Final Clinical Study Report
Protocol C2501004

CLINICAL STUDY REPORT SYNOPSIS
Sponsor: Pfizer Inc
Investigational Product: PF-06826647
Clinical Study Report Synopsis: Protocol C2501004
Protocol Title: A Phase 2, Randomized, Double Blind, Placebo-Controlled, Study to
Evaluate the Safety and Efficacy of PF-06826647 in Participants With Moderate to Severe
Plaque Psoriasis
Investigators: Refer to Appendix 16.1.4.1 for a list of investigators involved in this study.
Study Center(s): This study was conducted at 36 centers (7 in Canada, 6 in Japan, 6 in
Poland, and 17 in United States). Refer to Appendix 16.1.4.1 for a list of sites involved inthis study.
Publications Based on the Study: None
Study Initiation Date: 27 June 2019
Study Completion Date: 26 November 2020 (primary completion date: 21 May 2020).
Report Date: 16 April 2021
Previous Report Date(s): Not Applicable
Phase of Development: Phase 2b
Study Objectives and Endpoints: The study objectives and endpoints are provided inTable S1 and Table S2 for the Investigational Treatment Period (up to Week 16) and theExtension Treatment Period (Week 16 to Week 40), respectively. The terms “participant”
and “subject” are used interchangeably in this Synopsis.

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Table S1. Study Objectives and Endpoints for Investigational Treatment Period
Type
Primary
Efficacy

Secondary
Efficacy

Efficacy

Efficacy

EfficacyPRO

PRO

Objective

Endpoint

To compare the efficacy of multiple dose levels
of PF-06826647 versus placebo on the
proportion of participants with moderate tosevere plaque psoriasis achieving PASI 90.



To compare the efficacy of multiple dose levels
of PF-06826647 versus placebo on the
proportion of participants with moderate tosevere plaque psoriasis achieving PASI 75.
To compare the efficacy of multiple dose levels
of PF-06826647 versus placebo on PGA scorein participants with moderate to severe plaquepsoriasis.
To compare the efficacy of multiple dose levels
of PF-06826647 versus placebo on the
proportion of participants with moderate tosevere plaque psoriasis achieving PASI 50 and
PASI 100.
To compare the efficacy of multiple dose levels
of PF-06826647 versus placebo on PASI scoresin participants with moderate to severe plaquepsoriasis.
To compare the effect of multiple dose levels
of PF-06826647 versus placebo in PP-NRS
score in participants with moderate to severeplaque psoriasis.
To compare the effect of multiple dose levels
PF-06826647 versus placebo on measures of
disease and symptom severity in participants
with moderate to severe plaque psoriasis.

Key secondary endpoint: Proportion of participants achieving PASI 75 (75% or greater improvement frombaseline) at time points specified in the SoA.


Proportion of participants achieving PASI 90 (90% or greater improvement frombaseline) at Week 16.

Proportion of participants with PGA score clear (0) or almost clear (1) and ≥2 points
improvement from baseline at time points specified in the SoA.
Proportion of participants with PGA score clear (0) or almost clear (1) at time points
specified in the SoA.
Proportion of participants achieving PASI 50 (50% or greater improvement frombaseline), PASI 100 (100% from baseline) at time points specified in the SoA.



Change from baseline and percent change from baseline in PASI scores at time points
specified in the SoA.



Change from baseline in PP-NRS score at time points specified in the SoA.



Proportion of participants with PSI overall score ≤8 with 0 or 1 for every individual
domain at time points specified in the SoA.

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CLINICAL STUDY REPORT SYNOPSIS
Table S1. Study Objectives and Endpoints for Investigational Treatment Period
Type
SafetyObjective
To assess the safety and tolerability of
PF-06826647 in participants with moderate tosevere plaque psoriasis.

To compare the efficacy of multiple dose levels
PF-06826647 versus placebo on measures of
disease and symptom severity in participants
with moderate to severe plaque psoriasis.

Endpoint
Incidence and severity of AEs, SAEs and withdrawals due to AEs.
Change from baseline in clinical laboratory values (chemistry, hematology and lipids).
Incidence of clinically significant changes in ECG (heart rate, QT, QTc, PR and QRS
intervals).
Change from baseline in vital signs (blood pressure, pulse rate and temperature
measurements).
Change from baseline PSI at time points specified in the SoA.

To compare efficacy of multiple dose levels of
PF-06826647 versus placebo in L-PASI andpsoriatic BSA in participants with moderate tosevere plaque psoriasis.
To compare the effect of multiple dose levels
of PF-06826647 versus placebo on selected
PRO in participants with moderate to severeplaque psoriasis.

Change from baseline in L-PASI score at time points specified in the SoA.
Absolute and change from baseline in psoriatic BSA at time points specified in SoA.



Change from baseline in Night-time Itch scale at time points specified in the SoA.
Change from baseline in dermatology-specific QoL as measured by the DLQI at time
points specified in the SoA.
Proportion of participants who achieved DLQI response of ≥4 improvement frombaseline at time points specified in the SoA.
Change from baseline in the generic QoL as measured by the SF-36v2 standard survey attime points specified in the SoA.
Change from baseline in PtGA of Psoriasis at time points specified in the SoA.
Proportion of participants who achieved PtGA response of clear (0) or almost clear (1) attime points specified in the SoA
PF-06826647 concentrations at time points specified in the SoA.



Change from baseline over time of lymphocyte subsets (TBNK) in peripheral blood.
Change from baseline in hsCRP levels at time points specified in the SoA.






PRO

Exploratory
Efficacy

PRO






PK
PD

To evaluate PK of PF-06826647 in participants
with moderate to severe plaque psoriasis.
To compare the effect of multiple dose levels
of PF-06826647 versus placebo on biomarkers
in participants with moderate to severe plaquepsoriasis.

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Table S1. Study Objectives and Endpoints for Investigational Treatment Period
Type
Bankedbiospecimen

Objective
Endpoint
To enable exploratory research through Potential results from exploratory analysis of banked biospecimens (these results may orcollection of banked biospecimens, unless
may not be generated in the context of the present study).
prohibited by local regulations or ethics
committee decision.
Abbreviations: AE = adverse event; BSA = Body Surface Area; DLQI = Dermatology Life Quality Index; ECG = electrocardiogram; hsCRP = high sensitivity
C-reactive protein; L-PASI = linear method Psoriasis Area and Severity Index; PASI = Psoriasis Area and Severity Index; PASI 50 = at least 50% reduction frombaseline in the PASI total score; PASI 75 = at least 75% reduction from baseline in the PASI total score; PASI 90 = at least 90% reduction from baseline in the
PASI total score; PASI 100 = at least 100% reduction from baseline in the PASI total score; PD = pharmacodynamic(s); PGA = Physician’s Global Assessment;
PK = pharmacokinetic(s); PP-NRS = Peak-Pruritus Numerical Rating Scale; PRO = patient reported outcome; PSI = Psoriasis Symptom Inventory;
PtGA = Patient Global Assessment; QoL = quality of life; QTc = QT interval corrected; SAE =serious adverse event; SF-36v2 = Short Form-36 Health survey
Version 2; SoA = Schedule of Activities; TBNK = T cells, B cells and Natural Killer cells.

