Clinical trial NCT03895372
Conditions: Psoriasis
Sponsor: Pfizer
Start date: 2019-06-27; Completion date: 2020-11-26
Enrollment: 179 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This multicenter study is being conducted to provide additional PF-06826647 safety and tolerability data, and to further explore the clinical efficacy of PF-06826647 in the treatment of moderate to severe plaque psoriasis. Additionally, the study is intended to enable selection of oral dose and dosing regimen for the future clinical development of PF-06826647.

Detailed description:

Arms: arm 1: Delivered orally for 16 weeks during the Investigational Treatment Period arm 2: Delivered orally for 16 weeks during the Investigational Treatment Period arm 3: Delivered orally for 16 weeks during the Investigational Treatment Period arm 4: Delivered orally for 16 weeks during the Investigational Treatment Period then 24 weeks in Extension Period. arm 5: Delivered orally for 16 weeks then for 24 weeks in Extension Period.
Interventions: intervention 1: PF-06826647 or Placebo intervention 2: PF-06826647
Intervention descriptions: intervention 1: Delivered orally (tablet) once daily (QD) for 16 weeks during the Investigational Treatment Period intervention 2: Delivered orally (tablet) once daily (QD) for 24 weeks during the Extension Period

Protocol documents:
Prot_000.pdf: 
PF-06826647
Protocol C2501004
Final Protocol Amendment 1, 01 October 2019
PFIZER CONFIDENTIAL
Page 1
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 
Investigational Product Number:
PF-06826647
Investigational Product Name:
Not Available (N/A)
United States (US) Investigational New 
Drug (IND) Number:
European Clinical Trials Database 
(EudraCT) Number:
2018-004669-16
Protocol Number:
C2501004
Phase:
2b
This document and accompanying materials contain confidential information belonging to Pfizer.  Except as 
otherwise agreed to in writing, by accepting or reviewing these documents, you agree to hold this information in 
confidence and not copy or disclose it to others (except where required by applicable law) or use it for 
unauthorized purposes.  In the event of any actual or suspected breach of this obligation, Pfizer must be 
promptly notified.
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Protocol Amendment Summary of Changes Table
Document
Version Date
Summary of Changes and Rationale
Amendment 1
01 October 2019
1. Amendment 1 has become necessary to 
update the contraception language and to 
align with emerging development of 
program safety requirements (protocol 
C2501003 for ulcerative colitis).  
Rationale: the purpose of the update is to 
mitigate a theoretical risk of CYP3A 
induction by PF-06826647 and thereby 
potentially lowering the efficacy of 
hormonal contraceptives.  Given the 
potential teratogenicity risk of 
PF-06826647, the addition of a barrier 
method for female participants on hormonal 
contraception is included. 
Since the expected maximum change in 
exposure based on fraction metabolized [fm] 
value is approximately 2-fold, the 
ethinylestradiol containing contraceptives 
are now allowed.  See Section 4.3, 5.3.1 & 
Appendix 10.4.2 and 10.4.4 for details.  
2. Removed body mass index (BMI) see 
Section 5.1 Inclusion Criteria #6.
Rationale: It does not impact PK or PD.
3. Added two exclusion criteria see 
Section 5.2 Exclusion Criteria: 
#13. History of recurrent (>2) venous 
thrombosis or any arterial 
thromboembolism or known blood clotting 
disorders.
#14. History of acute coronary syndrome 
(eg, myocardial infarction, unstable angina 
pectoris) and any history of cerebrovascular 
disease within 24 weeks before screening.
Rational: to clarify and provide more 


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specific language on the criteria.
4. Added language to Discontinuation of
Study Intervention involving
thromboembolic events see Section 7.1.
Rationale: to provide consistency across the 
program.
5. Added language to Safety Adjudication 
Committee Section 9.5.2.
Rational: to align with program language to 
specifically include events requiring 
adjudication are cardiovascular events 
including venous thromboembolic events 
(VTE).
6. The content of five Protocol Administrative 
Clarification Letters (PACLs) # 1-5 was 
added.

PACL 1: 1) HIV serology should also 
include Hep B tests as described in 
EC #21.  2) Appendix 2 should include 
the above.  3) PROs should be 
completed in a certain same order 
(pre and post Day 15).
Rationale: to ensure consistency throughout 
protocol.

PACL 2: typographical error of absolute 
lymph count (should be 1000 not 800).
Rationale: clarification.

PACL 3 JAPAN Only: EC #23 clarified 
subjects will have HBV DNA testing if 
there is no documentation of HBV 
vaccination.
Rationale: country requirement.

PACL 4: Concomitant medications 
guselkumab and risankizumab were 
added to the agents requiring 6-month 


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washout.
Rationale: frequently asked question by 
Investigators regarding new therapeutics.

PACL 5: 1) C-SSRS footnote to clarify 
the use of “Lifetime” version at 
baseline.  2) PRO footnote to clarify 
pre-dose to be consistent with other 
sections.  3) discrepancy clarified that 
no live vaccines allowed 8 weeks after 
last dose.  4) Justification for Dose 
section 4.3 discrepancy corrected to 
confirm 83% not 82%.
Rationale: to ensure consistency throughout 
protocol.

Additional discrepancies were 
eliminated, and typographical errors 
corrected.
Original protocol
14 December 2018
N/A
This amendment incorporates all revisions to date, including amendments made at the 
request of country health authorities and institutional review boards (IRBs)/ethics committees 
(ECs).


