n d re p ort s uc h 
a n assess me nt i n acc or da nce wit h t he S A E re p orti n g re q uire me nts, if a p plica ble.  A n 
i n vesti gat or’s ca usality assess m e nt is t he deter mi nati o n of w het her there e xis ts a reas o na ble 
p ossi b ilit y t hat t he i n vesti gati o nal pr o d uct ca use d or c o ntri b ute d t o a n A E; ge nerall y t he facts 
(e vi de nce) or ar g u me nts t o s u g gest a ca usal relati o ns hi p s h o ul d be pr o vi de d.  If t he 
i n vesti gat or d oes n ot k n o w w het he r or n ot t he i n vesti gati onal pr o d uct ca use d t he e ve nt, t he n 
t he e ve nt will be ha n dle d as “relate d t o i n vesti gati o nal pr o d uct” f or re p orti n g p ur p oses, as 
defi ne d b y t he s p o ns or.  If t he i n vesti gat or's ca usalit y assess me nt is “ u n k n o w n b ut n ot 
relate d” t o i n vesti gati o nal pr o d uct, t hi s s h o ul d be clearly d o c u me nte d o n st u d y rec or ds. 

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I n a d diti o n, if t he i n vesti gat or deter mi nes t hat a n S A E is ass ociate d wit h st u d y pr oce d ures, 
t he i n vesti gat or m ust rec or d t his ca usal relati o ns hi p i n t he s o urce d oc u me nts a n d C R F, a n d 
re p ort s uc h an assess m e nt i n t he de dicate d s ecti o n of t he C T S A E Re p ort F or m a n d i n 
acc or da nce wit h t he S A E re p orti n g re q uire me nts.
8. 1. 6. S p o ns or’s Re p orti n g Re q uire me nts t o Re g ul at or y A ut h orities
A E re p orti n g, i ncl u di n g s us pecte d u ne x pec te d seri o us a d verse reacti o ns, will be carrie d o ut 
i n acc or da nce with a p plica ble l ocal re g ulati o ns.
8. 2. Defi niti o ns
8. 2. 1. A d verse E ve nts
A n A E is a n y u nt o war d me dical occ urre nce i n a st u d y s u bject a d mi nistere d a pr o d uct or 
me dical de vice; t he e ve nt nee d n ot necessar il y ha ve a ca usal relati o ns hi p wit h t he treat m e nt 
or usa ge.  E xa m ple s of A Es i ncl u de, but are n ot li mite d t o: 

A b n or mal test fi n di n gs;

Cli nicall y  si g nifica nt si g ns a n d s ym pt o ms;

C ha n ges i n p h ys ical e xa mi nati o n fi n di n gs;

H y perse nsiti vit y ;

Pr o gressi o n/ w orse n i n g of u n derlyi n g dis ease; 

Dr u g a b us e;

Dr u g d e pe n de nc y.
A d diti o nall y, A Es ma y i ncl u de si g ns a n d sy m pt o ms res ulti n g fr o m:

Dr u g o ver d ose;

Dr u g wit h dra wal;

Dr u g mis use; 

Dr u g i nteracti o ns;

E xtra vasati o n;

E x p os ure d uri n g pre g na nc y  ( E D P);

E x p os ure via breastfe e di n g;

Me dicati o n err or;

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
Occ u pati o nal e x p os ure.
8. 2. 2. A b n or m al Test Fi n di n gs
A b n or mal o bjecti ve test fi n di n gs s h o ul d be rec or de d as A Es w he n a n y of t he f oll o wi n g 
c o n diti o ns are met: 

Test res ult is ass ociate d wit h acc o m pa n yi n g s y m pt o ms; a n d/ or

Test res ult re q uir es a d diti o nal dia g n os tic testi n g or me dical/s ur gical i nter ve nti o n; 
an d/ or

Test res ult l ea ds t o a c ha n ge i n st u d y d osi n g ( o utsi de of a n y pr ot oc ol -s pecifie d d ose 
a dj ust me nts) or disc o nti n uati o n fr o m t he st u d y , si g nifica nt a d diti o nal c o nc o mita nt 
dr u g treat me n t, or ot her t hera p y; a n d/ or

Test res u lt is c o nsi dere d t o be a n A E by t he i n vesti gat or or s p o ns or.
Merel y re peati n g a n a b n or mal test, i n t he a bse nce of a n y of t he a b o ve c o n diti o ns, d oes n ot 
c o nstit ute a n A E.  A n y a b n or mal test res ult t hat is deter mi ne d t o b e a n err or d oes n ot r e q uire 
rec or di n g as a n A E.
8. 2. 3. Seri o us A d verse E ve n ts
A seri o us a d vers e e ve nt is a n y u nt o war d me dical occ urre nce at a n y d ose t hat:

Res ults i n deat h;

Is life-t hreate ni n g (i m me diate ris k of deat h);

Re q uires i n patie nt h os pitalizati o n or pr ol o n gati o n of e xisti n g h os pitalizati o n;

Res ults i n persiste nt or si g nif ica nt disa bilit y/i nca pacit y (s u bsta ntial disr u pti o n of t he 
a bilit y t o c o n d uct n or mal life f u ncti o ns);

Res ults i n c o n ge nital a n o mal y / birt h defect.
Or t hat is c o nsi dere d t o be:

A n i m p orta nt me dical e ve n t.
Me dica l a n d scie ntific j u d g me nt is e xercise d i n determi ni n g w het her a n e ve nt is a n i m p orta nt 
me dical e ve nt.  A n i m p orta nt me dical e ve nt ma y  n ot be i m me diatel y life-t hreate ni n g a n d/ or 
res ult i n deat h or h os pitalizati o n.  H o we ver, if it is deter mi ne d t hat t he e ve nt ma y je o par dize
t he s u bject or ma y re q uire i nter ve nti o n t o pre ve n t o ne of t he ot her A E o utc o mes, t he 
i m p orta nt me dical e ve nt s h o ul d be re p orte d as seri o us.

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E xa m ples of s uc h e ve nts are i nte nsi ve treat me nt i n a n e mer ge nc y  r o o m or at h o me f or 
aller gic br o nc hos pas m; bl o o d d y scrasias or c o n v ulsi o ns t hat d o n ot res ult i n h os p italizati o n; 
or de vel o p me nt of dr u g de pe n de nc y  or dr u g a b use.
8. 2. 4. H os pit aliz ati o n
H os pitalizati o n is defi ne d as a n y i nitial a d missi o n (e ve n less t ha n 2 4 h o urs) i n a h os pital or 
e q ui vale nt healt h care facilit y, or a n y pr ol o n gati o n of a n e xistin g a d missi o n.  A d mi ssi o n als o 
i ncl u des tra nsfer wit hi n t he h os pital t o a n ac ute/i nte nsi ve care u nit (e g, fr o m t he ps yc hiatric 
wi n g t o a me dical fl o or, me dical fl o or t o a c or o nar y  care u nit, or ne ur ol o gical fl oor t o a 
t u berc ulosis u nit).  A n e mer ge nc y  r o o m visit d oes n ot nece ssarily c o nstit ute a h os pitalizati o n; 
h o we ver, t he e ve nt lea di n g t o t he e mer ge nc y  r o o m visit is assesse d f or me dical i m p orta nce.
H os pitalizati o n d oes n ot i ncl u de t he f ol l o win g:

Re ha bilitati o n facilities;

H o s pice facilities;

Res pite care (e g, care gi ver relief);

S kille d n ursi n g facilities;

N ursi n g h o mes;

Sa me -d a y  s ur geries (as o ut patie nt/sa me-d a y /a m b ulat or y pr oce d ures).
H os pitalizati o n or pr ol o n gati o n of h os pitalizati o n i n t he a bse nce of a preci pitati n g cli nical 
A E is n ot i n itself a n S A E. E xa m ples i ncl u de:

A d missi o n f or treat me nt of a pree xisti n g c o n diti o n n ot ass ociate d wit h t he 
de vel o p me nt of a ne w A E or wit h a w orse ni n g of t he pree xisti n g c o n diti o n (e g, f or 
w or k u p of a pers iste nt pretreat ment la b orat or y  a bn or malit y );

S ocial a d missi o n (e g, s u bject has n o p lace t o slee p);

A d mi nistrati ve a d missi o n (e g, f or ye arl y p h ys ical e xa mi nati o n);

Pr ot oc ol -s pecifie d a d missi o n d uri n g a st u dy (e g, f or a pr oce d ure re q uire d b y t he st u d y 
pr ot oc ol);

O pti o nal a d m issi o n n ot ass ociate d wit h a preci pitati n g cli nical A E (e g, f or electi ve 
c os metic s ur ger y);

H os pitalizati o n f or o bser vati o n wit h o ut a me dical A E;

Pre pla n ne d treat me nts or s ur gical pr oce d ures.  T hese s h o ul d be n ote d i n t he baseli ne 
d oc u me nt ati o n f or t he e nt ire pr ot oc ol a n d/ or f or t he i n di vi d ual s u bject.

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Dia g n ostic a n d t he ra pe utic n o ni n vasi ve a n d i n vasi ve pr oce d ures, s uc h as s ur ger y, s h o ul d n ot 
be re p orte d as S A Es.  H o we ver, t he me dical c o n diti o n f or w hic h t he pr oce d ure was 
perf or me d s h o u l d be re p orte d if it meets t he defi niti o n of a n S A E.  F or e xa m ple, a n ac ute 
a p pe n diciti s t hat be gi ns d uri n g t he re p orti n g peri o d s h o ul d be re p orte d if t he S A E 
re q uire me nts are met, a n d t he res ulti n g a p pe n dect o m y s h o ul d be rec or de d as treat me nt of t he 
A E.
8. 3. S e verit y Assess me nt
If re q uire d o n t he A E pa ge of t he C R F, t he i n vesti gat or will use t he a djecti ves MI L D, 
M O D E R A T E, or S E V E R E t o descri be t he ma xi m u m i nte nsit y  of t he A E.  F or p ur p oses of 
c o nsiste nc y, t hese i nte nsit y gra des are defi ne d as f oll o ws:
MI L D
D oe s n ot i nterfere wit h s u bject's us ual f u ncti o n.
M O D E R A T E
I nterferes t o s o me e xte nt wit h s u bject's us ual f u ncti o n.
S E V E R E
I nterferes si g nifica ntly wit h s u bject's us ual f u ncti o n.
N ote t he disti ncti o n bet wee n t he se verit y a n d t he seri o us ness of a n A E.  A se vere e ve nt is n ot 
nec essaril y a n S A E.  F or e xa m ple, a hea dac he ma y  be se vere (i nterfere s si g nifica ntl y wit h 
t he s u bject's us ual f u ncti o n) b ut w o ul d n ot be classifie d as seri o us u nless it met o ne of t he 
criteria f or S A Es, liste d a b o ve.
8. 4. S peci al Sit u ati o n s
8. 4. 1. Pr ot oc ol -S pecifie d Seri o us A d verse E ve n ts
T here are n o pr ot oc ol -s pecifie d S A Es i n t his stu d y.  All S A Es will be re p orte d t o Pfizer 
Safet y  b y t he i n vesti gat or as descri be d i n pre vi o us secti o ns, a n d will be ha n dle d as S A Es i n 
t he safety data base. 
8. 4. 2. P ote nti al C a ses of Dr u g-I n d uce d Li ver I nj ur y
H u ma ns e x p ose d t o a dr u g w h o s h o w no si g n of li ver i nj ur y  (as deter mi ne d b y ele vati o ns i n 
tra nsa mi nases) are ter me d “t olerat ors,” w hile t h ose w h o s h o w tra nsie nt li ver i nj ur y, b ut a da pt 
are ter me d “a da pt ors.”  I n s o me s u bjects, tra nsa mi nase ele vati o ns are a har bi n ger of a m ore 
seri o us p ote ntial o utc o me.  T hese s u bjects fail t o a da pt a n d t heref ore are "s usce pti ble" t o 
pr o gressi ve a n d seri o us li ver i nj ur y , c o m m o nl y referre d t o as dr u g-i n d uce d li ver i nj ur y 
( DI LI).  S u bjects w h o e x perie nce a tra nsa mi nase ele vati o n a b o ve 3 ti mes t he u p per limit of
n or mal ( × U L N) s h o ul d be m o nit ore d m ore fre q ue ntl y  t o deter mi ne if t he y are a n “a da pt or” 
or are “s usce pti ble.”
I n t he maj orit y of DI LI cases, ele vati o ns i n as partate a mi n otra nsferase ( A S T) a n d/ or ala ni ne 
a mi notra nsferase ( A L T) prece de t otal bilir u bi n ( T Bi li) ele vati o ns ( > 2 × U L N) b y  se veral 
da y s or wee ks.  T he i ncrease i n T Bili t ypicall y occ urs w hile A S T/ A L T is/are still ele vate d 
a b o ve 3 × U L N (ie, A S T/ A L T a n d T Bili val ues will be ele vate d wit hi n t he sa me la b sa m ple).  
I n rare i nsta nces, b y t he ti me T Bili ele vati o ns are dete cte d, A S T/ A L T val ues mi g ht ha ve 
decrease d.  T his occ urre nce is still re gar de d as a p ote ntial DI LI.  T heref ore, a b n or mal 
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are c o nsi dere d p ote n tial DI LI (assesse d per Hy’s la w criteria) cases a n d s h o ul d al wa ys be 
c o nsi dere d i m p orta nt me dical e ve nts, e ve n bef ore all ot her p ossi ble ca uses of li ver i nj ur y 
ha ve bee n e xcl u de d.
T he t hres h ol d of la b orat or y  a b n or malities f or a p o te ntial DI LI case de pe n ds o n t h e s u bject’s 
i n di vi dual baseli ne val ues a n d u n derl yi n g c o n diti o ns.  S u bjects w h o prese nt wit h t he 
f oll o wi n g la b orat or y a b n or malities s h o ul d be e val uate d f urt her as p ote ntial DI LI ( H y’s la w)
cases t o defi niti vel y deter mi ne t he eti ol o g y of t he a b n or mal la b orat or y val ues:

S u bjec ts wit h A S T/ A LT a n d T Bili baseli ne val ues wit hi n t he n or mal ra n ge w h o 
s u bse q ue ntl y prese nt wit h A S T O R A L T val ues > 3 × U L N A N D a T Bili val ue 
> 2 × U L N wit h n o e vi de nce of he m ol ys is a n d a n al kali ne p h os p hatas e val ue 
< 2 × U L N or n ot a vaila b le;

F or s u bjects wi t h baseli ne A S T O R A L T O R T Bili val ues a b o ve t he U L N, t he 
f oll o wi n g t hres h ol d val ues are use d i n t he defi niti o n me nti o ne d a b o ve, as nee de d, 
de pe n di n g o n w hic h val ues are a b o ve t he U L N at bas eli ne:

Pree xisti n g A S T or A L T baseli ne va l ues ab o ve t he n or mal ra n ge: A S T or A L T 
val ues > 2 ti mes t he baseli ne val ues A N D > 3 × U L N; or > 8 × U L N ( w hic he ver is 
s maller).