Table S2. Study Objectives and Endpoints for Extension Treatment Period
Type
Primary
SafetyObjective
To assess the safety and tolerability of
PF-06826647 in participants with moderate tosevere plaque psoriasis.

EndpointIncidence and severity of AEs, SAEs and withdrawals due to AEs.
Change from baseline in clinical laboratory values (chemistry, hematology and lipids).
Incidence of clinically significant changes in ECG (heart rate, QT, QTc, PR and QRS
intervals).
Change from baseline in vital signs (blood pressure, pulse rate and temperature
measurements).

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Table S2. Study Objectives and Endpoints for Extension Treatment Period
Type
Exploratory
Efficacy/PRO

Objective
To compare long-term efficacy and durabilityof multiple dose levels of PF-06826647 inparticipants with moderate to severe plaquepsoriasis.

Endpoint







PK





Proportion of participants achieving PASI 50/75/90/100.
Proportion of participants with PGA score clear (0) or almost clear (1) and ≥2 points
improvement from baseline at time points specified in the SoA.
Proportion of participants with PGA score clear (0) or almost clear (1) at time points
specified in the SoA.
The proportion of participants who achieved a PSI score of 0 (not at all) or 1 (mild) on
every item at time points specified in the SoA.
Change from baseline in PP-NRS score at time points specified in the SoA.
Change from baseline and percent change from baseline in PASI scores at time points
specified in the SoA.
Change from baseline in L-PASI score at time points specified in the SoA.
Absolute and change from baseline in psoriatic BSA at time points specified in SoA.
PF-06826647 concentrations and parameters (data permitting) obtained from blood
samples at time points specified in the SoA.

To characterize PK of PF-06826647 dosing
regimens in participants with moderate tosevere plaque psoriasis.
Abbreviations: AE = adverse event; BSA = Body Surface Area; ECG = electrocardiogram; L-PASI = linear method Psoriasis Area and Severity Index;
PASI = Psoriasis Area and Severity Index; PASI 50 = at least 50% reduction from baseline in the PASI total score; PASI 75 = at least 75% reduction frombaseline in the PASI total score; PASI 90 = at least 90% reduction from baseline in the PASI total score; PASI 100 = at least 100% reduction from baseline in the
PASI total score; PGA = Physician’s Global Assessment; PK = pharmacokinetic(s); PP-NRS = Peak-Pruritus Numerical Rating Scale; PRO = patient reported
outcome; PSI = Psoriasis Symptom Inventory; QTc = QT interval corrected; SAE =serious adverse event.

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CLINICAL STUDY REPORT SYNOPSISMETHODS
Study Design: This was a Phase 2b, randomized, double-blind, placebo-controlled,parallel-group, and multicenter study in participants with moderate to severe plaquepsoriasis. Placebo and 4 PF-06826647 daily oral dose levels (50 mg, 100 mg, 200 mg or
400 mg) were used in the study. The study schema is provided in Figure S1. Approximately
160 participants (40 participants in each of the following arms: placebo, 200 mg, and
400 mg; and 20 participants in each of the following arms: 50 mg and 100 mg) wererandomly assigned to a treatment group in order to ensure a minimum of 128 evaluableparticipants completing Week 16 (assuming a 20% dropout rate).
Figure S1. Study Schema

Abbreviation: QD = once daily.

Diagnosis and Main Criteria for Inclusion: Male or female participants between the agesof 18 (or the minimum country-specific age of consent if >18) and 75 years, inclusive, atscreening, and with body weight >40 kg, who had a diagnosis of plaque psoriasis (psoriasis
vulgaris) for at least 6 months prior to baseline/Day 1, and had a Psoriasis Area and Severity
Index (PASI) score ≥12, a Physician’s Global Assessment (PGA) score of 3 (moderate) or
4 (severe) and a psoriatic Body Surface Area (BSA) ≥10% of total BSA at baseline/Day 1,
were eligible for participating in the study.
Study Treatment: Blinded PF-06826647 and matching placebo were provided as tablets fororal administration (Table S3). PF-06826647 was provided in dosage strengths of 100 mg
and 25 mg tablets. PF-06826647 and matching placebo were supplied in blister cards andlabeled according to local regulatory requirements.
PF-06826647 and the placebo were administered once daily (QD) during the Investigational
Treatment Period and the Extension Treatment Period. Participants swallowed theinvestigational product whole with ambient temperature water to a total volume of
approximately 240 mL, and did not manipulate or chew the investigational product prior to
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swallowing. It was recommended to be taken with food. Participants administered theinvestigational product as outpatients, except on study visit days. On study visit days,
participants took their dose of study drug when instructed to do so by the investigator ordesignated study site staff while at the study site.
Table S3. Investigational Product Description
Investigational Product Description
Placebo oval tablet (2:1, MCC:lactose)
PF-06826647 25 mg round white to
off-white tablet (250 mg/g SDD)
PF-06826647 100 mg oval white to
off-white tablet (250 mg/g SDD)
PF-06826647 100 mg oval white to
off-white tablet (250 mg/g SDD)
Placebo 8 mm tablet (2:1, MCC:lactose)
PF-06826647 100 mg oval white to
off-white tablet (250 mg/g SDD)
PF-06826647 100 mg oval white to
off-white tablet (250 mg/g SDD)
PF-06826647 100 mg oval white to
off-white tablet (250 mg/g SDD)
PF-06826647 100 mg oval white to
off-white tablet (250 mg/g SDD)
PF-06826647 100 mg oval white to
off-white tablet (250 mg/g SDD)
PF-06826647 100 mg oval white to
off-white tablet (250 mg/g SDD)
PF-06826647 25 mg round white to
off-white tablet (250 mg/g SDD)
PF-06826647 100 mg oval white to
off-white tablet (250 mg/g SDD)
PF-06826647 100 mg oval white to
off-white tablet (250 mg/g SDD)
PF-06826647 100 mg oval white to
off-white tablet (250 mg/g SDD)
PF-06826647 100 mg oval white to
off-white tablet (250 mg/g SDD)
PF-06826647 100 mg oval white to
off-white tablet (250 mg/g SDD)
Abbreviation: N/A = not applicable.

