Clinical trial NCT05375955
Conditions: Atopic Dermatitis Plaque Psoriasis
Keywords: Eczema topical
Sponsor: Pfizer
Start date: 2022-09-26; Completion date: 2023-07-31
Enrollment: 263 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The purpose of this clinical trial is to learn about the safety, how well the study medicine works, extent to which side effects can be tolerated, and how the study medicine is changed and eliminated from your body after you apply it on your skin. The study medicine is in ointment form.

This study is seeking participants who

If they have Atopic Dermatitis (AD):

* Have a diagnosis for at least 3 months
* Have a diagnosis of mild or moderate disease assessed using Investigator's Global Assessment (IGA)
* Have percent Body Surface Area (%BSA) covering 5% up to 40%
* A Peak Pruritus Numerical Rating Scale (PP-NRS) average score of ≥2 during the screening period

If they have plaque psoriasis (PsO):

* Have a diagnosis for at least 6 months
* Have a diagnosis of mild, moderate, or severe disease assessed using Physician's Global Assessment (PGA)
* Have percent Body Surface Area (%BSA) covering 2% up to 20%

All participants in this study will receive either 0.01% PF-07038124, 0.03% PF-07038124, or a vehicle ointment. In addition, some participants with PsO will receive 0.06% PF- PF-07038124. Participants will not know which dose level they have received. The participants will be randomly assigned to each dose group.

PF-07038124 ointment will be applied topically to affected areas once daily. We will compare the experiences of people receiving the different dose levels of the ointment to those who receive the vehicle ointment. This will help us determine if PF-07038124 ointment is safe and effective.

Participants will take part in this study for approximately 21 weeks. Participants will apply the study medicine once daily for 12 weeks followed by a safety follow-up period of 4-5 weeks from last application of study medicine to last visit.

Detailed description:

Arms: arm 1: Atopic Dermatitis arm 2: Atopic Dermatitis arm 3: Atopic Dermatitis arm 4: Plaque Psoriasis arm 5: Plaque Psoriasis arm 6: Plaque Psoriasis arm 7: Plaque Psoriasis
Interventions: intervention 1: PF-07038124 ointment 0.01% intervention 2: Vehicle ointment intervention 3: PF-07038124 ointment 0.03% intervention 4: PF-07038124 ointment 0.06%
Intervention descriptions: intervention 1: Atopic Dermatitis and Plaque Psoriasis intervention 2: Atopic Dermatitis and Plaque Psoriasis intervention 3: Atopic Dermatitis and Plaque Psoriasis intervention 4: PF-07038124 ointment 0.06% (Plaque Psoriasis only)

Protocol documents:
Prot_000.pdf: 
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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 
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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 :
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St u d y I nter ve nti o n N a me:
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U S I N D N u m ber:
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E u dr a C T N u m ber:
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Cli nic al Tri als. g o v I D:  
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Pr ot oc ol N u m ber:
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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
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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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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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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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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. 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.
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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 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.
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 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.
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 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 
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 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.
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 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 .
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 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.
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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 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)

SAP_001.pdf: 
Protocol C3941005 (PF-07038124 ) Statistical Analysis Plan 
 
 
DMB02-GSOP-RF02 7.0 Statistical Analysis Plan Template 31-Jan-2022 
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Protocol C3941005 
 
 
 
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 
 
 
Statistical Analysis Plan  
(SAP) 
 
 
 
 
 
 
 
Version: 
3.0 
 
Date:  
18Aug2023  
 


Protocol C3941005 (PF-07038124 ) Statistical Analysis Plan 
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TABLE OF CONTENTS 
TABLE OF CONTENTS ...........................................................................................................2 
1. VERSION HISTORY ............................................................................................................6 
2. INTRODUCTION .................................................................................................................7 
2.1. Modifications to the Analysis Plan Described in the Protocol ..................................7 
2.2. Study Objectives, Endpoints, and Estimands ............................................................7 
2.2.1. Primary Estimand .......................................................................................14 
2.2.2. Secondary Estimand ...................................................................................16 
2.2.3. Additional Estimand(s) ...............................................................................17 
2.3. Study Design ...........................................................................................................17 
3. ENDPOINTS AND BASELINE VARIABLES:  DEFINITIONS AND 
CONVENTIONS ................................................................................................................18 
3.1. Primary Endpoint(s) ................................................................................................18 
3.2. Secondary Endpoint(s) ............................................................................................19 
3.3. Tertiary/Exploratory Endpoint(s) ............................................................................20 
3.4. Baseline Variables ...................................................................................................22 
3.5. Safety Endpoints .....................................................................................................23 
3.5.1. Adverse Events ...........................................................................................23 
3.5.2. Laboratory Data ..........................................................................................23 
3.5.3. Vital Sign ....................................................................................................24 
3.5.4. Electrocardiograms .....................................................................................24 
3.5.5. Local Skin Tolerability ...............................................................................24 
4. ANALYSIS SETS (POPULATIONS FOR ANALYSIS) ...................................................24 
5. GENERAL METHODOLOGY AND CONVENTIONS ....................................................25 


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5.1. Hypotheses and Decision Rules ..............................................................................25 
5.2. General Methods .....................................................................................................26 
5.2.1. Analyses for Binary Endpoints ...................................................................26 
5.2.2. Analyses for Continuous Endpoints ...........................................................26 
5.2.3. Analyses for Categorical Endpoints ...........................................................27 
5.2.4. Analyses for Time-to-Event Endpoints ......................................................27 
5.3. Methods to Manage Missing Data ..........................................................................27 
5.3.1. Efficacy Data ..............................................................................................27 
5.3.2. Pharmacokinetic Concentrations and Biomarker Data ...............................28 
6. ANALYSES AND SUMMARIES ......................................................................................28 
6.1. Primary Endpoint(s) ................................................................................................28 
6.1.1. Main Analysis .............................................................................................28 
6.1.2. Sensitivity/Supplementary Analyses ..........................................................29 
6.2. Secondary Endpoint(s) ............................................................................................30 
6.2.1. Binary Secondary Endpoints ......................................................................30 
6.2.2. Continuous Secondary Endpoints ...............................................................30 
6.3. Tertiary/Exploratory Endpoints ...............................................................................31 
6.3.1. Binary Tertiary/Exploratory Endpoints ......................................................31 
6.3.2. Continuous Tertiary/Exploratory Endpoints ...............................................31 
6.3.3. PRO Endpoints ...........................................................................................32 
6.4. Other Endpoint(s) ....................................................................................................32 
6.4.1. PK Endpoints ..............................................................................................32 
6.5. Subset Analyses .......................................................................................................32 