Pree xisti n g val ues of T Bili a b o ve t he n or mal ra n ge: T Bili le vel i ncr ease d fr o m 
baseli ne v al ue b y a n a m o u nt of at least 1 × U L N or if t he val ue reac hes > 3 × U L N 
( w hic he ver is s maller).
Rises i n A S T/ A L T a n d T Bili se parate d b y m ore t ha n a fe w wee ks s h o ul d be assesse d 
i n di vi d uall y base d o n cli nical j u d g me nt; a n y case w here u ncertai nt y re mai ns as to w het her it 
re prese nts a p ote ntial H y’s la w case s h o ul d be re vie we d wit h t he s p o ns or.
T he s u bject s h o ul d ret ur n t o t he i n vesti gat or site a n d be e val uate d as s o o n as p ossi ble, 
prefera bl y wit hi n 4 8 h o urs fr o m a ware ness of t he a b n or mal r es ults.  T his e val uat i o n s h o ul d 
i ncl ude la b orat or y  tests, detaile d hist or y, a n d p h ysical assess me nt. 
I n a d diti o n t o re peati n g meas ure me nts of A S T a n d A LT a n d T Bili, la b orat or y  tests s h o ul d 
i ncl u de al b u mi n, creati ne ki nase ( C K), direct a n d i n direct bilir u bi n, ga m ma-gl uta m yl  
tra nsferase ( G G T), pr ot hr o m bi n ti me ( P T)/i n ter nati o nal n or malize d rati o (I N R), t otal bile 
aci ds, al kali ne p h os p hatase a n d aceta mi n o p he n dr u g a n d/ or pr otei n a d d uct le vels.  
C o nsi derati o n s h o ul d als o be gi ve n t o dra wi n g a se parate t u be of cl otte d bl o o d a n d a n 
a ntic oa g ulate d t u be of bl o o d f or f urt her testi ng, as nee de d, f or f urt her c o nte m p ora ne o us 
a nal ys es at t he ti me of t he rec o g nize d i nitial a b n or malities t o deter mi ne eti ol o g y .  A detaile d 
hist or y , i ncl u di n g rele va nt i nf or mati o n, s uc h as re vie w of et ha n ol, aceta mi n o p he n (eit her b y 
itself or as a c o-for m ula te d pr o d uct i n prescri pti o n or o ver-t he-c o u nter me dicati o ns) , 
recreati o nal dr u g, s u p ple me nt ( her bal) use a n d c o ns u m pti o n, fa mil y hist or y, se x ual hist or y, 
tra vel hist or y, hist or y of c o ntact wit h a ja u n dice d per s o n, s ur ger y, blo o d tra nsf usi o n, hist or y  
of li v er or aller gic disease, a n d p ote ntial occ u pati o nal e x p os ure t o c he micals, s h o ul d be 

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c ollecte d.  F urt her testi n g f or ac ute he patitis A, B, C, D, a n d E i nfecti o n a n d li ver i ma gi n g 
(e g, biliar y tract) ma y be warra nte d. 
All case s de m o nstrate d o n re peat testi ng as meeti n g t he la b orat or y  criteria of A S T/ A LT a n d 
T Bili ele vati o n defi ne d a b o ve s h o ul d be c o nsi dere d p ote ntial DI LI ( H y ’s la w) cases if n o 
ot her reas o n f or t he li ver f u ncti o n test ( L F T) a b n or malities has yet bee n f o u n d.  S u c h 
p ote nti al DI LI ( H y’s l a w) c a ses are t o be re p orte d as S A Es, irres pecti ve of a v ail a bilit y 
of all t he res ults of t he i n vesti g ati o ns perf or me d t o deter mi ne eti ol o g y of t he L F T 
a b n or m alities.
A p ote ntial DI LI ( H y ’s la w) case bec o mes a c o nfi r me d case o nly a fter all res ults of 
reas o na ble i n vesti gati o ns ha ve bee n recei ve d a n d ha ve e xcl u de d a n alter nati ve eti ol o g y .
8. 4. 3. E x p os ure t o t he I n vesti g ati o n al Pr o d uct D uri n g Pre g n a nc y or Bre astfee di n g, a n d 
Occ u p ati o n al E x p os ure
E x p os ure t o t he i n vesti gati o nal pr o d uct u n der s t u d y d uri n g pre g na ncy or breast fee di n g a n d 
occ u pat i o nal e x p os ure are re p orta ble t o Pfizer Safet y wit hi n 2 4 h o urs of i n vesti gat or 
a ware ness.
8. 4. 3. 1. E x p os ure D uri n g Pre g n a nc y
F or b ot h u na p pr o ve d/ u nlice nse d pr o d ucts a n d f or mar ke te d pr o d ucts, a n e x p os ure d uri n g 
pre g na nc y  ( E D P) occ urs if:

A fe male bec o mes, or is f o u n d t o be, pre g na nt eit her w hile recei vi n g or ha vi n g bee n 
e x p ose d (e g, beca use of treat me nt or e n vir o n me ntal e x p os ure) t o t he i n vesti gati o nal 
pr o d uct; or t he fe male bec o m es or is f o u n d t o be pre g na nt after d isc o nti n ui n g a n d/ or 
bei n g e x p os e d t o t he i n vesti ga ti o nal pr o d uct;

A n e xa m ple of e n vir o n me ntal e x p os ure w o ul d be a case i n v ol vi n g direct c o ntact 
wit h a Pfizer pr o d uct i n a pre g na nt w o ma n (e g, a n urse re p orts t hat s he is pre g na nt 
a n d has bee n e x p ose d t o c he m ot hera pe utic pr o d uct s);

A male has bee n e x p ose d (e g, beca use of treat me nt or e n vir o n me ntal e x p os ure) t o t he 
i n vesti gati o nal pr o d uct pri or t o or ar o u n d t he ti me of c o nce pti o n a n d/ or is e x p ose d 
d uri n g his part ner’s pre g na n c y . 
If a s u bject or s u bject’s part ner bec o mes or is f o un d t o be pr e g na nt d uri n g t he s u bject’s 
treat me nt wit h t he i n vesti gati o nal pr o d uct, t he i n vesti gat or m ust re p ort t his i nf or mati o n t o 
Pfizer Safet y  o n t he C T S A E Re p ort F or m a n d a n E D P s u p ple me ntal f orm, re gar dless of 
w het her a n S A E has o cc urre d.   I n a d diti o n, t he i n vesti gat or m ust s u b mit i nf or mati o n 
re gar di n g e n vir o n me ntal e x p os ure t o a Pfizer pr o d uct i n a pre g na nt w o ma n (e g, a s u bject 
re p orts t hat s he is pre g na nt a n d has bee n e x p ose d t o a c yt ot o xic pro d uct b y i n halati o n o r 
s pilla ge) t o Pfizer Safet y usi n g the E D P s u p p le me ntal f or m.  T his m ust be d o ne irres pecti ve 
of w het her a n A E has occ urre d a n d wit hi n 2 4 h o urs of a ware ness of t he e x p os ure.  T he 
i nf or mati o n s u b mitte d s h o ul d i ncl u de t he a ntici pate d date of deli ver y (see bel o w f or 
i nf or mati o n relate d t o ter minati o n of p re g na nc y).

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F oll o w - up is c o n d ucte d t o o btai n ge neral i nf or mati o n o n t he pre g na nc y  a n d its o utc o me f or 
all E D P re p orts wit h a n u n k n o w n o utc o me.  T he i n vesti gat or will f oll o w t he pre g na nc y  u ntil 
c o m pleti o n ( or u ntil pre g na nc y ter mi nati o n) a n d n otify Pfizer Sa fety of t he o utc o me as a 
f oll o w- u p t o t he i nitial E D P s u p ple me ntal f or m.  I n t he case of a li ve birt h, t he str uct ural 
i nte grity of t he ne o nate ca n be assesse d at t he ti me of birt h.  I n t he e ve nt of a ter mi nati o n, t he 
reas o n(s) f or ter mi nati o n s ho ul d be s pe cifie d a n d, if cli n icall y p ossi ble, t he str uct ural 
i nte grity of t he ter mi nate d fet us s h o ul d be assesse d b y gr oss vis ual i ns pecti o n ( u nless 
pre -pr oce d ure test fi n di n gs are c o ncl usi ve f or a c o n ge nital a n o mal y a n d t he fi n di n gs a re 
re p orte d).
If t he o utc o me of t he pre g na nc y meets t he criteria f or a n S A E (ie, ect o pic pre g na nc y, 
s p o nta ne o us a b orti o n, i ntra uteri ne fetal de mise, ne o natal deat h, or c o n ge nital a n o mal y [i n a 
li ve-b or n ba b y, a ter mi nat e d fet us, a n i ntra ute ri ne fetal de mise, or a ne o natal deat h]), t he 
in vesti gat or s h o ul d f oll o w t he pr oce d ures f or re p orti n g S A Es.
A d diti o nal i nf or mati o n a b o ut pre g na nc y  o utc o mes t hat are re p orte d t o Pfizer Safety as S A Es 
f oll o ws: 

S p o nta ne o us a b orti o n i ncl u des miscarria ge a n d m isse d a b orti o n;

Ne o natal deat hs t hat occ ur wit h i n 1 m o nt h of birt h s h o ul d be re p orte d, wit h o ut re gar d 
t o ca usalit y, as S A Es.  I n a d diti o n, i nfa nt deat hs after 1 m o nt h s h o ul d be re p orte d as 
S A Es w he n t he i n vesti gat or assesses t he i nfa nt deat h as relate d or p ossi bl y  relate d t o 
e x p os ure t o t he i n vesti gatio nal pr o d uct;
A d dit i o nal i nf or mati o n re gar di n g t he E D P ma y be re q ueste d b y t he s p o ns or.  F urt her 
f oll o w- u p of birt h o utc o mes will be ha n dle d o n a case-b y -case basis (e g, f oll o w- u p o n 
prete r m i nfa nts t o i de ntify de vel o p me ntal dela y s).  In t he cas e of pater n al e x p os ure, t he 
i nvesti gat or will pr o vi de t he s u bject wit h t he Pre g na nt Part ner Release of I nf or mati o n F or m 
t o deli ver t o his part ner.  T he i n vesti gat or m ust d oc u me nt i n t he s o urce d oc u ments t hat t he 
s u bject was gi ve n t he Pr e g na nt Part ner Relea se of I nf ormati o n F or m t o pr o v i de t o his 
part ner.
8. 4. 3. 2. E x p os ure D uri n g Bre astfee di n g
Sce nari os of e x p os ure d uri n g breastfee di n g m ust be re p orte d, irres pecti ve of t he prese nce of 
a n ass ociate d S A E, t o Pfiz er Safet y wit hi n 2 4 h o urs of t he i n vesti gat or’s a ware ness, usi n g t he
C T S A E Re p ort F or m .  A n e x p os ure d uri n g breastfee di n g re p ort is n ot create d w he n a Pfizer 
dr u g s pecificall y  a p pr o ve d f or use i n breastfee di n g w o me n (e g, vita mi ns) is a d mi nistere d i n 
acc ord wit h a ut h orize d use .  H o we ver, if the i nfa nt e x perie nces a n S A E as s ociate d wit h s uc h 
a dr u g’s a d mi nistrati o n, t he S A E is re p orte d t o get her wit h t he e x p os ure d uri n g breastfee di n g.
8. 4. 3. 3. Occ u p ati o n al E x p os ure
A n occ u pati o nal e x p os ure occ urs w he n, d uri n g t he perf or ma nce of j o b d uties , a pers o n 
(w het her a healt hcare pr ofessi o nal o r ot her wise) gets in u n pla n ne d direct c o ntact wit h t he 
pr o d uct, w hic h ma y  or ma y n ot lea d t o t he occ urre nce of a n A E.

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A n occ u pati o nal e x p os ure is re p orte d t o Pfizer Safet y  wit hi n 2 4 h o urs of t he i n vesti gat or’s
a ware ness, usi n g t he C T S A E Re p ort F or m, re gar dless of w het her t h ere is a n ass ociate d 
S A E.  Si nce t he i nf or mati o n d oes n ot pertai n t o a s u bject e nr olle d i n t he st u d y , t he 
i nf or mati o n is n ot rec or de d o n a C R F; h o we ver, a c o p y of t he c om plete d C T S A E Re p ort
F or m is mai ntai ne d i n t he i n vesti gat or site fi le.
8. 4. 4. Me dic ati o n Err o rs 
Ot her e x p os ures t o t he i n vesti gati o nal pr o d uct u n der st u d y  m a y occ ur i n cli nical trial setti n gs, 
s uc h as me dicati o n err ors.
S afet y E ve nt
Rec or de d o n t he C R F
Re p orte d o n t he C T S A E 
Re p ort F or m t o Pfi zer 
S afet y Wit hi n 2 4 H o urs of 
A w are ness
Me dicati o n er r ors
All (re gar dless of w het her 
ass ociate d wit h a n A E)
O nl y  if ass ociate d wit h a n 
S A E
8. 4. 4. 1. Me dic ati o n Err ors
Me dicati o n err ors ma y  res ult fr o m t he a d mi nistrati o n or c o ns u m pti o n of t he i n vesti gati o nal 
pr o d uct b y t he wr o n g s u bject, or at t he wr o n g ti me, or at t he wr o n g d osa ge stre n gt h. 
Me dicati o n err ors i ncl u de :

Me dicati o n err ors i n v ol vi n g s u bject e x p os ure t o t he i n vesti gati o nal pr o d uct;

P ote ntial me dicati o n err ors or uses o ut si de of w hat is f oresee n i n t he pr ot o c ol t hat d o 
or d o n ot i n v ol ve t he partici pati n g s u bject;

Refer t o Secti o n 5. 4 f or e xa m ples of me dicati o n err ors relate d t o c o m plia nce wit h 
i n vesti gati o nal pr o d uct.
S uc h me dicati o n err ors occ urr i n g t o a st u d y partici pa nt are t o be ca pt ure d o n t he me dicati o n 
err or pa ge of t he C R F, w hic h is a s pecific versi o n of t he A E pa ge.
I n t he e ve nt of a me dicati o n d osi n g err or, t he s p o ns or s h o ul d be n otifie d i m me diatel y.
W het her or n ot t he me d icati o n err or is acc o m pa nie d b y a n A E, as determi ne d b y  t he 
i n vesti gat or, t he me dicati o n err or is rec or de d on t he me dicati o n err or pa ge of t he C R F a n d, if 
a p plica ble, a n y ass ociate d A E(s), seri o us a n d n o n -seri o us, are rec or de d o n a n A E pa ge of t he 
C R F.
M e dicati o n err ors s h o ul d be re p orte d t o Pfizer Safet y wit hi n 2 4 h o u rs o n a C T S A E Re p ort 
F or m o nl y w he n ass oc i ate d wit h a n S A E.

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9. D A T A A N A L Y SI S/ S T A TI S TI C A L M E T H O D S
Detaile d met h o d ol o g y  f or s u m mar y a n d statistical a nalys es of t he data c oll ecte d i n t his st u d y 
is o utli ne d here a n d f urt her detaile d i n a stati stical a nalys is plan ( S A P), w hic h will be 
mai ntai ne d b y  t he s p o ns or.  T he S A P ma y m o dif y w hat is o utli ne d i n t he pr ot oc ol w here 
a p pr o priate; h o we ver, a n y maj or m o dificati o ns of t he c o-pri m ar y e n d p oi nt defi niti o ns or t heir 
a nal yses will als o be reflecte d i n a pr ot oc ol a me n d ment.
9. 1. S a m ple Size Deter mi n ati o n
A t otal of 6 0 0 s u bjects wit h 2 0 0 recei vi n g P F-0 4 9 6 5 8 4 2 2 0 0 m g Q D, 2 0 0 recei vi n g 
P F - 0 4 9 6 5 8 4 2 1 0 0 m g Q D, a n d 2 0 0 recei vi n g place b o ( 1: 1: 1 ra nd o mizati o n) will pr o v i de 
9 4 % p o wer t o detect a rati o of me dia n ti me t o flare of at least 1. 5 ti mes bet wee n eit her d ose 
of P F -0 4 9 6 5 8 4 2 ( 2 0 0 m g or 1 0 0 m g) a n d place b o.  T he T y pe I err or rate is set at
5 % ( 2-si de d).  Ass u mi n g base d o n pri or data, t hat a b o ut 44 % of s u bjects w o ul d meet t he 
pr ot oc o l- defi ne d criteria t o be a res po n der at Wee k 1 2, a p pr o xi matel y  1 3 7 0 s u bjects w o ul d 
nee d t o e nter t he o pe n la bel r u n -i n peri o d of t he st u d y t o e ns ure t hat 6 0 0 s u bjects are 
a vaila ble f or ra n d o mizati o n.
9. 2. Effic ac y A n al ysis
9. 2. 1. A n al ysis Sets 
T he sta tistical o bjective of t he st u d y  is t o c haracterize t he l oss of res p o nse wit h eac h 
ra n d o mize d gr o u p after ac hie vi n g res p o nse at Wee k 1 2 f oll o wi n g o pe n -la bel treat me nt wit h 
2 0 0 m g P F - 0 4 9 6 5 8 4 2 Q D. 
T he pri mar y  a nalys is p o p ulati o n f or efficac y data will be t he F ull A nal ys is Set ( F A S -R A) 
defi ne d as all ra n d o mize d s u bjects w h o are dis pe nse d at least o ne d ose of st u d y  me dicati o n.  
T his is a res p o n der -e nric he d p o p ulati o n w h o are eli gi ble t o e nter t he ra n d o mize d, 
d o u ble -bli n d peri o d of t he st u d y .  All a nal yses will be re p orte d b y t reat me nt 
re gi me n/se q ue nce.  T he pri mar y  efficac y en d p oi nt a n d t he ke y  seco n dar y  efficac y e n d p oi nts 
will als o be a nal yz e d f or t he Per-Pr ot oc ol A nal ys is Set ( P P A S) defi ne d as a s u bset of 
F A S - R A w h o ha d n o maj or pr ot oc ol vi olati o ns.  Maj or pr o t oc ol vi olati o ns w o ul d c o nsist of 
n ot meeti n g i nclusi o n criteria or meeti n g a n e xcl usi o n crtieria or n ot ha vi n g ta ke n t he c orrect 
ra n d o mize d treat me nt f or at least 8 0 % of t he assi g ne d a m o u nt or ha vi n g ta ke n a pr o hi bite d 
c o nc o mita nt me dicati o n (as detaile d i n Secti o n 5. 9. 2 ) or a ny ot her maj or pr ot oc ol vi olati o n as 
deter mi ne d b y t he cli nical tea m or me dical m o nit or pri or t o data base l oc k. T he s u b jects 
e xcl u de d fr om t he P P A S will be deter mi ne d a n d d oc u me nte d bef ore t he st u d y  is u n- bli n de d.  
F or all a nal y ses, baseli ne val ue will be base d o n o bser vati o ns c ollecte d pre-d ose.
A n a d diti o nal s u b gr o u p of s u bjects w h o ha ve recei ve d at least o ne d ose of resc ue treat me nt 
(f oll o wi n g a pr ot oc ol-defi ne d flare d uri n g t he ra n d o mize d, d o u ble -bli n d peri o d) will als o be 
defi ne d as t he F A S -R E s u b gr o u p.  I n a d diti o n t o t hese s u b gr o u ps, a nal yses will als o be 
perf or me d f or all s u bjects parti ci pati n g i n t he o pe n -la bel r u n-i n peri o d ( defi ne d as t he 
F A S -O L s u b gr o u p).

