A PHASE 2B, RANDOMIZED, DOUBLE BLIND, VEHICLE CONTROLLED, PARALLEL GROUP STUDY TO ASSESS THE EFFICACY, SAFETY, TOLERABILITY AND PHARMACOKINETICS OF MULTIPLE DOSE LEVELS OF PF-07038124 OINTMENT FOR 12 WEEKS IN PARTICIPANTS 12 YEARS AND OLDER AND WITH MILD-TO-MODERATE ATOPIC DERMATITIS OR MILD-TO-SEVERE PLAQUE PSORIASIS
Phase: PHASE2
Conditions: Atopic Dermatitis, Plaque Psoriasis
Sponsor: Pfizer

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A P H A S E 2 B, R A N D O MI Z E D, D O U B L E B LI N D, V E HI C L E C O N T R O L L E D, 
P A R A L L E L G R O U P S T U D Y T O A S S E S S T H E E F FI C A C Y, S A F E T Y, 
T O L E R A BI LI T Y A N D P H A R M A C O KI N E TI C S O F M U L TI P L E D O S E L E V E L S
O F 
P F -0 7 0 3 8 1 2 4 OI N T M E N T F O R 1 2 W E E K S I N P A R TI CI P A N T S 1 2 Y E A R S A N D 
O L D E R A N D WI T H MI L D -T O -M O D E R A T E A T O PI C D E R M A TI TI S O R
MI L D -T O -S E V E R E P L A Q U E P S O RI A SI S
St u d y I nter ve nti o n N u m ber :
P F -0 7 0 3 8 1 2 4
St u d y I nter ve nti o n N a me:
N/ A
U S I N D N u m ber:
1 4 4 2 1 7
E u dr a C T N u m ber:
N/ A
Cli nic al Tri als. g o v I D:  
N C T 0 5 3 7 5 9 5 5
Pr ot oc ol N u m ber:
C 3 9 4 1 0 0 5
P h ase:
2 b
Brief Title: A P hase 2 b Efficac y, Safet y, T olera bilit y a n d P har mac o ki netics St u d y wit h M ulti ple D ose 
Le vels of P F -0 7 0 3 8 1 2 4 Oi nt me nt i n Partici pa nts 1 2 Y ears a n d O l der a n d W it h Mil d t o M o derate At o pic 
Der m atitis or Mil d t o Se vere Pla q ue Ps oriasis
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 o c u me nts, yo 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.
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D oc u me nt Hist or y
D oc u me nt
Versi o n D ate
A me n d me nt 1
0 2 N o ve m ber 2 0 2 2
Ori gi nal pr ot oc ol
2 1 A pril 2 0 2 2
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 R Bs/ E Cs a n d a n y pr ot oc ol a d mi nistrati ve c ha n ge 
letter(s).
Pr ot oc ol A me n d me nt S u m m ar y of C h a n ges T a ble
A m e n d me nt 1 ( 0 2 N o ve m ber 2 0 2 2)
O ver all R ati o n ale f or t he A me nd me nt: T he a me n d me nt is m a ki n g a s u bst a nti al c h a n ge 
i n per mitte d c o ntr ace pti o n met h o ds of fe m ale p artici p a nts .
Secti o n # 
a n d N a me
Descri pti o n of C h a n ge
Brief R ati o n ale
S u bst a nti al or 
N o ns u bst a nti al
Secti o n 
1 0 . 4.2
Fe male 
Partici pa nt 
Re pr o d ucti ve 
I ncl usi o n 
Criteria
1. A d de d re q uire me nt of 
c o nc urre nt use of a 
barrier met h o d w he n 
hi g hl y effecti ve 
c o ntrace pti o n met h o ds 
t hat are user- de pe n de nt 
are use d.
C o nc urre nt use of a 
barrier met h o d of 
c o ntrace pti o n pr o vi des 
a d diti o nal pr otecti o n wit h 
hi g hl y effecti ve user 
de pe n de nt met h o ds as 
re q uire d per Secti o n 4. 2. 2.
S u bs ta ntial
Secti o n 
1 0. 4. 4 
C o ntrace pti o n 
Met h o ds
1.
M o difie d list of
hi g hl y  
effecti ve c o ntrace pti o n 
met h o d s b y  a d di n g 
“ + barrier” t o met h o ds 
w hic h were user 
de pe n de nt . 
2.
Hi g hli g hte d acce pta ble 
use of barrier met h o ds.
3.
Delete d list of met h o ds
( #9 - # 1 2) t o a v oi d 
t h ose bei n g c o nsi dere d 
as hi g hl y effecti ve , 
w he n n ot use d i n 
c o nj u ncti o n wit h ot her 
met h o ds.
C o nc urre nt use of a 
barrier met h o d of 
c o ntrace pti o n pr o vi des 
a d diti o nal pr otecti o n wit h 
hi g hl y effecti ve user 
de pe n de nt met h o ds.
S u bsta ntial
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Secti o n # 
a n d N a me
Descri pti o n of C h a n ge
Brief R ati o n ale
S u bst a nti al or 
N o ns u bst a nti al
Title Pa ge
A d de d cli nicaltrials. g o v 
I D
A vaila bilit y  of I D as trial 
is re gistere d o n 
cli nicaltrials. g o v .
N o ns u bsta ntial
Secti o n 1. 3. 1 
At o pic 
Der matitis, 
F o ot n ote ‘j’
Secti o n 1. 3. 2. 
Pla q ue 
Ps oriasis 
F o ot n ote ‘i’
U p date d f o ot n otes i n S o A 
ta bles t o clarif y t hat if a 
partici pa nt has n’t 
wit h dra w n c o nse nt fr o m 
partici pati o n fr o m t he 
st u d y, e-diar y  ma y be 
c ollecte d at E T or E O S 
visits .
Clarificati o n pr o vi des 
sites wit h o pti o n of n ot 
c ollecti n g e-diar y  if 
st ora ge s pace at t he site is 
li mite d, t here b y re d uci n g 
b ur de n.
N o ns u bsta ntial
Secti o n 1. 3. 1 
At o pic 
Der matitis, 
F o ot n ote ‘ k’
Secti o n 1. 3. 2. 
Pla q ue 
Ps oriasis, 
F o ot n ote ‘j’
U p date d f o ot n otes i n S o A 
ta bles t o clarif y i nsta nce 
w he n l ocal t olera bilit y  
assess me nt is n ot re q uire d.
L ocal t olera bilit y  
assess me nt perf or me d 
i m me diatel y after 
a p plicati o n of t he I P o n 
n o n -lesi o nal s ki n a n d 
pri or t o a p plicati o n o n 
lesi o nal s ki n. T heref ore, if 
I P a p plicati o n is n ot 
pla n ne d, l ocal t olera bilit y  
assess me nt is n ot re q uire d. 
N o ns u bsta ntial
Secti o n 
1 0. 4. 3. 
W o me n of 
C hil d beari n g 
P ote ntia l
A d de d n ote t o all o w F S H 
testi n g f or w o me n o ver 
6 0 ye ars of a ge, per PI 
discreti o n .
Alt h o u g h n ot a ntici pate d, 
o n rare occasi o ns, base d 
o n t he me dical a n d 
me dicati o n hist or y  of a 
fe male partici pa nt, PI ma y 
dee m it necessar y t o 
c o nfir m p ost-me n o pa usal 
stat us usi n g F S H le vels.
N o ns u bsta ntial
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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 0
1. P R O T O C O L  S U M M A R Y................................................................................................... 1 1
1. 1. S y n o psis .................................................................................................................. 1 1
1. 2. Sc he ma .................................................................................................................... 1 6
1. 3. Sc he d ule of Acti vities ............................................................................................. 1 7
1. 3. 1. At o pic Der matitis ........................................................................................ 1 7
1. 3. 2. Pla q ue Ps oriasis.......................................................................................... 2 1
2. I N T R O D U C TI O N ............................................................................................................... 2 5
2. 1. St u d y  Rati o nale....................................................................................................... 2 5
2. 2. Bac k gr o u n d ............................................................................................................. 2 5
2. 2. 1. Cli ni cal O ver vie w ....................................................................................... 2 8
2. 3. Be nefit/ Ris k Assess me nt ......................................................................................... 3 0
......................................................................................... 3 1
2. 3. 2. Be nefit Assess me nt ..................................................................................... 3 3
2. 3. 3. O verall Be nefit/ Ris k C o ncl usi o n ................................................................ 3 3
3. O BJ E C TI V E S, E N D P O I N T S, A N D E S TI M A N D S ........................................................... 3 4
4. S T U D Y D E SI G N ................................................................................................................. 3 9
4. 1. O verall Desi g n ......................................................................................................... 3 9
4. 2. Scie ntific Rati o nale f or St u d y  Desi g n..................................................................... 4 0
4. 2. 1. Di versit y  of St u d y P o p ulati o n .................................................................... 4 1
4. 2. 2. C h oice of C o ntrace pti o n/ Barrier Re q uire me nts ......................................... 4 1
4. 2. 3. C ollecti o n of Retai ne d Researc h Sa m ples .................................................. 4 1
4. 3. J ustificati o n f or D ose ..............................................................................................4 1
4. 4. E n d of St u d y  Defi niti o n .......................................................................................... 4 4
5. S T U D Y P O P U L A T I ON ...................................................................................................... 4 4
5. 1. I ncl usi o n C riteria..................................................................................................... 4 4
5. 1. 1. Ge neral I ncl usi o n Criteria A p plica ble f or b ot h A D a n d Ps O .....................4 4
5. 1. 2. Disease -S pecific I ncl usi o n Criteria: ........................................................... 4 5
5. 1. 2. 1. A D S pecific I ncl usi o n Criteria .................................................. 4 5
5. 1. 2. 2. Ps O S pecific I ncl usi o n Criteria ................................................. 4 5
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C CI

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5. 2. E xcl usi o n Criteria ....................................................................................................4 5
5. 3. L ifest yle C o nsi derati o ns..........................................................................................4 7
5. 3. 1. C o ntrace pti o n ..............................................................................................4 7
5. 3. 2. Dietar y  S u p ple me nts...................................................................................4 8
5. 3. 3. Me dicati o ns/ Treat me nts Disc o nti n uati o n, N o n -Me dicate d E m ollie nts
.....4 8
5. 3. 4. Ot her Lifest yl e Re q uire me nts..................................................................... 4 9
5. 4. Scree n Fail ures ........................................................................................................5 0
6. S T U D Y I N T E R V E N TI O N( S) A N D C O N C O MI T A N T T H E R A P Y .................................5 0
6. 1. St u d y  Inter ve nti o n(s) A d mi nistere d ........................................................................5 0
6. 1. 1. A d mi nistrati o n ............................................................................................5 1
6. 2. Pre parati o n, Ha n dli n g, St ora ge, a n d Acc o u nta bilit y ...............................................5 3
6. 2. 1. Pre parati o n a n d Dis pe nsi n g ........................................................................5 4
6. 2. 2. St u d y  Inter ve nti o n Acc o u nta bilit y ..............................................................5 5
6. 2. 3. Destr ucti o n of St u d y  Inter ve nti o n S u p plies ................................................5 5
6. 3. Meas ures t o Mi ni mize Bias: Ra n d o mizati o n a n d Bli n di n g .....................................5 6
6. 3. 1. All ocati o n t o St u d y I nter ve nti o n ................................................................5 6
6. 3. 2. Brea ki n g t he Bli n d ......................................................................................5 6
6. 4. St u d y  Inter ve nti o n C o m plia nce ...............................................................................5 6
6. 5. D ose M o dificati o n ...................................................................................................5 7
6. 6. C o nti n ue d Access t o St u d y  Inter ve nti o n After t he E n d of t he St u d y ......................5 7
6. 7. Treat me nt of O ver d ose................................ ............................................................5 7
6. 8. C o nc o mita nt T hera p y ..............................................................................................5 8
6. 8. 1. Resc ue Me dici ne .........................................................................................5 8
7. DI S C O N TI N U A TI O N O F S T U D Y I N T E R V E N TIO N A N D P A R TI CI P A N T 
DI S C O N TI N U A TI O N/ WI T H D R A W A L ...........................................................................5 8
7. 1. Disc o nti n uati o n of St u d y  Inter ve nti o n ....................................................................5 8
7. 1. 1. L i ver I nj ur y.................................................................................................5 9
7. 1. 2. E C G C ha n ges ..............................................................................................5 9
7. 1. 3. Pre g na nc y ...................................................................................................5 9
7. 1. 4. L ocal T olera bilit y .......................................................................................5 9
7. 1. 5. A Es .............................................................................................................6 0
7. 1. 6. Te m p orar y  Disc o nti n uati o n........................................................................6 0
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7. 2. Partici pa nt Disc o nti n uati o n/ Wit h dra wal Fr o m t he St u d y ....................................... 6 0
7. 2. 1. Wit h dra wal of C o nse nt ............................................................................... 6 1
7. 3. L ost t o F oll o w -U p ................................................................................................... 6 1
8. S T U D Y A S S E S S M E N T S A N D P R O C E D U R E S ...............................................................6 2
8. 1. Efficac y  Assess me nts..............................................................................................6 2
8. 1. 1. Efficac y  Assess me nts f or A D..................................................................... 6 2
8. 1. 1. 1. P h y sicia n Assess me nts ..............................................................6 3
....................................................... 6 4
...................................................................... 6 5
..............................................................6 5
....................................................... 6 6
8. 1. 3. Rater Q ualificati o ns .................................................................................... 6 7
8. 2. Safet y Assess me nts ................................................................................................. 6 8
8. 2. 1. Me dical a n d Me dicati o n Hist or y ................................................................ 6 8
8. 2. 2. P h y sical E xa mi nati o ns (Incl u di n g Hei g ht a n d Wei g ht) ............................. 6 9
8. 2. 3. Electr ocar di o gra ms ..................................................................................... 6 9
8. 2. 4. Vital Si g ns .................................................................................................. 7 0
8. 2. 5. Cli nical Safet y  La b orat or y Assess me nts.................................................... 7 1
8. 2. 6. S uici dal I deati o n a n d Be ha vi or Ris k M o nit ori n g - C-S S R S ...................... 7 1
8. 2. 7. L ocal T olera bilit y  Assess me nt ................................................................... 7 2
8. 2. 8. Pre g na nc y  Testi n g ...................................................................................... 7 2
8. 3. A d verse E ve nts, Seri o us A d verse E ve nts, a n d Ot her Safet y Re p orti n g ................. 7 2
8. 3. 1. Ti me Peri o d a n d F re q ue nc y f or C ollecti n g A E a n d S A E I nf or mati o n....... 7 3
8. 3. 1. 1. Re p orti n g S A Es t o Pfizer Safet y ............................................... 7 4
8. 3. 1. 2. Rec or di n g N o nseri o us A Es a n d S A Es o n t he C R F ................... 7 4
8. 3. 2. Met h o d of Detecti n g A Es a n d S A Es .......................................................... 7 4
8. 3. 3. F oll o w -U p of A Es a n d S A Es ...................................................................... 7 4
8. 3. 4. Re g ulat or y  Re p orti n g Re q uire me nts f or S A Es...........................................7 4
8. 3. 5. E n vir o n me ntal E x p os ure, E x p os ure 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 ..................................................... 7 5
8. 3. 5. 1. E x p os ure D uri n g Pre g na nc y ......................................................7 5
8. 3. 5. 2. E x p os ure D uri n g Breastfee di n g ................................................ 7 7
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C CI
C CI
C CI
C CI

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8. 3. 5. 3. Occ u pati o nal E x p os ure ............................................................. 7 7
8. 3. 6. Car di o vasc ular a n d Deat h E ve nts ...............................................................7 7
8. 3. 7. Disease -Relate d E ve nts a n d/ or Disease - Relate d O utc o mes N ot 
Q ualif yi n g as A Es or S A Es .............................................................................. 7 7
8. 3. 8. A d verse E ve nts of S pecial I nterest ............................................................. 7 8
8. 3. 8. 1. Lac k of Efficac y ........................................................................ 7 8
8. 3. 9. Me dical De vice Deficie ncies ...................................................................... 7 8
8. 3. 1 0. Me dicati o n Err ors ..................................................................................... 7 8
.................................................................................................... 7 9
8. 5. G e netics ................................................................................................................... 8 0
8. 5. 1. S pecifie d Ge netics ...................................................................................... 8 0
8. 5. 2. Retai ne d Researc h Sa m ples f or Ge netics ................................................... 8 0
8. 6. Bi o mar kers .............................................................................................................. 8 0
8. 6. 1. S peci fie d Ge ne E x pressi o n ( R N A) Researc h ............................................. 8 0
8. 6. 2. S pecifie d Pr otei n Researc h ......................................................................... 8 0
............................................................................. 8 0
...............................................................8 1
....................................................................... 8 1
.......................................................................... 8 1
8. 6. 3. S pecifie d Meta b ol o mic Researc h ...............................................................8 1
8. 6. 4. Retai ne d Researc h Sa m ples f or Bi o mar kers ............................................... 8 1
8. 7. I m m u n o ge nicit y Assess me nts ................................................................................. 8 1
8. 8. Healt h Ec o n o mics ................................................................................................... 8 1
8. 9. B S A f or St u d y I nter ve nti o n Nee d ( Treata ble B S A)................................................ 8 2
8. 1 0. E x pl orat or y  Assess me nts ...................................................................................... 8 2
8. 1 0. 1. Ta pe Stri p S u b- st u d y ................................................................................ 8 2
8. 1 0. 2. P h ot o gra p h y S u b -st u d y............................................................................. 8 2
9. S T A TI S TI C A L C O N SI D E R A TI O N S ................................................................................8 3
9. 1. Statistical H y p ot heses ............................................................................................. 8 3
9. 1. 1. Esti ma n ds .................................................................................................... 8 3
9. 1. 1. 1. Pri mar y  Esti ma n d...................................................................... 8 3
9. 1. 1. 2. Sec o n dar y  Esti ma n d.................................................................. 8 4
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C CI
C CI
C CI
C CI
C CI

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Fi nal Pr ot oc ol A me n d me nt 1 , 0 2 N o ve m ber 2 0 2 2
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9. 1. 2. M ulti plicit y  A dj ust me nt.............................................................................. 8 5
9. 2. A nal y sis Sets ........................................................................................................... 8 5
9. 3. Statistical A nal y ses ................................................................................................. 8 5
9. 3. 1. Ge neral C o nsi derati o ns ............................................................................... 8 5
9. 3. 2. A nal y ses f or Bi nar y E n d p oi nts................................................................... 8 5
9. 3. 3. A nal y ses f or C o nti n u o us E n d p oi nts ........................................................... 8 6
9. 3. 4. Pri mar y  E n d p oi nt(s)/ Esti ma n d(s) A nalys is................................................ 8 6
9. 3. 5. Sec o n dar y  E n d p oi nt(s)/ Esti ma n d(s) A nalys is............................................ 8 6
9. 3. 6. Tertiar y / E x plorat or y  E n d p oi nt(s) ...............................................................8 6
9. 3. 7. Safet y A nal ys es .......................................................................................... 8 6
9. 3. 7. 1. Electr ocar di o gra m A nal y ses...................................................... 8 7
9. 3. 8. Ot her A nal ys es ............................................................................................ 8 7
....................................................... 8 7
9. 3. 8. 2. I nteri m A nal ys es ....................................................................... 8 7
9. 4. Sa m ple Size Deter mi nati o n .....................................................................................8 7
9. 4. 1. Sa m ple Size Deter mi nati o n f or A D ............................................................ 8 7
9. 4. 2. Sa m ple Size Deter mi nati o n f or Ps O ........................................................... 8 8
1 0. S U P P O R TI N G D O C U M E N T A TI O N A N D O P E R A TI O N A L 
C O N SI D E R A TI O N S .......................................................................................................... 8 9
1 0. 1. A p pe n di x 1: Re g ulat or y , Et hical, a n d St u d y O versi g ht C o nsi derati o ns............... 8 9
1 0. 1. 1. Re g ulat or y a n d Et hical C o nsi derati o ns .................................................... 8 9
1 0. 1. 1. 1. Re p orti n g of Safet y  Iss ues a n d Seri o us Breac hes of t he 
Pr ot oc ol or I C H G C P ......................................................................... 9 0
1 0. 1. 2. Fi na ncial Discl os ure .................................................................................9 0
1 0. 1. 3. I nf or me d C o nse nt/asse nt Pr ocess .............................................................9 0
1 0. 1. 4. Data Pr otecti o n ......................................................................................... 9 1
1 0. 1. 5. C o m mittees Str uct ure ...............................................................................9 2
1 0. 1. 5. 1. Data M o nit ori n g C o m mittee ................................................... 9 2
1 0. 1. 6. Disse mi nati o n of Cli nical St u d y  Data ...................................................... 9 2
1 0. 1. 7. Data Q ualit y Ass ura nce ............................................................................ 9 3
1 0. 1. 8. S o urce D oc u me nts .................................................................................... 9 5
1 0. 1. 9. St u d y  a n d Site Start a n d Cl os ure ..............................................................9 5
0 9 0 1 7 7 e 1 9 b b 9 c 5f d\ A p pr o v e d\ A p pr o v e d O n: 0 3- N o v- 2 0 2 2 1 1: 4 8 ( G M T)
C CI

P F -0 7 0 3 8 1 2 4
Pr ot oc ol C 3 9 4 1 0 0 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 2 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 Marc h 2 0 2 1)
Pa ge 9
................................................................................... 9 6
1 0. 1. 1 1. S p o ns or’s Q ualifie d Me dical Pers o n nel ................................................. 9 7
1 0. 2. A p pe n di x 2: Cli nical La b orat or y  Tests................................................................. 9 8
1 0. 3. A p pe n di x 3: A d verse E ve nts: Defi niti o ns a n d Pr oce d ures f or Rec or di n g, 
E val uati n g, F oll o w -U p, a n d Re p orti n g ..................................................................... 9 9
1 0. 3. 1. Defi niti o n of A E ....................................................................................... 9 9
1 0. 3. 2. Defi niti o n of a n S A E .............................................................................. 1 0 0
1 0. 3. 3. Rec or di n g/ Re p orti n g a n d F oll o w -U p of A Es a n d/ or S A Es D uri n g 
t he Acti ve C ollecti o n Peri o d.......................................................................... 1 0 2
1 0. 3. 4. Re p orti n g of S A Es .................................................................................. 1 0 5
1 0. 4. A p pe n di x 4: C o ntrace pti v e a n d Barrier G ui da nce .............................................. 1 0 7
1 0. 4. 1. Male Partici pa nt Re pr o d ucti ve I ncl usi o n Criteria .................................. 1 0 7
1 0. 4. 2. Fe male Partici pa nt Re pr o d ucti ve I ncl usi o n Criteria ............................... 1 0 7
1 0. 4. 3. W o ma n of C hil d beari n g P ote ntial .......................................................... 1 0 8
1 0. 4. 4. C o ntrace pti o n Met h o ds ........................................................................... 1 0 9
1 0. 5. A p pe n di x 5: Ge netics .......................................................................................... 1 1 1
1 0. 6. A p pe n di x 6: L i ver Safet y: S u g geste d Acti o ns a n d F oll o w-U p Assess me nts ..... 1 1 2
1 0. 7. A p pe n di x 7: E C G Fi n di n gs of P ote ntial Cli nical C o ncer n ................................. 1 1 4
1 0. 8. A p pe n di x 8: Pr o hi bite d Pri or a n d C o nc o mita nt Me dicati o ns ............................. 1 1 6
1 0. 8. 1. Pr o hi bite d Pri or a n d C o nc o mita nt Me dicati o ns ..................................... 1 1 6
1 0. 8. 2. Pr o hi bite d C o nc o mita nt Me dicati o ns w hic h ma y  Res ult i n D DI........... 1 1 8
1 0. 9. A p pe n di x 9: Alter nati ve Meas ures D uri n g P u blic E mer ge ncies ........................ 1 1 9
1 0. 9. 1. Tele healt h Visits ..................................................................................... 1 1 9
1 0. 9. 2. Alter nati ve Facilities f or Safet y Assess me nts ........................................ 1 2 0
1 0. 9. 2. 1. La b orat or y  Testi n g................................................................ 1 2 0
1 0. 9. 2. 2. Electr ocar di o gra ms ................................................................ 1 2 1
1 0. 9. 3. St u d y  Inter ve nti o n .................................................................................. 1 2 1
1 0. 9. 4. H o me Healt h Visits .................................................................................1 2 1
1 0. 9. 5 . A d verse E ve nts a n d Seri o us A d verse E ve nts.........................................1 2 2
1 0. 9. 6. Efficac y  Assess me nts .............................................................................1 2 2
1 0. 1 0. A p pe n di x 1 0: Dia g n osis Criteria f or A D .......................................................... 1 2 3
1 0. 1 1. A p pe n di x 1 1: C -S S R S ....................................................................................... 1 2 4
0 9 0 1 7 7 e 1 9 b b 9 c 5f d\ A p pr o v e d\ A p pr o v e d O n: 0 3- N o v- 2 0 2 2 1 1: 4 8 ( G M T)
C CI

P F -0 7 0 3 8 1 2 4
Pr ot oc ol C 3 9 4 1 0 0 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 2 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 Marc h 2 0 2 1)
Pa ge 1 0
1 0. 1 2. A p pe n di x 1 2: Disease -S pecific Assess me nts .................................................... 1 2 5
1 0. 1 2. 1. A D -s pecific assess me nts ...................................................................... 1 2 5
1 0. 1 2. 1. 1. I G A ...................................................................................... 1 2 5
1 0. 1 2. 1. 2. E A SI .................................................................................... 1 2 5
1 0. 1 2. 1. 3. B S A ..................................................................................... 1 2 8
1 0. 1 2. 1. 4. Se vere Lesi o n T S S ..............................................................1 2 8
1 0. 1 2. 2. Ps oriasis -s pecific assess me nts ..............................................................1 2 9
1 0. 1 2. 2. 1. P G A ..................................................................................... 1 2 9
1 0. 1 2. 2. 2. P A SI .................................................................................... 1 2 9
1 0. 1 2. 2. 3. B S A ..................................................................................... 1 3 1
1 0. 1 3. A p pe n di x 1 3: A b bre viati o ns ............................................................................. 1 3 2
1 1. R E F E R E N C E S ................................................................................................................ 1 3 6
LI S T O F T A B L E S
Ta ble 1.
P F -0 7 0 3 8 1 2 4 
 – C o m plete d St u dies 
as of Ja n uar y 2 0 2 2.................................................................................... 3 0
Ta ble 2.
Partici pa nt Distri b uti o n ............................................................................. 4 0
 
.................................. 4 2
 
....................... 4 3
Ta ble 5.
S ki n T olera bilit y  Gra di n g Sys te m f or N o n-lesi o nal S ki n......................... 7 2
Ta ble 6.
Pr ot oc ol Re q uire d Safet y L a b orat or y Assess me nts.................................. 9 8
Ta ble 7.
I n vesti gat or's Gl o bal Assess me nt f or A D ............................................... 1 2 5
Ta ble 8.
Cli nical Si g n Se verit y  Sc ori n g Criteria f or E A SI................................... 1 2 6
Ta ble 9.
E A SI  Area Sc ore Criteria ....................................................................... 1 2 7
Ta ble 1 0.
B o d y  Re gi o n Wei g hti n g.........................................................................1 2 7
Ta ble 1 1.
Se vere Lesi o n T S S ..................................................................................1 2 8
Ta ble 1 2.
P h y sicia n Gl o bal Assess me nt ( P G A) Sc ore ...........................................1 2 9
Ta ble 1 3. 
C o m p o ne nt Sc ori n g Criteria f or P A SI................................ ....................1 3 0
Ta ble 1 4.
P A SI  Area Sc ore Criteria........................................................................1 3 0
Ta ble 1 5.
B o d y Re gi o n Wei g hti n g .........................................................................1 3 1
0 9 0 1 7 7 e 1 9 b b 9 c 5f d\ A p pr o v e d\ A p pr o v e d O n: 0 3- N o v- 2 0 2 2 1 1: 4 8 ( G M T)
C CI
C CI
C CI

P F -0 7 0 3 8 1 2 4
Pr ot oc ol C 3 9 4 1 0 0 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 2 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 Marc h 2 0 2 1)
Pa ge 1 1
1. P R O T O C O L S U M M A R Y 
1. 1. S y n o psis 
Brief Title:
A P hase 2 b efficac y, safet y, t olera bility a n d p har mac o ki netics st u d y wit h m ulti ple d ose le vels 
of P F - 0 7 0 3 8 1 2 4 oi nt me nt i n partici pa nts 1 2 y ears a n d ol der a n d wit h mil d -t o-m o derate 
at o pic der matitis or mil d -t o-se vere pla q ue ps oriasis.
R ati o n ale
T his m ultice nter, ra n d o mize d, d o u ble bli n d, ve hicle c o ntr olle d, parallel gr o u p st u d y  is bei n g 
c o n d ucte d t o assess efficac y, safety, t olera bilit y a n d P K of P F -0 7 0 3 8 1 2 4 oi nt me nt vers us 
ve hicle c o ntr ol i n t he treat me nt of partici pa nts 1 2 y ears a n d ol der, a n d wit h mil d -t o-m o derate 
A D or mil d -t o-se vere Ps O .
O bjecti ves , E n d p oi nts , a n d Esti m a n ds
A T O PI C D E R M A TI TI S
O bjecti ves
E n d p oi nts
Esti m a n ds
Pri m ar y: 
Pri m ar y:
Pri m ar y: 

T o c o m pare t he efficac y of 
2 d ose le vels of P F -0 7 0 3 8 1 2 4 
oi nt me nt vers us ve hicle, usi n g 
I G A s uccess as t he e n d p oi nt i n 
partici pa nts wit h mil d or 
m o derate A D.

Pr o p orti o n of partici pa nts 
ac hie vi n g I G A sc ore of clear ( 0) 
or al m ost clear ( 1) ( o n a 5-p oi nt 
scale) a n d a re d ucti o n fr o m 
baseli ne of ≥2 p oi nts at 
Wee k
1 2.

Esti ma n d E 1: t he differe nce i n 
pr o p orti o ns of t he bi nar y 
e n d p oi nt bet wee n I P treate d 
( 0. 0 1 % or 0. 0 3 % P F -0 7 0 3 8 1 2 4 
oi nt me nt ) a n d ve hicle i n 
partici pa nts wit h mil d or 
m o derate A D wit h o ut t he 
be nefit of a d diti o nal pr o hi bite d 
me dicati o ns a n d re gar dless of 
treat me nt c o m plia nce.
Sec o n d ar y: 
Sec o n d ar y:
Sec o n d ar y: 

T o c o m pare t he efficac y of 
2 d ose le vels of P F -0 7 0 3 8 1 2 4 
oi nt me nt vers us ve hicle usi n g 
E A SI -7 5 as a n e n d p oi nt i n 
partici pa nts wit h mil d or 
m o derate A D.

Pr o p orti o n of partici pa nts 
ac hie vi n g E A SI -7 5 
( 7 5 % i m pr o ve me nt fr o m 
baseli ne ) at all st u d y visit ti me 
p oi nts s pecifie d i n t he S o A .

Esti ma n d E 1 descri be d a b o ve .
T o c o m pare t he efficac y of 
2 d ose le vels of P F -0 7 0 3 8 1 2 4 
oi nt me nt vers us ve hicle, usi n g 
I G A s uccess as t he e n d p oi nt i n 
partici pa nts wit h mil d or 
m o derate A D.
Pr o p orti o n of partici pa nts 
ac hie vi n g I G A sc ore of clear ( 0) 
or al m ost clear ( 1) ( o n a 5 -p oi nt 
scale) a n d a re d ucti o n fr o m 
baseli ne of ≥2 p o i nts at all st u d y 
visit ti me p oi nts s pecifie d i n t he 
S o A , e xce pt at Wee k 1 2 .
Esti ma n d E 1 descri be d a b o ve .
0 9 0 1 7 7 e 1 9 b b 9 c 5f d\ A p pr o v e d\ A p pr o v e d O n: 0 3- N o v- 2 0 2 2 1 1: 4 8 ( G M T)

P F -0 7 0 3 8 1 2 4
Pr ot oc ol C 3 9 4 1 0 0 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 2 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 Marc h 2 0 2 1)
Pa ge 1 2

T o c o m pare t he efficac y of 
2 d ose le vels of P F -0 7 0 3 8 1 2 4 
oi nt me nt vers us ve hicle, usi n g 
perce nt C F B i n E A SI as t he 
e n d p oi nt i n partici pa nts wit h 
mil d or m o derate A D.
Perce nt C F B i n E A SI t otal sc ore 
at all st u d y visit ti me p oi nts 
s pecifie d i n t he S o A .
Esti ma n d E 2: t he differe nce i n 
mea n of t he c o nti n u o us 
e n d p oi nt bet wee n I P treate d 
( 0. 0 1 % or 0. 0 3 % P F -0 7 0 3 8 1 2 4
oi nt me nt ) a n d ve hicle i n 
partici pa nts wit h mil d or 
m o derate A D wit h o ut t he 
be nefit of a d diti o nal pr o hi bite d 
me dicati o ns a n d re gar dless of 
treat me nt c o m plia nce.
T o c o m pare t he efficac y of 
2 d ose le vels of P F -0 7 0 3 8 1 2 4 
oi nt me nt vers us ve hicle, usi n g 
I G A clear or al m ost clear as t he 
e n d p oi nt i n partici pa nts wit h 
mil d or m o derate A D.
Pr o p orti o n of partici pa nts 
ac hie vi n g I G A sc ore of clear ( 0) 
or al m ost clear ( 1) at all st u d y 
visit ti me p oi nts s pecifie d i n t he 
S o A .
Esti ma n d E 1 descri be d a b o ve.
T o c o m pare t he efficac y of 
2 d ose le vels of P F -0 7 0 3 8 1 2 4 
oi nt me nt vers us ve hicle, usi n g 
meas ures of P P -N R S P R O, i n 
partici pa nts wit h mil d or 
m o derate A D.
Pr o p orti o n of partici pa nts 
ha vi n g ≥4 p oi nts of re d ucti o n 
fr o m baseli ne i n wee kl y 
a vera ges of P P- N R S at st u d y 
visit ti me p oi nts s pecifie d i n t he 
S o A .
Esti ma n d E 1 descri be d a b o ve .
T o c o m pare t he efficac y of 
2 d ose le vels of P F -0 7 0 3 8 1 2 4 
oi nt me nt vers us ve hicle, usi n g 
B S A as t he e n d p oi nt i n 
partici pa nts wit h mil d or 
m o derate A D.
Perce nt C F B i n affecte d B S A at 
all st u d y visit ti me p oi nts 
s pecifie d i n t he S o A .
Esti ma n d E 2 descri be d a b o ve .
T o c haracterize t he safet y a n d 
t olera bilit y of 2 d ose le vels of  
P F -0 7 0 3 8 1 2 4 oi nt me nt vers us 
ve hicle i n partici pa nts wit h mil d 
or m o derate A D.
I nci de nce of treat me nt e mer ge nt 
A E s a n d seri o us a d verse e ve nts 
S A Es, cli nicall y si g nifica nt 
c ha n ges i n vital si g ns, E C G, a n d 
la b orat or y tests.
I nci de nce of i ncrease i n l ocal 
t olera bilit y se verit y gra des at 
ti mes i n dicate d i n t he S o A .
N ot A p plica ble .
C o m plete list of Ex pl or at ory/ Tert i ary O bjectives a n d E n d p oi nts are i n Secti o n 3 .
0 9 0 1 7 7 e 1 9 b b 9 c 5f d\ A p pr o v e d\ A p pr o v e d O n: 0 3- N o v- 2 0 2 2 1 1: 4 8 ( G M T)

P F -0 7 0 3 8 1 2 4
Pr ot oc ol C 3 9 4 1 0 0 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 2 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 Marc h 2 0 2 1)
Pa ge 1 3
P L A Q U E P S O RI A SI S
O bjecti ves
E n d p oi nts
Esti m a n ds
Pri m ar y: 
Pri m ar y:
Pri m ar y: 

T o c o m pare t he efficac y of 
m ulti ple d ose le vels of 
P F -0 7 0 3 8 1 2 4 oi nt me nt vers us 
ve hicle, usi n g P G A s uccess as 
t he e n d p oi nt i n partici pa nts wit h 
mil d -t o-se vere Ps O.

Pr o p orti o n of partici pa nts 
ac hie vi n g P G A sc ore of clear 
( 0) or al m ost clear ( 1) ( o n a 
5- p oi nt scale) a n d a re d ucti o n 
fr o m baseli ne of ≥2 p oi nts at 
Wee k 1 2.
Esti ma n d E 1: t he differe nce i n 
pr o p orti o ns of t he bi nar y 
e n d p oi nt bet wee n I P treate d 
( 0. 0 1 %, 0. 0 3 %, or 0. 0 6 % 
P F -0 7 0 3 8 1 2 4 oi nt me nt ) a n d 
ve hicle i n partici pa nts wit h 
mil d -t o-se vere Ps O wit h o ut t he 
be nefit of a d diti o nal pr o hi bite d 
me dicati o ns a n d re gar dless of 
treat me nt c o m plia nce.
Sec o n d ar y: 
Sec o n d ar y:
Sec o n d ar y: 
T o c o m pare t he efficac y of 
m ulti ple d ose le vels of 
P F -0 7 0 3 8 1 2 4 oi nt me nt vers us 
ve hicle usi n g P A SI -7 5 as a n 
e n d p oi nt, i n partici pa nts wit h 
mil d -t o-se vere Ps O.
Pr o p orti o n of partici pa nts 
ac hie vi n g P A SI -7 5 
( 7 5 % i m pr o ve me nt fr o m 
baseli ne) at ti mes i n dicate d i n 
t he S o A .
Esti ma n d E 1 descri be d a b o ve .
T o c o m pare t he efficac y of 
m ulti ple d ose le vels of 
P F -0 7 0 3 8 1 2 4 oi nt me nt vers us 
ve hicle, usi n g P G A s uccess as 
t he e n d p oi nt i n partici pa nts wit h 
mil d -t o-se vere Ps O.
Pr o p orti o n of partici pa nts 
ac hie vi n g P G A sc ore of clear 
( 0) or al m ost clear ( 1) ( o n a 
5- p oi nt scale) a n d a re d ucti o n 
fr o m baseli ne of ≥2 p oi nts at 
ti mes i n dicate d i n t he S o A , 
e xce pt at Wee k 1 2 .
Esti ma n d E 1 descri be d a b o ve .

T o c o m pare t he efficac y of 
m ulti ple d ose le vels of 
P F -0 7 0 3 8 1 2 4 oi nt me nt vers us 
ve hicle, usi n g C F B P A SI as t he 
e n d p oi nt i n partici pa nts wit h 
mil d -t o-se vere Ps O.

C ha n ge fr o m baseli ne i n P A SI 
at ti mes i n dicate d i n t he S o A .
Esti ma n d E 2: t he differe nce i n 
mea n of t he c o nti n u o us 
e n d p oi nt bet wee n I P treate d 
( 0. 0 1 %, 0. 0 3 %, or 0. 0 6 % 
P F -0 7 0 3 8 1 2 4 oi nt me nt ) a n d 
ve hicle i n partici pa nts wit h 
mil d -t o-se vere Ps O wit h o ut t he 
be nefit of a d diti o nal pr o hi bite d 
me dicati o ns a n d re gar dless of 
treat me nt c o m plia nce.
T o c o m pare t he efficac y of 
m ulti ple d ose le vels of 
P F -0 7 0 3 8 1 2 4 oi nt me nt vers us 
ve hicle, usi n g P G A clear or 
al most clear as t he e n d p oi nt i n 
partici pa nts wit h mil d -t o-se vere 
Ps O.
Pr o p orti o n of partici pa nts 
ac hie vi n g P G A sc ore of clear 
( 0) or al m ost clear ( 1) at all 
st u d y visit ti me p oi nts s pecifie d 
i n t he S o A .
Esti ma n d E 1 descri be d a b o ve .
0 9 0 1 7 7 e 1 9 b b 9 c 5f d\ A p pr o v e d\ A p pr o v e d O n: 0 3- N o v- 2 0 2 2 1 1: 4 8 ( G M T)

P F -0 7 0 3 8 1 2 4
Pr ot oc ol C 3 9 4 1 0 0 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 2 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 Marc h 2 0 2 1)
Pa ge 1 4
T o c o m pare t he efficac y of 
m ulti ple d ose le vels of 
P F -0 7 0 3 8 1 2 4 oi nt m e nt vers us 
ve hicle, usi n g meas ures of 
P P -N R S P R O, i n a d ult 
partici pa nts ( 1 8– 7 5 years ol d)
wit h mil d -t o-se vere Ps O.
Pr o p orti o n of a d ult partici pa nts 
( 1 8– 7 5 years ol d) ha vi n g 
≥4 p oi nts of re d ucti o n fr o m 
baseli ne i n wee kl y a vera ges of 
P P -N R S at st u d y visit ti me 
p oi nts s pecifie d i n t he S o A .
Esti ma n d E 1 descri be d a b o ve .
T o c o m pare t he efficac y of 
m ulti ple d ose le vels of 
P F -0 7 0 3 8 1 2 4 oi nt me nt vers us 
ve hicle, usi n g B S A as t he 
e n d p oi nt i n partici pa nts wit h 
mil d -t o-se vere Ps O.
Perce nt C F B i n affecte d B S A 
at all st u d y visit ti me p oi nts 
s pecifie d i n t he S o A .
Esti ma n d E 2 descri be d a b o ve .
T o c haracterize t he safet y a n d 
t olera bilit y of m ulti ple d ose 
le vels of P F-0 7 0 3 8 1 2 4 oi nt me nt 
vers us ve hicle i n partici pa nts 
wit h mil d- t o-se vere Ps O.
I nci de nce of treat me nt e mer ge nt 
A E s a n d S A Es, cli nicall y 
si g nifica nt c ha n ges i n vital 
si g ns, E C G, a n d la b orat or y 
tests.
I nci de nce of i ncrease i n l ocal 
t olera bilit y se verit y gra des at 
ti mes i n dicate d i n t he S o A .
N ot A p plica ble
C o m plete list of Ex pl or at ory/ Tert i ary O bjectives a n d E n d p oi nts are i n Secti o n 3 .
O ver all Desi g n
Brief S u m m ar y
T his is a m ultice nter, P hase 2 b, ra n d o mize d, d o u ble- bli n d, ve hicle-c o ntr olle d, parallel -gr o u p 
st u d y a n d will assess efficac y , safety, t olera bilit y , a n d P K of m ulti ple d oses of P F - 0 7 0 3 8 1 2 4 
oi nt me nt i n t he treat me nt of mil d-t o-m o derate A D a n d mil d-t o-se vere Ps O . 
Partici pa nts will be scree ne d wit hi n 4 wee ks pri or t o t he Da y  1 a p plicati o n of st u d y 
i nter ve nti o n t o c o nfir m t he y meet t he selecti o n criteria f or t he st u d y. T he treat me nt peri o d 
will be o nce -dail y a p plicati o n of P F -0 7 0 3 8 1 2 4 oi nt me nt or ve hicl e oi nt me nt f or 1 2 wee ks, 
wit h a f oll o w-u p peri o d of 4 t o 5 wee ks. 
T here will be 2 s u b -st u dies: Ta pe stri p pi n g a n d P h ot o gra p hy.  T hese s u b-st u dies will be 
c o n d ucte d at selecte d sites a n d o pti o nal f or partici pa nts.
N u m ber of P artici p a nts
A t otal of a p pr o xi matel y 2 4 0 partici pa nts wit h A D or Ps O will be ra n d o ml y assi g ne d t o st u d y 
i nter ve nti o n ( P F-0 7 3 0 8 1 2 4 or ve hicle).  