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TABLE OF CONTENTS
LIST OF TABLES...................................................................................................................10
1. PROTOCOL SUMMARY...................................................................................................11
1.1. Synopsis ..................................................................................................................11
1.2. Schema ....................................................................................................................16
1.3. Schedule of Activities (SoA)...................................................................................17
2. INTRODUCTION ...............................................................................................................21
2.1. Study Rationale .......................................................................................................21
2.2. Background .............................................................................................................21
2.2.1. Non-Clinical Safety Studies with PF-06826647.........................................22
2.2.2. Non-Clinical Pharmacokinetics and Metabolism.......................................22
2.2.3. Clinical Overview.......................................................................................23
2.3. Benefit/Risk Assessment.........................................................................................25
3. OBJECTIVES, ESTIMANDS, AND ENDPOINTS ...........................................................26
3.1. Study Objectives, Endpoints and Estimands -- Investigational Treatment 
Period.........................................................................................................................26
4. STUDY DESIGN.................................................................................................................31
4.1. Overall Design.........................................................................................................31
4.2. Scientific Rationale for Study Design.....................................................................32
4.3. Justification for Dose ..............................................................................................33
4.4. End of Study Definition ..........................................................................................35
5. STUDY POPULATION......................................................................................................36
5.1. Inclusion Criteria.....................................................................................................36
5.2. Exclusion Criteria....................................................................................................37
5.3. Lifestyle Considerations..........................................................................................41
5.3.1. Contraception..............................................................................................42
5.3.2. Vaccination.................................................................................................42
5.3.3. Other Lifestyle Requirements.....................................................................43
5.4. Screen Failures ........................................................................................................44
6. STUDY INTERVENTION..................................................................................................44
6.1. Study Intervention(s) Administered........................................................................44
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6.1.1. Administration............................................................................................46
6.2. Preparation/Handling/Storage/Accountability ........................................................46
6.2.1. Preparation and Dispensing........................................................................48
6.2.2. Investigational Product Accountability ......................................................48
6.2.3. Destruction of Investigational Product Supplies ........................................48
6.3. Measures to Minimize Bias: Randomization and Blinding.....................................49
6.3.1. Allocation to Investigational Product .........................................................49
6.3.2. Breaking the Blind......................................................................................49
6.4. Study Intervention Compliance...............................................................................50
6.5. Concomitant Therapy..............................................................................................50
6.5.1. Rescue Medicine.........................................................................................52
6.6. Dose Modification...................................................................................................52
6.7. Intervention after the End of the Study...................................................................53
7. DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL...........................................................................53
7.1. Discontinuation of Study Intervention ....................................................................53
7.2. Participant Discontinuation/Withdrawal from the Study........................................54
7.3. Lost to Follow-up....................................................................................................56
8. STUDY ASSESSMENTS AND PROCEDURES...............................................................56
8.1. Efficacy Assessments..............................................................................................57
8.1.1. Psoriasis Area and Severity Index (PASI)..................................................57
8.1.2. Physician Global Assessment (PGA) .........................................................60
8.1.4. Rater Qualifications....................................................................................62
8.2. Safety Assessments .................................................................................................62
8.2.1. Assessments at Screening only...................................................................63
8.2.1.1. Tuberculosis (TB) Testing ........................................................63
8.2.1.2. Chest Radiograph ......................................................................63
8.2.1.3. Medical History.........................................................................64
8.2.1.4. Suicidal Ideation and Behavior Risk Monitoring......................64
8.2.2. Assessment During Study...........................................................................64
8.2.2.1. Full Physical and Brief Physical Examinations ........................64
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8.2.2.2. Weight and Height ....................................................................64
8.2.2.3. Vital Signs (Blood pressure, pulse rate, and temperature)........65
8.2.3. Electrocardiograms.....................................................................................65
8.2.4. Clinical Safety Laboratory Assessments ....................................................66
8.2.5. Suicidal Ideation and Behavior Risk Monitoring.......................................66
8.2.5.1. Columbia Suicide Severity Rating Scale ..................................67
8.2.6. Herpetiform Rash Surveillance...................................................................67
8.2.7. Glomerular Filtration Rate..........................................................................67
8.2.8. Pregnancy Testing ......................................................................................67
8.3. Adverse Events and Serious Adverse Events..........................................................68
8.3.1. Time Period and Frequency for Collecting AE and SAE Information.......68
8.3.1.1. Reporting SAEs to Pfizer Safety...............................................68
8.3.1.2. Recording Nonserious AEs and SAEs on the CRF...................69
8.3.2. Method of Detecting AEs and SAEs ..........................................................69
8.3.3. Follow-up of AEs and SAEs.......................................................................69
8.3.4. Regulatory Reporting Requirements for SAEs...........................................69
8.3.5. Exposure During Pregnancy or Breastfeeding, and Occupational 
Exposure ..........................................................................................................70
8.3.5.1. Exposure During Pregnancy......................................................70
8.3.5.2. Exposure During Breastfeeding ................................................70
8.3.5.3. Occupational Exposure .............................................................70
8.3.6. Medication Errors .......................................................................................70
8.4. Treatment of Overdose............................................................................................71
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8.9. Health Economics ...................................................................................................75
8.10. Patient Reported Outcome Measures ....................................................................75
8.10.1. Psoriasis Symptom Inventory...................................................................76
8.10.2. Peak-Pruritus Numerical Rating Scale .....................................................76
9. STATISTICAL CONSIDERATIONS ................................................................................77
9.1. Estimands and Statistical Hypotheses.....................................................................77
9.1.1. Estimands....................................................................................................77
9.2. Sample Size Determination.....................................................................................78
9.3. Populations for Analysis .........................................................................................78
9.4. Statistical Analyses .................................................................................................78
9.4.1. Efficacy Analyses .......................................................................................79
9.4.2. Safety Analyses ..........................................................................................80
9.4.2.1. Electrocardiogram Analyses......................................................80
9.5. Interim Analyses .....................................................................................................81
9.5.1. Data Monitoring Committee.......................................................................81
9.5.2. Safety Adjudication Committees................................................................82
10. SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS..........................................................................................................83
10.1. Appendix 1: Regulatory, Ethical, and Study Oversight Considerations...............83
10.1.1. Regulatory and Ethical Considerations ....................................................83
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10.1.1.1. Reporting of Safety Issues and Serious Breaches of the 
Protocol or ICH GCP.........................................................................83
10.1.2. Financial Disclosure .................................................................................84
10.1.3. Informed Consent Process ........................................................................84
10.1.4. Data Protection .........................................................................................85
10.1.5. Dissemination of Clinical Study Data ......................................................85
10.1.6. Data Quality Assurance ............................................................................87
10.1.7. Source Documents....................................................................................88
10.1.8. Study and Site Closure..............................................................................89
10.1.9. Publication Policy.....................................................................................89
10.1.10. Sponsor’s Qualified Medical Personnel .................................................90
10.2. Appendix 2: Clinical Laboratory Tests .................................................................91
10.3. Appendix 3: Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow-up, and Reporting ......................................................................92
10.3.1. Definition of AE .......................................................................................92
10.3.2. Definition of SAE.....................................................................................93
10.3.3. Recording/Reporting and Follow-up of AEs and/or SAEs.......................94
10.3.4. Reporting of SAEs....................................................................................97
10.4. Appendix 4: Contraceptive Guidance and Collection of Pregnancy 
Information................................................................................................................99
10.4.1. Male Participant Reproductive Inclusion Criteria....................................99
10.4.2. Female Participant Reproductive Inclusion Criteria.................................99
10.4.3. Woman of Childbearing Potential (WOCBP) ..........................................99
10.4.4. Contraception Methods...........................................................................100
10.5. Appendix 5: Genetics..........................................................................................104
10.6. Appendix 6: Liver Safety: Suggested Actions and Follow-up Assessments ......105
10.7. Appendix 7: ECG Findings of Potential Clinical Concern .................................107
10.8. Appendix 8: Prohibited Concomitant Medications.............................................109
10.9. Appendix 9: Columbia Suicide Severity Rating Scale (C-SSRS) for 
Screening and Baseline Visit...................................................................................112
10.10. Appendix 10: Psoriasis Symptom Inventory (PSI) (Daily Assessment)...........116
10.11. Appendix 11: Peak Pruritus Numeric Rating Scale (PP-NRS).........................118
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10.17. Appendix 17: Physician Global Assessment.....................................................130
10.18. Appendix 18: eGFR Calculations .....................................................................131
10.19. Appendix 19: Abbreviations .............................................................................132
11. REFERENCES ................................................................................................................136
LIST OF TABLES
 
 
Table 4.
Psoriasis Area and Severity Index (PASI) Area Score Criteria................58
Table 5.
Psoriasis Area and Severity Index (PASI) Area Score Criteria................59
Table 6.
Component Scoring Criteria for the Physician's Global Assessment 
(PGA)........................................................................................................60
Table 7.
Physician's Global Assessment (PGA) Score...........................................61
Table 8.
Handprint Determination of Body Region Surface Area .........................61
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1. PROTOCOL SUMMARY 
1.1. Synopsis 
Rationale: This multicenter study is being conducted to provide additional PF-06826647 
safety and tolerability data, and to further explore the clinical efficacy of PF-06826647 in the 
treatment of moderate to severe plaque psoriasis.  Additionally, the study is intended to 
enable selection of oral dose and dosing regimen for the future clinical development of 
PF-06826647.
Objectives, Endpoints, and Estimands:
Investigational Treatment Period:
Objectives
Endpoints
Estimands
Primary: 
Primary:
Primary: 
To compare the efficacy of multiple 
dose levels of PF-06826647 versus 
placebo on the proportion of 
participants with moderate to severe 
plaque psoriasis achieving PASI 90.