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9. 2. 2. Testi n g Pr oce d ure f or M ulti ple C o m p aris o ns
T here are si x ke y  h yp ot heses t o be teste d f or eac h pair wise c o m paris o n bet wee n t w o 
P F -0 4 9 6 5 8 4 2 d oses ( 2 0 0 m g Q D a n d 1 0 0 m g Q D) a n d place b o , f or t he pri mary a n d ke y 
sec o n dar y e n d p oi nts. F or t hese h y p ot hes es, t he fa mil ywise T y pe- I err or rate will be str o n gly 
c o ntr olle d at 5 % usi n g a se q ue ntial, gate kee pi n g pr oce d ure. 
T he pr oce d ure will first test t he h y p ot hesis of n o dif fere nce f or t he pri mar y e n d p oi nt bet w ee n
2 0 0 m g Q D a n d place b o at 5 % le vel of si g nificance. If t his hy p ot hesis is rejecte d, statistical 
si g nifica nce will be assesse d f or t he hy p ot hesis of n o differe nce f or t he ke y sec o n dar y 
e n d p oi nt bet wee n 2 0 0 m g  Q D a n d place b o at 5 % le vel o f si g nifica nce. If rejected, t he 
pr oce d ure wil l c o nti n ue wit h t he h y p ot hesis of n o differe nce f or t he pri mar y  e n d p oi nt 
bet wee n 1 0 0 m g  Q D a n d place b o a n d if rejecte d, c o nti n ui n g wit h t he hy p ot hesis of n o 
differe nce bet wee n 1 0 0 m g Q D a n d place b o f or t he ke y sec o n dar y e n d p oi nt. Fi nal l y, if all 
t he a b o ve h y p ot heses are rej ecte d, t he pr oce d ure will c o nti n ue wit h t he h y p ot hesis of n o 
differe nce bet wee n 2 0 0 m g Q D a n d 1 0 0 m g Q D f or t he pri mar y  e n d p oi nt a n d if rejecte d, 
c o nti n ui n g wit h t he h y p ot hesis of n o differe nce bet wee n 2 0 0 m g  Q D a n d 10 0 m g Q D f or t he 
ke y sec o n dar y e n d p oi nt. All tests will be c o n d ucte d at 5 % le vel of si g nifica nce.  Statistical 
si g nifica nce f or s u bse q ue nt tests will n ot be f or mall y clai me d if t he pre vi o us h yp ot hesis has 
n o t bee n rejecte d.
H y p o t heses f or all ot her e n d p oints n ot descri be d he re are t o be teste d at t he n o mi nal
5 % le vel, wit h o ut ma ki n g a dj ust me nts f or m ulti ple c o m paris o ns.
9. 2. 3. A n al ysis of t he Pri m ar y a n d Ke y Sec o n d ar y E n d p oi nts 
T he pri mar y  a nalys es f or b ot h e n d p oints will be base d o n t he F A S -R A s u b set.  Sec o n dar y 
a nal ys es will be base d o n t he P P A S. F or a nal ys is of t he pri mar y a n d ke y sec o n dar y 
e n d p oi nts, a c o m bi nati o n of gra p hical a n d a nal ytical met h o ds will be use d.  T he ti me 
(i n wee ks) t o pr ot oc ol -defi ne d flare will be use d t o e val ua te t he pri mar y en d p oi nt w hile t he 
ti me (i n weeks) t o ac hie ve a n IG A sc ore of 2 will be use d t o e val uate t he ke y  sec o n dar y 
e n d p oi nt.  S u bjects w h o d o n ot re p ort a n e ve nt (ie pr ot oc ol-defi ne d flare or I G A 2) or 
disc o nti n ue t he st u d y  duri n g t he d o u ble- bli n d ra n d o mize d peri o d will ha ve t heir ti me t o e vent 
ce ns ore d at t heir last k n o w n visit i n t his peri o d.  Ka pla n-Meier c ur ves will be use d t o dis pla y  
t he ti me t o e ve nt a n d re p ort t he me dia n ti me t o e ve nt (a n d its 9 5 % c o nfi de nce i nter val) 
am o n g t he t hree ra n d o mi ze d gr o u ps.  T h e l o g-ra n k test will be use d t o c o m pare t hese c ur v es.  
Pr o p orti o ns of s u bjects wit h a n e ve nt a n d c o nfi de nce i nter vals will als o be re p orte d b y  
ra n d o mize d gr o u p.
9. 2. 4. A n al ysis of Sec o n d ar y E n d p oi nts
I n ge neral, bi nar y e n d p oi nts (s uc h as E A SI- 5 0, EA SI -9 0 or t he p ro p orti o n of s u bjects 
ac hie vi n g 4 p oi nt i m pr o ve me nt i n se verit y of pr urit us N R S meas ure) will be a nal yz e d usi n g 
t he ( C oc hra n-Ma ntel -Hae nszel) test a dj uste d b y  ra n d o mizati o n strata (a ge gr o u ps) a n d 
baseli ne disease se ve rity .  T he differe nce bet wee n treat ment gr o u ps i n t he pr o p orti o n of 
s u bjects ac hie vi n g a res p o nse al o n g wit h its 9 5 % c o nfi de nce i nter val ( usi n g t he n or mal 
a p pr o xi mati o n f or t he differe nce i n bi n o mial pr o p orti o ns) will be re p orte d.  If a s u bject 
wit h dra ws f r o m t he st u d y, t he n t his s u bject will be c o u nte d as a n o n -res p o n der f or e n d p oi nts 

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after wit h dra wal.  I n a d diti o n, a s u bject i n t he F A S-R A s u b set w h o recei ves resc ue treat me nt 
d ue t o pr ot oc ol - defi ne d flare will be c o nsi dere d a n o n -res p o n der.
F or c o nti n u o us e n d p oi nts, s uc h as per ce nt c ha n ge fr o m baseli ne i n t he E A SI t otal sc ore a n d 
B S A or c ha n ge fr o m baseli ne i n S C O R A D, P S A A D, D L QI/ C D L QI, P O E M, H A D S, a n d 
c ha n ge fr o m baseli ne i n t he pr urit us se verit y usi n g t he N R S meas ure , a mi xe d-effect m o del 
wit h re peate d me as ures ( M M R M) will be use d.  T his m o d el will i ncl u de t he fact ors (fi xe d 
effects) f or treat me nt gr o u p, ra n d o mizati o n strata (a ge gr o u ps ), a n d baseli ne disease se verit y,
visit, treat me nt -b y - visit i nteracti o n, a n d rele va nt baseli ne val ue.  Wit hi n t he fra me w ork of 
M M R M, differe nces
bet wee n gr o u ps will be teste d usi n g esti mates fr o m t he M M R M m o del.
F or all bi nar y  e n d p oi nts, missi n g data will be ha n dle d b y c o nsi deri n g s u bjects w h o w it h dra w 
or ra n d o mize d s u bjects recei vi n g resc ue treat me nt as n o n-res p o n ders. N o i m p utati o ns will 
be ma d e f or c o nti n u o u s data a n d missi n g data will be c o nsi dere d t o be M A R.
I n ge neral all sec o n dar y e n d p oi nts will be a nal yse d f or t he F A S-R A s u b set.  F or t he s u bjects 
re q uiri n g resc ue t hera py ( F A S-R E s u b set), t he res p o nse ac hie ve d at t he en d of t he resc ue 
peri o d will be asses se d i n relati o n t o t he start of t he resc ue peri o d.  I n a d diti o n t o t hese t w o
a nal ys is sets, sec o n dar y e n d p oi nts will als o be s u m marize d f or all s u bjects partici pati n g i n 
t he o pe n-la bel r u n-i n peri o d ( F AS- O L s u b set).
H y p ot heses f or all rele va nt sec o n dar y e nd p oi nts will be teste d at t he n o mi nal 5 % le vel of 
si g nifica nce, wit h o ut a dj ust me nts f or m ulti ple c o m paris o ns.
9. 3. S afet y A n al ysis
T he safet y data will be s u m marize d i n acc or da nce wit h Pfizer Dat a Sta n dar ds.  All s u bjects 
w h o recei ve i n vesti gati o nal pr o d uct (sa fety p o p ulati o n) will be i ncl u de d i n t he safet y 
a nal ys es.  All safet y data will be s u m marize d descri pti vel y t hr o u g h a p pr o priate data 
ta b ulati o ns, descri pti ve statistics, cate g orical s u m maries, a n d gra p hical prese ntati o ns.  Safet y 
e n d p oi nts for t he st u d y i ncl u de:

Treat me nt -e mer ge nt A Es a n d S A Es;

Wit h dra wals fr o m acti ve treat me nt d ue t o A Es;

Seri o us i nfecti o ns, defi ne d as a n y i nfecti o n ( viral, bacterial, a n d f u n gal) re q uiri n g 
h os pitalizati o n or pare nteral a nti micr o bials or meets ot her criteria t hat re q uire it t o be
classifie d as a seri o us a d vere e ve nt, will be s u m marize d;

Safet y  la b orat or y tests (e g, he mat ol o g y [i ncl u di n g c oa g ulati o n pa nel], c he mistr y a n d 
li pi d pr ofiles);

Vital si g ns;

E C G para meters if a p plica ble.

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C ha n ge fr o m baseli ne o n la b orat or y data a n d vi tal sig ns will be a d diti o nall y s u m marize d.
S u bject listi n gs will als o be pr o d uce d f or t hese safet y  e n d p oi nts.
All safet y data will be s u m marize d se paratel y f or eac h of t he f oll o wi n g ke y s u b gr o u ps:

S u bjects w h o ha ve rece i ve d at least o ne d ose o f st u d y dr u g d uri n g t he o pe n la bel 
r u n-i n peri o d.  T hese s u bjects w o ul d ha ve a c u m ulati ve e x p os ure t o 2 0 0 m g Q D 
P F - 0 4 9 6 5 8 4 2 of u p t o 1 2 wee ks;

S u bjects w h o ha ve bee n ra n d o mize d a n d ha ve recei ve d at least o ne d ose of 
ra n d o mize d st u d y treat me nt.  S u m maries o f safety data will be re p orte d f or t hese 
s u bjects b y ra n d o mize d treat me nt re gi me n;

S u bjects w h o meet l oss of res p o nse criteria d uri n g t he ra n d o mize d, d o u ble -bli n d 
peri o d a n d recei v e at least o ne d ose of resc ue treat me nt.  S u m maries of safet y  data 
will be re p orte d f or these s u bjects b y  ra n d o mize d treat me nt re gi me n.
9. 4. A n al ysis of P h ar m ac o ki netic E n d p oi nts 
P o p ulati o n P K data f or P F- 0 4 9 6 5 8 4 2 will be s u m marize d t hr o u g h a p pr o priate data 
tab ulati o ns, descri pti ve statistics, a n d gra p hical prese ntati o n.  A p o p ulati o n P K m o del wil l be 
d e vel o pe d f or t he p ur p ose of esti mati n g P K para meters.  A d diti o nal details of t he 
met h o d ol o g y  will be ca pt ure d i n a se parate m o deli n g pla n a n d t he res ults will als o be 
re p orte d se parately.
9. 5. E xter n al D at a M o nit ori n g C o m mittee 
T his st u d y  wi ll use a n e xter nal data m o nit ori n g c o m mittee ( E -D M C ).  T he E-D M C will be 
res p o nsi ble f or o n g oi n g m o nit ori n g of t he efficac y, safety a n d P Ks of s u bjects i n t he st u d y 
acc or di n g t o t h e c harter.  T he rec o m me n dati o ns ma de b y  t he E-D M C t o alter t he c o n d uct of 
t he st u d y will be f or war de d t o Pfizer f or fi nal decisi o n.  Pfizer will f or war d s uc h decisi o ns, 
w hic h ma y  i ncl u de s u m maries of a g gre gate a nal yses of e n d p oi nt e ve nts a n d of safety data
t hat are n ot e n d p oi nts, t o re g ulat or y a ut h orities, as a p pr o priate.  C o m p o siti o n of t he E-D M C 
an d pr ocesses u n der w hic h t he E -D M C o perates will be d oc u me nte d i n t he E -D M C c harter.
9. 6. S afet y A dj u dic ati o n C o m mittees
T o hel p assess t he s pecific, c o m ple x safet y e ve nts relate d t o mali g na ncies, car di o vasc ular 
e ve nts, a n d o p p ort u nistic i nfecti o n (i ncl u di n g ecze ma her petic u m a n d ot her i nfecti o ns of 
s pecial i nterest) i n t his st u d y, Safety A dj u dicati o n C o m mittees, c o nsisti n g of cli nical e x perts 
i n eac h of t he rele va nt cli nical areas, will be set u p t o har m o nize a n d sta n dar dize 
assess me nts.  In or der t o all o w f or a n u n biase d safet y assess me nt, t he me m bers of t hese 
c o m mittees will be bli n de d t o treat me nt assi g n me nt.  F urt her i nf or mati o n a b o ut t he Safet y  
A dj u dicati o n C o m mit tees ca n be f o u n d i n t heir res pecti ve c harters, i nclu di n g a s pecific 
descr i pti o n of t he sc o pe o f t heir res p o nsi bilities, a pla n w here c o m m u nicati o n ti meli nes are 
defi ne d, a n d t he e xact pr ocess a n d defi niti o ns use d b y  eac h c o m mittee t o a dj u dicate t he 

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safety e ve nts t hat t he y will a dj u dicate.  Ot her safet y  e vents f or a dj u dicati o n m a y be i de ntifie d 
a n d i ncl u de d i n t he re mit of t he Safety A dj u dicati o n C o m mittees as a p pr o priate.
1 0. Q U A LI T Y C O N T R O L A N D Q U A LI T Y A S S U R A N C E
Pfizer or its a ge nt will c o n d uct peri o dic m o nit ori n g visits d uri n g st u d y c o n d uct t o e ns ure t hat 
t he pr ot oc ol a n d G o o d Cli ni cal Practices ( G C Ps) are bei n g f oll o we d.  T he m o nit ors ma y 
re vie w s o urce d oc u me nts t o c o nfir m t hat t he data rec or de d o n C R Fs are acc urate.  T he 
i n vesti gat or a n d i nstit uti o n will all o w Pfizer m o nit ors/a u dit ors or its a ge nts a n d a p pr opriate 
re g ulat or y a ut hor ities direct access t o s o urce d oc u me nts t o perf or m t his verificati o n.  T his 
verificati o n ma y  als o occ ur after st u d y c o m pleti o n.
D uri n g st u d y c o n d uct a n d/ or after st u d y c o m pleti o n, t he i n vesti gat or site ma y be s u bject t o 
re vie w by t h e I RB/ E C, a n d/ or t o q u alit y ass ura nce a u dits perf or me d by Pfizer, or c o m pa nies 
w or ki n g wit h or o n be half of Pfizer, a n d/ or t o i ns pecti o n b y  a p pr o priate re g ulat or y 
a ut h orities.
T he i n vesti gat or(s) will n ot if y Pfizer or its a ge nts i m me diatel y of a n y re g ulat or y i ns pecti o n 
n otifica tio n i n relati o n t o t he st u d y .  F urt her m ore, t he i n vesti gat or will c o o perate wit h Pfizer 
or its a ge nts t o pre pare t he i n vesti gat or site f or t he i ns pecti o n a n d will all o w Pfizer or it s 
a ge nt, w he ne ver feasi ble, t o be prese nt d uri n g t he i ns pecti o n.  T he i n vesti gat or site an d 
i n vesti gat or will pr o m ptl y res ol ve a n y discre pa ncies t hat are i de ntifie d bet wee n t he st u d y 
data a n d t he s u bject's me dical rec or ds.  T he i n vesti gat or will pr o m ptl y p r o vi de c o pies of t he 
i ns pecti o n fi n di n gs t o Pfizer or its a ge nt.  Bef ore resp o nse s u b miss i o n t o t he re g ulat or y 
a ut h orities, t he i n vesti gat or will pr o vi de Pfizer or its a ge nts wit h a n o p p ort u nit y  t o re vie w 
a n d c o m me nt o n res p o nses t o a n y  s uc h fi n di n gs.
It is i m p orta nt t hat t he i n vesti gat or(s) a n d t heir rele va nt pers o n nel are a vai l able d uri n g t h e 
m o ni t ori n g visits a n d p ossi ble a u dits or i ns pecti o ns a n d t hat s ufficie nt ti me is de v ote d t o t he 
pr ocess.
1 1. D A T A H A N D LI N G A N D R E C O R D K E E PI N G
1 1. 1. C ase Re p ort F or ms ( C R F)/ D at a C ollecti o n T o ols ( D C Ts)/ Electr o nic D at a Rec or d
As use d i n t his pr ot oc ol, t he ter m C R F/ D C T s h o ul d be u n derst o o d t o refer t o eit her a pa per 
f or m or a n electr o nic data rec or d or b ot h, de pe n di n g o n t he data c ollecti o n met h o d use d i n 
t his st u d y.
A C R F/ D C T is re q uire d a n d s h o ul d be c o m plete d f or eac h i ncl u de d su bject.  T he c o m plete d
o ri gi nal C R Fs/D C Ts a re t he s ole pr o perty of Pfizer a n d s h o ul d n ot be ma de a vaila ble i n a n y 
f or m t o t hir d parties, e xce pt f or a ut h orize d re prese ntati ves of Pfizer or a p pr o priate re g ulat or y 
a ut h orities, wit h o ut writte n per missi o n fr o m Pfizer.   T he i n vesti ga t or s hall e ns ure t hat t he 
C R Fs/ D C Ts are sec urel y st ore d at t he st u d y site i n e ncr y pte d electr o nic a n d/ or pa per f or m 
a n d will be pass w or d pr otecte d or sec ure d i n a l oc ke d r o o m t o pre v e nt access b y 
u na ut h orize d t hir d parties.