F or A D, a p pr o xi matel y 1 2 0 partici pa nts will be ra n d o ml y  assi g ne d 1: 1: 1 t o recei ve 
eit her 0. 0 1 % P F -0 7 0 3 8 1 2 4 oi nt me nt, 0. 0 3 % P F- 0 7 0 3 8 1 2 4 oi nt me nt or a ve hicle 
oi nt me nt. 
0 9 0 1 7 7 e 1 9 b b 9 c 5f d\ A p pr o v e d\ A p pr o v e d O n: 0 3- N o v- 2 0 2 2 1 1: 4 8 ( G M T)

P F -0 7 0 3 8 1 2 4
Pr ot oc ol C 3 9 4 1 0 0 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 2 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 Marc h 2 0 2 1)
Pa ge 1 5

F or Ps O , a p pr o xi matel y 1 2 0 partici pa nts will be ra n d o ml y  assi g ne d 1: 1: 1: 1 t o recei ve 
eit her 0. 0 1 % P F -0 7 0 3 8 1 2 4 oi nt me nt, 0. 0 3 % P F - 0 7 0 3 8 1 2 4 oi nt me nt, 0. 0 6 % 
P F -0 7 0 3 8 1 2 4 or a ve hicle oi nt me nt.
I nter ve nti o n Gr o u ps a n d D ur ati o n
P artici p a nt P o p ul ati o n
St u d y I nter ve nti o n
A p pr o xi m ate N u m ber of P artici p a nts 
R a n d o mize d
A D
0. 0 1 % P F -0 7 0 3 8 1 2 4
4 0
0. 0 3 % P F -0 7 0 3 8 1 2 4
4 0
Ve hicle
4 0
Ps O
0. 0 1 % P F -0 7 0 3 8 1 2 4
3 0
0. 0 3 % P F -0 7 0 3 8 1 2 4
3 0
0. 0 6 % P F -0 7 0 3 8 1 2 4
3 0
Ve hicle
3 0
D at a M o nit ori n g C o m mittee
or Ot her I n de pe n de nt O versi g ht C o m mittee : 
A n i n de pe n de nt, i nter nal re vie w c o m mittee will be use d t o re vie w efficac y, safety a n d 
t olera bilit y data as descri be d i n Secti o n 1 0. 1. 5. 1 .
St atistic al Met h o ds
A D :
T he pri mar y  esti ma n d will be t he differe nce i n pr o p orti o ns of t he bi nar y e n d p oi nt bet wee n I P 
treate d ( 0. 0 1 % or 0. 0 3 % P F -0 7 0 3 8 1 2 4 oi nt me nt ) a n d ve hicle i n partici pants wit h mil d or 
m o derate A D wit h o ut t he be nefit of a d diti o nal pr o hi bite d me dicati o ns a n d re gar dless of 
treat me nt c o m plia nce.
T he sec o n dar y  esti ma n d will be t he differe nce i n mea n of t he c o nti n u o us e n d p oi nt bet wee n 
I P treate d ( 0. 0 1 % or 0. 0 3 % P F - 0 7 0 3 8 1 2 4 oint me nt ) a n d ve hicle i n partici pa nts wit h mil d or 
m o derate A D wit h o ut t he be nefit of a d diti o nal pr o hi bite d me dicati o ns a n d re gar dless of 
treat me nt c o m plia nce.
Ps O:
T he pri mar y  esti ma n d will be t he differe nce i n pr o p orti o ns of t he bi nar y  e n d p oi nt bet wee n I P 
treate d ( 0. 0 1 %, 0. 0 3 %, or 0. 0 6 % P F -0 7 0 3 8 1 2 4 oi nt me nt ) a n d ve hicle i n partici pa nts wit h 
mil d , m o derate, or se vere Ps O wit h o ut t he be nefit of a d diti o nal pr o hi bite d me dicati o ns a n d 
re gar dless of treat me nt c o m plia nce.
T he sec o n dar y esti ma n d will be t he differe nce i n mea n of t he c o nti n u o us e n d p oi nt bet wee n 
I P treate d ( 0. 0 1 %, 0. 0 3 %, or 0. 0 6 % P F -0 7 0 3 8 1 2 4 oi nt me nt ) a n d ve hicle i n partici pa nts wit h 
mil d, m o derate, or se vere Ps O wit h o ut t he be nefit of a d diti o nal pr o hi bite d me dicati o ns a n d 
re gar dless of treat me nt c o m plia nce .
0 9 0 1 7 7 e 1 9 b b 9 c 5f d\ A p pr o v e d\ A p pr o v e d O n: 0 3- N o v- 2 0 2 2 1 1: 4 8 ( G M T)

P F -0 7 0 3 8 1 2 4
Pr ot oc ol C 3 9 4 1 0 0 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 2 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 Marc h 2 0 2 1)
Pa ge 1 6
1. 2. Sc he m a
0 9 0 1 7 7 e 1 9 b b 9 c 5f d\ A p pr o v e d\ A p pr o v e d O n: 0 3- N o v- 2 0 2 2 1 1: 4 8 ( G M T)

P F -0 7 0 3 8 1 2 4
Pr ot oc ol C 3 9 4 1 0 0 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 2 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 Marc h 2 0 2 1)
Pa ge 1 7
1. 3. S c he d ule of Acti v ities
T he S o A 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  AS S E S S M E N T S A N D 
P R O C E D U R E S secti o n 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 hed ule visits ( u n pla n ne d visits) i n a d ditio n t o t h ose liste d in t he S o A 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 partici pa nt .
1. 3. 1. At o pic Der m atitis
At o pic Der m atitis
Visit I de ntifier a
A b bre viati o ns use d i n t his ta ble ma y be f o u n d i n
A p pe n di x 1 3
Scree ni n g
Tre at m e nt P h ase
A ll assess me nt s/pr oce d ures are pre -d ose , u nless ot her wise st ate d
F oll o w - U p
(E O S)
E T
D a y 1
( B aseli ne) W ee k 1 W ee k 2
W ee k 4
W ee k 6 W ee k 8 W ee k 1 0
Wee k 1 2 
( E O T)
Visit Wi n d o w
D a y -2 8
t o - 1
N/ A
D a y 8
± 2
D a y 1 5
± 2
D a y 2 9
± 2
D a y 4 3
± 2
D a y 5 7
± 2
D a y 7 1
± 2
D a y 8 5
± 2
2 8 – 3 5 d a ys 
p ost -l ast 
d ose
N A
Visit N u m ber
1
2
3
4
5
6
7
8
9
1 0
N A
E nr oll me nt Pr oce d ures
I nf or me d c o nse nt/asse nt
X
Ge neral me dical a n d A D hist or y
X
X
Me dicati o n hist or y
X
X
D e m o gra p h y
X
Eli gi bilit y assess me nt
X
X b
Wei g ht 
X
X
Hei g ht
X
Cli nic al Assess me nts
P h ysical e xa mi nati o n c
X
X
X
X
X
X
E C G
X
X
X
X
Vital si g ns
X
X
X
X
C -S S R S d
X
0 9 0 1 7 7 e 1 9 b b 9 c 5f d\ A p pr o v e d\ A p pr o v e d O n: 0 3- N o v- 2 0 2 2 1 1: 4 8 ( G M T)

P F -0 7 0 3 8 1 2 4
Pr ot oc ol C 3 9 4 1 0 0 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 2 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 Marc h 2 0 2 1)
Pa ge 1 8
At o pic Der m atitis
Visit I de ntifier a
A b bre viati o ns use d i n t his ta ble ma y be f o u n d i n
A p pe n di x 1 3
Scree ni n g
Tre at m e nt P h ase
A ll assess me nt s/pr oce d ures are pre -d ose , u nless ot her wise st ate d
F oll o w - U p
(E O S)
E T
D a y 1
( B aseli ne) W ee k 1 W ee k 2
W ee k 4
W ee k 6 W ee k 8 W ee k 1 0
Wee k 1 2 
( E O T)
Visit Wi n d o w
D a y -2 8
t o - 1
N/ A
D a y 8
± 2
D a y 1 5
± 2
D a y 2 9
± 2
D a y 4 3
± 2
D a y 5 7
± 2
D a y 7 1
± 2
D a y 8 5
± 2
2 8 – 3 5 d a ys 
p ost -l ast 
d ose
N A
Visit N u m ber
1
2
3
4
5
6
7
8
9
1 0
N A
A D -Rel ate d Cli nic al Assess me nts
I G A 
X
X
X
X
X
X
X
X
X
X
X
E A S I
X
X
X
X
X
X
X
X
X
X
B S A
X
X
X
X
X
X
X
X
X
X
X
L a b or at or y Assess me nts
H e m at ol o g y, C he mistr y a n d Uri nal ysis
X
X
X
X
X
X
Ser u m F S H ( W O N C B P o nl y) 
X
Ser u m Pre g na nc y Test ( W O C B P o nl y)
X
Uri ne Pre g na nc y testf
X
X
X
X
X
X
X
X
X
X
P h ar m ac o ki netics
Bi o m ar ker Assess me nts
Ret ai ne d Rese arc h S a m ples
Pre p B 1. 5 ( plas ma)
X
X
X
X
Pre p B 2. 5 (ser u m)
X
X
X
X
e -Di ar y
Dis pe nse e -diar y a n d i nstr uct o n usa ge
X
0 9 0 1 7 7 e 1 9 b b 9 c 5f d\ A p pr o v e d\ A p pr o v e d O n: 0 3- N o v- 2 0 2 2 1 1: 4 8 ( G M T)
C CI
C CI
C CI
C CI

P F -0 7 0 3 8 1 2 4
Pr ot oc ol C 3 9 4 1 0 0 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 2 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 Marc h 2 0 2 1)
Pa ge 1 9
At o pic Der m atitis
Visit I de ntifier a
A b bre viati o ns use d i n t his ta ble ma y be f o u n d i n
A p pe n di x 1 3
Scree ni n g
Tre at m e nt P h ase
A ll assess me nt s/pr oce d ures are pre -d ose , u nless ot her wise st ate d
F oll o w - U p
(E O S)
E T
D a y 1
( B aseli ne) W ee k 1 W ee k 2
W ee k 4
W ee k 6 W ee k 8 W ee k 1 0
Wee k 1 2 
( E O T)
Visit Wi n d o w
D a y -2 8
t o - 1
N/ A
D a y 8
± 2
D a y 1 5
± 2
D a y 2 9
± 2
D a y 4 3
± 2
D a y 5 7
± 2
D a y 7 1
± 2
D a y 8 5
± 2
2 8 – 3 5 d a ys 
p ost -l ast 
d ose
N A
Visit N u m ber
1
2
3
4
5
6
7
8
9
1 0
N A
C o m plete assi g ne d P R Os a n d rec or d st u d y 
i nter ve nti o n a p plicati o n
X i
X
 
 
 
 
 

X
C ollect e -diar y
X j
X
X
St u d y I nter ve nti o n
Calc ulate B S A f or st u d y i nter ve nti o n nee d
X
X
X
X
X
X
X
X
Mar k / u p date areas of a p plicati o n o n b o d y ma p
X
X
X
X
X
X
X
Wei g h a n d dis pe nse st u d y i nter ve nti o n t u bes
X
X
X
X
X
X
X
St u d y i nter ve nti o n a p plicati o n a n d o bser vati o n
X
X
X
X
X
X
X
X
C ollect a n d wei g h ret ur ne d st u d y i nter ve nti o n t u bes 
X
X
X
X
X
X
X
X
Re vie w of  e -diar y f or c o m plia nce
X
X
X
X
X
X
X
X
X
S afet y M o nit ori n g
C o nc o mita nt Me dicati o n
X  
X  
X  
X  
X  
X  
X  
X  
X  
X
C o ntrace pti o n usa ge c o nfir mati o n
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X
L ocal tolera bilit y assess me nt k
X  
X  
X  
X  
X  
X  
X  
X
X
Seri o us a n d n o n -seri o us A E m o nit ori n g
X
 
 
 
 
 
 
 

X  
X
T a pe Stri p S u b -st u dy n
0 9 0 1 7 7 e 1 9 b b 9 c 5f d\ A p pr o v e d\ A p pr o v e d O n: 0 3- N o v- 2 0 2 2 1 1: 4 8 ( G M T)
C CI
C CI

P F -0 7 0 3 8 1 2 4
Pr ot oc ol C 3 9 4 1 0 0 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 2 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 Marc h 2 0 2 1)
Pa ge 2 0
At o pic Der m atitis
Visit I de ntifier a
A b bre viati o ns use d i n t his ta ble ma y be f o u n d i n
A p pe n di x 1 3
Scree ni n g
Tre at m e nt P h ase
A ll assess me nt s/pr oce d ures are pre -d ose , u nless ot her wise st ate d
F oll o w - U p
(E O S)
E T
D a y 1
( B aseli ne) W ee k 1 W ee k 2
W ee k 4
W ee k 6 W ee k 8 W ee k 1 0
Wee k 1 2 
( E O T)
Visit Wi n d o w
D a y -2 8
t o - 1
N/ A
D a y 8
± 2
D a y 1 5
± 2
D a y 2 9
± 2
D a y 4 3
± 2
D a y 5 7
± 2
D a y 7 1
± 2
D a y 8 5
± 2
2 8 – 3 5 d a ys 
p ost -l ast 
d ose
N A
Visit N u m ber
1
2
3
4
5
6
7
8
9
1 0
N A
P h ot o gr a p h y S u b -st u d y n
= o n g oi n g/c o nti n u o us e ve nt
a.
D a y  relati ve t o start of st u d y i nter ve nti o n ( Da y 1). E xce pt f or Scree ni n g Visit a n d Da y 1 Visit, Alter nati ve Meas ures ma y be i m ple me nte d i n case of p u blic 
e mer ge ncies. Refer t o A p pe n di x 9 f or t he details a b o ut t he assess me nts t hat ma y be perf or me d d uri n g a Tele healt h Visit or a H o me Healt h Visit.
b.
Selecte d eli gi bilit y criteria s h o ul d be met. Refer t o Secti o n 5. 1 f or details.  
c.
F oll o w i n g Da y 1 visit, e xa mi nati o n ma y be tar gete d t o s ki n a n d pre vi o us fi n di n gs, ne w/ o pe n A Es, or i n vesti gat or discreti o n.
d.
Site staff is t o a d mi nister t he C -S S R S t o all partici pa nts at Scree ni n g a n d sc ore i m me diatel y.
f.
A ne gati ve res ult fr o m uri ne pre g na nc y test is re q uire d bef ore recei vi n g st u d y i nter ve nti o n. 
j.
O nl y f or partici p a nts w h o d o n ot meet eli gi bilit y criteria. If a partici pa nt has n’t wit h dra w n c o nse nt fr o m partici pati o n fr o m t he st u d y, e-diar y ma y be 
c ollecte d at E T or E O S visits.
k.
L ocal t olera bilit y at a n o n -lesi o nal site of st u d y i nter ve nti o n a p plicati o n will be assesse d i m me diatel y p ost -a p plicati o n. At E T, l ocal t olera bilit y assess me nt 
will be perf or me d o nl y if I P a p plicati o n w as pla n ne d at t hat visit, b ut was n’t c o n d ucte d d ue t o t olera bilit y assess me nt o utc o me of Gra de 3 (se v ere) or 
Gra de 4 ( ver y se vere), res ulti n g i n disc o nti n uati o n of t he st u d y i nter ve nti o n as o utli ne d i n Secti o n 7. 1. 4 .
0 9 0 1 7 7 e 1 9 b b 9 c 5f d\ A p pr o v e d\ A p pr o v e d O n: 0 3- N o v- 2 0 2 2 1 1: 4 8 ( G M T)
C CI
C CI
C CI
C CI

P F -0 7 0 3 8 1 2 4
Pr ot oc ol C 3 9 4 1 0 0 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 2 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 Marc h 2 0 2 1)
Pa ge 2 1
1. 3. 2. Pl a q ue Ps or iasis
Pl a q ue Ps ori asis
Visit I de ntifier a
A b bre viati o ns use d i n t his ta ble ma y be f o u n d i n 
A p pe n di x 1 3 .
Scree ni n g
Tre at m e nt P h ase
A ll assess me nt s/pr oce d ures are pre -d ose , u nless ot her wise st ate d.
F oll o w -U p
( E O S)
E T
D a y 1
( B aseli ne)
W ee k 1 W ee k 2 W ee k 4 W ee k 6 W ee k 8 W ee k 1 0 Wee k 1 2 
( E O T)
Visit Wi n d o w
D a y -2 8
t o - 1
N A
D a y 8
± 2
D a y 1 5
± 2
D a y 2 9
± 2
D a y 4 3
± 2
D a y 5 7
± 2
D a y 7 1
± 2
D a y 8 5
± 2
2 8 – 3 5 d a ys 
p ost - l ast 
d ose
N A
Visit N u m ber
1
2
3
4
5
6
7
8
9
1 0
N A
E nr oll me nt Pr oce d ures
I nf or me d c o nse nt/asse nt
X
Ge neral m e dical a n d Ps O hist or y
X
X
Me dicati o n hist or y
X
X
D e m o gra p h y
X
Eli gi bil it y assess me nt
X
X b
Wei g ht
X
X
Hei g ht
X
Cli nic al Assess me nts
P h ysical e xa mi nati o n c
X
X
X
X
X
X
E C G
X
X
X
X
Vital si g ns
X
X
X
X
C -S S R S d
X
Ps O- Rel ate d Cli nic al Assess me nts
P G A 
X
X
X
X
X
X
X
X
X
X
X
P A SI
X
X
X
X
X
X
X
X
X
X
B S A
X
X
X
X
X
X
X
X
X
X
X
L a b or at or y Assess me nts
H e m at ol o g y, C he mistr y a n d Uri nal ysis
X
X
X
X
X
X
Ser u m F S H ( W O N C B P o nl y)
X
Ser u m Pre g na nc y Test ( W O C B P o nl y)
X
Uri ne Pre g na nc y Test e
X
X
X
X
X
X
X
X
X
X
P h ar m ac o ki netics
0 9 0 1 7 7 e 1 9 b b 9 c 5f d\ A p pr o v e d\ A p pr o v e d O n: 0 3- N o v- 2 0 2 2 1 1: 4 8 ( G M T)
C CI

P F -0 7 0 3 8 1 2 4
Pr ot oc ol C 3 9 4 1 0 0 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 2 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 Marc h 2 0 2 1)
Pa ge 2 2
Pl a q ue Ps ori asis
Visit I de ntifier a
A b bre viati o ns use d i n t his ta ble ma y be f o u n d i n 
A p pe n di x 1 3 .
Scree ni n g
Tre at m e nt P h ase
A ll assess me nt s/pr oce d ures are pre -d ose , u nless ot her wise st ate d.
F oll o w -U p
( E O S)
E T
D a y 1
( B aseli ne)
W ee k 1 W ee k 2 W ee k 4 W ee k 6 W ee k 8 W ee k 1 0 Wee k 1 2 
( E O T)
Visit Wi n d o w
D a y -2 8
t o - 1
N A
D a y 8
± 2
D a y 1 5
± 2
D a y 2 9
± 2
D a y 4 3
± 2
D a y 5 7
± 2
D a y 7 1
± 2
D a y 8 5
± 2
2 8 – 3 5 d a ys 
p ost - l ast 
d ose
N A
Visit N u m ber
1
2
3
4
5
6
7
8
9
1 0
N A
Ret ai ne d Rese arc h S a m ples
Pre p B 1. 5 ( plas ma)
X
X
X
X
Pre p B 2. 5 (ser u m)
X
X
X
X
e-di ar y
Dis pe nse e-diar y a n d i nstr uct o n usa ge
X
C o m plete assi g ne d P R Os a n d r ec or d st u d y 
i nter ve nti o n a p plicati o n
X h
 
 
 
 
 
 

X
C ollect e -diar y
X i
X
X
St u d y I nter ve nti o n
Calc ulate B S A f or st u d y i nter ve nti o n nee d
X
X
X
X
X
X
X
X
Mar k / u p date areas of a p plicati o n o n b o d y ma p
X
X
X
X
X
X
X
Wei g h a n d dis pe nse st u d y i nter ve nti o n t u bes
X
X
X
X
X
X
X
St u d y inter ve nti o n a p plicati o n a n d o bser vati o n
X
X
X
X
X
X
X
X
C ollect a n d wei g h ret ur ne d st u d y i nter ve nti o n t u bes
X
X
X
X
X
X
X
X
Re vie w of  e-diar y f or c o m plia nce
X
X
X
X
X
X
X
X
X
S afet y M o nit ori n g
C o nc o mita nt Me dicati o n
X  
X  
X  
X  
X  
X  
X  
X  
X  
X
C o ntrace pti o n usa ge c o nfir mati o n
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X
L ocal tolera bilit y assess me nt j
X  
X  
X  
X  
X  
X  
X  
X
X
Seri o us a n d n o n -seri o us A E m o nit ori n g
X
 
 
 
 
 
 
 

X  
X
0 9 0 1 7 7 e 1 9 b b 9 c 5f d\ A p pr o v e d\ A p pr o v e d O n: 0 3- N o v- 2 0 2 2 1 1: 4 8 ( G M T)
C CI
C CI

P F -0 7 0 3 8 1 2 4
Pr ot oc ol C 3 9 4 1 0 0 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 2 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 Marc h 2 0 2 1)
Pa ge 2 3
Pl a q ue Ps ori asis
Visit I de ntifier a
A b bre viati o ns use d i n t his ta ble ma y be f o u n d i n 
A p pe n di x 1 3 .
Scree ni n g
Tre at m e nt P h ase
A ll assess me nt s/pr oce d ures are pre -d ose , u nless ot her wise st ate d.
F oll o w -U p
( E O S)
E T
D a y 1
( B aseli ne)
W ee k 1 W ee k 2 W ee k 4 W ee k 6 W ee k 8 W ee k 1 0 Wee k 1 2 
( E O T)
Visit Wi n d o w
D a y -2 8
t o - 1
N A
D a y 8
± 2
D a y 1 5
± 2
D a y 2 9
± 2
D a y 4 3
± 2
D a y 5 7
± 2
D a y 7 1
± 2
D a y 8 5
± 2
2 8 – 3 5 d a ys 
p ost - l ast 
d ose
N A
Visit N u m ber
1
2
3
4
5
6
7
8
9
1 0
N A
T a pe Stri p S u b -st u dy n
P h ot o gr a p h y S u b -st u d y n
= o n g oi n g/c o nti n u o us e ve nt
a.
D a y  relati ve t o start of st u d y i nter ve nti o n ( Da y 1). E xce pt f or Scree ni n g Visit a n d Da y 1 Visit, Alter nati ve Meas ures ma y be i m ple me nte d i n case of p u blic 
e mer ge ncies. Refer t o A p pe n di x 9 f or t he details a b o ut t he assess me nts t hat ma y be perf or me d d uri n g a Tele healt h Visit or a H o me Healt h Visit.
b.
Selecte d eli gi bilit y criteria s h o ul d be met. Refer t o Secti o n 5. 1 f or details.
c.
F oll o w i n g Da y 1 visit, e xa mi nati o ns ma y be tar gete d t o s ki n a n d p re vi o us fi n di n gs, ne w/ o pe n A Es, or i n vesti gat or discreti o n.
d.
Site staff is t o a d mi nister t he C -S S R S t o all partici pa nts at Scree ni n g a n d sc ore i m me diatel y.
e.
A ne gati ve res ult fr o m uri ne pre g na nc y tests is re q uire d bef ore recei vi n g st u d y i nter ve nti o n.
0 9 0 1 7 7 e 1 9 b b 9 c 5f d\ A p pr o v e d\ A p pr o v e d O n: 0 3- N o v- 2 0 2 2 1 1: 4 8 ( G M T)
C CI
C CI
C CI
C CI

P F -0 7 0 3 8 1 2 4
Pr ot oc ol C 3 9 4 1 0 0 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 2 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 Marc h 2 0 2 1)
Pa ge 2 4
i.
O nl y f or partici pa nts w h o d o n ot meet eli gi bilit y criteria . If a partici pa nt has n’t wit h dra w n c o nse nt fr o m partici pati o n fr o m t he st u d y, e-diar y ma y be 
c ollecte d at E T or E O S visits.
j.
L ocal t olera bilit y at a n o n-lesi o nal site of st u d y i nter ve nti o n a p plicati o n will be assesse d i m me diatel y p ost-a p plicati o n. At E T, l ocal t olera bilit y assess me nt 
will be perf or me d o nl y if I P a p plicati o n w as pla n ne d at t hat visit, b ut was n’t c o n d u cte d d ue t o t olera bilit y assess me nt o utc o me of Gra de 3 (se vere) or 
Gra de 4 ( ver y se vere), res ulti n g i n disc o nti n uati o n of t he st u d y i nter ve nti o n as o utli ne d i n Secti o n 7. 1. 4 .
l.
T o be c o m plete d usi n g e -diar y, we e kl y after Da y 1 at h o me/resi de nce or d uri n g site visit, if sc he d ule d. 
0 9 0 1 7 7 e 1 9 b b 9 c 5f d\ A p pr o v e d\ A p pr o v e d O n: 0 3- N o v- 2 0 2 2 1 1: 4 8 ( G M T)
C CI
C CI

P F -0 7 0 3 8 1 2 4
Pr ot oc ol C 3 9 4 1 0 0 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 2 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 Marc h 2 0 2 1)
Pa ge 2 5
2. I N T R O D U C TI O N
P F - 0 7 0 3 8 1 2 4 is a t o pical P D E 4 i n hi bit or t hat is c urre ntly bei n g i n vesti gate d i n treat me nt of 
A D a n d Ps O .
2. 1. St u d y R ati o n ale 
T he p ur p ose of t he st u d y  is t o i n vesti gate t he efficac y, safety, t olera bilit y a n d 
p har mac o ki netics of t o pical P F -0 7 0 3 8 1 2 4 i n partici pa nts , 1 2 years a n d ol der a n d wit h 
mil d -t o-m o derate A D or mil d -t o-se vere Ps O . Partici pa nts will a p pl y eit her P F- 0 7 0 3 8 1 2 4 
oi nt me nt or a ve hicle oi nt me nt f or 1 2 wee ks.
2. 2. B ac k gr o u n d 
R ole of Pr oi nfl a m m at or y C yt o ki nes i n A D a n d Ps O
A T O PI C D E R M A TI TI S: 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 ky 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. A D ca n affect a n y a ge gr o u p. Pre vale nce esti mates s u g gest 
a p pr o xi matel y 1 0 % of a d ults a n d 1 0 %- 2 0 % of c hil dre n s uffer fr o m A D, a n d u p t o 1 8 % of 
t h ose affecte d wit h A D s uffer wit h se vere disease. Alt h o u g h A D affects patie nts of all a ges, 
it 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 affecti n g 1 5 %-3 0 % of 
all c hil dre n i n t he U S. T here are a li mite d n u m ber of t o pical s ki n treat me nts a vaila ble f or 
A D. C urre nt treat me nts f or A D i ncl u de e m ollie nts, t o pical c ortic oster oi ds
(e g, 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 
(e g, pi mecr oli m us, tacr oli m us), a n d c oal tar pre parati o ns. T here ha ve bee n m ore rece nt 
t o pical treat me nts. Crisa b or ole, a P D E -4 i n hi bit or, has bee n use d f or tre at me nt of 
mil d -t o-m o derate A D. T o pical J A K i n hi bit ors ha ve als o bee n use d f or tre at me nt o f 
mil d -t o-m o derate A D. R u x oliti ni b, a rece ntl y  a p pr o ve d J A K i n hi bit or f or t o pical use i n 
mil d -t o- mo derate A D ca n be use d o nl y i nter mitte ntl y a n d s h ort -ter m, d ue t o its s yste mic 
effects . Del g ociti ni b has bee n s h o w n t o be m o destl y effecti ve i n treat me nt of 
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, U V A li g ht wit h or wit h o ut ps orale n) 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 I F N-, m yc o p he n olate m ofetil, met h otre xate). 
N o ne of t he c urre ntl y  a vaila ble t hera pies offer 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, i ncrease t he ti me bet wee n rela pses, 
re d uce pr urit us a n d re d uce t he res ulti n g slee p dist ur ba nces. F or m ost A D patie nts n ot 
res p o n di n g t o t o pical t hera pies a n d p h ot ot hera py, off -la bel use of sys te mic a ge nts, w hic h 
i ncl u des b ot h oral c ortic oster oi ds a n d 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. M ore rece ntl y, t here ha ve bee n oral J A K i n hi bit ors t hat ha ve bee n a p pr o ve d 
f or treat me nt of m o derate-t o-se vere at o pic der matitis, s uc h as A br ociti ni b a n d U padaciti ni b.
D u pil u ma b i njecti o n, a n I L -4 rece pt or al p ha a nta g o nist, was a p pr o ve d f or use i n patie nts wit h 
m o derate -t o-se vere A D. S yste 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 heref ore, t he pr o mi ne nt u n met me dical nee d 
i n A D is f or a n effecti ve, safe t o pical a ge nt f or o nce -a-d a y d osi n g wit h o ut restricti o ns o n 
l o n g-ter m or c o nti n u o us use, a n d wit h o ut l ocal or s yste mic si de effects.
0 9 0 1 7 7 e 1 9 b b 9 c 5f d\ A p pr o v e d\ A p pr o v e d O n: 0 3- N o v- 2 0 2 2 1 1: 4 8 ( G M T)

P F -0 7 0 3 8 1 2 4
Pr ot oc ol C 3 9 4 1 0 0 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 2 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 Marc h 2 0 2 1)
Pa ge 2 6
T he T h 2 res p o nse c o ntri b ute s t o A D-ass ociate d s ki n i nfla m mati o n a n d itc h. 1 T he pat h o ge nic 
r ole t hat t he T h 2 deri ve d c yt o ki nes, I L-4 a n d I L-1 3, pla y  i n A D has bee n de m o nstrate d 
t hr o u g h t he cli nical efficac y of d u pil u ma b, a n a nti b o d y t o t he I L-4 rece pt or t hat bl oc ks t he 
acti vit y of b ot h I L- 4 a n d I L-1 3. 2
P S O RI A SI S: T he m ost c o m m o n varia nt of ps oriasis, Ps O ( ps oriasis v ul garis), is a c hr o nic 
i nfla m mat or y s ki n disease c haracterize d b y re d, scal y, raise d pla q ues. C hr o nic Ps O is a 
c o m m o n s ki n dis or der wit h a w orl d wi de pre vale nce of 2 %. Alt h o u g h ps oriasis pri maril y  
affects t he s ki n a n d is n ot a life -t hreate ni n g disease, it ca n pr of o u n dly i m pact t he patie nt’s 
Q o L  res ulti n g i n a n i m pair me nt a ki n to ot her maj or diseases, s uc h as t y pe 2 dia betes, 
m y ocar dial i nfarcti o n, a n d art hritis. C urre nt treat me nts f or ps oriasis i ncl u de t o picals, 
p h ot ot hera p y, s ys te mic n o n-bi ol o gical t hera pies ( met h otre xate, c y cl os p ori n, acitreti n, 
a pre milast [ Otezla ® ]) a n d bi ol o gics. Pr oi nfla m mat or y c yt o ki nes s uc h as T N F-, I F N-a n d 
I L-2 3/ T -hel per -1 7 res p o nse c y t o ki nes pla y a n i m p orta nt r ole i n t he pat h o ge nesis of 
ps oriasis. 3 Se veral bi ol o gic m o n ocl o nal a nti b o dies t hat tar get t hese pr oi nfla m mat or y  
c yt o ki nes ha ve bee n s h o w n t o be effecti ve f or t he treat me nt of ps oriasis i n cli nical trials.4
Bi ol o gic a ge nts use d i n t he treat me nt of ps oriasis i ncl u de m ulti ple a nti -T N F a ge nts (s uc h as 
i nfli xi ma b, a dali m u ma b, eta nerce pt), a nti-I L-1 2/I L -2 3 a nti b o dies a n d a nti -I L- 1 7 a nti b o dies. 
P D E 4 i n hi bit ors s uc h as a pre milast ( Otezla ® ) ma y red uce pr o d ucti o n of pr o -i nfla m mat or y 
T N F -a n d I F N-b y  i ncreasi n g c A M P le vels.
Descri pti o n of I n vesti g ati o n al Pr o d uct: Mec h a nis m of Acti o n 
P h os p h o dia esterases are a fa mil y of e nzy m es t hat brea k d o w n t he u bi q uit o us sec o n d 
messe n gers, c A M P a n d c G M P, t hat re g ulate vari o us cell ular pr ocesses. P D E 4 is a s u bfa mil y  
t hat i ncl u des t he 4 is oz y mes, eac h e nc o de d by s e parate ge nes, P D E 4 A, B, C a n d D. 
I n hi bit ors of t he P D E 4 fa mil y ha ve bee n t he f oc us of i nte nse dr u g de vel o p me nt o ver ma n y 
ye ars d ue t o t heir br oa d p ote ntial i n i nfla m mat or y  diseases s uc h as A D a n d ps oriasis. F or 
e xa m ple, a pre milast ( Otezla ® ) is a n oral s mall- m olec ule i n hi bit or of P D E 4 t hat is a p pr o ve d 
f or t he treat me nt of patie nts wit h m o derate- t o-se vere Ps O a n d acti ve ps oriatic art hritis. 
Crisa b or ole ( E ucrisa ® , Sta q uis® ) is a t o picall y deli vere d P D E 4 i n hi bit or t hat has 
de m o nstrate d efficac y  i n cli nical trials5 a n d is a p pr o ve d f or t he treat me nt of mil d- t o-m o derate 
A D as descri be d pre vi o usl y . I n a d diti o n, ot her t o pical P D E 4 i n hi bit ors, s uc h as r ofl u milast 
( A R Q-1 5 1), ha ve s h o w n acti vit y  i n t he treat me nt of ps oriasis. 6
P F - 0 7 0 3 8 1 2 4 is desi g ne d t o be a best-i n-class, o xa b or ole-base d p ote nt P D E 4 i n hi bit or  
 
 
P F -0 7 0 3 8 1 2 4 is a p ote nt a n d selecti ve P D E 4 i n hi bit or i nte n de d t o be use d f or t o pical 
a d mi nistrati o n f or t he treat me nt of A D a n d Ps O .
 
 
0 9 0 1 7 7 e 1 9 b b 9 c 5f d\ A p pr o v e d\ A p pr o v e d O n: 0 3- N o v- 2 0 2 2 1 1: 4 8 ( G M T)
C CI
C CI

P F -0 7 0 3 8 1 2 4
Pr ot oc ol C 3 9 4 1 0 0 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 2 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 Marc h 2 0 2 1)
Pa ge 2 7
Precli nic al S afet y D at a
0 9 0 1 7 7 e 1 9 b b 9 c 5f d\ A p pr o v e d\ A p pr o v e d O n: 0 3- N o v- 2 0 2 2 1 1: 4 8 ( G M T)
C CI
C CI

P F -0 7 0 3 8 1 2 4
Pr ot oc ol C 3 9 4 1 0 0 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 2 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 Marc h 2 0 2 1)
Pa ge 2 8
2. 2. 1. Cli nic al O ver vie w
T o date, cli nical e x perie nce wit h P F - 0 7 0 3 8 1 2 4 oi nt me nt c o m prises 3 st u dies: 
1.
A P hase 1, m ulti ple asce n di n g d ose st u d y i n a d ult healt h y partici pa nts ( C 3 9 4 1 0 0 1, 
c o m plete d ).
 
 
2.
A P hase 2a ra n d o mize d, d o u ble- bli n d st u d y  i n partici pa nts wit h mil d-t o-m o derate A D or 
Ps O , treate d wit h 0. 0 1 % P F - 0 7 0 3 8 1 2 4 oi nt me nt or ve hicle oi nt me nt Q D f or 6 wee ks
( C 3 9 4 1 0 0 2, c o m plete d). T he t otal d urati o n of st u d y  partici pati o n was a p pr o xi matel y 1 7 
wee ks, i ncl u di n g a scree ni n g peri o d of u p t o 6 wee ks, a d o u ble -bli n d, ve hicle -c o ntr olle d 
treat me nt peri o d of 6 wee ks, a n d a safety f oll o w -u p peri o d of 4 -5 wee ks fr o m las t d ose of 
st u d y dr u g t o last st u d y visit.
I n t his st u dy, t here were n o deat hs or S A Es. All treat me nt -relate d (all-ca usalit y a n d 
treat me nt-relate d) se vere A Es ( 4 partici pa nts) occ urre d i n t he ve hicle gr o u p. T here were 
n o treat me nt -relate d A Es i n t he 0. 0 1 % P F- 0 7 0 3 8 1 2 4 oi nt me nt gr o u p. T he n u m ber of 
T E A Es (all -ca usalit y) a n d partici pa nts re p orti n g T E A Es were hi g her i n t he ve hicle gr o u p 
( 1 5 [ 2 9. 4 %] partici pa nts wit h 2 6 e ve nts) c o m pare d t o t he P F-0 7 0 3 8 1 2 4 gr o u p 
( 1 2 [ 2 2. 6 %] partici pa nts wit h 1 6 e ve nts).
T he m ost c o m m o n all -ca usalit y T E A Es by S O C i n t he 0. 0 1 % P F -0 7 0 3 8 1 2 4 oi nt me nt 
gr o u p s was I nfecti o ns a n d Infestati o ns ( 1 1. 3 %), a n d i n ve hicle gr o u p was S ki n a n d 
S u bc uta ne o us Tiss ue Dis or ders ( 1 3. 7 %). T here were n o partici pa nts wit h a p plicati o n site 
pai n or ot her s ki n reacti o n at a p plicati o n site i n t he 0. 0 1 % P F - 0 7 0 3 8 1 2 4 oi nt me nt gr o u ps.
T here were 3 ( 5. 9 %) partici pa nts i n t he ve hicle gr o u p wit h 3 T E A Es relate d t o 
C O VI D -1 9, a n d 1 ( 2. 0 %) partici pa nt ha d a te m p orar y  disc o nti n uati o n d ue t o C O VI D-1 9. 
N o partici pa nts i n t he 0. 0 1 % P F - 0 7 0 3 8 1 2 4 oi nt me nt gr o u ps e x perie nce d A E relate d t o 
C O VI D - 1 9.
0 9 0 1 7 7 e 1 9 b b 9 c 5f d\ A p pr o v e d\ A p pr o v e d O n: 0 3- N o v- 2 0 2 2 1 1: 4 8 ( G M T)
C CI
C CI

P F -0 7 0 3 8 1 2 4
Pr ot oc ol C 3 9 4 1 0 0 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 2 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 Marc h 2 0 2 1)
Pa ge 2 9
T he st u d y  met t he statistical si g nifica nce f or t he pri mar y e n d p oi nt f or b ot h i n dicati o ns.
A D
P F - 0 7 0 3 8 1 2 4 ( 0. 0 1 % oi nt me nt Q D ) met t he pri mar y efficac y e n d p oi nt i n t he C 3 9 4 1 0 0 2 
st u d y f or A D: P F -0 7 0 3 8 1 2 4 ( 0. 0 1 % oi nt me nt Q D) was statisticall y  si g nifica ntl y differe nt 
fr o m ve hicle i n perce nta ge c ha n ge fr o m baseli ne i n E A SI sc ore at Wee k 6.
T here was a statistically si g nifica nt differe nce i n t he k e y  sec o n dar y e n d p oi nt: res p o nse 
rate f or I G A (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 
Wee k
6 bet wee n P F - 0 7 0 3 8 1 2 4 ( 0. 0 1 % oi nt me nt Q D) gr o u p a n d ve hicle gr o u p, w hic h 
s u p p orte d t he fi n di n gs of t he pri mar y  e n d p oi nt a nal ysis.
T he res ults fr o m ot her i m p orta nt sec o n dar y e n d p oi nts i ncl u di n g E A SI-7 5 a n d P P -N R S 
res p o nse at Wee k 6 were c o nsiste nt wit h t he pri mar y a n d ke y sec o n dar y e n d p oi nt 
fi n di n gs.
P s O
P F -0 7 0 3 8 1 2 4 ( 0. 0 1 % oi nt me nt Q D) met t he pri mar y  efficac y e n d p oi nt i n t he C 3 9 4 1 0 0 2 
st u d y f or Ps O: P F-0 7 0 3 8 1 2 4 ( 0. 0 1 % oi nt me nt Q D) was statisticall y  si g nifica ntl y 
differe nt fr o m ve hicle i n c ha n ge fr o m baseli ne i n P A SI  sc ore at Wee k 6.
T here was n o statisticall y si g nifica nt differe nce i n t he k e y  sec o n dar y e n d p oi nt: res p o nse 
rate f or P G A (clear = 0 or al m ost clear = 1 an d a re d ucti o n fr o m baseli ne of ≥2 p oi nts) at 
Wee k
6 bet wee n P F -0 7 0 3 8 1 2 4 ( 0. 0 1 % oi nt me nt Q D) gr o u p a n d ve hicle gr o u p, alt h o u g h 
o bser ve d res p o nse rate was hi g her i n P F- 0 7 0 3 8 1 2 4 ( 0. 0 1 % oi nt me nt Q D) gr o u p t ha n 
ve hicle gr o u p.
T he res ults fr o m P A SI -7 5 at Wee k 6 were c o nsiste nt wit h t he pri mar y  fi n di n gs.
3.
A P hase 1, ra n d o mize d , d o u ble- bli n d, ve hicle-c o ntr olle d, parallel c o h ort st u d y t o e val uate 
t he safety, t olera bilit y , s ki n irritati o n p ote ntial a n d p har mac o ki netics of m ulti ple-d ose , 
t o pical a d mi nistrati o n of P F - 0 7 0 3 8 1 2 4 t o Ja pa nese healt hy partici pa nts ( C 3 9 4 1 0 03 , 
e nr oll me nt c o m plete, C S R pe n di n g). Preli mi nar y  data s u g gest t hat 0. 0 1 % P F- 0 7 0 3 8 1 2 4 
oi nt me nt is ge nerall y safe a n d well t olerate d i n Ja pa nese healt h y  partici pa nts.
0 9 0 1 7 7 e 1 9 b b 9 c 5f d\ A p pr o v e d\ A p pr o v e d O n: 0 3- N o v- 2 0 2 2 1 1: 4 8 ( G M T)

P F -0 7 0 3 8 1 2 4
Pr ot oc ol C 3 9 4 1 0 0 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 2 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 Marc h 2 0 2 1)
Pa ge 3 0
T a ble 1.
P F -0 7 0 3 8 1 2 4 
 – C o m plete d St u dies as of 
J a n u ar y 2 0 2 2
St u d y I D
Descri pti o n
P F -0 7 0 3 8 1 2 4 
D ose/ Re gi me n
N u m ber of 
P artici p a nts
C 3 9 4 1 0 0 1
(c o m plete d)
Part A: 
Part A e val uate d t he s ki n irritati o n 
p ote ntial of 0. 0 6 % P F -0 7 0 3 8 1 2 4 
( C o h ort 1; 0. 0 6 %) a n d ve hicle ( place b o) 
a p plie d t o n or mal s ki n wit h a s mall 
s urface area of 0. 1 % B S A ( 2 0 c m 2).
Part B: 
Part B e val uate d t he safet y, t olera bilit y, 
s ki n irritati o n p ote ntial a n d P K f oll o wi n g 
a p plicati o n of P F-0 7 0 3 8 1 2 4 at i ncreasi n g
c o nce ntrati o ns ( C o h orts 1- 4; 0. 0 1 % , 
0. 0 3 % , a n d 0. 0 6 %) a n d ve hicle ( place b o) 
t o 1 0 % B S A ( 2 0 0 0 c m2).
C 3 9 4 1 0 0 2
(c o m plete d)
A P hase 2a, ra n d o mize d, d o u ble bli n d, 
ve hicle c o ntr olle d, parallel gr o u p st u d y 
t o assess efficac y, safet y, t olera bilit y a n d 
p har mac o ki netics of P F -0 7 0 3 8 1 2 4 
oi nt me nt i n partici pa nts wit h A D a n d 
Ps O. 
0. 0 1 % Q D a p plie d t o 
2 0 0 0 -4 0 0 0 c m 2 ( 5-2 0 % 
f or A D; 5-1 5 % Ps O)
f or 6 wee ks.
 
1 0 4
A D: 3 6 acti ve; 
3 4 ve hicle
Ps O: 1 7 acti ve; 
1 7 ve hicle
C 3 9 4 1 0 0 3
(e nr oll me nt 
c o m plete , C S R 
pe n di n g )
Ra n d o mize d, d o u ble -bli n d, ve hicle -
c o ntr olle d, parallel c o h ort st u d y t o 
e val uate t he safet y, t olera bilit y, s ki n 
irritati o n p ote ntial a n d P K
0. 0 1 % Q D a p plie d t o 
2 0 0 0 ( 1 0 % B S A) or 
4 0 0 0 c m 2 ( 2 0 % B S A) 
f or 1 0 da ys.
 
1 2 
4 acti ve; 2
ve hicle a p plie d 
at 2 0 0 0 c m 2,
4 acti ve; 2
ve hicle a p plie d 
at 4 0 0 0 c m 2
Cli nical data f or c o m plete d st u dies, C 3 9 4 1 0 0 1 a n d C 3 9 4 1 0 0 2, are pr o vi de d i n t he c urre nt 
versi o n of t he I B.
2. 3. Be nefit/ Ris k Assess me nt
M ore detaile d i nf or mati o n a b o ut t he k n o w n a n d e x pecte d be nefits a n d ris ks a n d reas o na bl y 
e x pecte d A Es of P F -0 7 0 3 8 1 2 4 ma y  be f o u n d i n t he I B, w hic h is t he S R S D f or t his st u d y. 
0 9 0 1 7 7 e 1 9 b b 9 c 5f d\ A p pr o v e d\ A p pr o v e d O n: 0 3- N o v- 2 0 2 2 1 1: 4 8 ( G M T)
C CI
C CI
C CI
C CI
C CI

P F -0 7 0 3 8 1 2 4
Pr ot oc ol C 3 9 4 1 0 0 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 2 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 Marc h 2 0 2 1)
Pa ge 3 1
P ote nti al Ris k of Cli nic al Si g nific a nce
S u m m ar y of D at a/ R ati o n ale f or Ris k
Miti g ati o n Str ate g y
St u d y I nter ve nti o n P F -0 7 0 3 8 1 2 4
S ki n Se nsitizati o n - n o n -cli nical fi n di n gs
 
 
 
Partici pa nts will be assesse d f or safet y at re g ular 
i nter vals t hr o u g h o ut t he st u d y, i ncl u di n g 
assess me nt of t he a d mi nistrati o n site. 
Partici pa nts wit h a n y hist or y of a n gi oe de ma or 
a na p h yla xis t o t o pical pr o d ucts or k n o w n 
se nsiti vit y t o a n y of t he c o m p o ne nts of t he 
i n vesti gati o nal pr o d ucts will be e xcl u de d fr o m t he 
st u d y.
St u d y treat me nt ma y be te m p oraril y disc o nti n ue d 
if se vere or ver y se vere ap plicati o n site reacti o n
occ ur .
P D E 4 -relate d ner v o us s yste m a n d gastr oi ntesti nal 
effect (a class effect of A Es o bser ve d wit h P D E 4 
i n hi bit ors) – n o n- cli nical fi n di n gs
Cli nical si g ns i n dicati ve of ner v o us s yste m 
effects (e g, ata xia, decrease d acti vit y, h u nc he d 
p ost ure, t witc hi n g, a n d/ or tre m ors) a n d 
gastr oi ntesti nal effects (e mesis, sali vati o n, a n d/ or 
s oft/li q ui d feces) were o bser ve d i n rats, d o g s, 
a n d/ or mi ni pi gs, at n o n -t olerate d d oses.
I P a p plicati o n will be u p t o 4 0 % B S A re d uci n g t he 
ris k of s yste mic e x p os ure. 
S y ste mic e x p os ure will be assesse d i n t he st u d y.
Partici pa nts will be assesse d f or safet y at re g ular 
i nter vals t hr o u g h o ut t he st u d y.
W orse ni n g of disease ( A D or Ps O ) 
1.
Partici pa nts i n ve hicle ( or i n l o wer d ose 
ar m) ma y e x perie nce a w orse ni n g of 
disease .
2.
Partici pa nts ma y e x perie nce a 
w orse ni n g of disease d uri n g was h o ut 
a n d/ or f oll o w-u p peri o ds .
A D a n d Ps O are n ot life -t hreate ni n g diseases.
Partici pa nts ma y disc o nti n ue treat me nt or 
wit h dra w fr o m t he st u d y at a n y ti me f or a n y 
reas o n.
Partici pa nts meeti n g wit h dra wal/ disc o nti n uati o n 
criteria ma y be a ble t o use alter nati ve treat me nts 
after wit h dra wal fr o m t he st u d y.
Partici pa nts will be assesse d f or safet y at re g ular 
i nter vals t hr o u g h o ut t he st u d y. 
0 9 0 1 7 7 e 1 9 b b 9 c 5f d\ A p pr o v e d\ A p pr o v e d O n: 0 3- N o v- 2 0 2 2 1 1: 4 8 ( G M T)
C CI
C CI

P F -0 7 0 3 8 1 2 4
Pr ot oc ol C 3 9 4 1 0 0 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 2 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 Marc h 2 0 2 1)
Pa ge 3 2
Ot her 
Ris k of S A R S -C o V -2 i nfecti o n 
Partici pa nts atte n di n g site visit ma y be e x p ose d .  
Use of tele healt h, h o me healt h, etc a n d a p pr o priate 
l ocal a n d gl o bal restricti o ns g ui deli nes will be 
utilize d a n d f oll o we d t o mi ni mize p ote ntial 
e x p os ure of trial partici pa nts t o S A R S -C o V -2 (see 
A p pe n di x 9 ).
0 9 0 1 7 7 e 1 9 b b 9 c 5f d\ A p pr o v e d\ A p pr o v e d O n: 0 3- N o v- 2 0 2 2 1 1: 4 8 ( G M T)

P F -0 7 0 3 8 1 2 4
Pr ot oc ol C 3 9 4 1 0 0 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 2 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 Marc h 2 0 2 1)
Pa ge 3 3
2. 3. 2. Be nefit Assess me nt
Base d o n its c y t o ki ne i n hi biti o n pr ofile, t o pical a d mi nistrati o n of P F- 0 7 0 3 8 1 2 4 is a ntici pate d 
t o pr o vi de p ote ntial t hera pe utic be nefit i n t he treat me nt of A D 
 
 a n d i n t he treat me nt of Ps O
. Ot her P D E 4 
i n hi bit ors, s uc h as crisa b or ole ( E ucrisa® , Sta q uis® ), a pre milast ( Otezla® ), a n d r ofl u milast 
( A R Q-1 5 1) 6 ha ve de m o nstrate d efficac y  i n t he treat me nt of A D or Ps O . I n a d diti o n, i n 
cli nical S t u d y C 3 9 4 1 0 0 2 wit h partici pa nts wit h A D a n d Ps O, sig nal of efficac y was n ote d . 
Base d o n t he cli nical data f o r t hese P D E 4 i n hi bit ors, partici pa nts i n t his st u d y ma y recei ve a 
be neficial effect, i n a d diti o n t o re g ular i nte nsi ve cli nical trial assess me nt t o s u p p ort 
partici pa nts’ ma na ge me nt of A D or Ps O .
T he i ncl u de d ve hicle has i m p orta nt e m ollie nt pr o perties. S o me ve hicle e xci pie nts ha ve a 
m ore pr o n o u nce d be neficial effect o n t he s ki n a n d ca n i m pr o ve cli nical a p peara nce a n d s ki n 
barrier f u ncti o n. I n partic ular, w hite petr olat u m, t he pri mar y  e xci pie nt a n d base of 
P F - 0 7 0 3 8 1 2 4 oi nt me nt was selecte d f or its e m ollie nt pr o perties a n d fa v ora ble t olera bilit y 
pr ofile. T he use of t o pical e m ollie nts is a n esse ntial ele me nt of A D a n d Ps O treat me nt a n d is 
rec o m me n de d by p u blis he d g ui deli nes.
2. 3. 3. O ver all Be nefit /Ris k C o ncl usi o n
Ta ki n g i nt o acc o u nt t he meas ures t o mi ni mize ris k t o st ud y partici pa nts , t he p ote ntial ris ks 
i de ntifie d i n ass ociati o n wit h P F - 0 7 0 3 8 1 2 4 are j ustifie d b y t he a ntici pate d be nefits t hat ma y 
be aff or de d t o partici pa nts wit h A D or Ps O .
T he Be nefit/ Ris k bala nce of P F -0 7 0 3 8 1 2 4 is c o nsi dere d fa v ora ble a n d s u p p orte d b y :

T he satisfact or y  safety a n d l ocal t olera bilit y pr ofile o n P F-0 7 0 3 8 1 2 4 t o date base d o n 
n o n-cli nical st u dies a n d cli nical S t u dies C 3 9 4 1 0 0 1 , C 3 9 4 1 0 0 2 , a n d C 3 9 4 1 0 0 3.

T he e x pecte d efficac y  of P F-0 7 0 3 8 1 2 4 f or t he treat me nt of A D a n d Ps O base d o n 
pre -cli nical data ge nerate d wit h P F-0 7 0 3 8 1 2 4 , si g nal of efficac y i n cli nical S t u d y 
C 3 9 4 1 0 0 2, a n d efficac y of ot her a p pr o ve d t o pical P D E 4 i n hi bit ors f or t he treat me nt 
of mil d -t o-m o derate A D ( E ucrisa ® / Sta q uis® ) a n d oral P D E 4 i n hi bit ors f or t he 
treat me nt of mil d-t o-se vere ps oriasis ( Otezla ® ).
Partici pa nts will be m o nit ore d cl osel y d uri n g t he st u d y f or safet y a n d l ocal t olera bilit y 
a d verse e ve nts b y t he st u d y  i n vesti gat ors a n d s p o ns or t o e ns ure partici pa nt safety.
I n c o ncl usi o n, Pfizer c o nsi ders t hat t he cli nical e x perie nce t o date wit h P F- 0 7 0 3 8 1 2 4 s u p p ort 
t he c o nti n ue d de vel o p me nt of P F-0 7 0 3 8 1 2 4 f or t he treat me nt of A D a n d Ps O s u p p orti n g t he 
i nitiati o n of P hase 2b S t u d y C 3 9 4 1 0 05.
A d diti o nal bac k gr o u n d i nf or mati o n o n P F -0 7 0 3 8 1 2 4 ca n be f o u n d i n t he c ur re nt versi o n of 
t he I B ( versi o n 3. 0, 2 0 2 2), es peciall y t he S u m mar y of Data a n d G ui da nce f or t he I n vesti gat or 
( Secti o n 7 of t he I B).
0 9 0 1 7 7 e 1 9 b b 9 c 5f d\ A p pr o v e d\ A p pr o v e d O n: 0 3- N o v- 2 0 2 2 1 1: 4 8 ( G M T)
C CI
C CI

P F -0 7 0 3 8 1 2 4
Pr ot oc ol C 3 9 4 1 0 0 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 2 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 Marc h 2 0 2 1)
Pa ge 3 4
3. O B J E C TI V E S, E N D P OI N T S, A N D E S TI M A N D S
A T O PI C D E R M A TI TI S
O bjecti ves
E n d p oi nts
Esti m a n ds
Pri m ar y: 
Pri m ar y:
Pri m ar y: 

T o c o m pare t he efficac y of 
2 d ose le vels of P F -0 7 0 3 8 1 2 4
oi nt me nt vers us ve hicle, usi n g 
I G A s uccess as t he e n d p oi nt i n 
partici pa nts wit h mil d or 
m o derate A D.

Pr o p orti o n of partici pa nts 
ac hie vi n g I G A sc ore of clear ( 0) 
or al m ost clear ( 1) ( o n a 5 -p oi nt 
scale) a n d a re d ucti o n fr o m 
baseli ne of ≥2 p oi nts at 
Wee k
1 2 .

Esti ma n d E 1 : the differe nce i n 
pr o p orti o ns of t he bi nar y 
e n d p oi nt bet w ee n I P treate d 
(0. 0 1 % or 0. 0 3 % P F -0 7 0 3 8 1 2 4 
oi nt me nt ) a n d ve hicle i n 
partici pa nts wit h mil d or 
m o derate A D wit h o ut t he 
be nefit of a d diti o nal pr o hi bite d 
me dicati o ns a n d re gar dless of 
treat me nt c o mplia nce .
Sec o n d ar y: 
Sec o n d ar y:
Sec o n d ar y: 

T o c o m pare t he efficac y of 
2 d ose le vels of P F -0 7 0 3 8 1 2 4 
oi nt me nt vers us ve hicle usi n g 
E A SI -7 5 as a n e n d p oi nt i n 
partici pa nts wit h mil d or 
m o derate A D.

Pr o p orti o n of partici pa nts 
ac hie vi n g E A SI -7 5 
( 7 5 % i m pr o ve me nt fr o m 
baseli ne ) at all st u d y visit ti me 
p oi nts s pecifie d i n t he S o A .
Esti ma n d E 1 descri be d a b o ve .
T o c o m pare t he efficac y of 
2 d ose le vels of P F -0 7 0 3 8 1 2 4 
oi nt me nt vers us ve hicle, usi n g 
I G A s uccess as t he e n d p oi nt i n 
partici pa nts wit h mil d or 
m o derate A D.
Pr o p orti o n of partici pa nts 
ac hie vi n g I G A sc ore of clear ( 0) 
or al m ost clear ( 1) ( o n a 5 -p oi nt 
scale) a n d a re d ucti o n fr o m 
baseli ne of ≥2 p oi nts at all st u d y 
visit ti me p oi nts s pecifie d i n t he 
S o A , e xce pt at Wee k 1 2 .
Esti ma n d E 1 descri be d a b o ve .