Protocol C3941005 (PF-07038124 ) Statistical Analysis Plan 
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6.6. Baseline and Other Summaries and Analyses .........................................................32 
6.6.1. Baseline Summaries ....................................................................................32 
6.6.2. Study Conduct and Participant Disposition ................................................33 
6.6.3. Study Treatment Exposure .........................................................................33 
6.6.4. Concomitant Medications and Nondrug Treatments ..................................33 
6.7. Safety Summaries and Analyses .............................................................................33 
6.7.1. Adverse Events ...........................................................................................34 
6.7.2. Laboratory Data ..........................................................................................34 
6.7.3. Vital Signs ..................................................................................................34 
6.7.4. Electrocardiograms .....................................................................................34 
6.7.5. Local Skin Tolerability ...............................................................................35 
7. INTERIM ANALYSES .......................................................................................................35 
7.1. Introduction .............................................................................................................35 
7.2. Interim Analyses and Summaries ............................................................................35 
8. REFERENCES ....................................................................................................................36 
9. APPENDICES .....................................................................................................................37 
APPENDIX 1. SUMMARY OF EFFICACY ANALYSES ...................................................37 
APPENDIX 2. DOSE RESPONSE ANALYSIS FOR PSO ..................................................38 
APPENDIX 3. DEFINITION AND USE OF VISIT WINDOWS IN REPORTING ............40 
APPENDIX 4. SAMPLE SAS CODE ....................................................................................41 
LIST OF TABLES 
Table 1. 
Summary of Major Changes in SAP Amendments ....................................6 
 


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LIST OF FIGURES 
Figure 1 Study Design Schema ................................................................................................18 
 
 
 


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1. VERSION HISTORY 
This SAP for Study C3941005 is based on the protocol amendment dated 02Nov2022. 
Table 1. 
Summary of Major Changes in SAP Amendments 
Version/ 
Date 
Associated 
Protocol 
Amendment 
Change 
Rationale 
1/19May2022 
 
 
Original 
21Apr2022 
Not Applicable 
Not Applicable 
2/7Jul2023 
Protocol 
amendment 1 
02Nov2022 
Section 1 updated 
protocol version 
Protocol amendment 
 
 
Section 4. 
Added handling rules 
for multiple enrollment 
A participant with 
multiple enrollment was 
identified 
 
 
Section 6.1.2: Clarified 
intended weight used for 
stratified analysis is 
minimum risk weight 
instead of Mantel-
Haenszel weight.   
Minimum risk weights 
are designed to improve 
precision and reduce bias 
and can minimize the 
power loss that can occur 
when constant odds ratio 
is not met. 
 
 
Section 6.5: Deleted 
subset analysis for 
adolescent 
There were only few 
adolescent enrolled for 
the study. 


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3 
Protocol 
amendment 1 
02Nov2022 
Section 4: added 
statement about 
excluding evaluation at 
visits by non-qualified 
raters 
A rater unqualified for 
PGA/PASI evaluated 10 
PsO participants at 
several visits and such 
data need to be excluded. 
2. INTRODUCTION 
This statistical analysis plan (SAP) provides the detailed methodology for summary and 
statistical analyses of the data collected in Study C3941005.   
2.1. Modifications to the Analysis Plan Described in the Protocol 
NA 
2.2. Study Objectives, Endpoints, and Estimands 
 
ATOPIC DERMATITIS 
Type 
Objectives 
Endpoints 
Estimands 
 
Primary:  
Primary: 
Primary:  
Efficacy 
To compare the efficacy of 
2 dose levels of PF-
07038124 ointment versus 
vehicle, using IGA success 
as the endpoint in 
participants with mild or 
moderate AD. 
Proportion of participants 
achieving IGA score of 
clear (0) or almost clear (1) 
(on a 5-point scale) and a 
reduction from baseline of 
 12. 
Estimand E1: the 
difference in proportions 
of the binary endpoint 
between IP treated (0.01% 
or 0.03% PF-07038124 
ointment) and vehicle in 
participants with mild or 
moderate AD without the 
benefit of additional 
prohibited medications 
and regardless of 
treatment compliance. 


Protocol C3941005 (PF-07038124 ) Statistical Analysis Plan 
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Secondary:  
Secondary: 
Secondary:  
Efficacy 
To compare the efficacy of 
2 dose levels of PF-
07038124 ointment versus 
vehicle using EASI-75 as 
an endpoint in participants 
with mild or moderate AD. 
Proportion of participants 
achieving EASI-75 
(75% improvement from 
baseline) at all study visit 
time points specified in the 
SoA. 
Estimand E1 described 
above. 
Efficacy 
To compare the efficacy of 
2 dose levels of PF-
07038124 ointment versus 
vehicle, using IGA success 
as the endpoint in 
participants with mild or 
moderate AD. 
Proportion of participants 
achieving IGA score of 
clear (0) or almost clear (1) 
(on a 5-point scale) and a 
reduction from baseline of 
time points specified in the 
SoA, except at Week 12. 
Estimand E1 described 
above. 
Efficacy 
To compare the efficacy of 
2 dose levels of PF-
07038124 ointment versus 
vehicle, using percent CFB 
in EASI as the endpoint in 
participants with mild or 
moderate AD. 
Percent CFB in EASI total 
score at all study visit time 
points specified in the SoA.
Estimand E2: the 
difference in mean of the 
continuous endpoint 
between IP treated (0.01% 
or 0.03% PF-07038124 
ointment) and vehicle in 
participants with mild or 
moderate AD without the 
benefit of additional 
prohibited medications 
and regardless of 
treatment compliance. 
Efficacy 
To compare the efficacy of 
2 dose levels of PF-
07038124 ointment versus 
vehicle, using IGA clear or 
almost clear as the endpoint 
in participants with mild or 
moderate AD.
Proportion of participants 
achieving IGA score of 
clear (0) or almost clear (1) 
at all study visit time points 
specified in the SoA. 
Estimand E1 described 
above.  
 


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Efficacy
To compare the efficacy of 
2 dose levels of PF-
07038124 ointment versus 
vehicle, using measures of 
PP-NRS PRO, in 
participants with mild or 
moderate AD.
Proportion of participants 
reduction from baseline in 
weekly averages of PP-
NRS at study visit time 
points specified in the SoA.
Estimand E1 described 
above. 
Efficacy
To compare the efficacy of 
2 dose levels of PF-
07038124 ointment versus 
vehicle, using BSA as the 
endpoint in participants 
with mild or moderate AD.
Percent CFB in affected 
BSA at all study visit time 
points specified in the SoA.
Estimand E2 described 
above. 
Safety
To characterize the safety 
and tolerability of 2 dose 
levels of PF-07038124 
ointment versus vehicle in 
participants with mild or 
moderate AD.
Incidence of treatment 
emergent AEs and SAEs, 
clinically significant 
changes in vital signs, 
ECG, and laboratory tests.
Incidence of increase in 
local tolerability severity 
grades at times indicated in 
the SoA.
Not Applicable.
Tertiary/Exploratory: 
Tertiary/Exploratory:
Tertiary/Exploratory: 


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Biomarker
Tape Stripping Sub-study
To evaluate 
pharmacological effects of 
applying multiple doses of 
PF-07038124 ointment 
versus vehicle ointment 
using tape stripping method 
that is used to collect upper 
part of epidermis.
Efficacy
Photography Sub-study
To compare the efficacy of 
two dose levels of PF-
07038124 ointment versus 
vehicle using 
To document effects of 
applying multiple doses of 
PF-07038124 ointment 
versus vehicle ointment 
using photographic images.