Proportion of participants 
achieving PASI 90 
(90% or greater 
improvement from 
Baseline) at Week 16.
Estimand E1:
This estimand is intended to 
provide a population level estimate 
of the treatment effect of the IP 
alone on a binary responder 
endpoint; without the benefit of 
additional prohibited medications, 
regardless of participants 
compliance with the IP dosing.
Population: Participants with 
moderate to severe plaque 
psoriasis as defined by the 
inclusion and exclusion criteria 
without the benefit of additional 
prohibited medication regardless 
of compliance.
Intercurrent Events: A) Prohibited 
medication –response will be 
considered negative for 
participants after receiving 
prohibited medication.  
B) Withdrawal and all other events 
leading to missing data will be 
treated as in A.  C) Inadequate 
compliance – participants data will 
be used as recorded.
Population level summary: The 
difference in proportions between 
treated and placebo response rates.


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Secondary: 
Secondary:
Secondary: 
To compare the efficacy of multiple 
dose levels of PF-06826647 versus 
placebo on the proportion of 
participants with moderate to severe 
plaque psoriasis achieving PASI 75.
Key secondary endpoint:

Proportion of participants 
achieving PASI 75 
(75% or greater 
improvement from 
Baseline) at time points 
specified in the Schedule 
of Activities (SoA).
The binary secondary endpoints, 
when appropriate, will be analyzed 
descriptively and using estimand 
E1.
To compare the efficacy of multiple 
dose levels of PF-06826647 versus 
placebo on PGA score in participants 
with moderate to severe plaque 
psoriasis.

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.
To compare the efficacy of multiple 
dose levels of PF-06826647 versus 
placebo on the proportion of 
participants with moderate to severe 
plaque psoriasis achieving PASI 50 and 
PASI 100.

Proportion of participants 
achieving PASI 50 
(50% or greater 
improvement from 
Baseline), PASI 100 
(100% from Baseline) at 
time points specified in 
the SoA.
To compare the efficacy of multiple 
dose levels of PF-06826647 versus 
placebo on PGA and PASI scores in 
participants with moderate to severe 
plaque psoriasis.

Change from baseline and 
percent change from 
baseline in PASI scores at 
time points specified in 
the SoA.
Estimand E2: 
This estimand is intended to 
provide a population level estimate 
of the treatment effect of the IP 
alone on a continuous endpoint; 
without the benefit of additional 
prohibited medications, regardless 
of participants compliance with 
the IP dosing.
Population: Participants with 
moderate to severe plaque 
psoriasis as defined by the 
inclusion and exclusion criteria
without the benefit of additional 
prohibited medications regardless 
of compliance.
Intercurrent Events: A) Prohibited 
medication – all scores after 
participants receive prohibited 
To compare the effect of multiple dose 
levels of PF-06822647 versus placebo 
in Peak-Pruritus Numerical Rating 
Scale score in participants with 
moderate to severe plaque psoriasis.

Absolute score and 
change from baseline in 
Peak-Pruritus Numerical 
Rating Scale score at time 
points specified in the 
SoA.


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medication will be omitted 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 will be 
treated similarly as in A.
C) Inadequate compliance –
participants data will be used as 
recorded.
Population level summary: 
The mean difference between 
treated and placebo arms of the 
change from baseline PASI score.
All continuous endpoint, when 
appropriate will be analyzed 
descriptively and using estimand E2 
described above when appropriate.
To assess the safety and tolerability of 
PF-06826647 in participants with 
moderate to severe plaque psoriasis.

Incidence and severity of 
adverse events, serious 
adverse events and 
withdrawals due to 
adverse events. 

Change from baseline in 
clinical laboratory values 
(chemistry and 
hematology, 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).
There is no defined estimand for 
these endpoints and they will be 
analyzed using Pfizer data standards 
as applicable.
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.

Absolute score and 
change from baseline 
Psoriasis Symptom 
Inventory at time points 
specified in the SoA.
These endpoints will be analyzed 
descriptively and using estimand E2 
described above when appropriate.


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Extension Treatment Period:
Objectives
Endpoints
Estimands
Primary: 
Primary:
Primary: 
To assess the safety and tolerability of 
PF-06826647 in participants with 
moderate to severe plaque psoriasis.

Incidence and severity of 
adverse events, serious 
adverse events and 
withdrawals due to 
adverse events. 

Change from baseline in 
clinical laboratory values 
(chemistry, hematology 
& 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).
Not Applicable-will be analyzed 
descriptively and according to the 
Pfizer standard.
Overall Design:
This is a Phase 2b, randomized, double blind, placebo controlled, and multicenter study in 
participants with moderate to severe plaque psoriasis.  Following a Screening period of up to 
6 weeks, is a 16 week placebo controlled Investigational Treatment Period with double blind 
oral daily treatment using the following doses: 50 mg, 100 mg, 200 mg, 400 mg.  All 
participants completing the 16 week Investigational Period may continue on to a 24 week 
non-placebo controlled Extension Treatment Period with double blind oral daily treatment, if 
per the Investigator judgment the participant is compliant with study procedures and 
continued participation presents no safety risks.  The participants continuing into the 
Extension Treatment Period that were originally randomized to the 200 mg and 400 mg 
treatment groups will continue on their respective doses, while those randomized to one of 
the other treatment groups (including placebo) will be randomly assigned (at study baseline) 
to receive either 200 mg or 400 mg during the Extension Treatment Period.  The total 
duration of study participation will be approximately 50 weeks, including up to 6 weeks 
Screening, 16 week Investigational Treatment Period, 24 week Extension Treatment Period 
and a Follow-Up visit 4 weeks after the Extension Period ends.


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Number of Participants:
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) 
will be randomly assigned to a treatment group in order to ensure a minimum of 
128 evaluable participants completing Week 16 (assuming a 20% dropout rate).
Intervention Groups and Duration:
During the Investigational Treatment Period (Weeks 0 through 16), the 160 participants will 
receive PF-06826647 (50 mg, 100 mg, 200 mg, 400 mg) once daily, or matching placebo and 
the same participants will continue onto the Extension Treatment Period. 
After completion of the 16 week placebo controlled Investigational Study Period, participants 
may transition directly into the 24 week Extension Study Period.
The total duration of study participation will be approximately 50 weeks, including up to 
6 weeks Screening, 16 week Investigational Treatment Period, the 24 week Extension 
Treatment Period and a Follow-Up visit 4 weeks after the Extension Period ends.
Data Monitoring Committee: 
This study will use an internal review committee (IRC) (Section 9.5.1).
Statistical Methods:
The primary estimand will be the population average treatment effect on PASI 90 rates at 
Week 16 relative to placebo without regard to compliance in the absence of prohibited 
medication. 
The analysis of the primary estimand will be of the proportion of participants achieving: 
PASI 75 (75% or greater improvement from Baseline); PGA score clear (0) or almost 
clear (1) and ≥2 points improvement from baseline; PGA score clear (0) or almost clear (1);
PASI 50 (50% or greater improvement from Baseline) and PASI 100 (100% or greater 
improvement from Baseline).  The analysis of the secondary estimand will be of the change 
from baseline and percent change from baseline in PASI scores; and absolute score and 
change from baseline in Peak-Pruritus Numerical Rating Scale score.
All other key secondary continuous clinical endpoints will be analyzed using the secondary 
estimand, while all other key secondary categorical clinical endpoints will be analyzed using 
the primary estimand.