T o c o m pare t he efficac y of 
2 d ose le vels of P F -0 7 0 3 8 1 2 4 
oi nt me nt vers us ve hicle, usi n g 
p erce nt C F B i n E A SI as t he 
e n d p oi nt i n partici pa nts wit h 
mil d or m o derate A D.
Perce nt C F B i n E A SI t otal sc ore 
at all st u d y visit ti me p oi nts 
s pecifie d i n t he S o A .
Esti ma n d E 2: t he differ e nce i n 
mea n of t he c o nti n u o us 
e n d p oi nt bet wee n I P treate d 
( 0. 0 1 % or 0. 0 3 % P F -0 7 0 3 8 1 2 4 
oi nt me nt ) a n d ve hicle i n 
partici pa nts wit h mil d or 
m o derate A D wit h o ut t he 
be nefit of a d diti o nal pr o hi bite d 
me dicati o ns a n d re gar dless of 
treat me nt c o m plia nce.
T o c o m pare t he efficac y of 
2 d ose le vels of P F -0 7 0 3 8 1 2 4 
oi nt me nt vers us ve hicle, usi n g 
I G A clear or al m ost clear as t he 
e n d p oi nt i n partici pa nts wit h 
mil d or m o derate A D.
Pr o p orti o n of partici pa nts 
ac hie vi n g I G A sc ore of clear ( 0) 
or al m ost clear ( 1) at al l st u d y 
visit ti me p oi nts s pecifie d i n t he 
S o A .
Esti ma n d E 1 descri be d a b o ve .
0 9 0 1 7 7 e 1 9 b b 9 c 5f d\ A p pr o v e d\ A p pr o v e d O n: 0 3- N o v- 2 0 2 2 1 1: 4 8 ( G M T)

P F -0 7 0 3 8 1 2 4
Pr ot oc ol C 3 9 4 1 0 0 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 2 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 Marc h 2 0 2 1)
Pa ge 3 5
T o c o m pare t he efficac y of 
2 d ose le vels of P F -0 7 0 3 8 1 2 4 
oi nt me nt vers us ve hicle, usi n g 
meas ures of P P -N R S P R O, i n 
partici pa nts wit h mil d or 
m o derate A D.
Pr o p orti o n of partici pa nts 
ha vi n g ≥4 p oi nts of re d ucti o n
fr o m baseli ne i n wee kl y 
a vera ges of P P -N R S at st u d y 
visit ti me p oi nts s pecifie d i n t he 
S o A .
Esti ma n d E 1 descri be d a b o ve .
T o c o m pare t he efficac y of 
2 d ose le vels of P F -0 7 0 3 8 1 2 4 
oi nt me nt vers us ve hicle, usi n g 
B S A as t he e n d p oi nt i n 
partici pa nts wit h mil d or 
m o derate A D.
Perce nt C F B i n affecte d B S A at 
all st u d y visit ti me p oi nts 
s pecifie d i n t he S o A .
Esti ma n d E 2 descri be d a b o ve .
T o c haracte rize t he safet y a n d 
t olera bilit y of 2 d ose le vels of  
P F -0 7 0 3 8 1 2 4 oi nt me nt vers us 
ve hicle i n partici pa nts wit h mil d 
or m o derate A D.
I nci de nce of treat me nt e mer ge nt 
A E s a n d S A Es, cli nicall y 
si g nifica nt c ha n ges i n vital 
si g ns, E C G, a n d la b orat or y 
tests.
I nci de nce of i ncrease i n l ocal 
t olera bilit y se verit y gra des at 
ti mes i n dicate d i n t he S o A .

N ot A p plica ble .
0 9 0 1 7 7 e 1 9 b b 9 c 5f d\ A p pr o v e d\ A p pr o v e d O n: 0 3- N o v- 2 0 2 2 1 1: 4 8 ( G M T)
C CI

P F -0 7 0 3 8 1 2 4
Pr ot oc ol C 3 9 4 1 0 0 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 2 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 Marc h 2 0 2 1)
Pa ge 3 6
T a pe Stri p pi n g S u b -st u d y
T o e val uate p har mac ol o gical 
effects of a p pl yi n g m ulti ple 
d oses of P F - 07 0 3 8 1 2 4 oi nt me nt 
vers us ve hicle oi nt me nt usi n g 
ta pe stri p pi n g met h o d t hat is 
use d t o c ollect u p per part of 
e pi der mis.
P h ot o gr a p h y S u b -st u d y
T o c o m pare t he efficac y of t w o 
d ose le vels of P F -0 7 0 3 8 1 2 4 
oi nt me nt vers us ve hicle  
 
 
 
T o d oc u me nt effects of a p pl yi n g 
m ulti ple d oses of P F -0 7 0 3 8 1 2 4 
oi nt me nt vers us ve hicle 
oi nt me nt usi n g p h ot o gra p hic 
i ma ges.
P L A Q U E P S O RI A SI S
O bjecti ves
E n d p oi nts
Esti m a n ds
Pri m ar y: 
Pri m ar y:
Pri m ar y: 

T o c o m pare t he efficac y of 
m ulti ple d ose le vels of 
P F -0 7 0 3 8 1 2 4 oi nt me nt vers us 
ve hicle, usi n g P G A s uccess as 
t he e n d p oi nt i n partici pa nts wit h 
mil d -t o-se vere Ps O.

Pr o p orti o n of partici pa nts 
ac hie vi n g P G A sc ore of clear 
( 0) or al m ost clear ( 1) ( o n a 
5- p oi nt scale) a n d a re d ucti o n 
fr o m baseli ne of ≥2 p oi nts at 
Wee k 1 2.
Esti ma n d E 1: t he differe nce i n 
pr o p orti o ns of t he bi nar y
e n d p oi nt bet wee n I P treate d 
(0. 0 1 %, 0. 0 3 % , or 0. 0 6 % 
P F -0 7 0 3 8 1 2 4 oi nt me nt ) a n d 
ve hicle i n partici pa nts wit h 
mil d -t o-se vere Ps O wit h o ut t he 
be nefit of a d diti o nal pr o hi bite d 
me dicati o ns a n d re gar dless of 
treat me nt c o m plia nce.
Sec o n d ar y: 
Sec o n d ar y:
Sec o n d ar y: 
T o c o m pare t he efficac y of 
m ulti ple d ose le vels of 
P F -0 7 0 3 8 1 2 4 oi nt me nt vers us 
ve hicle usi n g P A SI -7 5 as a n 
e n d p oi nt, i n partici pa nts wit h 
mil d -t o-se vere Ps O .
Pr o p orti o n of partici pa nts 
ac hie vi n g P A SI -7 5 
( 7 5 % i m pr o ve me nt fr o m 
baseli ne) at ti mes i n dicate d i n 
t he S o A .
Esti ma n d E 1 descri be d a b o ve .
0 9 0 1 7 7 e 1 9 b b 9 c 5f d\ A p pr o v e d\ A p pr o v e d O n: 0 3- N o v- 2 0 2 2 1 1: 4 8 ( G M T)
C CI
C CI

P F -0 7 0 3 8 1 2 4
Pr ot oc ol C 3 9 4 1 0 0 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 2 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 Marc h 2 0 2 1)
Pa ge 3 7
T o c o m pare t he efficac y of 
m ulti ple d ose le vels of 
P F -0 7 0 3 8 1 2 4 oi nt me nt vers us 
ve hicle, usi n g P G A s uccess as 
e n d p oi nt i n partici pa nts wit h 
mil d -t o-se vere Ps O .
Pr o p orti o n of partici pa nts 
ac hie vi n g P G A sc ore of clear 
( 0) or al m ost clear ( 1) ( o n a 
5- p oi nt scale) a n d a re d ucti o n 
fr o m baseli ne of ≥2 p oi nts at 
ti mes i n dicate d i n t he S o A , 
e xce pt at Wee k 1 2 .
Esti ma n d E 1 descri be d a b o ve .

T o c o m pare t he efficac y of 
m ulti ple d ose le vels of 
P F -0 7 0 3 8 1 2 4 oi nt me nt vers us 
ve hicle, usi n g C F B P A SI as t he 
e n d p oi nt i n partici pa nts wit h 
mil d -t o-se vere Ps O .

C ha n ge fr o m baseli ne i n P A SI
at ti mes i n dicate d i n t he S o A .
Esti ma n d E 2: t he differe nce i n 
mea n of t he c o nti n u o us 
e n d p oi nt bet wee n I P treate d 
(0. 0 1 %, 0. 0 3 %, or 0. 0 6 % 
P F -0 7 0 3 8 1 2 4 oi nt me nt ) a n d 
ve hicle i n partici pa nts wit h 
mil d -t o-se vere Ps O wit h o ut t he 
be nefit of a d diti o nal pr o hi bite d 
me dicati o ns a n d re gar dless of 
treat me nt c o m plia nce.
T o c o m pare t he efficac y of 
m ulti ple d ose le vels of 
P F -0 7 0 3 8 1 2 4 oi nt me nt vers us 
ve hicle, usi n g P G A clear or 
al most clear as t he e n d p oi nt i n 
partici pa nts wit h mil d -t o-se vere 
Ps O .
Pr o p orti o n of partici pa nts 
ac hie vi n g P G A sc ore of clear 
( 0) or al m ost clear ( 1) at all 
st u d y visit ti me p oi nts s pecifie d 
i n t he S o A .
Esti ma n d E 1 descri be d a b o ve .
T o c o m pare t he efficac y of 
m ulti ple d ose le vels of 
P F -0 7 0 3 8 1 2 4 oi nt me nt vers us 
ve hicle, usi n g meas ures of 
P P -N R S P R O, i n a d ult 
( 1 8-7 5 years ol d) partici pa nts 
wit h mil d -t o-se vere Ps O.
Pr o p orti o n of a d ult ( 1 8-7 5 years 
ol d) partici pa nts ha vi n g 
≥4 p oi nts of re d ucti o n fr o m 
baseli ne i n wee kl y a vera ges of 
P P -N R S at st u d y visit ti me 
p oi nts s pecifie d i n t he S o A .
Esti ma n d E 1 descri be d a b o ve .
T o c o m pare t he efficac y of 
m ulti ple d ose le vels of 
P F -0 7 0 3 8 1 2 4 oi nt me nt vers us 
ve hicle, usi n g B S A as t he 
e n d p oi nt i n partici pa nts wit h 
mil d -t o-se vere Ps O.
Perce nt C F B i n affecte d B S A at 
all st u d y visit ti me p oi nts 
s pecifie d i n t he S o A .
Esti ma n d E 2 descri be d a b o ve .
T o c haracterize t he safet y a n d 
t olera bilit y of m ulti ple d ose 
le vels of P F-0 7 0 3 8 1 2 4 oi nt me nt 
vers us ve hicle i n partici pa nts 
wit h mil d- t o-se vere Ps O.
I nci de nce of treat me nt e mer ge nt 
A E s a n d S A Es, cli nicall y 
si g nifica nt c ha n ges i n vital 
si g ns, E C G, a n d la b orat or y 
tests.
I nci de nce of i ncrease i n l ocal 
t olera bilit y se verit y gra des at 
ti mes i n dicate d i n t he S o A .
N ot A p plica ble .
0 9 0 1 7 7 e 1 9 b b 9 c 5f d\ A p pr o v e d\ A p pr o v e d O n: 0 3- N o v- 2 0 2 2 1 1: 4 8 ( G M T)

P F -0 7 0 3 8 1 2 4
Pr ot oc ol C 3 9 4 1 0 0 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 2 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 Marc h 2 0 2 1)
Pa ge 3 8
T a pe Stri p pi n g S u b -st u d y
T o e val uate p har mac ol o gical 
effects of a p pl yi n g m ulti ple 
d oses of P F -0 7 0 3 8 1 2 4 oi nt me nt 
vers us ve hicle oi nt me nt usi n g 
ta pe stri p pi n g met h o d t hat is 
use d t o c ollect u p per part of 
e pi der mis.
P h ot o gr a p h y S u b -st u d y

T o d oc u me nt effects of 
a p pl yi n g m ulti ple d oses of 
P F -0 7 0 3 8 1 2 4 oi nt me nt vers us 
ve hicle oi nt me nt usi n g 
p h ot o gra p hic i ma ges.
0 9 0 1 7 7 e 1 9 b b 9 c 5f d\ A p pr o v e d\ A p pr o v e d O n: 0 3- N o v- 2 0 2 2 1 1: 4 8 ( G M T)
C CI
C CI

P F -0 7 0 3 8 1 2 4
Pr ot oc ol C 3 9 4 1 0 0 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 2 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 Marc h 2 0 2 1)
Pa ge 3 9
4. S T U D Y D E SI G N
4. 1. O ver all Desi g n
T his is a p hase 2 b, ra n d o mize d, d o u ble bli n d, ve hicle c o ntr olle d, parallel gr o u p, m ultice nter 
st u d y t o assess t he efficac y, safety a n d t olera bilit y, a n d P K of m ulti ple d oses of P F - 0 7 0 3 8 1 2 4 
oi nt me nt vers us ve hicle i n treat me nt of partici pa nts , 1 2 ye ars a n d ol der, a n d wit h A D or Ps O. 
I n t his st u dy, a t otal of a p pr o xi matel y 2 4 0 partici pa nts wit h A D or Ps O will be ra n d o ml y 
assi g ne d t o st u d y i nter ve nti o n (P F - 0 7 03 8 1 2 4 or ve hicle ).
Partici pa nts will be scree ne d f or eli gi bilit y  t o partici pate i n t he trial wit hi n 4 wee ks of 
ra n d o mizati o n, o n Da y  1. D uri n g Scree ni n g peri o d, partici pa nts will be gi n d oc u me nt i n g t heir 
disease s y m pt o ms i n t he e-diar y , at least 7 d a y s pri or t o ra n d o mizati o n. After c o nfir mi n g 
eli gi bilit y o n Da y  1, as o utli ne d i n Secti o n 1. 3. 1 a n d Secti o n 1. 3. 2 f or A D a n d Ps O 
res pecti vely , ra n d omizati o n will occ ur a n d treat me nt wit h t he st u d y i nter ve nti o n will be gi n . 
Treat me nt wit h st u d y  i nter ve nti o n ( P F- 0 7 0 3 81 2 4 oi nt me nt o r ve hicle oi nt me nt) will be o nce 
dail y  f or 1 2 wee ks f oll o we d b y a safet y f oll o w -u p peri o d of 4 -5 wee ks fr o m last a p plicati o n 
of st u d y  dr u g t o last st u d y visit. T he t otal d urati o n of st u d y  partici pati o n is a p pr o xi matel y 
2 1 wee ks. 

F or A D, a p pr o xi matel y 1 2 0 partici pa nts will be ra n d o ml y  assi g ne d 1: 1: 1 t o recei ve 
eit her 0. 0 1 % P F -0 7 0 3 8 1 2 4 oi nt me nt, 0. 0 3 % P F -0 7 0 3 8 1 2 4 oi nt me nt or a ve hicle 
oi nt me nt .

Ra n d o mizati o n will be stratifie d b y baseli ne disease se verit y ( mil d [I G A = 2] vs 
m o derate [I G A = 3]) a n d b y  ta pe stri p pi n g s u b-st u d y partici pati o n. 
 
 

F or Ps O, a p pr o xi matel y 1 2 0 partici pa nts will be ra n d o ml y  assi g ned 1: 1: 1: 1 t o recei ve 
eit her 0. 0 1 % P F -0 7 0 3 8 1 2 4 oi nt me nt, 0. 0 3 % P F - 0 7 0 3 8 1 2 4 oi nt me nt, 0. 0 6 % 
P F -0 7 0 3 8 1 2 4 or a ve hicle oi nt me nt.

Ra n d o mizati o n will be stratifie d b y baseli ne disease se verit y ( mil d [ P G A = 2], 
m o derate [ P G A = 3], se vere [ P G A = 4]) a n d b y ta pe stri p pi n g s u b-st u d y 
partici pati o n .
 
0 9 0 1 7 7 e 1 9 b b 9 c 5f d\ A p pr o v e d\ A p pr o v e d O n: 0 3- N o v- 2 0 2 2 1 1: 4 8 ( G M T)
C CI
C CI

P F -0 7 0 3 8 1 2 4
Pr ot oc ol C 3 9 4 1 0 0 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 2 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 Marc h 2 0 2 1)
Pa ge 4 0
T a ble 2. 
P artici p a nt Distri b uti o n
P artici p a nt P o p ul ati o n
St u d y I nter ve nti o n
A p pr o xi m ate n u m ber of P artici p a nts 
C o m pleti n g t he St u d y
A D
0. 0 1 % P F -0 7 0 3 8 1 2 4
4 0
0. 0 3 % P F -0 7 0 3 8 1 2 4
4 0
Ve hicle
4 0
P s O
0. 0 1 % P F -0 7 0 3 8 1 2 4
3 0
0. 0 3 % P F -0 7 0 3 8 1 2 4
3 0
0. 0 6 % P F -0 7 0 3 8 1 2 4
3 0
Ve hicle
3 0
M ulti ple safet y , efficac y, P K a n d bi o mar ker assess me nts will be perf or me d d uri n g t he 
treat me nt a n d f oll o w-u p peri o d. 
T he st u d y  will i ncl u de 2 s u b -st u dies:
4. 2. Scie ntific R ati o n ale f or St u d y Desi g n
A si n gle , pri mar y  e n d p oi nt base d o n re g ulat or y prece de nce is pla n ne d f or b ot h A D a n d Ps O.
F D A re q uires pri mar y  e n d p oi nt f or A D a n d Ps O t o be I G A a n d P G A, res pecti vely a n d 
sec o n dar y e n d p oi nts t o be E A SI a n d P A SI. Si nce I GA a n d E A SI i n A D a n d P G A a n d P A SI
i n Ps O are n ot i n de pe n de nt varia bles a n d s h o ul d trac k i n parallel, t here is a hi g h pr o ba bilit y 
t hat t hese will be c o nsiste nt. T hese are well -vali date d e n d p oi nts a n d ha ve bee n use d as 
re g ulat or y a n d cli nical e n d p oi nts i n A D/ Ps O st u dies f or ma n y ye ars, t heref ore, f or A D, I G A
is c h ose n t o be t he pri mar y  e n d p oi nt a n d E A SI as sec o n dar y. Si milarly, f or Ps O, P G A is 
c h ose n as t he pri mar y  e n d p oi nt a n d P A SI as sec o n dar y.
 
 
 
 
0 9 0 1 7 7 e 1 9 b b 9 c 5f d\ A p pr o v e d\ A p pr o v e d O n: 0 3- N o v- 2 0 2 2 1 1: 4 8 ( G M T)
C CI
C CI

P F -0 7 0 3 8 1 2 4
Pr ot oc ol C 3 9 4 1 0 0 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 2 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 Marc h 2 0 2 1)
Pa ge 4 1
 
 
4. 2. 1. Di versit y of St u d y P o p ul ati o n
Reas o na ble atte m pts will be ma de t o e nr oll partici pa nts wit h t he distri b uti o n of 
c haracteristics wit h res pect t o race, et h nicit y, a n d a ge t o e ns ure t he st u d y p o p ulati o n is 
re prese ntati ve of t he patie nt p o p ulati o n t hat will use st u d y i nter ve nti o n i n cli nical practice .
4. 2. 2. C h oice of C o ntr ace pti o n/ B arrier Re q uire me nts
H u ma n re pr o d ucti ve safet y  data are li mite d f or P F - 0 7 0 3 8 1 2 4, b ut t here is n o s us pici o n of 
h u ma n terat o ge nicit y base d o n t he i nte n de d p har mac ol o g y of t he c o m p o u n d. T heref ore, t he 
use of a hi g hl y effecti ve met h o d of c o ntrace pti o n is re q uire d (see A p pe n di x 4 ).
4. 2. 3. C ollecti o n of Ret ai ne d Rese arc h S a m ples
Retai ne d Researc h Sa m ples will be c ollecte d a n d st ore d f or f urt her a nal ys es w hic h ma y, f or 
e xa m ple, pr o vi de greater u n dersta n di n g of t he st u d y  i nter ve nti o n.
4. 3. J ustific ati o n f or D ose
T he n o ncli nical safet y pr ofile of P F -0 7 0 3 8 1 2 4 f oll o wi n g sys te mic a d mi nistrati o n t o rats a n d 
t o pical a p plicati o n t o mi ni pi gs s u p p orts h u ma n cli nical st u dies of u p t o 3 m o nt hs i n d urati o n 
( See Secti o n 2. 2 ).
T he d ose s pr o p ose d f or t his st u d y  were deter mi ne d c o nsi deri n g all rele va nt i nf or mati o n
o btai ne d fr o m n o ncli nical safet y st u dies, i nc or p orati n g t he N O A E L fr o m 3 -m o nt h st u dies i n 
mi ni pi gs, t o get her wit h t he s y ste mic e x p os ure a n d t olera bilit y o bser ve d f oll o wi n g t o pical 
a p plicati o n of P F-0 7 0 3 8 1 2 4 t o healt h y  partici pa nts i n S t u dy C 3 9 4 1 0 0 1 (Ta ble 3 ) a n d S t u d y 
C 3 9 4 1 0 0 3 ( preli mi nar y  data), a n d i n partici pa nts wit h A D or Ps O i n 6-wee k S t u d y 
C 3 9 4 1 0 0 2. 
I n S t u d y C 3 9 4 1 0 0 2, at Wee k 6, u p t o 6 h o urs p ost -d ose, greater t ha n 8 6 % a n d 9 8 % of plas ma 
P K sa m ples of P F -0 7 0 3 8 1 2 4 were B L Q of 1 0 p g/ m L  i n A D a n d Ps O partici pa nts, 
res pecti vely. 
 
 
 In a d diti o n, t he u p date d f or m ulati o n 
 
was als o i n vesti gate d i n healt h y  Ja pa nese partici pa nts ( C 3 9 4 1 0 0 3) a n d t he fi n di n gs were 
c o nsiste nt wit h t he e x p os ure o bser ve d i n A D a n d Ps O patie nts ( C 3 9 4 1 0 0 2). 
0 9 0 1 7 7 e 1 9 b b 9 c 5f d\ A p pr o v e d\ A p pr o v e d O n: 0 3- N o v- 2 0 2 2 1 1: 4 8 ( G M T)
C CI
C CI
C CI

P F -0 7 0 3 8 1 2 4
Pr ot oc ol C 3 9 4 1 0 0 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 2 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 Marc h 2 0 2 1)
Pa ge 4 2
 
 
D ose stre n gt hs selecte d f or t his st u d y  are 0. 0 1 %, 0. 0 3 % a n d 0. 0 6 % P F -0 7 0 3 8 1 2 4.  
 
 
 
 
 
 
T he cli nical tra nslati o n of t hese i n vitr o s y ste ms is u n k n o w n.
Base d o n t he fi n di n gs fr o m t he P hase 2a st u d y (C 3 9 4 1 0 0 2 ), t he cli nical efficac y criteri o n f or 
%c ha n ge fr o m base li ne i n E A SI a n d %I G A res p o n ders i n A D were met usi n g t he 0. 0 1 % d ose 
stre n gt h f oll o wi n g Q D a p plicati o n, a n d c o m para ble t o efficac y wit h ot her t o pical a ge nts 
a p pr o ve d f or mil d- t o- m o derate A D. T he d ose stre n gt hs of P F- 0 7 0 3 8 1 2 4 selecte d f or t his 
st u d y are 0. 01 % a n d a hi g her d ose of 0. 0 3 % i n partici pa nts wit h A D t o i n vesti gate t he a bilit y 
t o ac hie ve greater efficac y  c o m pare d t o ot her t o pical a ge nts, w hile still mi ni mizi n g s y ste mic 
e x p os ure . F or Ps O, e ve n t h o u g h t he cli nical efficac y  criteri o n of c ha n ge fr o m baseli ne i n 
P A SI  sc ore was met wit h t he 0. 0 1 % Q D re gi me n, t he efficac y criteri o n f or % P G A 
res p o n ders was n ot ac hie ve d. As a res ult , t he i nte nt of t his P hase 2 b st u d y  is t o esta blis h 
ma xi m u m efficac y  a n d safety i n t his i n dicati o n wit h e x pl or ati o n of t he lar gest p ossi ble d ose 
ra n ge (e g, 0. 0 1 %, 0. 0 3 %, a n d 0. 0 6 %) is re q uire d.
0 9 0 1 7 7 e 1 9 b b 9 c 5f d\ A p pr o v e d\ A p pr o v e d O n: 0 3- N o v- 2 0 2 2 1 1: 4 8 ( G M T)
C CI
C CI
C CI

P F -0 7 0 3 8 1 2 4
Pr ot oc ol C 3 9 4 1 0 0 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 2 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 Marc h 2 0 2 1)
Pa ge 4 3
0 9 0 1 7 7 e 1 9 b b 9 c 5f d\ A p pr o v e d\ A p pr o v e d O n: 0 3- N o v- 2 0 2 2 1 1: 4 8 ( G M T)
C CI

P F -0 7 0 3 8 1 2 4
Pr ot oc ol C 3 9 4 1 0 0 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 2 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 Marc h 2 0 2 1)
Pa ge 4 4
4. 4. E n d of St u d y Defi niti o n
T he e n d of t he st u d y is defi ne d as t he date of t he last visit of t he last partici pa nt i n t he st u d y.
A partici pa nt is c o nsi dere d t o ha ve c o m plete d t he st u d y  if he/s he has c o m plete d all peri o ds of 
t he st u d y, i ncl u di n g t he last visit.
5. S T U D Y P O P U L A TI O N
T his st u d y  ca n f ulfill its o bjecti ves o nl y if a p pr o priate partici pa nt s 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 partici pa nt s 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 me 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 partici pa nt is s uita ble f or t his 
pr ot oc ol .
Pr os pecti ve a p pr o val of pr ot oc ol de viati o ns t o recr uit me nt a n d e nr oll me nt criteria , als o 
k n o w n as pr ot oc ol wai vers or e xe m pti o ns, is n ot per mitte d.
5. 1. I ncl usi o n Criteri a
T he i ncl usi o n criteria f or A D a n d Ps O are o verla p pi n g b ut differe nt. Det ails of t he 
o verla p pi n g i ncl usi o n criteria are pr o vi de d i n Secti o n 5. 1. 1 ; Disease-s pecific i ncl usi o n 
criteria are pr o vi de d i n Secti o n 5. 1. 2. 1 a n d Secti o n 5. 1. 2. 2 f or A D a n d Ps O, res pecti vely.
5. 1. 1. Ge ner al I ncl usi o n Criteri a A p plic a ble f or b ot h A D a n d Ps O
Partici pa nts are eli gi ble t o be i ncl u de d i n t he st u d y o nl y if all of t he f oll o wi n g criteria a p ply:
A ge a n d Se x :
1.
P artici pa nts a ges 12 ye ars (i ncl usi ve) a n d a b o ve, at Scree ni n g .

Refer t o A p pe n di x 4 f or re pr o d ucti ve criteria f or male (Secti o n 1 0. 4. 1 ) a n d fe male 
(Secti o n 1 0. 4. 2 ) partici pa nts.
T y pe of P artici p a nt a n d Dise ase C h ar acteristics:
2.
Partici pa nts w h o are willi n g a n d a ble t o c o m pl y wit h all sc he d ule d visits, treat me nt 
pla n, la b orat or y  tests, lifest yle c o nsi derati o ns, a n d ot her st u d y pr oce d ures.
I nf or me d C o nse nt/ asse nt:
3.
Ca pa ble of gi vi n g si g ne d i nf or me d c o nse nt /asse nt as descri be d i n A p pe n di x 1 , w hic h 
i ncl u des c o m plia nce wit h t he re q uire me nts a n d restricti o ns liste d i n t he I CD a n d i n 
t his pr ot oc ol.
T he i n vesti gat or, or a pers o n desi g nate d b y t he i n vesti gat or, will o btai n 
writte n/electr o nicall y  si g ne d i nf or me d c o nse nt fr o m eac h st u d y partici pa nt’s le gal 
g uar dia n (as defi ne d i n A p pe n di x 1 ) a n d t he partici pa nt’s asse nt, w he n a p plica ble, 
0 9 0 1 7 7 e 1 9 b b 9 c 5f d\ A p pr o v e d\ A p pr o v e d O n: 0 3- N o v- 2 0 2 2 1 1: 4 8 ( G M T)

P F -0 7 0 3 8 1 2 4
Pr ot oc ol C 3 9 4 1 0 0 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 2 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 Marc h 2 0 2 1)
Pa ge 4 5
bef ore a n y st u d y- s pecific acti vit y is perf or me d u nless a wai ver of i nf or me d c o nse nt 
has bee n gra nte d b y a n I R B/ E C. All le gal g uar dia ns s h o ul d be f ull y i nf or me d, a n d 
partici pa nts s h o ul d be i nf or me d t o t he f ull est e xte nt p ossi ble, a b o ut t he st u d y  i n 
la n g ua ge a n d ter ms t he y are a ble t o u n dersta n d. T he i n vesti gat or will retai n t he 
ori gi nal c o p y of eac h partici pa nt's si g ne d c o nse nt/asse nt d oc u me nt.
5. 1. 2. Dise ase - S pecific I ncl usi o n Criteri a:
5. 1. 2. 1. A D S pecific I ncl usi o n Criteri a
4.
Ha ve bee n dia g n ose d wit h A D f or at least 3 m o nt hs pri or t o Scree ni n g .
N ote : T he cli nical dia g n osis of A D will be c o nfir me d acc or di n g t o t he criteria of 
Ha nifi n a n d Raj ka 7 (A p pe n di x 1 0 ).
5.
Ha ve a n I G A sc ore of 2 ( mil d), or 3 ( m o derate) at Scree ni n g a n d Da y 1, pri or t o 
ran d o mizati o n . Refer t o Secti o n 8. 1. 1. 1. 1 a n d A p pe n di x 1 2 f or t he assess me nt of 
5 -p oi nt I G A.
6.
Ha ve A D c o veri n g 5 % a n d u p t o 4 0 % of B S A (e xcl u di n g t he hair -beari n g scal p) at 
Scree ni n g a n d Da y  1, pri or t o ra n d o mizati o n. Refer t o Sect i o n 1 0. 1 2. 1. 3
(A p pe n di x 1 2 ) f or detaile d met h o ds of calc ulati n g treata ble % B S A .
7.
Ha ve a P P -N R S a vera ge sc ore of ≥2 assesse d at Da y  1, pri or t o ra n d o mizati o n.
5. 1. 2. 2. P s O S pecific I ncl usi o n Criteri a
8.
Ha ve a dia g n osis of Ps O ( ps oriasis v ul garis) f or at least 6 m o nt hs pri or t o Scree ni n g .
9.
Ha ve a P G A sc ore of 2 ( mil d), 3 ( m o derate), or 4 (se vere) at Scree ni n g a n d Da y 1 , 
pri or t o ra n d o mizati o n. Refer t o Secti o n 8. 1. 2. 1. 1 a n d A p pe n di x 1 2 f or t he assess me nt 
of 5 -p oi nt P G A .
1 0. Ha v e Ps O c o veri n g 2 % t o 2 0 % (i ncl usi ve) of B S A ( e xcl u di n g t he hair -beari n g scal p, 
pal ms, s oles, fi n ger nails a n d t oe nails ) at Scree ni n g a n d Da y 1, pri or t o 
ra n d o mizati o n. Refer t o Secti o n 1 0. 1 2. 2. 3 (A p pe n di x 1 2 ) f or detaile d met h o ds of 
calc ulati n g treata ble B S A .
5. 2. E xcl usi o n Criteri a
T he e xcl usi o n criteri a f or A D a n d Ps O p o p ul ati o n are t he s a me.
Partici pa nts are e xcl u de d fr o m t he st u d y  if a n y of t he f oll o wi n g criteria a p pl y:
Me dic al C o n diti o ns:
1.
Prese nce of s ki n c o m or bi dities t hat w o ul d i nterfere wit h st u d y  assess me nt or res p o nse 
t o treat me nt.
0 9 0 1 7 7 e 1 9 b b 9 c 5f d\ A p pr o v e d\ A p pr o v e d O n: 0 3- N o v- 2 0 2 2 1 1: 4 8 ( G M T)

P F -0 7 0 3 8 1 2 4
Pr ot oc ol C 3 9 4 1 0 0 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 2 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 Marc h 2 0 2 1)
Pa ge 4 6
2.
A n y  psyc hiatric c o n diti o n i ncl u di n g rece nt or acti ve s u ici dal i deati o n or be ha vi or t hat 
meets a n y of t he criteria i n A p pe n di x 1 1 , at Scree ni n g .
3.
C urre nt or rece nt hist or y  ( wit hi n a p pr o xi matel y 3 m o nt hs pri or t o Da y 1) of se vere, 
pr o gressi ve, or u nc o ntr olle d re nal, he patic, he mat ol o gical, gastr oi ntesti nal, meta b olic, 
e n d ocri ne, p ul m o nar y, car di o vasc ular, or ne ur ol o gical disease.
4.
A hist or y  ( wit hi n a p pr o xi matel y 3 m o nt hs pri or t o Da y 1) of s ys te mic, c hr o nic or 
ac ute s ki n i nfecti o n ( wit hi n a p pr o xi matel y  2 wee ks pri or t o Da y 1) 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  
si g nifica nt by t he i n vesti gat or.
5.
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 pri or t o S cree ni n g.
6.
Ha ve a hist or y  of ca ncer wit hi n 5 years or has u n der g o ne treat me nt f or a n y t ype of 
ca ncer, wit h t he e xce pti o n of a de q uatel y  treate d or e xcise d n o n-metastatic basal cell 
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 wit h n o e vi de nce of 
rec urre nce.
7.
Ha ve a hist or y  of a n gi oe de ma or a na p h yl a xis t o t o pical pr o d ucts or k n o w n se nsiti vit y  
t o a n y of t he c o m p o ne nts of t he i n vesti gati o nal pr o d ucts.
8.
Ot her me dical or ps y c hiatric c o n diti o n i ncl u di n g rece nt ( wit hi n t he past year) or 
acti ve s uici dal i deati o n/be ha vi or or la b orat or y  a b n or malit y t hat m a y  i ncrease t he ris k 
of st u d y partici pati o n or, i n t he i n vesti gat or’s j u d g me nt, ma ke t he partici pa nt 
i na p pr o priate f or t he st u d y.
Pri or/ C o nc o mit a nt T her a p y:
9.
C urre nt use of a n y  pr o hi bite d c o nc o mita nt me dicati o n(s) or t h ose u n willi n g/ u na ble t o 
use a per mitt e d c o nc o mita nt me dicati o n(s). Refer t o Secti o n 6. 8 a n d Secti o n 1 0. 8 f or 
g ui da nce o n per mitte d a n d pr o hi bite d c o nc o mita nt me dicati o ns .
Pri or/ C o nc urre nt Cli nic al St u d y E x perie nce:
1 0. Pre vi o us a d mi nistrati o n wit h a n i n vesti gati o nal dr u g wit hi n 3 0 d a y s ( or as deter mi ne d 
b y  t he l ocal re q uire me nt) or 5 half -li ves prece di n g t he first d ose of st u d y i nter ve nti o n
use d i n t his st u d y ( w hic he ver is l o n ger).
N ote : A n y i n vesti gati o nal or e x peri me ntal t hera p y ta ke n or pr oce d ure perf or me d f or 
A D, Ps O , Ps A or R A i n t he pre vi o us ye ar s h o ul d be disc usse d wit h t he Pfizer m e dical 
m o nit or ( or desi g nee). Partici pa nts 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 ny ti me d uri n g t heir 
partici pati o n i n t his st u d y .
0 9 0 1 7 7 e 1 9 b b 9 c 5f d\ A p pr o v e d\ A p pr o v e d O n: 0 3- N o v- 2 0 2 2 1 1: 4 8 ( G M T)

P F -0 7 0 3 8 1 2 4
Pr ot oc ol C 3 9 4 1 0 0 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 2 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 Marc h 2 0 2 1)
Pa ge 4 7
Di a g n ostic Assess me nts:
1 1. Partici pa nts wit h 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 s p o ns or defi ne d la b orat or y a n d c o nfir me d by a si n gle 
re peat (t he last val ue will be use d t o deter mi ne eli gi bilit y), if dee me d necessar y:

Re nal im pair me nt as defi ne d b y  a n e G F R of < 4 0 m L / mi n/ 1. 7 3 m2 calc ulate d usi n g 
t he ser u m creati ni ne-base d C K D -E PI  f or m ula f or a d ults a n d ser u m creati ni ne 
> 1. 5 x U L N i n a d olesce nts ( 1 2 -1 8 y ears ol d).

H e patic d ys f u ncti o n defi ne d as total bilir u bi n ≥2 x U L N ( ≥3 x U L N f or Gil bert’s 
disease) , A S T ≥2. 5 x U L N , A L T ≥2. 5 x U L N.
1 2. Baseli ne sta n dar d 1 2 -lea d E C G t hat de m o nstrates cli nicall y rele va nt a b n or malities 
t hat ma y affect partici pa nt safety or i nter pretati o n of st u d y res ults (e g, Q Tc F i nter val 
> 4 5 0 msec, c o m plete L B B B, si g ns of a n ac ute or i n deter mi nate a ge m y ocar dial 
i nfarcti o n, S T- T i nter val c ha n ges s u g gesti ve of m yocar dia l isc he mia, sec o n d or t hir d
de gree A V bl oc k, or seri o us bra d yarr h yt h mias or tac h y arr h yt h mias). If t he baseli ne 
u nc orrecte d Q T i nter val is > 4 5 0 msec, t his i nter val s h o ul d be rate c orrecte d usi n g t he 
Fri dericia met h o d a n d t he res ulti n g Q Tc F s h o ul d be use d f o r decisi o n ma ki n g a n d 
re p orti n g. If Q TcF e xcee ds 4 5 0 msec, or Q R S e xcee ds 1 2 0 msec, t he E C G s h o ul d be 
re peate d 2 m ore ti mes a n d t he a vera ge of t he 3 Q Tc F or Q R S val ues s h o ul d be use d 
t o deter mi ne t he partici pa nt’s eli gi bilit y. C o m p uter i nter prete d E C Gs s h oul d be 
o verrea d b y a p h ys icia n e x perie nce d i n rea di n g E C Gs bef ore e xcl u di n g a partici pa nt.
Ot her E xcl usi o ns:
1 3. 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 Scree ni n g 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. I n vesti gat or site staff or Pfizer e m pl o yees directl y i n v ol ve d i n t he c o n d uct of t he 
st u d y, site staff ot her wise s u per vise d b y t he i n vesti gat or, a n d t heir res pecti ve fa mil y 
me m bers .
5. 3. Lifest yle C o nsi der ati o ns
5. 3. 1. C o ntr ace pti o n 
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 partici pa nt, will c o nfir m t hat 
t he partici pa nt has selecte d a n a p pr o priate met h o d of c o ntrace pti o n f or t he i n di vi d ual 
partici pa nt a n d his or her part ner(s) fr o m t he per mitte d list of c o ntrace pti o n met h o ds ( see
A p pe n di x 4 Secti o n 1 0. 4. 4 ) a n d will c o nfir m t hat t he partici pa nt 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 S o A , t he i n vesti gat or or desi g nee 
will i nf or m t he partici pa nt of t he nee d t o use acce pta ble effecti ve c o ntrace pti o n c o nsiste ntl y 
a n d c orrectl y a n d d oc u me nt t he c o n v ersati o n a n d t he partici pa nt’s affir mati o n i n t he
partici pa nt’s c hart ( partici pa nts nee d t o affir m t heir 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) c o nsi deri n g t hat t heir ris k f or pre g na nc y ma y ha ve 
0 9 0 1 7 7 e 1 9 b b 9 c 5f d\ A p pr o v e d\ A p pr o v e d O n: 0 3- N o v- 2 0 2 2 1 1: 4 8 ( G M T)

P F -0 7 0 3 8 1 2 4
Pr ot oc ol C 3 9 4 1 0 0 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 2 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 Marc h 2 0 2 1)
Pa ge 4 8
c ha n ge d si nce t he last visit. In a d diti o n, t he i n vesti gat or or desi g nee will i nstr uct t he 
partici pa nt 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 partici pa nt or part ner.
5. 3. 2. Diet ar y S u p ple me nts
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, 
p urifie d f o o d s u bsta nces, a n d her bals wit h p har mace utical pr o perties. 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 ociat e d wit h a d verse 
effects (s uc h as h y p er vita mi n osis). Her bal s u p ple me nts are o nl y all o we d o n a case -b y -case 
basis; please c o ntact t he Pfizer staff. Her bals e g, St. J o h n’s W ort t hat are k n o w n t o ha ve a n 
effect o n dr u g meta b olis m m ust be disc o nti n ue d at least 4 wee ks or 5 half -li ves ( w hic he ver is 
l o n ger) bef ore Da y 1.
5. 3. 3. Me dic ati o ns/ Tre at me nts Disc o nti n u ati o n, N o n -Me dic ate d E m ollie nts
Partici pa nts 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 as 
descri be d i n A p pe n di x 8 .

All t o pical me dicati o ns a n d treat me nts t hat c o ul d affect A D or Ps O s ki n areas m ust be 
disc o nti n ue d pri or t o Da y  1, as s pecifie d i n A p pe n di x 8 , if t he s ki n areas are t o be 
treate d wit h st u d y i nter ve nti o n. 

U nless s pecifie d i n A p pe n di x 8 , a n y ot her c o nc o mita nt me dicati o n f or A D or Ps O
will be c o nsi dere d o n a case- b y -case basis b y t he i n vesti gat or i n c o ns ultati on wit h t he 
s p o ns or me dical m o ni t or. 

Partici pa nts will st o p a p pl y i n g bla n d ( n o n -me dicate d , urea- a n d lactic aci d free -) 
e m ollie nts a n d s u nscree n o n A D /Ps O affecte d s ki n 2 4 h o urs pri or t o Da y 1.

After Da y  1 Visit, use of n o n-me dicate d bla n d e m ollie nt(s) is per mitte d d uri n g t he 
st u d y t o ma na ge dr y s ki n i n areas s urr o u n di n g b ut n ot o n or o verla p pi n g t he 
treata ble A D /Ps O affecte d s ki n areas, n or mal s ki n or areas w hic h were ne ver 
treate d wit h st u dy i nter ve nti o n (ie pal ms, s oles or nails f or Ps O ). A n y 
n o n -me dicate d e m ollie nt use d b y  t he partici pa nt d uri n g t he st u d y s h o ul d be 
d oc u me nte d i n st u d y  rec or ds a n d t he C R F.

D ue t o t he p ote ntial t o affect A D a n d Ps O wit h ultra vi olet li g ht e x p os ure, partici pa nts 
m ust 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 a v oi d t he use of 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. Please see A p pe n di x 8 f or 
details o n pr o hi bite d li g ht t hera p y.

L o w or least p ote nt ( Class 6 or 7) t o pical c ortic o ster oi ds ( H ydr oc ortis o ne ≤1 % a n d 
h y dr oc ortis o ne acetate ≤1 %) are t he o nl y t o pical c ortic oster oi ds per mitte d f or t he 
treat me nt of areas ne ver treate d wit h I P (e g, pal ms, s oles, a n d fi n ger a n d t oe nails 
[ Ps O o nl y ]). Scal p tar pre parati o ns, salic ylic aci d pre parati o ns a n d s ha m p o os free of 
c ortic oster oi ds are per mitte d f or t he treat me nt of scal p.
0 9 0 1 7 7 e 1 9 b b 9 c 5f d\ A p pr o v e d\ A p pr o v e d O n: 0 3- N o v- 2 0 2 2 1 1: 4 8 ( G M T)

P F -0 7 0 3 8 1 2 4
Pr ot oc ol C 3 9 4 1 0 0 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 2 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 Marc h 2 0 2 1)
Pa ge 4 9
5. 3. 4. Ot her Lifest yle Re q uire me nts

Partici pa nts s h o ul d n ot a p pl y  occl usi ve dressi n g(s) t o t he areas treate d wit h st u d y 
i nter ve nti o n.

Partici pa nts s h o ul d n ot s wi m, bat he, be bat he d or ha ve treat me nt areas was he d f or at 
least 4 h o urs after a p plicati o n of t he st u d y i nter ve nti o n.

T he partici pa nt s h o ul d a v oi d wi pi n g t he st u d y i nter ve nti o n off t he s ki n a n d t he st u d y 
i nter ve nti o n s h o ul d n ot be re-a p plie d t o areas t hat were i na d verte ntl y wi pe d u ntil t he 
ne xt sc he d ule d d ose.

Partici pa nts will a gree t o a v oi d stre n u o us e xercise d uri n g t he st u d y , es peciall y wit hi n 
4 8 h o urs pri or t o t he sc he d ule d st u d y  visits a n d mai ntai n a de q uate h ydrati o n, if 
p ossi ble.

O n st u d y  visit da ys, t he partici pa nts will n ot s m o ke or use nic oti ne -c o ntai ni n g 
pr o d ucts, or i n gest caffei ne (e g, tea, c offee, s o me s oft dri n ks/c olas/e ner g y  dri n ks a n d 
p o wer bars) d uri n g t he 2 h o urs pri or t o bl o o d press ure a n d p ulse ( heart) rate 
meas ure me nts.

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 m oist urizi n g will n ot be d o ne.

O n st u d y  visit da ys, prescri be d per mitte d c o nc o mita nt me dicati o n will be ta ke n, as 
nee de d.

T he partici pa nts will c o ntact t he st u d y  site i n vesti gat or if t here are a ny c ha n ges or 
a d diti o ns t o c o nc o mita nt me dicati o ns.

T he partici pa nts will a v oi d ha vi n g maj or electi ve s ur ger y  u ntil after t he fi nal st u d y 
assess me nts.

T he partici pa nts s h o ul d c o nti n ue all n o n- p har mac ol o gical t hera pies, s uc h as p h y sical 
t hera py, as i n dicate d. H o we ver, t he partici pa nts s h o ul d a v oi d c ha n gi n g t he t y pe or 
i nte nsit y of t hera p y or i nitiati n g ne w t hera p y u ntil after Wee k 1 2 visit.

W he n a p pl y i n g t he st u d y i nter ve nti o n, t he partici pa nt will n ot be re q uire d t o wear 
gl o ves. H o we ver, partici pa nts s h o ul d be i nstr ucte d t o was h t heir ha n ds wit h mil d s oa p 
a n d water bef ore a n d after eac h a p plicati o n.

If st u d y partici pa nts nee d s o me o ne else t o assist wit h a p pl yi n g st u d y i nter ve nti o n o n 
har d -t o-reac h areas (e g, bac k), t his pers o n m ust wear gl o ves t o a v oi d acci de ntal 
e x p os ure t o t he st u d y i nter ve nti o n.
0 9 0 1 7 7 e 1 9 b b 9 c 5f d\ A p pr o v e d\ A p pr o v e d O n: 0 3- N o v- 2 0 2 2 1 1: 4 8 ( G M T)

P F -0 7 0 3 8 1 2 4
Pr ot oc ol C 3 9 4 1 0 0 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 2 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 Marc h 2 0 2 1)
Pa ge 5 0
5. 4. Scree n F ail ures
Scree n fail ures are defi ne d as partici pa nts w h o c o nse nt t o partici pate i n t he cli nical st u d y  b ut 
are n ot s u bse q ue ntl y ra n d o ml y assi g ne d t o st u d y i nter ve nti o n. A mi ni mal set of scree n fail ure 
i nf or mati o n is re q uire d t o e ns ure tra ns pare nt re p orti n g of scree n fail ure partici pa nts t o meet 
t he C O N S O R T p u blis hi n g re q uire me nts a n d t o res p o n d t o q ueries fr o m re g ulat or y 
a ut h orities. Mi ni mal i nf or mati o n i ncl u des de m o gra p h y , scree n fail ure details, eli gi bilit y 
criteria, a n d a n y S A E.
I n di vi d uals w h o d o n ot meet t he criteria f or partici pati o n i n t his st u d y (scree n fail ure) 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, u nless t he reas o n f or t he scree n fail ure is t he disease se verity i ncl usi o n 
criteria. Partici pa nts ma y n ot be rescree ne d u nless a p pr o ve d b y t he s p o ns or. As a n e xce pti o n, 
a partici pa nt w h o ot her wise q ualifie d f or t his st u d y  b ut di d n ot e nr oll d ue t o p ositi ve 
C O VI D -1 9 test, d ue t o rece nt vacci nati o n, or d ue t o e x hi biti n g C O VI D- 1 9-relate d s y m pt o ms 
or p ote ntial e x p os ure, ma y be rescree ne d after a n a p pr o priate i nter val, if j u d ge d a p pr o priate 
b y  t he i n vesti gat or. I n s uc h cases, all scree ni n g pr oce d ures m ust be re peate d. Rescree ne d 
partici pa nts s h o ul d be assi g ne d a ne w partici pa nt n u m ber.
6. S T U D Y I N T E R V E N TI O N( S ) A N D C O N C O MI T A N T T HE R A P Y
St u d y  i nter ve nti o n is defi ne d as a n y i n vesti gati o nal i nter ve nti o n(s), mar kete d pr o d uct(s), 
place b o, me dical de vice(s) , or st u d y pr oce d ure(s) i nte n de d t o be a d mi nistere d t o a st u d y 
partici pa nt acc or di n g t o t he st u d y  pr ot oc ol.
F or t he p ur p oses of t his pr ot oc ol, st u d y  i nter ve nti o n refers t o:

P F - 0 7 0 3 8 1 2 4 0. 0 1 % oi nt me nt;

P F - 0 7 0 3 8 1 2 4 0. 0 3 % oi nt me nt;

P F - 0 7 0 3 8 1 2 4 0. 0 6 % oi nt me nt ;

Ve hicle oi nt me nt ( place b o). 
6. 1. St u d y I nter ve nti o n(s) A d mi nistere d
St u d y I nter ve nti o ns(s)
I nter ve nti o n 
N a m e
P F -0 7 0 3 8 1 2 4 
0. 0 1 % oi nt me nt
P F -0 7 0 3 8 1 2 4 
0. 0 3 % oi nt me nt
P F -0 7 0 3 8 1 2 4 
0. 0 6 % oi nt me nt
P F -0 7 0 3 8 1 2 4 
ve hicle oi nt me nt
A R M N a m e
( gr o u p of p atie nts 
recei vi n g a 
s pecific tre at me nt 
( or n o tre at me nt)
Partici pa nts wit h 
mil d or m o derate 
A D, a n d mil d , 
m o derate , or se vere 
Ps O
Partici pa nts wit h 
mil d or m o derate 
A D, a n d mil d , 
m o derate , or se vere 
Ps O
Partici pa nts wit h 
mil d , m o derate , or 
se vere Ps O
Partici pa nts wit h 
mil d or m o derate 
A D, a n d mil d , 
m o derate , or se vere
Ps O
T y pe
Dr u g
Dr u g
Dr u g
Dr u g
0 9 0 1 7 7 e 1 9 b b 9 c 5f d\ A p pr o v e d\ A p pr o v e d O n: 0 3- N o v- 2 0 2 2 1 1: 4 8 ( G M T)

P F -0 7 0 3 8 1 2 4
Pr ot oc ol C 3 9 4 1 0 0 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 2 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 Marc h 2 0 2 1)
Pa ge 5 1
St u d y I nter ve nti o ns(s)
D ose F or m ul ati o n
Oi nt me nt
Oi nt me nt
Oi nt me nt
Oi nt me nt
U nit D ose 
Stre n gt h(s)
0. 1 m g/ g o i nt me nt 
i n 6 0-gra m t u be
0. 3 m g/ g o i nt me nt 
i n 6 0-gra m t u be
0. 6 m g/ g o i nt me nt 
i n 6 0-gra m t u be
0 m g/ g o i nt me nt i n 
6 0 -gra m t u be
D os a ge Le vel(s)
0. 0 1 % ( w t/ wt), Q D
0. 0 3 % ( w t/ wt), Q D
0. 0 6 % ( w t/ wt), Q D
0 % ( w t/ wt), Q D
R o ute of 
A d mi nistr ati o n
T o pical
T o pical
T o pical
T o pical
Use
E x peri me ntal 
E x peri me ntal 
E x peri me ntal
Place b o
I M P or NI M P
I M P
I M P
I M P
I M P
S o urci n g
Pr o vi de d ce ntrall y 
b y t he s p o ns or.
Pr o vi de d ce ntrall y 
b y t he s p o ns or.
Pr o vi de d ce ntrall y 
b y t he s p o ns or.
Pr o vi de d ce ntrall y 
b y t he s p o ns or.
P ac k a gi n g a n d 
L a beli n g
St u d y i nter ve nti o n 
will be pr o vi de d i n 
cart o ns. Eac h 
cart o n will c o ntai n 
o ne t u be. B ot h t he 
cart o n a n d t u be
will be la bele d i n a 
bli n de d f or mat as 
re q uire d per 
c o u ntr y 
re q uire me nt.
St u d y inter ve nti o n 
will be pr o vi de d i n 
cart o ns. Eac h 
cart o n will c o ntai n 
o ne t u be. B ot h t he 
cart o n a n d t u be
will be la bele d i n a 
bli n de d f or mat as 
re q uire d per 
c o u ntr y 
re q uire me nt.
St u d y inter ve nti o n 
will be pr o vi de d i n 
cart o ns. Eac h 
cart o n will c o ntai n 
o ne t u be. B ot h t he 
cart o n a n d t u be
will be la bele d i n a 
bli n de d f or mat as 
re q uire d per 
c o u ntr y 
re q uire me nt.
St u d y inter ve nti o n 
will be pr o vi de d i n 
cart o ns. Eac h 
cart o n will c o ntai n 
o ne t u be. B ot h t he 
cart o n a n d t u be
will be la bele d i n a 
bli n de d f or mat as 
re q uire d per 
c o u ntr y 
re q uire me nt.
P F - 0 7 0 3 8 1 2 4 o i nt me nt, 0. 1 m g/ g, 0. 3 m g/ g a n d 0. 6 m g/ g will be pr o vi de d as t he acti ve 
i n gre die nt wit h
 
Ve hicle ( place b o, n o acti ve dr u g i n t he f or m ulati o n) oi nt me nt will be pr o vi de d as t he 
 
6. 1. 1. A d mi nistr ati o n
A D treata ble areas will be all areas affecte d b y  A D, e xce pt hair -beari n g scal p.
P s O treata ble areas will be all areas affecte d b y Ps O , e xce pt hair -beari n g scal p, pal ms, s oles, 
fi n ger nails, a n d t oe nails.
A la y er of st u d y i nter ve nti o n oi nt me nt will be a p plie d at a tar get a p plicati o n rate of 
a p pr o xi matel y 3 m g/c m 2 b y  usi n g a fi n gerti p u nit met h o d.
0 9 0 1 7 7 e 1 9 b b 9 c 5f d\ A p pr o v e d\ A p pr o v e d O n: 0 3- N o v- 2 0 2 2 1 1: 4 8 ( G M T)
C CI
C CI

P F -0 7 0 3 8 1 2 4
Pr ot oc ol C 3 9 4 1 0 0 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 2 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 Marc h 2 0 2 1)
Pa ge 5 2
D a y  1 Visit
At t he Da y  1 v isit, bef ore t he Da y 1 i nitial st u d y i nter venti o n a p plicati o n is perf or me d, t he 
desi g nate d areas f or treat me nt will be i de ntifie d a n d d oc u me nte d i n t he partici pa nt’s s o urce 
d oc u me nt st u d y  rec or ds ( b o d y ma p). T he partici pa nt a n d/ or care gi ver will be pr o vi de d wit h a 
pa per versi o n of t he b o d y ma p. 
Partici pa nts a n d/ or care gi vers will be e nc o ura ge d t o o bser ve a n d partici pate i n t he i nitial 
st u d y i nter ve nti o n a p plicati o n o n Da y 1. 
P ost Da y  1
F oll o wi n g D a y 1 v isit t hr o u g h t he fi nal d ose at Wee k 1 2 visit, t he st u d y i nter ve nti o n s h o ul d 
be a p plie d o nce d ail y (ar o u n d sa me ti me of t he da y), t o all treata ble A D or Ps O i n v ol ve d 
areas i de ntifie d at t he Da y 1 visit as well as t o ne w areas i de ntifie d as “treata ble” d uri n g t he 
c o urse of 1 2 wee ks . All partici pa nts will be s u p plie d wit h i nstr ucti o ns o n a p plicati o n. 