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T he i n vest i gat or has ulti mate res po nsi bilit y  f or t he c ollecti o n a n d re p orti n g of all cli nical, 
safety, a n d la b orat or y data e ntere d o n t he C R Fs/ D C Ts a n d a n y ot her data c ollecti o n f or ms 
(s o urce d oc u me nts) a n d e ns uri ng t hat t he y  are acc urate, a ut he ntic/ ori gi nal, attri buta ble, 
c o m plete, c o ns iste nt, le gi ble, ti mel y (c o nte m p ora ne o us), e n d uri n g, a n d a vaila ble w he n 
re q uire d.  T he C R Fs/ D C Ts m ust be si g ne d by t he i n vesti gat or or b y a n a ut h orize d staff 
me m ber t o attest t hat t h e data c o ntai ne d o n t he C R Fs/ D C Ts are tr ue.  A n y c or recti o ns t o 
e ntries made i n t he C R Fs/D C Ts o r s o urce d oc u me nts m ust be date d, i nitiale d, a n d e x plai ne d 
(if necessar y) a n d s h o ul d n ot o bsc ure t he ori gi nal e ntr y. 
I n m ost cases, t he s o urce d oc u me nts are t he h os pital or t he p hys icia n s u bject c hart.  I n t hese 
cases, data c ollecte d o n t he C R Fs/ D C Ts m ust matc h t he data i n t h ose c harts. 
I n s o me cases, t he C R F/ D C T ma y als o ser ve as t he s o urce d oc u me nt.  I n t hese cases, a 
d oc u me nt s h o ul d be a vaila ble at t he i n vest i gat or site a n d at Pfizer t hat clearl y i de ntifies t hose 
data t hat will be rec or de d o n t he C R F/ D C T, a n d f or w hic h t he C R F/ D C T will sta n d as t he 
s o urce d oc u me nt.
1 1. 2. Rec or d Rete nti o n
T o e na ble e val uati o ns a n d/ or i ns pecti o ns/a u dits fr o m re g ulat or y a ut h orities or Pfizer, t he 
i n vesti gat or a grees t o kee p rec or ds, i ncl u di n g t he i de ntit y of all partici pati n g s ubjects 
(s ufficie nt i nf or mati o n t o li n k rec or ds, e g, C R Fs/ D C Ts a n d h os pital rec or ds), all ori gi nal 
si g ne d i nf or me d c o nse nt/asse nt d oc u me nts, c o pies of all C R Fs/ D C Ts, safet y re p orti n g f or ms, 
s o urce d oc u me nts, a n d detaile d rec or ds of treat me nt dis p ositi o n, a n d a de q uate d oc u me ntati o n 
of rele va nt c orres p o n de nce (e g, letters, meeti n g mi n utes, a n d tele p h o ne call re p orts).  T he 
rec or ds s h o ul d be retai ne d b y t he i n vesti gat or acc or di n g t o t he I C H g ui deli nes, acc or di n g t o 
l ocal re g ulati o ns, or as s pecifie d i n t h e cli nical st u d y a gree me nt ( C S A), w hic he ver is l o n ger. 
T he i n vesti gat or m ust e ns ure t ha t t he rec or ds c o nti n ue t o be st ore d sec urely f or s o l o n g as 
t he y are retai ne d.
If t he i n vesti gat or bec o mes u na ble f or a ny reas o n t o c o nti n ue t o retai n stu d y rec or ds f or t he 
re q uire d peri o d (e g, retire me nt, rel ocati o n), Pfizer s h o ul d be pr os pecti vel y n otifie d.  T he 
st u d y rec or ds m ust be tra nsferre d t o a desi g nee acce pta ble t o Pfizer, s uc h as a n ot her 
i n vesti gat or, a n ot her i nstit uti o n, or a n i n de pe n de nt t hir d p art y arra n ge d b y  Pfizer. 
I n vesti gat or rec or ds m ust be ke pt f or a mi ni m u m of 1 5 ye ars after c o m pleti o n or 
disc o nti n uati o n of t he st u d y or f or l o n ger if re q uire d b y  a p plica ble l ocal re g ulati o ns.
T he i n vesti gat or m ust o btai n Pfizer' s writte n per missi o n before dis p osi n g of a n y rec or ds, 
e ve n if rete nti o n re q uire me nts ha ve bee n met.
1 2. E T HI C S
1 2. 1. I nstit uti o n al Re vie w B o ar d/ Et hics C o m mittee

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It is t he res p o nsi bilit y of t he i n vesti gat or t o ha ve pr os pecti ve a p pr o val of t he st u d y  pr ot oc ol, 
pr ot oc ol a me n d me nts, i nf or me d c onse nt/asse nt d oc u me nts, a n d ot her rele va nt d oc u me nts, 
e g, recr uit me nt a d vertise me nts, if a p plica ble, fr o m t he IR B/ E C.  All c orres p o n de nce wit h t he 
I RB/ E C s h o ul d be retai ne d i n t he i n vesti gat or file.  C o pies of IR B/ E C a p pr o vals s h o ul d be 
f or war de d t o Pfizer.
T he o nl y  circ u msta nce i n w hic h a n a me n d me nt ma y  be i nitiate d pri or t o I R B/ E C a p pr o val is 
w here t he c ha n ge is necessar y  t o eli mi nate a p pare nt i m me diate hazar ds t o t he s u bjects.  In 
t hat e ve nt, t he i n vesti gat or m ust n otif y t he I R B/ EC a n d Pfizer i n writi n g i m me diatel y after 
t he i m ple me ntati o n.
1 2. 2. Et hic al C o n d uct of t he St u d y
T he st u d y  will be c o n d ucte d i n acc or da nce wit h t he pr ot oc ol, le gal a n d re g ulat or y 
re q uire me nts, a n d t he ge neral pri nci ples set f ort h i n t he Inter nati o nal Et hical G ui deli nes f or 
Bi o me dical R esearc h I n v ol vi n g H u ma n S u bjects ( C o u ncil f or I nter nati o nal Or ga nizati o ns of 
Me dical Scie nces 2 0 0 2), I C H G ui deli ne f or G o o d Cli nical Practice, a n d t he Declarati o n of 
Helsi n ki.
1 2. 3. S u bj ect I nf or m ati o n a n d C o nse nt
All parties will c o m pl y  wit h all a p plica ble la ws , i ncl u di n g la ws re gar di n g t he i m ple me ntati o n 
of or ga nizati o nal a n d tec h nical meas ures t o e ns ure pr otecti o n of s u bject pers o nal data.  S uc h 
meas ures will i ncl u de o mitti n g s u bject n a mes or ot her directl y i de ntifia ble data i n a n y 
re p orts, p u blicati o ns, or other discl os ur es, e x ce pt w here re q uire d b y a p plica ble la ws. 
T he pers o nal data will be st ore d at t he st u d y  site i n e ncr ypte d electr o nic a n d/ or pa per f or m 
a n d will be pass w or d pr otec te d or sec ure d i n a l oc ke d r o o m t o e ns ure t hat o nl y a ut h orize d 
st u d y staff h a ve access.  T he st u d y  site will i m ple me nt a p pr o priate tec h nical a n d 
or ga nizati o nal meas ures t o e ns ure t hat t he pers o nal data ca n be rec o vere d i n t he e ve nt of 
disaster.  I n t he e ve nt of a p ote ntial pers o nal data breac h, t he st u d y si te s hall be res p o nsi ble 
f or deter mi nin g w he t her a pers o nal data breac h has i n fact occ urre d a n d, if s o, pr o vi di n g 
breac h n otificati o ns as re q uire d b y  la w.
T o pr otect t he ri g hts a n d free d o ms of nat ural per s o ns wit h re gar d t o t he pr ocessi n g of 
pers o nal data, w he n st u d y  data are co m pile d f or tra nsfer t o Pfizer a n d ot her a ut h orize d 
parties, s u bject na mes will be re m o ve d a n d will be re place d b y a si n gle, s pecific, n u merical 
c o de, base d o n a n u m beri n g s ys te m defi ne d by Pfizer.  All ot her i de ntifia ble data tra nsfe rre d 
t o Pfizer or ot her a ut h orize d parties will be i de ntifie d b y  t his si n gle, s u bject-s pecific c o de.  
T he i n vesti gat or site will mai ntai n a c o nfi de ntial list of s u bjects w h o partici pate d i n t he 
st u d y, li nki n g eac h s u bject’s n u merical c o de t o his or her act ual i de ntit y .  I n case o f data 
tra nsfer, Pfizer will mai ntai n hi g h sta n dar ds of c o nfi de ntialit y a n d pr otecti o n of s u bjects’ 
pers o nal data c o nsiste nt wit h t he Cli nical St u d y A gree me nt a n d a p plica ble pri vac y la ws.
T he i nf or me d c o nse nt /asse nt d oc u me nts a n d a n y s u bject recr uit me nt ma terials m ust be i n 
c o m plia nce wit h I C H G C P, l ocal re g ulat or y  re q uire me nts, a n d le gal re q uire me nts, i ncl u di n g 
a p plica ble pri vac y la ws.

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T he i nf or me d c o nse nt /asse nt d oc u me nts use d d ur i n g t he i nf or me d c o nse nt pr ocess a n d a n y 
s u bject recr uit me nt materials m ust be re vie we d a n d a p p r o ve d by Pfizer, a p pr o ve d b y t he 
I RB/ E C bef ore use, a n d a vaila ble f or i ns pecti o n.
T he i n vesti gat or m ust e ns ure t hat eac h st u d y  s u bject, or his or her le gall y acc e pta ble 
re prese ntati ve, or pare nt(s) or le gal g uar dia n if a mi n or, is f ully i nf or me d a b o ut t he nat ure 
a n d o bjecti ves of t he st u d y, t he s hari n g of data relati n g t o t he st u d y a n d p ossi ble ris ks 
ass ociate d wit h partici pati o n, i ncl u di n g t he ris ks ass ociate d wit h t he pr ocessi n g of t he 
s u bject’s pers o nal data.  The i n vesti gat or f urt he r m ust e ns ure t hat ea c h st u d y s u bject, or his 
or her le gall y  acce pta ble re prese ntati ve, or pare nt(s) or le gal g uar dia n if a mi n or, is f ull y 
i nf or me d a b o ut his or her ri g ht t o access a n d c orrect his or her pers o nal data a n d t o wit h dra w
c o nse nt f or t he pr ocessi n g of his or her p ers o nal data.
W he ne ver c o nse nt is o btai ne d fr o m a s u bject’s le gally acce pta ble re prese ntati ve/ pare nt(s) or 
le gal g uar dia n, t he s u bject’s asse nt (affir mative a gree me nt) m ust s u bse q ue ntl y  be o btai ne d 
w he n t he s u bjec t has t he ca pacit y t o pr o vi de asse nt, as deter mi ne d by t he I R B/ E C.  If t he 
i n vesti gat or deter mi nes t hat a s u bject’s decisi o nal ca pacit y is s o li mite d t hat he or s he ca n n ot 
reas o na bly be c o ns ulte d, t he n, as per mitte d by t he I R B/ E C a n d c o nsiste nt wit h l ocal 
re g ulat or y a n d le gal re quire me nts, t h e s u bj ect’s asse nt ma y be wai ve d wit h s o urce 
d oc u me ntati o n of t he reas o n asse nt was n ot o btai ne d.  If t he st u d y s u bject d oes n ot pr o vi de 
his or her o w n c o nse nt, t he s o urce d oc u me nts m ust rec or d w hy t he s u bject di d n ot p r o vi de 
c o nse nt (e g, mi n o r, decisi o nall y i m paire d a d ult), h o w t he i n vesti gat or deter mi ne d t hat t he 
pers o n si g ni n g t he c o nse nt was t he s u bject’s le gall y acce pta ble re prese ntati ve, t he c o nse nt 
si g ner’s relati o ns hi p t o t he st u d y s u bject (e g, pare nt, s p o use), a n d t hat t he s u bject’s asse nt 
was o bta i ne d or wai ve d.  If asse nt is o btai ne d ver ball y, it m ust be d oc u me nte d i n t he s o urce 
d oc u me nts .
If t he st u dy i ncl u des mi n or s u bjects w h o reac h t he a ge of maj ori t y d uri n g t he st u d y, as 
rec o g nize d u n der l ocal la w, t he y m ust rec o nse nt as a d ults to re mai n i n t he st u d y .  If t he 
e nr oll me nt of e ma nci pate d mi n ors is per mitte d b y  t he st u d y a ge criteria, t he IR B/ E C, a n d 
l ocal la w, t he y m ust pr o vi de d oc u me ntati o n of le gal stat us t o gi ve c o nse nt wit h o ut t he 
per missi o n of a pare nt or le gal g uar dia n. 
T he i nvesti gat or, o r a pers o n desi g nate d b y t he i n vesti gat or, will o btai n writte n i nf or me d 
c o nse nt fr o m eac h s u bject or t he s u bject's le gall y acce pta ble re prese ntati ve, pare nt(s), or le gal 
g uar dia n a n d t he s u bject’s asse nt, w he n a p plica bl e, bef ore a n y st u d y- s pecific acti vit y is 
pe rf or me d, u nless a wai ver of i nf or me d c o nse nt has bee n gra nte d by a n I RB/ E C.  T he 
i n vesti gat or will retai n t he ori gi nal of eac h s u bject's si g ne d c o nse nt/asse nt d oc u me nt.
1 2. 4. Re p orti n g of S afet y Iss ues a n d Seri o us Bre ac hes of t he Pr ot oc ol or IC H G C P
I n t he e ve nt of a n y  pr o hi biti o n or restricti o n i m p ose d (ie, cli nical h ol d) b y a n a p plica ble 
re g ulat or y a ut h ority i n a n y area of t he w orl d, or if t he i n vesti gat or is a ware of a n y  ne w 
i nf or mati o n t hat mi g ht i nfl ue nce t he e val uati o n of t he be nefits an d ris ks of t he i n vesti gati o nal 
pr o d uct, Pfizer s h o ul d be i nf or me d i m me diatel y. 