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PLAQUE PSORIASIS 
Type 
Objectives 
Endpoints 
Estimands 
 
Primary:  
Primary: 
Primary:  
Efficacy 
To compare the efficacy of 
multiple dose levels of 
PF-07038124 ointment 
versus vehicle, using PGA 
success as the endpoint in 
participants with mild-to-
severe PsO. 
Proportion of participants 
achieving PGA score of 
clear (0) or almost clear (1) 
(on a 5-point scale) and a 
reduction from baseline of 
 
Estimand E1: the 
difference in proportions 
of the binary endpoint 
between IP treated 
(0.01%, 0.03%, or 0.06% 
PF-07038124 ointment) 
and vehicle in participants 
with mild-to-severe PsO 
without the benefit of 
additional prohibited 
medications and 
regardless of treatment 
compliance. 
 
Secondary:  
Secondary: 
Secondary:  
Efficacy 
To compare the efficacy of 
multiple dose levels of 
PF-07038124 ointment 
versus vehicle using 
PASI-75 as an endpoint, in 
participants with mild-to-
severe PsO.
Proportion of participants 
achieving PASI-75 
(75% improvement from 
baseline) at times indicated 
in the SoA. 
Estimand E1 described 
above.  
 


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Efficacy 
To compare the efficacy of 
multiple dose levels of 
PF-07038124 ointment 
versus vehicle, using PGA 
success as endpoint in 
participants with mild-to-
severe PsO. 
Proportion of participants 
achieving PGA score of 
clear (0) or almost clear (1) 
(on a 5-point scale) and a 
reduction from baseline of 
in the SoA, except at Week 
12. 
Estimand E1 described 
above.  
 
Efficacy 
To compare the efficacy of 
multiple dose levels of 
PF-07038124 ointment 
versus vehicle, using CFB 
PASI as the endpoint in 
participants with mild-to-
severe PsO. 
Change from baseline in 
PASI at times indicated in 
the SoA. 
Estimand E2: the 
difference in mean of the 
continuous endpoint 
between IP treated 
(0.01%, 0.03%, or 0.06% 
PF-07038124 ointment) 
and vehicle in participants 
with mild-to-severe PsO 
without the benefit of 
additional prohibited 
medications and 
regardless of treatment 
compliance. 
Efficacy 
To compare the efficacy of 
multiple dose levels of 
PF-07038124 ointment 
versus vehicle, using PGA 
clear or almost clear as the 
endpoint in participants 
with mild-to-severe PsO. 
Proportion of participants 
achieving PGA score of 
clear (0) or almost clear (1) 
at all study visit time points 
specified in the SoA. 
Estimand E1 described 
above.  
 
Efficacy 
To compare the efficacy of 
multiple dose levels of 
PF-07038124 ointment 
versus vehicle, using 
measures of PP-NRS PRO, 
in adult (18-75 years old) 
participants with mild-to-
severe PsO.
Proportion of adult (18-75 
years old) participants 
 points of 
reduction from baseline in 
weekly averages of 
PP-NRS at study visit time 
points specified in the SoA.
Estimand E1 described 
above.  
 
 


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Efficacy
To compare the efficacy of 
multiple dose levels of 
PF-07038124 ointment 
versus vehicle, using BSA 
as the endpoint in 
participants with mild-to-
severe PsO.
Percent CFB in affected 
BSA at all study visit time 
points specified in the SoA.
Estimand E2 described 
above. 
Safety
To characterize the safety 
and tolerability of multiple 
dose levels of PF-07038124 
ointment versus vehicle in 
participants with mild-to-
severe PsO.
Incidence of treatment 
emergent AEs and SAEs, 
clinically significant 
changes in vital signs, 
ECG, and laboratory tests.
Incidence of increase in 
local tolerability severity 
grades at times indicated in 
the SoA.
Not Applicable.
Tertiary/Exploratory: 
Tertiary/Exploratory:
Tertiary/Exploratory: 


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Efficacy
Tape Stripping Sub-study
To evaluate 
pharmacological effects of 
applying multiple doses of 
PF-07038124 ointment 
versus vehicle ointment 
using tape stripping method 
that is used to collect upper 
part of epidermis.
Efficacy
Photography Sub-study
To document effects of 
applying multiple doses of 
PF-07038124 ointment 
versus vehicle ointment 
using photographic 
images.
2.2.1. Primary Estimand 
The estimand (E1) is defined by the following attributes:


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Atopic Dermatitis: 
Treatment condition: received treatment: PF-07038124 ointment 0.01%, 0.03% or vehicle, 
without the benefit of additional prohibited medications and regardless of treatment 
compliance.  
Population: Participants with mild or moderate AD as defined by the inclusion and exclusion 
criteria. 
Variables: Proportion of participants achieving IGA score of clear (0) or almost clear (1) and 
a reduction from 
 points at Week 12 and other binary endpoints. 
Psoriasis: 
Treatment condition: received treatment: PF-07038124 ointment 0.01%, 0.03%, 0.06% or 
vehicle, without the benefit of additional prohibited medications and regardless of treatment 
compliance.  
Population: Participants with mild, moderate, or severe PsO as defined by the inclusion and 
exclusion criteria. 
Variables: Proportion of participants with PGA score clear (0) or almost clear (1) and a 
 points at Week 12 and other binary endpoints. 
Inter-current Events: A) Prohibited medication  response will be considered as failure for 
time points after start date of the event for participants who receive prohibited medication 
post-randomization. B) Withdrawal and all other events, except COVID-19 pandemic, 
leading to missing data will be treated similarly assuming that participants no longer receive 
benefit from the study intervention and hence will be considered as failure. C) COVID-19 
pandemic: if a participant misses a visit due to COVID-19, he/she will be excluded from the 
analysis for that visit; If a participant discontinues treatment or withdraws from the study due 
to COVID-19, he/she will be excluded from the analyses after the treatment discontinuation 
visit or study withdrawal visit, respectively. D) Inadequate compliance  participants data 
will be used as recorded.  