N ote: A n y  ne w A D or Ps O areas i de ntifie d b y t he partici pa nt or care gi ver(s) s h o ul d 
als o be treate d wit h t he st u d y i nter ve nti o n after assess me nt by t he investi g at or or 
his/ her desi g nee . A n u nsc he d ule d visit f or assess me nt of t he ne w lesi o n ma y be 
re q uire d at t he discreti o n of t he In vesti gat or. If t he ne w lesi o n is i de ntifie d as 
treata ble, t he n bo d y  ma p will be u p date d, a n d st u d y i nter ve nti o n nee d will be 
re-assesse d .
T he st u d y i nter ve nti o n will be a p plie d at h o me/resi de nce e xce pt o n t he da ys of i n -cli nic 
vi sits. O n t he d a ys of sc he d ule d i n -cli nic visit, p artici p a nts will be i nstr ucte d t o refr ai n 
fr o m a p pl yi n g t he st u d y i nter ve nti o n at h o me /resi de nce. T he last d ose of st u d y 
i nter ve nti o n will be a p plie d d uri n g t he Wee k 1 2 i n-cli nic visit ( E O T visit) as s pecifie d i n t he
S o A .

N ote: If d ue t o p u blic e mer ge nc y , l ocal re g ulati o ns d o n’t all o w partici pa nt t o visit t he 
cli nic o n sc he d u le d visit da ys, t he partici pa nt will refrai n fr o m a p pl yi n g t he st u d y 
i nter ve nti o n u ntil selecte d assess me nts ca n be c o m plete d usi n g tele visit or h o me
healt h visit. 
T he partici pa nt a n d/ or care gi ver will be i nstr ucte d t o c o m plete t he d osi n g diar y  secti o n of t he 
e-diar y , starti n g wit h t he first d ose a p plie d i n t he cli nic o n Da y 1 t hr o u g h Wee k 1 2 (eac h ti me 
st u d y i nter ve nti o n is a p plie d). If a partici pa nt misses a p pl yi n g a d ose, t he partici pa nt s h o ul d 
a p pl y t his d ose pr o vi de d t his d ose s h o ul d ha ve bee n a p plie d wit hi n t he last 6 h o urs. F or 
l o n ger i nter vals, t he d ose s h o ul d be s ki p pe d. T he misse d d ose s h o ul d be rec or de d i n t he 
d osi n g diar y . T he ne xt d ose s h o ul d be a p plie d acc or di n g t o t he re g ular d osi n g re gi me n. 
Tre ate d are a i de ntifie d o n D a y 1 s h o ul d c o nti n ue t o be tre ate d e ve n if s u bst a nti al 
i m pr o ve me nt or cle arin g of A D or Ps O occ urs .
0 9 0 1 7 7 e 1 9 b b 9 c 5f d\ A p pr o v e d\ A p pr o v e d O n: 0 3- N o v- 2 0 2 2 1 1: 4 8 ( G M T)

P F -0 7 0 3 8 1 2 4
Pr ot oc ol C 3 9 4 1 0 0 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 2 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 Marc h 2 0 2 1)
Pa ge 5 3
T he reas o n f or mai ntai ni n g st u d y i nter ve nti o n treat me nt areas t he sa me as i de ntifie d at Da y 1 
is t o u n dersta n d t he efficac y, sys te mic safety, a n d l ocal t olera bilit y of P F -0 7 0 3 8 1 2 4 oi nt me nt 
w he n a p plie d t o f or 1 2 wee ks i n partici pa nts wit h A D or Ps O .
U n der n o circ u msta nces will t he st u d y i nter ve nti o n a p plicati o n re gi me n be m o difie d 
(e g, fre q ue nc y of a p plicati o n i ncrease d or re d uce d, n ot st o p pe d, or t he a p plicati o n rate [tar get 
3 m g/c m 2] i ncrease d or re d uce d) d uri ng t he st u d y . Te m p orar y disc o nti n uati o n of st u d y 
i nter ve nti o n ma y  be a p pr o priate u n der s o me circ u msta nces (e g, s ur ger y, n o n-seri o us 
i nfecti o ns) a n d s h o ul d be disc usse d wit h t he me dical m o nit or ( or desi g nee) prefera bly pri or 
t o te m p orar y disc o nti n uati o n of the st u d y  i nter ve nti o n.
St u d y  i nter ve nti o n a d mi nistrati o n details will be rec or de d o n t he C R F.
6. 2. Pre p ar ati o n , H a n dli n g , St or a ge , a n d Acc o u nt a bilit y
1.
T he i n vesti gat or or desi g nee m ust c o nfir m a p pr o priate te m perat ure c o n diti o ns ha ve 
bee n mai ntai ne d d uri n g tra nsi t f or all st u d y i nter ve nti o ns recei ve d a n d a ny 
discre pa ncies are re p orte d a n d res ol ve d bef ore use of t he st u d y  i nter ve nti o n. 
2.
O nl y  partici pa nts e nr olle d i n t he st u d y ma y recei ve st u d y i nter ve nti o n a n d o nl y 
a ut h orize d site staff ma y  s u p pl y or a d mi nister st ud y  i nter ve nti o n. All st u d y 
i nter ve nti o ns m ust be st ore d i n a sec ure, e n vir o n me ntall y c o ntr olle d, a n d m o nit ore d 
( ma n ual or a ut o mate d rec or di n g) area i n acc or da nce wit h t he la bele d st ora ge 
c o n diti o ns wit h access li mite d t o t he i n vesti gat or a n d a ut h orize d sit e staff. 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 
m ust be d oc u me nte d a n d a vaila ble u p o n re q uest. Data f or n o n w or ki n g da y s m ust 
i n dicate t he mi ni m u m a n d ma xi m u m te m perat ures si nce pre vi o usl y d oc u me nte d f or 
all site st ora ge l ocati o ns u p o n ret ur n t o b usi ness.
3.
A n y  e xc ursi o ns fr o m t he st u d y i nter ve nti o n la bel st ora ge c o n diti o ns s h o ul d be 
re p orte d t o Pfizer u p o n disc o ver y al o n g wit h a ny acti o ns ta ke n. 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 st u d y i nter v e nti o n 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. O nce a n e xc ursi o n is i de ntifie d, t he 
st u d y i nter ve nti o n m ust be q uara nti ne d a n d n ot use d u ntil Pfizer pr o vi des per missi o n 
t o use t he st u d y i nter ve nti o n. S pecific details re gardi n g t he defi niti o n of a n e xc ursi o n 
a n d 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.
4.
A n y  st ora ge c o n diti o ns state d i n t he 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 la bel.
5.
St u d y  i nter ve nti o ns s h o ul d be st ore d i n t heir ori gi nal c o ntai ners.
6.
Site staff will i nstr uct partici pa nts o n t he pr o per st ora ge re q uire me nts f or ta ke -h o me 
st u d y i nter ve nti o n.
0 9 0 1 7 7 e 1 9 b b 9 c 5f d\ A p pr o v e d\ A p pr o v e d O n: 0 3- N o v- 2 0 2 2 1 1: 4 8 ( G M T)

P F -0 7 0 3 8 1 2 4
Pr ot oc ol C 3 9 4 1 0 0 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 2 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 Marc h 2 0 2 1)
Pa ge 5 4
7.
T he i n vesti gat or, i nstit uti o n, or t he hea d of t he me dical i nstit uti o n ( w here a p plica ble)
is res p o nsi ble f or st u dy i nter ve nti o n acc o u nta bilit y, rec o nciliati o n, a n d rec or d 
mai nte na nce (ie, recei pt, rec o nciliati o n, a n d fi nal dis p ositi o n rec or ds) , s uc h as t he 
I P A L or s p o ns or-a p pr o ve d e q ui vale nt . All st u d y i nter ve nti o ns will be acc o u nte d f or 
usi n g a st u d y i nter ve nti o n acc o u nta bilit y f or m/rec or d. All st u d y i nter ve nti o n t hat is 
ta ke n h o me by t he partici pa nt, b ot h use d a n d u n use d, m ust be ret ur ne d t o t he 
i n vesti gat or by t he partici pa nt. Ret ur ne d st u d y i nter ve nti o n m ust n ot be re dis pe nse d 
t o t he partici pa nts.
8.
F urt her g ui da nce a n d i nf or mati o n f or t he fi nal dis p ositi o n of u n use d st u d y  
i nter ve nti o ns are pr o vi de d i n t he IP m a n ual. All destr ucti o n m ust be a de q uatel y  
d oc u me nte d. If destr ucti o n is a ut h orize d t o ta ke place at t he i n vesti gat or site, t he 
i n vesti gat or m ust e ns ure t hat t he materials are destr o ye 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 o ns 
pr o vi de d b y Pfizer.
U p o n i de ntificati o n of a pr o d uct c o m plai nt, n otif y t he s p o ns or w it hi n 1 b usi ne ss da y of 
disc o ver y  IP ma n ual.
6. 2. 1. Pre p ar ati o n a n d Dis pe nsi n g
Wit hi n t his pr ot oc ol, pre parati o n refers t o t he i n vesti gat or site acti vities perf or me d t o ma ke 
t he st u d y i nter ve nti o n rea d y f or a p plicati o n or dis pe nsi n g t o t he partici pa nt/care gi ver by 
q ualifie d st aff.
Dis pe nsi n g is defi ne d as t he pr o visi o n of st u d y i nter ve nti o n, c o nc o mita nt treat me nts, a n d 
acc o m pa n yi n g i nf or mati o n b y  q ualifie d staff me m ber(s) t o a healt hcare pr o vi der, partici pa nt, 
or care gi ver i n acc or da nce wit h t his pr ot oc ol. L ocal healt h a ut h orit y re g ulati o ns or 
i n vesti gat or site g ui deli nes ma y use alter nati ve ter ms f or t hese acti vities.
T he st u d y i nter ve nti o n will be dis pe nse d i n a bli n de d fas hi o n usi n g a n I R T s y ste m at 
D a y 1/ Baseli ne, Wee k 1, Wee k 2, Wee k 4, Wee k 6, Wee k 8 a n d Wee k 1 0 visits. A q ualifie d 
staff me m ber will dis pe nse t he st u d y i nter ve nti o n via u ni q ue c o ntai ner n u m bers o n t he 
cart o ns pr o vi de d, i n q ua ntities a p pr o priate f or t he st u d y  visit sc he d ule a n d t he treata ble 
% B S A.
F or d oses t o be a p plie d at h o me, t he partici pa nt or care 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 its ori gi nal pac ka ge 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 
pr o d uct a n d its ori gi nal pac ka ge (i ncl u di n g e m pt y,  partial use d a n d u n use d t u bes) t o t he site 
at t he ne xt st u d y visit. 
St u d y  i nterve nti o n will be assi g ne d t o partici pa nts at t he Da y  1 visit o nce t he partici pa nt is 
s uccessf ully ra n d o mize d t hr o u g h t he I RT s ys te m. T he i n vesti gat or, a p pr o priate dele gate or 
site pers o n nel will access t he IR T s ys te m at Scree ni n g a n d all s u bse q ue nt st u d y i nter ve nti o n
dis pe nsi n g visits t o e nter i nf or mati o n i ncl u di n g, b ut n ot li mite d t o , % affecte d B S A , hei g ht , 
a n d wei g ht t o recei ve c orrect t u be n u m bers t o be dis pe nse d t o t he partici pa nt. Alter nati vel y, 
0 9 0 1 7 7 e 1 9 b b 9 c 5f d\ A p pr o v e d\ A p pr o v e d O n: 0 3- N o v- 2 0 2 2 1 1: 4 8 ( G M T)

P F -0 7 0 3 8 1 2 4
Pr ot oc ol C 3 9 4 1 0 0 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 2 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 Marc h 2 0 2 1)
Pa ge 5 5
t he t o ol t o sta n dar dize t he st u d y i nter ve nti o n n ee d calc ulati o n acr oss partici pa nts a n d st u d y  
sites ma y be pr o vi de d b y t he s p o ns or.
T he calc ulati o n of treata ble % B S A is descri be d i n Secti o n 1 0. 1 2. 1. 3 a n d Secti o n 1 0. 1 2. 2. 3
f or A D a n d Ps O, res pecti vel y.
Al l t u bes of i n vesti gati o nal pr o d uct dis pe nse d or ret ur ne d will be rec or de d a n d d oc u me nte d.
6. 2. 2. St u d y I nter ve nti o n 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 her dis p ositi o n of t he st u d y i nter ve nti o n s u p plies. All st u d y i nter ve nti o n 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. All t u bes of t he st u d y i nter ve nti o n m ust be 
ret ur ne d t o t he i n vesti gat or b y t he partici pa nt at e ver y visit a n d at t he e n d of t he trial.
T he partici pa nt wil l be as ke d t o bri n g all dis pe nse d st u d y i nter ve nti o n (i ncl u di n g e m pty, 
partiall y  use d a n d u n use d t u bes) at e ver y visit; partici pa nts will be as ke d t o bri n g e-diar y  t o 
t he cli nic at e ver y cli nic visit. All pre vi o usl y dis pe nse d st u d y i nter ve nti o n t u bes will be 
retai ne d by t he site. F or eac h partici pa nt, st u d y i nter ve nti o n t u bes wit h ca ps will be wei g he d 
i n di vi d uall y b y t he st u d y site bef ore dis pe nsi n g a n d after ret ur n a n d t he wei g hts will be 
rec or de d. T he s p o ns or will use t he rec or de d wei g hts t o esti mate usa ge 
(e g, m g/c m 2/a p plicati o n) f or eac h partici pa nt. N ote t hat t he wei g ht rec or de d o n t he st u d y 
i nter ve nti o n la bel is a n o mi nal wei g ht a n d n ot a n e xact wei g ht of t he st u d y i nter ve nti o n a n d 
t u be. Detaile d dr u g acc o u nta bilit y rec or ds, i ncl u di n g t u be wei g hts measure d i n t he cli nic, 
will be mai ntai ne d b y  st u d y staff f or eac h partici pa nt.
T he ori gi nal st u d y i nter ve nti o n acc o u nta bilit y l o g, or e q ui vale nt d oc u me nt, m ust be 
acc uratel y c o m plete d, si g ne d b y t he in vesti gat or, a n d retai ne d at t he st u d y s ite ( wit h a c o py 
s u p plie d t o t he sp o ns or) w he n t he st u d y is c o m plete.
6. 2. 3. Destr u cti o n of St u d y I nter ve nti o n S u p plies 
F or all st u d y i nter ve nti o n ret ur ne d t o t he i n vesti gat or b y t he partici pa nt, t he i n vesti gat or will 
mai n tai n t he ret ur ne d s u p pl y u ntil destr ucti o n is a ut h orize d.
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 st u d y 
i nter ve nti o n (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 gat or site, 
t he i n vesti gat or m ust e ns ure t hat t he materials are destr o ye 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 o ns pr o vi de d b y 
Pfizer, a n d all destr ucti o n m ust be a de q uatel y d oc u me nte d.
F urt her g ui da nce a n d i nf or mati o n f or t he fi nal dis p ositi o n of u n use d st u d y  i nter ve nti o ns are 
pr o vi de d i n t he I P ma n ual.
0 9 0 1 7 7 e 1 9 b b 9 c 5f d\ A p pr o v e d\ A p pr o v e d O n: 0 3- N o v- 2 0 2 2 1 1: 4 8 ( G M T)

P F -0 7 0 3 8 1 2 4
Pr ot oc ol C 3 9 4 1 0 0 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 2 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 Marc h 2 0 2 1)
Pa ge 5 6
6. 3. Me as ures t o Mi ni mize Bi as: R a n d o miz ati o n a n d Bli n di n g
6. 3. 1. All oc ati o n t o St u d y I nter ve nti o n
All ocati o n of partici pa nts t o treat me nt gr o u ps will pr ocee d t hr o u g h t he use of a n I R T s ys te m 
(IW R). 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 mite d t o t he user’s I D a n d pass w or d, t he pr ot oc ol 
n u m ber, a n d t he partici pa nt n u m ber. 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, ra n d o mizati o n n u m ber, a n d D U or c o ntai ner n u m ber w he n st u d y 
i nter ve nti o n is bei n g s u p plie d via t he IR T s ys te m. T he IR T s y ste m will pr o vi de a 
c o nfir mati o n re p ort c o ntai ni n g t he partici pa nt n u m ber, ra n d o mizati o n 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. 
St u d y  i nter ve nti o n will be dis pe nse d at t he st u d y visits s u m marize d i n t he S o A . 
Ret ur ne d st u d y i nter ve nti o n m ust n ot be re- dis pe nse d t o t he partici pa nts.
T he st u d y -s pecific IR T refere nce ma n ual a n d I P 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 s ys te m.
6. 3. 2. Bre a ki n g t he Bli n d 
T he I R T will be pr o gra m me d wit h bli n d -brea ki n g i nstr ucti o ns. I n case of a n e mer ge nc y , t he 
i n vesti gat or has t he s ole res p o nsi bilit y f or deter mi ni n g if u n bli n di n g of a partici pa nt’s 
treat me nt assi g n me nt is warra nte d. Partici pa nt safet y m ust al wa ys be t he first c o nsi derati o n 
i n ma ki n g s uc h a deter mi nati o n. If t he i n vesti gat or deci des t hat u n bli n di n g is warra nte d, t he 
i n vesti gat or s h o ul d ma ke e ver y eff ort t o c o ntact t he s p o ns or pri or t o u n bli n di n g a 
partici pa nt’s treat me nt assi g n me nt u nless t hi s c o ul d dela y f urt her ma na ge me nt of t he 
partici pa nt. If a partici pa nt’s treat me nt assi g n me nt is u n bli n de d, t he s p o ns or m ust be n otifie d 
wit hi n 2 4 h o urs after brea ki n g t he bli n d. T he date a n d reas o n t hat t he bli n d was br o ke n m ust 
be rec or de d i n t he s o urce d oc u me ntati o n a n d C R F .
T he st u d y -s pecific IR T refere nce ma n ual a n d I P 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 s ys te m.
6. 4. St u d y I nter ve nti o n C o m pli a nce
Partici pa nts will be i nstr ucte d t o bri n g t o t he cli nic all use d , partially use d a n d e m pt y st u d y 
i nter ve nti o n t u bes i n t heir ori gi nal c o ntai ners f or wei g hi n g, at eac h visit . 
Partici pa nt c o m plia nce wit h st u d y i nter ve nti o n will be assesse d o n visits i de ntifie d i n t he 
S o A . C o m plia nce will be assesse d b y re vie w of t he partici pa nt/care gi ver c o m plete d d osi n g 
diar y  secti o n of t he e-diar y  a n d t ho r o u g h re vie w of d osi n g i nstr ucti o ns at e ver y visit. T he 
differe nce i n wei g ht(s) of t he ret ur ne d st u d y i nter ve nti o n t u bes will be use d t o esti mate t he 
d oses a p pli e d at t he e n d of t he st u d y. S o urce d oc u me nts will be place d i n t he partici pa nt’s 
st u d y file. De viati o n(s) fr o m t he prescri be d d osa ge re gi me n s h o ul d be rec or de d i n t he C R F.
0 9 0 1 7 7 e 1 9 b b 9 c 5f d\ A p pr o v e d\ A p pr o v e d O n: 0 3- N o v- 2 0 2 2 1 1: 4 8 ( G M T)

P F -0 7 0 3 8 1 2 4
Pr ot oc ol C 3 9 4 1 0 0 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 2 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 Marc h 2 0 2 1)
Pa ge 5 7
Fr o m Da y  1 t hr o u g h Wee k 1 2 visit, n o n -c o m plia nce is defi ne d as a p plicati o n of st u d y 
i nter ve nti o n less t ha n 8 0 % i n a wee k or m ore t ha n 1 2 0 % of st u d y i nter ve nti o n a p plicati o ns. If 
n o n-c o m plia nce is i de ntifie d, or e ve n if a fe w d ose a p plicati o ns are misse d or o ver- a p plie d
(as i nf or me d by t he partici pa nt t o t he site staff) , t he n, partici pa nts will be re -trai ne d o n t he 
i m p orta nce a n d t he pr ocess of pr o per st u d y i nter ve nti o n a p plicati o n. If n o n -c o m plia nce 
persists, t he i n vesti gat or, i n c o ns ultati o n wit h t he s p o ns or, ma y wit h dra w a n y partici pa nt 
fr o m t he st u d y f or reas o ns of n o n-c o m plia nce wit h t he d osi n g re gi me n. I n vesti gat ors s h o ul d 
i n dicate o n t he a p pr o priate C R F pa ge n o nc o m plia nce wit h st u d y i nter ve nti o n a n d pr o vi de a n 
e x pla nati o n. 
I n ve nt or y c o ntr ol of all st u d y i nter ve nti o n m ust be ri g or o usl y mai ntai ne d t hr o u g h o ut t he 
d urati o n of t he st u d y  until all me dicati o n has bee n acc o u nte d f or a n d/ or ret ur ne d t o t he 
s p o ns or. A n y discre pa ncies n ote d bet wee n dr u g dis pe nsi n g rec or ds a n d t he dr u g i n ve nt or y 
m ust be re p orte d t o Pfizer.
6. 5. D ose M o dific ati o n
N ot a p plica ble.
6. 6. C o nti n ue d Access t o St u d y I nter ve nti o n A fter t he E n d of t he St u d y
N o i nter ve nti o n will be pr o vi de d t o st u d y  partici pa nts at t he e n d of t heir st u d y partici pati o n .
6. 7. Tre at me nt of O ver d ose
F or t his st u d y , a n y d ose of st u d y i nter ve nti o n greater t ha n 1 d ose wit hi n a 1 2 - h o ur ti me 
peri o d will be c o nsi de re d a n o ver d ose.  
I n vesti gat ors s h o ul d be a ware t hat a d mi nistrati o n t o si g nifica ntly greater area ma y  als o be 
treate d as a n o ver d ose at in vesti gat or discreti o n.
T he s p o ns or d oes n ot rec o m me n d s pecific treat me nt f or a n o ver d ose.
I n t he e ve nt of a n o ver d ose, t he i n vesti gat or s h o ul d:
1.
C o ntact t he me dical m o nit or wit hi n 2 4 h o urs.
2.
Cl osel y  m o nit or t he partici pa nt f or a ny A Es/ S A Es a n d la b orat or y  a b n or malities f or at 
least 2 8 cale n dar da ys after t he o ver d ose of st u d y i nter ve nti o n.
3.
D oc u me nt t he q ua ntit y of t he e xces s d ose as well as t he d urati o n of t he o ver d ose i n 
t he C R F.
4.
O ver d ose is re p orta ble t o Pfizer Safet y  o nly w he n ass ociate d wit h a n S A E.
 
 
0 9 0 1 7 7 e 1 9 b b 9 c 5f d\ A p pr o v e d\ A p pr o v e d O n: 0 3- N o v- 2 0 2 2 1 1: 4 8 ( G M T)
C CI

P F -0 7 0 3 8 1 2 4
Pr ot oc ol C 3 9 4 1 0 0 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 2 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 Marc h 2 0 2 1)
Pa ge 5 8
Decisi o ns re gar di n g d ose i nterr u pti o ns or m o dificati o ns will be ma de b y  t he i n vesti gat or i n 
c o ns ultati o n wit h t he me dical m o nit or base d o n t he cli nical e val uati o n of t he partici pa nt. 
6. 8. C o nc o mit a nt T her a p y
Me dicati o ns ta ke n after t he first d ose of st u d y i nter ve nti o n 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 o n, dail y  d ose, a n d start a n d st o p dates of 
a d mi nistrati o n. Partici pa nts 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 me dicati o ns a n d treat me nts, 
a n d vacci nati o ns) at eac h 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 mita 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 Es. 
Refer t o A p pe n di x 8 f or t he list of pr o hi bite d me dicati o ns a n d t he ti mefra me f or w hic h t he y 
m ust be st o p pe d.  
H or m o nal c o ntrace pti ves t hat meet t he re q uire me nts of t his st u d y  are all o we d t o be use d i n 
partici pa nts w h o are W O C B P (see A p pe n di x 4 ).
M e dicati o ns f or ot her sta ble c hr o nic me dical c o n diti o ns are per mitte d d uri n g t he st u d y u nless 
t he me dicati o n/t hera py is s pecificall y pr o hi bite d b y t he pr ot oc ol or is e x pecte d t o affect t he 
st u d y assess me nts. N o nster oi dal a nti-i nfla m mat or y dr u gs are all o we d t hr o u g h o ut t he st u d y. 
R o uti ne pre ve ntati ve i m m u niz ati o ns are per mitte d d uri n g t he st u d y;  h o we ver, it is preferre d 
t hat i m m u nizati o ns be a d mi nistere d at least 2 8 da ys bef ore t he start or f oll o wi n g t he 
c o m pleti o n of t he partici pati o n i n st u d y . Vacci nes use d i n t he e ve nt of a disease o ut brea k or 
pa n de mic are all o we d.
6. 8. 1. Resc ue Me dici ne
T here is n o resc ue t hera p y t o re verse t he A Es o bser ve d wit h P F - 0 7 0 3 8 1 2 4; sta n dar d me dical 
s u p p orti ve care m ust be pr o vi de d t o ma na ge t he A Es. 
7. DI S C O N TI N U A TI O N O F S T U D Y I N T E R V E N TI O N A N D P A R TI CI P A N T 
DI S C O N TI N U A TI O N/ WI T H D R A W A L
7. 1. Disc o n ti n u ati o n of St u d y I nter ve nti o n
It ma y be necessar y f or a partici pa nt t o per ma ne ntl y disc o nti n ue st u d y i nter ve nti o n. Reas o ns 
f or per ma ne nt disc o nti n uati o n of st u d y  i nter ve nti o n i ncl u de t he f oll o wi n g: Li ver i nj ur y , E C G 
c ha n ges, pre g na nc y, l ocal t olera bilit y, a n d A Es.
N ote t hat disc o nti n uati o n of st u d y i nter ve nti o n d oes n ot re prese nt wit h dra wal fr o m t he st u d y.
If st u d y i nter ve nti o n is per ma ne ntl y disc o nti n ue d, t he partici pa nt will re mai n i n t he st u d y  t o 
be e val uate d f or safety. See t he S o A f or data t o be c ollecte d at t he ti me of disc o nti n uati o n of 
st u d y i nter ve nti o n a n d f oll o w-u p f or a n y f urt her e val uati o ns t hat nee d t o be c o m plete d.
0 9 0 1 7 7 e 1 9 b b 9 c 5f d\ A p pr o v e d\ A p pr o v e d O n: 0 3- N o v- 2 0 2 2 1 1: 4 8 ( G M T)

P F -0 7 0 3 8 1 2 4
Pr ot oc ol C 3 9 4 1 0 0 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 2 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 Marc h 2 0 2 1)
Pa ge 5 9
I n t he e ve nt of disc o nti n uati o n of st u d y i nter ve nti o n, it m ust be d oc u me nte d o n t he 
a p pr o priate C R F/i n t he me dical rec or ds w het her t he partici pa nt is disc o nti n ui n g f urt her 
recei pt of st u dy i nter ve nti o n or als o fr o m st u d y  pr oce d ures, p osttreat me nt st u d y f oll o w- u p, 
a n d/ or f ut ure c ollecti o n of a d diti o nal i nf or mati o n.
7. 1. 1. Li ver I nj ur y
Please refer t o Secti o n 1 0. 6 f or P ote ntial Cases of Dr u g-I n d uce d Li ver I nj ur y ( DI LI; H y’s 
la w). 
7. 1. 2. E C G C h a n ges
A partici pa nt w h o meets eit her b ullete d c riteria base d o n t he a vera ge of tri plicate E C G 
rea di n gs will be wit h dra w n fr o m t he st u dy i nter ve nti o n. 

Q Tc F > 5 0 0 ms ec.

C ha n ge fr o m baseli ne: Q Tc F > 6 0 ms ec a n d Q Tc F > 4 5 0 msec .
If a cli nicall y si g nifica nt fi n di n g is i de ntifie d (i ncl u di n g, b ut n ot li mite d t o, c ha n ges fr o m 
baseli ne i n Q T c F after e nr oll me nt ), t he i n vesti gat or or q ualifie d desi g nee will deter mi ne if 
t he partici pa nt ca n c o nti n ue i n t he st u d y a n d if a n y c ha n ge i n partici pa nt ma na ge me nt is 
nee de d. T his re vie w of t he E C G pri nte d at t he ti me of c olle cti o n m ust be d oc u me nte d. A n y 
ne w cli nicall y rele va nt fi n di n g s h o ul d be re p orte d as a n A E.
7. 1. 3. Pre g n a nc y 
Pre g na nc y  c o nfir me d b y ser u m -h C G testi n g. sp o ns or cli nicia n or sp o ns or me dical m o nit or
s h o ul d be n otifie d i m me diatel y. 
T w o ne gati ve pre g na nc y  tests are re q uire d bef ore ra n d o mizati o n ( 1 ne gati ve ser u m 
pre g na nc y  test at S cree ni n g a n d 1 ne gati ve uri ne pre g na nc y  test at Da y 1 visit). I f uri ne 
pre g na nc y  test is p ositi ve after st u d y i nter ve nti o n a p plicati o n, ser u m pre g na nc y test will be 
c o n d ucte d, st u d y i nter v e nti o n a p plicati o n pa use d a n d s p o ns or cli nicia n or s p o ns or m e dical 
m o nit or n otifie d i m me diatel y.
7. 1. 4. L oc al T oler a bilit y
If a partici pa nt e x perie nces se verity Gra de 3 (se vere) or 4 ( ver y  se vere) o n t he l ocal 
t olera bilit y assess me nt (Secti o n 8. 2. 7 ), st u d y treat me nt will be disc o nti n ue d per ma ne ntly, a n d 
partici pa nt will pr ocee d t o E T visit a n d f oll o w- u p as descri be d i n S o A . 
If a partici pa nt e x perie nces a p plicati o n site reacti o n of Gra de 2 ( m o derate) o n t he l ocal 
t olera bilit y assess me nt, i n vesti gat or ma y te m p oraril y disc o nti n ue a p plicati o n of st u d y 
i nter ve nti o n f or u p t o 4 8 h o urs wit h o ut c o ns ulti n g t he s p o ns or. If i n t he cli nical j u d g me nt of 
t he i n vesti gat or st u d y i nter ve nti o n i nterr u pti o n be yo n d 4 8 h o urs is a d visa ble, t he i n vesti gat or 
m ust o btai n a gree me nt fr o m t he Pfizer me dical m o nit or t o c o nti n ue wit h h ol di n g st u d y 
i nter ve nti o n. If te m p orar y st ud y  i nter ve nti o n i nterr u pti o n f or m ore t ha n 5 c o nsec uti ve da ys is 
0 9 0 1 7 7 e 1 9 b b 9 c 5f d\ A p pr o v e d\ A p pr o v e d O n: 0 3- N o v- 2 0 2 2 1 1: 4 8 ( G M T)

P F -0 7 0 3 8 1 2 4
Pr ot oc ol C 3 9 4 1 0 0 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 2 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 Marc h 2 0 2 1)
Pa ge 6 0
nee de d, t he n t he partici pa nt s h o ul d be per ma ne ntl y wit h dra w n fr o m treat me nt a n d s h o ul d 
f oll o w u p wit h t he site u ntil c o m plete or near c o m plete res ol uti o n of t he A E. T his d osi n g ga p 
ma y  occ ur o nl y o nce f or t he sa me partici pa nt.
7. 1. 5. A Es
H y perse nsiti vit y  Reacti o ns: If si g ns a n d sy m pt o ms of h y perse nsiti vit y  are attri b uta ble t o t he 
i n vesti gati o nal pr o d uct, i ncl u di n g c o ntact urticaria, it m ust be disc o nti n ue d i m me diatel y, a n d 
a p pr o priate t hera p y i nitiat e d. 
7. 1. 6. Te m p or ar y Disc o nti n u ati o n
Te m p orar y  disc o nti n uati o ns of st u d y i nter ve nti o n:

Will occ ur i n cases of p ositi ve uri ne pre g na nc y  test w hic h if c o nfir me d by ser u m 
pre g na nc y  test will lea d t o per ma ne nt disc o nti n uati o n (Secti o n 7. 1 ). 

Ma y  a p ply i n s o me cases of a p plicati o n site reacti o n d uri n g l ocal t olera bilit y  
assess me nts (Secti o n 8. 2. 7 ). 

A d diti o nal i nsta nces of te m p orar y  disc o nti n uati o n ma y be a p pr o priate (e g, s ur ger y, 
i nfecti o n, etc). 
All te m p orar y  disc o nti n uati o ns s h o ul d be disc usse d wit h s p o ns or cli nicia n or s p o ns or
me dical m o nit or t o deter mi ne if partici pa nt ma y c o nti n ue i n t he st u d y. If p ossi ble, site will 
c o ns ult t he s p o ns or pri or t o te m p orar y disc o nti n uati o n.
7. 2. P artici p a nt Disc o nti n u ati o n/ Wit h dr a w al F r o m t he St u d y
A partici pa nt ma y  wit h dra w fr o m t he st u d y at a ny ti me at his/ her o w n re q uest. Reas o ns f or 
disc o nti n uati o n fr o m t he st u d y  m a y  i ncl u de t he f oll o wi n g:

Ref use d f urt her st u d y pr oce d ures;

L ost t o f oll o w - u p;

Deat h ;

St u d y  ter mi nate d b y s p o ns or.
At t he ti me of disc o nti n ui n g fr o m t he st u d y, if p ossi bl e, a n earl y disc o nti n uati o n visit s h o ul d 
be c o n d ucte d. See t he S o A f or assess me nts t o be c ollecte d at t he ti me of st u d y 
disc o nti n uati o n a n d f oll o w- u p a n d f or a n y f urt her e val uati o ns t hat nee d t o be c o m plete d.
T he earl y  disc o nti n uati o n visit a p plies o nl y  t o partici pa nts w h o are e nr olle d/ ra n d o mize d a n d 
t he n are pre mat urel y wit h dra w n fr o m t he st u d y . Partici pa nts s h o ul d be q uesti o ne d re gar di n g 
t heir reas o n f or wit h dra wal.
0 9 0 1 7 7 e 1 9 b b 9 c 5f d\ A p pr o v e d\ A p pr o v e d O n: 0 3- N o v- 2 0 2 2 1 1: 4 8 ( G M T)

P F -0 7 0 3 8 1 2 4
Pr ot oc ol C 3 9 4 1 0 0 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 2 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 Marc h 2 0 2 1)
Pa ge 6 1
If a partici pa nt wit h dra ws fr o m t he st u d y, he/s he ma y  re q uest destr ucti o n of a n y re mai ni n g 
sa m ples ta ke n a n d n ot teste d , a n d the i n vesti gat or m ust d oc u me nt a n y  s uc h re q uests i n t he 
site st u d y rec or ds a n d n otif y t he s p o ns or acc or di n gl y.
If t he partici pa nt 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 (see Secti o n 7. 2. 1 ) 
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 b e c ollecte d. T he s p o ns or ma y retai n a n d c o nti n ue t o use a n y data 
c ollecte d bef ore s uc h wit h dra wal of c o nse nt.
7. 2. 1. Wit h dr a w al of C o nse nt
Partici pa nt s w h o re q uest t o disc o nti n ue recei pt of st u d y i nter ve nti o n will re mai n i n t he st u d y  
a n d m ust c o nti n ue t o be f oll o we d f or pr ot oc ol-s pecifie d f oll o w- u p pr oce d ures. T he o nly 
e xce pti o n t o t his is w he n a partici pa nt s pecifically 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 partici pa nt t o pr o vi de t his 
i nf or mati o n. P artici pa nt s 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 wit h dra wal of c o nse nt s h o ul d be 
e x plai ne 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 dr a wal is 
o nl y  fr o m f urt her recei pt of st u d y i nter ve nti o n 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 ntere d o n t he a p pr o priate C R F pa ge. I n t he e ve nt t hat 
vital stat us ( w het her t he partici pa nt 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.
7. 3. L ost t o F ol l o w- Up 
A partici pa nt will be c o nsi dere d l ost t o f oll o w- u p if he or s he re peate dl y fails t o ret ur n f or 
sc he d ule d visits a n d is u na ble t o be c o ntacte d b y t he st u d y  site.
T he f oll o wi n g acti o ns m ust be ta ke n if a partici pa nt fails t o ret ur n t o t he cli nic f or a re q uire d 
st u d y visit:

T he site m ust atte m pt t o c o ntact t he partici pa nt a n d resc he d ule t he misse d visit as 
s oo n as p ossi ble . Co u nsel t he partici pa nt o n t he i m p orta nce of mai ntai ni n g t he 
assi g ne d visit sc he d ule, a n d ascertai n w het her t he partici pa nt wis hes t o a n d/ or s h o ul d 
c o nti n ue i n t he st u d y;

Bef ore a partici pa nt is dee me d l ost t o f oll o w- u p, t he i n vesti gat or or desi g nee m ust 
ma ke e ver y  eff ort t o re gai n c o ntact wit h t he partici pa nt ( w here p ossi ble, 3 tele p h o ne 
calls a n d, if necessar y, a certifie d letter t o t he partici pa nt’s last k n o w n maili n g 
a d dress or l ocal e q ui vale nt met h o ds). T hese c o ntact atte m pts s h o ul d be d oc u me nte d 
i n t he partici pa nt’s me dical rec or d;

S h o ul d t he partici pa nt c o nti n ue t o be u nreac ha ble, he/s he will be c o nsi dere d t o ha ve 
wit h dra w n fr o m t he st u d y. 
0 9 0 1 7 7 e 1 9 b b 9 c 5f d\ A p pr o v e d\ A p pr o v e d O n: 0 3- N o v- 2 0 2 2 1 1: 4 8 ( G M T)

P F -0 7 0 3 8 1 2 4
Pr ot oc ol C 3 9 4 1 0 0 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 2 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 Marc h 2 0 2 1)
Pa ge 6 2
8. S T U D Y A S S E S S M E N T S A N D P R O C E D U R E S
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) m ust o btai n a si g ne d a n d 
date d I C D/asse nt bef ore perf or mi n g a n y st u d y- s pecific pr oce d ures.  
St u d y  pr oce d ures a n d t heir ti mi n g are s u m marize d i n t he S o A . Pr ot oc ol wai vers or 
e xe mpti o ns are n ot all o we d.
S afet y iss ues s h o ul d be disc usse d wit h t he s p o ns or i m me diatel y  u p o n occ urre nce or 
a ware ness t o deter mi ne w het her t he partici pa nt s h o ul d c o nti n ue or disc o nti n ue st u d y 
i nter ve nti o n.
A d here nce t o t he st u d y desi g n re q uire me nts, i ncl u di ng t h ose s pecifie d i n t he S o A , is esse ntial 
a n d re q uire d f or st u d y c o n d uct.
All scree ni n g e val uati o ns m ust be c o m plete d a n d re vie we d t o c o nfir m t hat p ote ntial 
partici pa nts meet all eli gi bilit y  criteria. T he i n vesti gat or will mai ntai n a scree ni n g l o g t o 
rec or d details of all partici pa nts scree ne d a n d t o c o nfir m eli gi bilit y or rec or d reas o ns f or 
scree ni n g fail ure, as a p plica ble.
E ver y  eff ort s h o ul d be ma de t o e ns ure t hat 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 ma y  be 
circ u msta nces o utsi de t he c o ntr ol of t he i n vesti gat or t hat ma y  ma ke it u nfeasi ble t o perf or m 
t he test. In t hese cases, t he i n vesti gat or m ust ta ke all ste ps necessar y  t o e ns ure t he safety a n d 
w ell-bei n g of t he partici pa nt . 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 he misse d test a n d a ny 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 re q uire d 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 m ust be i nf or me d of t hese i nci de nts i n a ti mel y ma n ner.
F or sa m ples bei n g c ollecte 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 v esti gat or site pri or 
t o i nitiati o n of t he st u d y.
T he t otal bl o o d sa m pli n g v ol u me f or i n di vi d ual partici pa nt s i n t his st u d y is a p pr o xi matel y 
1 4 0 m L  f or partici pa nts wit h A D a n d 1 20 m L  f or partici pa nts wit h Ps O. T he act ual c ollecti o n 
ti mes of bl o o d sa m pli n g ma y  c ha n ge. A d diti o nal bl o o d sa m ples ma y be ta ke n f or safety 
assess me nts at ti mes s pecifie d b y Pfizer, pr o vi de d t he t otal v ol u me ta ke n d uri n g t he st u d y 
d oes n ot e xcee d 5 5 0 m L  d uri n g a ny peri o d of 5 6 c o nsec uti ve da ys.
8. 1. Effic ac y Assess me nts
8. 1. 1. Effic ac y Assess me n ts f or A D
All efficac y  assess me nts will be base d o n areas treate d wit h st u d y i nter ve nti o n.
0 9 0 1 7 7 e 1 9 b b 9 c 5f d\ A p pr o v e d\ A p pr o v e d O n: 0 3- N o v- 2 0 2 2 1 1: 4 8 ( G M T)

P F -0 7 0 3 8 1 2 4
Pr ot oc ol C 3 9 4 1 0 0 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 2 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 Marc h 2 0 2 1)
Pa ge 6 3
8. 1. 1. 1. P h ysici a n Assess me nt s
8. 1. 1. 1. 1. I G A
T he I G A of A D is sc ore d o n a 5- p oi nt scale ra n gi n g fr o m 0 (clear) t o 4 (se vere), reflecti n g a 
gl o bal c o nsi derati o n of t he er y t he ma, i n d urati o n a n d scali n g. T he cli nical e val uat or of A D 
will perf or m a n assess me nt of t he o verall se verit y of A D 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 Secti o n 1 0. 1 2. 1. 1 (A p pe n di x 1 2 ). 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. 
8. 1. 1. 1. 2. E A SI
T he E A SI q ua ntifies t he se verit y of a partici pa nt’s A D base d o n b ot h se verit y  of lesi o n by 
cli nical si g ns a n d t he perce nt of B S A affecte d. E A SI  is a c o m p osite sc ori n g of t he de gree of 
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 (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 f or 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 ole b o d y.8 T he cl i nical e val uat or of 
A D will perf or m a n assess me nt of se verity a n d area i n v ol ve d as descri be d i n
Secti o n 1 0. 1 2. 1. 2 (A p pe n di x 1 2 ).
8. 1. 1. 1. 3. B S A
Assess me nt of B S A f or efficac y is perf or me d se parately f or f o ur areas of t he b o d y: 

Hea d , i ncl u di n g nec k a n d face b ut excl u di n g hair -beari n g scal p;

Tr u n k , i ncl u di n g a xillae a n d gr oi n;

U p per li m bs ; 

L o wer li m bs , i ncl u di n g b utt oc ks.
T he perce nta ge s urface area affecte d b y A D is esti mate d b y  mea ns of t he “ ha n d pri nt 
met h o d”, w here t he f ull ha n d of t he partici pa nt (ie, t he partici pa nt’s f ull y  e xte n de d pal m, 
fi n gers a n d t h u m b t o get her) re prese nts a p pr o xi matel y 1 % of t he t otal B S A.
T he cli nical e val uat or of A D will perf or m a n assess me nt of t he % B S A as descri be d i n 
Secti o n 1 0. 1 2. 1. 3 (A p pe n di x 1 2 ).
0 9 0 1 7 7 e 1 9 b b 9 c 5f d\ A p pr o v e d\ A p pr o v e d O n: 0 3- N o v- 2 0 2 2 1 1: 4 8 ( G M T)
C CI

P F -0 7 0 3 8 1 2 4
Pr ot oc ol C 3 9 4 1 0 0 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 2 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 Marc h 2 0 2 1)
Pa ge 6 4
8. 1. 1. 2. 1. P P -N R S
T he P P -N R S is a dail y  patie nt-re p orte d assess me nt of i nte nsit y of pr urit us o n a n 1 1-p oi nt 
n u merical rati n g scale, wit h a 2 4 -h o ur recall peri o d. 2 T he P P -N R S will be c o m plete d Q D , 
starti n g at least 7 d a y s pri or t o Da y 1 a n d t he n, c o m plete d Q D e ver y da y fr o m Da y 1 t o 
Wee k
1 2 bef ore st u d y i nter ve nti o n d ose is a p plie d , prefera bl y at t he sa me ti me of eac h da y, 
as n ote d i n t he S o A . All partici pa nts will c o m plete t he q uesti o n naire at t he f oll o w-u p visit i n 
cli nic.
N ote t hat t he a vera ge of 7 da y s ( mi ni m u m of 4 da ys) of P P -N R S sc ores i m me diatel y 
prece di n g ra n d o mizati o n will be use d t o calc ulate t he baseli ne a vera ge sc ore a n d assess 
eli gi bilit y, as i n Secti o n 5. 1 .
0 9 0 1 7 7 e 1 9 b b 9 c 5f d\ A p pr o v e d\ A p pr o v e d O n: 0 3- N o v- 2 0 2 2 1 1: 4 8 ( G M T)
C CI
C CI

P F -0 7 0 3 8 1 2 4
Pr ot oc ol C 3 9 4 1 0 0 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 2 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 Marc h 2 0 2 1)
Pa ge 6 5
0 9 0 1 7 7 e 1 9 b b 9 c 5f d\ A p pr o v e d\ A p pr o v e d O n: 0 3- N o v- 2 0 2 2 1 1: 4 8 ( G M T)
C CI
C CI

P F -0 7 0 3 8 1 2 4
Pr ot oc ol C 3 9 4 1 0 0 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 2 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 Marc h 2 0 2 1)
Pa ge 6 6
 
 

T he P P -N R S a n d 
 q uesti o n naire s will be c o m plete d at t he partici pa nts’ 
h o me /resi de nce, usi n g t he e-diar y  pr o vi de d by s p o ns or. T he P P -N R S will be 
c o m plete d o nl y  b y  partici pa nts 1 8 t o 7 5 y ears ol d at Scree ni n g, starti n g fr o m at least 
7 da y s pri or t o Da y 1.
8. 1. 2. 2. 1. P P -N R S
T he P P -N R S is a dail y  patie nt-re p orte d assess me nt of i nte nsit y of pr urit us o n a n 1 1-p oi nt 
n u merical rati n g scale, wit h a 2 4 h o ur recall peri o d. 2 T he P P -N R S will be c o m plete d Q D , 
starti n g at least 7 d a y s pri or t o Da y 1 a n d t he n, c o m plete d Q D e ver y da y fr o m Da y 1 t o 
Wee k
1 2 be f ore st u d y i nter ve nti o n d ose is a p plie d, prefera bly at t he sa me ti me of eac h da y, 
as n ote d i n t he S o A . All a d ult ( 1 8-7 5 y ears ol d at Scree ni n g) partici pa nts will c o m plete t he 
q uesti o n n aire at t he f oll o w-u p visit i n -cli nic.
0 9 0 1 7 7 e 1 9 b b 9 c 5f d\ A p pr o v e d\ A p pr o v e d O n: 0 3- N o v- 2 0 2 2 1 1: 4 8 ( G M T)
C CI
C CI
C CI
C CI

P F -0 7 0 3 8 1 2 4
Pr ot oc ol C 3 9 4 1 0 0 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 2 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 Marc h 2 0 2 1)
Pa ge 6 7
8. 1. 3. R ater Q u alific ati o ns
F or s pecific rati n g assess me nts, o nl y  q ualifie d raters will be all o we d t o e val uate a n d/ or rate 
partici pa nts i n t his st u d y . T he mi ni m u m q ualificati o ns a rater m ust meet f or eac h st u d y rati n g 
assess me nt will be o utli ne d i n t he Rater Assess me nt G ui de or Rater Q ualificati o n Pla n . T he 
le vel of e x perie nce wit h t he tar get p o p ulati o n ( or e q ui vale nt), s pecific scale e x perie nce ( or 
e q ui vale nt), a n d certificati o n re q uire d (if a p plica ble) will be liste d a n d use d t o deter mi ne 
w het her a rater is a p pr o ve d f or a gi ve n assess me nt.
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 s h o ul d assess all 
der m at ol o gic al cli nic al e v al u ati o ns f or a n y i n di vi d u al p artici p a nt t hr o u g h o ut t he st u d y 
w he ne ver p ossi ble .
0 9 0 1 7 7 e 1 9 b b 9 c 5f d\ A p pr o v e d\ A p pr o v e d O n: 0 3- N o v- 2 0 2 2 1 1: 4 8 ( G M T)
C CI

P F -0 7 0 3 8 1 2 4
Pr ot oc ol C 3 9 4 1 0 0 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 2 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 Marc h 2 0 2 1)
Pa ge 6 8

A bac k u p e x perie nce d a n d q ualifie d pr ot oc ol -trai ne d e val 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 nc 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 or m t he e val uati o n.