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I n a d diti o n, t he i n vesti gat or will i nf or m Pfizer i m me diatel y of a n y ur ge nt safety meas ures 
ta ke n b y t he i n vesti gat or t o pr otect t he st u d y s u bjects a gai ns t a ny i m me diate hazar d , a n d of 
a n y seri o us breac hes of t his pr ot oc ol or of I C H G C P t hat t he i n vesti gat or bec o mes a ware of.
1 3. D E FI NI TI O N O F E N D O F T RI A L
1 3. 1. E n d of Tri al i n All P artici p ati n g C o u ntries
E n d of trial i n all c o u ntries is defi ne d as t he last s u bject l ast visit ( LS L V).
1 4. S P O N S O R DI S C O N TI N U A TI O N C RI T E RI A
Pre mat ure ter mi nati o n of t his st u d y  ma y occ ur beca use of a re g ulat or y a ut h orit y decisi o n, 
c ha n ge i n o pi ni o n of t he I R B/ E C, or i n vesti gati o nal pr o d uct safet y pr o ble ms, or at t he 
discreti o n of Pfizer.  I n a d diti o n, Pfizer retai ns t he ri g ht t o disc o nti n ue de vel o p me nt of 
P F -0 4 9 6 5 8 4 2 at a n y ti me.
If a st u dy is pre mat urel y ter mi nate d, Pfizer will pr o m ptl y n otif y t he i n vesti gat or.  After 
n otificati o n, t he i n vesti gat or m ust c o ntact all partici pati n g s u bjects a n d t h e h os pital p har mac y 
(if a p plica ble) wit hi n 7 da y s.  As directe d b y Pfizer, all st u d y materials m ust be c ollecte d a n d 
all C R Fs c o m plete d t o t he greatest e xte nt p ossi ble.
1 5. P U B LI C A T I O N O F S T U D Y R E S U L T S
1 5. 1. C o m m u nic ati o n of Res ults b y Pfizer
Pfizer f ulfills its c o m mit me nt t o p u blicl y  discl ose cli nical trial res ults t hr o u g h p osti n g t he 
res ults of st u dies o n w w w.cli nicaltrials. g o v ( Cli nical Trials. g o v), t he E ur o pea n Cli nical Trials 
Data base ( E u dra C T), a n d/ or w w w. pfizer.c o m, a n d ot her p u blic re gistries i n acc or da nce with 
a p plica ble l ocal la ws/re g ulati o ns. 
I n all cases, st u dy res ults are re p orte d b y Pfizer i n a n o bjecti ve, acc urate, bala nce d, a n d 
c o m plete ma n ner a n d are re p orte d re gar dless of t he o utc o me of t he st u d y or t he c o u ntr y i n 
w hic h t he st u d y  was c o n d ucte d.
w w w.c li nicaltrials. g o v
Pfiz er p osts cli nic al trial U S Basic Res ults o n w w w.cli nicaltrials. g o v f or Pfizer- s p o ns ore d 
i nter ve nti o nal st u dies (c o n d ucte d i n patie nts) t hat e val uate t he safety a n d/ or efficac y of a 
Pfizer pr o d uct, re gar dless of t he ge o gra p hical l ocati o n i n w hic h t he st u d y  is c o n d ucte d.  U S 
Bas ic Res ults are s u b mitte d f or p osti n g wit hi n 1 year of t he pri mar y c o m pleti o n date ( P C D) 
f or st u dies i n a d ult p o p ulati o ns or wit hi n 6 mo nt hs of t he P C D f or st u dies i n pe diatric 
p o p ulati o ns.
P C D is defi ne d as t he da te t hat t he fi nal s u bject was e xa mi ned or r ecei ve d a n i nter ve nti o n f or 
t he p ur p oses of fi nal c ollecti o n of data f or t he pri mar y o utc o me, w het her t he cli nical st u d y 
c o ncl u de d acc or di n g t o t he pre -s pecifie d pr ot oc ol or was ter mi nate d.

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E u dra C T
Pfizer p osts E u r o pea n U ni o n ( E U) Basic Res ults o n E u dra C T f or all Pfizer-s p o ns ore d 
i nter ve nti o nal st u dies t hat are i n sc o pe of E U re q uire me nts.  E U Basic Res ults are s u b mitte d 
f or p osti n g wit hi n 1 year of t he P C D f or st u dies i n a d ult p o p ulati o ns or wit hi n 6 m o nt hs of 
t he P C D f or st u dies i n pe di atric p o p ulat i o ns.
w w w. pfizer.c o m
Pfizer p osts P u blic Discl os ure S y n o pses (cli nical st u d y  re p ort s yn o pses i n w hic h a n y  data 
t hat c o ul d be use d t o i de ntify i n di vi d ual patie nts has bee n re m o ve d) o n w w w. pfizer.c o m f or 
Pfizer -s p o ns ore d i nter ve nti o nal st u dies at t he sa me time t he U S Basic Res ults d oc u me nt is 
p oste d t o w w w.cli nicaltrials. g o v.
1 5. 2. P u blic ati o ns b y I n vesti g at ors
Pfizer s u p p orts t he e xercise of aca de mic free d o m a n d has n o o bjecti o n t o p u blicati o n b y t he 
pri nci pal i n vesti gat or ( PI) of t he res ults of t he st u d y base d o n i nf ormati o n c ollecte d or 
ge nerate d b y t he PI, w het her or n ot t he res ults are fa v ora ble t o t he Pfizer pr o d uct.  H o we ver, 
t o e ns ure a gai nst i na d verte nt discl os ure of c o nfi de ntial i nf or mati o n or u n pr otecte d 
i n ve nti o ns, t he i n vesti gat or will pr o v i de Pfizer a n o p p or t u nit y t o re vie w a n y pr o p ose d 
p u blicati o n or ot her t y pe of discl os ure of t he res ults of t he st u d y (c ollecti vel y, “ p u blicati o n”) 
bef ore it is s u b mitte d or ot her wise discl ose d.
T he i n vesti gat or will pr o vi de a n y  p u blicati o n t o Pfizer at least 3 0 d a y s bef ore it is s u b mitte d 
f or p u blicati o n or ot her wise discl ose d.  If a n y pate nt acti o n is re q uire d t o pr otect i ntellect ual 
pr o pert y ri g hts, t he i n vesti gat or a grees t o dela y t he discl os ure f or a peri o d n ot t o e xcee d a n 
a d diti o nal 6 0 da y s.
T he i n v esti gat or will, o n re q uest, re m o ve a n y pre vi o usl y  u n discl ose d c o nfi de ntial 
i nf or mati o n bef ore discl os ure, e xce pt f or a ny st u d y - or Pfizer pr o d uct -relate d inf or mati o n 
necessar y  t o t he a p pr o priate scie ntific prese ntati o n or u n dersta n di ng of t he st u d y  res ults.
If t he st u dy is part of a m ultice nter st u d y, t he i n vesti gat or a grees t hat t he first p u blicati o n is 
t o be a j oi nt p u blicati o n c o veri n g all i n vesti gat or sites, a n d t hat a ny s u bse q ue nt p u blicati o ns 
b y  t he PI will refere nce t hat pri mar y p u blicati o n.  H o we ver , if a j oi nt man uscri pt has n ot 
bee n s u b mitte d f or p u blicati o n wit hi n 1 2 m o nt hs of c o m pleti o n or ter mi nati o n of t he st u d y  at 
all partici pati n g sites, t he i n vesti gat or is free t o p u blis h se paratel y, s u bject t o t he ot her 
re q uire me nts of t his secti o n.
F or all p u blicati o ns r elati ng t o t he st u d y, t he i nstit uti o n will c o m pl y  wit h rec o g nize d et hical 
sta n dar ds c o ncer ni n g p u blicati o ns a n d a ut h ors hi p, i ncl u di n g Secti on II - “ Et hical 
C o nsi derati o ns i n t he C o n d uct a n d Re p orti n g of Researc h” of t he U nif or m Re q uire me nts f or 
Ma n uscri pts
S u b mi tte d t o Bi o me dical J o ur nals, htt p:// w w w.ic mje. or g/i n de x. ht ml #a ut h ors hi p, 
esta blis he d b y t he I nter nati o nal C o m mittee of Me dical J o ur nal E dit ors.

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P u blicati o n of st u d y  res ults is als o pr o vi de d f or i n t he C S A bet wee n Pfizer a n d t he 
i nstit utio n.  I n t his secti on e ntitle d P u blicati o ns b y  In vesti gat ors , t he defi ne d ter ms s hall ha ve 
t he mea ni n gs gi ve n t o t he m i n t he C S A.
If t here is a ny c o nflict bet wee n t he C S A a n d a n y attac h me nts t o it, t he ter ms of t he C S A 
c o ntr ol.  If t here is a n y c o nflict bet wee n t his pr ot oc ol a n d t he C S A, t his pr ot oc ol will c o ntr ol 
as t o a n y iss ue re gar di n g treat me nt of st u d y s u bjects, a n d t he C S A will c o ntr ol as t o all ot her 
iss ues.

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1 6. R E F E R E N C E S
1.
Eic he nfiel d L F, Ellis C N, Ma nci n i AJ, et al. At o pic der matitis: e pi demi ol o g y a n d 
pat h o ge nesis u p date. Se mi n C uta n Me d S ur g 2 0 1 2; 3 1( 3 S u p pl)( Se p): S 3 - 5.
2.
Leic ht S, Ha n g gi M. At o pic der matitis. H o w t o i nc or p orate a d va nces i n ma na ge me nt. 
P ost gra d Me d 2 0 0 1; 1 0 9( 6)(J u n): 1 1 9- 2 7.
3.
Mar g olis J S, A b ua bara K, Bil ker W, et a l. Persiste nce of mil d t o m o derate at o pic 
der matitis. J A M A Der mat ol 2 0 1 4; 1 5 0( 6): 5 9 3- 6 0 0.
4.
Slater N A, M orrell D S. S y ste mic t hera p y of c hil d h o o d at o pic der matitis. Cli n Der mat ol 
2 0 1 5; 3 3( 3): 2 8 9 - 2 9 9.
5.
Le u n g D Y, Bie ber T. At o pic der matitis. La ncet 2 0 0 3; 3 6 1( 9 3 5 2) : 15 1 - 1 6 0.
6.
Ri n g J, Al o mar A, Bie ber T, et al. G ui deli nes f or treat me nt of at o pic ecze ma (at o pic 
der matitis) part I. J E ur Aca d Der mat ol Ve nere ol 2 0 1 2; 2 6( 8): 1 0 4 5 - 6 0.
7.  
A urie m ma M, Via nale G, A meri o P, et al. C y t o ki nes a n d T cells i n at o pic der matitis E ur 
C y t o ki ne Net w 2 0 1 2; 2 4( 1): 3 7 - 4 4.
8.  
M ortz C, A n derse n K, Dell gre n C, et al. At o pic der matitis fr o m a d olesce nts t o 
a d ult h o o d i n t he T O A C S c o h ort: pre vale nce, persiste nce a n d c o m or bi dities. Aller g y  
2 0 1 5; 7 0: 8 3 6 - 4 5. 
9.
Sa n dstr o m M., Faer ge ma n n J. P r o g n osis a n d pr o g n ostic fact ors i n a dult pa tie nts wit h 
at o pic der matitis: a l o n g -ter m f oll o w-u p q uesti o n naire st u d y . Britis h J. of Der mat ol o g y 
2 0 0 4; 1 5 0: 1 0 2 - 1 0.
1 0.
Dec kers I, Mc Lea n A S, Li nsse n S, M o m mers M, et al. I n vesti gati n g i nter nati o nal ti me 
tre n ds i n t he i nci de nce a n d pre vale n ce of at o pic ecz e ma 1 9 9 0 -2 0 1 0: a s y ste matic re vie w 
of e pi de mi ol o gical st u dies P L o S O ne 2 0 1 2; 7( 7):e 3 9 8 0 3.
1 1.
Sil ver ber g J I, Ha nifi n J M. A d ult ecze ma pre vale nce a n d ass ociati o ns wit h ast h ma a n d 
ot her healt h a n d de m o gra p hic fact ors: a U S p o p ulati o n -base d st u d y . J Aller g y Clin 
Im m u n ol 2 0 1 3; 1 3 2( 5): 1 1 3 2 - 1 1 3 8.
1 2.
Lee C H, C h ua n g H Y, H o n g C H, H ua n g S K, et al. Lifeti me e x p os ure t o ci garette 
s m o ki n g a n d t he de vel o p me nt of a d ult-o nset at o pic der matitis. Br J Der mat ol 
2 0 1 1; 1 6 4( 3): 4 8 3 - 9.
1 3.
H o me y  B, Stei nh off M, R uzic ka T, et al. C yt o ki nes an d c hem o ki nes orc hestrate at o pic 
s ki n i nfla m mati o n.J Aller g y Cli n I m m u n ol 2 0 0 6; 1 1 8( 1): 1 7 8- 8 9.
1 4.
C or nelisse n C, L usc her -Firzlaff J, Bar o n J M, et al. Si g nali n g b y I L-3 1 a n d f u ncti o nal 
c o nse q ue nces. E ur J Cell Bi ol 2 0 1 2; 9 1( 6- 7): 5 5 2 -6 6.

P F- 0 4 9 6 5 8 4 2
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Pa ge 1 3 9
1 5.
Gittler J K , S he mer A, S ua rez-Fa ri nas M, F ue ntes- D uc ula n J, 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 haracterizes 
ac ute a n d c hr o nic at o pic der matitis. J Aller g y  Cli n Im m u n ol 2 0 1 2; 1 3 0( 6): 1 3 4 4 - 5 4.
1 6.
J u ni per E F, O' B yr ne P M, G u y att G H, et al. D e vel o p me nt a n d vali dati o n of a 
q uesti o n naire t o meas ure ast h ma c o ntr ol. E ur Res pir J 1 9 9 9; 1 4: 9 0 2 – 9 0 7.
1 7.
J u ni per E F, B o us q uet J, A betz L, Bate ma n E D. I de ntif yi n g ' well-c o ntr olle d' a n d ' n ot 
well -c o ntr olle d' ast h ma us i n g t he Ast h ma C o ntr ol Q uesti o n naire. Re s pirat or y Me dici ne 
2 0 0 6 ( 1 0 0): 6 1 6 – 6 2 1.
1 8.
P os ner K, O q ue n d o M A, G o ul d M, et al. C ol u m bia Classificati o n Al g orit h m of S uici de 
Assess me nt ( C - C A S A): classificati o n of s uici dal e ve nts i n t he F D A's pe diatric s uici dal 
ris k anal ys is of a nti de pressa nts. A m J Ps ychia tr y 2 0 0 7; 1 6 4( 7): 1 0 3 5 - 4 3.
1 9.
Ra bi n R, G u de x C, Selai C, et al. Fr o m tra nslati o n t o versi o n ma na ge me nt: a hist or y  a n d 
re vie w of met h o ds f or t he c ult ural a da ptati o n of t he E ur o Q ol fi ve-di me nsi o nal 
q uesti o n naire. Val ue i n H ealt h 2 0 1 4; 1 7( 1): 7 0 - 6.  
2 0.
Va n H o ut B, Ja nssen M F, Fe n g Y S, et al. I nteri m sc ori n g f or t he E Q- 5 D-5 L : ma p pi n g 
t he E Q- 5 D-5 L  t o E Q- 5 D-3 L  val ue sets. Val ue i n Healt h 2 0 1 2; 1 5( 5): 7 0 8-1 5.  
2 1.
Ra m os -G o ñi J M, Pi nt o -Pra des J L,  O p pe M, et al. Val uati o n a n d m o deli n g of E Q- 5 D- 5 L  
healt h states u sin g a h y bri d a p pr oac h. Me dical care 2 0 1 7; 5 5( 7):e 5 1 - 8.  
2 2.
Ya n g Y, Brazier J, L o n g w ort h L . E Q-5 D i n s ki n c o n diti o ns: a n assess me nt of vali dit y  
a n d res p o nsi ve ness. E ur J Healt h Ec o n. 2 0 1 5; 1 6( 9): 9 2 7- 9 3 9.
2 3.
Ja nsse n M F, Pic kar d A S, G olic ki D, et al. Meas ure me nt pro p erties of t he E Q - 5 D-5 L  
c o m pare d t o t he E Q - 5 D-3 L  acr oss ei g ht patie nt gr o u ps: a m ulti-c o u ntr y st u d y. Q ualit y 
of L ife Researc h. 2 0 1 3; 2 2( 7): 1 7 1 7- 2 7.  
2 4.
A g b orsa n ga y a C B, La hti ne n M, C o o ke T, J o h ns o n J A. C o m pari n g t he E Q -5 D 3 L a n d 
5 L : meas ure me nt pr o perties a nd ass ociati o n wit h c hr o nic c o n diti o ns a n d m ulti m or bi dit y 
i n t he ge neral p o p ulati o n. Healt h a n d q uality of life o utc o mes 2 0 1 4; 1 2( 1): 7 4.
2 5.
Her d ma n M, G u de x C, Ll o y d A, et al. De vel o p me nt a n d preli mi nar y  testi n g of t he ne w 
fi ve-le vel versio n of E Q -5 D ( E Q - 5 D-5 L ). Q ualit y  of life researc h 2 0 1 1; 2 0( 1 0): 1 7 2 7 - 3 6. 
2 6.
Wille N, Ba dia X, B o nsel G, B urstr o m K, Ca vri ni G, De vli n N, E g mar A C, Grei ner W, 
G usi N, Her d ma n M, Jels ma J  De vel o p me nt of t he E Q - 5 D-Y: a c hil d -frie n dl y versi o n 
of t he E Q -5 D.  Q ual L ife Res 2 0 1 0 A u g; 1 9( 6): 87 5 - 8 8 6. 
2 7.
Ra ve ns- Sie berer U, Wille N, Ba dia X, et al. Feasi bilit y , relia bilit y, a n d vali dit y of t he 
E Q - 5 D-Y: res ults fr o m a m ulti nati o nal st u d y . Q ual Life Res 2 0 1 0; 1 9( 6): 8 8 7- 9 7. 