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1.3. Schedule of Activities (SoA)
The SoA table provides an overview of the protocol visits and procedures.  Refer to the STUDY ASSESSMENTS AND 
PROCEDURES section of the protocol for detailed information on each procedure and assessment required for compliance with the 
protocol. 
The investigator may schedule visits (unplanned visits) in addition to those listed in the SoA table, in order to conduct evaluations or 
assessments required to protect the well-being of the participant
Study Procedure
Screening
Baseline
Investigational Treatment Period
Extension Treatment Period
Follow-
Upb
Early 
Terminationc
Visit Identifier (Week)
-6 to -1
0
1
2
4
6
8
12
16
18/20/24/28/32/36
40
20 or 44
Study Daya
-42 to -1
1
8
15
29
43
57
85
113
127/141/169/197/225/253
281
141 or 309
Visit Window (Days)
N/A
±1
±1
±2
±2
±2
±2
±2
±3
±3
±3
Enrollment Procedures
Informed consent
X
Medical history &
demography
X
Eligibility assessment
X
X
Medication History
X
Randomization
X
Clinical Assessments
Full Physical Exam
X
X
X
X
X
Brief Physical Exam
X
X
X
X
X
X
X
X
Vital signsd
X
X
X
X
X
X
X
X
X
X
X
X
X
ECGd
X
X
X
X
X
X
Height/Weighte
X
X
X
X
Chest radiographf
X
C-SSRSg
X
X
X
X
Laboratory Assessments
Hematology/Blood 
chemistry
X
X
X
X
X
X
X
X
X
X
X
X
X
Lipid panelh (fasting) 
X
X
X
X
Urinalysisi
X
X
X
X
X
FSHj
X
Serum -HCGk
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Study Procedure
Screening
Baseline
Investigational Treatment Period
Extension Treatment Period
Follow-
Upb
Early 
Terminationc
Visit Identifier (Week)
-6 to -1
0
1
2
4
6
8
12
16
18/20/24/28/32/36
40
20 or 44
Study Daya
-42 to -1
1
8
15
29
43
57
85
113
127/141/169/197/225/253
281
141 or 309
Visit Window (Days)
N/A
±1
±1
±2
±2
±2
±2
±2
±3
±3
±3
Urine β-HCGl (done at site)
X
X
X
X
X
X
X
X
X
X
X
X
HIV serology/HBsAg, 
HBcAb, (HepB reflex 
testing), and HCVAbm
X
Tuberculosis testn
X
 
 
Study treatment
IP dispensingq
X
X
X
X
X
X
X
X
X
IP accountability
X
X
X
X
X
X
X
X
X
X
Dosing diaryr
X
X
X
X
X
X
X
X
X
X
Clinical Assessments of 
psoriasis
PASI, 
PGA
X
X
X
X
X
X
X
X
X
X
X
X
X
PROss
Psoriasis Symptom 
Inventory
X
X
X
X
X
X
X
Xt
X
X
X
PP-NRS
X
X
X
X
X
X
X
Xt
X
X
X
 
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Study Procedure
Screening
Baseline
Investigational Treatment Period
Extension Treatment Period
Follow-
Upb
Early 
Terminationc
Visit Identifier (Week)
-6 to -1
0
1
2
4
6
8
12
16
18/20/24/28/32/36
40
20 or 44
Study Daya
-42 to -1
1
8
15
29
43
57
85
113
127/141/169/197/225/253
281
141 or 309
Visit Window (Days)
N/A
±1
±1
±2
±2
±2
±2
±2
±3
±3
±3
 
Monitoring 
Contraception Checkv
X
X
X
X
X
X
X
X
X
X
X
X
Concomitant Treatment(s)
X
X
X
X
X
X
X
X
X
X
X
X
AE monitoring
X
X
X
X
X
X
X
X
X
X
X
X
X
Abbreviations: AE= adverse event; 
 C-SSRS= Columbia Suicide Severity Rating Scale; 
 