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Population level summary: The difference in success rates between each dose level and 
vehicle. 
2.2.2. Secondary Estimand 
All binary secondary endpoints estimands are similar to the primary endpoints.  
The continuous endpoint estimand (E2) is defined by the following attributes: 
Atopic Dermatitis: 
Treatment condition: received treatment: PF-07038124 ointment 0.01%, 0.03% or vehicle, 
without the benefit of additional prohibited medications and regardless of treatment 
compliance.  
Population: Participants with mild or moderate AD as defined by inclusion and exclusion 
criteria. 
Variables: Percent change from baseline in EASI total score and percent CFB in affected 
BSA at all study visit time points specified in SoA.  
Psoriasis: 
Treatment condition: received treatment: PF-07038124 ointment 0.01%, 0.03%, 0.06% or 
vehicle, without the benefit of additional prohibited medications and regardless of treatment 
compliance.  
Population: Participants with mild, moderate, or severe PsO as defined by the inclusion and 
exclusion criteria. 
Variables: Change from baseline in PASI total score and Percent CFB in affected BSA at all 
study visit time points specified in the SoA. 
Intercurrent events: A) Prohibited medication  all scores measured at time points after start 
date of the event for participants who receive prohibited medication post randomization will 


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be excluded from the analysis and treated as missing scores. Missing scores will be imputed 
based on the assumption that participants do not benefit from the IP treatment. 
B) Withdrawal and all other events leading to missing data, except COVID-19 pandemic, 
will be treated similarly assuming participants have efficacy values similar to control 
participants. C) COVID-19 pandemic: if a participant misses a visit due to COVID-19, 
he/she will be excluded from the analysis for that visit; If a participant discontinues treatment 
or withdraws from the study due to COVID-19, he/she will be excluded from the analyses 
after the treatment discontinuation visit or study withdrawal visit, respectively. D) Inadequate 
compliance  participants data will be used as recorded. 
Population-level summary: The mean difference between each dose level and vehicle. 
2.2.3. Additional Estimand(s) 
There is no defined estimand for other endpoints, and they will be analyzed using Pfizer data 
standards as applicable. 
2.3. Study Design 
This is a phase 2b, randomized, double blind, vehicle controlled, parallel group, multicenter 
study to assess the efficacy, safety and tolerability, and PK of multiple doses of PF-07038124 
ointment versus vehicle in treatment of participants, 12 years and older, and with AD or PsO.  
In this study, a total of approximately 240 participants with AD or PsO will be randomly 
assigned to study intervention (PF-07308124 or vehicle).  


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Figure 1 Study Design Schema 
3. ENDPOINTS AND BASELINE VARIABLES: DEFINITIONS AND 
CONVENTIONS
3.1. Primary Endpoint(s)
Proportion of participants achieving IGA score of clear (0) or almost clear (1) (on a 5-
point scale) and a reduction from baseline of 
12.


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Proportion of participants achieving PGA score of clear (0) or almost clear (1) (on a 
5-
 12. 
3.2. Secondary Endpoint(s) 
For AD: 
Proportion of participants achieving EASI-75 (75% improvement from baseline) 
at all study visit time points specified in the SoA. 
Proportion of participants achieving IGA score of clear (0) or almost clear (1) (on 
a 5-point scale) and a reduction from baseline of 2 points at all study visit time 
points specified in the SoA, except at Week 12. 
Percent CFB in EASI total score at all study visit time points specified in the SoA. 
Proportion of participants achieving IGA score of clear (0) or almost clear (1) at 
all study visit time points specified in the SoA. 
Proportion of participants having 4 points of reduction from baseline in weekly 
averages of PP-NRS at study visit time points specified in the SoA. 
Percent CFB in affected BSA at all study visit time points specified in the SoA. 
Incidence of treatment emergent AEs and SAEs, clinically significant changes in 
vital signs, ECG, and laboratory tests. 
Incidence of increase in local tolerability severity grades at times indicated in the 
SoA. 
For Psoriasis: 
Proportion of participants achieving PASI-75 (75% improvement from baseline) 
at times indicated in the SoA. 


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Proportion of participants achieving PGA score of clear (0) or almost clear (1) (on 
a 5-point scale) and a reduction from baseline of 2 points at times indicated in 
the SoA, except at Week 12.
Change from baseline in PASI at times indicated in the SoA.
Proportion of participants achieving PGA score of clear (0) or almost clear (1) at 
all study visit time points specified in the SoA.
Proportion of adult participants (18-75 years old) having 4 points of reduction 
from baseline in weekly averages of PP-NRS at study visit time points specified 
in the SoA.
Percent CFB in affected BSA at all study visit time points specified in the SoA.
Incidence of treatment emergent AEs and SAEs, clinically significant changes in 
vital signs, ECG, and laboratory tests.
Incidence of increase in local tolerability severity grades at times indicated in the 
SoA.
3.3. Tertiary/Exploratory Endpoint(s)
For AD:


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3.4. Baseline Variables
In general, for all analyses, baseline will be defined based on observations collected prior to 
first dose. Baseline values for demographics and height will be based on measures collected 
at Visit 1/Screening visit.  Study Day 1 is defined as the day the participant receives first 
dose of study drug. For purposes of all other analyses including analyses for change from 
baseline, the baseline value will be defined as the last measurement before first dose on Day 
1.  If a value is missing on Day 1, then the last available observation before Day 1 will be 


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used.  For the PP-NRS score, baseline will be defined as the average of all values recorded 
between Day -7 and Day -1.   
3.5. Safety Endpoints 
Safety will be assessed by reporting of AEs, ECG, vital signs, local skin tolerability, and 
clinical laboratory results in all participants who receive at least one dose of the 
investigational product.  Unscheduled safety assessments may be performed at any time 
during the study to assess any perceived safety concerns.  Endpoints will be assessed as: 
Incidence of treatment emergent adverse events. 
Incidence of SAEs and AEs leading to discontinuation. 
Incidence of clinical abnormalities in clinical laboratory values, ECG measurements, 
and vital signs. 
Change from baseline in ECG measurements and vital signs. 
Incidence of skin tolerability 
The safety endpoints will be defined in accordance with Clinical Data Interchange Standards 
Consortium (CDISC) and Pfizer Standards (CaPS). 
3.5.1. Adverse Events 
All adverse events that start on or after the first dosing date and time, if collected, but before 
the last dose plus the lag time (35 days) will be flagged as TEAEs.  The algorithm will not 
consider any events that started prior to the first dose date. Missing AE start date and time 
components will be imputed conservatively as the earliest date and time possible.  
3.5.2. Laboratory Data 
The laboratory tests will be performed at time points identified in the Schedule of Activities. 
Unscheduled clinical labs may be obtained at any time during the study to assess any 
 


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3.5.3. Vital Sign 
Vital signs (blood pressure, pulse, and temperature) will be measured after a minimum of 
5 minutes rest as indicated in the SoA.    
3.5.4. Electrocardiograms 
Standard 12-lead ECGs should be collected at times specified in the SoA.  
3.5.5. Local Skin Tolerability 
The investigator or designee will assess tolerability at the site of study intervention 
application, focusing on the non-lesion skin, immediately post application of the study 
intervention as indicated in the Schedule of Activities. 
4. ANALYSIS SETS (POPULATIONS FOR ANALYSIS) 
Data for all participants will be assessed to determine if participants meet the criteria for 
inclusion in each analysis population prior to releasing the database and classifications will 
be documented per standard operating procedures. For participants with multiple enrollment, 
only the participant identifier and data under initial enrollment will be included and 
summarized. Data collected for other enrollments will be included only in listings and 
narratives. For IGA, PGA, EASI and PASI related endpoints that require qualified raters, 
evaluations at visits by non-qualified raters will be excluded. 
Participant Analysis Set 
Description 
ITT Analysis Set    
All participants randomly assigned to study intervention. Participants will 
be analyzed according to the randomized intervention. 
Safety Analysis Set 
All participants randomly assigned to study intervention who took at least 
1 dose of study intervention. A randomized but not treated participant will 
be excluded from the safety analyses. Participants will be analyzed 
according to the intervention received. 