Vendor Lot
Number
B16156

Pfizer Lot
Number16-005224

Strength/Potency
0 mg

DosageForm
TabletN/A

17-000496

25 mg

TabletN/A

18-000477

100 mgTabletN/A
N/A

18-000478
18-001357

100 mg0 mg

TabletTablet19-DP-00025

19-001288

100 mgTablet19-DP-00026

19-001289

100 mgTablet19-DP-00027

19-001290

100 mgTablet19-DP-00048

19-002536

100 mgTablet19-DP-00049

19-002537

100 mgTablet19-DP-00058

19-002809

100 mgTablet19-DP-00007

19-000554

25 mg

Tablet19-DP-00008

19-000555

100 mgTablet19-DP-00009

19-000556

100 mgTablet19-DP-00010

19-000557

100 mgTablet19-DP-00056

19-002807

100 mgTablet19-DP-00057

19-002808

100 mgTabletEfficacy Evaluations:

The PASI quantifies the severity of a participant’s psoriasis based on both lesion severity
and the percentage of body surface area affected. The PASI score can vary in incrementsof 0.1 unit from 0.0 to 72.0, with higher scores representing increasing severity ofpsoriasis. A second method of linear method Psoriasis Area and Severity Index (L-PASI)
was also applied to PASI calculation.
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CLINICAL STUDY REPORT SYNOPSISThe PGA of psoriasis was scored on a 5-point scale, reflecting a global consideration of
the erythema, induration and scaling across all psoriatic lesions. Average erythema,induration and scaling were rated separately over the whole body according to a 5-point
severity scale (from 0 to 4), with appropriate morphologic descriptors. The severity ratingscores were summed, and the average was taken and rounded to the nearest whole
number score to determine the PGA. The 5-point scale for PGA: 0, “clear”; 1, “almost
clear”; 2, “mild”; 3, “moderate”; 4 “severe”.

Assessment of BSA involved in psoriasis was performed separately for 4 areas of the
body: head and neck, upper limbs, trunk (including axillae and groin) and lower limbs(including buttocks). The percentage surface area affected by psoriasis was estimated bymeans of the “handprint method”, which represents approximately 1% of the total BSA.
Based on the same body region weighting employed in the PASI calculation, the numberof handprints of psoriatic skin in a body region was used to determine the extent (%) to
which a body region had psoriatic involvement.

Patient-Reported Outcomes (PROs):

Peak-Pruritus Numerical Rating Scale (PP-NRS): an 11-category numeric rating scalefrom 0 to 10 to assess the intensity pruritus. Participants were asked to assess their itchover the past 24 hours, anchored by the terms “no itch” (0) and “worst itch
imaginable” (10) at the ends.

Psoriasis Symptom Inventory (PSI): a self-administered 8 item questionnaire to measure
the severity of psoriasis symptoms over the past 24 hours and the past 7 days. Participants
were asked to respond to each item using a 5-point Likert response scale (0: not at all, 1:
mild, 2: moderate, 3: severe and 4: very severe).

Night-Time Itch scale: a single-item, 0 to 10 horizontal numeric rating scale to assess theseverity of itch due to psoriasis. Participants were asked to assess their itch at the worst
moment during the most recent night’s sleep on a Numeric Rating Scale (NRS) anchoredby the terms “no itch” (0) and “worst itch imaginable” (10) at the ends. Participants werealso asked the frequency of itch on a 5-point Likert scale.



Dermatology Life Quality Index (DLQI): a general dermatology questionnaire consistingof 10 items that assess participant health-related quality of life (daily activities, personal
relationships, symptoms and feelings, leisure, work and school, and treatment) over thelast week.



Short Form-36 Health survey Version 2 (SF-36v2): a validated 36-item generic healthstatus measure. Lower scores indicate worse physical and mental health status.



Patient Global Assessment (PtGA) of Psoriasis: a single-item, 5-point scale to evaluate
the overall cutaneous disease at that point in time. The same category labels used for the
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PtGA of Psoriasis, ie, “severe”, “moderate”, “mild”, “almost clear”, and “clear (nopsoriasis)”.
Pharmacokinetic and Pharmacodynamic Evaluations:Pharmacokinetic(s): Blood samples were collected pre-dose at each visit and also at 0.5, 1, 2
and 4 hours post-dose at Week 8 and Week 40, for measurement of plasma concentrations of
PF-06826647. Plasma samples were analyzed for concentrations of PF-06826647 using avalidated high-performance liquid chromatography coupled with tandem mass spectrometry(HPLC-MS/MS) analytical method in compliance with applicable standard operatingprocedures (SOPs).
Pharmacodynamic(s): Blood samples were collected and analyzed by fluorescent activatedcell sorting (FACS) for the assessment of percent and absolute lymphocyte subsets (T cells,
B cells and Natural Killer cells [TBNK]). Blood samples were collected to provide serum formeasurement of high sensitivity C-reactive protein (hsCRP). Samples were analyzed using
fit-for-purpose or validated analytical methods in compliance with Pfizer SOPs.
Safety Evaluations: Safety evaluations included adverse event (AE) monitoring, safety
laboratory tests, vital signs (heart rate, blood pressure and temperature),12-leadelectrocardiograms (ECGs), physical examinations and Columbia Suicide Severity Rating
Scale (C-SSRS).
Statistical Methods: The full analysis set (FAS) population was defined as all randomized
participants who received at least 1 dose of investigational product. The safety analysis set
was defined as all participants who received at least 1 dose of investigational product. The
PK analysis set was defined as all participants who received at least 1 dose of PF-06826647
and in whom at least 1 concentration value was reported. The efficacy and PRO endpoints
were analyzed using the FAS. The safety endpoints were analyzed using the safety analysis
set. PK endpoints were analyzed using the PK analysis set.
Efficacy and PRO: Analysis was done pairwise between each of the PF-06826647 treatedgroups and the placebo group. An analysis with point estimates of the difference, theassociated 90% confidence intervals (CIs) and p-values were also reported.
Hypotheses and Decision Rules: Statistical inference was made on the primary endpoint.
The global null hypothesis was that there was no difference between any arm of
PF-06826647 and placebo arm. The alternative hypothesis was that one of the
PF-06826647 arms being tested was superior to the placebo arm at Week 16. The study
was to be considered positive if the null hypothesis was rejected. The familywise error
rate was controlled in strong sense at the 1-sided 0.05 level for these tests with a
Hochberg step-up procedure.