ECG = electrocardiogram;
FSH= follicle stimulating hormone; HBsAg= hepatitis B surface 
antigen; HBcAb= hepatitis B core antibody; HCVAb= hepatitis C virus antibody; β-HCG= human chorionic gonadotropin; HIV= human immunodeficiency virus; IP = 
Investigational Product; PASI = Psoriasis Area and Severity Index; PP-NRS= Peak-Pruritus Numerical Rating Scale PE= physical exam; PGA= Physician’s Global Assessment; 
PRO = patient reported outcome; WOCBP= women of child-bearing potential.
a.
Days relative to Day 1.
b.
Perform Follow-Up visit to the Investigational Treatment Period at Week 20 only if the participant does not continue into the Extension Treatment Period.  
Otherwise Follow-Up is completed at Week 44.
c.
Participants who prematurely withdraw during Investigational Treatment Period or during the Extension Treatment Period should return for an Early 
Termination (ET) visit occurring 1 week after their last dose whenever possible and continue visits per Investigator’s discretion until the event has returned 
to normal or baseline levels or is deemed clinically stable.
d.
12-lead locally read singlicate ECG should be performed after the participant has rested quietly for at least 10 minutes and before laboratory blood 
collection.  Vital signs consist of blood pressure, pulse rate, and temperature and should be performed before laboratory blood collection and after 5 minutes 
rest while preferably sitting (supine is allowed).  Participants should not smoke or ingest caffeine 30 minutes prior to blood pressure and pulse rate 
measurements.
e.
Height only measured at Screening; height and weight will be measured without shoes.
f.
Chest X-ray or other appropriate chest diagnostic imaging (ie, CT or MRI) may be performed within 12 weeks prior to Day 1. 
g.
Use C-SSRS “Lifetime” version at Screening and Baseline and “Since Last Visit” version at visits indicated in SoA.  Participants who have recent or active 
suicidal ideation or behaviors will be excluded from study entry or after Day 1, would be discontinued from treatment and referred to a mental health 
professional for appropriate evaluation and treatment.
h.
Participants must be fasting (water only) for at least 8 hours prior to visits, when lipid panel is being assessed. 
i.
Dipstick in all cases; microscopy analysis is indicated if urinalysis is positive for blood, nitrite, leukocyte esterase and/or protein.  Urine culture is performed 
if urinalysis is positive for nitrite and/or leukocyte esterase or if clinically indicated.
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j.
To be done in females (<60 years of age) who are amenorrheic for at least 12 consecutive months. 
k.
Required for WOCBP at Screening
l.
Required for WOCBP prior to dosing at baseline and at all subsequent visits.  To be conducted at the site.  Pregnancy tests (serum or urine) may also be 
repeated more frequently as per request of IRBs/ECs or if required by local regulations. 
m. HepB reflex testing only if HBsAg negative but HBcAb positive at Screening. If result of HCVAb is positive, or if Hepatitis C Virus (HCV) antibody result 
is indeterminate, then a HCV RNA AMPLIPREP TAQMAN 2.0 will automatically be performed.  In Japan see Section 5.1 for HBV and HCV details.
n.
If not performed within 12 weeks prior to Screening (see Assessments Section 8.2.1.1 for details). 
o.
PK samples will be collected per SoA prior to dosing, and at 0.5 hour (±5 min); at 1 and 2 hours (±10 min) and 4 hours (±20 min) post dose hours.
q.
Participants should take blinded study medication daily during the Investigational Treatment Period and Extension Period; however, on study visit days, 
participants are instructed to refrain from dosing at home, and are to take the dose in the clinic. 
r.
Participants will be reminded to complete the dosing diary daily throughout the study.
s.
All procedures should be performed before dosing of IP.  Effort should be made to complete all PRO questionnaires before any other assessments except at 
Baseline when eligibility needs to be confirmed.
t.
Psoriasis Symptom Inventory, Peak-Pruritus Numerical Rating Scale
 scales to be completed daily for the first two weeks pre -dose as
per SoA and at visits Weeks 4, 8, 12, 16, 24, 36 and Follow-up. 
v.
To confirm that contraception, if assigned, is used consistently and correctly.
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2. INTRODUCTION
PF-06826647 is a potent tyrosine kinase 2 (TYK2) inhibitor with a favorable selectivity 
profile over other human kinases and is being investigated in participants with plaque 
psoriasis.  Based on its cytokine inhibition profile, PF-06826647 is expected to target the
T-helper 1 (Th1), T-helper 17 (Th17), and Types I interferon signaling pathways directly by 
inhibiting TYK2. This should provide therapeutic benefit in the treatment of inflammatory 
conditions driven by Th1/Th17 and interferon immune responses.
2.1. Study Rationale
The purpose of this multicenter, placebo controlled double blind study is to provide 
additional efficacy, safety, tolerability 
 data regarding PF-06826647 in 
the oral treatment of moderate to severe plaque psoriasis.  It is intended to enable dose 
selection for the future development of PF-06826647.
2.2. Background 
The most common variant of psoriasis or plaque psoriasis, is a chronic inflammatory 
autoimmune skin disease characterized by red, scaly, raised plaques.  Chronic plaque 
psoriasis is a common skin disorder with a worldwide prevalence of 2% and afflicts an 
estimated 7.4 million Americans.  Although psoriasis primarily affects the skin and is not a 
life threatening disease, it can profoundly impact the patient’s quality of life (QoL) resulting
in impairment akin to other major diseases, such as diabetes, cardiovascular disease, and 
psoriatic arthritis.1
The Janus kinase (JAK) family, which includes JAK1, JAK2, JAK3 and TYK2, is a group of 
cytoplasmic tyrosine kinases that mediate signal transduction via interactions with Type 1 
and Type 2 cytokine receptors critical for immune cell function, survival, activation, and 
proliferation.2 TYK2 pairs with JAK1 to mediate type I interferon (IFN) signaling and with 
JAK2 to transmit interleukin (IL) IL-12 and IL-23 signaling.  Both of these key cytokines are 
implicated in the pathophysiology of plaque psoriasis.  IL-12 and IL-23 require TYK2 for 
signal transduction,3 indicating that inhibition of TYK2 mediated signaling could be 
efficacious in the treatment of these inflammatory conditions.
Over activation of Th17 and the main effector cytokines of Th17 cells has been linked to 
various inflammatory diseases, including psoriasis.4  Th17 cells are elevated in psoriatic 
lesions, along with levels of proinflammatory cytokines, including IL-17A, IL-17F, IL-17C, 
which are expressed by Th17 cells and are likely mediators of inflammation and tissue 
damage.5  Human genetic studies implicate the Th17 pathway in psoriasis, and have 
uncovered likely risk alleles which include genes involved in IL-23 signaling and genes that 
function downstream of the IL-17 receptor.6  In addition to genetic evidence, several 
effective psoriasis therapies target Th17 cytokine production, suggesting a central role of 
Th17 and IL-17 in the disease.  The newest and most effective therapeutics are directed to the 
cytokines and cytokine signaling of interleukin-23/type 17 T cell (IL-23/T17) axis.7  
Additionally, the TYK2-selective inhibitor, BMS-986165, recently showed efficacy in a 
Phase 2 psoriasis study.8  Thus, there is strong rationale for targeting the Th17 pathway in the 
treatment of psoriasis.
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2.2.1. Non-Clinical Safety Studies with PF-06826647
No adverse findings were observed in oral repeat dose toxicity studies with PF-06826647 in
rats and monkeys up to 6 and 9 months in duration, respectively.  Test article related, 
nonadverse, target organs identified include the immune and hemolymphatic systems 
(thymus, spleen, lymph nodes, bone marrow, erythron, and leukon), liver (increased 
transaminases), and bone (increased trabecular thickness).  The findings in the immune and 
hemolymphatic systems are consistent with the pharmacological activity of PF-06826647.  In 
the 6-month toxicity study in rats, the no-observed-adverse-effect level (NOAEL) was 
500 mg/kg/day (250 mg/kg BID) with unbound and total maximum concentration Cmax
values of 1680 and 9360 ng/mL, respectively, and unbound and total AUC24 (area under the 
curve 24 hours) values of 16,600 and 92,000 ng•h/mL, respectively.  In the 9-month toxicity 
study in monkeys, the NOAEL was 220 mg/kg/day with unbound and total Cmax values of 
663 and 1950 ng/mL, respectively, and unbound and total AUC24 values of 8130 and 
23,900 ng•h/mL, respectively.  In an embryo fetal development study in rabbits, adverse 
PF-06826647-related embryolethality due to higher incidence of late resorptions resulting in 
higher postimplantation loss and lower number of live fetuses was observed at 
500 mg/kg/day (unbound Cmax of 1290 ng/mL and AUC24 of 17,300 ng•h/mL).  The 
developmental NOAEL in rats was 500 mg/kg/day (unbound Cmax of 1850 ng/mL and AUC24
of 19,600 ng•h/mL), and in rabbits was 150 mg/kg/day (unbound Cmax of 864 ng/mL and 
AUC24 of 9930 ng•h/mL).  PF-06826647 was not mutagenic in bacterial reverse mutation 
assays.  Although PF-06826647 was positive for micronuclei formation in vitro (through an 
aneugenic mechanism), it did not induce micronuclei in vivo in rats at 500 mg/kg/day 
(250 mg/kg BID) (unbound Cmax of 2110 ng/mL and AUC24 of 24,100 ng•h/mL), the highest 
dose tested in the 1-month study.  No evidence of PF-06826647 related phototoxicity in the 
skin or eyes of pigmented rats in a 3-day phototoxicity study was observed up to the highest 
dose tested of 500 mg/kg/day, demonstrating that PF-06826647 was not a phototoxicant, 
in vivo.
Further details of the nonclinical safety program are provided in the current investigator’s 
brochure.
2.2.2. Non-Clinical Pharmacokinetics and Metabolism
Single dose pharmacokinetic studies with PF-06826647 were conducted after oral and
intravenous (IV) administration to mice and rats.  PF-06826647 had moderate oral 
bioavailability (26% to 51%) utilizing a sprayed-dried dispersion (SDD) formulation versus 
0.5% methyl cellulose (<1% to 12%).  After IV administration, PF-06826647 demonstrated a 
steady state volume of distribution (Vss) of approximately 0.9 to 1.4 L/kg and a low plasma 
clearance (CL [10 to 18 mL/min/kg]), relative to mouse and rat liver blood flows.  Systemic 
exposures (maximum observed concentrations [Cmax] and area under the concentration time 
curve [AUC]) of PF-06826647 after repeat oral dosing in the pivotal toxicity studies 
increased with increasing dose in rats (up to 500 mg/kg/day) and monkeys (up to 
300 mg/kg/day) in a less than dose-proportional manner.  No sex-related differences in 
exposure and no accumulation of PF-06826647 were observed over the dosing period in 
either species.  In vitro, PF-06826647 showed high apparent passive permeability and may be 
a substrate for P-glycoprotein (P-gp).  PF-06826647 binding to plasma proteins ranged 