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Participant Analysis Set
Description
5. GENERAL METHODOLOGY AND CONVENTIONS
The primary analysis will be performed when all randomized participants have either 
completed their 12-week study participation period or withdrawn early, or the study stop
prematurely due to any reason, and the database is released.
5.1. Hypotheses and Decision Rules
Statistical inference will be made on the primary endpoints: IGA/PGA success rate at 
Week 12. The null hypothesis is that there is no difference between any PF-07038124 doses
being tested and vehicle. The alternative hypothesis is that at least one PF-07038124 dose
being tested is superior to vehicle with a higher IGA/PGA success rate. The study will be
considered positive for each indication when the corresponding null hypothesis is rejected.
For each indication, the overall family wise Type I error rate will be controlled at 1-sided
0.025 level using the Hochberg step up procedure.
A sufficient number of AD participants will be screened to achieve approximately 
120 participants randomly assigned to study intervention. The sample size calculation is 
based on the primary efficacy estimand IGA success at Week 12. Assuming 15% IGA 
success rate for the vehicle arm, a sample size of 40 per arm will have 89% power to detect a 
treatment difference of 35% under a 1-sided type 1 error 0.0125 for each of the 2 dose levels 
comparison to vehicle by the unconditional exact test, with an overall Type 1 error 0.025 1-
sided. In addition, this sample size will provide 96% power to detect a 42% difference in 
EASI-75 between an active arm (62% EASI-75) and vehicle (20% EASI-75).


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A sufficient number of PsO participants will be screened to achieve approximately 
120 participants randomly assigned to study intervention. The sample size calculation is 
based on the primary efficacy estimand PGA success at Week 12. Assuming 8% PGA 
success rate for the vehicle arm, a sample size of 30 per arm will have 92% power to detect a 
treatment difference of 42% under a 1-sided type 1 error 0.008 for each of the three dose 
levels comparison to vehicle by the unconditional exact test, with an overall Type 1 error 
0.025 1-sided. In addition, this sample size will provide 96% power to detect a 
44% difference in PASI-75 between an active arm (50% PASI-75) and vehicle (6% PASI-
75). 
 
5.2. General Methods 
5.2.1. Analyses for Binary Endpoints 
For landmark (cross-sectional) analyses of binary endpoints, Blyth-Still-Casella method will 
be used for estimates and confidence interval for each treatment arm, and 
exact confidence interval (CI) method1 will be used for differences between treatment arms.  
For all binary endpoints, a summary of number and percentage of participants in each 
category by treatment arm and time will be produced and the response rate will also be 
plotted against time by treatment.   
5.2.2. Analyses for Continuous Endpoints 
Landmark (cross-sectional) analyses of key continuous endpoints will be performed by 
analysis of covariance (ANCOVA). The ANCOVA model will include treatment arm as 
fixed effect and baseline dependent variable as a covariate. Estimates of least square mean 
(LSM) values and the LSM differences between each PF-07038124 dose and vehicle will be 
derived. The corresponding p-values and 95% confidence intervals will also be presented. 
Mixed model repeated measures (MMRM) models may be used when there are multiple time 
points.  The fixed effects of treatment, visit, and treatment by visit interaction will be 
included.  Baseline value will be included as a covariate.  Unstructured covariance matrix 
will be assumed for the model errors when possible.  Compound symmetry covariance matrix 


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will be used if the model with unstructured covarian
 At each visit, 
estimates of least square mean (LSM) values and the LSM differences between each 
PF-07038124 dose and vehicle will be derived. The corresponding p-values and 95% 
confidence intervals will also be presented.  
Unless stated otherwise, descriptive summary statistics of absolute values, change and 
percent from baseline for all continuous variables will be presented by treatment and time. 
These statistics will include n, mean, median, standard deviation, minimum and maximum. 
5.2.3. Analyses for Categorical Endpoints 
A summary of number and percentage of participants in each category will be presented by 
treatment and time point.   
5.2.4. Analyses for Time-to-Event Endpoints 
NA.  
5.3. Methods to Manage Missing Data  
5.3.1. Efficacy Data 
Analysis of binary data including primary endpoints will use the primary estimand (E1).  All 
missing values, except missing due to COVID-19 pandemic, will be set to a failure (Section 
6.1.1). 
Continuous secondary endpoint analysis will use the secondary estimand (E2).  For each 
landmark analysis (e.g., cross sectional analysis by week) missing data, except missing due 
to COVID-19 pandemic, will be imputed using a control-based imputation method (Section 
6.2.2). 
Summaries of tertiary/exploratory continuous data will use the observed data only and no 
additional considerations are needed. 
If a participant misses a visit due to COVID-19, he/she will be excluded from the analysis for 
that visit; If a participant discontinues treatment or withdraws from the study due to 


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COVID-19, he/she will be excluded from the analyses after the treatment discontinuation 
visit or study withdrawal visit, respectively.   
5.3.2. Pharmacokinetic Concentrations and Biomarker Data  
Concentrations outside the limit of quantification. 
In summary statistics for pharmacokinetic and biomarker data, assayed values below 
the lower limit of quantification (LLOQ) will be set to zero.  Other imputations (e.g., 
½ LLOQ) may also be considered in other analyses (e.g., Pop-PK and PK/PD 
analyses), if deemed appropriate.  In listings, values below LLOQ will be reported as 
of quantification.  The LLOQ for various PK and biomarker concentrations will be 
noted in all tables and listings.  
Missing concentrations. 
If a concentration value is not collected or cannot be analyzed due to sample quality 
issues, it will be considered as missing data and will not be imputed.  
Missing actual sampling time.  
If actual sampling time (date or hour) value is missing, the protocol-stated nominal 
time will be used. 
6. ANALYSES AND SUMMARIES 
6.1. Primary Endpoint(s) 
6.1.1. Main Analysis 
Estimand strategy: Primary Estimand (Section 2.2.1). This estimand is intended to 
provide an estimate of the treatment effect in the absence of prohibited medication 
use in a population that may or may not be fully compliant with the treatment. 
Analysis set: ITT Analysis Set (Section 4). 