Analyses for Binary Endpoints: Landmark (cross-sectional) analyses of key binary
endpoints calculated and tested for risk differences using the method of (Chan and Zhang
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CLINICAL STUDY REPORT SYNOPSIS
1999). Covariates were not included in the primary analyses. Risk differences and
90% CIs were presented. All key binary endpoints that were measured repeatedly overtime were analyzed using generalized linear mixed effect model (GLMM) with treatmentgroup (defined as factor variable), visit, treatment group by visit interaction and subjects
as the random effect. An unstructured covariance matrix was used to fit such model.
Analyses for Continuous Endpoints: Landmark (cross-sectional) analysis of key
continuous endpoints used analysis of covariance (ANCOVA). Least squares (LS) meansat the mean overall baseline score were presented along with 90% CIs. Mixed model
repeated measures (MMRM) models were used. The fixed effects of treatment, visit(Weeks 1 2, 4, 6, 8, 12 and 16), and treatment by visit interaction were included. At each
visit, estimates of LS mean values and the LS mean differences between the
PF-06826647 treated groups and placebo group were derived from the model. The
corresponding p-values and 90% CIs were also derived from the model.



Exploratory endpoints, including PROs, were analyzed with respect to an estimand, andwere also analyzed descriptively. All endpoints for the Extension Treatment Period wereanalyzed with descriptive statistics and graphical displays when appropriate.

PK: PK concentrations were summarized and presented with descriptive statistics. Summary
statistics (N, geometric mean, geometric coefficient of variation [CV], median, arithmetic
mean, CV, minimum, maximum) of concentrations of PF-06826647 at nominal time ofcollection were calculated for each dose groups.
Safety: The safety data were summarized descriptively through appropriate data tabulations,descriptive statistics, categorical summaries, and graphical presentations.
RESULTSFor Results sections, the treatment groups will be referred to as follows in the text.
Placebo QD  PF-06826647 200 mg QD group: placebo to 200 mg QD group.

Placebo QD  PF-06826647 400 mg QD group: placebo to 400 mg QD group.



PF-06826647 50 mg QD  PF-06826647 200 mg QD group: 50 to 200 mg QD group.



PF-06826647 50 mg QD  PF-06826647 400 mg QD group: 50 to 400 mg QD group.



PF-06826647 100 mg QD  PF-06826647 200 mg QD group: 100 to 200 mg QD group.



PF-06826647 100 mg QD  PF-06826647 400 mg QD group: 100 to 400 mg QD group.



PF-06826647 200 mg QD  PF-06826647 200 mg QD group: 200 to 200 mg QD group.



PF-06826647 400 mg QD  PF-06826647 400 mg QD group: 400 to 400 mg QD group.
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Subject Disposition and Demography: A total of 179 participants were randomized, and178 participants were treated. All 178 treated participants were included in the full analysis
set and safety analysis set.
A total of 178 participants entered and 153 (86%) participants completed the Investigational
Treatment Period. A total of 153 participants entered and 130 (85%) participants completed
the Extension Treatment Period (Table S4). The discontinuation rate overall wasapproximately 14% and 15% for the Investigational Treatment Period and the Extension
Treatment Period, respectively. The most frequent reason for early termination waswithdrawal by subject (11 [6.2%] during the Investigational Treatment Period and 7 [3.9%]
during the Extension Treatment Period).
Demographic characteristics were similar across treatment groups. The majority of thetreated participants were male (68.5%) and White (88.8%). The median age was 45.0 years(range: 18-72 years). The mean weight was 86.7 kg (standard deviation [SD]: 20.37), and themean body mass index (BMI) was 28.9 kg/m2 (SD: 5.91). The disease characteristics atbaseline was comparable for participants in all treatment groups.

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Table S4. Disposition Events Summary - Safety Analysis Set (Protocol C2501004)

Number (%) of Subjects

Disposition phase: Screening
Subjects Entered:
Discontinued
Reason for
discontinuation
Adverse Event
Lack of Efficacy
Lost to Follow-Up
Pregnancy
Protocol Deviation
Withdrawal By
Subject
Other
Completed
Ongoing
Disposition phase:
Investigational Treatment
PeriodSubjects Entered:
Discontinued

Placebo QD Placebo QD PF-06826647 PF-06826647 PF-06826647 PF-06826647 PF-06826647 PF-06826647->->
50 mg QD
50 mg QD
100 mg QD
100 mg QD
200 mg QD
400 mg QD
PF-06826647 PF-06826647
->
->
->
->
->
->
200 mg QD
400 mg QD PF-06826647 PF-06826647 PF-06826647 PF-06826647 PF-06826647 PF-06826647(N=23)(N=22)
200 mg QD
400 mg QD
200 mg QD
400 mg QD
200 mg QD
400 mg QD(N=11)(N=11)(N=12)(N=11)(N=45)(N=43)
n (%)
n (%)
n (%)
n (%)
n (%)
n (%)
n (%)
n (%)

Total
(N=178)n (%)

23 (100.0)022 (100.0)011 (100.0)011 (100.0)0

12 (100.0)011 (100.0)045 (100.0)043 (100.0)0178 (100.0)
0

0
0
0
0
0
0

0
0
0
0
0
0

0
0
0
0
0
0

0
0
0
0
0
0

0
0
0
0
0
0

0
0
0
0
0
0

0
0
0
0
0
0

0
0
0
0
0
0

0
0
0
0
0
0

0
23 (100.0)00
22 (100.0)00
11 (100.0)00
11 (100.0)00
12 (100.0)00
11 (100.0)0045 (100.0)00
43 (100.0)00
178 (100.0)023 (100.0)
4 (17.4)

22 (100.0)
3 (13.6)

11 (100.0)
1 (9.1)

11 (100.0)
2 (18.2)

12 (100.0)011 (100.0)
2 (18.2)

45 (100.0)
8 (17.8)

43 (100.0)
5 (11.6)

178 (100.0)
25 (14.0)

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Table S4. Disposition Events Summary - Safety Analysis Set (Protocol C2501004)

Number (%) of Subjects
Reason for
discontinuation
Adverse Event
Lack of Efficacy
Lost to Follow-Up
Pregnancy
Protocol Deviation
Withdrawal By
Subject
Other
Completed
Ongoing
Disposition phase: Extention
Treatment Period
Subjects Entered:
Discontinued
Reason for
discontinuation
Adverse Event
Lack of Efficacy
Lost to Follow-Up
Pregnancy
Protocol Deviation