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between 62% to 82%, and PF-06826647 does not preferentially partition into red blood cells 
from nonclinical species and humans.
Renal and biliary excretion of PF-06826647 was limited in the rat.  No unique human 
metabolites were observed in vitro compared to metabolite profiles in rat and monkey.  The 
major human clearance pathway for PF-06826647 is expected to be hepatic cytochrome P450 
(CYP)-mediated metabolism by CYP1A2 (fraction metabolized [fm] = 0.53), CYP2D6 (fm = 
0.26) and CYP3A (fm = 0.21). PF-06826647 did not inhibit the major cytochrome CYP450 
or UDP- glucuronosyltransferase enzymes (UGT) (half maximal inhibitory concentration 
IC50 >25 μM).  PF-06826647 induced CYP3A4 messenger Ribonucleic acid (mRNA) 
expression in 1 of 3 lots of hepatocytes (≥4.7-fold increase at ≥10 μM), but no corresponding 
induction was seen in CYP3A4 enzymatic activity.  Induction of CYP1A2 enzyme activity
occurred in 2 lots of hepatocytes (approximately 2-fold at ≥10 μM), and PF-06826647 did 
not induce CYP2B6 mRNA levels or enzymatic activity.  Based on its in vitro profile, the 
potential for PF-06826647 mediated CYP450 or UGT drug interactions is low at clinically 
relevant concentrations (Cmax 355 nM; Cmax,u 135 nM).
PF-06826647 showed little to no inhibition of the multidrug and toxin extrusion protein 
(MATE1), multidrug resistant protein 1 (MDR1), multidrug resistance-associated protein 
(MRP2), MRP3, sodium/taurocholate co-transporting polypeptide (NTCP), organic anion 
transporting polypeptide (OATP) 1B1, OATP1B3 and organic cation transporter (OCT) 2.  
However, PF-06826647 did inhibit MATE2K with an estimated IC50 value of 0.53 μM. 
2.2.3. Clinical Overview
The clinical development program for PF-06826647 is currently comprised of a
placebo-controlled Phase 1 study (C2501001).  In this study, six Single Ascending Dose 
(SAD) cohorts and five Multiple Ascending Dose (MAD) cohorts in healthy participants 
completed, with 69 healthy adult participants randomized and treated with PF-06826647 or 
placebo. The study also included one cohort of 6 healthy Japanese participants who received
400 mg once daily (QD) and 2 cohorts of participants (total 40) with moderate to severe 
plaque psoriasis (First-in-Patient) who received 400 mg or 100 mg QD of PF-06826647 or 
placebo.  Psoriasis participants received active treatment with PF-06826647 (100 mg or 
400 mg QD for 28 days) had clinically meaningful decreases in disease activity as measured 
by Psoriasis Area and Severity Index (PASI), the defined primary endpoint.
Safety, efficacy,
 results from this study support further development 
of PF-06826647 in plaque psoriasis.  The Phase 1 study (C2501001) demonstrated an 
acceptable safety and pharmacokinetic profile at single doses of PF-06826647 ranging from 
3 mg to 1600 mg in the SAD portion and ten-day dosing from 10 mg to 1200 mg daily in the 
MAD portion of the study.  Dose escalation stopping rules were not triggered.  There were no 
clinically meaningful findings in vital signs, electrocardiograms (ECG), or potential Hy’s 
Law cases reported during this study.  In addition, there were no serious adverse events 
(including death) or Suspected, Unexpected, Serious Adverse Reactions (SUSARs) reported.  
Based on preliminary review of treatment group data, all reported treatment emergent 
adverse events have been of mild intensity.
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Additionally, clinical benefit was observed in participant cohorts with plaque psoriasis as 
measured by the change from baseline in PASI scores over a 28-day treatment period. In the 
participants completing 28 days of treatment with PF-06826647, the mean placebo-adjusted 
change from baseline PASI score at Week 4 was -14.02 (n=20) for the 400 mg QD cohort 
and -4.55 (n=15) for the 100 mg QD cohort. 
Please refer to Benefit/Risk Assessment Section 2.3 for more details on the clinical safety of
PF-06826647.
 
 
 
 
 
 
 
 
 
 
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2.3. Benefit/Risk Assessment
PF-06826647 is expected to offer therapeutic benefit in the treatment of psoriasis.  More 
specifically, inhibition of IL-12 and IL-23 signaling mediated by TYK2 inhibitory activity 
may provide a new and improved therapeutic benefit due to potential achievement of disease 
control, improvement of signs and symptoms, as well as improvements in quality of life.
Overall, the safety profile observed during the Phase 1 program for PF-06826647 appears to 
be acceptable at dosages up to 1200 mg daily administered orally over 10 days.  A longer 
dosing duration was explored in participants with moderate to severe psoriasis, who received 
the maximum PF-06826647 dose level of 400 mg and 100 mg daily for 28 days.  No serious 
or severe AEs were reported in the Phase 1 study. There was one psoriasis participant in the 
400 mg cohort who met the protocol pre-specified stopping criteria due to decreased level of 
lymphocytes, although this participant had borderline low lymphocytes at baseline.  As with 
other immunomodulators, the risk of infection is a potential concern due to the 
immunosuppressive effects of PF-06826647. 
In conclusion, the sponsor considers that the available information from the nonclinical and 
clinical data to date regarding PF-06826647 provide a favorable benefit-risk profile and 
supports its continued investigation as a potential treatment for plaque psoriasis. 
More detailed information about the known and expected benefits and risks and reasonably 
expected adverse events (AEs) of PF-06826647 may be found in the investigator’s brochure, 
which is the single reference safety document (SRSD) for this study. 
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3. OBJECTIVES, ESTIMANDS, AND ENDPOINTS
3.1. Study Objectives, Endpoints and Estimands -- Investigational Treatment Period
Objectives
Endpoints
Estimands
Primary: 
Primary:
Primary: 
To compare the efficacy of multiple 
dose levels of PF-06826647 versus 
placebo on the proportion of 
participants with moderate to severe 
plaque psoriasis achieving PASI 90.