T he rater (s) m ust bec o me certifie d t o perf or m selecte d st u d y assess me nts bef ore he or 
s he ca n partici pate i n t he c o n d uct of t he st u dy.
F or s pecificall y defi ne d assess me nts, rater trai ni n g a n d sta n dar dizati o n e xercises ma y be 
c o n d ucte d, a n d writte n d oc u me ntati o n will be pr o vi de d b y t he site f or eac h rater’s 
certificati o n. In ret ur n, eac h site will be pr o vi de d writte n d oc u me ntati o n o utli ni n g eac h 
rater’s certificati o n f or s pecific st u dy assess me nts. Recertificati o n ma y be re q uire d at 
peri o dic i nter vals d uri n g t he st u d y . T he raters w ho a d mi nister s pecific st u d y  assess me nts will 
be d oc u me nte d i n a ce ntralize d l ocati o n a n d all site staff w h o a d mi nister rati n gs will be 
verifie d i n t he site st u d y d oc u me ntati o n d uri n g t he c o n d uct of t he st u d y.
8. 2. S afet y Assess me nts
Pla n ne d ti me p oi nts f or all safet y assess me nts are pr o vi de d i n t he S o A . U nsc he d ule d cli nical 
la b orat or y meas ure me nts ma y  be o btai ne d at a n y ti me d uri n g t he st u dy t o assess a n y 
percei ve d safet y  iss ues.
8. 2. 1. Me dic al a n d Me dic ati o n Hist or y
I n vesti gat ors s h o ul d ma ke all reas o na ble eff orts t o o btai n a n acc urate a n d c o m plete me dical 
hist or y  a n d hist or y of pri or me dicati o n use w he n e val uati n g w het her a partici pa nt is eli gi ble 
f or t he st u dy. 
T he f oll o wi n g will be c ollecte d at Scree ni n g: c o m plete me dical hist or y, A D or Ps O disease 
hist or y , me dicati o n s a n d n on- me dicati o n t hera pies hist or y , a n d alc o h ol a n d t o bacc o use 
stat us/hist or y . 

C o m plete A D or Ps O disease hist or y  i ncl u des c ollecti o n of details of A D or Ps O : A D 
or Ps O dia g n osis, t he use of t o pical treat me nts, s yste mic tr eat me nts a n d ot her 
treat me nts (e g, use of bi ol o gic dr u gs) f or A D or Ps O ta ke n d uri n g t he 9 0 da y s pri or t o 
Scree ni n g wit h d ose, d urati o n of treat me nt, a n d reas o n f or disc o nti n uati o n. All ot her 
dr u gs (i ncl u di n g s u nscree n, o ver t he c o u nter me dicati o n, vita mi n s, a n d dietar y 
s u p ple me nts) ta ke n wit hi n 2 8 da ys pri or t o t he Scree ni n g visit s h o ul d be rec or de d. 
If t he stat us of a partici pa nt’s me dical hist or y is i n d o u bt or i nf or mati o n pertai ni n g t o a 
critical varia ble is c o nflicti n g, e ver y  reas o na ble ste p t o sec ure pr o per d oc u me ntati o n of 
c orrect me dical stat us s h o ul d be atte m pte d. D oc u me ntati o n of t he me dical a n d me dicati o n 
hist ories o ver t he pr ot oc ol- defi ne d ti me peri o ds s h o ul d be a vaila ble f or s p o ns or re vie w 
d uri n g t he s o urce data verificati o n pr ocess. Q uesti o ns a b o ut pri or me dicati o ns or eli gi bilit y  
s h o ul d be directe d t o t he s p o ns or cli nicia n or s p o ns or me dical m o nit or .
Me dical h ist or y will be c ollecte d at t he Scree ni n g visit a n d re vie we d at t he Baseli ne Da y 1 
visit f or a n y c ha n ges.
0 9 0 1 7 7 e 1 9 b b 9 c 5f d\ A p pr o v e d\ A p pr o v e d O n: 0 3- N o v- 2 0 2 2 1 1: 4 8 ( G M T)

P F -0 7 0 3 8 1 2 4
Pr ot oc ol C 3 9 4 1 0 0 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 2 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 Marc h 2 0 2 1)
Pa ge 6 9
8. 2. 2. P h ysic al E x a mi n ati o ns (I ncl u di n g Hei g ht a n d Wei g ht)
P h y sical e xa mi nati o ns, i ncl u di n g c o m plete p h ysical e xa mi nati o n, tar gete d p h ysical 
e xa mi nati o n, hei g ht a n d wei g ht will be perf or me d at ti mes s pecifie d i n t he S o A .
P h y sical 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 hcare pr ofessi o nal per l ocal g ui deli nes. I n vesti gat ors s h o ul d pa y  s pecial atte nti o n t o 
cli nical si g ns relate d t o pre vi o us seri o us ill nesses. 

It is rec o m me n de d t hat wei g ht be meas ure d i n k g t o t he nearest 0. 1 k g a n d t hat hei g ht 
be meas ure d i n c m wit h s h oes re m o ve d. F or meas uri n g wei g ht, a scale wit h 
a p pr o priate ra n ge a n d res ol uti o n is use d a n d m ust be place d o n a sta ble, flat s urface. 
Partici pa nts m ust re m o ve s h oes, b ul k y  la yers of cl ot hi n g, a n d jac kets s o t hat o nl y  
li g ht cl ot hi n g re mai ns. T he y m ust als o re m o ve t he c o nte nts of t heir p oc kets a n d 
re mai n still d uri n g meas ure me nt of wei g ht. 

A co m plete p h ys ical e xa mi nati o n will i ncl u de, at a mi ni m u m, assess me nts of t he 
ge neral a p peara nce, s ki n ( prese nce of ras h), H E E N T, l u n gs (a usc ultati o n), heart 
(a usc ultati o n f or prese nce of m ur m urs, gall o ps, r u bs), a b d o me n ( pal pati o n a n d 
a usc ultati o n), m usc ul os keletal ( prese nce of peri p heral e de ma), ne ur ol o gic ( me ntal 
stat us, stati o n, gait, refle xes, m ot or a n d se ns or y f u ncti o n, c o or di nati o n) a n d l ym p h 
n o des. 

Disease f oc use d p h y sical exa mi nati o n: i ncl u des all A D or Ps O i n v ol ve d s ki n (i n 
treata ble a n d n o n-treata ble areas) a n d e val uati o n of a n y c urre nt or re p orte d s ym pt o ms 
f or cli nically si g nifica nt c ha n ges. 
A n y  cli nicall y si g nifica nt c ha n ges fr o m t he m ost rece nt p hys ical e xa mi nati o n s h o ul d be 
rec or de d as A Es. Lac k of efficac y is ge nerally n ot c o nsi dere d a n A E. 
I n vesti gat ors s h o ul d pa y s pecial atte nti o n t o cli nical si g ns relate d t o pre vi o us seri o us 
ill nesses.
Please see Secti o n 8. 2. 7 f or s ki n Local T olera bilit y  Assess me nt.
P h y sical e xa mi nati o n fi n di n gs c ollecte d d uri n g t he st u d y will be c o nsi dere d s o urce data a n d 
will n ot be re q uire d t o be re p orte d, u nless ot her wise n ote d. A n y u nt o war d p h ysical 
e xa mi nati o n fi n di n gs t hat are i de ntifie d d uri n g t he acti ve c ollecti o n peri o d a n d meet t he 
defi niti o n of a n A E or S A E (A p pe n di x 3 ) m ust be re p orte d acc or di n g t o t he pr ocesses i n 
Secti o ns 8. 3. 1 t o 8. 3. 3 .
8. 2. 3. Electr oc ar di o gr a ms
Sta n dar d 1 2 -lea d EC Gs utilizi n g li m b lea ds ( wit h a 1 0 sec o n d r h yt h m stri p) s h o ul d be 
c ollecte d at ti mes s pecifie d i n t he S o A secti o n of t his pr ot oc ol usi n g a n E C G mac hi ne t hat 
a ut o maticall y calc ulates t he heart rate a n d meas ures P R, Q T, a n d Q Tc i nter vals a n d Q R S 
c o m ple x . Alter nati ve lea d place me nt met h o d ol o g y usi n g t ors o lea ds (e g, Mas o n -Li kar) 
0 9 0 1 7 7 e 1 9 b b 9 c 5f d\ A p pr o v e d\ A p pr o v e d O n: 0 3- N o v- 2 0 2 2 1 1: 4 8 ( G M T)

P F -0 7 0 3 8 1 2 4
Pr ot oc ol C 3 9 4 1 0 0 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 2 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 Marc h 2 0 2 1)
Pa ge 7 0
s h o ul d n ot be use d gi ve n t he p ote ntial ris k of discre pa ncies wit h E C Gs ac q uire d usi n g 
sta n dar d li m b lea d place me nt. All sc he d ule d E C Gs s h o ul d be perf or me d after t he partici pa nt
has reste d q uietl y f or at least 5 mi n ute s i n a s u pi ne p ositi o n. 

D uri n g scree ni n g, if partici pa nts ha ve i nitial scree ni n g val ue Q Tc F > 4 5 0 ms ec, E C G 
s h o ul d be re peate d t w o m ore ti mes a n d t he a vera ge of t he 3 Q Tc F s h o ul d be use d t o 
deter mi ne t he partici pa nt eli gi bilit y . 

T o e ns ure safet y of t he pa rtici pa nt, a q ualifie d i n di vi d ual (e g, s u b-i n vesti gat or) at t he 
i n vesti gat or site will ma ke c o m paris o ns t o baseli ne meas ure me nts ta ke n at Da y 1. I n 
t he e ve nt of mar ke d pr ol o n gati o n of t he Q Tc F i nter val t o > 5 0 0 msec or > 6 0 msec 
c ha n ge fr o m baseli ne ( Da y  1), t he E C G s h o ul d be re peate d 2 m ore ti mes a n d t he 
a vera ge of t he t hree Q Tc F s h o ul d be use d t o deter mi ne t he disc o nti n uati o n of st u d y  
i nter ve nti o n (Secti o n 7. 1 Disc o nti n uati o n of St u d y I nter ve nti o n).

If a) a p ost- d ose Q Tc F i nter val re mai ns ≥6 0 msec fr o m t he baseli ne a n d is 
> 4 5 0 msec; or b) a n a bs ol ute Q T val ue is ≥5 0 0 msec f or a n y sc he d ule d E C G f or 
g reater t ha n 4 h o urs ( or s o o ner , at t he discreti o n of t he i n vesti gat or); or c) Q Tc F
i nter vals get pr o gressi vel y l o n ger, t he partici pa nt s h o ul d u n der g o c o nti n u o us E C G 
m o nit ori n g . A car di ol o gist s h o ul d be c o ns ulte d if Q Tc F i nter vals d o n ot ret ur n t o 
less t ha n t he criteria liste d a b o ve after 8 h o urs of m o nit ori n g ( or s o o ner , at t he 
discreti o n of t he i n vesti gat or). 
I n s o me cases, it ma y be a p pr o priate t o re peat a b n or mal E C Gs t o r ule o ut i m pr o per lea d 
place me nt as c o ntri b uti n g t o t he E C G a b n or malit y. It is i m p or ta nt t hat lea ds be place d i n t he 
sa me p ositi o ns eac h ti me i n or der t o ac hie ve precise E C G rec or di n gs. If a mac hi ne -rea d Q Tc 
val ue is pr ol o n ge d, as defi ne d a b o ve, re peat meas ure me nts ma y  n ot be necessar y if a 
q ualifie d me dical pr o vi der ’s i nter pretati o n deter mi nes t hat t he Q Tc F val ues are i n t he 
acce pta ble ra n ge.
W he n t he ti mi n g of t hese meas ure me nts c oi nci des wit h a bl o o d c ollecti o n, t he E C G s h o ul d be 
o btai ne d pri or t o t he n o mi nal ti me of t he bl o o d c ollecti o n. 
E C G val ues of p ote ntial cli nical c o ncer n are liste d i n A p pe n di x 7 .
8. 2. 4. Vit al Si g ns
Te m perat ure, p ulse rate, a n d bl o o d press ure will be assesse d.

B o d y te m perat ure will be c ollecte d usi n g o ral, ty m pa nic, axillar y  or te m p oral
m et h o ds a n d t he sa me met h o d s h o ul d be use d c o nsiste ntl y  t hr o u g h o ut t he st u d y.

Bl o o d press ure a n d p ulse rate meas ure me nts will be assesse d wit h t he partici pa nt i n a 
s u pi ne or seate d p ositi o n usi n g a c o m pletel y  a ut o mate d de vice. Ma n ual tec h ni q ues 
will be use d o nl y  if a n a ut o mate d de vice is n ot a vaila ble. A p pr o priatel y size d c uff 
s h o ul d be use d a n d it is preferre d t hat t he sa me ar m ( prefera bly t he d o mi na nt ar m) 
0 9 0 1 7 7 e 1 9 b b 9 c 5f d\ A p pr o v e d\ A p pr o v e d O n: 0 3- N o v- 2 0 2 2 1 1: 4 8 ( G M T)

P F -0 7 0 3 8 1 2 4
Pr ot oc ol C 3 9 4 1 0 0 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 2 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 Marc h 2 0 2 1)
Pa ge 7 1
a n d sa me p ositi o n be use d t hr o u g h o ut t he st u d y f or a n i n di vi d ual partici pa nt. Bl o o d 
press ure a n d p ulse rate meas ure me nts s h o ul d be prece de d b y at least 5 mi n utes of rest 
f or t he partici pa nt i n a q uiet setti n g wit h o ut distracti o ns (e g, tele visi o n, cell p h o nes).
Assess me nt of vital si g ns s h o ul d prece de bl o o d dra w f or cli nical la b orat or y  visits.
8. 2. 5. Cli nic al S afet y L a b or at or y Assess me nts
See A p pe n di x 2 f or t he list of cli nical safety la b orat or y tests t o be perf or me d a n d t he S o A f or 
t he ti mi n g a n d fre q ue nc y. All pr ot oc ol -re q uire d la b orat or y assess me nts, as defi ne d i n 
A p pe n di x 2 , m ust be c o n d ucte d i n acc or da nce wit h t he la b orat or y ma n ual a n d t he S o A .
U nsc he d ule d cli nical la b orat or y  meas ure me nts ma y be o btai ne d at a n y ti me d uri n g t he st u d y 
t o assess a ny percei ve d safet y iss ues.
T he i n vesti gat or m ust re vie w t he la b orat or y  re p ort, d oc u me nt t his re vie w, a n d rec or d a n y 
cli nicall y rele va nt c ha n ges occ urri n g d uri n g t he st u d y  i n t he A E secti o n of t he C R F.
Cli nicall y  si g nifica nt a b n or mal la b orat or y fi n di n gs are t h ose w hic h are n ot ass ociate d wit h 
t he u n derlyi n g disease, u nless j u d ge d b y  t he i n vesti gat or t o be m ore se vere t ha n e x pecte d f or 
t he partici pa nt's c o n diti o n.
All la b orat or y  tests wit h val ues c o nsi dere d cli nicall y si g nifica ntly a b n or mal d uri n g 
partici pati o n i n t he st u d y  or wit hi n 2 8 da y s after t he last d ose of st u d y i nter ve nti o n s h o ul d be 
re peate d u ntil t he val ues ret ur n t o n or mal or baseli ne or are n o l on ger c o nsi dere d cli nicall y  
si g nifica nt by t he i n vesti gat or or me dical m o nit or.
If s uc h val ues d o n ot ret ur n t o n or mal/ baseli ne wit hi n a peri o d of ti me j u d ge d reas o na ble b y 
t he i n vesti gat or, t he eti ol o g y s h o ul d be i de ntifie d a n d t he s p o ns or n otifie d.
See A p pe n di x 6 f or s u g geste d acti o ns a n d f oll o w- u p assess me nts i n t he e ve nt of p ote ntial 
dr u g -i n d uce d li ver i nj ur y.
8. 2. 6. S uici d al I de ati o n a n d Be h a vi or Ris k M o nit ori n g - C- S S R S
T he C -S S R S is a vali date d t o ol f or i n vesti gati ve sta ff t o use t o e val uate s uici dal i deati o n a n d 
be ha vi or. 1 2 At t he Scree ni n g visit , per E xcl usi o n Criteri o n #2 , if t here is s uici dal i deati o n 
ass ociate d wit h act ual i nte nt a n d/ or pla n i n t he past y ear, or pre vi o us hist or y of s uici dal 
be ha vi ors i n t he past 5 ye ars, t he partici pa nt will n ot be i ncl u de d i n t he st u d y ( See 
A p pe n di x 1 1 f or details). Trai ne d site staff is t o a d mi nister t he C- S S R S t o all partici pa nts at 
Scree ni n g a n d assess t he partici pa nt’s eli gi bilit y base d o n t he a ns wers.
F or partici pa nts meeti n g e xcl usi o nar y  res ults of t he C-S S R S, it is rec o m me n de d t hat t he 
partici pa nt’s P C P s h o ul d be i nf or me d, a n d t he partici pa n t 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.
0 9 0 1 7 7 e 1 9 b b 9 c 5f d\ A p pr o v e d\ A p pr o v e d O n: 0 3- N o v- 2 0 2 2 1 1: 4 8 ( G M T)

P F -0 7 0 3 8 1 2 4
Pr ot oc ol C 3 9 4 1 0 0 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 2 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 Marc h 2 0 2 1)
Pa ge 7 2
8. 2. 7. L oc al T oler a bilit y Assess me nt
T he i n vesti gat or or desi g nee will assess t olera bilit y  at t he site of st u d y i nter ve nti o n
a p plicati o n, i m me di atel y p ost-a p plic ati o n of t he st u d y i nter ve nti o n . T his assess me nt1 3
will f oc us o n t he n o n -lesi o n al s ki n usi n g t he scale i n Ta ble 5 . All partici pa nt re p orte d a n d 
o bser ve d a p p licati o n site A Es s h o ul d be rec or de d al o n g wit h t he b o d y re gi o n l ocati o n, 
se verity, d urati o n a n d o utc o me as i n dicate d o n t he C R F. See Secti o n 7. 1 f or per ma ne nt a n d 
te m p orar y disc o nti n uati o n criteria base d o n l ocal t olera bilit y assess me nt. 
T a ble 5 .
S ki n T oler a bilit y Gr a di n g S yste m f or N o n- lesi o n al S ki n
Gr a de
Se verit y
Descri pti o n
0
N o ne
N o e vi de nce of l ocal i nt olera nce
1
Mil d
Mi ni mal er yt he ma a n d/ or e de ma, sli g ht glaze d a p peara nce
2
M o derate
Defi nite er yt he ma a n d/ or e de ma wit h peeli n g a n d/ or 
crac ki n g b ut nee ds n o a da ptati o n of p os ol o g y
3
Se vere (t o be re p orte d as a n A E)
Er yt he ma, e de ma glazi n g wit h fiss ures, fe w vesicles or 
pa p ules: c o nsi der re m o vi n g t o pical a ge nt (if still i n place)
4
Ver y  se vere (t o be re p orte d as a n A E)
Str o n g reacti o n s prea di n g be y o n d t he treate d area, b ull o us 
reacti o n, er osi o ns: re m o val of t o pical a ge nt (if still i n 
place)
8. 2. 8. Pre g n a nc y Testi n g 
Pre g na nc y  tests ma y be uri ne or ser u m tests b ut m ust ha ve a se nsiti vit y of at least 
2 5 mI U/ m L. Pre g na nc y  tests will be perf or me d i n W O C B P at t he ti mes liste d i n t he S o A . 
F oll o wi n g a ne gati ve pre g na nc y  test res ult at scree ni n g, a p pr o priate c o ntrace pti o n m ust be 
c o m me nce d a n d a sec o n d ne gati ve pre g na nc y test res ult will be re q uire d at t he baseli ne visit 
pri or t he partici pa nt ’s recei vi n g t he st u d y i nter ve nti o n. 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) a n d at t he e n d of t he st u d y. Pre g na nc y tests ma y als o be 
re peate d if re q ueste d by I R Bs/ E Cs or if re q uire d b y l ocal re g ulati o ns. 
If a uri ne test ca n n ot be c o nfir me d as ne gati ve (e g, a n a m bi g u o us res ult), a ser u m pre g na nc y  
test is re q uire d. I n s uc h cases, t he partici pa nt m ust be e xcl u de d if t he ser u m pre g na nc y res ult 
is p ositi ve.
T w o ne gati ve pre g na nc y  tests are re q uire d bef ore ra n d o mizati o n ( 1 ne gati ve ser um 
pre g na nc y  test at Scree ni n g a n d 1 ne gati ve uri ne pre g na nc y test at Da y 1 visit).
If uri ne pre g na nc y test is p ositi ve after st u d y i nter ve nti o n a p plicati o n, ser u m pre g na nc y test 
will be c o n d ucte d, st u d y i nter ve nti o n a p plicati o n pa use d a n d s p o ns or cli nicia n a n d s p o ns or 
me dical m o nit or n otifie d i m me diatel y .
8. 3. A d verse E ve nts , Seri o us A d verse E ve nts , a n d Ot her S afet y Re p orti n g
T he defi niti o ns of a n A E a n d a n S A E ca n be f o u n d i n A p pe n di x 3 .
0 9 0 1 7 7 e 1 9 b b 9 c 5f d\ A p pr o v e d\ A p pr o v e d O n: 0 3- N o v- 2 0 2 2 1 1: 4 8 ( G M T)

P F -0 7 0 3 8 1 2 4
Pr ot oc ol C 3 9 4 1 0 0 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 2 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 Marc h 2 0 2 1)
Pa ge 7 3
A Es ma y  arise fr o m sy m pt o ms or ot h er c o m plai nts re p orte d t o t he i n vesti gat or b y  t he 
partici pa nt ( or, w he n a p pr o priate, b y a care gi ver, s urr o gate, or t he partici pa nt's le gall y 
a ut h orize d re prese ntati ve), or t he y  ma y arise fr o m cli nical fi n di n gs of t he I n vesti gat or or 
ot her healt hcare pr o vi ders (cli nical si g ns, test res ults, etc.).
T he i n vesti gat or a n d a n y q ualifie d desi g nees are res p o nsi ble f or detecti n g, d oc u me nti n g, a n d 
rec or di n g e ve nts t hat meet t he defi niti o n of a n A E or S A E a n d re mai n res p o nsi ble t o 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 t he 
e ve nt meets t he criteria f or classificati o n as a n S A E or ca use d t he partici pa nt t o dis c o nti n ue 
t he st u d y i nter ve nti o n (see Secti o n 7. 1 ). 
D uri n g t he acti ve c ollecti o n peri o d as descri be d i n Secti o n 8. 3. 1 , eac h partici pa nt /pare nt/le gal 
g uar dia n will be q uesti o ne d a b o ut t he occ urre nce of A Es i n a n o nlea di n g ma n ner.
I n a d diti o n , t he i n vesti gat or ma y be re q ueste d by P fizer Safety 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.
8. 3. 1. Ti me Peri o d a n d Fre q ue nc y f or C ollecti n g A E a n d 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 partici pa nt be gi ns fr o m t he ti me t he partici pa nt pr o vi des i nf or me d 
c o nse nt /asse nt, w hic h is o btai ne d bef ore t he partici pa nt ’s partici pati o n i n t he st u dy (ie, bef ore 
u n der g oi n g a n y st u d y- relate d pr oce d ure a n d/ or recei vi n g st u d y i nter ve nti o n), 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 after t he last a d mi nistrati o n of t he st u d y 
i nter ve nti o n.
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 A E or S A E 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.
F or partici pa nts 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.
If t he partici pa nt 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 t he c ollecti o n of 
f ut ure i nf or mati o n, t he acti ve c ollecti o n peri o d e n ds w he n c o nse nt is wit h dra w n.
If a partici pa nt per ma ne ntl y disc o nti n ues or te m p oraril y disc o nti n ues st u d y i nter ve nti o n 
beca use of a n A E or S A E, t he A E or S A E m ust be rec or de d o n t he C R F a n d t he S A E 
re p orte d usi n g t he C T S A E Re p ort F or m.
I n vesti gat ors are n ot o bli gate d t o acti vel y see k i nf or mati o n o n A E s or S A E s after t he 
partici pa nt has c o ncl u de d st u d y partici pati o n. H o we ver, if t he i n vesti gat or lear ns of a n y S A E, 
i ncl u di n g a deat h, at a ny ti me after a partici pa nt has c o m plete d t he st u d y, a n d he/s he 
c o nsi ders t he e ve nt t o be reas o na bl y relate d t o t he st u d y  i nter ve nti o n, t he i n vesti gat or m ust 
pr o m ptl y  re p ort t he S A E t o Pfizer usi n g t he C T S A E Re p ort F or m.
0 9 0 1 7 7 e 1 9 b b 9 c 5f d\ A p pr o v e d\ A p pr o v e d O n: 0 3- N o v- 2 0 2 2 1 1: 4 8 ( G M T)

P F -0 7 0 3 8 1 2 4
Pr ot oc ol C 3 9 4 1 0 0 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 2 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 Marc h 2 0 2 1)
Pa ge 7 4
8. 3. 1. 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 partici pa nt d uri n g t he acti ve c ollecti o n peri o d as descri be d i n
Secti o n 8. 3. 1 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 i m me diatel y  u p o n 
a ware ness a n d u n der n o circ u msta nce s h o ul d t his e xcee d 2 4 h o urs, as i n dicate d i n 
A p pe n di x 3 . T he i n vesti gat or will s u b mit a n y u p date d S A E data t o t he s p o ns or wit hi n 
2 4 h o urs of it bei n g a vaila ble.
8. 3. 1. 2. Rec or di n g N o nseri o us A Es a n d S A Es o n t he C R F
All n o nseri o us A Es a n d S A Es occ urri n g i n a partici pa nt d uri n g t he acti ve c ollecti o n peri o d , 
w hic h be gi ns after o btai ni n g i nf or me d c o nse nt /asse nt as descri be d i n Secti o n 8. 3. 1 , will be 
rec or de d o n t he A E secti o n of t he C R F.
T he i n vesti gat or is t o rec or d o n t he C R F all directl y  o bser ve d a n d all s p o nta ne o usl y re p orte d 
A Es a n d S A Es re p orte d b y t he partici pa nt.
8. 3. 2. Met h o d of Detecti n g A Es a n d S A Es
T he met h o d of rec or di n g, e val uati n g, a n d assessi n g ca usalit y  of AEs a n d S A E s a n d t he 
pr oce d ures f or c o m pleti n g a n d tra ns mitti n g S A E re p orts are pr o vi de d i n A p pe n di x 3 .
Care will be ta ke n n ot t o i ntr o d uce bias w he n detecti n g A Es a n d/ or S A Es. O pe n -e n de d a n d 
n o nlea di n g ver bal q uesti o ni n g of t he partici pa nt is t he preferre d met h o d t o i n q uire a b o ut 
A E occ urre nces.
8. 3. 3. F oll o w - Up of A Es a n d S A Es
After t he i nitial A E or S A E re p ort, t he i n vesti gat or is re q uire d t o pr oacti vel y  f oll o w eac h 
partici pa nt at s u bse q ue nt visits/c o ntacts. F or ea c h e ve nt, t he i n vesti gat or m ust p urs ue a n d 
o btai n a de q uate i nf or mati o n u ntil res ol uti o n, sta bilizati o n, t he e ve nt is ot her wise e x plai ne d, 
or t he partici pa nt is l ost t o f oll o w- u p (as defi ne d i n Secti o n 7. 3 ).
I n ge neral, f oll o w- u p i nf or mati o n will i ncl u de a descri pti o n of t he e ve nt i n s ufficie nt detail 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 ny 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 n d ill nesses, m ust be pr o vi de d. I n t he case of a partici pa nt deat h, a s u m 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. 
F urt her i nf or mati o n o n f oll o w -u p pr oce d ures is gi ve n i n A p pe n di x 3 .
8. 3. 4. Re g ul at or y Re p orti n g Re q uire me nts f or S A Es
Pr o m pt n otificati o n b y  t he i n vesti gat or t o t he s p o ns or of an S A E is esse ntial s o t hat le gal 
o bli gati o ns a n d et hical res p o nsi bilities t o war d t he safet y of partici pa nts a n d t he safet y of a 
st u d y i nter ve nti o n u n der cli nical i n vesti gati o n are met.
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P F -0 7 0 3 8 1 2 4
Pr ot oc ol C 3 9 4 1 0 0 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 2 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 Marc h 2 0 2 1)
Pa ge 7 5
T he s p o ns or has a le gal res p o nsi bilit y  t o n otif y b ot h t he l ocal re g ulat or y a ut h orit y a n d ot her 
re g ulat or y a ge ncies a b o ut t he safety of a st u d y i nter ve nti o n u n der cli nical i n vesti gati o n. T he 
s p o ns or will c o m pl y wit h c o u ntr y-s pecific re g ulat or y re q uire me nts relati n g t o safety 
re p orti n g t o t he re g ulat or y a ut horit y, I R B s/ E Cs, a n d i n vesti gat ors.
I n vesti gat or safet y re p orts m ust be pre pare d f or S U S A Rs acc or di n g t o l ocal re g ulat or y 
re q uire me nts a n d s p o ns or p olic y a n d f or war de d t o i n vesti gat ors as necessar y.
A n i n vesti gat or w h o recei ves S U S A R s or ot her s pecific saf et y i nf or mati o n (e g, s u m mar y or 
listi n g of S A Es) fr o m t he s p o ns or will re vie w a n d t he n file it al o n g wit h t he S R S D (s) f or t he 
st u d y a n d will n otif y t he I R B/ E C, if a p pr o priate acc or di n g t o l ocal re q uire me nts.
8. 3. 5. E n vir o n me nt al E x p os ure, E x p os ure 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 n vir o n me ntal e x p os ure, occ urs w he n a pers o n n ot e nr olle d i n t he st u d y  as a partici pa nt 
recei ves u n pla n ne d direct c o ntact wit h or e x p os ure t o t he st u d y i nter ve nti o n. S uc h e x p os ure 
ma y  or ma y n ot lea d t o t he occ urre nce of a n A E or S A E. Pers o ns at ris k f or e n vir o n me ntal 
e x p os ure i ncl u de healt hcare pr o vi ders, fa mil y me m bers, a n d ot hers w h o ma y be e x p ose d . A n 
e n vir o n me ntal e x p os ure ma y i ncl u de e x p os ure d uri n g pre g na nc y, e x p os ure d uri n g 
breastfee di n g , a n d occu pati o nal e x p os ure .
A n y  s uc h ex p os ure t o t he st u d y i nter ve nti on u n der st u d y  are re p orta ble t o Pfizer Safety 
wit hi n 2 4 h o urs of i n vesti gat or a ware ness.
8. 3. 5. 1. E x p os ure D uri n g Pre g n a nc y
A n E D P occ urs if:

A fe male partici pa nt is f o u n d t o be pre g na nt w hile recei vi n g or after disc o nti n ui n g 
st u d y i nter ve nti o n.

A male partici pa nt w h o is recei vi n g or has disc o nti n ue d st u d y  i nter ve nti o n e x p oses a 
fe male part ner pri or t o or ar o u n d t he ti me of c o nce pti o n.

A fe male is f o u n d t o be pre g na nt w hile bei n g e x p ose d or ha vi n g bee n e x p ose d t o 
st u d y i nter ve nti o n d ue t o e n vir o n me ntal e x p os ure. Bel o w are e xa m ples of 
e n vir o n me ntal E D P : 

A fe male fa mil y  me m ber or healt hcare pr o vi der re p orts t hat s he is pre g na nt after 
ha vi n g bee n e x p ose d t o t he st u d y  i nter ve nti o n b y i n gesti o n or s ki n c o ntact.

A male fa mil y me m ber or healt hcare pr o vi der w h o has bee n e x p ose d t o t he st u d y  
i nter ve nti o n b y i n gesti o n or s ki n c o ntact t he n e x p oses his fe male part ner pri or t o 
or ar o u n d t he ti me of c o nce pti o n.
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P F -0 7 0 3 8 1 2 4
Pr ot oc ol C 3 9 4 1 0 0 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 2 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 Marc h 2 0 2 1)
Pa ge 7 6
T he i n vesti gat or m ust re p ort E D P 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, irres pecti ve of w het her a n S A E has occ urre d. T he i nitial 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 mi nati o n of pre g na nc y). 

If E D P occ urs i n a partici pa nt or a partici pa nt’s part ner, 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 or m, re gar dless of w het her a n S A E has occ urre d. Details of t he 
pre g na nc y  will be c ollecte d after t he start of st u d y i nter ve nti o n a n d u ntil 2 8 cale n dar 
da y s after t he last d ose.

If E D P occ urs i n t he setti n g of e n vir o n me ntal e x p os ure, t he i n vesti gat or m ust re p ort 
i nf or mati o n t o Pfizer Safet y usi n g t he C T S A E Re p ort F or m a n d E D P S u p ple me ntal 
F or m. Si nce t he e x p os ure i nf or mati o n d oes n ot pertai n t o t he partici pa nt 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 o m 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 file.
F oll o w - u p 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 otif y Pfizer Safety 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 h o ul d be s pecifie d a n d, if cli nicall y p ossi ble, t he str uct ural 
inte grit y 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 are 
re p orte d).
A b n or mal pre g na nc y  o utc o mes are c o nsi dere d S A Es. 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 nate d fet us, a n 
i ntra uteri ne fetal de mise, or a ne o natal deat h), t he i n 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 Safet y  as S A Es f oll o ws: 

S p o nta ne o us a b orti o n i ncl u d i n g miscarria ge a n d misse d a b orti o n;

Ne o natal deat hs t hat occ ur wit hi 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 dea t h as relate d or p ossi bl y relate d t o 
e x p os ure t o t he st u d y i nter ve nti o n. 
A d diti 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 
preter m i nfa nts t o i de ntif y de vel o p me ntal dela ys). I n t he case of pater nal e x p os ure, t he 
i n vesti gat or will pr o vi de t he partici pa nt 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 me nts t ha t 
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P F -0 7 0 3 8 1 2 4
Pr ot oc ol C 3 9 4 1 0 0 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 2 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 Marc h 2 0 2 1)
Pa ge 7 7
t he partici pa nt was gi ve n t he Pre g na nt Part ner Release of I nf or mati o n F or m t o pr o vi de t o his 
part ner.
8. 3. 5. 2. E x p os ure D uri n g Bre astfee di n g
A n e x p os ure d uri n g breastfee di n g occ urs if:

A fe male partici pa nt is f o u n d t o be breastfee di n g w hile recei vi n g or after 
di sc o nti n ui n g st u d y i nter ve nti o n.

A fe male is f o u n d t o be breastfee di n g w hile bei n g e x p ose d or ha vi n g bee n e x p ose d t o 
st u d y i nter ve nti o n (ie, e n vir o n me ntal e x p os ure). A n e xa m ple of e n vir o n me ntal 
e x p os ure d uri n g breastfee di n g is a fe male fa mil y me m ber or heal t hcare pr o vi der w h o 
re p orts t hat s he is breastfee di n g after ha vi n g bee n e x p ose d t o t he st u d y i nter ve nti o n
b y i n gesti o n or s ki n c o ntact.  
T he i n vesti gat or m ust re p ort e x p os ure d uri n g breastfee di n g t o Pfizer Safet y  wit hi n 2 4 h o urs 
of t he i n vesti gat or’s a war e ness, irres pecti ve of w het her a n S A E has occ urre d. T he 
i nf or mati o n m ust be re p orte d usi n g t he C T S A E Re p ort F or m. W he n e x p os ure d uri n g 
breastfee di n g occ urs i n t he setti n g of e n vir o n me ntal e x p os ure, t he e x p os ure i nf or mati o n d oes 
n ot pertai n t o t he partici p a nt e nr olle d i n t he st u d y, s o 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 o m 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 file.
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 or d wit h 
a ut h orize d use. H o we ver, if t he i nfa nt e x perie nces a n S A E ass ociate d wit h s uc h a dr u g, 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. 3. 5. 3. Occ u p ati o n al E x p os ure
T he i n vesti gat or m ust re p ort a n y i nsta nce of occ u pati o nal e x p os ure t o Pfizer Safety 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 here is a n ass ociate d S A E. Si nce t he i nf or mati o n a b o ut t he occ u pati o nal e x p os ure
d oes n ot pertai n t o a partici pa nt 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 o m plete d C T S A E Re p ort F or m m ust be mai ntai ne d i n t he 
i n vesti gat or site file.
8. 3. 6. C ar di o v asc ul ar a n d De at h E ve nts
N ot a p plica ble.
8. 3. 7. Dise ase -Rel ate d E ve nts a n d/ or Dise ase -Rel ate d O utc o mes N ot Q u alif yi n g as A Es 
or S A Es
N ot a p plica ble.
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P F -0 7 0 3 8 1 2 4
Pr ot oc ol C 3 9 4 1 0 0 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 2 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 Marc h 2 0 2 1)
Pa ge 7 8
8. 3. 8. A d ve rse E ve nts of S peci al I nterest
N ot a p plica ble.
8. 3. 8. 1. L ac k of Effic ac y
T he i n vesti gat or m ust re p ort si g ns, sy m pt o ms, a n d/ or cli nical se q uelae res ulti n g fr o m lac k of 
efficac y. Lac k of efficac y or fail ure of e x pecte d p har mac ol o gical acti o n is re p orta ble t o 
Pfizer Safet y  o nl y if ass oci ate d wit h a n S A E .  
8. 3. 9. Me dic al De vice Deficie ncies
N ot a p plica ble.
8. 3. 1 0. 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 st u d y 
i nter ve nti o n b y  t he wr o n g partici pa nt , 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.
E x p os ures t o t he st u d y i nter ve nti o n 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 Pfizer S afet y Wit hi n 
2 4 H o urs of A w are ness
Me dicati o n err 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
Me dicati o n err ors i ncl u de:

Me dicati o n err ors i n v ol vi n g partici pa nt e x p os ure t o t he st u d y i nter ve nti o n.

P ote ntial me dicati o n err ors or uses o utsi de of w hat is f oresee n i n t he pr ot oc ol t hat d o 
or d o n ot i n v ol ve t he st u d y partici pa nt .

T he a d mi nistrati o n of a n i nc orrect st u d y i nter ve nti o n.

T he a d mi nistrati o n of a n i nc orrect d osa ge.
S uc h me dicati o n err ors occ urri 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 wit hi n 2 4 h o urs .
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P F -0 7 0 3 8 1 2 4
Pr ot oc ol C 3 9 4 1 0 0 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 2 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 Marc h 2 0 2 1)
Pa ge 7 9
W het her or n ot t he me dicati o n err or is acc o m pa nie d b y  a n A E, as deter mi ne d b y t he 
i n vesti gat or, t he me dicati o n err or is rec or de d o n 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 nseri o us, are rec or de d o n t he A E pa ge of t he 
C R F.
Me 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 urs o n a C T S A E Re p ort 
F or m o nl y w he n ass oci ate d wit h a n S A E.
0 9 0 1 7 7 e 1 9 b b 9 c 5f d\ A p pr o v e d\ A p pr o v e d O n: 0 3- N o v- 2 0 2 2 1 1: 4 8 ( G M T)
C CI

P F -0 7 0 3 8 1 2 4
Pr ot oc ol C 3 9 4 1 0 0 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 2 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 Marc h 2 0 2 1)
Pa ge 8 0
8. 5. Ge netics
8. 5. 1. S pecifie d Ge netics
Ge netics (s pecifie d a nal yses) are n ot e val uate d i n t his st u d y .
8. 5. 2. Ret ai ne d Rese arc h S a m ples f or Ge netics
 
Retai ne d Researc h Sa m ples ma y  be use d f or researc h relate d t o t he st u d y i nter ve nti o n, A D, 
Ps O , a n d/ or relate d i nfla m mat or y diseases.
 
 
. Details o n pr ocesses f or 
c ollecti o n a n d s hi p me nt of t hese sa m ples ca n be f o u n d i n t he la b orat or y ma n ual.
8. 6. Bi o m ar kers
8. 6. 1. S pecifie d Ge ne E x pressi o n ( R N A) Rese arc h 
S pecifie d ge ne e x pressi o n ( R N A) researc h is n ot i ncl u de d i n t his st u d y.
8. 6. 2. S pecifie d Pr otei n Rese arc h
S pecifie d pr otei n researc h is i ncl u de d i n t his st u d y. T he sa m ples will be a nal yze d f or 
e x pl orat or y researc h. Details o n pr ocesses f or c ollecti o n a n d s hi p me nt of t hese sa m ples ca n 
be f o u n d i n t he lab orat or y  ma n ual.
S a m ples ma y be st ore d at a facility selecte d b y t he s p o ns or f or a ma xi m u m of 1 0 ye ars ( or 
acc or di n g t o l ocal re g ulati o ns) f oll o wi n g t he last partici pa nt’s last visit f or t he st u d y .
0 9 0 1 7 7 e 1 9 b b 9 c 5f d\ A p pr o v e d\ A p pr o v e d O n: 0 3- N o v- 2 0 2 2 1 1: 4 8 ( G M T)
C CI
C CI
C CI
C CI
C CI

P F -0 7 0 3 8 1 2 4
Pr ot oc ol C 3 9 4 1 0 0 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 2 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 Marc h 2 0 2 1)
Pa ge 8 1
8. 6. 3. S pecifie d Met a b ol o mic Rese arc h 
S pecifie d meta b ol o mic researc h is n ot i ncl u de d i n t his st u d y .
8. 6. 4. Ret ai ne d Rese arc h S a m ples f or Bi o m ar kers
T hese Retai ne d Researc h Sa m pl es will be c ollecte d i n t his st u d y:
 

A 6 -m L  w h ole bl o o d Pre p B 2. 5 o pti mize d f or ser u m;

A 6 -m L  w h ole bl o o d Pre p B 1. 5 o pti mize d f or plas ma.
Retai ne d Researc h Sa m ples will be c ollecte d as l ocal re g ulati o ns a n d IR B/ E Cs all o w
acc or di n g t o t he S o A .  
Retai ne d Researc h Sa m ples ma y  be use d f or researc h relate d t o t he st u d y i nter ve nti o n, A D, 
ps oriasis, a n d or relate d i nfla m mat or y diseases .
 