Placebo QD Placebo QD PF-06826647 PF-06826647 PF-06826647 PF-06826647 PF-06826647 PF-06826647->->
50 mg QD
50 mg QD
100 mg QD
100 mg QD
200 mg QD
400 mg QD
PF-06826647 PF-06826647
->
->
->
->
->
->
200 mg QD
400 mg QD PF-06826647 PF-06826647 PF-06826647 PF-06826647 PF-06826647 PF-06826647(N=23)(N=22)
200 mg QD
400 mg QD
200 mg QD
400 mg QD
200 mg QD
400 mg QD(N=11)(N=11)(N=12)(N=11)(N=45)(N=43)
n (%)
n (%)
n (%)
n (%)
n (%)
n (%)
n (%)
n (%)

Total
(N=178)n (%)

1 (4.3)1 (4.3)000
2 (8.7)00
0
00
3 (13.6)000001 (9.1)0000
1 (9.1)1 (9.1)

0
0
0
0
0
0

0
0
0
0
0
1 (9.1)4 (8.9)0
1 (2.2)00
3 (6.7)3 (7.0)00000

8 (4.5)1 (0.6)
1 (0.6)0
1 (0.6)
11 (6.2)

019 (82.6)
00
19 (86.4)
00
10 (90.9)
009 (81.8)00
12 (100.0)0

1 (9.1)9 (81.8)
0037 (82.2)02 (4.7)38 (88.4)
03 (1.7)153 (86.0)019 (82.6)
3 (13.0)

19 (86.4)
5 (22.7)

10 (90.9)
09 (81.8)
1 (9.1)

12 (100.0)
3 (25.0)

9 (81.8)
1 (9.1)37 (82.2)
4 (8.9)38 (88.4)
6 (14.0)

153 (86.0)
23 (12.9)

0
0
0
0
0

1 (4.5)
0
0
0
0

0
0
0
0
0

1 (9.1)
0
0
0
0

0
0
0
1 (8.3)
0

0
0
0
0
0

3 (6.7)0000

3 (7.0)0000

8 (4.5)00
1 (0.6)0

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Table S4. Disposition Events Summary - Safety Analysis Set (Protocol C2501004)

Number (%) of Subjects
Withdrawal By

Placebo QD Placebo QD PF-06826647 PF-06826647 PF-06826647 PF-06826647 PF-06826647 PF-06826647->->
50 mg QD
50 mg QD
100 mg QD
100 mg QD
200 mg QD
400 mg QD
PF-06826647 PF-06826647
->
->
->
->
->
->
200 mg QD
400 mg QD PF-06826647 PF-06826647 PF-06826647 PF-06826647 PF-06826647 PF-06826647(N=23)(N=22)
200 mg QD
400 mg QD
200 mg QD
400 mg QD
200 mg QD
400 mg QD(N=11)(N=11)(N=12)(N=11)(N=45)(N=43)
n (%)
n (%)
n (%)
n (%)
n (%)
n (%)
n (%)
n (%)

Total
(N=178)n (%)

2 (8.7)1 (4.5)00

1 (8.3)1 (9.1)1 (2.2)1 (2.3)7 (3.9)1 (4.3)16 (69.6)
0

3 (13.6)
14 (63.6)
00
10 (90.9)
008 (72.7)01 (8.3)9 (75.0)00
8 (72.7)
0033 (73.3)
02 (4.7)32 (74.4)
0

7 (3.9)130 (73.0)0

16 (69.6)
0

16 (72.7)
1 (4.5)10 (90.9)
08 (72.7)09 (75.0)08 (72.7)
033 (73.3)
033 (76.7)
1 (2.3)133 (74.7)
2 (1.1)

0
0
0
0
0
0

0
0
0
0
0
0

0
0
0
0
0
0

0
0
0
0
0
0

0
0
0
0
0
0

0
0
0
0
0
0

0
0
0
0
0
0

1 (2.3)00
0
00

1 (0.6)
0
0
0
0
0

0
16 (69.6)
0

1 (4.5)15 (68.2)
00
10 (90.9)
008 (72.7)00
9 (75.0)00
8 (72.7)
0033 (73.3)
00
32 (74.4)
01 (0.6)131 (73.6)
0Subject
Other
Completed
Ongoing
Disposition phase: FollowUp
Subjects Entered:
Discontinued
Reason for
discontinuation
Adverse Event
Lack of Efficacy
Lost to Follow-Up
Pregnancy
Protocol Deviation
Withdrawal By
Subject
Other
Completed
Ongoing

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Table S4. Disposition Events Summary - Safety Analysis Set (Protocol C2501004)

Number (%) of Subjects

Placebo QD Placebo QD PF-06826647 PF-06826647 PF-06826647 PF-06826647 PF-06826647 PF-06826647->->
50 mg QD
50 mg QD
100 mg QD
100 mg QD
200 mg QD
400 mg QD
PF-06826647 PF-06826647
->
->
->
->
->
->
200 mg QD
400 mg QD PF-06826647 PF-06826647 PF-06826647 PF-06826647 PF-06826647 PF-06826647(N=23)(N=22)
200 mg QD
400 mg QD
200 mg QD
400 mg QD
200 mg QD
400 mg QD(N=11)(N=11)(N=12)(N=11)(N=45)(N=43)
n (%)
n (%)
n (%)
n (%)
n (%)
n (%)
n (%)
n (%)

PFIZERSDTM Creation: 23DEC2020 (00:59) Source Data: adds Table Generation: 11JAN2021 (05:07)
Output File: ./nda1_cdisc/C2501004_CSR/adds_s001_i
Table 14.1.1.2.1 PF-06826647 is for Pfizer internal use.

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Efficacy Results:
Primary Efficacy Endpoint: All the active treatment groups had greater proportions ofparticipants achieving PASI 90 response at Week 16 compared with the placebo group(Table S5). There were statistically significant differences from the placebo QD group in the
proportion of participants achieving PASI 90 response at Week 16 for the 400 mg QD groupand the 200 mg QD group.

Table S5. Statistical Summary of Subjects Achieving PASI90 Response at Week 16 Chan and Zhang, NRI - FAS (Protocol C2501004)
N2 n (%)

90% CIa

Analysis
Visit

Treatment Group

Week 16

Placebo QD (N=45) 42 2 ( 4.8) ( 1.27, 13.53)
PF-06826647 50 mg 22
3 ( ( 5.12, 31.13)
QD (N=22)
13.6)
PF-06826647 100
21 2 ( 9.5) ( 2.56, 24.50)
mg QD (N=23)
PF-06826647 20045
17 ((25.96,mg QD (N=45)37.8)
50.95)
PF-06826647 400
41
21 ((37.44,mg QD (N=43)
51.2)
64.86)

Risk
Difference

Difference from Placebo QD
90% CIb
One-sided
Hochberg PP-value
value

8.87

(-4.50, 26.26)

0.15870.2621

4.76(-7.07, 21.48)

0.2621

0.262133.02(18.01, 47.11)