Proportion of 
participants achieving 
PASI 90 (90% or 
greater improvement 
from Baseline) at 
Week 16.
Estimand E1:
This estimand is intended to 
provide a population level estimate 
of the treatment effect of the IP 
alone on a binary responder 
endpoint; without the benefit of 
additional prohibited medications, 
regardless of participant’s 
compliance with the IP dosing.
Population: Participants with 
moderate to severe plaque 
psoriasis as defined by the 
inclusion and exclusion criteria 
without the benefit of additional 
prohibited medication regardless 
of compliance.
Intercurrent Events: A) Prohibited 
medication –response will be 
considered negative for 
participants after receiving 
prohibited medication.  B) 
Withdrawal and all other events 
leading to missing data will be 
treated as in A).  C) Inadequate 
compliance – participants data will 
be used as recorded.
Population level summary: The 
difference in proportions between 
treated and placebo response rates.
Secondary: 
Secondary:
Secondary: 
To compare the efficacy of multiple 
dose levels of PF-06826647 versus 
placebo on the proportion of 
participants with moderate to severe 
plaque psoriasis achieving PASI 75.
Key secondary endpoint:

Proportion of 
participants achieving 
PASI 75 (75% or 
greater improvement 
from Baseline) at time 
points specified in the 
Schedule of Activities 
(SoA).
The binary secondary endpoints, 
when appropriate, will be analyzed 
descriptively and using estimand 
E1.
To compare the efficacy of multiple 
dose levels of PF-06826647 versus 
placebo on PGA score in participants 

Proportion of 
participants with PGA 
score clear (0) or 


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with moderate to severe plaque 
psoriasis.
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.
To compare the efficacy of multiple 
dose levels of PF-06826647 versus 
placebo on the proportion of 
participants with moderate to severe 
plaque psoriasis achieving PASI 50 and 
PASI 100.

Proportion of 
participants achieving 
PASI 50 (50% or 
greater improvement 
from Baseline), 
PASI 100 (100% from 
Baseline) at time 
points specified in the 
SoA.
To compare the efficacy of multiple 
dose levels of PF-06826647 versus 
placebo on PGA and PASI scores in 
participants with moderate to severe 
plaque psoriasis.

Change from baseline 
and percent change 
from baseline in PASI 
scores at time points 
specified in the SoA.
Estimand E2: 
This estimand is intended to 
provide a population level estimate 
of the treatment effect of the IP 
alone on a continuous endpoint; 
without the benefit of additional 
prohibited medications, regardless 
of participant’s compliance with 
the IP dosing.
Population: Participants with 
moderate to severe plaque 
psoriasis as defined by the 
inclusion and exclusion without 
the benefit of additional prohibited 
medications regardless of 
compliance.
Intercurrent Events: A) Prohibited 
medication – all scores after 
participants receive prohibited 
medication will be omitted 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 will be 
treated similarly as in A).  
C) Inadequate compliance –
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To compare the effect of multiple dose 
levels of PF-06822647 versus placebo 
in Peak-Pruritus Numerical Rating 
Scale score in participants with 
moderate to severe plaque psoriasis.
•
Absolute score and 
change from baseline 
in Peak-Pruritus 
Numerical Rating 
Scale score at time 
points specified in the 
SoA.
To assess the safety and tolerability of 
PF-06826647 in participants with 
moderate to severe plaque psoriasis.
•
Incidence and severity 
of adverse events, 
serious adverse events 
and withdrawals due to 
adverse events. 
•
Change from baseline 
in clinical laboratory 
values (chemistry, 
hematology & 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).
There is no defined estimand for 
these endpoints and they will be 
analyzed using Pfizer data standards 
as applicable.
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.
•
Absolute score and 
change from baseline 
Psoriasis Symptom 
Inventory at time 
points specified in the 
SoA.
This endpoint will be analyzed 
descriptively and using estimand E2 
described above when appropriate.
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Study Objectives, Endpoints and Estimands -- Extension Treatment Period
Objectives
Endpoints
Estimands
Primary: 
Primary:
Primary: 
To assess the safety and tolerability 
of PF-06826647 in participants with 
moderate to severe plaque psoriasis.
•
Incidence and severity of 
adverse events, serious 
adverse events and 
withdrawals due to 
adverse events. 
•
Change from baseline in 
clinical laboratory values 
(chemistry, hematology 
& 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).
Not Applicable, will be analyzed 
descriptively and according to the 
Pfizer standard.
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4. STUDY DESIGN
4.1. Overall Design
This is a Phase 2b, randomized, double blind, placebo controlled, parallel group, multicenter 
study in participants with moderate to severe plaque psoriasis.  After a screening period 
of - up to 6 weeks, eligible participants will be randomized in a 2:1:1:2:2 ratio such that 
participants will receive placebo or either one of four PF-06826647 daily dose levels (50 mg, 
100 mg, 200 mg or 400 mg) every day during the Investigational Treatment Period for 
16 weeks in a blinded fashion.  All participants completing the 16-week Investigational 
Period will continue to a 24-week non-placebo-controlled Extension Treatment Period with 
double blind oral daily treatment, if per the Investigator judgment the participant is compliant 
with study procedures and continued participation presents no safety risks.  The participants 
continuing into the Extension Treatment Period that were originally randomized to the 
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200 mg and 400 mg treatment groups will continue their respective doses, while those 
randomized to one of the other treatment groups (including placebo) will be randomly 
assigned (at study baseline) to receive either 200 mg or 400 mg during the Extension 
Treatment Period.  Participants who discontinue prior to Week 16 visit will have an Early 
Termination visit and will not be eligible for the Extension Period.
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) 
will be randomly assigned to a treatment group in order to ensure a minimum of 
128 evaluable participants completing Week 16 (assuming a 20% dropout rate).
The total duration of study participation will be approximately 50 weeks, including up to 
6 weeks Screening Period, 16-week Investigational Treatment Period, the 24-week Extension 
Treatment Period and a Follow-Up visit 4 weeks after the Extension Treatment Period.
If a participant is withdrawn from investigational product (IP) treatment, the participant will 
proceed with the Early Termination (ET) and Follow Up visits per Schedule of Activities. 
4.2. Scientific Rationale for Study Design
This study is being conducted to provide data on efficacy, safety, tolerability,
 
 of PF-06826647 in the oral treatment of moderate to severe plaque 
psoriasis.  The chronic toxicology package supports the planned study duration.
The treatment duration of 16 weeks in this Phase 2 study (C2501004) will allow for further 
exploration of the clinical safety and efficacy that was observed in the 4-week Phase 1
(C2501001) study in a small (n=40) number of psoriasis participants.  The PASI 90 score at 
Week 16 will be assessed as the study’s primary endpoint.  The 50 mg once daily (QD) 
PF-06826647 dose will be explored in order to identify the minimal clinically efficacious 
dose after 16 weeks of treatment.  In order to further characterize the dose-response 
relationship, this study will explore 100 mg, 200 mg and 400 mg for 16 weeks during the 
Investigational Treatment Period of the study.  Based on the exposure-response modeling 
with the PASI data observed up to Week 4, the projected PASI 90 response rates at 200 mg 
and 400 mg are 47% and 83% at Week 16 respectively, while 50 mg and 100 mg are 
expected to provide <15% PASI 90 response rate.  For this reason, the 50 mg and 100 mg 
treatment groups will have a smaller allocation of participants as compared to the other 
treatment groups.  Furthermore, participants randomized to placebo, 50 mg, and 100 mg 
doses during the Investigational Treatment Period will receive either 200 mg or 400 mg
during the Extension Study Period in order to evaluate additional safety, tolerability, and 
durability of response to PF-06826647 at expected clinically efficacious doses.
Since PF-06826647 is metabolized primarily by CYP1A2, CYP3A4 and CYP2D6, the strong 
and moderate inducers and inhibitors of these drug metabolizing enzymes are prohibited.  
Dofetilide being a MATE substrate is also prohibited because PF-06826647 is a MATE2K 
substrate and can potentially increase exposure. 
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The requirement for female participants using hormonal contraceptives to use an additional 
barrier method may be removed if supported by the outcome of an ongoing oral 
contraceptive PK interaction study (Study C2501005).
  