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B 7 4 5 1 0 1 4
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Pa ge 1 4 0
2 8.
E ur o Q ol Gr o u p. E ur o Q olea ne w facilit y f or t he meas ure m e nt of healt h -relate d q ualit y 
of life . The E ur o Q ol Gr o u p. Healt h P olic y  1 9 9 0; 1 6: 1 9 9- 2 0 8.
2 9.
Si m ps o n E L , Ga d kari A, W or m M, et al. D u pil u ma b t hera p y pr o vi des cli nicall y 
mea ni n gf ul i m pr o ve me nt i n patie nt-re p orte d o utc o mes ( P R Os): A p hase II b, 
ra n d o mize d, place bo - c o ntr olle d, cli nical trial i n a d ult pa tients wit h m o derate t o se vere 
at o pic der matitis ( A D). J A m Aca d Der mat ol. 2 0 1 6; 7 5( 3): 5 0 6- 5 1 5.
3 0.
Si m ps o n E L , Bie ber T, G utt ma n-Yass k y E, et al. T w o P hase 3 trials of d u pil u ma b 
vers us place b o i n at o pic der matitis. N E n g l J Me d. 2 0 1 6; 3 7 5: 2 3 3 5- 23 4 8.
3 1.
P o ole C D , Cha m bers C, Si d h u M K, et al. Healt h -relate d utilit y a m o n g a d ults wit h 
at o pic der matitis treate d wit h 0. 1 % tacr oli m us oi nt me nt as mai nte na nce t hera p y o ver 
t he l o n g ter m: fi n di n gs fr o m t he Pr ot o pic C O N T R O L st u d y. Br J Der mat ol 
2 0 0 9; 1 6 1( 6): 1 3 3 5 - 4 0.
3 2.
Ki m C, P ar k K Y , A h n S, et al. Ec o n o mic i m pact of at o pic der matitis i n K orea n patie nts. 
A n n Der mat ol. 2 0 1 5; 2 7( 3): 2 9 8- 3 0 5. 
3 3.
Fi nla y  A Y, K ha n G K. Der mat ol o g y Life Q ualit y In de x ( D L QI): A si m ple practical 
meas ure f or r o uti ne cli nica l use. Cli nical a n d E xpe ri me ntal Der mat ol o gy 1 9 9 4; 1 9: 
2 1 0 - 2 1 6.
3 4.
Le wis -J o nes M S, Fi nla y A Y. T he C hil dre n's Der mat ol o g y Life Q ualit y In de x ( C D L QI ): 
I nitial vali dati o n a n d practical use. Britis h J o ur nal of Der mat ol o g y 1 9 9 5; 1 3 2: 9 4 2- 4 9. 
3 5.
Ersser SJ, C o w dell F, L atter S, et al. Ps y c h olo g ical a n d e d ucati o nal i nter ve nti o ns f or 
at o pic ecze ma i n c hil dre n. T he C oc hra ne Li brar y . 2 0 1 4;Ja n 1. 
3 6.
Sc h mitt J, La n ga n S, Willia ms H et al. W hat are t he best o utc o me meas ure me nts f or 
at o pic ecze ma? A s yste matic re vie w. J Aller g y Clinical I m m u n ol 2 0 0 7; 1 2 0 ( 6): 1 3 8 9- 9 8. 
3 7.
W hite D , Leac h C, Si ms R, et al. Vali dati o n of t he H os pital A n xiet y a n d De pressi o n 
Scale f or use wit h a d olesce nts. Br J Ps y c hiatr y 1 9 9 9; 1 7 5( 5): 4 5 2- 4.  
3 8.
Ware J, K osi ns ki M, Bj or ner J, et al. Deter mi ni n g i m p orta nt differe n ces i n sc ores. 
User's Ma n ual f or t he S F - 3 6 v2 ® Healt h S ur ve y . Li nc ol n ( RI): Q ualit yMetric 
I nc or p orate d; 2 0 0 7: 1 2 5- 3 3. ( Refere nce a vaila ble u p o n re q uest.).
3 9.
Cella D, Lai J S, C ha n g C H, et al. Fati g ue i n ca ncer patie nts c o m pare d wit h fati g ue i n 
t he ge neral U nited States p o p ula ti o n. Ca ncer 2 0 0 2; 9 4( 2 ): 5 2 8-3 8. 
4 0.
Os ma n A, Ba g ge C L, G utierrez P M, et al. T he S uici dal Be ha vi ors 
Q uesti o n naire -Re vise d ( S B Q - R): vali dati o n wit h cli nical a n d n o ncli nical sa m ples. 
Assess me nt. 2 0 0 1; 8( 4): 4 4 3 - 5 4.

P F- 0 4 9 6 5 8 4 2
B 7 4 5 1 0 1 4
Fi nal P r otoc ol A me n d me nt 5, 2 8 Oct o ber 2 0 1 9
P FI Z E R C O N FI D E N TI A L
Pa ge 1 4 1
4 1.
Kr oe n ke K., Stri ne, T., S pitzer C ., et al, T he PH Q -8 as a meas ure of c urre nt de pressi o n 
i n t he ge neral p o p ulati o n 2 0 0 9. J Affect Dis or d 2 0 0 9; 1 1 4( 1-3); 1 6 3 – 7 3. 
4 2.
Lai J, Cella D., H ol m S, et al, Meas uri n g Fati g ue f or C hil dre n wit h Ca ncer: 
De vel o p me nt a n d Vali dati o n of t he Pe diatric F u ncti o nal Assess me nt of C hr o nic Ill ness 
T hera p y Fati g ue ( P E D S F A CI T- F). J Pe diatr He mat ol O nc ol 2 0 0 7; 2 9( 7): 4 7 1 - 9.
4 3.
Ha nifi n J M, Raj ka G. Dia g n ostic feat ures of at o pic der matitis. Acta Der m Ve nere ol 
1 9 8 0; 9 2(s u p pl): 4 4- 7.
4 4.
Y osi p o vitc h G, Rea ne y  M, Maste y V, et al. Vali dati o n of t he pea k pr urit us n u merical 
rati n g scale: Res ults fr o m cli nical st u dies of d u pil u ma b i n a d ult patie nts wit h m o derate 
t o se vere at o pic der matitis: 5 0 6 3. J o ur nal of t he A merica n Aca de my of Der mat ol o g y. 
2 0 1 7 J u n 1; 7 6( 6): A B 2 7 8.
4 5.
J u ni per E F, S ve nss o n K, M or k A - C, et al., Meas ureme nt pr o perti es a n d i nter pretati o n of 
t hree s h orte ne d versi o ns of t he ast h ma c o ntr ol q uesti o n naire. Res pirat or y Me dici ne. 
2 0 0 5; 9 9: 5 5 3 - 5 5 8.

P F- 0 4 9 6 5 8 4 2
B 7 4 5 1 0 1 4
Fi nal P r otoc ol A me n d me nt 5, 2 8 Oct o ber 2 0 1 9
P FI Z E R C O N FI D E N TI A L
Pa ge 1 4 2
A p pe n di x 1. A b bre vi ati o ns 
T his f oll o wi n g is a list of a b bre viati o ns t hat ma y  be use d i n t he pr ot oc ol. 
A b bre vi ati o n
Te r m
A C Q
A st h ma C o ntr ol Q uest i o n naire
A D
at o pic der matitis
A E
a d verse e ve nt
A L T
ala ni ne a mi n otra nsferase
A S T
as partate a mi n otra nsferase
A T P
a de n osi ne tri p h os p hate
A U C
Area u n der t he c ur ve
A U C i nf
Area u n der t he c ur ve fr o m 0 t o i nfi nit y
A U C last
rea u n der t he cur ve fr o m 0 t o last
B C G
Bacille Cal mette G uéri n
BI D
t wice a da y
B P
bl o o d press ure
B S A
b o d y s urface area
C ma x
ma xi m u m c o nce ntrati o n 
C D
Cl uster of differe ntiati o n
C D L QI
C hil dre n’s Der mat ol o g y L ife Q ualit y I n de x
C F B
cha n ge fr o m ba seli ne
CI
c o nfi de nce i nter val
C L/ F
cleara nce/fracti o n of d ose a bs or be d
C O 2
car b o n di o xi de
C K
creati ne ki nase
C R F
case re p ort f or m
C S A
cli nical st u d y a gree me nt
Cs A
c ycl os p ori n A
C S F
cere br os pi nal fl ui d
C S R
cli nical st u d y re p ort
C -S S R S
C ol u m bia S ui ci de Se verit y Rati n g Scale
C T
cli nical trial
C T A
cli nical trial a p plicati o n
C T C A E
C o m m o n Ter mi n ol o g y Criteria f or A d verse E ve nts
C V
C oefficie nt of variati o n
C Y P
C y t oc hr o me P
D C T
Data C ollecti o n T o ol
DI LI
dr u g -i n duce d li ver i nj ur y
D L Q I
Der m at ol o g y L ife Q ualit y I n de x
D M C
data m o nit ori n g c o m mittee
D N A
de o x yri b o n ucleic aci d
D U
dis pe nsa ble u nit
E A SI
Ecze m a Area a n d Se verit y I n de x
E B V
E pstei n Barr vir us
E C
et hics c o m mittee
E C G
electr ocar di o gra m
E -D M C
e xter nal d ata m o nit ori n g c o m mitt ee
E D P
e x p os ure d uri n g pre g na nc y
E LI S A
E nz y me -Li n ke d I m m u n os or be nt Assa y
E M A
E ur o pea n Me dici nes A ge nc y
C CI

P F- 0 4 9 6 5 8 4 2
B 7 4 5 1 0 1 4
Fi nal P r otoc ol A me n d me nt 5, 2 8 Oct o ber 2 0 1 9
P FI Z E R C O N FI D E N TI A L
Pa ge 1 4 3
A b bre vi ati o n
Te r m
E O S
e n d of st u d y
E O T
e n d of treat me nt
E P O
er yt hr o p oieti n
e P R O
electr o nic Patie nt Re p orte d O utc o me 
E Q -5 D -5 L
E ur o Q ol Q ualit y of Life 5 -Di me nsi o n 5 -Le vel Scale
E Q -5 D -Y
E ur o Q ol Q ualit y of Life 5 -Di me nsi o n Y o ut h Scale
E T
earl y ter mi nati o n 
E U
E ur o pea n U ni o n
E u dra C T
E ur o pea n Cli nical Trials Data base
F A CI T -F
F u ncti o nal Assess me nt of C hr o nic Ill ness T hera p y Fati g ue Scale
F A Cs
fl u oresce nce-acti vate d cell s orti n g
F A S
f ull a nal ysis set
F A S -M A R
f ull a nal ysis set – missi n g at ra n d o miz ati o n
F A S -O L
f ull a nal ysis set – o pe n la bel r u n -i n
F A S -R A
f ull a nal ysis set - ra n d o mize d
F A S -R E
f ull a nal ysis set - resc ue
F D A
F o o d a n d Dr u g A d mi nistrati o n 
F E V
F orce d e x pirat or y v o l u me
F S H
f ollicle-sti m ulati n g h or m o ne
G C P
G o o d Cli nical Practice
G G T
Ga m ma -gl uta m yl tra nsferase
G M -C S F
gra n ul oc yte -macr o p ha ge c ol o n y -sti m ulati n g fact or
H A D S
H os pital A n xiet y a n d De pressi o n Scale
H Bs A b
he patitis B s urface a nti b o d y
H Bs A g
he patitis B s urface a nti ge n
H Bc A b 
he patitis B c ore a nti b o d y
H B V
he patitis B vir us
H B V D N A
he patitis B vir us de o x yri b o n ucleic aci d
H C V
he patitis C vir us
H C V A b 
he patitis C a nti b o d y
H C V R N A
he patitis C viral ri b o n ucleic aci d
H D L
hi g h -de nsit y li p o pr ot ei n 
H E E N T
h ea d, e yes, ears, n ose a n d t hr oat
He p B
he patitis B
HI V
h u ma n i m m u n o deficie nc y vir us
H R Q L
healt h -relate d q ualit y of life
hs C R P
hi g h -se nsiti vit y C-reacti ve pr otei n
H S V
her pes si m ple x vir us
H T A
healt h tec h n ol o gies as sess me nt 
I B
I n vesti gator’s Br oc h ure
I C H
I nter nati o nal C o nfere nce o n Har m o nisati o n
I D
i de ntificati o n
I F N
i nterfer o n
I F N-
i nterfer o n-al p ha
I F N-
i nterfer o n-ga m ma
I G A
I n vesti gat or’s Gl o bal Assess me nt
I g E 
I m m u n o gl o b uli n E
I g G
i m m u n o gl o b uli n G
II V
i nter i n di vi d ual variabi lit y
I L
i nterle u kin
I N D
i n vesti gati o nal ne w dr u g a p plicati o n

P F- 0 4 9 6 5 8 4 2
B 7 4 5 1 0 1 4
Fi nal P r otoc ol A me n d me nt 5, 2 8 Oct o ber 2 0 1 9
P FI Z E R C O N FI D E N TI A L
Pa ge 1 4 4
A b bre vi ati o n
Te r m
I N R
i nter nati o nal n or malize d rati o
I P
i n vesti gati o nal pr o d uct
I R B
i nstit uti o nal re vie w b oar d
I R C
i nter nal re vie w c o m mittee
I R T
i nteracti ve res p o nse tec h n ol o g y
I U D
i ntra uteri ne de vice
IW R
i nteracti ve we b re s p o nse
J A K
Ja n us ki nase
J A K 1
Ja n us ki nase 1
J A K 2
Ja n us ki nase 2
J A K 3
Ja n us ki nase 3
K 2E D T A
di p otassi u m et h yle ne dia mi netetraacetic aci d
L D L
l o w-de nsit y li p o pr otei n
L F T
li ver f u ncti o n test
L L Q
l o wer li mit of q ua ntificati o n
L S L V
last s u bject last visit 
L T E
l o n g-ter m e xte nsi o n
M A A
mar keti n g a ut h orisati o n a p plicati o n
M C H
mea n c or p usc ular he m o gl o bi n
M C H C
mea n c or p usc ular he m o gl o bi n c o nce ntrati o n
M C V
mea n c or p usc ular v ol u me
M H P
me ntal healt h pr ofessi o nal
M M R M
mi xe d -effect m o de l wit h re peate d meas u res
M n B
me ni n giti dis ser o gr o u p B
M RI
ma g netic res o na nce i ma gi n g
M T X
met h otre xate
N/ A
n ot a p plica ble
N B -U V B
narr o w ba n d ultra vi olet B li g ht
N K
Nat ural Killer
N R S 
n u merical rati n g scale
O T C
o ver t he c o u nter
P C D
pri mar y c o m pleti o n date
P D
P har mac o d y na mics
P D E -4
P h os p h o diesterase 4
Pe ds -F A CI T -F
Pe diatric F u ncti o nal Assess me nt of C hr o nic Ill ness T hera p y Fati g ue Scale
P E E R
Pe diatric Ecze ma Electi ve Re gistr y
P F S
prefille d s yri n ge
P GI C
Patie nt Gl o bal I m press i o n of C ha n ge
P GI S
P a tie nt Gl o bal I mpressi o n of Se verit y
P G x
P har m ac o ge n o mics
P H P
Pri mar y Care P h ysicia n
P H Q 8
Patie nt Healt h Q uesti o n naire - 8 ite ms
PI
pri nci pal i n vesti gat or
P K
P har m ac o ki netics
P O C
pr o of of c o nce pt
P O E M
Patie nt -Orie nte d Ecze ma Mea s ure
P P A S
per -pr ot oc o l a nal ysis set
P P D
p urifie d pr otei n deri vati ve test
P R O
patie nt re p orte d o utc o me
P S A A D
Pr urit us a n d S y m pt o ms Assess me nt f or At o pic Der matitis
P T
pr ot hr o m bi n ti me
Pt G A 
Patie nt Gl o bal Assess me nt