0.00010.000446.46(30.62, 60.56)<.0001<.0001

PASI90: >=90% reduction from baseline in the PASI total score; NRI: imputed missing value to non-responder.
All data for a subject after the initiation of prohibited medications was set to non-responder. No NRI was done on missing
data collected via remote visit.
a. calculated using Blyth-Still-Casella (Casella (1986)) method.
b. calculated using Chan and Zhang (1999) method.
N=number of subjects in FAS population; N2=number of subjects after non-responder imputation applied (the subjects
discontinued due to COVID-19 were removed); n (%)=number of subjects achieving PASI90 response (percentage based on
N2).
90% CI and Risk Difference were represented as percent in the report.
Baseline was defined as the last available measurement prior to randomization on Day 1, if a Day 1 measurement was notavailable, the value from the Screening visit could be used.
PFIZERSDTM Creation: 18DEC2020 (06:35) Source Data: adps Table Generation: 12JAN2021 (21:12)
Output File: ./nda1_cdisc/C2501004_CSR/adps_s401_2_i
Table 14.2.1.4.1.1 PF-06826647 is for Pfizer internal use.

Key Secondary Efficacy Endpoint: Greater proportions of participants achieving PASI 75
responses compared with the placebo QD group were observed from Week 6 to Week 16 forall active treatment groups except for the 100 mg QD group at Weeks 6, 12 and 16(Figure S2). There were significant differences from the placebo QD group in the proportionof participants achieving PASI 75 responses for the 400 mg QD group and the 200 mg QD
group from Week 4 to Week 16, with the greatest difference in the 400 mg QD group
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observed at Week 12 (90% CI: 44.52%, 74.44%; one-sided p-value < 0.0001) and in the
200 mg QD group observed at Week 12 (90% CI: 25.56%, 55.93%; one-sided
p-value < 0.0001).
Figure S2. Proportion (90% CIs) of Subjects Achieving PASI 75 Response Up to
Week 16 - Blyth-Still-Casella, NRI - FAS

Other Efficacy Endpoints:
Proportion of Participants with PGA Score Clear (0) or Almost Clear (1) (and ≥2 Points
Improvement From baseline), Up to Week 16: There were significant differences from theplacebo QD group in the proportion of participants achieving PGA responses of clear or
almost clear and ≥2 points improvement from baseline for the 200 mg QD group and the
400 mg QD group from Week 4 to Week 16, with the greatest difference in the 400 mg QD
group observed at Week 12 (90% CI: 46.94%, 76.61%; one-sided p-value<0.0001), and in
the 200 mg QD group observed at Week 6 and Week 12 (with same 90% CI: 14.32%,
47.52%; one-sided p-value=0.0006). Identical results were shown for the proportion ofparticipants with PGA score clear or almost clear up to Week 16.
Change and Percent Change From Baseline in PASI Scores, Up to Week 16: Greater LSmean percent decreases from baseline in PASI score were observed for all active treatment
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groups from Week 6 to Week 16 compared with the placebo QD group. There weresignificant differences from the placebo QD group in the LS mean percent change frombaseline in PASI score for the 400 mg QD group and 200 mg QD group from Week 1 to
Week 16, with the greatest difference in the 400 mg QD group observed at Week 16(90% CI: -65.44%, -40.63%; one-sided p-value<0.0001) and in the 200 mg QD groupobserved at Week 16 (90% CI: -53.02%, -28.46%; one-sided p-value<0.0001). Similar
results were observed for the LS mean decreases from baseline in PASI score up to Week 16.
Categorical Summary of PASI Responses: Greater proportions of participants achieving
PASI 90, PASI 50 and PASI 100 responses compared with the placebo QD group wereobserved from Week 6 to Week 16 for all active treatment groups except for the 100 mg QD
group. For PASI 50, PASI 75 and PASI 90, generally there were gradual increases in the
proportion of participants achieving these responses over time from Week 18 for all thetreatment groups, which then stabilized up to Week 40. There were general increases in the
proportion of participants achieving PASI 100 responses from Week 18 to Week 40.
Change From Baseline in L-PASI Score: Greater mean decreases from baseline in L-PASIscore were observed for all active treatment groups up to Week 16 compared with theplacebo QD group except for the 50 mg QD group (at Weeks 4, 8 and 12) and the 100 mg
QD group (at Weeks 2 and 4). A mean decrease from baseline in L-PASI score was observedin all the treatment groups from Week 18 to Week 40, and remained stable throughout the
Extension Treatment Period.
Change and Percent Change From Baseline in PASI Scores, Week 16 to Week 40: A mean
decrease from baseline in PASI score was observed in all the treatment groups from Week 18
to Week 40, and remained stable throughout the Extension Treatment Period. The mean
percent decrease from baseline increased from Week 18 to Week 24 for all the treatmentgroups, and had a tendency to converge to a similar level across the treatment groups.
Absolute and Change From Baseline in Psoriatic BSA: Greater LS mean decreases frombaseline in psoriatic BSA were observed for the 400 mg QD group and the 200 mg QD groupup to Week 16 compared with the placebo QD group. A similar trend was observed for themean change from baseline in psoriatic BSA up to Week 16. A mean decrease from baselinein psoriatic BSA was observed in all the treatment groups from Week 18 to Week 40, andremained stable throughout the Extension Treatment Period.
Categorical Summary of PGA Scores, Week 16 to Week 40: Generally, a high proportion ofparticipants achieving PGA responses of clear or almost clear was maintained for all thetreatment groups from Week 18 to Week 40. Identical results were observed for the
proportion of participants achieving PGA responses of clear or almost clear and ≥2 points
improvement from baseline.

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CLINICAL STUDY REPORT SYNOPSISPRO Summary:

There were significant differences from the placebo QD group in the LS mean change
from baseline in PP-NRS score for the 400 mg QD group from Day 12 to Day 16 andfrom Week 4 to Week 16, and for the 200 mg QD group from Day 5 to Day 16 and from
Week 4 to Week 16. A similar trend was observed for the mean change from baseline in
PP-NRS scores up to Week 16. A mean decrease from baseline in PP-NRS score wasobserved in all the treatment groups from Week 24 to Week 40, and remained stable
during the period.



Significant differences from the placebo QD group in the proportion of participants
achieving a PSI score of 0 or 1 on every item were observed for the 400 mg QD group on
Days 6, 11, 12, from Day 14 to Day 16 and from Week 4 to Week 16, and for the 200 mg
QD group on Day 6, from Day 12 to Day 15 and from Week 4 to Week 16. The highproportion of participants achieving a PSI score of 0 or 1 on every item was maintained
for all the treatment groups from Week 24 to Week 40.