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Analysis methodology: A landmark analysis of the IGA/PGA success endpoints at 
Week 12 will be performed using the ITT analysis set. The proportions responding 
and the corresponding risk difference comparing active treatment arm to vehicle 
group will be analyzed using the unconditional exact method; the risk differences and 
the corresponding 2 sided unconditional exact 95% confidence intervals will be 
computed using Chan and Zhang (1999)1 method. The overall family wise Type I 
error rate will be controlled at the 1 sided 0.025 level using the Hochberg step up 
procedure. 
Intercurrent events and missing data: A) Prohibited medication  response will be 
considered as failure for time points after start date of the event for participants who 
receive prohibited medication post randomization. B) Withdrawal and all other 
events, except COVID-19 pandemic, leading to missing data will be treated similarly 
assuming that participants no longer receive benefit from the study intervention and 
hence will be considered as failure. C) COVID-19 pandemic: if a participant misses a 
visit due to COVID-19, he/she will be excluded from the analysis for that visit; If a 
participant discontinues treatment or withdraws from the study due to COVID-19, 
he/she will be excluded from the analyses after the treatment discontinuation visit or 
study withdrawal visit, respectively. D) Inadequate compliance  participants data 
will be used as recorded. 
Proportions, risk differences and 95% confidence intervals will be presented.   
6.1.2. Sensitivity/Supplementary Analyses 
Sensitivity Analyses: 
If there are enough data in each of the disease severity groups,  Cochran test stratified by 
baseline disease severity with the minimum risk weights proposed by Mehrotra and Railkar 
(2000) may be considered for IGA/PGA success at week 12.   
In addition, a generalized linear mix model may be used for the repeated measures of 
IGA/PGA success at all time points.  The fixed effects of treatment, visit, treatment by visit 
interaction be included in the model. If there are enough data in each of the disease severity 


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group, baseline disease severity may be included as additional fixed effect. Unstructured 
covariance will be used when possible.  At each visit, estimates of mean odds ratio between 
the active treated group and the placebo will be presented. The corresponding p-values and 
95% confidence intervals will also be derived from the model.  
Supplementary Analyses: 
For PGA success data with three active dose levels, a Bayesian Emax model may be used to 
characterize the dose response relationship (Appendix 2).  
6.2. Secondary Endpoint(s) 
6.2.1. Binary Secondary Endpoints 
IGA/PGA success at other timepoints, EASI/ PASI-75, PP-NRS success ( 4 points of 
reduction from baseline), IGA/PGA of clear or almost clear will be analyzed the same way as 
described in Section 6.1.1. PP-NRS success rate will be summarized for all participants in 
ITT Analysis Set in AD, and adult participants (18 75 years old) only in ITT Analysis Set   
for PsO.  
6.2.2. Continuous Secondary Endpoints 
Continuous secondary endpoints include percent CFB in EASI total score, CFB in PASI total 
score, and percent CFB in affected BSA. 
 
Estimand strategy: Secondary estimand (Section 2.2.2). This estimand is intended to 
provide an estimate of the treatment effect in the absence of prohibited medication 
use in a population that may or may not be fully compliant with the treatment. 
Analysis set: ITT Analysis Set (Section 4). 
Analysis methodology: A landmark analysis of these continuous endpoints at Week 
12 will be performed by ANCOVA with baseline as a covariate. Missing data, except 
missing due to COVID-19 pandemic, will be imputed using a control-based 
imputation method. PROC MI will first be called to impute missing vehicle 
observations under the assumption data are missing at random (MAR) and impute 


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missing active treatment observations assuming they are similar to corresponding 
vehicle arm. The imputation will utilize ANCOVA model including baseline as a 
covariate fitted using only vehicle arm data. The analysis will combine the results 
MIANALYZE. MMRM models may also be used on observed data at all time points 
as sensitivity analyses. The fixed effects of treatment, visit, and treatment by visit 
interaction will be included. Baseline value will be included as a covariate. No 
adjustments for multiplicity will be made.
Intercurrent events and missing data: A) Prohibited medication: all scores measured 
at time points after start date of the event for participants who receive prohibited 
medication post randomization will be excluded from the analysis and treated as 
missing scores. Missing scores will be imputed. B) Withdrawal and all other events 
leading to missing data, except COVID-19 pandemic: all missing scores will be 
imputed. C) COVID-19 pandemic: if a participant misses a visit due to COVID-19,
he/she will be excluded from the analysis for that visit; If a participant discontinues 
treatment or withdraws from the study due to COVID-19, he/she will be excluded 
from the analyses after the treatment discontinuation visit or study withdrawal visit, 
respectively. D) Inadequate compliance participants data will be used as recorded.
The least-squares (LS) means, the 95% confidence interval for the LS means, the 
difference between the LS means for each pair of treatment groups, and the 
corresponding 95% confidence interval will be presented.
6.3. Tertiary/Exploratory Endpoints
6.3.1. Binary Tertiary/Exploratory Endpoints
6.3.2. Continuous Tertiary/Exploratory Endpoints


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6.3.3. PRO Endpoints 
PP-NRS (for AD and adult PsO aged 18-75), 
6.4. Other Endpoint(s) 
6.4.1. PK Endpoints  
PF-07038124 concentration data will be summarized through appropriate data tabulations, 
descriptive statistics, and graphical presentation.  A population PK model may be developed 
for the purpose of estimating PK parameters. In addition, a relationship between 
doses/exposures and efficacy/safety endpoints may be evaluated using population 
PK/pharmacodynamic (PD) approach.  Details of the methodology will be captured in a 
separate modeling plan and the results will also be reported separately. 
6.5. Subset Analyses 
Proportion of IGA/PGA success at Week 12 may be summarized for the subsets below if we 
have sufficient number of participants in each stratum: 
Baseline Disease Severity: mild/moderate for AD and mild/moderate/severe for
PsO.
6.6. Baseline and Other Summaries and Analyses
6.6.1. Baseline Summaries
Demographic and baseline characteristics will be summarized by treatment for the safety 
analysis set. Key demographic and baseline variables include age, gender, race, ethnicity, 


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height, weight, body mass index, disease duration, baseline affected BSA (%), EASI and 
IGA score for AD participants, PASI and PGA for PsO participants. 
6.6.2. Study Conduct and Participant Disposition 
Participant
evaluation for analysis populations, disposition and discontinuation will be 
summarized according to CaPS. 
6.6.3. Study Treatment Exposure 
The exposure to study drug measured by number of days with dosing will be summarized. 
The number and percent of participants in exposure duration categories (<1 week to >12 
weeks with 1 week increments) will be presented. A summary of dosing compliance, defined 
as % days with dosing out of the duration between first and last dosing, will be provided by 
treatment. Number of percent of participants with treatment non-compliance (compliance < 
80% or more than 120% of study intervention application) will also be summarized. 
Ointment application rate, defined as amount of ointment applied per dose(mg) divided by 
treated BSA (cm**), will also be summarized by treatment and time. The treated BSA at 
subsequent visits should be equal to or greater than the value at Day 1 (Protocol section 8.9), 
and different from affected BSA as efficacy endpoint.  
6.6.4. Concomitant Medications and Nondrug Treatments 
Prior drug and non-drug treatment, concomitant drug and non-drug treatment will be 
summarized according to CaPS. 
6.7. Safety Summaries and Analyses 
The analysis population for safety is described in Section 4. Safety and tolerability will be 
assessed by clinical review of all relevant parameters including adverse experiences (AEs), 
ECG, vital signs, local skin tolerability and laboratory tests.  A complete list of laboratory 
parameters can be obtained in Appendix 2 of the protocol.  
All the tables, listings and graphs for adverse events, lab parameters and vital sign and ECG 
will follow CaPS.   