P F- 0 4 9 6 5 8 4 2
B 7 4 5 1 0 1 4
Fi nal P r otoc ol A me n d me nt 5, 2 8 Oct o ber 2 0 1 9
P FI Z E R C O N FI D E N TI A L
Pa ge 1 4 5
A b bre vi ati o n
Te r m
Q D
o nce dail y
Q F T - G
Q ua nti F E R O N -T B G ol d
Q T
Q T i nter va l
R ac
acc u m ulati o n rati o 
R B C
re d bl o o d cell
R N A
ri b o n ucleic aci d
S A E
seri o us a d verse e ve nt
S A P
statistical a nal ysis pla n
S B Q -R
S uici de Be ha vi ors Q uesti o n naire -Re vise d
S C O R A D 
S C O Ri n g At o pic Der matitis
S F -3 6
S h ort F or m -3 6
SI B
suici dal i deati o n a n d b e ha vi or
S O C
sta n dar d of care
S O P
sta n dar d o perati n g pr oce d ure
S R S D
si n gle refere nce safet y d oc u me nt
S T A T
si g nal tra ns d ucers a n d acti vat ors of tra nscri pti o n
S U S A R
s us pecte d u ne x pecte d seri o us a d verse reacti o n
T 1/ 2
Half -life
T m a x
ti me at w hic h C ma x oc c urre d
T A R C
t h y m us a n d acti vati o n re g ulate d c he m o ki ne
T B
t u berc ul osis
T Bili
t otal bilir u bi n
T CI
T o pical calci ne uri n i n hi bit ors
T C S
t o pical c ortic oster oi ds 
T d P
T orsa des de P oi ntes
T H 1
t ype 1 hel per T cell
T H 2
t ype 2 hel per T cell
T ma x
Ti m e t o ma xi m u m c o nce ntra ti o n
T P O
T hr o m b o p oieti n
T Y K 2
t yr osi ne ki nase 2
U L N
u p per li mit of n or mal
U S
U nite d States
U S A
U nite d States of A merica
U V A
ultra vi olet A li g ht
U V B
ultra vi olet B li g ht
V A S
vis ual a nal o g scale
V/ F
v ol u me of distr i b uti o n/fracti o n a bs orbe d
V Z V 
varic ella zoster vir us
W B C
w hite bl o o d cell
W H O
W orl d Healt h Or ga nizati o n
W O N C B P 
w o me n of n o n -c hil d beari n g p ote ntial

P F- 0 4 9 6 5 8 4 2
B 7 4 5 1 0 1 4
Fi nal P r otoc ol A me n d me nt 5, 2 8 Oct o ber 2 0 1 9
P FI Z E R C O N FI D E N TI A L
Pa ge 1 4 6
A p pe n di x 2. Di a g n ostic Criteri a f or At o pic Der m atitis
Per I ncl usi o n Criteri o n 3 , a su bject is t o ha ve a cl i nical dia g n osis of at o pic der matitis 
acc or di n g t o t he criteria of Ha nifi n a n d Raj ka. 4 3
H a nifi n a n d R aj k a’s Di a g n ostic Criteri a f or At o pic Der m atitis
M ust h a ve t hree or m ore b asic fe at ures descri be d bel o w:
Pr ur itus
T y pical m or p h ol o g y  a n d distri b uti o n:
Fle x ural lic he nificati o n i n a d ults
Facial a n d e xte ns or er u pti o ns i n i nfa nts a n d c hil dre n
C hr o nic or c hr o nicall y -rela psi n g der matitis
Pers o nal or fa mil y hist or y of at o p y (ast h ma, aller gic r hi nitis, at o pic der matitis)
M ust h a ve t hr ee or m ore f oll o wi n g mi n or fe at ures:
Xer osis
Ic ht h yosis/ pal mar h y perli nearit y , kerat osis pilaris
I m me diate (ty pe 1) s ki n test reacti o n
Ele vate d ser u m I g E
Earl y a ge of o nset
Te n de nc y  t o war d c uta ne o us i nfecti ons (es p. sta p h. a ure us an d her pes si m ple x), i m paire d 
cell-me diate d i m m u nit y
Te n de nc y  t o war d n o n-s pecific ha n d or f o ot der matitis
Ni p ple ecze ma
C heilitis
Rec urre nt c o nj u ncti vitis
De n nie -M or ga n i nfra or bital f ol d
Kerat oc o n us
A nteri or s u bca ps ular catara cts
Or bital dar ke ni n g
Facial pall or , facial er yt he ma
Pit y riasis al ba
A nteri or nec k f ol ds
Itc h w he n s weati n g
I nt olera nce t o w o ol a n d li pi d s ol ve nts
Peri of ollic ular acce nt uati o n
F o o d i nt olera nce
C o urse i nfl ue nce d b y e n vir o n me ntal a n d e m oti o nal fact o rs
W hite der m o gra p his m, dela y e d bla n c h

P F- 0 4 9 6 5 8 4 2
B 7 4 5 1 0 1 4
Fi nal P r otoc ol A me n d me nt 5, 2 8 Oct o ber 2 0 1 9
P FI Z E R C O N FI D E N TI A L
Pa ge 1 4 7
A p pe n di x 3. Pr o hi bite d C o nc o mit a nt Me dic ati o ns
Pr o hi bite d c o nc o mita nt me dicati o n liste d bel o w s h o ul d n ot be ta ke n wit h st u d y  dr u g. 
Patie nts re q uiri n g treat me nt wit h a liste d pr o hi bite d c o nc o mita nt me dicati o n s h o ul d be 
disc usse d wit h t he Me dical M o n itor. S uc h s u b jects ma y  still be eli gi ble/c o nti n ue i n t he st u d y 
if t he y d o n ot ha ve t o i nterr u pt d osi n g wit h st u d y dr u g f or m ore t ha n 2 8 c o nsec uti ve da ys.
C Y P 2 C 1 9 I n hi bit ors 
C Y P 2 C 1 9 I n d ucers
Fl uc o naz ole ( Difl uca n)
E nzal uta mi de ( Xta n di)
Fl u v o xa mi ne ( L u v o x)
Rifa m pi n
T icl o pi di ne ( Ticli d)
Es o me praz ole ( Ne xi u m)
Fl u o xeti ne ( Pr ozac)
M ocl o be mi de
O me praz ole ( Pril osec)
V oric o naz ole ( Vfe n d)
C Y P 2 C 9 I n hi bit ors 
C Y P 2 C 9 I n d ucers
Fl uc o naz ole ( Difl uca n)
Car ba maze pi ne ( Te gret ol)
A mi o d ar o ne ( C or dar o ne)
E nza l uta mi de ( Xta n di)
Fl u v o xa mi ne ( L u v o x)
Rifa m pi n
Mic o naz ole
O xa n dr ol o ne ( O xa n dri n)
V oric o naz ole ( Vfe n d)
T he was h o ut peri o d f or all C y t oc hr o me P ( C Y P) 2 C 9 a n d C Y P 2 C 1 9 i n hi bit ors is 1 wee k or 
5 half -li ves, w hic he ver is l o n ger.
T he was h o ut peri o d f or all C Y P 2 C 9 a n d al l C Y P 2 C 1 9 i n d ucers is 5 half -li ves pl us 1 4 da y s
pri or t o t he first d ose of i n vesti gati o nal pr o d uct . F or e xa m ple, t he a vera ge half-life of 
Car ba maze p i ne after re peat d osi n g is i n a vera ge 1 5 h o urs.   T he was h o ut peri o d is calc ulate d 
as t he s u m of 5 half -li ves (a p pr o xi matel y 3 d a y s) a n d a n a d diti o nal 1 4 d a y s f or a t otal of 
1 7 da y s.
T his is n ot a n all-i ncl usi ve list. St u d y  pers o n nel s h o ul d sta y c urre nt a n d c o ns ult wit h t heir 
p har mac y  t o e xcl u de all c o nc o mita nt me dicati o ns that are C Y P 2 C 9 or C Y P 2 C 1 9 i n hi bit ors 
or i n d ucers .  Half -life refers t o half-life of t he pare nt dr u g a n d its meta b olites w hic h are 
i n hi bit ors or i n d ucers. T he l o n g est half-life s h o ul d be use d t o calc ulate t he peri o d necessar y  
t o was h o ut a me dicati o n pri or t o t he first d ose of in vesti gati o nal pr o d uct.  F or e xa m ple, 
fl u o xeti ne a n d its meta b olite n orfl u o xeti ne are b ot h i n hi bot ors of C Y P 2 C 1 9.  T he ter mi nal 
half -life of fl u o xeti ne is u p t o 6 da y s; h o we ver, n orfl u o xeti ne has a l o n ger half-life, u p t o 
1 6 da y s.  T heref ore, t he was h o ut p eri o d s h o ul d be calc ulate d base d o n 5 ti mes t he half- life of 
n orfl u o xeti ne, f or a t otal of a p pr o xi matel y  8 0 da ys pri or t o t he first d ose of in vesti gati o nal 
pr o d u ct.

P F- 0 4 9 6 5 8 4 2
B 7 4 5 1 0 1 4
Fi nal P r otoc ol A me n d me nt 5, 2 8 Oct o ber 2 0 1 9
P FI Z E R C O N FI D E N TI A L
Pa ge 1 4 8
Use of c o nc o mita nt me dicati o ns t hat pr ol o n g t he Q T/ Q Tc F i nter val were e xcl usi o nar y f or 
e nr oll me nt i n t he st u d y.  After t he c o m pleti o n of e nr oll me nt t he restricti o n o n t hese 
pr o hi bite d me d icati o ns was re m o ve d.

P F- 0 4 9 6 5 8 4 2
B 7 4 5 1 0 1 4
Fi nal P r otoc ol A me n d me nt 5, 2 8 Oct o ber 2 0 1 9
P FI Z E R C O N FI D E N TI A L
Pa ge 1 4 9
A p pe n di x 4. G ui deli nes f or M o nit ori n g a n d Disc o nti n u ati o n 
M o nit ori n g Criteri a 
T he f oll o wi n g la b orat or y a b n or malities re q uire pr o m pt retesti n g:

Ne utr o p hil c o u nts < 1 0 0 0 ne utr o p hils/ m m 3; c o nfir me d pr o m ptl y b y re peat testi n g, 
i deall y wit hi n 3-5 da y s; 

L y m p h oc y te c o u nt < 5 0 0/ m m3; c o nfir me d pr o m ptl y b y re peat testi n g, wit hi n 4 8 h o urs;

Platelet c o u nts < 7 5, 0 0 0 platelets/ m m 3; c o nfir me d pr o m ptl y  b y re peat testi ng, i deall y  
wit hi n 3 - 5 da y s; 

A n y  si n gle he m o gl o bi n val ue <9. 0 g/ d L or o ne t hat dr o ps 2 g/ d L bel o w baseli ne; 
c o nfir me d pr o m ptl y b y re peat tes ti n g, i deally wit hi n 3 - 5 d a y s; 

A n y  si n gle A S T a n d/ or A LT ele vati o n > 3 ti mes t he u p per li mit of n or mal re gar dless 
o f acc o m pa nyi n g s ym pt o ms or t he t otal Bilir u bi n s h o ul d pr o m pt re peat testi n g.  T his 
s h o ul d als o pr o m pt re vie w of Secti o n 8. 4. 2 ; a d diti o nal i n vesti gati o ns m ust be 
c o n d ucte d.
Te m p or ar y I nterr u pti o n t o D osi n g 
A n i n vesti gat or ca n te m p orarily i nterr u pt d osi n g f or u p t o a ma xi m u m of 2 8 c o nsec uti ve da ys 
f or a s u bject, f or safety reas o ns or w hile m o nit ori n g a b n or mal la b orat or y  tests if t he 
i n vesti gat or j u d ges t hat t his is necessar y. T he i n vesti gat or s h o ul d use t heir j u d ge me nt wit h 
re gar d t o u nsc he d ule d visits/la b orat or y/cli nical assess me nts re q uire d t o m o nit or t he s u bject 
d uri n g t his ti me-f ra me. If wit hi n t his ti mefra me t he i n vesti gat or j u d ges t hat it is safe t o 
restart d osi n g, t he n t he s u bject ma y restart i n vesti gati o nal pr o d uct. If t he i n vesti gat or j u d ges 
t hat it is n ot safe t o restart d osi n g wit hi n t his ti mefra me t he n t he s u bject m ust be per ma ne ntl y 
disc o n ti n ue d fr o m treat me nt, ha ve a n E n d of Treat me nt visit a n d e nter t he 4-wee k f oll o w - u p 
peri o d.  D oses n ot ta ke n f or t he reas o ns me nti o ne d a b o ve d o n ot c o nstit ute pr ot oc ol 
de viati o ns or me dicati o n err ors a n d s h o ul d n ot be c o nsi dere d d osi n g err ors, b ut s h o ul d be 
n ote d i n t he d osi n g l o g wit h t he reas o n f or re d uce d dr u g c o ns u m pti o n c learl y descri be d.
Disc o nti n u ati o n Cri teri a
S u bjects m ust be per ma ne ntl y  disc o nti n ue d fr o m treat me nt if t he y meet a n y of t he f oll o wi n g 
criteria at a n y p oi nt i n t he st u d y:

Mar ke d pr ol o n gati o n of t he Fri dericia -c orrecte d Q T ( Q Tc F) i nter val t o > 5 0 0 ms or 
> 6 0 m s c ha n ge fr o m scree ni ng E C G.

Seri o us i nfecti o n (see defi niti o n f or Seri o us A d verse E ve nts i n Secti o n 8. 2. 3 ).

P F- 0 4 9 6 5 8 4 2
B 7 4 5 1 0 1 4
Fi nal P r otoc ol A me n d me nt 5, 2 8 Oct o ber 2 0 1 9
P FI Z E R C O N FI D E N TI A L
Pa ge 1 5 0

A n y  blee di ng e ve nt t h o u g ht t o be ass ociate d wit h a platelet c o u nt re d ucti o n per t he 
j u d ge me nt of t he i n vesti gat or (or, if necessar y / desire d, f oll o wi n g disc ussi o n wit h 
s p o ns or).

Ot her a d vers e e ve nt, per j u d g me nt of t he i n vesti gat or, re q uiri n g disc o nti n uati o n fr o m 
treat me nt ( or, if necessar y/ desire d, f oll o wi n g disc ussi o n wit h s p o ns or).

A n y  a d verse e ve nt or la b or at or y a b n or malit y, t hat per t he i n vesti gat or’s j u d ge me nt 
re q uires te m p orar y i nterr upti o n t o d osi n g of i n vesti gati o nal pr o d uct f or > 2 8 da y s.
N O T E: a n y i nitial la b val ue bel o w m ust be reteste d, wit hi n 4 8 h o urs.

T w o se q ue ntial platelet c o u nts < 5 0, 0 0 0/ m m 3.  If t he s u bject has a platelet c o u nt 
< 2 5, 0 0 0/ m m 3, i n vesti gati o nal pr o d uct s h o ul d be tem p oraril y  wit h hel d pe n di n g t he 
c o nfir mat or y retest.

T w o se q ue ntial ne utr o p hil c o u nts < 5 0 0/ m m 3.

T w o se q ue ntial l y m p h oc y te c o u nts < 5 0 0/ m m3.

T w o se q ue ntia l he m o gl o bi n assess me nts < 8. 0 g/ d L or 3 0 % fr o m baseli ne val ue.
A n y  of t he f oll o wi n g:

T w o se q ue ntial A S T or A L T ele vati o ns > 3 ti mes t he u p per li mit of n or mal wit h at 
least o ne t otal bilir u bi n val ue > 2 ti mes t he u p per li mit of n or mal.

T w o se q ue ntial A S T or A L T ele vati o ns > 3 ti mes t he u p per li mit of n or mal wit h a n 
a b n or mal I N R.

T w o se q ue ntial A S T or A L T ele vati o ns > 3 ti mes t he u p per li mit of n or mal 
acc o m pa nie d b y s y m p t o ms c o nsiste nt wit h he patic i nj ur y .

T w o se q ue ntial A S T or A L T ele vati o ns > 5 ti mes t he u p per li mit of n or mal, re gardless 
of t otal bilir u bi n or acc o m pa n y i n g sy m pt o ms.
N ote: A n y of t he a b o ve fi n di n gs s h o ul d pr o m pt re vie w of “ T he P ote nti al C ases of 
Dr u g -I n d uce d Li ver I nj ur y ”, Secti o n 8. 4. 1 f or w hic h a d diti o n a l i n vesti g ati o ns 
m ust be c o n d ucte d.

T w o se q ue ntial i ncreases i n ser u m creati ni ne t hat are > 5 0 % o ver t he a vera ge of 
scree ni n g an d baseli ne val ues A N D a n a bs ol ute i ncrease i n ser u m creati ni ne 
0. 5 m g/ d L.  At t he ti me of s t u d y c o m pleti o n or disc o nti n uati o n, i f a patie nt s h o ul d 
e x hi bit ele vati o ns i n ser u m creati ni ne 3 3 % a b o ve t he a vera ge of scree ni n g a n d 
baseli ne val ues, t he y  will be re-teste d e ver y 1 t o 2 wee ks u ntil t he ser u m creati ni ne 
ele vati o n is f ull y re verse d t o wit hi n 1 0 % of t he a vera ge of scree ni n g a n d baseli ne 
val ues or has sta bilize d.