 
 Details o n pr ocesses f or 
c ollecti o n a n d s hi p me nt of t hese sa m ples ca n be f o u n d i n la b orat or y ma n ual. 
8. 7. I m m u n o ge nicit y Assess me nts
I m m u n o ge nicity assess me nts are n ot i ncl u de d i n t his st u d y.
8. 8. He alt h Ec o n o mics
Healt h ec o n o mics/m e dical res o urce u tilizati o n a n d h ealt h ec o n o mics para meters are n ot 
e val uate d i n t his st u d y.
0 9 0 1 7 7 e 1 9 b b 9 c 5f d\ A p pr o v e d\ A p pr o v e d O n: 0 3- N o v- 2 0 2 2 1 1: 4 8 ( G M T)
C CI
C CI
C CI
C CI

P F -0 7 0 3 8 1 2 4
Pr ot oc ol C 3 9 4 1 0 0 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 2 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 Marc h 2 0 2 1)
Pa ge 8 2
8. 9. B S A f or St u d y I nter ve nti o n Nee d ( Tre at a ble B S A) 
E val uati o n of % B S A f or st u d y  i nter ve nti o n nee d is t he t otal B S A acr oss all b o d y l ocati o ns 
bei n g treate d wit h t he st u d y  i nter ve nti o n. T he % B S A f or st u d y  i nter ve nti o n nee d e val uati o n 
met h o d will be t he sa me as t he B S A wit h A D or Ps O f or efficac y assess me nt.
P ost Da y  1, if a n y ne w A D or Ps O areas bec o me eli gi ble f or treat me nt, t h ose s h o ul d be 
i ncl u de d i n t he % B S A f or st u d y  i nter ve nti o n nee d. T he % B S A at s u bse q ue nt visits s h o ul d be 
e q ual t o or greater t ha n t he val ue at Da y  1.
8. 1 0. E x pl or at or y Assess me nts
8. 1 0. 1. T a pe Stri p S u b -st u d y
8. 1 0. 2. P h ot o gr a p h y S u b -st u d y
0 9 0 1 7 7 e 1 9 b b 9 c 5f d\ A p pr o v e d\ A p pr o v e d O n: 0 3- N o v- 2 0 2 2 1 1: 4 8 ( G M T)
C CI
C CI

P F -0 7 0 3 8 1 2 4
Pr ot oc ol C 3 9 4 1 0 0 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 2 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 Marc h 2 0 2 1)
Pa ge 8 3
9. S T A TI S TI C A L C O N SI D E R A TI O N 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 ollecte 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 S A P, w hic h will be mai ntai ne d by 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 pri mar y  e n d p oi nt defi niti o ns or t heir a nalys es will als o be reflecte d i n a 
pr ot oc ol a me n d me nt.
9. 1. St atistic al H y p ot heses
Statistical i nfere nce will b e ma de o n t he pri mar y e n d p oi nts: IG A /P G A res p o nse at W ee k 1 2. 
T he n ull h y p ot hesis is t hat t here is n o differe nce bet wee n eac h P F - 0 7 0 3 8 1 2 4 d ose le vel a n d 
t he ve hicle ar m f or eac h i n dicati o n. T he alter nati ve h yp ot hesis is t hat t he P F - 0 7 0 3 8 1 2 4 d ose 
le vel is su peri or t o t he ve hicle ar m f or eac h i n dicati o n. 
9. 1. 1. Esti m a n ds
9. 1. 1. 1. Pri m ar y Esti m a n d 
T he esti ma n d is defi ne d b y  t he f oll o wi n g attri b utes:
A t o pic D er m atitis:
Treat me nt c o n diti o n: recei ve d treat me nt: P F -0 7 0 3 8 1 2 4 oi nt me nt 0. 0 1 % , 0. 0 3 % or ve hicle, 
wit h o ut t he be nefit of a d diti o nal pr o hi bite d me dicati o ns a n d re gar dless of treat me nt 
c o m plia nce .
P o p ulati o n: Partici pa nts wit h mil d or m o derate A D as defi ne d b y t he i ncl usi o n a n d e xcl usi o n 
criteria.
Varia bles: Pr o p orti o n of partici pa nts ac hie vi n g I GA 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 Wee k 1 2 a n d ot her bi nar y e n d p oi nts.
Ps ori asis:
Treat me nt c o n diti o n: recei ve d treat me nt: P F -0 7 0 3 8 1 2 4 oi nt me nt 0. 0 1 % , 0. 0 3 % , 0. 0 6 % or 
ve hicle , wit h o ut t he be nefit of a d diti o nal pr o hi bite d me dicati o ns a n d re gar dless of treat me nt 
c o m plia nce .
P o p ulati o n : Partici pa nts wit h mil d, m o derate, or se vere Ps O as defi ne d b y t he i ncl usi o n a n d 
e xcl usi o n criteria.
Varia bles: Pr o p orti o n of partici pa nts wit h P G A sc ore 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 Wee k 1 2 a n d ot her bi nar y e n d p oi nts.
I nter-c urre nt E ve nts: A) Pr o hi bite d me dicati o n – res p o nse will be c o nsi dere d as fail ure f or 
ti me p oi nts after start date of t he e ve nt f or partici pa nts w h o recei ve pr o hi bite d me dicati o n 
p ost -ra n d o mizati o n. B) Wit h dra wal a n d all ot her e ve nts, e xce pt C O VI D-1 9 pa n de mic, 
lea di n g t o missi n g data will be treate d si milarl y ass u mi n g t hat partici pa nts n o l o n ger recei ve 
0 9 0 1 7 7 e 1 9 b b 9 c 5f d\ A p pr o v e d\ A p pr o v e d O n: 0 3- N o v- 2 0 2 2 1 1: 4 8 ( G M T)

P F -0 7 0 3 8 1 2 4
Pr ot oc ol C 3 9 4 1 0 0 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 2 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 Marc h 2 0 2 1)
Pa ge 8 4
be nefi t fr o m t he st u d y i nter ve nti o n a n d he nce will be c o nsi dere d as fail ure. C) C O VI D - 1 9 
pa n de mic: if a partici pa nt misses a visit d ue t o C O VI D -1 9, he/s he will be e xcl u de d fr o m t he 
a nal ys is f or t hat visit; If a partici pa nt disc o nti n ues treat me nt or wit h dra ws fr o m t he st u d y  d ue 
t o C O VID- 1 9, he/s he will be e xcl u de d fr o m t he a nal y ses after t he treat me nt disc o nti n uati o n 
visit or st u d y  wit h dra wal visit, res pecti vel y. D) I na de q uate c o m plia nce – partici pa nts data 
will be use d as r ec or de d. 
P o p ulati o n le vel s u m mar y: T he differe nce i n s uccess rates bet wee n eac h d ose le vel a n d 
ve hicle .
9. 1. 1. 2. Sec o n d ar y Esti m a n d
All bi nar y  sec o n dar y e n d p oi nts esti ma n ds are si milar t o t he pri mar y e n d p oi nt. 
T he c o nti n u o us e n d p oi nt esti ma n d is defi ne d b y t he f o ll o wi n g attri b utes:
A t o pic D er m atitis:
Treat me nt c o n diti o n: recei ve d treat me nt: P F- 0 7 0 3 8 1 2 4 oi nt me nt 0. 0 1 %, 0. 0 3 % or ve hicle, 
wit h o ut t he be nefit of a d diti o nal pr o hi bite d me dicati o ns a n d re gar dless of treat me nt 
c o m plia nce. 
P o p ulati o n: Partici pa nts wit h mi l d or m o derate A D as defi ne d b y i ncl usi o n a n d e xcl usi o n 
criteria.
Varia bles: Perce nt c ha n ge fr o m baseli ne i n E A SI  t otal sc ore at all st u d y visit ti me p oi nts 
s pecifie d i n S o A . 
Ps ori asis:
Treat me nt c o n diti o n: recei ve d treat me nt: P F- 0 7 0 3 8 1 2 4 oi nt me nt 0. 0 1 %, 0. 0 3 %, 0. 0 6 % or 
ve hicle, wit h o ut t he be nefit of a d diti o nal pr o hi bite d me dicati o ns a n d re gar dless of treat me nt 
c o m plia nce. 
P o p ulati o n: Partici pa nts wit h mil d , m o derate, or se vere Ps O as defi ne d b y t he i ncl usi o n a n d 
e xcl usi o n criteria.
Varia bles: C ha n ge fr o m baseli ne i n P A SI  t otal sc ore at all st u d y visit ti me p oi nts s pecifie d i n 
S o A .
I nterc urre nt e ve nts: A) Pr o hi bite d me dicati o n – all sc ores meas ur e d at ti me p oi nts after start 
date of t he e ve nt f or partici pa nts w h o recei ve pr o hi bite d me dicati o n p ost ra n d o mizati o n will 
be e xcl u de d fr o m t he a nal ysis a n d treate d as missi n g sc ores. Missi n g sc ores will be i m p ute d 
base d o n t he ass u m pti o n t hat partici pa nts d o n ot be nefit fr o m t he I P treat me nt. 
B) Wit h dra wal a n d all ot her e ve nts lea di n g t o missi n g data, e xce pt C O VI D -1 9 pa n de mic, 
will be treate d si milarl y ass u mi n g partici pa nts ha ve efficac y val ues si milar t o c o ntr ol 
partici pa nts. C ) C O VI D-1 9 pa n de mic: if a pa rtici pa nt misses a visit d ue t o C O VI D- 1 9, 
0 9 0 1 7 7 e 1 9 b b 9 c 5f d\ A p pr o v e d\ A p pr o v e d O n: 0 3- N o v- 2 0 2 2 1 1: 4 8 ( G M T)

P F -0 7 0 3 8 1 2 4
Pr ot oc ol C 3 9 4 1 0 0 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 2 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 Marc h 2 0 2 1)
Pa ge 8 5
he/s he will be e xcl u de d fr o m t he a nal ys is f or t hat visit; If a partici pa nt disc o nti n ues treat me nt 
or wit h dra ws fr o m t he st u d y d ue t o C O VI D - 1 9, he/s he will be e xcl u de d fr o m t he a nalys es 
after t he treat me nt disc o nti n uati o n visit or st u d y  wit h dra wal visit, res pecti vel y. D) I na de q uate 
c o m plia nce – partici pa nts data will be use d as rec or de d.
P o p ulati o n -le vel s u m mar y: T he mea n differe nce bet wee n eac h d ose le vel a n d ve hicle.
9. 1. 2. M ulti plicit y A dj ust me nt
F or eac h i n dicati o n, t he o verall fa mily wise T y p e I err or rate will be c o ntr olle d at t he 1 -si de d 
0. 0 2 5 le vel usi n g t he H oc h ber g ste p u p pr oce d ure.
9. 2. A n al ysis Sets
F or p ur p oses of a nal y sis, t he f oll o wi n g a nal ys is sets are defi ne d:
P artici p a nt A n al ysis Set
Descri pti o n
F ull A nal ysis Set 
All partici pa nts ra n d o ml y assi g ne d t o st u d y i nter ve nti o n w h o ta ke at least 
1 d ose of st u d y i nter ve nti o n.
Safet y A nal ysis Set
All partici pa nts ra n d o ml y assi g ne d t o st u d y i nter ve nti o n w h o ta ke at least 
1 d ose of st u d y i nter ve nti o n. Partici pa nts will be a nal yze d acc or di n g t o 
t he pr o d uct t he y act uall y recei ve d.
Defi ne d A n al ysis Set
Descri pti o n
9. 3. St atistic al A n al yses
T he S A P will be de vel o pe d a n d fi nalize d bef ore a n y a nalys es are p erf or me d a n d will 
descri be t he a nal ys es a n d pr oce d ures f or acc o u nti n g f or missi n g, u n use d, a n d s p uri o us data.
T his secti o n is a s u m mar y of t he pla n ne d statistical a nal yses of t he pri mar y  a n d sec o n dar y 
e n d p oi nts.
9. 3. 1. Ge ner a l Co nsi der ati o ns
I n dicati o n will be s u m marize d se parately b y treat me nt. 
9. 3. 2. A n al yses f or Bi n ar y E n d p oi nts
A nal y sis of pri mar y bi nar y e n d p oi nts is s pecifie d i n Secti o n 9. 3. 4 . Ot her bi nar y e n d p oi nts at 
ti me p oi nts s pecifie d i n t he S o A will be a nal yz e d si milarly. N o a dj ust me nts f or m ulti plicit y  
will be ma de f or t hese e n d p oi nts.
0 9 0 1 7 7 e 1 9 b b 9 c 5f d\ A p pr o v e d\ A p pr o v e d O n: 0 3- N o v- 2 0 2 2 1 1: 4 8 ( G M T)
C CI

P F -0 7 0 3 8 1 2 4
Pr ot oc ol C 3 9 4 1 0 0 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 2 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 Marc h 2 0 2 1)
Pa ge 8 6
9. 3. 3. A n al yses f or C o nti n u o us E n d p oi nts
A nal y sis of sec o n dar y c o nti n u o us e n d p oi nts is s pecifie d i n Secti o n 9. 3. 5 . Ot her c o nti n u o us 
e n d p oi nts at ti me p oi nts s pecifie d i n t he S o A will be a nal yz e d descri pti vel y wit h n o 
i m p utati o n. N o a dj ust me nts f or m ulti plicit y will be ma de f or t hese e n d p oi nts.
9. 3. 4. Pri m ar y E n d p oi nt(s) / Esti m a n d(s) A n al ysis
A la n d mar k a nal y sis of t he c o m p osite IG A/ P G A s uccess e n d p oi nts at W ee k 1 2, defi ne d i n 
S ecti o n 9. 1. 1. 1 , will be perf or me d usi n g t he f ull a nal ysis set. T he pr o p orti o ns res p o n di n g a n d 
t he c orres p o n di n g ris k differe nce c o m pari n g acti ve treat me nt ar m t o ve hicle gr o u p will be 
a nal yz e d usi n g t he u nc o n diti o nal e xact met h o d; t he ris k differe nces a n d t he c orres p o n di n g 
2-si de d u nc o n diti o nal e xact 9 5 % c o nfi de nce i nter vals will be c o m p ute d usi n g C ha n a n d 
Z ha n g ( 1 9 9 9) 1 4 met h o d. T he o verall fa mil y  wise T ype I err or rate will be c ontr olle d at t he 
1- side d 0. 0 2 5 le vel usi n g t he H oc h ber g ste p u p pr oce d ure.
I n a d diti o n, Ema x or ot her a p p r o priate m o del s ma y  be use d t o c haracterize t he d ose res p o nse 
relati o ns hi p. Details of t he d ose res p o nse m o del will be descri be d i n t he S A P.
9. 3. 5. Sec o n d ar y E n d p oi nt(s )/ Esti m a n d(s) A n al ysis
Bi nar y  sec o n dar y e n d p oi nts will be a nal yze d si milarly t o t he pri mar y  e n d p oi nts. 
A la n d mar k a nal y sis of c o nti n u o us e n d p oi nts i ncl u di n g perce nt c ha n ge fr o m baseli ne i n 
E A SI  a n d c ha n ge fr o m baseli ne i n P A SI  at W ee k 1 2, defi ne d i n S ecti o n 9. 1. 1. 2 . will be 
perf or me d b y A N C O V A usi n g t he f ull a nal y sis set wit h baseli ne as a c o variate . Missi n g data, 
e xce pt missi n g d ue t o C O VI D -1 9 pa n de mic, will be i m p ute d usi n g a c o ntr ol -base d met h o d, 
ass u mi n g partici pa nts ha ve efficac y val ues si milar t o ve hicle partici pa nts , a n d data are M A R . 
T he i m p utati o n will utilize A N C O V A m o del i ncl u di n g baseli ne as a c o variate . T he a nal y sis 
will c o m bi ne t he res ults fr o m t he m ulti ple i m p utati o ns usi n g R u bi n’s r ule’s as i m ple me nt e d 
i n S A S P R O C MIA N A L Y Z E. M M R M m o dels ma y  als o be use d o n o bser ve d data at all ti me 
p oi nts as se nsiti vit y a nal yses. T he fi xe d effects of treat me nt, visit, a n d treat me nt b y visit 
i nteracti o n will be i ncl u de d. Baseli ne val ue will be i ncl u de d as a c o variate. N o a dj ust me nts 
f or m ulti plicit y will be ma de.
9. 3. 6. Terti ar y/ E x pl or at or y E n d p oi nt(s)
Tertiar y  a n d ex pl orat or y  e n d p oi nts will be a nal y ze d descri pti vel y.
 
 
 
9. 3. 7. S afet y A n al yses
T he safet y data will be s u m marize d i n acc or da nce wit h Pfizer Data Sta n dar ds. All safet y 
a nal ys es will be perf or me d o n t he safet y  p o p ulati o n. Safety e n d p oi nts i ncl u de I nci de nce of 
treat me nt e mer ge nt A Es a n d S A Es, cli nicall y si g nifica nt c ha n ges i n vital si g ns, E C G, a n d 
la b orat or y tests.
0 9 0 1 7 7 e 1 9 b b 9 c 5f d\ A p pr o v e d\ A p pr o v e d O n: 0 3- N o v- 2 0 2 2 1 1: 4 8 ( G M T)
C CI

P F -0 7 0 3 8 1 2 4
Pr ot oc ol C 3 9 4 1 0 0 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 2 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 Marc h 2 0 2 1)
Pa ge 8 7
9. 3. 7. 1. Electr oc ar di o gr a m A n al yses
C ha n ges fr o m baseli ne f or t he E C G para meters Q T i nter val, heart rate, Q Tc i nter val, P R 
i nter val, a n d Q R S c o m ple x will be s u m marize d b y treat me nt a n d ti me.
T he n u m ber ( %) of partici pa nt s wit h ma xi m u m p ost-d ose Q Tc val ues a n d ma xi m u m 
i ncreases fr o m baseli ne i n t he f oll o wi n g cate g ories will be ta b ulate d b y treat me nt: 
S afet y Q Tc Assess me nt
De gree of Pr ol o n g ati o n
Mil d
( msec)
M o der ate
( msec)
Se vere ( m sec)
A bs ol ute val ue
> 4 5 0 -4 8 0
> 4 8 0 -5 0 0
> 5 0 0
I ncrease fr o m b aseli ne
3 0 -6 0
> 6 0
9. 3. 8. Ot her A n al yses
 data fr o m Retai ne d Researc h Sa m ples ma y be c ollecte d 
d uri n g or after t he trial a n d retai ne d f or f ut ure a nal yses; t he res ults of s uc h a nal ys es are n ot 
pla n ne d t o be i ncl u de d i n t he C S R. 
9. 3. 8. 2. I nteri m A n al yses
A n i nteri m a nal ys is ma y  be perf or me d t o assess efficac y a n d safet y w he n a p pr o xi matel y
6 0 % of t he pla n ne d partici pa nts, ie, a p pr o xi matel y  2 5 partici pa nts per ar m i n A D a n d 
1 8 partici pa nts per ar m i n Ps O ha ve c o m pleted or ha d t he c ha nce t o c o m plete W ee k 8 visit . 
I nteri m a nalys is res ults ma y be use d f or decisi o ns re gar di n g st o p pi n g f or f utilit y a n d i nter nal 
pr o gra m de vel o p me nt . A d diti o nal i nteri m a nal ysis ma y  be perf or me d a n d will be detaile d i n 
t he IR C c harter. 
Bef ore a n y i nteri m a nal ysis is perf or me d , t he details of t he o bjecti ves, decisi o n criteria,
disse mi nati o n pla n , a n d met h o d of mai ntai ni n g t he st u d y  bli n d as per Pfizer’s S O Ps will be 
d oc u me nte d a n d a p pr o ve d i n a n I RC c harter . In a d diti o n, t he a nal ysis details will be 
d oc u me nte d a n d a p pr o ve d i n t he S A P.
9. 4. S a m ple Size Deter mi n ati o n
9. 4. 1. S a m ple Size Deter mi n ati o n f or A D
A s ufficie nt n u m ber of partici pa nts will be scree ne d t o ac hie ve a p pr o xi matel y 
1 2 0 partici pa nts ra n d o ml y  assi g ne d t o st u d y i nter ve nti o n. T he sa m ple size calc ulati o n is 
base d o n t he pri mar y  efficac y esti ma n d I G A s uccess at Wee k 1 2. Ass u mi n g 1 5 % I G A 
0 9 0 1 7 7 e 1 9 b b 9 c 5f d\ A p pr o v e d\ A p pr o v e d O n: 0 3- N o v- 2 0 2 2 1 1: 4 8 ( G M T)
C CI
C CI

P F -0 7 0 3 8 1 2 4
Pr ot oc ol C 3 9 4 1 0 0 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 2 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 Marc h 2 0 2 1)
Pa ge 8 8
s uccess rate f or t he ve hicle ar m, a sa m ple size of 4 0 per ar m will ha ve 8 9 % p o wer t o detect a 
treat me nt differe nce of 3 5 % u n der a 1- si de d T y pe 1 err or 0. 0 1 2 5 f or eac h of t he 2 d ose le vels 
c o m paris o n t o ve hicle b y t he u nc o n diti o nal e xact test , wit h a n overall T y pe 1 err or 
0. 0 2 5 1 -si de d. I n a d diti o n, t his sa m ple size will pr o vi de 96 % p o wer t o detect a 
4 2 % differe nce i n E A SI -7 5 bet wee n a n acti ve ar m (6 2 % E A SI -7 5) a n d ve hicle 
( 2 0 % E A SI -7 5).
9. 4. 2. S a m ple Size Deter mi n ati o n f or Ps O
A s ufficie nt n u m ber of partici pa nts will be s cree ne d t o ac hie ve a p pr o xi matel y  
1 2 0 partici pa nts ra n d o ml y  assi g ne d t o st u d y i nter ve nti o n. T he sa m ple size calc ulati o n is 
base d o n t he pri mar y  efficac y esti ma n d P G A s uccess at Wee k 1 2. Ass u mi n g 8 % P G A 
s uccess rate f or t he ve hicle ar m, a sa m ple size of 3 0 per ar m will ha ve 9 2 % p o wer t o detect a 
treat me nt differe nce of 4 2 % u n der a 1- si de d T y pe 1 err or 0. 0 0 8 f or eac h of t he t hree d ose 
le vels c o m paris o n t o ve hicle b y t he u nc o n diti o nal e xact test, wit h a n overall T y pe 1 err or 
0. 0 2 5 1 -si de d. I n a d diti o n, t his sa m ple size will pr o vi de 96 % p o wer t o detect a 
4 4 % differe nce i n P A SI -7 5 bet wee n a n acti ve ar m ( 5 0 % P A SI -7 5) a n d ve hicle 
( 6 % P A SI -7 5).
0 9 0 1 7 7 e 1 9 b b 9 c 5f d\ A p pr o v e d\ A p pr o v e d O n: 0 3- N o v- 2 0 2 2 1 1: 4 8 ( G M T)

P F -0 7 0 3 8 1 2 4
Pr ot oc ol C 3 9 4 1 0 0 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 2 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 Marc h 2 0 2 1)
Pa ge 8 9
1 0. S U P P O R TI N G D O C U M E N T A TI O N A N D O P E R A TI O N A L C O N SI D E R A TI O N S
1 0. 1. A p pe n di x 1: Re g ul at or y, Et hic al, a n d St u d y O v ersi g ht C o nsi der ati o ns
1 0. 1. 1. Re g ul at or y a n d Et hic al C o nsi der ati o ns
T his 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 a n d wit h t he f oll o wi n g:

C o nse ns us et hical pri nci ples deri ve d fr o m i nter nati o nal g ui deli nes , i ncl u di n g t he 
Declarati o n of Helsi n ki a n d CI O M S I nter nati o nal Et hical G ui deli nes ;

A p plica ble I C H G C P g ui deli nes ;

A p plica ble la ws a n d re g ulati o ns , i ncl u di n g a p plica ble pri vac y la ws.
T he pr ot oc ol, pr ot oc ol a me n d me nts, IC D, S R S D(s) , a n d ot her rele va nt d oc u me nts 
(e g, a d vertise me nts) m ust be re vie we d a n d a p pr o ve d b y t he s p o ns or, s u b mitte d t o a n IR B/ E C 
b y  t he i n vesti gat or, a n d re vie we d a n d a p pr o ve d b y  t he I R B/ E C bef ore t he st u d y is i nitiate d.
A n y  a me n d me nts t o t he pr ot oc ol will re q uire I R B/ E C a p pr o val bef ore i m ple me ntati o n of 
c ha n ges ma de t o t he st u d y desi g n, e xce pt f or c ha n ges necessar y  t o eli mi nate a n i m me diate 
hazar d t o st u d y  partici pa nts.
Pr ot oc ols a n d a n y s u bsta ntial a me n d me nts t o t he pr ot oc ol will re q uire healt h a ut h orit y  
a p pr o val pri or t o i nitiati o n e xce pt f or c ha n ges necessar y  t o eli mi nate a n i m me diate hazar d t o 
st u d y partici pa nts.
T he i n vesti gat or will be res p o nsi ble f or t he f oll o wi n g:

Pr o vi di n g writte n s u m maries of t he stat us of t he st u d y  t o t he I R B/ E C a n n uall y or 
m ore fre q ue ntl y  i n acc or da nce wit h t he re q uire me nts, p olicies, a n d pr oce d ures 
establis he d b y t he I R B/ E C ;

N otif y i n g t he I R B/ E C of S A Es or ot her si g nifica nt safety fi n di n gs as re q uire d b y 
I RB/ E C pr oce d ures ;

Pr o vi di n g o versi g ht of t he c o n d uct of t he st u d y at t he site a n d a d here nce t o 
re q uire me nts of 2 1 C F R, I C H G C P g ui deli nes, t he I R B/ E C, E ur o pea n re g ulati o n 
5 3 6/ 2 0 1 4 f or cli nical st u dies (if a p plica ble), E ur o pea n Me dical De vice Re g ulati o n 
2 0 1 7/ 7 4 5 f or cli nical de vice researc h (if a p plica ble), a n d all ot her a p plica ble l ocal 
re g ulati o ns;

F or re p orti n g cases of s us pecte d c hil d a b use a n d/ or ne g lect acc or di n g t o l ocal me dical 
ass ociati o n (e g, A A P) or healt h de part me nt g ui deli nes.
0 9 0 1 7 7 e 1 9 b b 9 c 5f d\ A p pr o v e d\ A p pr o v e d O n: 0 3- N o v- 2 0 2 2 1 1: 4 8 ( G M T)

P F -0 7 0 3 8 1 2 4
Pr ot oc ol C 3 9 4 1 0 0 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 2 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 Marc h 2 0 2 1)
Pa ge 9 0
1 0. 1. 1. 1. Re p orti n g of S afet y Iss ues a n d Seri o us Bre a c hes of t he Pr ot oc ol or I C H G C P
I n t he e ve nt of a ny 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 
reg 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 a n d ris ks of t he st u d y 
i nter ve nti o n, Pfizer s h o ul d be i nf or me d i m me diatel y. 
I n a d diti o n, t he i n vesti gator will i nf or m Pfizer i m me diatel y  of a n y ur ge nt safety meas ures 
ta ke n by t he i n vesti gat or t o pr otect t he st u d y partici pa nt s a gai nst 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 t he I C H G C P g ui deli nes t hat t he i n vesti gat or 
bec o me s a ware of.
1 0. 1. 2. Fi n a nci al Discl os ure
I n vesti gat ors a n d s u b-i n vesti gat ors will pr o vi de t he s p o ns or wit h s ufficie nt, acc urate 
fi na ncial i nf or mati o n as re q ueste d t o all o w t he s p o ns or t o s u b mit c o m plete a n d acc urate 
fi na ncial certificati o n or discl os ure state me nts t o t he a p pr o priate re g ulat or y a ut h orities.
I n vesti gat ors are res p o nsi ble f or pr o vi di n g i nf or mati o n o n fi na ncial i nterests d uri n g t he 
c o urse of t he st u d y a n d f or 1 year after c o m pleti o n of t he st u d y.
1 0. 1. 3. I nf or me d C o nse nt/ asse nt Pr ocess
T he i n vesti gat or or his / her re prese ntati ve will e x plai n t he nat ure of t he st u d y t o t he 
partici pa nt a n d his/ her pare nt(s)/le gal g uar dia n a n d a ns wer all q uesti o ns re gar di n g t he st u d y . 
T he partici pa nt a n d his/ her pare nt(s)/le gal g uar dia n s h o ul d be gi ve n s ufficie nt ti me a n d 
o p p ort u n it y t o as k q uesti o ns a n d t o deci de w het her or n ot t o partici pate i n t he trial. 
W he n c o nse nt is o btai ne d fr o m a partici pa nt’s pare nt(s)/le gal g uar dia n, t he partici pa nt’s 
asse nt (affir mati ve a gree me nt) m ust be s u bse q ue ntl y o btai ne d w he n t he partici pa nt has t he 
ca pacit y t o pr o vi de asse nt, as deter mi ne d b y t he I R B/ E C. If t he i n vesti gat or deter mi nes t hat a 
partici pa nt’s decisi o nal ca pacit y is s o li mite d he/s he ca n n ot reas o na bl y be c o ns ulte d, t he n, as 
per mitte d b y  t he I RB/ E C a n d c o nsiste nt wit h l ocal re g ulat or y  a n d le gal re q uire me nts, t he 
partici pa nt’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 partici pa nt d oes n ot pr o vi de his or her o w n asse nt, t he s o urce 
d oc u me nts m ust rec or d w h y  t he partici pa nt di d n ot pro vi de asse nt (f or e xa m ple, mi n or c hil d), 
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 partici pa nt’s 
pare nt(s)/le gal g uar dia n, t he c o nse nt si g ner’s relati o ns hi p t o t he st u d y  partici pa nt, a n d t hat 
t he partici pa nt’s asse nt was obtai 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 st u d y partici pa nts are mi n ors w h o reac h t he a ge of maj ority 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 be rec o nse nte d as a d ults t o 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 I RB/ 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 le gall y a ut h orize d 
re prese ntati ve. 
0 9 0 1 7 7 e 1 9 b b 9 c 5f d\ A p pr o v e d\ A p pr o v e d O n: 0 3- N o v- 2 0 2 2 1 1: 4 8 ( G M T)

P F -0 7 0 3 8 1 2 4
Pr ot oc ol C 3 9 4 1 0 0 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 2 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 Marc h 2 0 2 1)
Pa ge 9 1
Partici pa nts a n d t heir pare nt(s)/le gal g uar dia n m ust be i nf or me d t hat t heir partici pati o n is 
v ol u ntar y . Partici pa nt’s pare nt(s)/le gal g uar dia n will be re q uire d t o si g n a state me nt of 
i nf or me d c o nse nt t hat meets t he re q uire me nts of 2 1 C F R 5 0, l ocal re g ulati o ns, IC H 
g ui deli nes, HI P A A re q ui re me nts, w here a p plica ble, a n d t he I R B/ E C or st u d y ce nter. 
T he i n vesti gat or m ust e ns ure t hat eac h st u d y  partici pa nt’s pare nt(s)/le gal g uar dia n a n d t he 
st u d y partici pa nt as a p plica ble 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 relate d 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 partici pa nt’s pers o nal data.  
T he partici pa nt’s pare nt(s)/le gal g uar dia n m ust be i nf or me d t hat t he partici pa nt’s pers o nal 
st u d y-relate d data will be use d b y t he s p o ns or i n acc or da nce wit h l ocal data pr otecti o n la w. 
T he le vel of discl os ure m ust als o be e x plai ne d t o t he partici pa nt’s pare nt(s)/le gal g uar dia n. 
T he partici pa nt’s pare nt(s)/le gal g uar dia n m ust be i nf or me d t hat t he partici pa nt’s me dical 
rec or ds ma y be e xa mi ne d b y Cli nical Q uality Ass ura nce a u dit ors or ot her a ut h orize d 
pers o n nel a p p oi nte d b y t he s p o ns or, b y a p pr o priate I R B/ E C me m bers, a n d b y  i ns pect ors 
fr o m re g ulat or y a ut h orities. 
T he i n vesti gat or f urt her m ust e ns ure t hat eac h st u d y  partici pa nt’s pare nt(s)/le gal g uar dia n 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 c hil d’s 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 c hil d’s pers o nal data kee pi n g i n mi n d t he 
pri vac y  ri g hts t hat ma y restrict access of ol der a d olesce nts me dical rec or ds b y t heir 
pare nt(s)/le gal g uar dia n i n certai n re gi o ns .
T he s o urce d oc u me ntati o n m ust i ncl u de a state me nt t hat writte n i nf or me d c o nse nt a n d as 
a p plica ble, asse nt, was o btai ne d bef ore t he partici pa nt was e nr olle d i n t he st u d y  a n d t he date 
t he writte n c o nse nt/asse nt was o btai ne d. T he a ut h orize d pers o n o btai ni n g t he i nf or me d 
c o nse nt m ust als o si g n t he IC D. 
Pare nt(s)/le gal g uar dia n a n d t he partici pa nt m ust be rec o nse nte d t o t he m o st c urre nt versi o n 
of t he I C D(s)/asse nt d uri n g t heir partici pati o n i n t he st u d y . 
A c o p y of t he I C D(s) a n d asse nt, if writte n, m ust be pr o vi de d t o t he pare nt(s)/le gal g uar dia n 
a n d t he partici pa nt. 
Partici pa nts w h o are rescree ne d are re q uire d t o si g n a ne w I CD.
1 0. 1. 4. D at a Pr otecti o n
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 partici pa nt data.
Partici pa nts’ 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 otecte 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 ha 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 
0 9 0 1 7 7 e 1 9 b b 9 c 5f d\ A p pr o v e d\ A p pr o v e d O n: 0 3- N o v- 2 0 2 2 1 1: 4 8 ( G M T)

P F -0 7 0 3 8 1 2 4
Pr ot oc ol C 3 9 4 1 0 0 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 2 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 Marc h 2 0 2 1)
Pa ge 9 2
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 site will be res p o nsi ble f or 
deter mi ni n g w het 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 partici pa nts wit h re gar d t o t he pr ocessi n g of pers o nal 
data, partici pa nts will be assi g ne d a si n gle, partici pa nt -s pecific n u merical c o de. A n y 
partici pa nt rec or ds or data sets t hat are tra nsferre d t o t he s p o ns or will c o ntai n t he n u merical 
c o de; partici pa nt na mes will n ot be tra nsferre d. All ot her i de ntifia ble data tra nsferre d t o t he 
s p o ns or will be i de ntifie d b y t his si n gle, partici pa nt -s pecific c o de. T he st u d y site will 
ma i ntai n a c o nfi de ntial list of partici pa nt s w h o partici pate d i n t he st u d y, li n ki n g eac h 
partici pa nt ’s n u merical c o de t o his or her act ual i de ntit y a n d me dical rec or d I D. I n case of 
data tra nsfer, t he s p o ns or will pr otect t he c o nfi de ntialit y  of partici pa nt s’ pers o nal data 
c o nsiste nt wit h t he cli nical st u d y agree me nt a n d a p plica ble pri vac y  la ws.
1 0. 1. 5. C o m mittees Str uct ure
1 0. 1. 5. 1. D at a M o nit ori n g C o m mittee 
T his st u d y  will use a n I R C. T he IR C is i n de pe n de nt of t he st u d y tea m a n d i ncl u des o nl y  
i nter nal me m bers. T he I R C c harte r descri bes t he r ole of t he I R C i n m ore detail.
T he I R 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  a n d safet y of partici pa nts 
i n t he st u d y acc or di n g t o t he c harter. T he rec o m me n dati o ns ma de b y  t he I R C will be 
f or war de d t o t he a p pr o priate a ut h orize d Pfizer pers o n nel f or re view a n d fi nal decisi o n. Pfizer 
will c o m m u nicate 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 nalys es of 
e n d p oi nt e ve nts a n d of safet y data t hat are n ot e n d p oi nts, t o re g ulat or y a ut h orities, 
i n vesti gat ors, as a ppr o priate. 
T his st u d y  will n ot use a D M C.
1 0. 1. 6. Disse mi n ati o n of Cli nic al St u d y D at a
Pfizer f ulfills its c o m mit me nt t o p u blicl y  discl ose cli nical st u d y 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 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 wit h a p plica ble l ocal 
la ws/re g ulati o ns. I n a d diti o n, Pfizer re p orts st u d y res ults o utsi de of t he re q uire me nts of l ocal 
la ws/re g ulati o ns p urs ua nt t o its S O Ps.
I n all cases, st u dy res ults are r e 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 .cli nicaltrials. g o v
Pfizer p osts cli nical trial 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 safet y a n d/ or efficac y of a 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. T hese r es ults are 
s u b mitte d f or p ostin g i n acc or da nce wit h t he f or mat a n d ti meli nes set f ort h b y U S la w.
0 9 0 1 7 7 e 1 9 b b 9 c 5f d\ A p pr o v e d\ A p pr o v e d O n: 0 3- N o v- 2 0 2 2 1 1: 4 8 ( G M T)

P F -0 7 0 3 8 1 2 4
Pr ot oc ol C 3 9 4 1 0 0 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 2 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 Marc h 2 0 2 1)
Pa ge 9 3
E u dra C T
Pfizer p osts cli nical trial res ults o n E u dra C T f or Pfizer -s p o ns ore d i nter ve nti o nal st u dies i n 
acc or da nce wit h t he f or mat a n d ti meli nes set f ort h b y  E U re q uire me nts.
w w w . pfizer.c o m
Pfizer p osts p u blic discl os ure s y n o pses ( C S R s y n o pses i n w hic h a n y data t hat c o ul d be use d 
t o i de ntif y i n di vi d ual partici pa nts ha ve 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 ti me t he c orres p o n di n g st u d y res ults are
p oste d t o w w w.cli nicaltrials. g o v .
D oc u me nts wit hi n mar keti n g a ut h orizati o n pac ka ges/s u b missi o ns
Pfizer c o m plies wit h t he E ur o pea n U ni o n P olic y  0 0 7 0, t he pr oacti ve p u blicati o n of cli nical 
data t o t he E M A we bsite. Cli nical data, u n der P hase 1 of t his p o lic y, i ncl u des cli nical 
o ver vie ws, cli nical s u m maries, C S Rs, a n d a p pe n dices c o ntai ni n g t he pr ot oc ol a n d pr ot oc ol 
a me n d me nts, sa m ple C R Fs, a n d statistical met h o ds. Cli nical data, u n der P hase 2 of t his 
p olic y , i ncl u des t he p u blis hi n g of i n di vi d ual partici pa nt data. P olic y 0 0 7 0 a p plies t o ne w 
mar keti n g a ut h orizati o n a p plicati o ns s u b mitte d via t he ce ntralize d pr oce d ure si nce 
0 1 Ja n uar y 2 0 1 5 a n d a p plicati o ns f or li ne e xte nsi o ns a n d f or ne w i n dicati o ns s u b mitte d via 
t he ce ntralize d pr oce d ure si nce 0 1 J ul y 2 0 1 5.
D ata shari n g
Pfizer pr o vi des researc hers sec ure access t o patie nt- le vel data or f ull C S Rs f or t he p ur p oses 
of “ b o na -fi de scie ntific researc h” t hat c o ntri b utes t o t he scie ntific u n dersta n di n g of t he 
disease, tar get, or c o m p o u n d class. Pfizer will ma ke data f r o m t hese trials a vaila ble 
2 4 m o nt hs after st u d y  c o m pleti o n. Patie nt-le vel data will be a n o ny m ize d i n acc or da nce wit h 
a p plica ble pri vac y la ws a n d re g ulati o ns. C S Rs will ha ve pers o nall y i de ntifia ble i nf or mati o n 
re dacte d.
Data re q uests are c o nsi dere d fr o m q ualifie d researc hers wit h t he a p pr o priate c o m pete ncies t o 
perf or m t he pr o p ose d a nal y ses. Researc h tea ms m ust i ncl u de a bi ostatisticia n. Data will n ot 
be pr o vi de d t o a p plica nts wit h si g nifica nt c o nflicts of i nterest, i ncl u di n g i n di vi d uals 
re q uesti n g access f or c o m mercial/c o m petiti ve or le gal p ur p oses.
1 0. 1. 7. D at a Q u alit y Ass ur a nce
All partici pa nt data relati n g t o t he st u d y will be rec or de d o n pri nte d or electr o nic C R F u nless 
tra nsmitt e d t o t he s p o ns or or desi g nee electr o nicall y  (e g, la b orat or y data). T he i n vesti gat or is 
res p o nsi ble f or verif yi n g t hat data e ntries are acc urate a n d c orrect b y p h ysicall y or 
electr o nicall y si g ni n g t he C R F.
G ui da nce o n c o m pleti o n of C R Fs will be pr o vi de d i n t he C R F C o m pleti o n Re q uire me nts 
d oc u me nt .
0 9 0 1 7 7 e 1 9 b b 9 c 5f d\ A p pr o v e d\ A p pr o v e d O n: 0 3- N o v- 2 0 2 2 1 1: 4 8 ( G M T)

P F -0 7 0 3 8 1 2 4
Pr ot oc ol C 3 9 4 1 0 0 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 2 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 Marc h 2 0 2 1)
Pa ge 9 4
T he i n vesti gat or m ust e ns ure t hat t he C R Fs 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 are 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 ve nt access b y u na ut h orize d t hir d parties.
Q T L s are pre defi ne d para meters t hat are m o nit ore d d uri n g t he st u d y . I m p orta nt de viati o ns 
fr o m t he Q T Ls a n d a n y re me dial acti o ns ta ke n will be s u m marize d i n t he cli nical st u d y 
re p ort.
T he i n vesti gat or m ust per mit st u d y -relate d m o nit ori n g, a u dits, I R B/ E C re vie w, a n d 
re g ulat or y a ge nc y i ns pecti o ns a n d pr o vi de direct access t o s o urce data d oc u me nts. T his 
verificati o n ma y  als o occ ur after st u d y c o m pleti o n. 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 vaila ble d uri n g t he m o nit 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.
M o nit ori n g details descri bi n g strate g y , i ncl u di n g defi niti o n of st u d y critical data ite ms a n d 
pr ocesses (e g, -ris k base d i nitiati ves i n o perati o ns a n d q ualit y s uc h as ris k m a na ge me nt a n d 
m iti gati o n strate gies a n d anal yt ical -ris k base d m o nit ori n g), met h o ds, res p o nsi bilities , a n d 
re q uire me nts, i ncl u di n g ha n dli n g of n o nc o m plia nce iss ues a n d m o nit ori n g tec h ni q ues 
(ce ntral, virt ual , or o n-site m o nit ori n g), are pr o vi de d i n t he data ma na ge me nt pla n a n d 
m o nit ori n g p la n mai ntai ne d a n d util ize d b y t he s p o ns or or desi g nee.
T he s p o ns or or desi g nee is res p o nsi ble f or t he data ma na ge me nt of t his st u d y , i ncl u di n g 
q ualit y  c hec ki n g of t he data.
Rec or ds a n d d oc u me nts, i ncl u di n g si g ne d I C D s, pertai ni n g t o t he c o n d uct of t his st u d y m ust 
be retai ne d b y t he i n vesti gat or f or 1 5 ye ars after st u d y c o m pleti o n u nless l ocal re g ulati o ns or 
i nstit uti o nal p olicies re q uire a l o n ger rete nti o n peri o d. N o rec or ds ma y be destr o ye d d uri n g 
t he rete nti o n peri od wit h o ut t he writte n a p pr o val of t he s p o ns or. N o rec or ds ma y  be 
tra nsferre d t o a n ot her l ocati o n or part y wit h o ut writte n n otificati o n t o t he s p o ns or. T he 
i n vesti gat or m ust e ns ure t hat t he rec or ds c o nti n ue t o be st ore d sec urely f or as l o n g as t he y are 
mai n tai ne d.
W he n partici pa nt data are t o be delete d, t he i n vesti gat or will e ns ure t hat all c o pies of s uc h 
data are pr o m ptl y  a n d irre v oca bly delete d fr o m all s yste ms.
T he i n vesti gat or(s) will n otif y t he s p o ns or or its a ge nts i m me diatel y of a n y re g ulat or y retai n
n otificati o 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 t he 
s p o ns or 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 t he 
s p o ns or or its a ge nt, w he ne ver feasi ble, t o be prese nt d uri n g t he i nspecti o n. T he i n vesti gat or 
site a n d i n vesti gat or will pr o m ptl y res ol ve a ny 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 partici pa nt's me dical rec or ds. T he i n vesti gat or will pr o m ptl y pr o vi de 
c o pies of t he i ns pecti o n fi n di n gs t o t he s p o ns or or its a ge nt. Bef ore res p o nse s u b missi 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 t he s p o ns or 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.
0 9 0 1 7 7 e 1 9 b b 9 c 5f d\ A p pr o v e d\ A p pr o v e d O n: 0 3- N o v- 2 0 2 2 1 1: 4 8 ( G M T)

P F -0 7 0 3 8 1 2 4
Pr ot oc ol C 3 9 4 1 0 0 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 2 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 Marc h 2 0 2 1)
Pa ge 9 5
1 0. 1. 8. S o urce D oc u me nts
S o urce d oc u me nts pr o vi de e vi de nc e f or t he e xiste nce of t he partici pa nt a n d s u bsta ntiate t he 
i nte grity of t he data c ollecte d. S o urce d oc u me nt s are file d at t he i n vesti gat or site.
Data re p orte d o n t he C R F or e ntere d i n t he e C R F t hat are fr o m s o urce d oc u me nts m ust be 
c o nsiste nt wit h t he s o u rce d oc u me nts or t he discre pa ncies m ust be e x plai ne d. T he 
i n vesti gat or ma y nee d t o re q uest pre vi o us me dical rec or ds or tra nsfer rec or ds, de pe n di n g o n 
t he st u d y. Als o, c urre nt me dical rec or ds m ust be a vaila ble.
I n t his st u dy, t he C R F will ser ve as t he s o urce d oc u me nt. A d oc u me nt m ust be a vaila ble at 
t he i n vesti gati ve site t hat i de ntifies t h ose data t hat will be rec or de d o n t he C R F a n d f or w hic h 
t he C R F will be t he s o urce d oc u me nt.
Defi niti o n of w hat c o nstit utes s o urce data a n d its ori gi n ca n be f o u n d i n st u d y m o nit ori n g 
pla n , w hic h is mai ntai ne d b y t he s p o ns or.
Descri pti o n of t he use of t he c o m p uterize d s yste m is d oc u me nte d i n t he Data Ma na ge me nt 
Pla n , w hic h is mai ntai ne d b y t he s p o ns or.
T he i n vesti gat or m ust mai ntai n acc urate d oc u me ntati o n (s o urce data) t hat s u p p orts t he 
i nf or mati o n e ntere d i n t he C R F.
St u d y  m o nit ors will perf or m o n g oi n g s o urce data verificati o n t o c o nfir m t hat data e ntere d 
i nt o t he C R F b y a ut h orize d site pers o n nel are acc urate, c o m plete, a n d verifia ble fr o m s o urce 
d oc u me nts; t hat t he safet y a n d ri g hts of partici pa nts are bei n g pr otecte d; a n d t hat t he st u d y  is 
bei n g c o n d ucte d i n acc or da nce wit h t he c urre ntl y  a p pr o ve d pr ot oc ol a n d a n y ot her st u d y 
a gree me nts, IC H G C P g ui deli nes , a n d all a p plica ble re g ulat or y re q uire me nts.
1 0. 1. 9. St u d y a n d Site St art a n d Cl os ure
T he st u d y  start date is t he date o n w hic h t he cli nical st u d y will be o pe n f or recr uit me nt of 
partici pa nts.
T he first act of recr uit me nt is t he date of t he first partici pa nt’s first visit a n d will be t he st u d y  
start date.
T he s p o ns or desi g nee reser ves t he ri g ht t o cl ose t he st u d y  site or ter mi nate t he st u d y at a n y 
ti me f or a ny reas o n at t he s ole discreti o n of t he s p o ns or. St u d y  sites will be cl ose d u p o n st u d y 
c o m pleti o n. A st u d y site is c o nsi dere d cl ose d w he n all re q uire d d oc u me nts a n d st u d y 
s u p plies ha ve bee n c ollecte d a n d a st u dy- site cl os ure visit has bee n perf or me d.
T he i n vesti gat or ma y  i nitiate st u d y-site cl os ure at a n y ti me u p o n n otificati o n t o t he s p o ns or 
or desi g nee/ C R O if re q ueste d t o d o s o b y  t he res p o nsi ble IR B/ E C or if s uc h ter mi nati o n is 
re q uire d t o pr otect t he healt h of st u d y partici pa nts.
0 9 0 1 7 7 e 1 9 b b 9 c 5f d\ A p pr o v e d\ A p pr o v e d O n: 0 3- N o v- 2 0 2 2 1 1: 4 8 ( G M T)

P F -0 7 0 3 8 1 2 4
Pr ot oc ol C 3 9 4 1 0 0 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 2 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 Marc h 2 0 2 1)
Pa ge 9 6
Reas o ns f or t he earl y cl os ure of a st u d y site b y t he s p o ns or ma y i ncl u de b ut are n ot li mite d 
t o:

Fail ure of t he i n vesti gat or t o c o m pl y  wit h t he pr ot ocol, t he re q uire me nts of t he 
I RB/ E C or l ocal healt h a ut h orities, t he s p o ns or's pr oce d ures, or t he I C H G C P 
g ui deli nes ;

I na de q uate recr uit me nt of partici pa nts b y  t he i n vesti gat or;

Disc o nti n uati o n of f urt her st u d y  i nter ve nti o n de vel o p me nt.
If t he st u dy is pre mat urel y  ter mi nate d or s us pe n de d, t he s p o ns or s hall pr o m ptl y i nf or m t he 
in vesti gat ors, t he E Cs/I R Bs, t he re g ulat or y  a ut h orities, a n d a n y C R O (s) use d i n t he st u d y of 
t he reas o n f or ter mi nati o n or s us pe nsi o n, as s pecifie d b y t he a p plica ble re g ulat or y 
re q uireme nts. T he in vesti gat or s hall pr o m ptl y  i nf or m t he partici pa nt a n d s h o ul d ass ure 
a p pr o priate partici pa nt t hera p y a n d/ or f oll o w- u p.
St u d y  ter mi nati o n is als o pr o vi de d f or i n t he cli nical st u d y a gree me nt. If t here is a n y c o nflict 
bet wee n t he c o ntract a n d t his pr ot oc ol , t he c o ntract will c o ntr ol as t o ter mi nati o n ri g hts.
0 9 0 1 7 7 e 1 9 b b 9 c 5f d\ A p pr o v e d\ A p pr o v e d O n: 0 3- N o v- 2 0 2 2 1 1: 4 8 ( G M T)
C CI

P F -0 7 0 3 8 1 2 4
Pr ot oc ol C 3 9 4 1 0 0 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 2 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 Marc h 2 0 2 1)
Pa ge 9 7
1 0. 1. 1 1. 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 pers o 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 st u d y tea m o n de ma n d s yste m. 
T o facilitate access t o a p pr o priatel y q ualifie d me dical pers o n nel f or st u d y -relate d me dical 
q uesti o ns or pr o ble ms, partici pa nts are pr o vi de d wit h a n E C C) at t he ti me of i nf or me d 
c o nse nt /asse nt. T he E C C c o ntai ns, at a mi ni m u m, (a) pr ot oc ol a n d st u d y i nter ve nti o n 
i de ntifiers, ( b) partici pa nt’s st u d y  i de ntificati o n n u m ber, (c) site e mer ge nc y p h o ne n u m ber 
acti ve 2 4 h o urs/ da y , 7 da ys per wee k, a n d ( d) Pfizer C all C e nter n u m ber.
T he E C C is i nte n de d t o a u g me nt, n ot re place, t he esta blis he d c o m m u nicati o n pat h wa y s 
bet wee n t he i n vesti gat or, site staff, a n d st u d y tea m. T he E C C is t o be use d b y healt hcare 
pr ofessi o nals n ot i n v ol ve d i n t he researc h st u d y o nl y , as a mea ns of reac hi n g t he i n vesti gat or 
or site staff relate d t o t he care of a partici pa nt. T he Pfizer Call Ce nter n u m ber s h o ul d o nl y  be 
use d w he n t he i n vesti gat or a n d site staff ca n n ot be reac he d. T he Pfizer Call Ce nter n u m ber is 
n ot i nte n de d f or use b y t he partici pa nt directl y ; if a partici pa nt calls t hat n u m ber directly, he 
or s he will be directe d bac k t o t he i n vesti gat or s ite.
0 9 0 1 7 7 e 1 9 b b 9 c 5f d\ A p pr o v e d\ A p pr o v e d O n: 0 3- N o v- 2 0 2 2 1 1: 4 8 ( G M T)
C CI

P F -0 7 0 3 8 1 2 4
Pr ot oc ol C 3 9 4 1 0 0 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 2 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 Marc h 2 0 2 1)
Pa ge 9 8
1 0. 2. A p pe n di x 2: Cli nic al L a b or at or y Tests
T he f oll o wi n g safet y la b orat or y  tests will be perf or me d at ti mes defi ne d i n t he S o A secti o n of 
t his pr ot oc ol. A d diti o nal la b orat or y res ults ma y be re p orte d o n t hese sa m ples as a res ult of 
t he met h o d of a nalys is or t he t ype of a nal yz er use d b y t he cli nical la b orat or y, or as deri ve d 
fr o m calc ulate d val ues. T hese a d diti o nal tests w o ul d n ot re q uire a d diti o nal c ollecti o n of 
bl o o d. U nsc he d ule d cli nical la b orat or y meas ure me nts ma y be o btai ne d at a n y ti me d uri n g t he 
st u d y t o assess a ny percei ve d safet y iss ues.
T a ble 6.
Pr ot oc ol Re q uire d S afet y L a b or at or y Assess me nts
H e m at ol o g y
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 c o u nt a n d i n dices 
M C V
M C H
M C H C
W B C c o u n t 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 ytes ( A bs)
Bas o p hils ( A bs)
L y m p h oc ytes ( A bs)
Platelet c o u nt
B U N a n d creati ni ne
Creati ni ne Ki nase
Gl uc ose 
Ca lci u m
S o di u m
P otassi u m
C hl ori de
T otal C O 2 ( bicar b o nate)
A S T, A L T
T otal b ilir u bi n
Direct Bilir u bi n a
Al kali ne p h os p hatase
Uric aci d
Al b u mi n
T otal pr otei n
Pr otei n ( q ual )
Bl o o d ( q ual)
Nitrites
Le u k oc yte esterase
Micr osc o p y
b
F S H c
Pre g na nc y test ( β- h C G )d
a.
O nl y if t otal bilir u bi n is ele vate d.
b.
O nl y if uri ne di pstic k is p ositi ve f or bl o o d, pr otei n, nitrites, or le u k oc yte esterase.
c.
F or c o nfir mati o n of p ost me n o pa usal stat us, i n fe males w h o are a me n orr heic f or at least 1 2 c o nsec uti ve 
m o nt hs. At Scree ni n g o nl y.
d.
Ser u m or uri ne β- h C G f or fe male partici pa nt s of c hil d beari n g p ote ntial per S o A . Ser u m pre g na nc y test 
m ust be perf or me d at Scree ni n g .
T he i n vesti gat or m ust re vie w t he la b orat or y  re p ort, d oc u me nt t his re vie w, a n d rec or d a n y 
cli nicall y rele va nt c ha n ges occ urri n g d uri n g t he st u d y i n t he A E secti o n of t he C R F. 
La b orat or y res ults t hat c o ul d u n bli n d t he st u d y will n ot be re p orte d t o i n vesti gat or sites or 
ot her bli n de d pers o n nel u ntil t he st u d y  has bee n u n bli n de d.
0 9 0 1 7 7 e 1 9 b b 9 c 5f d\ A p pr o v e d\ A p pr o v e d O n: 0 3- N o v- 2 0 2 2 1 1: 4 8 ( G M T)

P F -0 7 0 3 8 1 2 4
Pr ot oc ol C 3 9 4 1 0 0 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 2 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 Marc h 2 0 2 1)
Pa ge 9 9
1 0. 3. A p pe n di x 3: A d verse E ve nts: Defi niti o ns a n d Pr oce d ures f or Rec or di n g, 
E v al u ati n g, F oll o w - Up, a n d Re p orti n g
1 0. 3. 1. Defi niti o n of A E
A E Defi niti o n

A n A E is a n y u nt o war d me dical occ urre nce i n a patie nt or cli nical st u d y 
partici pa nt, te m p orall y ass ociate d wit h t he use of st u d y i nter ve nti o n, w het her or n ot 
c o nsi dere d relate d t o t he st u d y  i nter ve nti o n.

N ote : A n A E ca n t heref ore be a ny u nfa v ora ble a n d u ni nte n de d si g n (i ncl u di n g a n 
a b n or mal la b orat o r y fi n di n g), sy m pt o m, or disease ( ne w or e xacer bate d) te m p orall y  
ass ociate d wit h t he use of st u d y  i nter ve nti o n.
E ve nts Meeti n g
t he A E Defi niti o n

A n y  a b n or mal la b orat or y test res ults ( he mat ol o g y, cli nical c he mistr y, or uri nal ysis) 
or ot her safet y assess m e nts (e g, E C G, ra di ol o gical sca ns, vital si g n meas ure me nts), 
i ncl u di n g t h ose t hat w orse n fr o m baseli ne, c o nsi dere d cli nically si g nifica nt i n t he 
me dical a n d scie ntific j u d g me nt of t he i n vesti gat or . A n y a b n or mal la b orat or y test 
res ults t hat meet a ny of t he c o n diti o ns bel o w m ust be rec or de d as a n A E:

Is ass ociate d wit h acc o m pa n yi n g sy m pt o ms .

Re q uires a d diti o nal dia g n ostic testi n g or me dical/s ur gical i nter ve nti o n .

Lea 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 nt, or ot her t hera p y.

E xacer bati o n of a c hr o nic or i nter f ulle nt pree xisti n g c o n diti o n , i ncl u di n g eit her a n 
i ncrease i n fre q ue nc y a n d/ or i nte nsit y of t he c o n diti o n.