There were significant differences from the placebo QD group in the LS mean change
from baseline in PSI score for the 400 mg QD group on Day 6, from Day 8 to Day 16 andfrom Week 4 to Week 16, and for the 200 mg QD group from Day 4 to Day 16 and from
Week 4 to Week 16. A similar trend was observed for the mean change from baseline in
PSI score up to Week 16.

Greater mean decreases from baseline in Night-Time Itch Scale were observed for all
active treatment groups up to Week 16 compared with the placebo QD group except forthe 100 mg QD group (up to Day 16, and at Week 4), the 50 mg QD group (on Days 2
and 5) and the 400 mg QD group (on Days 2 and 3).

There were significant differences from the placebo QD group in the LS mean change
from baseline in DLQI for the 400 mg QD group and the 200 mg QD group from Week 4
to Week 16. A similar trend was observed for the mean change from baseline in DLQI up
to Week 16.

A higher proportion of participants achieving DLQI response of ≥4 improvement frombaseline was observed for all the active treatment groups compared with the placebo QD
group from Week 4 to Week 16. Significant differences from the placebo QD group in
the proportion of participants achieving this DLQI response were observed for the
400 mg QD group and the 200 mg QD group from Week 4 to Week 16.



A numerically greater LS mean increase from baseline was observed in all the
10 domains of SF-36v2 in the 400 mg QD group and the 200 mg QD group at Week 4
and Week 16 compared with the placebo QD group, except for physical functioning at
Week 16 and mental health at Week 4 in the 200 mg QD group.

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A greater mean decrease from baseline in PtGA was observed for all the active treatmentgroups up to Week 16 compared with the placebo QD group. The greatest difference
from the placebo QD group was observed in the 400 mg QD group, followed by the
200 mg QD group.

Significant differences from the placebo QD group in the proportion of participants
achieving PtGA response of clear or almost clear were observed for the 400 mg QD
group from Week 2 to Week 16, and for the 200 mg QD group from Week 4 to Week 16.
Significant difference from the placebo QD group was also observed for the 50 mg QD
group at Week 12.

Pharmacokinetic and Pharmacodynamic Results:
Pharmacokinetic Results

The median pre-dose plasma concentration appears to achieve steady state by Week 1.
The median pre-dose concentrations across visits at steady state at 50 mg QD and 100 mg
QD were similar. The increase in mean pre-dose plasma concentrations across visits at
400 mg QD compared with the 200 mg QD did not appear to be dose-proportional. The
post-dose mean and median concentrations of PF‑06826647 at Week 8 generally
increased less than proportionally with dose, with a high degree of overlap in observed
post-dose concentrations between 50 mg QD and 100 mg QD, and between 200 mg QD
and 400 mg QD. The geometric percent coefficients of variation (%CVs) of pre-doseconcentrations across all visits up to Week 16 and all PF-06826647 treatment groups at
steady state ranged between 164% and 692%.



The median pre-dose concentrations across visits after Week 16 and up to Week 40
generally overlapped among all treatments. Similarly, there was a high degree of overlap
in observed post-dose concentrations across treatment groups. The geometric %CVs ofpre-dose concentration across all visits between Week 16 and Week 40 and all treatmentgroups ranged between 109% and 1469%.

Pharmacodynamic Results

The mean decrease from baseline in hsCRP in the 200 mg QD group was generally
numerically greater than the placebo QD group up to Week 16. The mean decrease frombaseline in hsCRP in the 100 mg QD group was generally numerically lower than theplacebo QD group up to Week 16. CIs in all active treatment groups overlapped with CIs
in the placebo QD group.



There was a greater mean decrease from baseline in natural killer (NK) cell absolutecounts in the 200 mg QD and 400 mg QD group compared with the placebo QD group up
to Week 4 and then the value was maintained up to Week 16. There were generally
greater mean increases from baseline in B cell absolute counts in all the active treatmentgroups up to Week 16 compared with the placebo QD group. The mean change fromPFIZER
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baseline in T cells and helper T cells in the 200 mg QD group was generally numericallyhigher than the placebo QD group up to Week 16, though the data showed wide
variability and CIs for all active treatment groups generally overlapped with CIs for theplacebo QD group. No obvious differences from the placebo group in the mean change
from baseline in cytotoxic T cells were observed in all the active treatment groups up to
Week 16.
Safety Results:
Adverse Event:Up to Week 16: All AEs described in this Synopsis were treatment-emergent unlessotherwise specified. The proportion of participants with AEs up to Week 16 was comparable
across all the treatment groups, but numerically higher in the active treatment groups (59.1%
to 69.6%) than that in the placebo group (51.1%). Two (1.1%) participants were reportedwith serious adverse events (SAEs). A total of 9 (5.1%) participants discontinued from thestudy due to AEs. No deaths were reported. The most frequently reported all-causality AEs
by system organ class (SOC) were Infections and Infestations (62 [34.8%] participants) andInvestigations (31 [17.4%] participants). The majority of the participants in each treatmentgroup experienced mild or moderate AEs. The most frequently reported all-causality AEs
regardless of SOC were nasopharyngitis (29 [16.3%] participants), upper respiratory tract
infection (14 [7.9%] participants) and blood pressure increased (12 [6.7%] participants).
Week 16 to Week 40: The proportion of participants with AEs from Week 16 to Week 40 wascomparable across all the treatment groups (44.4% to 77.8%). Four (2.6%) participants werereported with SAEs. A total of 9 (5.9%) participants discontinued from the study due to AEs.
No deaths were reported. The most frequently reported all-causality AEs by SOC were
Infections and Infestations (36 [23.7%] participants) and Investigations(36 [23.7%] participants). The majority of the participants in each treatment groupexperienced mild or moderate AEs. The most frequently reported all-causality AEs
regardless of SOC was blood creatine phosphokinase increased (12 [7.9%] participants).
Laboratory Values:
For participants with confirmed (through re-testing within 48 hours) laboratory abnormalities
meeting the pre-specified criteria, the study drug was permanently discontinued:


There was a confirmed case of 2 sequential hemoglobin <10.0 g/dL for 1 participant in
the 200 to 200 mg QD group, which led to the discontinuation of study drug.

There was a confirmed case of 2 sequential alanine aminotransferase (ALT) >3×upper
limit of normal (ULN) for 1 participant in the placebo QD group, which led to thediscontinuation of study drug.