P F- 0 4 9 6 5 8 4 2
B 7 4 5 1 0 1 4
Fi nal P r otoc ol A me n d me nt 5, 2 8 Oct o ber 2 0 1 9
P FI Z E R C O N FI D E N TI A L
Pa ge 1 5 1
A p pe n di x 5. Fitz p atric k S ki n T y pe 

P F- 0 4 9 6 5 8 4 2
B 7 4 5 1 0 1 4
Fi nal P r otoc ol A me n d me nt 5, 2 8 Oct o ber 2 0 1 9
P FI Z E R C O N FI D E N TI A L
Pa ge 1 5 2
A p pe n di x 6. Pr urit us Se verit y a n d Fre q ue nc y ( Pr urit us N R S)
Se verit y of Pr uri t us
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 “ 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?
Fre q ue nc y of Pr urit us
Select t he n u m ber t hat best descri bes fre q ue nc y  of itc hi n g d ue t o At o pic Der matit is o ver t he 
past 2 4 h o urs (c hec k o ne n u m ber o nl y ).
1 0
9
8
7
6
5
4
3
2
1
0
1 0
9
8
7
6
5
4
3
2
1
0
N o 
itc h
W orst 
itc h 
i ma gi na ble
1 0
9
8
7
6
5
4
3
2
1
0
1 0
9
8
7
6
5
4
3
2
1
0
Ne ver / N o 
itc hi n g
Al wa y s/c o nsta nt
itc hi n g

P F- 0 4 9 6 5 8 4 2
B 7 4 5 1 0 1 4
Fi nal P r otoc ol A me n d me nt 5, 2 8 Oct o ber 2 0 1 9
P FI Z E R C O N FI D E N TI A L
Pa ge 1 5 3
A p pe n di x 7. P atie nt Gl o b al Asses s me nt ( Pt G A)
Clear 
Al m ost Clear
Mil d
M o derate
Se vere
O verall, h o w w o ul d y o u descri be y o ur At o pic Der matitis ri g ht n o w ?
C h o ose o nl y O N E res p o nse.

P F- 0 4 9 6 5 8 4 2
B 7 4 5 1 0 1 4
Fi nal P r otoc ol A me n d me nt 5, 2 8 Oct o ber 2 0 1 9
P FI Z E R C O N FI D E N TI A L
Pa ge 1 5 4
A p pe n di x 8. E ur o pe a n Q u alit y of Li fe 5-Di me nsi o n 5 -Le vel Sc ale ( E Q - 5 D-5 L) a n d 
E ur o pe a n Q u alit y of Life 5- Di me nsi o n Y o ut h Sc ale ( E Q - 5 D-Y i n select c o u ntries)
E Q - 5 D- 5 L
U n der eac h hea di n g, please c hec k t he O N E b o x t hat best descri bes y o ur healt h T O D A Y.
M O BI LI T Y
I ha ve n o pr o ble m s wal ki n g

I ha ve sli g ht pr o ble ms wal ki n g

I ha ve m o derate pr o ble ms wal ki n g

I ha ve se vere pr o ble ms wal ki n g

I a m u na ble t o wal k

S E L F -C A R E
I ha ve n o pr o ble ms was hi n g or dressi n g m yself

I ha ve sli g ht pr o ble ms was hi ng or dressi n g m yself

I ha ve m o derate pr o ble ms was hi n g or dressi n g m yself

I ha ve se vere pr o ble ms was hi n g or dressi n g m yself

I a m u na ble t o was h or dress m y s elf

U S U A L A C TI VI TI E S (e g, w ork, st u dy, h o use w ork, f a mily or leis ure 
activities)
I ha ve n o pr o ble m s d oi n g m y us ual acti vities

I ha ve sli g ht pr o ble ms d oi n g m y us ual acti vities

I ha ve m o derate pr o ble ms d oi n g m y us ual acti vities

I ha ve se vere pro ble ms d oi n g m y us ua l acti vities

I a m u na ble t o d o m y us ual acti vities

P AI N/ DI S C O M F O R T
I ha ve n o pai n or di sc o mf ort

I ha ve sli g ht pai n or disc o mf ort

I ha ve m o derate pai n or disc o mf ort

I ha ve se vere pai n or disc o mf ort

I ha ve e xtre me pai n or disc o mf ort

A N XI E T Y/ D E P R E S SI O N
I a m n ot a n xi o us or de presse d

I a m sli g htl y a n xi o us or de presse d

I a m m o deratel y a n xi o us or de presse d

I a m se verel y a n xi o us or de presse d

I a m e xtre mel y a n xi o us or de presse d


P F- 0 4 9 6 5 8 4 2
B 7 4 5 1 0 1 4
Fi nal P r otoc ol A me n d me nt 5, 2 8 Oct o ber 2 0 1 9
P FI Z E R C O N FI D E N TI A L
Pa ge 1 5 5

We w o ul d li ke t o k n o w h o w g o o d or ba d y o ur 
heal t h is T O D A Y.

T his scale is n u m bere d fr o m 0 t o 1 0 0.

1 0 0 mea ns t he best hea lt h yo u ca n i ma gi ne.

0 mea ns t he w ors t healt h y o u ca n i ma gi ne.

Mar k a n X o n t he scale t o i n dicate h o w y o ur 
healt h is T O D A Y.

N o w, please write t he n u m ber y o u mar ke d o n 
t he scale i n t he b o x bel o w.
Y O U R H E A L T H T O D A Y =
1 0 0
9 5
9 0
8 5
8 0
7 5
7 0
6 5
6 0
5 5
5 0
4 5
4 0
3 5
3 0
2 5
2 0
1 5
1 0
5
0
T h e b e st h e alt h 
y o u c a n i ma gi n e
T h e w o r st h e alt h 
y o u c a n i ma gi n e

P F- 0 4 9 6 5 8 4 2
B 7 4 5 1 0 1 4
Fi nal P r otoc ol A me n d me nt 5, 2 8 Oct o ber 2 0 1 9
P FI Z E R C O N FI D E N TI A L
Pa ge 1 5 6
E Q - 5 D- Y
Descri bi n g y o ur he alt h T O D A Y
U n der eac h hea di n g, please c hec k t he O N E b o x t hat best descri bes yo ur healt h T O D A Y.
M o bilit y ( w al ki n g ar o u n d)
I ha ve n o pr o ble m s wal ki n g ar o u n d

I ha ve s ome pr o ble ms wal ki n g ar o u n d

I ha ve a l ot of pr o ble ms wal ki n g ar o u n d

T a ki n g c are of m ysel f
I ha ve n o pr o ble m s ta ki n g a bat h or s h o wer b y m yself or getti n g dresse d b y 
m yself

I ha ve s o me pr o ble ms ta ki n g a bat h or s h o w er b y m yself or getti n g dresse d b y  
m yself

I ha ve a l ot of pr o ble ms ta ki n g a bat h or s h o w er b y m yself or getti n g dresse d 
b y m yself

D oi n g us u al acti vities (f o r e x a mple, g oi n g t o sc h o ol, h o b bies, s p orts, 
pl a yi n g, d oi n g t hi n gs wit h f a mil y or frie n ds)
I ha ve n o pr o ble m s d oi n g m y us ual acti vities

I ha ve s o me pr o ble ms d oi n g m y us ual acti vities

I ha ve a l ot of pr o ble ms d oi n g m y us ual acti vities

H a vi n g p ai n or disc o m f ort
I ha ve n o pai n or disc o mf ort

I ha ve s o me pai n or disc o mf ort

I ha ve a l ot of pai n or disc o mf ort

Feeli n g w orrie d, s a d, or u n h a p p y
I a m n ot w o rrie d, sa d, or u n ha p p y

I a m a little w orrie d, sa d , or u n ha p p y

I a m v er y w orrie d, sa d, or u n ha p p y


P F- 0 4 9 6 5 8 4 2
B 7 4 5 1 0 1 4
Fi nal P r otoc ol A me n d me nt 5, 2 8 Oct o ber 2 0 1 9
P FI Z E R C O N FI D E N TI A L
Pa ge 1 5 7
H o w g o o d is y o ur he alt h T O D A Y 

We w o ul d li ke t o k n o w h o w g o o d or 
ba d y o ur healt h is T O D A Y.

T his li ne is n u m b ere d fr o m 0 t o 1 0 0.

1 0 0 mea ns t he best healt h y o u ca n 
i ma gi ne.

0 mea ns t he w orst healt h y o u c a n 
i ma gi ne.

Please mar k a n X o n t he s cale t o 
i n dicate h o w y o ur healt h is T O D A Y.
1 0 0
9 5
9 0
8 5
8 0
7 5
7 0
6 5
6 0
5 5
5 0
4 5
4 0
3 5
3 0
2 5
2 0
1 5
1 0
5
0
T h e b e st h e alt h 
y o u c a n i ma gi n e
T h e w o r st h e alt h 
y o u c a n i ma gi n e

P F- 0 4 9 6 5 8 4 2
B 7 4 5 1 0 1 4
Fi nal P r otoc ol A me n d me nt 5, 2 8 Oct o ber 2 0 1 9
P FI Z E R C O N FI D E N TI A L
Pa ge 1 6 0

P F- 0 4 9 6 5 8 4 2
B 7 4 5 1 0 1 4
Fi nal P r otoc ol A me n d me nt 5, 2 8 Oct o ber 2 0 1 9
P FI Z E R C O N FI D E N TI A L
Pa ge 1 6 1
A p pe n di x 1 0. P atie nt - Orie nte d Ecze m a Me as ure ( P O E M)

P F- 0 4 9 6 5 8 4 2
B 7 4 5 1 0 1 4
Fi nal P r otoc ol A me n d me nt 5, 2 8 Oct o ber 2 0 1 9
P FI Z E R C O N FI D E N TI A L
Pa ge 1 6 2
A p pe n di x 1 1. H os pit al A n xiet y a n d De pressi o n Sc ale ( H A D S)

P F- 0 4 9 6 5 8 4 2
B 7 4 5 1 0 1 4
Fi nal P r otoc ol A me n d me nt 5, 2 8 Oct o ber 2 0 1 9
P FI Z E R C O N FI D E N TI A L
Pa ge 1 6 3

P F- 0 4 9 6 5 8 4 2
B 7 4 5 1 0 1 4
Fi nal P r otoc ol A me n d me nt 5, 2 8 Oct o ber 2 0 1 9
P FI Z E R C O N FI D E N TI A L
Pa ge 1 6 4
C CI

P F- 0 4 9 6 5 8 4 2
B 7 4 5 1 0 1 4
Fi nal P r otoc ol A me n d me nt 5, 2 8 Oct o ber 2 0 1 9
P FI Z E R C O N FI D E N TI A L
Pa ge 1 6 5
C CI

P F- 0 4 9 6 5 8 4 2
B 7 4 5 1 0 1 4
Fi nal P r otoc ol A me n d me nt 5, 2 8 Oct o ber 2 0 1 9
P FI Z E R C O N FI D E N TI A L
Pa ge 1 6 6
C CI

P F- 0 4 9 6 5 8 4 2
B 7 4 5 1 0 1 4
Fi nal P r otoc ol A me n d me nt 5, 2 8 Oct o ber 2 0 1 9
P FI Z E R C O N FI D E N TI A L
Pa ge 1 6 7

P F- 0 4 9 6 5 8 4 2
B 7 4 5 1 0 1 4
Fi nal P r otoc ol A me n d me nt 5, 2 8 Oct o ber 2 0 1 9
P FI Z E R C O N FI D E N TI A L
Pa ge 1 6 8
A p pe n di x 1 3. S h ort F or m -3 6 Versi o n 2 ( S F -3 6 v 2)

P F- 0 4 9 6 5 8 4 2
B 7 4 5 1 0 1 4
Fi nal P r otoc ol A me n d me nt 5, 2 8 Oct o ber 2 0 1 9
P FI Z E R C O N FI D E N TI A L
Pa ge 1 6 9

P F- 0 4 9 6 5 8 4 2
B 7 4 5 1 0 1 4
Fi nal P r otoc ol A me n d me nt 5, 2 8 Oct o ber 2 0 1 9
P FI Z E R C O N FI D E N TI A L
Pa ge 1 7 0

P F- 0 4 9 6 5 8 4 2
B 7 4 5 1 0 1 4
Fi nal P r otoc ol A me n d me nt 5, 2 8 Oct o ber 2 0 1 9
P FI Z E R C O N FI D E N TI A L
Pa ge 1 7 1

P F- 0 4 9 6 5 8 4 2
B 7 4 5 1 0 1 4
Fi nal P r otoc ol A me n d me nt 5, 2 8 Oct o ber 2 0 1 9
P FI Z E R C O N FI D E N TI A L
Pa ge 1 7 2

P F- 0 4 9 6 5 8 4 2
B 7 4 5 1 0 1 4
Fi nal P r otoc ol A me n d me nt 5, 2 8 Oct o ber 2 0 1 9
P FI Z E R C O N FI D E N TI A L
Pa ge 1 7 3

P F- 0 4 9 6 5 8 4 2
B 7 4 5 1 0 1 4
Fi nal P r otoc ol A me n d me nt 5, 2 8 Oct o ber 2 0 1 9
P FI Z E R C O N FI D E N TI A L
Pa ge 1 7 4
A p pe n di x 1 4. F u ncti o n al Assess me nt of C hr o nic Ill ness T her a p y F ati g ue Sc ale 
( F A CI T-F)

P F- 0 4 9 6 5 8 4 2
B 7 4 5 1 0 1 4
Fi nal P r otoc ol A me n d me nt 5, 2 8 Oct o ber 2 0 1 9
P FI Z E R C O N FI D E N TI A L
Pa ge 1 7 5

P F- 0 4 9 6 5 8 4 2
B 7 4 5 1 0 1 4
Fi nal P r otoc ol A me n d me nt 5, 2 8 Oct o ber 2 0 1 9
P FI Z E R C O N FI D E N TI A L
Pa ge 1 7 6
A p pe n di x 1 5. C ol u m bi a Se verit y S uici d e R ati n g Sc ale ( C-S S R S) f or Scree ni n g a n d 
B aseli ne Visits

P F- 0 4 9 6 5 8 4 2
B 7 4 5 1 0 1 4
Fi nal P r otoc ol A me n d me nt 5, 2 8 Oct o ber 2 0 1 9
P FI Z E R C O N FI D E N TI A L
Pa ge 1 7 7

P F- 0 4 9 6 5 8 4 2
B 7 4 5 1 0 1 4
Fi nal P r otoc ol A me n d me nt 5, 2 8 Oct o ber 2 0 1 9
P FI Z E R C O N FI D E N TI A L
Pa ge 1 7 8

P F- 0 4 9 6 5 8 4 2
B 7 4 5 1 0 1 4
Fi nal P r otoc ol A me n d me nt 5, 2 8 Oct o ber 2 0 1 9
P FI Z E R C O N FI D E N TI A L
Pa ge 1 7 9
A p pe n di x 1 6. C ol u m bi a Se verit y S uici de R ati n g Sc ale ( C- S S R S) Si nce L ast Visit

P F- 0 4 9 6 5 8 4 2
B 7 4 5 1 0 1 4
Fi nal P r otoc ol A me n d me nt 5, 2 8 Oct o ber 2 0 1 9
P FI Z E R C O N FI D E N TI A L
Pa ge 1 8 0

P F- 0 4 9 6 5 8 4 2
B 7 4 5 1 0 1 4
Fi nal P r otoc ol A me n d me nt 5, 2 8 Oct o ber 2 0 1 9
P FI Z E R C O N FI D E N TI A L
Pa ge 1 8 1
A p pe n di x 1 7. S uici de Be h a vi ors Q uesti o n n aire – Re vise d ( S B Q- R) 

P F- 0 4 9 6 5 8 4 2
B 7 4 5 1 0 1 4
Fi nal P r otoc ol A me n d me nt 5, 2 8 Oct o ber 2 0 1 9
P FI Z E R C O N FI D E N TI A L
Pa ge 1 8 2
A p pe n di x 1 8. P atie nt He alt h Q uesti o n n aire – 8 ite ms ( P H Q - 8)

P F- 0 4 9 6 5 8 4 2
B 7 4 5 1 0 1 4
Fi nal P r otoc ol A me n d me nt 5, 2 8 Oct o ber 2 0 1 9
P FI Z E R C O N FI D E N TI A L
Pa ge 1 8 3
A p pe n di x 1 9. Ast h m a C o ntr ol Q uesti o n n aire ( A C Q)