Ne w c o n diti o n detecte d or dia g n ose d after st u d y  i nter ve nti o n a d mi nistrati o n, e ve n 
t h o u g h it ma y ha ve bee n prese nt bef ore t he start of t he st u d y.

Si g ns, s y m pt o ms, or t he cli nical se q uelae of a s us pecte d dr u g -dr u g i nteracti o n.

Si g ns, s y m pt o ms, or t he cli nical se q uelae of a s us pecte d o ver d ose of eit her st u d y 
i nter ve nti o n or a c o nc o mita nt me dicati o n. O ver d ose per se will n ot be re p orte d as 
a n A E or S A E u nless it is a n i nte nti o nal o ver d ose ta ke n wit h p ossi ble 
s uici dal/self-har mi n g i nte nt. S uc h o ver d oses s h o ul d be re p orte d re gar dless of 
se q uelae.
0 9 0 1 7 7 e 1 9 b b 9 c 5f d\ A p pr o v e d\ A p pr o v e d O n: 0 3- N o v- 2 0 2 2 1 1: 4 8 ( G M T)

P F -0 7 0 3 8 1 2 4
Pr ot oc ol C 3 9 4 1 0 0 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 2 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 Marc h 2 0 2 1)
Pa ge 1 0 0
E ve nts N O T Meeti n g t he A E Defi niti o n

A n y  cli nicall y si g nifica nt a b n or mal la b orat or y fi n di n gs or ot her a b n or mal safety 
assess me nts t hat are ass ociate d wit h t he u n derl yi n g disease, u nless j u d ge d b y  t he 
i n vesti gat or t o be m ore se vere t ha n e x pecte d f or t he partici pa nt’s c o n diti o n.

T he disease/ dis or der bei n g st u die d or e x pecte d pr o gressi o n, si g ns, or s y m pt o ms of 
t he disease/ dis or der bei n g st udie d, u nless m ore se vere t ha n e x pecte d f or t he 
partici pa nt’s c o n diti o n.

Me dical or s ur gical pr oce d ure (e g, e n d osc o p y, a p pe n dect o m y): t he c o n diti o n t hat 
lea ds t o t he pr oce d ure is t he A E.

Sit uati o ns i n w hic h a n u nt o war d me dical occ urre nce di d n ot occ ur (s oci al a n d/ or 
c o n ve nie nce a d missi o n t o a h os pital).

A ntici pate d da y -t o-d a y  fl uct uati o ns of pree xisti n g disease(s) or c o n diti o n(s) prese nt 
or detecte d at t he start of t he st u d y t hat d o n ot w orse n.
1 0. 3. 2. Defi niti o n of a n S A E
A n S A E is defi ne d as a n y u nt o w ar d me dic al occ urre nce t h at, at a n y d ose , meets o ne 
or m ore of t he criteri a liste d bel o w:
a.
Res ults i n de at h
b.
Is life-t hre ate ni n g
T he ter m “life-t hreate ni n g” i n t he defi niti o n of “seri o us” refers t o a n e ve nt i n w hic h t he 
partici pa nt was at ris k of deat h at t he ti me of t he e ve nt. It d oes n ot refer t o a n e ve nt t hat
h y p ot heticall y  mi g ht ha ve ca use d deat h if it were m ore se vere.
c.
Re q uires i n p atie nt h os pit aliz ati o n or pr ol o n g ati o n of e xisti n g h o s pit aliz ati o n
I n ge neral, h os pitalizati o n si g nifies t hat t he partici pa nt has bee n a dmitte d ( us uall y 
i n v ol vi n g at least a n o ver ni g ht sta y) at t he h os pital or e mer ge nc y war d f or o bser vati o n 
a n d/ or treat me nt t hat w o ul d n ot ha ve bee n a p pr o priate i n t he p h ys icia n’s office or 
o ut patie nt setti n g. C o m plicati o ns t hat occ ur d uri n g h os pitalizati o n are A Es. If a 
c o m plicati o n pr ol o n gs h os pitalizati o n or f ulfills a n y ot her seri o us criteria, t he e ve nt is 
seri o us. W he n i n d o u bt as t o w het her “ h os pitalizati o n” occ urre d or w as necessar y, t he 
A E s h o ul d be c o nsi dere d seri o us.
0 9 0 1 7 7 e 1 9 b b 9 c 5f d\ A p pr o v e d\ A p pr o v e d O n: 0 3- N o v- 2 0 2 2 1 1: 4 8 ( G M T)

P F -0 7 0 3 8 1 2 4
Pr ot oc ol C 3 9 4 1 0 0 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 2 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 Marc h 2 0 2 1)
Pa ge 1 0 1
H os pitalizati o n f or electi ve treat me nt of a pree xisti n g c o n diti o n t hat di d n ot w orse n 
fr o m baseli ne is n ot c o nsi dere d a n A E.
d.
Res ults i n persiste nt or si g nific a nt dis a bilit y/i nc a p acit y

T he ter m disa bilit y  mea ns a s u bsta ntial disr u pti o n of a pers o n’s a bilit y  t o c o n d uct 
n or mal life f u ncti o ns.

T his defi niti o n is n ot i nte n de d t o i ncl u de e x perie nces of relati vel y mi n or me dical 
si g nifica nce, s uc h as u nc o m plicate d hea dac he, na usea, v o miti n g, diarr hea, 
i nfl ue nza, a n d acci de ntal tra u ma (e g, s prai ne d a n kle), t hat m a y  i nterfere wit h or 
pre ve nt e ver y d a y  life f u ncti o ns b ut d o n ot c o nstit ute a s u bsta ntial disr u pti o n.
e.
Is a c o n ge nit al a n o m al y/ birt h defect
f.
Is a s us pecte d tr a ns missi o n vi a a Pfizer pr o d uct of a n i nfecti o us a ge nt, p at h o ge nic 
or n o n- p at h o ge nic, is c o nsi dere d seri o us 
T he e ve nt ma y  be s us pecte d fr o m cli nical sy m pt o ms or la b orat or y  fi n di n gs i n dicati n g 
a n i nfecti o n i n a partici pa nt e x p ose d t o a Pfi zer pr o d uct. T he ter ms “s us pecte d 
tra ns missi o n” a n d “tra ns missi o n” are c o nsi dere d s yn o n y m o us. T hese cases are 
c o nsi dere d u ne x pecte d a n d ha n dle d as seri o us e x pe dite d cases b y p har mac o vi gila nce 
pers o n nel. S uc h cases are als o c o nsi dere d f or re p orti n g as pr o d u ct defects, if 
a p pr o priate.
g.
Ot her sit u ati o ns:

Me dical or scie ntific j u d g me nt s h o ul d be e xercise d b y  t he i n vesti gat or i n deci di n g 
w het her S A E re p orti n g is a p pr o priate i n ot her sit uati o ns, s uc h as si g nifica nt
me dical e ve nts t hat ma y je o par dize t he partici pa nt or ma y  re q uire me dical or 
s ur gical i nter ve nti o n t o pre ve nt o ne of t he ot her o utc o mes liste d i n t he a b o ve 
defi niti o n. T hese e ve nts s h o ul d us uall y  be c o nsi dere d seri o us.

E xa m ples of s uc h e ve nts i ncl u de i n vasi ve or mali g na nt ca ncers, i nte nsi ve treat me nt 
i n a n e mer ge nc y r o o m or at h o me f or aller gic br o nc h os pas m, bl o o d d yscrasias or
c o n v ulsi o ns t hat d o n ot res ult i n h os pitalizati o n , or de vel o p me nt of dr u g 
de pe n de nc y  or dr u g a b use.
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P F -0 7 0 3 8 1 2 4
Pr ot oc ol C 3 9 4 1 0 0 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 2 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 Marc h 2 0 2 1)
Pa ge 1 0 2
1 0. 3. 3. Rec or di n g / Re p orti n g a n d F oll o w - Up of A E s a n d/ or S A E s D uri n g t he Acti ve 
C ollecti o n Peri o d 
A E a n d S A E Rec or di n g / Re p orti n g
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 A Es o n t he C R F a n d f or 
re p orti n g S A E s o n t he C T S A E Re p ort F or m t o Pfizer Safet y t hr o u g h o ut t he acti ve 
c ollecti o n peri o d. T hese re q uire me nts are deli neate d f or 3 t y pes of e ve nts: ( 1) S A Es; 
( 2) n o nseri o us A Es ; a n d ( 3) e x p os ure t o t he st u d y i nter ve nti o n 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. 
It s h o ul d be n ote d t hat t he C T S A E Re p ort F or m f or re p orti n g of S A E i nf 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 ot h t he C R F a n d t he C T SA E 
Re p ort F or m f or re p orti n g of S A E i nf or mati o n.
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 nseri o us A E
All
N o ne
E x p os ure t o t he st u d y 
i nter ve nti o n u n der st u d y 
d uri n g pre g na nc y  or 
breastfee di n g, 
All A Es or S A Es ass ociate d 
wit h e x p os ure d uri n g 
pre g na nc y  or breastfee di n g
N ote: I nsta nces of E D P or 
E D B n ot ass ociate d wit h a n 
A E or S A E are n ot ca pt ure d 
i n t he C R F.
All i nsta nces of E D P are 
re p orte d ( w hether or n ot 
t here is a n ass ociate d 
S A E) *
All i nsta nces of E D B are 
re p orte d ( w het her or n ot 
t here is a n ass ociate d 
S A E). * *
E n vir o n me ntal or 
occ u pati o nal e x p os ure t o 
t he pr o d uct u n der st u dy t o 
a n o n-partici pa nt ( n ot 
i n v ol vi n g E D P or E D B).
N o ne. E x p os ure t o a st u d y 
n o n- partici pa nt is n ot 
c ollecte d o n t he C R F.
T he e x p os ure ( w het her or 
n ot t here is a n ass ociate d 
A E or S A E) m ust be 
re p orte d. * * *
*
E D P ( wit h or wit h o ut a n ass ociate d A E or S A E): a n y pre g na nc y i nf or mati o n is re p orte d t o Pfizer 
Safet y usi n g C T S A E Re p ort F or m a n d E D P S u p ple me ntal F or m; if t he E D P is ass ociate d w it h a n 
S A E, t he n t he S A E is re p orte d t o Pfizer Safet y usi n g t he C T S A E Re p ort F or m . 
* * 
E D B is re p orte d t o Pfizer Safet y usi n g t he C T S A E Re p ort F or m w hic h wo ul d als o i ncl u de details of 
a n y S A E t hat mi g ht be ass ociate d wit h t he E D B. 
* * * E n vir o n me nt al or Occ u p ati o n al e x p os ure: A E s or S A Es ass ociate d wit h occ u pati o nal e x p os ure are 
rep orte d t o Pfizer Safet y usi n g t he C T S A E Re p ort F or m. 
0 9 0 1 7 7 e 1 9 b b 9 c 5f d\ A p pr o v e d\ A p pr o v e d O n: 0 3- N o v- 2 0 2 2 1 1: 4 8 ( G M T)

P F -0 7 0 3 8 1 2 4
Pr ot oc ol C 3 9 4 1 0 0 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 2 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 Marc h 2 0 2 1)
Pa ge 1 0 3

W he n a n A E
or S A E occ urs, it is t he res p o nsi bilit y  of t he i n vesti gat or t o re vie w all 
d oc u me ntati o n (e g, h os pital pr o gress n otes, la b orat or y  re p orts, a n d dia g n ostic 
re p orts) relate d t o t he e ve nt.

T he i n vesti gat or will t he n rec or d all rele va nt A E or S A E i nf or mati o n i n t he C R F.

It is n ot acce pta ble f or t he i n vesti gat or t o se n d p h ot oc o pies of t he partici pa nt’s 
me dical rec or ds t o Pfizer Safet y  i n lie u of c o m pleti o n of t he C T S A E Re p ort 
F or m / A E or S A E C R F p a ge.

T here ma y  be i nsta nces w he n c o pies of me dical rec or ds f or certai n cases are 
re q ueste d by Pfizer Safet y . I n t his case, all partici pa nt i de ntifiers, wit h t he 
e xce pti o n of t he partici pa nt n u m ber, will be re dacte d o n t he c o pies of t he me dical 
rec or ds bef ore s u b missi o n t o Pfizer Safet y .

T he i n vesti gat or will atte m pt t o esta blis h a dia g n osis of t he e ve nt base d o n si g ns, 
s ym pt o ms, a n d/ or ot her cli nical i nf or mati o n. W he ne ver p ossi ble, t he dia g n osis ( n ot 
t he i n di vi d ual si g ns/s ym pt o ms) will be d oc u me nte d as t he A E or S A E.
Assess me nt of I nte nsit y
T he i n vesti gat or will ma ke a n assess me nt of i nte nsit y f or eac h A E a n d S A E re p orte d 
d uri n g t he st u d y a n d assi g n it t o 1 of t he f oll o wi n g cate g ories: 

Mil d: As y m pt o matic or mil d s y m pt o ms; cli nical or dia g n ostic o bser vati o ns o nl y ; 
i nter ve nti o n n ot i n dicate d.

M o derate: Mi ni mal, l ocal or n o ni n vasi ve i nter ve nti o n i n dicate d; li miti n g a ge -
a p pr o priate i nstr u me ntal A D L. I nstr u me ntal A D L refers t o pre pari n g meals, 
s h o p pi n g f or gr oceries or cl ot hes, usi n g t he tele p h o ne, mana gi n g m o ne y , etc.  

Se vere: Se vere or me dicall y  si g nifica nt b ut n ot i m me diatel y life-t hreate ni n g; 
h os pitalizati o n or pr ol o n gati o n of h os pitalizati o n i n dicate d; disa bli n g, li miti n g self 
care A D L. Self care A D L refers t o bat hi n g, dressi n g a n d u n dressi n g, fe e di n g self, 
usi n g t he t oilet, ta ki n g me dicati o ns, a n d n ot be dri d de n. 
A n e ve nt is defi ne d as “seri o us” w he n it meets at least 1 of t he pre defi ne d o utc o mes as 
descri be d i n t he defi niti o n of a n S A E, N O T w he n it is rate d as se vere.
0 9 0 1 7 7 e 1 9 b b 9 c 5f d\ A p pr o v e d\ A p pr o v e d O n: 0 3- N o v- 2 0 2 2 1 1: 4 8 ( G M T)

P F -0 7 0 3 8 1 2 4
Pr ot oc ol C 3 9 4 1 0 0 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 2 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 Marc h 2 0 2 1)
Pa ge 1 0 4
Assess me nt of C a us alit y

T he i n vesti gat or is o bli gate d t o assess t he relati o ns hi p bet wee n st u d y i nter ve nti o n 
a n d eac h occ urre nce of eac h A E or S A E. T he i n vesti gat or will use cli nical 
j u d g me nt t o deter mi ne t he relati o ns hi p.

A “reas o na ble p ossi bilit y” of a relati o ns hi p c o n ve ys t hat t here are facts, e vi de nce, 
a n d/ or ar g u me nts t o s u g gest a ca usal relati o ns hi p, rat her t ha n a relati o ns hi p ca n n ot 
be r ule d o ut.

Alter nati ve ca uses, s uc h as u n derl yi n g disease(s), c o nc o mita nt t hera p y, a n d ot her 
ris k fact ors, as well as t he te m p oral relati o ns hi p of t he e ve nt t o st u dy i nter ve nti o n 
a d mi nistrati o n , will be c o nsi dere d a n d i n vesti gate d.

T he i n vesti gat or will als o c o ns ult t he I B a n d/ or p r o d uct inf or mati o n, f or mar kete d 
pr o d ucts, i n his/ her assess me nt.

F or eac h A E or S A E, t he i n vesti gat or m ust d oc u me nt i n t he me dical n otes t hat 
he/s he has re vie we d t he A E or S A E a n d has pr o vi de d a n assess me nt of ca usalit y .

T here ma y  be sit uati o ns i n w hic h a n S A E has occ urre d a n d t he i n vesti gat or has 
mi ni mal i nf or mati o n t o i ncl u de i n t he i nitial re p ort t o t he s p ons or . H o we ver, it is 
ver y i m p ort a nt t h at t he i n vesti g at or al w a ys m a ke a n assess me nt of c a us alit y 
f or e ver y e ve nt bef ore t he i niti al tr a ns missi o n of t he S A E d at a t o t he s p o ns or.

T he i n vesti gat or ma y  c ha n ge his/ her o pi ni o n of ca usalit y i n li g ht of f oll o w- u p 
i nf or mati o n a n d se n d an S A E f oll o w -u p re p ort wit h t he u p date d ca usalit y  
assess me nt.

T he ca usalit y  assess me nt is o ne of t he criteria use d w he n deter mi ni n g re g ulat or y 
re p orti n g re q uire me nts.

If t he i n vesti gat or d oes n ot k n o w w het her or n ot t he st u d y i nter ve nti o n 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 st u d y i nter ve nti o n” f or re p orti n g 
p ur p oses, as defi ne d b y t he s p o ns or . 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 a n 
assess me nt i n t he de dicate d secti 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.
0 9 0 1 7 7 e 1 9 b b 9 c 5f d\ A p pr o v e d\ A p pr o v e d O n: 0 3- N o v- 2 0 2 2 1 1: 4 8 ( G M T)

P F -0 7 0 3 8 1 2 4
Pr ot oc ol C 3 9 4 1 0 0 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 2 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 Marc h 2 0 2 1)
Pa ge 1 0 5
F oll o w - Up of A Es a n d S A Es

T he i n vesti gat or is o bli gat e d t o perf or m or arra n ge f or t he c o n d uct of s u p ple me ntal 
meas ure me nts a n d/ or e val uati o ns, as me dicall y i n dicate d or as re q ueste d b y t he 
s p o ns or, t o el uci date t he nat ure a n d/ or ca usality of t he A E or S A E as f ull y as 
p ossi ble. T his ma y  i ncl u de a d diti o nal la b orat or y tests or i n vesti gati o ns, 
hist o pat h ol o gical e xa mi nati o ns, or c o ns ultati o n wit h ot her healt hcare pr o vi ders .

If a partici pa nt dies d uri n g partici pati o n i n t he st u d y or d uri n g a rec o g nize d 
f oll o w- u p peri o d, t he i n vesti gat or will pr o vi de Pfizer Safet y wit h a c o p y of a n y 
p ost m orte m fi n di n gs , i ncl u di n g hist o pat h ol o g y.

Ne w or u p date d i nf or mati o n will be rec or de d i n t he ori gi nall y  s u b mitte d 
d oc u me nts .

T he i n vesti gat or will s u b mit a n y  u p date d S A E data t o t he s p o ns or wit hi n 2 4 h o urs 
of recei pt of t he i nf or mati o n.
1 0. 3. 4. Re p orti n g of S A Es
S A E Re p orti n g t o Pfizer S afet y vi a a n Electr o nic D at a C ollecti o n T o ol

T he pri mar y  mec ha nis m f or re p orti n g a n S A E t o Pfizer Safet y will be t he 
electr o nic data c ollecti o n t o ol.

If t he electr o nic sys te m is u na vaila ble, t he n t he site will use t he pa per S A E data 
c ollecti o n t o ol (see ne xt secti o n) t o re p ort t he e ve nt wit hi n 2 4 h o urs.

T he site will e nter t he S A E data i nt o t he electr o nic s y ste m as s o o n as t he data
bec o me a vaila ble.

After t he st u d y is c o m plete d at a gi ve n site, t he electr o nic data c ollecti o n t o ol will 
be ta ke n off -li ne t o pre ve nt t he e ntr y of ne w data or c ha n ges t o e xisti n g data.

If a site recei ves a re p ort of a ne w S A E fr o m a st u d y partici pa nt or recei ves u p date d 
dat a o n a pre vi o usl y re p orte d S A E after t he electr o nic data c ollecti o n t o ol has bee n 
ta ke n off-li ne, t he n t he site ca n re p ort t his i nf or mati o n o n a pa per S A E f or m (see 
ne xt secti o n) or t o Pfizer Safet y  b y tele p h o ne.
0 9 0 1 7 7 e 1 9 b b 9 c 5f d\ A p pr o v e d\ A p pr o v e d O n: 0 3- N o v- 2 0 2 2 1 1: 4 8 ( G M T)

P F -0 7 0 3 8 1 2 4
Pr ot oc ol C 3 9 4 1 0 0 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 2 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 Marc h 2 0 2 1)
Pa ge 1 0 6
S A E Re p orti n g t o Pfizer S afet y vi a C T S A E Re p ort F or m

Facsi mile tra ns missi o n of t he C T S A E Re p ort F or m is t he preferre d met h o d t o 
tra ns mit t his i nf or mati o n t o Pfizer Safet y .

I n circ u msta nces w he n t he facsi mile is n ot w or ki n g, n otificati o n b y tele p h o ne is 
acce pta ble wit h a c o p y of t he C T S A E Re p ort F or m se nt b y o ver ni g ht mail or 
c o urier ser vice.

I nitial n otificati o n via tele p h o ne d oes n ot re place t he nee d f or t he i n vesti gat or t o 
c o m plete a n d si g n t he C T S A E Re p ort F or m pa ges wit hi n t he desi g nate d re p orti n g 
ti me fra mes.
0 9 0 1 7 7 e 1 9 b b 9 c 5f d\ A p pr o v e d\ A p pr o v e d O n: 0 3- N o v- 2 0 2 2 1 1: 4 8 ( G M T)

P F -0 7 0 3 8 1 2 4
Pr ot oc ol C 3 9 4 1 0 0 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 2 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 Marc h 2 0 2 1)
Pa ge 1 0 7
1 0. 4. A p pe n di x 4: C o ntr ace pti ve a n d B arrier G ui d a nce 
1 0. 4. 1. M ale P artici p a nt Re pr o d ucti ve I ncl usi o n Criteri a
Male partici pa nts are eli gi ble t o partici pate if t he y  a gree t o t he f oll o wi n g re q uire me nts d uri n g 
t he i nter ve nti o n peri o d a n d f or at least 2 8 d a y s after t he last d ose of st u dy i nter ve nti o n , w hic h 
c orres p o n ds t o t he ti me nee de d t o eli mi nate re pr o d ucti ve safety ris k of t he st u d y 
i nter ve nti o n(s): 

Refrai n fr o m d o nati n g s per m .
P L U S eit her:

Be a bsti ne nt fr o m heter ose x ual or h o m ose x ual i nterc o urse as t heir preferre d a n d us ual 
lifest yle (a bsti ne nt o n a l o n g-ter m a n d persiste nt basis) a n d a gree t o re mai n a bsti ne nt.
O R

M ust a gree t o use c o ntrace pti o n/ barrier as detaile d bel o w .

A gree t o use a male c o n d o m w he n e n ga gi n g i n a n y  acti vit y t hat all o ws f or 
passa ge of ejac ulate t o a n ot her pers o n .
1 0. 4. 2. Fe m ale P artici p a nt Re pr o d ucti ve I ncl usi o n Criteri a
A fe male partici pa nt is eli gi ble t o partici pate if s he is n ot pre g na nt or breastfee di n g, a n d at 
least 1 of t he f oll o wi n g c o n diti o ns a p plies:

Is n ot a W O C B P (see defi niti o ns bel o w i n Secti o n 1 0. 4. 3 ).
O R

Is a W O C B P a n d a grees t o use a hi g hl y effecti ve c o ntrace pti ve met h o d (fail ure rate 
< 1 % per ye ar) d uri n g t he i nt er ve nti o n peri o d a n d f or a mi ni m u m of 2 8 da ys after t he 
last d ose of st u d y i nter ve nti o n. If a hi g hl y effecti ve, user -de pe n de nt met h o d is 
c h ose n, s he a grees t o c o nc urre ntl y use a n effecti ve barrier met h o d of c o ntrace pti o n. 
T he i n vesti gat or s h o ul d e val uate t he effecti ve ness of t he c o ntrace pti ve met h o d i n 
relati o ns hi p t o t he first d ose of st u d y i nter ve nti o n.
F or a fe male partici pa nt w h o bec o mes pre g na nt, t his i nf or mati o n will be s hare d wit h t he 
st u d y partici pa nt’s pare nt/ g uar dia n if t he partici pa nt’s a ge is 1 2-1 7 y ears ol d or as re q uire d 
b y  l ocal re g ulati o ns.
T he i n vesti gat or is res p o nsi ble f or re vie w of me dical hist or y , me nstr ual hist or y, a n d rece nt 
se x ual acti vit y t o decrease t he ris k f or i ncl usi o n of a w o ma n wit h a n early u n detecte d 
pre g na nc y . 
0 9 0 1 7 7 e 1 9 b b 9 c 5f d\ A p pr o v e d\ A p pr o v e d O n: 0 3- N o v- 2 0 2 2 1 1: 4 8 ( G M T)

P F -0 7 0 3 8 1 2 4
Pr ot oc ol C 3 9 4 1 0 0 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 2 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 Marc h 2 0 2 1)
Pa ge 1 0 8
1 0. 4. 3. W o m a n
of C hi l d be ari n g P ote nti al
A w o ma n is c o nsi dere d fertile f oll o wi n g me narc he a n d u ntil bec o mi n g p ost me n o pa usal 
u nless per ma ne ntl y sterile (see bel o w).
If fertilit y is u nclear (e g, a me n orr hea i n a d olesce nts or at hletes) a n d a me nstr ual c ycle ca n n ot 
be c o nfir me d bef ore t he first d ose of st u d y i nter ve nti o n, a d diti o nal e val uati o n s h o ul d be 
c o nsi dere d.
W o me n i n t he f oll o wi n g cate g ories are n ot c o nsi dere d W O C B P:
1.
Pre me narc hal .
2.
Pre me n o pa usal fe male wit h 1 of t he f oll o wi n g:

D oc u me nte d h ys terect o m y;

D oc u me nte d bilateral sal pi n gect o m y;

D oc u me nte d bilateral o o p h orect o m y.
F or i n di vi d uals wit h per ma ne nt i nfertilit y  d ue t o a n alter nate me dical ca use ot her t ha n t he 
a b o ve, (e g, m ulleria n a ge nesis, a n dr o ge n i nse nsiti vit y), i n vesti gat or discreti o n s h o ul d be 
a p plie d t o deter mi ni n g st u d y e ntr y.
N ote: D oc u me ntati o n f or a n y of t he a b o ve cate g ories ca n c o me fr o m t he site pers o n nel’s 
re vie w of t he partici pa nt’s me dical rec or ds, me dical e xa mi nati o n, or me dical hist or y 
i nter vie w. T he met h o d of d oc u me ntati o n s h o ul d be rec or de d i n t he partici pa nt’s me dical 
rec or d f or t he st u dy.
3.
P ost me n o pa usal fe male :

A p ost me n o pa usal state is defi ne d as n o me nses f or 1 2 m o nt hs wit h o ut a n 
alter nati ve me dical ca use. I n a d diti o n:

A hi g h F S H le vel i n t he p ost me n o pa usal ra n ge m ust be use d t o c o nfir m a 
p ost me n o pa us al state i n w o me n u n der 6 0 ye ars of a ge a n d n ot usi n g h or m o nal 
c o ntrace pti o n or H R T. 
N ote: F or w o me n o ver 6 0 y ears of a ge, F S H ma y still be teste d, b ut is left t o 
t he discreti o n of t he PI.

A f e male o n H R T a n d w h ose me n o pa usal stat us is i n d o u bt will be re q uire d t o 
use o ne of t he n o n -estr o ge n h or m o nal hi g hl y effecti ve c o ntrace pti o n met h o ds 
if t he y wis h t o c o nti n ue t heir H R T d uri n g t he st u d y. Ot her wise, t he y  m ust 
disc o nti n ue H R T t o all o w c o nfir mati o n of p ost me n o pa usal stat us bef ore st u d y  
e nr oll me nt.
0 9 0 1 7 7 e 1 9 b b 9 c 5f d\ A p pr o v e d\ A p pr o v e d O n: 0 3- N o v- 2 0 2 2 1 1: 4 8 ( G M T)

P F -0 7 0 3 8 1 2 4
Pr ot oc ol C 3 9 4 1 0 0 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 2 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 Marc h 2 0 2 1)
Pa ge 1 0 9
1 0. 4. 4. C o ntr ace pti o n Met h o ds
C o ntrace pti ve use b y me n or w o me n s h o ul d be c o nsiste nt wit h l ocal a vaila bilit y /re g ulati o ns 
re gar di n g t he use of c o ntrace pti ve met h o ds f or t h ose partici pati n g i n cli nical trials.
T he f oll o wi n g c o ntrace pti ve met h o ds are a p pr o priate f or t his st u d y :
1.
I m pla nta ble pr o gest o ge n-o nl y  h or m o ne c o ntrace pti o n ass ociate d wit h i n hi biti o n of 
o v ulati o n .
2.
I ntra uteri ne de vice.
3.
I ntra uteri ne h or m o ne-releasi n g sys te m.
4.
Bilateral t u bal occl usi o n (e g, bilateral t u bal li gati o n).
5.
Vasect o mize d part ner :

A v asect o mize d part ner is a hi g hl y effecti ve c o ntrace pti ve met h o d pr o vi de d t hat 
t he 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 a n d 
t he a bse nce of s per m has bee n c o nfir me d. If n ot, a n a d diti o nal hi g hly effecti ve 
met h o d of c o ntrac e pti o n s h o ul d be use d. T he s per mat o ge nesis c y cle is 
a p pr o xi matel y 9 0 da ys.
6.
C o m bi ne d (estr o ge n - a n d pr o gest o ge n -c o ntai ni n g) h or m o nal c o ntrace pti o n ass ociate d 
wit h i n hi biti o n of o v ulati o n :

O ral + barrier * ;

I ntra va gi nal + barrier * ;

T ra ns der mal + barrier * .
7.
Pr o gest o ge n - o nly h or m o ne c o ntrace pti o n ass ociate d wit h i n hi biti o n of o v ulati o n :

O ral + barrier * ;

Injecta ble + barrier * .
* I n a d diti o n, o ne of t he f oll o wi n g effecti ve barrier met h o ds m ust als o be use d  w he n 
o pti o ns 6 or 7 are c h ose n a b o ve : 

Male or fe male c o n d o m, wit h or wit h o ut s per mici de;

Cer vical ca p, dia p hra g m, or s p o n ge wit h s per mici de;
0 9 0 1 7 7 e 1 9 b b 9 c 5f d\ A p pr o v e d\ A p pr o v e d O n: 0 3- N o v- 2 0 2 2 1 1: 4 8 ( G M T)

P F -0 7 0 3 8 1 2 4
Pr ot oc ol C 3 9 4 1 0 0 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 2 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 Marc h 2 0 2 1)
Pa ge 1 1 0

A c o m bi nati o n of male c o n d o m wit h eit her cer vical ca p, dia p hra g m, or s p o n ge 
wit h s per mici de ( d o u ble -barrier met h o ds).
8.
Se x ual a bsti ne nce :

Se x ual a bsti ne nce is c o nsi dere d a hi g hl y effecti ve met h o d o nl y  if defi ne d as 
refrai ni n g fr o m heter ose x ual i nterc o urse 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  i nter ve nti o n. T he relia bilit y  of se x ual a bsti ne nce nee ds t o be 
e val uate d i n relati o n t o t he d urati o n of t he st u d y  a n d t he preferre d a n d us ual 
lifest yle of t he partici pa nt.
0 9 0 1 7 7 e 1 9 b b 9 c 5f d\ A p pr o v e d\ A p pr o v e d O n: 0 3- N o v- 2 0 2 2 1 1: 4 8 ( G M T)

P F -0 7 0 3 8 1 2 4
Pr ot oc ol C 3 9 4 1 0 0 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 2 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 Marc h 2 0 2 1)
Pa ge 1 1 1
1 0. 5. A p pe n di x 5: Ge netics
Use/ A n al ysis of D N A

Ge netic variati o n ma y  i m pact a partici pa nt’s res p o nse t o st u d y i nter ve nti o n, 
s usce pti bilit y t o, a n d se verit y a n d pr o gressi o n of disease. T heref ore, w here l ocal 
re g ulati o ns a n d I R Bs/ E Cs all o w, a bl o o d sa m ple will be c ollecte d f or D N A a nal ys is.

T he sc o pe of t he g e netic researc h ma y be narr o w (e g , 1 or m ore ca n di date ge nes ) or 
br oa d (e g , t he e ntire ge n o me), as a p pr o priate t o t he scie ntific q uesti o n u n der 
i n vesti gati o n.

T he sa m ples ma y  be a nal yze d as part of a m ulti st u d y assess me nt of ge netic fact ors 
i n v ol ve d i n t he res p o nse t o P F - 0 7 0 3 8 1 2 4 or st u d y  i nter ve nti o ns of t his class t o 
u n dersta n d treat me nts f or t he disease(s) u n der st u d y  or t he disease(s) t he msel ves.

T he res ults of ge netic a nal y ses ma y be re p orte d i n C S R or i n a se parate st u d y 
s u m mar y, or ma y be use d f or i nter nal decisi o n ma ki n g wit h o ut bei n g i ncl u de d i n a 
st u d y re p ort.

T he s p o ns or will st ore t he D N A sa m ples i n a sec ure st ora ge s pace wit h a de q uate 
mea s ures t o pr otect c o nfi de ntialit y. 

T he sa m ples will be retai ne d as i n dicate d:

Retai ne d s a m ples will be st ore d i n defi nitel y  or f or a not her peri o d as per l ocal 
re q uire me nts.

Partici pa nt s ma y wit h dra w t heir c o nse nt f or t he st ora ge a n d/ or use of t heir Retai ne d 
Researc h Sa m ples at a n y ti me b y ma ki n g a re q uest t o t he i n vesti gat or; i n t his case, 
a n y re mai ni n g material will be destr o ye d. Data alrea d y ge nerate d fr o m t he sa m ples 
will be retai ne d t o pr otect t he i nte grit y of e xisti n g a nal ys es.

Sa m ples f or ge netic res earc h will be la bele d wit h a c o de. T he ke y  bet wee n t he c o de 
a n d t he partici pa nt ’s pers o nall y i de ntif yi n g i nf or mati o n (e g, na me, a d dress) will be 
hel d sec urel y at t he st u d y site. 
0 9 0 1 7 7 e 1 9 b b 9 c 5f d\ A p pr o v e d\ A p pr o v e d O n: 0 3- N o v- 2 0 2 2 1 1: 4 8 ( G M T)

P F -0 7 0 3 8 1 2 4
Pr ot oc ol C 3 9 4 1 0 0 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 2 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 Marc h 2 0 2 1)
Pa ge 1 1 2
1 0. 6. A p pe n di x 6: Li ver S afet y: S u g geste d Acti o ns a n d F oll o w - Up Assess me nts 
P ote nti al C ases 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 n o 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 so me partici pa nt s, 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 partici pa nt s 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 DI LI. 
Partici pa nt s w h o e x perie nce a tra nsa mi nase ele vati o n a b o ve 3 × 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 da pt ors” or are “s usce pti ble.”
I n t he maj orit y of DI LI cases, ele vati o ns i n A S T a n d/ or A L T prece de T Bili ele vati o ns 
( > 2 × U L N) b y  se veral da ys or wee ks. T he i ncrease i n T Bili t y picall 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 orat or y sa m ple). I n rare i nsta nces, b y t he ti me T Bili ele vati o ns 
are detecte 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 ele vati o ns i n eit her A S T O R A L T i n a d diti o n t o T Bili 
t hat meet t he criteria o utli ne d bel o w are c o nsi dere d p ote ntial DI LI (assesse d per H y’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 ote ntial DI LI case de pe n ds o n t he 
partici pa nt ’s i n di vi d ual baseli ne val ues a n d u n derl yi n g c o n diti o ns. Partici pa nt s 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 
( Hy’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:

Partici pa nt s wit h A S T/A L T 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 LT 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 hatase val ue 
< 2 × U L N or n ot a vaila ble.

F or partici pa nt s wit 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 baseli ne:

Pree xisti n g A S T or A L T baseli ne val ues a b 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 ncrease d fr o m 
baseli ne val 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 h ic he ver is s maller).
0 9 0 1 7 7 e 1 9 b b 9 c 5f d\ A p pr o v e d\ A p pr o v e d O n: 0 3- N o v- 2 0 2 2 1 1: 4 8 ( G M T)

P F -0 7 0 3 8 1 2 4
Pr ot oc ol C 3 9 4 1 0 0 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 2 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 Marc h 2 0 2 1)
Pa ge 1 1 3
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 t o 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 partici pa nt 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 res ults. T his e val uati o n s h o ul d 
i ncl u de 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 f or s us pecte d H y’s la w
cases , a d diti o nal la b orat or y tests s h o ul d i ncl u de al b u mi n, C K, direct a n d i n direct bilir u bi n, 
G G T, P T/I N R, t otal bile aci ds, a n d al kali ne p h os p hatase. C o nsi der ati 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 n g, as nee de d, f or f urt her c o nte m p ora ne o us a nal yses 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 / paraceta m ol (eit her b y itself or as a c o-f or m ulate 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, or 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 pers o n, s ur ger y , bl o o d tra nsf usi o n, hist or y of li ver 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 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 , li ver i ma gi n g (e g, biliar y tract), a n d c ollecti o n of ser u m 
sa m ples f or aceta mi n o p he n/ paraceta m ol dr u g a n d/ or pr otei n a d d uct le vels ma y  be warra nte d. 
All cases de m o nstrate d o n re peat testi n g 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 L F T a b n or malities has yet bee n f o u n d. S uc h p ote nti al DI LI ( H y’s l a w) 
c ases 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 nfir me d case o nly after 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 xclu de d a n alter nati ve eti ol o g y .
0 9 0 1 7 7 e 1 9 b b 9 c 5f d\ A p pr o v e d\ A p pr o v e d O n: 0 3- N o v- 2 0 2 2 1 1: 4 8 ( G M T)

P F -0 7 0 3 8 1 2 4
Pr ot oc ol C 3 9 4 1 0 0 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 2 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 Marc h 2 0 2 1)
Pa ge 1 1 4
1 0. 7. A p pe n di x 7: E C G Fi n di n gs of P ote nti al Cli nic al C o ncer n
E C G Fi n di n gs T h at M a y Q u alif y as A Es

Mar ke d si n us b ra dyc ar dia (rate < 4 0 b p m) lasti n g mi n utes .

Ne w P R i nter val pr ol o n gati o n > 2 8 0 ms ec.

Ne w pr ol o n gati o n of Q Tc F t o > 4 8 0 ms ec (a bs ol ute) or by ≥6 0 ms ec fr o m baseli ne.

Ne w - onset atrial fl utter or fi brillati o n, wit h c o ntr olle d ve ntric ular res p o nse rate: 
ie, rate < 1 2 0 b p m .

Ne w - onset ty pe I sec o n d - de gree ( We nc ke bac h) A V b l oc k of > 3 0 sec o n ds’
d urati o n .

Fre q ue nt P V Cs, tri plets, or s h ort i nter vals ( < 3 0 sec o n ds) of c o nsec uti ve ve ntric ular 
c o m ple xes .
E C G Fi n di n gs T h at M a y Q u alif y as S A Es

Q Tc F pr ol o n gati o n > 5 0 0 ms ec.

Ne w S T -T c ha n ges s u g gesti ve of m y ocar dial isc he mia .

Ne w - onset left b u n dle b ra nc h b l oc k ( Q R S > 1 2 0 ms ec).

Ne w - onset ri g ht b u n dle b ra nc h b l oc k ( Q R S > 1 2 0 ms ec).

S y m pt o matic b ra dyc ar dia.

As y st ole:

I n a wa ke, sy m pt o m -free patie nts i n si n us r h yt h m, wit h d oc u me nte d peri o ds of 
as yst ole ≥3. 0 sec o n ds or a n y  esca pe rate < 4 0 b p m, or wit h a n esca pe r h yt h m 
t hat is bel o w t he A V n o de; 

I n a wa ke, sy m pt o m -free patie nts wit h atrial fi brillati o n a n d bra d yc ar dia wit h 
1 or m ore pa uses of at least 5 sec o n ds or l o n ger ; 

Atrial fl utter or fi brillati o n, wit h ra pi d ve ntric ular res p o nse rate: ra pi d = rate 
> 1 2 0 b p m.

S ustai ne d su pra ve ntric ular tac h yc ar dia (rate > 1 2 0 b p m) ( “s ustai ne d” = s h ort 
d urati o n wit h rele va nt s y m pt o ms or lasti n g > 1 mi n ute) .
0 9 0 1 7 7 e 1 9 b b 9 c 5f d\ A p pr o v e d\ A p pr o v e d O n: 0 3- N o v- 2 0 2 2 1 1: 4 8 ( G M T)

P F -0 7 0 3 8 1 2 4
Pr ot oc ol C 3 9 4 1 0 0 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 2 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 Marc h 2 0 2 1)
Pa ge 1 1 5

Ve ntric ular r h y t h ms > 3 0 sec o n ds’ d urati o n, i ncl u di n g i di o ve ntric ular r h y t h m (heart 
rate < 4 0 b p m), accelerate d i di o ve ntric ular r hyt h m ( H R 4 0 b p m t o < 1 0 0 b p m), a n d 
m o n o m or p hic/ p ol y m or p hic ve ntric ular tac h ycar dia ( H R > 1 0 0 b p m (s uc h as
torsa des de p oi ntes) ).

T y pe II sec o n d- de gree ( M o bitz II) A V b l oc k.

C o m plete (t hir d- de gree) h eart b l oc k.
E C G Fi n di n gs T h at Q u alif y as S A Es

C ha n ge i n patter n s u g gesti ve of ne w m y ocar dial i nfarcti o n .

S ustai ne d v e ntric ular ta c h yarr h yt h mias ( > 3 0 sec o n ds’ d urati o n) .

Sec o n d - or t hir d - de gree A V bl oc k re q uiri n g pace ma ker place me nt.

As y st olic pa uses re q uiri n g pace ma ker place me nt.

Atrial fl utter or fi brillati o n wit h ra pi d ve ntric ular res p o nse re q uiri n g car di o versi o n.

Ve ntric ular fi brillati o n/fl utter.

At t he discreti o n of t he i n vesti gat or, a n y arr h yt h mia classifie d as a n a d verse 
e x perie nce.
T he e n u merate d list of maj or e ve nts of p ote ntial cli nical c o ncer n are rec o m me n de d as “alerts” or 
n otificati o ns fr o m t he c ore E C G la b orat or y t o t he i n vesti gat or a n d Pfizer st u d y tea m, a n d n ot t o be 
c o nsi dere d as all i ncl usi ve of w hat t o be re p orte d as A Es/ S A Es.
0 9 0 1 7 7 e 1 9 b b 9 c 5f d\ A p pr o v e d\ A p pr o v e d O n: 0 3- N o v- 2 0 2 2 1 1: 4 8 ( G M T)

P F -0 7 0 3 8 1 2 4
Pr ot oc ol C 3 9 4 1 0 0 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 2 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 Marc h 2 0 2 1)
Pa ge 1 1 6
1 0. 8. A p pe n di x 8 : Pr o hi bite d Pri or a n d C o nc o mit a nt Me dic ati o ns 
1 0. 8. 1. Pr o hi bite d Pri o r a n d C o nc o m it a nt Me dic ati o ns
T he pr o hi bite d c o nc o mita nt me dicati o ns liste d bel o w s h o ul d n ot be ta ke n wit h P F - 0 7 0 3 8 1 2 4 
f or t he peri o d of ti me at least e q ual t o t he re q uire d was h o ut peri o d liste d i n t he ta ble, a n d 
t hr o u g h o ut t he c o n d uct of t he st u d y.  
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 s p o ns 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 
partici pati o n of a n y partici pa nt wit h pr o hi bite d me dicati o n use d uri n g t he st u d y.
Dr u g C a te g or y 
Dr u gs ( E x a m ples bel o w)
Re q uire d W as h o ut Peri o d 
R e q uire me nt P ri or t o 
D a y 1/ R a n d o m iz ati o n
A n y cell de pleti n g 
a ge nts
rit u xi ma b or ot her selecti ve 
B- l y m p h oc yte de pleti n g a ge nts 
(i ncl u di n g e x peri me ntal a ge nts), 
ale mt uz u ma b ( Le mtra da ® or 
Ca m Pat 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 y m p h oi d 
irra diati o n, etc.
6 m o nt hs or 5 half -li ves (if k n o w n), 
w hic he ver is l o n ger, or u ntil l y m p h oc yte 
c o u nt ret ur ns t o n or mal, w hic he ver is 
l o n ger.
I L-1 7 i n hi bit or, 
I L-1 2/ 2 3 i n hi bit or, or 
I L-2 3 i n hi bit or
sec u ki n u ma b ( C ose nt y x ® ), 
i xe kiz u ma b ( Taltz® ), uste ki n u ma b 
( Stelara ®), br o dal u ma b ( Sili q® ), 
g usel k u ma b ( Tre mf ya ® ), 
risa n kiz u ma b ( S k yrizi® ), 
til dra kiz u ma b (Il u m ya® ), a n d 
bi m e kiz u ma b,
1 2 w ee ks. 
T N F i n hi bit or
a dali m u ma b ( H u mira ® or bi osi milars), 
cert oliz u ma b ( Ci mzia ® ), g oli m u ma b 
( Si m p o ni® a n d Si m p o ni Aria ® ).
1 0 w ee ks or 5 half-li ves ( w hic he ver is 
l o n ger) ( N ote: I nfli xi ma b ( Re mica de® or 
bi osi milars) 8 wee ks, Eta nerce pt 
( E n brel® or bi osi milars) 4 we e ks).
Ot her bi ol o gics
d u pil u ma b ( D u pi xe nt® ), efaliz u ma b 
( Ra pti va® ), a batace pt ( Ore ncia® ).
1 2 w ee ks u nless ot her wise s pecifie d i n 
t his ta ble.
T o pic al P D E 4 
i n hi bit ors ( a n y w here 
o n t he b o d y), or al 
P D E 4 i n hi bit ors
crisa b or ole ( E ucrisa ® ), r ofl u milast 
( Dalires p® , A R Q-1 5 1), a pre milast 
( Otezla® ), difa milast.
2 we e ks. 
S yste mic 
c ortic oster oi ds ( or al, 
p are nter al)
4 w ee ks 
(sta ble use /re g ular re gi me n of 
i ntra nasal/i n hale d/ o p ht hal mic 
c ortic oster oi ds wit h ≥1 4 da ys of 
c o nsiste nt use pri or t o 
Da y 1/ Ra n d o mizati o n are per mitte d t o 
c o nti n ue b ut m ust n ot alter or st o p 
re gi me n d uri n g t he st u d y).
0 9 0 1 7 7 e 1 9 b b 9 c 5f d\ A p pr o v e d\ A p pr o v e d O n: 0 3- N o v- 2 0 2 2 1 1: 4 8 ( G M T)

P F -0 7 0 3 8 1 2 4
Pr ot oc ol C 3 9 4 1 0 0 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 2 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 Marc h 2 0 2 1)
Pa ge 1 1 7
Dr u g C a te g or y 
Dr u gs ( E x a m ples bel o w)
Re q uire d W as h o ut Peri o d 
R e q uire me nt P ri or t o 
D a y 1/ R a n d o m iz ati o n
S yste mic 
i m m u n os u p pressi ve 
a ge nts a n d ot her or al 
n o n bi ol o gic tre at m e nts
met h otre xate, lefl u n o mi de, 
s ulfasalazi ne, h y dr o x yc hl or o q ui ne, 
azat hi o pri ne, c ycl os p ori ne, 
miz ori bi ne, tacr oli m us, M M F, 
h y dr o x ycar ba mi de ( h y dr o x y urea), 
f u maric aci d deri vati ves, acitreti n.
4 w ee ks.
Or al J A K i n hi bit ors
t ofaciti ni b ( Xelja nz® ), bariciti ni b 
( Ol u mia nt® ), u pa daciti ni b, peficiti ni b, 
fil g oti ni b, a br ociti ni b ( Ci bi n q o ® ).
4 w ee ks.
I nterfer o n g a m m a
i nterfer o n ga m ma-1 b ( Acti m m u ne ® ).
4 we e ks.
Li g ht t her a p y etc.
s u n bat hi n g, ta n ni n g be d use, or li g ht 
t hera p y (U V, U V -B, P U V A), e xci mer 
laser ( 3 0 8 n m).
4 w ee ks. 
T o pic al reti n oi ds, 
Vit a m i n D a n al o g ues, 
B P O, a nt hr ali n 
( dit hr a n ol), 
ker at ol ytics (s alic ylic 
aci d), t ars, o n st u d y 
tre at a ble lesi o ns
tazar ote ne, calci p otrie ne. 
2 w ee ks (sta ble re gi me n wit h ≥1 4 da ys 
of c o nsiste nt use pri or t o 
Da y 1/ Ra n d o mizati o n a n d n ot o n t he 
st u d y treata ble lesi o ns are per mitte d t o 
c o nti n ue b ut m ust n ot alter or st o p t heir 
re gi me n d uri n g t he st u d y.
S yste mic a nti bi otics
2 w ee ks ( S h ort c o urses ( ≤1 4 da ys) of 
s yste mic a nti bi otics ma y be gi ve n 
d uri n g t he st u d y if cli nicall y necessar y 
f or t he treat me nt of ne w o nset 
i nfecti o ns).
T C S, C l ass I t o V, 
a n y w here o n t he b o d y
beta met has o ne, cl o betas ol, 
difl oras o ne, hal o bet as ol, a mci n o ni de, 
des o xi metas o ne, fl u oci n o ni de, 
halci n o ni de, m o metas o ne, 
tria mci n ol o ne, cl oc ort ol o ne, 
fl ura n dre n oli de, fl uticas o ne, 
fl u oci n ol o ne, pre d nicar bate, 
h y dr oc ortis o ne b ut yrate, 
h y dr oc ortis o ne pr o b utate, 
h y dr oc ortis o ne valerate.
2 w ee ks. 
T CI or J A K i n hi bit or , 
a n y w here o n t he b o d y
t o pical tacr oli m us ( Pr ot o pic® ), t o pical 
pi m ecr oli m us ( Eli del ® ), d el g ociti ni b .
2 w ee ks. 
T o pic al a nti hist a mi nes 
a n y w here o n t he b o d y
d o xe pi n.
2 w ee ks (t o pical a nti hista mi nes f or 
seas o nal aller gies are all o we d pr o vi de d 
sta ble d oses wit hi n 7 d a y s of 
Da y 1/ Ra n d o mizati o n). 
0 9 0 1 7 7 e 1 9 b b 9 c 5f d\ A p pr o v e d\ A p pr o v e d O n: 0 3- N o v- 2 0 2 2 1 1: 4 8 ( G M T)

P F -0 7 0 3 8 1 2 4
Pr ot oc ol C 3 9 4 1 0 0 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 2 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 Marc h 2 0 2 1)
Pa ge 1 1 8
Dr u g C a te g or y 
Dr u gs ( E x a m ples bel o w)
Re q uire d W as h o ut Peri o d 
R e q uire me nt P ri or t o 
D a y 1/ R a n d o m iz ati o n
T o pic al a nti b acteri al 
me dic ati o ns or 
pr o d ucts, i ncl u di n g 
s o a ps, ble ac h b at hs, or 
t o pic al s o di u m 
h y p oc hl orite - b ase d 
pr o d ucts a n y w here o n 
t he b o d y
7 da ys. 
S yste mic se d ati n g 
a nti hist a mi nes
h y dr o x yzi ne, di p he n h y dra mi ne,
7 da ys, 
S yste mic n o n -se d ati n g 
a nti hist a mi nes i n a 
n o nst a ble 
(e g, esc al ati n g, 
decre asi n g, or P R N) 
re gi me n
cetirizi ne,
7 da ys (sta ble n o n -se dati n g s yste mic 
a nti hista mi ne re gi me n wit h ≥7 da ys of 
c o nsiste nt use pri or t o 
Da y 1/ Ra n d o mizati o n are per mitte d t o 
c o nti n ue b ut m ust n ot alter or st o p t heir 
re gi me n d uri n g t he st u d y).
Use of bl a n d 
( n o n-me dic ate d , ure a-
a n d l actic aci d - free) 
e mollie nts o n tre at a ble 
lesi o ns
2 4 h o urs ( After t he 
Da y 1/ Ra n d o mizati o n Visit, use of 
bla n d ( n o n -me dicate d) e m ollie nt(s) is 
per mitte d d uri n g t he st u d y t o ma na ge 
dr y s ki n i n areas s urr o u n di n g b ut n ot o n 
or o verla p pi n g t he treata ble lesi o ns ).
A n y ot her bi ol o gic 
i n vesti g ati o n al t her a p y 
f or A D, ps ori asis or 
ps ori atic art hritis
6 m o nt hs u nless ot her wise s pecifie d i n 
t his ta ble.
A n y ot her n o n -
bi ol o gic al 
i n vesti g ati o n al t her a p y 
or pr oce d ure f or A D, 
ps ori asis or ps ori atic 
art hritis
1 2 w ee ks u nless ot her wise s pecifie d i n 
t his ta ble.
Pr o hi bite d 
C o nc o m it a nt 
Me dic ati o ns w hic h 
m a y res ult i n dr u g -
dr u g i nter acti o n 
See Secti o n 1 0. 8. 2 bel o w .
7 da ys or 5 half -li ves ( w hic he ver is 
l o n ger).
1 0. 8. 2. Pr o hi bite d C o nc o mit a nt Me dic ati o ns w hic h m a y R es ult i n D DI 
U p o n t o pical a p plicati o n of P F - 0 7 0 3 8 1 2 4, sys te mic e x p os ure t o date has bee n l o w. 
Ma xi m u m plas ma c o nce ntrati o n has n ot e xcee de d 1 n M; w hic h is a p pr o xi matel y  1 0 0 0-f ol d 
less t ha n t he IC 5 0 val ues f or C Y P 4 5 0 a n d U G T i n hi biti o n, as well as vari o us tra ns p orters. 
T heref ore, P F -0 7 0 3 8 1 2 4 has a l o w ris k of a n y dr u g -dr u g i nteracti o n. F or m ore details, please 
refer t o t he I n vesti gat or’s Br oc h ure.
0 9 0 1 7 7 e 1 9 b b 9 c 5f d\ A p pr o v e d\ A p pr o v e d O n: 0 3- N o v- 2 0 2 2 1 1: 4 8 ( G M T)

P F -0 7 0 3 8 1 2 4
Pr ot oc ol C 3 9 4 1 0 0 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 2 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 Marc h 2 0 2 1)
Pa ge 1 1 9
1 0. 9. A p pe n di x 9 : Alter n ati ve Me as ures D uri n g P u bli c E mer ge ncies
T he alter nati ve st u d y meas ures descri be d i n t his secti o n are t o be f oll o we d d uri n g p u blic 
e mer ge ncies, i ncl u di n g t he C O VI D -1 9 pa n de mic. T his a p pe n di x a p plies f or t he d urati o n of 
t he C O VI D-1 9 pa n de mic gl o ball y a n d will bec o me effecti ve f or ot h er p u blic e mer ge ncies 
o nl y  u p o n writte n n otificati o n fr o m Pfizer. 
Use of t hese alter nati ve st u d y  meas ures are e x pecte d t o cease u p o n t he ret ur n of b usi ness as 
us ual circ u msta nces (i ncl u di n g t he lifti n g of a n y q uara nti nes a n d tra vel ba ns/a d vis ories). 
1 0. 9. 1. Tele he alt h Visits
I n t he e ve nt t hat i n-cli nic st u d y visits ca n n ot be c o n d ucte d, e ver y  eff ort s h o ul d be ma de t o 
f oll o w u p o n t he safet y of st u d y partici pa nts at sc he d ule d visits per t he Sc he d ule of Acti vities
or u nsc he d ule d visits. Tele h ealt h visits ma y be use d t o c o nti n ue t o assess partici pa nt safet y 
a n d c ollect data p oi nts. Tele healt h i ncl u des t he e xc ha n ge of healt hcare i nf or mati o n a n d 
ser vices via telec o m m u nicati o n tec h n ol o gies (e g, a u di o, vi de o, vi de o-c o nfere nci n g s oft ware) 
re m otel y, all o wi n g t he partici pa nt a n d t he i n vesti gat or t o c o m m u nicate o n as pects of cli nical 
care, i ncl u di n g me dical a d vice, re mi n ders, e d ucati o n, a n d safet y m o nit ori n g. T he f oll o wi n g 
assess me nts m ust be perf or me d d uri n g a tele healt h visit :

Re vie w a n d rec or d st u d y i nter ve nti o n(s), i ncl u di n g c o m plia nce a n d misse d d oses.