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6.7.1. Adverse Events 
AE endpoints including below will be listed and summarized in accordance with the CaPS: 
Treatment-emergent AEs , SAEs, treatment area AEs and treatment related AEs. 
Discontinuation of treatment due to AEs and treatment area AEs. 
Table display will be by descending order of frequency in all treatment arms. 
6.7.2. Laboratory Data 
Laboratory data will be listed and summarized in accordance with the CaPS.  . Categorical 
summaries of participants meeting pre-specified abnormality criteria will be created.   
6.7.3. Vital Signs 
The absolute value, and change from baseline will be summarized by treatment and time. 
Categorical summary of participants meeting pre-specified clinical criteria will be provided 
by treatment and time.   
6.7.4. Electrocardiograms 
The absolute value and changes from baseline for the ECG parameters QT interval, heart 
rate, QTc interval, PR interval, and QRS complex will be summarized by treatment and time.  
The number (%) of participants with maximum post-dose QTc values and maximum 
increases from baseline in the following categories will be tabulated by treatment:  
Safety QTc Assessment 
Degree of Prolongation 
Mild (msec) 
Moderate (msec) 
Severe (msec) 
Absolute value 
>450-480 
>480-500 
>500 
Increase from baseline 
 
30-60 
>60 


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6.7.5. Local Skin Tolerability 
Categorical summary tables will be provided by treatment and time. In addition, a summary 
of number and percent of participants by worst local skin tolerability grade during the whole 
study period will be created. 
7. INTERIM ANALYSES 
7.1. Introduction 
An interim analysis may be performed to assess efficacy and safety when approximately 
60% of the planned participants, i.e., approximately 25 participants per arm in AD and 
18 participants per arm in PsO have completed or had the chance to complete Week 8 visit. 
Interim analysis results may be used for decisions regarding stopping for futility and internal 
program development. The detailed decision boundary will be  detailed in the IRC charter. 
Additional interim analysis may be performed and will be detailed in the IRC charter. 
7.2. Interim Analyses and Summaries 
At interim, analyses specified in Section 6.1.1 will be performed for IGA/PGA success and 
EASI/PASI-75 at week 8. In addition, safety data including primarily adverse event, 
tolerability and PK data will be analyzed.  
Interim predictive probability of success (PoS) in primary endpoints based on the interim 
data will be calculated assuming a non-informative uniform prior for IGA/PGA success rate. 
The trial may stop for futility (non-binding) if the interim PoS <20%.  
Interim Predictive Probability of Success 
 
Let 
 and 
 be the probability of success for active arm and vehicle arm, both following a 
Beta(1,1)  prior. Let 
 and 
 be the number of successes observed out of 
 and 
 
participants at stage i for the active and vehicle arm.   
For a given criteria at the end of stage 2:  Posterior Prob( 
d|
 >c, 
where d is a target value and c is a probability cut-off to be detailed in IRC charter, since  


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we can calculate interim (stage 1) predictive probability of success of such criteria as 
Predictive Prob {Posterior Prob ( 
d|
using below predictive distributions property:
 Binomial(
), 
 Binomial(
), where 
 and 
  
Decision will primarily be based on interim data at week 8 and corresponding success 
criteria, as it is expected to have limited week 12 data at interim.  
 
 
8. REFERENCES 
1.
Chan ISF and Zhang Z. Test based exact confidence intervals for the difference of two 
binomial proportions. Biometrics, 1999, 55:1201 1209. 
2.
Mehrotra, D. V., & Railkar, R. (2000). Minimum risk weights for comparing treatments 
in stratified binomial trials. Statistics in medicine, 19(6), 811-825 


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9. APPENDICES
Appendix 1. Summary of Efficacy Analyses
Efficacy Endpoint
Analysis Type
Population
Data Inclusion and 
Rules for Handling 
Intercurrent 
Events and Missing 
Data 
Analysis Model
Week 12 IGA / PGA 
Response
Primary
ITT
NRI
Chan & Zhang
Sensitivity
ITT
NRI
Minimum Risk
Supportive
ITT
NRI
Generalized 
Linear Mixed
Model
Supportive
ITT
NRI
Bayesian Emax
Week 12 EASI/PASI-75
Response
Secondary
ITT
NRI
Chan & Zhang
Week 12 PCFB in EASI /
CFB in PASI
Secondary
ITT
MI
ANCOVA
PCFB in EASI / CFB in 
PASI
Sensitivity
ITT
OC
MMRM
PP-NRS Rate / IGA of 
clear or almost clear / / 
PGA of clear or almost 
clear
Secondary
ITT
NRI
Chan & Zhang
Exploratory 
ITT
NRI
Chan & Zhang
PCFB= Percent change from baseline; CFB= Change from baseline; ANCOVA = Analysis of Covariance; NRI 
= Non-Responder Imputation; OC = Observed Cases.


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Appendix 2. Dose Response Analysis for PsO 
The 4-parameter Emax model will be fit using the latest version (currently v2.3.5) of the 
clinDR package. The below model will be applied the PGA success rate  at week 12. 
 
Weakly informative Priors Setup: 
A weakly-informative prior distribution 
t(mean= -2.44, scale = 4, df=5)  gives a 31% 
probability 
 and 7% probability 
 , and is robust enough to cover the 
historical vehicle data range (4% ~15%) for PGA success rate at week 6~12. The mean is 
based on meta-analysis results PGA success rate with a mean of 8% and 95% CI (4% ,15%) 
at week 6~12, including the C3941002 study result with observed success rate of 1/17 (5.9%) 
and 95% CI (0.3%, 27.8%) at week 6. 
We will specify the prior for the treatment effect 
 at a target dose (0.06% the maximum 
dose),  
. A prior distribution of  
t (mean= 1.23, scale =2, df=5) 
will be used.  C3941002 study at week 6 with observed PGA success rate of 3/17 (17.6%) for 
the low dose 0.01% and 1/17 (5.9%) for vehicle, results in an odds ratio of 3.43 with 95% CI 
(0.23, 191), or log odds ratio of 1.23 with 95% CI ( -1.5,5.25).  Such prior gives a 5% 
probability of log odds ratio>5.25 (equivalent of a change in success rate from 8% to 94%), 
and a 39% probability of log odds ratio>1.82 (equivalent of a change in success rate from 8% 
to 35%, the observed success rate at week 12 assuming observed treatment effect is linear in 
time), and 12% probability of  log odds ratio <-1.5 (equivalent of a change in success rate 
from 8% to 2%).  
ED50: log(ED50/P50)~t(mean=0, scale= 1.73, df=5), Log(lambda)~t(mean=0, 
scale=0.425, df=5) with a correlation of -0.45 between log(lambda) and log(ED50) are the 
default prior in clinDR package, under which the probability of ED50/P50>32.6 is 5%, and 
the probability of lambda>2.35 is 5%. P50 =0.02% is empirically estimated as mean of the 
first two lowest dose.  