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Hemoglobin: Abnormally low levels of hemoglobin (<0.8×lower limit of normal [LLN])
were reported for participants receiving either PF-06826647 400 mg QD or 200 mg QD(5 participants up to Week 16 and 2 participants from Week 16 to Week 40). A numericallygreater mean decrease from baseline in hemoglobin was observed for all active treatmentgroups compared with the placebo QD group from Week 2 to Week 16 and these decreases
were generally dose-related. The mean decrease from baseline in hemoglobin was maintained
over time for all the treatment groups from Week 16 to Week 40.
Reticulocyte: Abnormally low (<0.5×LLN) and high (>1.5×ULN) levels of reticulocytes
were reported for participants receiving PF-06826647 400 mg QD (2 participants withabnormally low levels and 2 participants with abnormally high levels up to Week 16, and2 participants with abnormally low levels and 2 participants with abnormally high levels
from Week 16 to Week 40). There appeared to be a dose-dependent decline in reticulocytes
in the active treatment groups within the first 2 weeks of treatment followed by a returntowards baseline after Week 2. The mean decrease from baseline in reticulocyte count was
similar across the treatment groups from Week 16 to Week 40 and was maintained over time
for all the treatment groups.
Platelet: Abnormally low platelet counts (<0.5×LLN) were reported for participantsreceiving PF-06826647 400 mg QD (1 participant up to Week 16 and 1 participant from
Week 16 to Week 40). A numerically greater mean increase from baseline in platelet counts
was observed for all the active treatment groups compared with the placebo QD group up to
Week 16, with the greatest difference from the placebo QD group in the 400 mg QD group or
200 mg QD group. The mean increase from baseline in platelet count was maintained overtime for all the treatment groups from Week 16 to Week 40.
Clinically significant laboratory abnormalities were reported as AEs by the investigator. The
most frequently reported laboratory abnormality AEs (treatment-related) during theInvestigational Treatment Period by Medical Dictionary for Regulatory Activities(MedDRA) SOC were: Investigations in 14 (7.9%) participants and Blood and Lymphatic
System Disorders in 6 (3.4%) participants. The most frequently reported laboratory
abnormality AEs (treatment-related) during the Extension Treatment Period by MedDRA
SOC were: Investigations in 13 (8.6%) participants and Blood and Lymphatic System
Disorders in 14 (9.2%) participants.
Other Safety Evaluations:
Clinically significant findings in vital signs data were reported as AEs by the investigator (allthe AEs were reported in participants in the active treatment groups unless otherwise
specified): the AE of hypertension was reported for 7 participants up to Week 16, and for
9 participants from Week 16 to Week 40; the AE of blood pressure increased was reported
for 12 participants up to Week 16 (1 participant was in the placebo QD group), and for
8 participants from Week 16 to Week 40; the AE of sinus tachycardia was reported for
1 participant from Week 16 to Week 40; the AE of blood pressure diastolic increased was

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CLINICAL STUDY REPORT SYNOPSIS
reported for 1 participant from Week 16 to Week 40; the AE of pyrexia was reported for
1 participant from Week 16 to Week 40.
Clinically significant findings in ECG data were reported as AEs by the investigator (all theAEs were reported in participants in the active treatment groups unless otherwise specified):
the AE of electrocardiogram PR prolongation was reported for 1 participant up to Week 16(the participant was in the placebo QD group); the AE of palpitations was reported for
1 participant up to Week 16; the AE of electrocardiogram QT prolonged was reported for
1 participant from Week 16 to Week 40; the AE of atrial fibrillation was reported for
2 participants from Week 16 to Week 40; the AE of atrioventricular block first degree for
1 participant from Week 16 to Week 40.
No clinically significant physical examination findings were reported. No suicidal behavior
or ideation, or no onset of post-baseline suicidality was reported.
Conclusions:

PF-06826647 400 mg QD and 200 mg QD were both statistically superior to placebo forthe proportion of participants achieving PASI 90 at Week 16. For both PF-06826647
400 mg QD and 200 mg QD groups, there were significant differences from placebo inthe proportion of participants achieving PASI 90 responses from Week 4 to Week 16.

PF-06826647 400 mg QD and 200 mg QD both showed significant efficacy over placebo
based on proportion of participants achieving PASI 75 and PGA response of clear or
almost clear; there was significant improvement compared with placebo based on the
proportion of participants achieving the responses from Week 4 to Week 16.

The observed efficacy responses were generally better in the PF-06826647 400 mg QD
and 200 mg QD groups compared with placebo for all secondary efficacy endpoints and
PRO results up to Week 16.

Generally, efficacy continued to improve for the PF-06826647 400 mg QD and 200 mg
QD groups compared with the placebo up to Week 16, and this efficacy was maintained
throughout the 24-week Extension Treatment Period.

For all the treatment groups including those transitioned from placebo, 50 mg QD and
100 mg QD to 200 or 400 mg QD, the efficacy continued to improve from Week 16 to
Week 40, and had a tendency to converge to a similar level across the treatment groups.

PF-06826647 was generally safe and well tolerated when administered in daily oral dosesof 50 mg, 100 mg, 200 mg and 400 mg for 16 weeks, and this continued following daily
doses of 200 mg and 400 mg for an additional 24 weeks, in participants with moderate tosevere psoriasis.

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There were no notable differences in the rate of AEs, SAEs and discontinuations due to
AEs between the active treatment groups and the placebo group up to Week 16.

The majority of AEs were mild or moderate.

For active treatment groups during the Investigational Treatment Period, there was ageneral trend of greater mean decrease from baseline in hemoglobin over time, with thegreatest decreases from baseline in the 400 mg QD group or 200 mg QD group. The
mean changes from baseline values across all treatment groups in the Extension
Treatment Period were maintained.



For active treatment groups during the Investigational Treatment Period, there appeared
to be a dose-dependent decline in reticulocytes in the active treatment groups within thefirst 2 weeks of treatment followed by a return towards baseline after Week 2. The meanchanges from baseline values across all treatment groups in the Extension Treatment
Period were maintained.



For active treatment groups during the Investigational Treatment Period, a numericallygreater mean increase from baseline in platelet count was observed for all the active
treatment groups compared with the placebo QD group up to Week 16, with the greatest
difference from the placebo QD group in the 400 mg QD group or 200 mg QD group.
The mean changes from baseline values across all treatment groups in the Extension
Treatment Period were maintained.



The median pre-dose plasma concentration appeared to achieve steady state by Week 1.
The median pre-dose concentrations across visits at steady state at 50 mg QD and 100 mg
QD were similar. The median pre-dose concentrations across visits at 200 mg QD werehigher than 400 mg QD; however, the mean pre‑dose concentrations across visits at
steady state at 400 mg QD were generally higher than those at 200 mg QD but theincrease in mean pre-dose plasma concentration did not appear to be dose-proportional.

Inter-participant variability of pre-dose concentration across all visits and all treatmentgroups, as assessed by %CV, was high for both the Investigational Treatment Period andthe Extension Treatment Period.

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