Re vie w a n d rec or d a n y   A Es a n d S A Es si nce t he last c o ntact. Refer t o Secti o n 8. 3 .

Re vie w a n d rec or d a n y ne w c o nc o mita nt me dicati o ns or c ha n ges i n c o nc o mita nt 
me dicati o ns si nce t he last c o ntact .

Re vie w a n d rec or d c o ntrace pti ve met h o d a n d res ults of pre g na nc y testi n g. C o nfir m 
t hat t he partici pa nt is a d heri n g t o t he c o ntrace pti o n met h o d(s) re q uire d i n t he 
pr ot oc ol. Re fer t o A p pe n di x 4 a n d Secti o n 1 0. 9. 2. 1 of t his a p pe n di x re gar di n g 
pre g na nc y  tests.

C o nfir mati o n t hat I P is a p plie d t o all treat me nt -eli gi ble areas re g ularl y. 

A d mi nis trati o n of P R Os , if a p plica ble f or t hat visit.

If a d mi nistere d, P R O assess me nt s h o ul d occ ur at t he be gi n ni n g of t he visit a n d t o 
be c o n d ucte d i n a q uiet, pri vate area (ie , n o o ne else ar o u n d a n d/ or a ble t o pr o vi de 
i n p ut or i nfl ue nce t heir res p o nses).

D oc u me nt r es p o nses t o 
 

T he site staff s h o ul d rea d t he i nstr ucti o ns a n d q uesti o ns t o t he partici pa nt a n d 
rec or d t he partici pa nt’s res p o nses i n s o urce d oc u me nts .
0 9 0 1 7 7 e 1 9 b b 9 c 5f d\ A p pr o v e d\ A p pr o v e d O n: 0 3- N o v- 2 0 2 2 1 1: 4 8 ( G M T)
C CI

P F -0 7 0 3 8 1 2 4
Pr ot oc ol C 3 9 4 1 0 0 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 2 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 Marc h 2 0 2 1)
Pa ge 1 2 0

Q uesti o ns s h o ul d be rea d ver bati m at clear a n d c o mf orta ble pace (re -rea d, if 
nee de d) wit h N O i n p ut fr o m site staff or p h y sicia ns.

D o n ot i nter pret a n y part of t he q uesti o n naire f or t he partici pa nt. If t he partici pa nt 
d oes n ot u n dersta n d, please re peat t he q uesti o n a n d res p o nse c h oices ver bati m a n d 
as k t he m t o select t he res p o nse t hat t he y  feel best re prese nts his/ her e x perie nce.

C o nfir m t he patie nt’s res p o nse selecti o n bef ore y o u rec or d t he a ns wer (e g , y o u 
w o ul d li ke me t o select “ m o derate pai n”, is t hat ri g ht?).

O bser vati o n of a p plicati o n of st u d y  i nter ve nti o n o n treata ble area (s) (if feasi ble).

Assess me nt of l ocal t olera bilit y, p ost a p plicati o n of I P o n n o n -lesi o nal areas.

Assess me nt of efficac y  o utc o me meas ures as descri be d i n Secti o n 1 0. 9. 6 .
St u d y  partici pa nts m ust be re mi n de d t o pr o m ptl y n otif y site staff a b o ut a ny c ha n ge i n t heir 
healt h stat us.
1 0. 9. 2. Alter n ati ve F acilities f or S afet y Assess me nts
1 0. 9. 2. 1. L a b or at or y Testi n g
If a st u dy partici pa nt is u na ble t o visit t he site f or pr ot oc ol -s pecifie d safet y la b orat or y 
e val uati o ns, testi n g m a y  be c o n d ucte d at a l ocal la b orat or y  if per mitte d b y l ocal re g ulati o ns.
T he l ocal la b orat or y  ma y be a sta n dal o ne i nstit uti o n or wit hin a h os pital. T he f oll o wi n g 
safety la b orat or y  e val uati o ns ma y be perf or me d at a l ocal la b orat or y: 

La b orat or y  Safety e val uati o ns, i ncl u di n g pre g na nc y  testi n g (Ta ble 6 ).
If a l ocal la b orat or y is use d, q ualifie d st u d y site pers o n nel m ust or der, recei ve, a n d re vie w 
res ults. Site staff m ust c ollect t he l ocal la b orat or y refere nce ra n ges a n d certificati o ns/
accre ditati o ns f or fili n g at t he site. La b orat or y test res ults are t o b e pr o vi de d t o t he site staff 
as s o o n as p ossi ble. T he l ocal la b orat or y  re p orts s h o ul d be file d i n t he partici pa nt’s s o urce 
d oc u me nts/ me dical rec or ds. Rele va nt data fr o m t he l ocal la b orat or y  re p ort s h o ul d 
be  rec or de d o n t he C R F.
If a partici pa nt re q uiri n g pre g na nc y testi n g ca n n ot visit a l ocal la b orat or y  f or pre g na nc y 
testi n g, a h o me uri ne pre g na nc y testi n g kit wit h a se nsiti vit y of at least 2 5 mI U/ m L ma y  be 
use d b y  t he partici pa nt t o perf or m t he test at h o me, if c o m plia nt wit h l ocal re g ulat or y 
re q uire me nts. T he pre g na nc y test o utc o me s h o ul d be d oc u me nte d i n t he partici pa nt’s s o urce 
d oc u me nts/ me dical rec or ds a n d rele va nt data rec or de d o n t he C R F. C o nfir m t hat t he 
partici pa nt is a d heri n g t o t he c o ntrace pti o n met h o d(s) re q uire d i n t he pr ot oc ol.
0 9 0 1 7 7 e 1 9 b b 9 c 5f d\ A p pr o v e d\ A p pr o v e d O n: 0 3- N o v- 2 0 2 2 1 1: 4 8 ( G M T)

P F -0 7 0 3 8 1 2 4
Pr ot oc ol C 3 9 4 1 0 0 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 2 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 Marc h 2 0 2 1)
Pa ge 1 2 1
1 0. 9. 2. 2. Electr oc ar di o gr a m s
If t he partici pa nt is u na ble t o visit t he st u d y site f or E C Gs, t he partici pa nt ma y visit a n 
alter nati ve facilit y t o ha ve t he E C Gs perf or me d. Q ualifie d st u d y site pers o n nel m ust or der, 
recei ve, a n d re vie w res ults. 
1 0. 9. 3. St u d y I nter ve nti o n
If t he safety of a trial partici pa nt is at ris k beca use t he y ca n n ot c o m plete re q uire d e val uati o ns 
or a d here t o critical miti gati o n ste ps, t he n disc o nti n ui n g t hat partici pa nt fr o m st u d y  
i nter ve nti o n m ust be c o nsi dere d.
St u d y  i nter ve nti o n m a y b e s hi p pe d b y  c o urier t o st u d y partici pa nts if per mitte d b y l ocal 
re g ulati o ns a n d i n acc or da nce wit h st ora ge a n d tra ns p ortati o n re q uire me nts f or t he st u d y 
i nter ve nti o n. Pfizer d oes n ot per mit t he s hi p me nt of st u d y i nter ve nti o n b y  mail. T he trac ki n g 
rec or d of s hi p me nts a n d t he c hai n of c ust o d y of st u d y i nter ve nti o n m ust be ke pt i n t he 
partici pa nt’s s o urce d oc u me nts/ me dical rec or ds.
1 0. 9. 4. H o me He alt h Visits
A h o me healt h care ser vice ma y be utilize d t o facilitate sc he d ule d visits per t he Sc he d ule of 
Acti vities . H o me healt h visits i ncl u de a healt hcare pr o vi der c o n d ucti n g a n i n- pers o n st u d y  
visit at t he partici pa nt’s l ocati o n, rat her t ha n a n i n -pers o n st u d y visit at t he site. T he 
f oll o wi n g ma y be perf or me d d uri n g a h o me healt h visit:

Re vie w a n d rec or d st u d y i nter ve nti o n(s), i ncl u di n g c o m plia nce a n d misse d d oses;

Re vie w a n d rec or d a n y   A Es a n d S A Es si nce t he last c o ntact. Refer t o Secti o n 8. 3;

Re vie w a n d rec or d a n y ne w c o nc o mita nt me dicati o ns or c ha n ges i n c o nc o mita nt 
me dicati o ns si nce t he last c o ntact ;

Re vie w a n d rec or d c o ntrace pti ve met h o d a n d res ults of pre g na nc y  testi n g. C o nfir m 
t hat t he partici pa nt is a d heri n g t o t he c o ntrace pti o n met h o d(s) re q uire d i n t he 
pr ot oc ol. Refer t o A p pe n di x 4 a n d Secti o n 1 0. 9. 2. 1 _ H o me _ Healt h _ Visits of t his 
a p pe n di x re gar di n g pre g na nc y  tests;

E C G ;

Vital si g ns ;

P h y sical assess me nt;

La b orat or y  sa m ples, 

C ollect a n d wei g h pre vi o us st u d y i nter ve nti o n t u bes;

Dis pe nsi n g of st u d y i nter ve nti o n;
0 9 0 1 7 7 e 1 9 b b 9 c 5f d\ A p pr o v e d\ A p pr o v e d O n: 0 3- N o v- 2 0 2 2 1 1: 4 8 ( G M T)
C CI

P F -0 7 0 3 8 1 2 4
Pr ot oc ol C 3 9 4 1 0 0 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 2 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 Marc h 2 0 2 1)
Pa ge 1 2 2

St u d y  i nter ve nti o n a p plicati o n a n d o bser vati o n ;

L ocal T olera bilit y  assess me nts;

Ot her, as deter mi ne d b y t he I n vesti gat or a n d/ or s p o ns or.
1 0. 9. 5. A d verse E ve nts a n d Seri o us A d verse E ve nts
If a partici pa nt has CO VI D -1 9 d uri n g t he st u d y , t his s h o ul d be re p orte d as a n A E or seri o us 
S A E a n d a p pr o priate me dical i nter ve nti o n pr o vi de d. Te m p orar y  disc o nti n uati o n of t he st u d y 
i nter ve nti o n ma y be me dicall y a p pr o priate u ntil t he partici pa nt has rec o vere d fr o m 
C O VI D - 1 9. 
It is rec o m me n de d t hat t he i n vesti gat or disc uss te m p orar y or per ma ne nt disc o nti n uati o n of 
st u d y i nter ve nti o n wit h t he st u d y me dical m o nit or. 
1 0. 9. 6. Effi c ac y Assess me nts
If re m ote vi de o visit is feasi ble a n d is bei n g c o n d ucte d as part of t he Tele healt h Visit i n t he
e ve nt t hat i n-cli nic st u d y visits ca n n ot be c o n d ucte d, t he f oll o wi n g pr oce d ures a n d 
assess me nts ma y be c o nsi dere d: 

Efficac y  Assess me nts f or A D, i ncl u di n g I G A, E A SI , B S A, a n d se vere lesi o n T S S (if 
a p plica ble).

Efficac y  Assess me nts f or Ps O , i ncl u di n g P G A, P A SI , a n d B S A.
O nl y  q ualifie d raters will be all o we d t o e val uate partici pa nts re m otely.
0 9 0 1 7 7 e 1 9 b b 9 c 5f d\ A p pr o v e d\ A p pr o v e d O n: 0 3- N o v- 2 0 2 2 1 1: 4 8 ( G M T)

P F -0 7 0 3 8 1 2 4
Pr ot oc ol C 3 9 4 1 0 0 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 2 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 Marc h 2 0 2 1)
Pa ge 1 2 3
1 0. 1 0. A p pe n di x 1 0 : Di a g n osis Criteri a f or A D
Per A D -s pecific I ncl usi o n Criteria as i n Secti o n 5. 1. 2. 1 , a partici pa nt is t o ha ve a cli nical 
dia g n osis of A D acc or di n g t o t he criteria of Ha nifi n a n d Raj ka. 7
H a nifi n a n d R aj k a’s Di a g n ostic Criteri a f or A D
M aj or Criteri a ( m ust h a ve at
le ast t hree)
Pr urit us
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, A D)
Mi n or Criteri a ( m ust h a ve at le ast t hree)
Xer osis
Ic ht h y osis/ kerat osis pilaris/ pal mar h y perli nearit y
I m me diate (t y 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 w ar d c uta ne o us i nfecti o ns (es p. sta p h. a ure us a n 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 w ar 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 cataracts
Or bital dar ke ni n g
Facial pall or, facial er yt he ma
Pit yriasis 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 wo 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 ors
W hite d er m o gra p his m, dela ye d bla nc h
0 9 0 1 7 7 e 1 9 b b 9 c 5f d\ A p pr o v e d\ A p pr o v e d O n: 0 3- N o v- 2 0 2 2 1 1: 4 8 ( G M T)

P F -0 7 0 3 8 1 2 4
Pr ot oc ol C 3 9 4 1 0 0 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 2 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 Marc h 2 0 2 1)
Pa ge 1 2 4
1 0. 1 1. A p pe n di x 1 1 : C- S S R S
Partici pa nt s s h o ul d be e val uate d f or an y  psyc hiatric c o n diti o n i ncl u di n g rece nt or acti ve 
s uici dal i deati o n or be ha vi or a n d e xcl u de d fr o m t he st u d y  w h o meets a n y  of t he f oll o wi n g 
criteria at Scree ni n g: 
a.
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 y ear: 
“ Yes” a ns wers o n ite ms 4 or 5 of t he C -S S R S;
b.
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 an y  of t he s uici dal be ha vi or ite ms of t he C-S S R S;
c.
A n y  lifeti me hist or y of seri o us or rec urre nt s uici dal be ha vi or;
d.
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;
e.
I n t he o pi ni o n of t he i n vesti gat or or Pfizer ( or desi g nee) e xcl usi o n is re q uire d.
0 9 0 1 7 7 e 1 9 b b 9 c 5f d\ A p pr o v e d\ A p pr o v e d O n: 0 3- N o v- 2 0 2 2 1 1: 4 8 ( G M T)

P F -0 7 0 3 8 1 2 4
Pr ot oc ol C 3 9 4 1 0 0 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 2 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 Marc h 2 0 2 1)
Pa ge 1 2 5
1 0. 1 2. A p pe n di x 1 2 : Dise ase - S pecific Assess me nts
1 0. 1 2. 1. A D -s pecific assess me nts
1 0. 1 2. 1. 1. I G A
T he I G A of A D is sc ore d o n a 5 -p oi nt scale ra n gi n g fr o m 0 (clear) t o 4 (se vere), reflecti n g a 
gl o bal c o nsi derati o n of t he er yt he ma, i n d urati o n a n d scali n g . T he cli nical e val uat or of A D 
will perf or m a n assess me nt of t he o verall se verit y of A D a n d assi g n a n I G A sc ore a n d 
cate g or y as descri be d bel o w.
T a ble 7. 
I n vesti g at or's Gl o b al Assess me nt f or A D
Sc ore
C ate g or y
Descri pti o n *
0
Clear
A D 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 
Clear
O verall, t he A D 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 me 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 nificati o n; e xc oriati o n a n d o ozi n g/cr usti n g are a bse nt.
2
Mil d
O verall, t he A D c o nsists of lesi 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 netrati 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 usti n g is a b se nt.
3
M o derate
O verall, t he A D c o nsists of lesi o ns t hat are re d; w it h 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; 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 k i 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 A D c o nsists of lesi o ns t hat are dee 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 vere o ozi n g/cr usti n g.
* T he I G A will e xcl u de hai r-beari n g scal p fr o m t he assess me nt/sc ori n g.
1 0. 1 2. 1. 2. E A SI
T he E A SI q ua ntifies t he se verit y of a partici pa nt’s A D base d o n b ot h se verit y  of lesi o n by 
cli nical si g ns a n d t he perce nt of B S A affecte d. E A SI  is a c o m p osite sc ori n g of t he de gree of 
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 (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 f or 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 ole b o d y.8 T he cli nical e val uat or o f 
A D will perf or m a n assess me nt of se verity a n d area i n v ol ve d as descri be d bel o w.
Lesi o n Se verit y  b y Cli nical Si g ns 
T he basic c haracteristics of A D lesi o ns (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) pr o vi de 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 cli nical si g ns is perf or me d se parately f or 4 b o d y  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 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 are sc ore d f or eac h b o d y 
0 9 0 1 7 7 e 1 9 b b 9 c 5f d\ A p pr o v e d\ A p pr o v e d O n: 0 3- N o v- 2 0 2 2 1 1: 4 8 ( G M T)

P F -0 7 0 3 8 1 2 4
Pr ot oc ol C 3 9 4 1 0 0 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 2 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 Marc h 2 0 2 1)
Pa ge 1 2 6
re gi o n acc or di n g t o a 4-p oi nt scale: 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 8 bel o w.
T a ble 8.
Cli nic al Si g n Se verit y Sc ori n g Criteri a f or E A SI
Sc ore
Descri pti o n
Er yt 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 me ntati o n a n d/ or 
h y p 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
I n 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 oriati 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 pic 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 urface 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 s ki n mar ki n gs, a n d 
lic 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 oarse 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 hair -beari n g scal p fr o m t he assess me nt/sc ori n g.
Area Sc ore
T he e xte nt ( % B S A ) t o w hic h eac h of t he f o ur b o d y re gi o ns ie hea d a n d nec k, u p per li m bs, 
tr u n k a n d l o wer li m bs is i n v ol ve d wit h A D is cate g orize d usi n g a n o n-li near scali n g met h o d 
t o a n u merical area sc ore acc or di n g t o t he f oll o wi n g B S A sc ori n g criteria ( Ta ble 9 ). T he 
% B S A is calc ulate d as descri be d i n Secti o n 1 0. 1 2. 1. 3 .
0 9 0 1 7 7 e 1 9 b b 9 c 5f d\ A p pr o v e d\ A p pr o v e d O n: 0 3- N o v- 2 0 2 2 1 1: 4 8 ( G M T)

P F -0 7 0 3 8 1 2 4
Pr ot oc ol C 3 9 4 1 0 0 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 2 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 Marc h 2 0 2 1)
Pa ge 1 2 7
T a ble 9.
E A SI Are a Sc ore Criteri a
Perce nt B S A * wit h A D i n a 
B o d y Re gi o n
Are a Sc ore
0 %
0
0 t o < 1 0 %
1
1 0 t o < 3 0 %
2
3 0 t o < 5 0 %
3
5 0 t o < 7 0 %
4
7 0 t o < 9 0 %
5
9 0 t o 1 0 0 %
6
* b ase d o n h a n d pri nt met h o d
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 dy 
(Ta ble 1 0 ). 
T a ble 1 0 . B o d y Re gi o n Wei g hti n g
B o d y Re gi o n
T ot al N u m ber of 
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 pr int
B o d y Re gi o n 
Wei g hti n g
He a d a n d Nec k
1 0
1 0 %
0. 1
U p per Li m bs
2 0
5 %
0. 2
Tr u n k (i ncl u di n g a xill ae a n d gr oi n)
3 0
3. 3 3 %
0. 3
L o wer Li m bs (i ncl u di n g b utt oc ks)
4 0
2. 5 %
0. 4
Calc ulati o n of E A SI Sc ore 
I n e ac h b o d y 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 gio 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 t he f oll o wi n g e q uati o n.
E A SI = 0. 1 A h( E h+I h+ E x h+ L h) + 0. 2 A u( Eu+I u+ E x u+ L u) + 0. 3 At( Et+I t+ E x t+ L t) + 
0. 4 Al( E l+I l+ E x l+ L l)
A = Area Sc ore; E = er yt he ma; 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 ore 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 A D. Si nce t he hair -beari n g scal p will be e xcl u de d fr o m t he 
E A SI  assess me nt i n t his st u d y, t he ma xi m u m p ossi ble sc ore will be less t ha n 7 2. 0.
0 9 0 1 7 7 e 1 9 b b 9 c 5f d\ A p pr o v e d\ A p pr o v e d O n: 0 3- N o v- 2 0 2 2 1 1: 4 8 ( G M T)

P F -0 7 0 3 8 1 2 4
Pr ot oc ol C 3 9 4 1 0 0 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 2 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 Marc h 2 0 2 1)
Pa ge 1 2 8
1 0. 1 2. 1. 3. B S A
Ide ntif y  t he s urface area e q ui vale nt of 1 ha n d pri nt i n eac h res pecti ve b o d y re gi on.
B o d y re gi o n val ue is t he n s u m me d acr oss all f o ur b o d y re gi o ns res ulti n g i n a t otal B S A wit h 
A D as descri be d i n t he f oll o wi n g e q uati o n:
B S A ( %) = 0. 1 S h + 0. 2 S u + 0. 3 St + 0. 4 Sl
w here S = b o d y re gi o n s urface area w it h A D; h = hea d & nec k; u = u p per li m bs; t = tr u n k; l = l o wer li m bs. 
1 0. 1 2. 1. 4. Se vere Lesi o n T S S
T he se vere lesi o n T S S is a n assess me nt of t he I n vesti gat or-i de ntifie d/selecte d se vere lesi o n i n 
eac h of t he f oll o wi n g: 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. Eac h 
of t hese are rate d usi n g t he 4 -p oi nt se verit y scale descri be d i n Ta ble 1 1 . T hese rati n gs are 
t he n a d de d t o create a t otal sc ore ( 1 2-p oi nt scale; ra n gi n g fr o m 0 t o 1 2 p oi nts).
T a ble 1 1.
Se vere Lesi o n T S S
Sc ore
Descri pti o n
Er yt he ma ( E ; Re d ness)
0
A bse nt
N o re d ness
1
Mil d
Mil dl y detecta ble er yt he ma; pi n k
2
M o derate
D ull re d; clearl y disti n g uis ha ble
3
Se vere
Dee p, dar k re d ; mar ke d a n d e xte nsi ve
I n d urati o n/ Pa p ulati o n (I)
0
A bse nt
N o ne
1
Mil d
Sli g htl y per ce pti ble ele vati o n
2
M o derate
Clearl y perce pti ble ele vati o n b ut n ot e xte nsi ve
3
Se vere
Mar ke d a n d e xte nsi ve ele vati o n
E xc oriati o n ( E x ; E vi de nce of Scratc hi n g)
0
A bse nt
N o e vi de nce of e xc oriati o n
1
Mil d
Mil d e xc oriati o n prese nt
2
M o derate
Defi nite e xc oriati o n prese nt
3
Se vere
Mar ke d, dee p, or e xte nsi ve e xc oriati o n prese nt
Lic he nificati o n ( L ; E pi der mal T hic ke ni n g)
0
A bse nt
N o e pi der mal t hic ke ni n g
1
Mil d
Mi n or e pi der mal t hic ke ni n g
2
M o derate
M o derate e pi der mal t hic ke ni n g; acce nt uate d s ki n li nes
3
Se vere
Se vere e pi der mal t hic ke ni n g; dee pl y acce nt uate d s ki n li nes
0 9 0 1 7 7 e 1 9 b b 9 c 5f d\ A p pr o v e d\ A p pr o v e d O n: 0 3- N o v- 2 0 2 2 1 1: 4 8 ( G M T)

P F -0 7 0 3 8 1 2 4
Pr ot oc ol C 3 9 4 1 0 0 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 2 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 Marc h 2 0 2 1)
Pa ge 1 2 9
1 0. 1 2. 2. Ps ori asis -s pecific assess me nts
1 0. 1 2. 2. 1. P G A
T he P G A of ps oriasis is sc ore d o n a descri pti ve 5- p oi nt scale. 9 T he 5 -p oi nt scale f or P G A is: 
0, “clear”; 1, “al m ost clear”; 2, “ mil d”; 3, “ m o derate”; 4 “se vere”. 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. T he cli nical e val uat or of 
ps oriasis will perf or m a n assess me nt of t he o verall se verit y a n d assi g n a n P G A sc ore a n d 
cate g or y as descri be d bel o w.
T a ble 1 2.
P h ysici a n Gl o b al Assess me nt ( P G A) Sc ore
P h ysici a n’s Gl o b al 
Assess me nt
Descri pti o n
0
Clear
N o si g ns of ps oriasis; p ost -i nfla m mat or y h y per pi g me ntati o n ma y be prese nt
1
Al m ost Clear
N o t hic ke ni n g; n or mal t o pi n k c ol orati o n; n o t o mi ni mal f ocal scali n g
2
Mil d
J ust detecta ble t o mil d t hic ke ni n g; pi n k t o li g ht re d c ol orati o n; pre d o mi na ntl y fi ne 
scali n g
3
M o derate
Clearl y disti n g uis ha ble t o m o derate t hic ke ni n g; d ull t o bri g ht re d, clearl y 
disti n g uis ha ble t o m o derate t hic ke ni n g; m o derate scali n g
4 
Se vere
Se vere t hic ke ni n g wit h har d e d ges; bri g ht t o dee p dar k re d c ol orati o n; 
se vere/c oarse scali n g c o veri n g al m ost all or all lesi o ns
* T he P G A will e xcl u de hair -beari n g scal p, pal ms , s oles, a n d fi n ger a n d t oe nails fr o m t he 
assess me nt/sc ori n g
1 0. 1 2. 2. 2. P A SI
Lesi o n Se verit y  Sc ore 
T he basic c haracteristics of ps oriatic lesi o ns (eryt he ma, i n d urati o n a n d scali n g) pr o vi de a 
mea ns f or assessi n g t he se verit y of lesi o ns. Assess me nt of t hese t hree mai n si g ns is 
perf or me d se paratel y f or f o ur areas of t he b o d y:  hea d, u p per li m bs, tr u n k, a n d l o wer li m bs. 
A vera ge er y t he ma, i n d urati o n a n d scali n g are rate d f or eac h b o d y area acc or di n g t o a 5-p oi nt 
scale: 0, n o i n v ol ve me nt; 1, sli g ht; 2, m o derate; 3, mar ke d; 4, ver y mar ke d. A p pr o priate 
m or p h ol o gic descri pt ors f or eac h se verit y  sc ore are s h o w n i n Ta ble 1 3 .
0 9 0 1 7 7 e 1 9 b b 9 c 5f d\ A p pr o v e d\ A p pr o v e d O n: 0 3- N o v- 2 0 2 2 1 1: 4 8 ( G M T)

P F -0 7 0 3 8 1 2 4
Pr ot oc ol C 3 9 4 1 0 0 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 2 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 Marc h 2 0 2 1)
Pa ge 1 3 0
T a ble 1 3.
C o m p o ne nt Sc ori n g Criteri a f or P A SI
C o m p o ne nt Sc ore
Descri pti o n
Er yt he ma ( E)
0
N o i n v ol ve me nt
N o ne; ma y ha ve resi d ual h y per pi g me ntati o n
1
Sli g ht
Pi n k or li g ht re d
2
M o derate
Dar ker pi n k -re d
3
Mar ke d
Re d
4
Ver y  Mar ke d
E xtre mel y re d, “ beef y” re d
I n d urati o n (I)
0
N o i n v ol ve me nt
N o ne
1
Sli g ht
Mi ni mal ele vati o n relati ve t o n or mal s urr o u n di n g s ki n
2
M o derate
Easil y pal pa ble wit h r o u n de d e d ges
3
Mar ke d
Ele vate d wit h har d, s har p b or ders
4
Ver y  Mar ke d
Ver y  ele vate d wit h ver y har d, s har p b or ders
Scali n g ( S)
0
N o i n v ol ve me nt
N o ne
1
Sli g ht
Mai nl y fi ne scale, s o me lesi o n partiall y c o vere d
2
M o derate
C oarser t hi n scale, m ost lesi o ns partiall y c o vere d
3
Mar ke d
C oarser t hic k scale, nearl y all lesi o ns c o vere d, r o u g h
4
Ver y  Mar ke d
Ver y  t hic k scale, all lesi o ns c o vere d, ver y r o u g h
* T he P A SI will e xcl u de hair -beari n g scal p, pal ms , s oles, a n d fi n ger a n d t oe nails fr o m t he 
assess me nt/sc ori n g
Area Sc ore
T he e xte nt ( % B S A) t o w hic h eac h of t he f o ur b o d y re gi o ns (ie hea d a n d nec k, u p per li m bs, 
tr u n k, a n d l o wer li m bs) is i n v ol ve d wit h ps oriasis is cate g orize d usi n g a n o n-li near scali n g 
met h o d t o a n u merical area sc ore acc or di n g t o t he f oll o wi n g B S A sc ori n g criteria ( Ta ble 1 4 ).
T he % B S A is calc ulate d as descri be d i n Secti o n 8. 1. 2. 1. 3 .
T a ble 1 4.
P A SI Are a Sc ore Criteri a
Perce nt B S A * wit h 
Ps ori asis i n a B o d y Re gi o n
Are a Sc ore
0 %
0
0 t o < 1 0 %
1
1 0 t o < 3 0 %
2
3 0 t o < 5 0 %
3
5 0 t o < 7 0 %
4
7 0 t o < 9 0 %
5
9 0 t o 1 0 0 %
6
* b ase d o n h a n d pri nt met h o d
0 9 0 1 7 7 e 1 9 b b 9 c 5f d\ A p pr o v e d\ A p pr o v e d O n: 0 3- N o v- 2 0 2 2 1 1: 4 8 ( G M T)

P F -0 7 0 3 8 1 2 4
Pr ot oc ol C 3 9 4 1 0 0 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 2 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 Marc h 2 0 2 1)
Pa ge 1 3 1
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 1 5 ). 
T a ble 1 5 . B o d y Re gi o n Wei g hti n g
B o d y Re gi o n
T ot al N u m ber of 
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 pr int
B o d y Re gi o n 
Wei g hti n g
He a d a n d Nec k
1 0
1 0 %
0. 1
U p per Li m bs
2 0
5 %
0. 2
Tr u n k (i ncl u di n g a xill ae a n d gr oi n)
3 0
3. 3 3 %
0. 3
L o wer Li m bs (i ncl u di n g b utt oc ks)
4 0
2. 5 %
0. 4
Calc ulati n g of P A SI sc ore
I n eac h b o dy re gi o n, t he s u m of t he Se verit y Sc ores f or er yt he ma, i n d urati o n a n d scali n g is 
m ulti plie d b y  t he Area Sc ore a n d b y t he B o d y 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 d y  re gi o ns res ulti n g i n a P A SI sc ore as 
descri be d i n t he f oll o wi n g e q uati o n: 
P A SI = 0. 1 A h( E h+I h+ S h) + 0. 2 A u( Eu+I u+ S u) + 0. 3 At( Et+I t+ S t) + 0. 4 Al( El+I l+ S l)
A = Area Sc ore; E = er yt he ma; I = i n d urati o n/ pa p ulati o n; S =scali n g; 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 P A SI  sc ore 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 ps oriasis.  
* Si nce t he hair -beari n g scal p, pal ms, s oles a n d nails will be e xcl u de d fr o m t he P A SI 
assess me nt i n t his st u d y, t he ma xi m u m p ossi ble sc ore will be less t ha n 7 2. 0.
1 0. 1 2. 2. 3. B S A
I de ntif y t he s urface area e q ui vale nt of 1 ha n d pri nt i n eac h res pecti ve b o d y  re gi o n.
B o d y re gi o n val ue is t he n s u m me d acr oss all f o ur b o d y re gi o ns res ulti n g i n a t otal B S A wit h 
ps oriasis as descri be d i n t he f oll o wi n g e q uati o n:
B S A ( %) = 0. 1 S h + 0. 2 S u + 0. 3 St + 0. 4 Sl
w here S = b o d y re gi o n s urface area w it h Ps O ; h = hea d & nec k; u = u p per li m bs; t = tr u n k; l = l o wer li m bs. 
0 9 0 1 7 7 e 1 9 b b 9 c 5f d\ A p pr o v e d\ A p pr o v e d O n: 0 3- N o v- 2 0 2 2 1 1: 4 8 ( G M T)

P F -0 7 0 3 8 1 2 4
Pr ot oc ol C 3 9 4 1 0 0 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 2 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 Marc h 2 0 2 1)
Pa ge 1 3 2
1 0. 1 3. A p pe n di x 1 3 : A b bre vi ati o ns
T he 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
Ter m
A A P
A merica n Aca de m y  of Pe diatrics
A bs
a bs ol ute
A D
at o pic der matitis
A D L
acti vities of dail y  li vi n g
A E
a d verse e ve nt
A L T
ala ni ne a mi n otra nsferase
A N C O V A
a nal ys is of c o varia nce
A S T
as partate a mi n otra nsferase
A U C
area u n der t he c ur ve
A V
atri o ve ntric ular
-h C G
beta -h u ma n c h ori o nic g o na d otr o pi n
B A P
bi o mar ker a nal ys is pla n
B P O
be nz o y l per o xi de 
BI D
t wice daily
B L Q
bel o w t he li mit of q ua ntificati o n
b p m
beats per mi n ute
B S A
b o d y  s urface area
B U N
bl o o d urea nitr o ge n
c A M P
c yclic a de n osi ne m o n o p h os p hate
C a v
a vera ge c o nce ntrati o ns
C F B
c ha n ge fr o m baseli ne
C F R
c o de of fe deral re g ulati o ns
c G M P
c yclic g ua n osi ne m o n o p h os p hate
CI O M S
C o u ncil f or I nter nati o nal Or ga nizati o ns of Me dical Scie nces
C K
creati ne ki nase
C K D -E PI
C hr o nic Ki d ne y  Disease -E pi de mi ol o g y  C olla b orati o n
C ma x
ma xi m u m o bser ve d c o nce ntrati o n
C O 2
car b o n di o xi de ( bicar b o nate)
C O N S O R T
C o ns oli date d Sta n dar ds of Re p orti n g Trials
C O VI D -1 9
c or o na vir us disease 2 0 1 9
C R F
case re p ort f or m
C R O
c o ntract researc h or ga nizati o n
C S R
Cli nical St u d y  Re p ort
C -S S R S
C ol u m bia S uici de Se verit y  Rati n g Scale
C T
cli nical trial
C Y P 4 5 0
c yt oc hr o me p 4 5 0
D DI
dr u g -dr u g i nteracti o n
0 9 0 1 7 7 e 1 9 b b 9 c 5f d\ A p pr o v e d\ A p pr o v e d O n: 0 3- N o v- 2 0 2 2 1 1: 4 8 ( G M T)
C CI

P F -0 7 0 3 8 1 2 4
Pr ot oc ol C 3 9 4 1 0 0 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 2 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 Marc h 2 0 2 1)
Pa ge 1 3 3
A b bre vi ati o n
Ter m
DI LI
dr u g -i n d uce d li ver i nj ur y
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 ma Area a n d Se verit y I n de x
E C
et hics c o m mittee
E C C
e mer ge nc y c o ntact car d
E C G
electr ocar di o gra m
e C R F
electr o nic case re p ort f or m
E D B
e x p os ure d uri n g breastfee di n g
E D P
e x p os ure d uri n g pre g na nc y
E F D
e m br yo -fetal de vel o p me nt
e G F R
esti mate d gl o mer ular filtrati o n rate
E M A
E ur o pea n Me dici nes A ge nc y
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 U
E ur o pea n U ni o n
E u dra C T
E ur o pea n U ni o n Dr u g Re g ulati n g A ut h orities Cli nical Trials 
( E ur o pea n Cli nical Trials Data base)
F A S
f ull a nal ysis set
F D A
F o o d a n d Dr u g A d mi nistrati o n 
FI H
first-i n-h u ma n
F S H
f ollicle-sti m ulati n g h or m o ne
f u p
fracti o n u n b o u n d plas ma
G C P
G o o d Cli nical Practice
G G T
ga m ma -gl uta m y l tra nsferase
H E E N T
hea d, e y es, ears, n ose a n d t hr oat
H R Q o L
healt h -relate d q ualit y of life
H R
heart rate
H R T
h or m o ne re place me nt t hera p y
I B
I n vesti gat or’s Br oc h ure
I C5 0
5 0 % i n hi biti ve c o nce ntrati o n
I C D
i nf or me d c o nse nt d oc u me nt
I C H
I nter nati o nal C o u ncil f or Har m o nisati o n of Tec h nical Re q uire me nts 
f or P har mace uticals f or H u ma n Use 
I D
i de ntificati o n
I GA
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 L
i nterle u ki n
I M P
i n vesti gati o nal me dici nal pr o d uct
0 9 0 1 7 7 e 1 9 b b 9 c 5f d\ A p pr o v e d\ A p pr o v e d O n: 0 3- N o v- 2 0 2 2 1 1: 4 8 ( G M T)
C CI

P F -0 7 0 3 8 1 2 4
Pr ot oc ol C 3 9 4 1 0 0 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 2 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 Marc h 2 0 2 1)
Pa ge 1 3 4
A b bre vi ati o n
Ter m
I ND
i n vesti gati o nal ne w dr u g
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 P A L
i n vesti gati o nal pr o d uct acc o u nta bilit y l o g
I RB
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 W R
i nteracti ve we b-base d res p o nse
J A K
ja n us ki nase
L B B B
left b u n dle bra nc h bl oc k
L F T
li ver f u ncti o n test
L L O Q
l o wer li mit of q ua ntificati o n
L P S
li p o p ol ysacc hari de
M A R
missi n g at ra n d o m
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 M F
m y c o p he n olate m ofetil
M M R M
m i xe d m o del re peate d meas ures
msec
millisec o n d
M W
m olec ular wei g ht
N A
n ot a p plica ble
NI M P
n o n -i n vesti gati o nal me dici nal pr o d uct
N O A E L
n o o bser ve d a d verse effect le vel
N O E L
n o o bser ve d effect le vel
P A SI
Ps oriasis Area a n d Se verit y  In de x
P B M C
peri p heral bl o o d m o n o n uclear cell 
P C P 
pri mar y  care pr o vi der
P D
p har mac o d y n a mic(s)
P D E
p h os p h o diesterase
P D E 4
p h os p h o diesterase 4
P G A
P h y sicia n Gl o bal Assess me nt
PI
pri nci pal i n vesti gat or
P K
p har mac o ki netic(s)
P P -N R S
Pea k Pr urit us N u merical Rati n g Scale
P R N
as nee de d
P R O
patie nt re p orte d o utc o mes
Ps O
pla q ue ps oriasis
0 9 0 1 7 7 e 1 9 b b 9 c 5f d\ A p pr o v e d\ A p pr o v e d O n: 0 3- N o v- 2 0 2 2 1 1: 4 8 ( G M T)
C CI
C CI
C CI

P F -0 7 0 3 8 1 2 4
Pr ot oc ol C 3 9 4 1 0 0 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 2 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 Marc h 2 0 2 1)
Pa ge 1 3 5
A b bre vi ati o n
Ter m
P T
pr ot hr o m bi n ti me
P U V A
ps orale n – ultra vi olet a
P V C
pre mat ure ve ntric ular c o ntracti o n/c o m ple x
Q D
o nce dail y
Q o L
q ualit y  of life
Q Tc
c orrecte d Q T i nter val
Q Tc F
Q T C c orrecte d usi n g Fri dericia’s f or m ula
R A
r he u mat oi d art hritis
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 y sis Pla n
S A R S -C o V -2
se vere ac ute res pirat or y s yn dr o me c or o na vir us 2
S o A
sc he d ule of acti vities
S O C
S y ste m or ga n class
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 SI D
si n gle s u bject i de ntificati 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 Bili
t otal bilir u bi n
T CI
t o pical calci ne uri n i n hi bit or
T C S
t o pical c ortic oster oi ds
T E A E
treat me nt e mer ge nt a d verse e ve nts
T h 2
t ype 2 hel per T cell 
T N F
t u m or necr osis fact or
T S S
T otal Si g n Sc ore 
u Ca v
u n b o u n d a vera ge c o nce ntrati o ns
U G T
uri di ne gl uc ur o n yl  tra nsferases
U L N
u p per li mit of n or mal
U S
U nite d States
U V
ultra vi olet
U V A
ultra vi olet A
U V B
ultra vi olet B
W B C
w hite bl o o d cell
W O C B P
w o ma n/ w o me n of c hil d beari n g p ote ntial
W O N C B P
w o ma n/ w o me n of n o n -c hil d beari n g p ote ntial
0 9 0 1 7 7 e 1 9 b b 9 c 5f d\ A p pr o v e d\ A p pr o v e d O n: 0 3- N o v- 2 0 2 2 1 1: 4 8 ( G M T)
C CI

P F -0 7 0 3 8 1 2 4
Pr ot oc ol C 3 9 4 1 0 0 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 2 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 Marc h 2 0 2 1)
Pa ge 1 3 6
1 1. R E F E R E N C E S
1.
Wei di n ger S, N o va k N. At o pic der matitis. La ncet. 2 0 1 6; 3 8 7( 1 0 0 2 3): 1 1 0 9 - 2 2.
2.
Y osi p o vitc h G, Rea ne y  M, Maste y V, et al. Pea k Pr urit us N u merical Rati n g Scale: 
ps y c h o metric vali dati o n a n d res p o n der defi niti o n f or assessi n g itc h i n m o derate -t o-
se vere at o pic der matitis. Br J Der mat ol. 2 0 1 9; 1 8 1( 4): 7 6 1- 6 9.
3.
Nestle F O, Ka pla n D H, Bar ker J. Ps oriasis. N E n gl J Me d. 2 0 0 9; 3 6 1( 5): 4 9 6 - 5 0 9.
4.
S bi dia n E, C hai ma ni A, Afac h S, et al. S ys te mic p har mac ol o gical treat me nts f or c hr o nic 
pla q ue ps oriasis: a net w or k meta -a nal ys is. C oc hra ne Data base Sys t Re v. 
2 0 2 0; 1: C D 0 1 1 5 3 5.
5.
Paller A S, T o m W L , Le b w o hl M G, et al. Efficac y a n d safety of crisa b or ole oi nt me nt, a 
n o vel, n o nster oi dal p h os p h o diesterase 4 ( P D E 4) i n hi bit or f or t he t o pical treat me nt of 
at o pic der matitis ( A D) i n c hil dre n a n d a d ults. J A m Aca d Der mat ol. 2 0 1 6; 7 5( 3): 4 9 4 -
5 0 3 e 6.
6.
Le b w o hl M G, Pa p p K A, Stei n G ol d L , et al. Trial of R ofl u milast Crea m f or C hr o nic 
Pla q ue Ps oriasis. N E n gl J Me d. 2 0 2 0; 3 8 3( 3): 2 2 9 - 3 9.
7.  
Ha nifi n J M. Dia g n ostic feat ures of at o pic der matitis. Acta Der m Ve nere ol. 
1 9 8 0; 9 2: 4 4 - 4 7.
8. 
T ofte S, Grae ber M, C herill R, et al. E cze ma area a n d se verit y i n de x ( E A SI): a ne w t o ol 
t o e val uate at o pic der matitis. J o ur nal of t he E ur o pea n Aca de my of Der mat ol o g y a n d 
Ve nere ol o g y . 1 9 9 8; 1 1( 2): S 1 9 7.
9.
La n gle y  R G, Fel d ma n S R, N yira dy J , et al. T he 5-p oi nt I n vesti gat or's Gl o bal 
Assess me nt (I G A) Scale: A m o difie d t o ol f or e val uati n g pla q ue ps oriasis se verit y i n 
cli nical trials. J Der mat ol o g Treat. 2 0 1 5; 2 6( 1): 2 3 - 3 1.
1 0.
Fre dri kss o n T, Petterss o n U. Se vere ps oriasis --oral t hera p y wit h a ne w reti n oi d. 
Der mat ol o gica. 1 9 7 8; 1 5 7( 4): 2 3 8 - 4 4.
1 1.
B us h nell D M, Marti n M L, Mc Carrier K, et al. Vali dati o n of t he Ps oriasis S y m pt o m 
I n ve nt or y ( P SI), a patie nt-re p orte d o utc o me meas ure t o assess ps oriasis sy m pt o m 
se verity. J Der mat ol o g Treat. 2 0 1 3; 2 4( 5): 3 5 6 - 6 0.
1 2.
P os ner K, Br o w n G K, Sta nle y  B, et al. T he C ol u m bia-S uici de Se veri t y Rati n g Scale: 
i nitial vali dit y a n d i nter nal c o nsiste nc y fi n di n gs fr o m t hree m ultisite st u dies wit h 
a d olesce nts a n d a d ults. A m J Ps y c hiatr y. 2 0 1 1; 1 6 8( 1 2): 1 2 6 6- 7 7.
1 3.
Nasir A, Biss o n nette R, Maari C, et al. A p hase 2a ra n d o mize d c o ntr olle d st u d y  t o 
e val uate t he p har mac o ki netic, safety, t olera bilit y  a n d cli nical effect of t o picall y a p plie d 
U mecli di ni u m i n s u bjects wit h pri mar y  a xillar y h yper hi dr osis. J E ur Aca d Der mat ol 
Ve nere ol. 2 0 1 8; 3 2( 1): 1 4 5 - 5 1.
0 9 0 1 7 7 e 1 9 b b 9 c 5f d\ A p pr o v e d\ A p pr o v e d O n: 0 3- N o v- 2 0 2 2 1 1: 4 8 ( G M T)

P F -0 7 0 3 8 1 2 4
Pr ot oc ol C 3 9 4 1 0 0 5
Fi nal Pr ot oc ol A me n d me nt 1 , 0 2 N o ve m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 0 2 -G S O P Cli nical Pr ot oc ol Te m plate P hase 1 2 3 4 ( 0 1 Marc h 2 0 2 1)
Pa ge 1 3 7
1 4.
C ha n I S, Z ha n g Z. Test - base d e xact c o nfi de nce i nter vals f or t he differe nce of t w o 
bi n o mial pr o p orti o ns. Bi o metrics. 1 9 9 9 Dec; 5 5( 4): 1 2 0 2 - 9.
0 9 0 1 7 7 e 1 9 b b 9 c 5f d\ A p pr o v e d\ A p pr o v e d O n: 0 3- N o v- 2 0 2 2 1 1: 4 8 ( G M T)