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The default MCMC burn-in and number of samples will be utilized, which will include 3 
chains to assess convergence. Model diagnostics will be examined including trace and auto-
correlations plots. If these raise concerns over model convergence, additional burn-ins, 
samples and thinning will be attempted to improve convergence. Non-monotone dose 
response relationship will be checked before model fitting.  
An independent statistician will conduct QC of the analysis. The outputs of the analysis will 
be provided as .csv files to the programming team for inclusion with the tables and figures in 
the reporting. 
 
 


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Appendix 3. Definition and Use of Visit Windows in Reporting 
Visit windows will be used for efficacy variables, and for any safety data that display or 
summarize by study visit. 
 
Visit 
No. 
Visit Label  
Target Day 
 Visit Window  
 
Screening  
N/A 
-28 
-1 
1 
Baseline* 
1  
 day = 1 
2 
Week 1 
8 
2
11 
3 
Week 2 
15  
22 
5 
Week 4 
29  
23
6 
6 
Week 6 
43 
37
50 
7 
Week 8 
57 
51
64 
8 
Week 10 
71 
65
78 
9 
Week 12 
85 
79
99 
10 
FUP/EOS 
N/A 
day >99 
e.g., those involving change 
from baseline).  That is, in case that Day 1 observation is missing, the last observation before the first dosing 
date may be considered as the baseline.  The baseline measurements for demography, height, pre-study 
medical history an
 
If two or more visits fall into the same window, keep the one closest to the Target Day.  If 
two visits are equally distant from the Target Day in absolute value, the later visit should be 
used. 
 
 


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Appendix 4. Sample SAS Code  
Sample SAS Code for Estimand 1  Risk Difference using Chan and Zhang (1999) 
PROC BINOMIAL DATA=<DATASET> GAMMA=0 ALPHA=<Value> OUT=<>; 
 
PD/EX ONE STD; 
 
PO <POPULATION VARIABLE>; 
 
OU <OUTCOME VARIABLE>; 
RUN; 
Sample SAS Code for the Confidence Interval of a Binomial Proportion 
(Blyth-Still-Casella) 
PROC BINOMIAL DATA=<DATASET> ALPHA=<value> OUT=<>; 
 
BI/BS; 
 
OU <RESPONSE VARIABLE>; 
RUN; 
Sample SAS Code for the Confidence Interval of two Binomial Proportion (Minimum 
Risk) 
 
PROC FREQ DATA= <DATASET>; 
 
TABLES <STRATA>*<TRT>*EVENT / COMMONRISKDIFF(CL=MR 
 
TEST=MR COLUMN=2) ) RELRISK ALPHA=<VALUE>;  
 
ods output CommonPdiff=<> CommonPdiffTests=<> 
RUN;  
Sample SAS Code for Generalized Linear Mixed Model 
 
PROC GLIMMIX DATA=<DATASET>;  
   
CLASS AVISIT <TRT> <STRATA> USUBJID; 
 
MODEL CRIT1FL(EVENT="Y")=<STRATA> <TRT>|AVISIT 
 
/ALPHA=0.05 DIST=BINARY DDFM = KR; 
    RANDOM  _RESIDUAL_/SUBJECT = USUBJID TYPE=UN; 
    LSMEANS <TRT>*AVISIT/ILINK COV DIFF CL ALPHA=<VALUE>; 
RUN; 


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Sample SAS Code for Estimand 2 ANCOVA 
libname c3941005  
 
data ps; 
              set c3941005.adps; 
run; 
data look; 
              set ps; 
              where param = "EASI02-Total Sum"  and viswin ne .; 
              keep subjid param paramn avisit age sex trta viswin visit xviswin aval base chg pchg 
trtan; 
run; 
data ex1; 
              set look; 
              
12  
 
regimen = "QD"; 
 
if trtan = 1 then dose=0; 
 
if trtan = 2 then dose=0.01; 
 
if trtan = 3 then dose=0.03; 
 
if trtan = 4 then dose=0.06; 
              keep subjid dose regimen chg aval base; 
run; 
proc means data=ex1; 
              class regimen dose; 
              var chg aval; 
run; 
proc sort data=ex1 out=ex2; 
    *data must be sorted by regimen before use in proc mi; 
              by regimen dose; 
run; 
*imputing aval=observed so range of endpoint 0-72 can be included in; 
*mi procedure; 
proc mi data=ex2 seed=1022 nimpute=1000 out=outimp  max=. 72 72 min=. 0 0; 
              by regimen; 


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              class dose; 
              monotone reg(aval= base/details); 
              mnar model( aval/modelobs = (dose="0")); 
              var base  aval; 
run; 
proc univariate data=outimp; 
var aval; 
histogram ; 
run; 
data outimp1; 
              set outimp; 
              chg = aval - base;**calculate chg from baseline 
run; 
proc sort data = outimp1 out = outimp2; 
    by _imputation_ regimen dose subjid; 
run; 
               
proc mixed data=outimp2; 
             by _imputation_; 
             class dose regimen; 
             model chg = base dose*regimen; 
             lsmeans dose*regimen/ diff alpha=<Value>; 
             ods output diffs=diffs lsmeans=lsmeans; 
run; 
               
data diffsout; 
              set diffs; 
              **only keep within regimen contrasts vs placebo; 
              where regimen = _regimen and dose = 0; 
run; 
**now use mianalyze on lsmean differences; 
**First sort by group, regimen and _dose (dose = 0 for all groups); 
proc sort data=diffsout out=diffsout1; 


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              by regimen _dose _imputation_; 
run; 
**now mianalyze by regimen and _dose; 
**NB mianalyze only uses estimates and standard errors not CI limits etc.; 
proc mianalyze data=diffsout1  alpha=<Value>; 
      by regimen _dose; 
      modeleffects estimate; 
      stderr stderr; 
      ods output parameterestimates=parameterestimates; 
run; 
 
Sample SAS Code for Estimand 2 MMRM 
proc mixed data=_dsnin order=internal alpha=<Value>; 
    by PARAMN; 
    class SUBJID AVISITN TRTPN; 
    model PCHG = BASE TRTPN AVISITN  TRTPN*AVISITN /solution ddfm=kr; 
repeated AVISITN/ participant =SUBJID type=un r rcorr;  
/**try UN first, if not converged, will use CS***/ 
    lsmeans TRTPN*AVISITN / diff cl alpha=<Value>;  
    ods output lsmeans=lsmeans diffs=diffs; 
run; 
/*For one-sided P-value calculation, the LOWER tail side should be used. */;