Patient reported outcomes will evaluate changes in psoriasis symptoms and health-related 
quality of life.  These utility scores will be further utilized for development of an early 
cost-effectiveness model. 
The potential risk of exposure to PF-06826647 in a sexual partner of a male participant in 
this study via ejaculate is low, and therefore no barrier contraception (condom) use in male 
participants is warranted.  The calculated safety margin is ≥100-fold between the estimated 
partner exposure due to seminal transfer and the no-observed-adverse-effect level (NOAEL) 
for serious manifestations of developmental toxicity in nonclinical studies.  The safety 
margin of 100-fold is based on applying a 10-fold safety factor for interspecies extrapolation 
and a 10-fold safety factor for susceptible populations.
 
 
4.3. Justification for Dose
Dose selection for this study was based on expected average inhibition of IL-12, IL-23, and 
IFNα as well as projected in vivo efficacy observed in psoriasis participants without 
significant JAK2 inhibition.  Four dosing (50 mg QD, 100 mg QD, 200 mg QD and 
400 mg QD) regimens of PF-06826647 and placebo were selected to explore the dose range 
in moderate to severe psoriasis participants given the practical considerations.
 
 
 
 
 
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Based on the exposure-response modeling with the PASI data observed up to Week 4, the 
projected PASI 90 response rates of 50 mg, 100 mg, 200 mg, and 400 mg were 3%, 13%, 
47%, and 83% at Week 16, respectively.  However, there is uncertainty in the extrapolation 
of response from Week 4 to Week 16.  Although the projected PASI 90 response rates of 
50 mg QD is low, the projected average inhibition (Table 3) based on in vitro IC50 value 
determined by phosphorylated signal transducer and activator of transcription (pSTAT)
modulation in human whole blood, red blood cell (RBC) partition ratio of 1.4 and assuming 
Hill coefficient of 1, the average daily inhibition of IL-12, IL-23, IFNα is approximately 
82%, 69% and 79%, respectively.  Considering both the projected PASI 90 response rate and 
the average inhibition of IL-12 and IL-23, 50 mg was selected as the lowest 
pharmacologically active dose that would be expected to be clinically minimally efficacious.  
The highest dose of 400 mg QD was selected based on practical considerations of daily tablet
burden to participants and projected high degree of inhibition (>90%) of IL-12, IL-23 and 
IFNα (Table 3) at steady state. 
Additionally, based on data observed to date in both healthy and psoriasis participants, these 
doses are expected to be safe and well tolerated.  All the adverse events (AEs) observed in 
healthy participants up to 1200 mg QD for 10 days and psoriasis participants up to 
400 mg QD for 28 days were mild in nature.  Although, the projected average inhibition of 
erythropoietin (EPO) (Table 3) was 67% and a transient decrease in reticulocyte was 
observed in psoriasis participants at 400 mg QD, no clinically meaningful change in 
hemoglobin was observed at the same dose for 28 days in psoriasis participants. The 
long-term impact of transient decrease in reticulocytes on hemoglobin is currently unknown. 
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As shown in the Table 3, highest dose of 400 mg QD at steady state is expected to provide 
margins of about 2-fold for Cmax and about 3-fold for AUC relative to the total exposure
(NOAEL) in the monkey 9-month chronic toxicity study.
In Study C2501001, the 6β-hydroxycortisol/cortisol ratio in urine was evaluated as a marker 
of CYP3A induction but there were no differences between PF-06826647 treated versus 
placebo participants. Thus, the risk of induction of metabolic pathways is considered low.
Ethinylestradiol (EE) containing oral contraceptives (OC) has been shown to increase the 
exposure of CYP1A2 substrates such as caffeine. Based on in vitro experiments, the major 
human clearance pathway for PF-06826647 is expected to be hepatic CYP-mediated 
metabolism by CYP1A2, CYP2D6 and CYP3A out of which CYP1A2 is expected to 
contribute ~53%. Therefore, the highest expected increase in exposure of PF-06826647 
based on CYP1A2 inhibition is ~2-fold. The predicted exposure margins for Total Cmax and 
Total AUC with ~2-fold increase in exposure at the highest dose of 400 mg QD is 
approximately 0.94 and 1.67, respectively.
With maximum expected increase in exposure of PF-06826647 due to interaction with EE, 
the maximum expected erythropoietin (EPO) inhibition at 400 mg QD will be approximately 
80%. Reticulocyte count and hemoglobin level will be monitored on a regular basis in the 
study for safety 
 for EPO inhibition. 
The Phase 1 study (C2501001) demonstrated an acceptable safety profile at single doses of 
PF-06826647 ranging from 3 mg to 1600 mg in the single ascending portion and ten-day 
doses from 10 mg to 1200 mg daily in the multiple ascending portion of the study.  Dose 
escalation stopping rules were not triggered.  There were no clinically meaningful findings in 
vital signs, ECGs, or potential Hy’s Law cases reported during this study.  In addition, there 
were no serious AEs (including death) or suspected, unexpected, serious adverse reactions 
(SUSARs) reported.  All reported Treatment Emergent Adverse Events (TEAEs) were of 
mild intensity.
The 200 mg and 400 mg doses were selected for the Extension Treatment Period due to the 
higher projected PASI 90 response rates at these doses.  Based on the exposure-response 
modeling with the PASI data observed up to Week 4, the projected PASI 90 response rates at 
200 mg and 400 mg are 47% and 83% at Week 16 respectively, while 50 mg and 100 mg are 
expected to provide <15% PASI 90 response rate. 
4.4. End of Study Definition
A participant is considered to have completed the study if he/she has completed all phases of 
the study including the last visit or the last scheduled procedure shown in the Schedule of 
Activities.
The end of the study is defined as the date of the last scheduled procedure shown in the 
Schedule of Activities for the last participant in the trial globally.
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5. STUDY POPULATION
This study can fulfill its objectives only if appropriate participants are enrolled.  The 
following eligibility criteria are designed to select participants for whom participation in the 
study is considered appropriate.  All relevant medical and nonmedical conditions should be 
taken into consideration when deciding whether a participant is suitable for this protocol.
Prospective approval of protocol deviations to recruitment and enrollment criteria, also 
known as protocol waivers or exemptions, is not permitted.
5.1. Inclusion Criteria
Participants are eligible to be included in the study only if all the following criteria apply:
Age and Sex:
1. Male or female participants between the ages of 18 (or the minimum country-specific 
age of consent if >18) and 75 years, inclusive, at Screening.
•
Refer to Appendix 4 for reproductive criteria for male (Section 10.4.1) and female 
(Section 10.4.2) participants.
Type of Participant and Disease Characteristics:
2. Participants who are willing and able to comply with all scheduled visits, treatment 
plan, laboratory tests, lifestyle considerations, and other study procedures.
3. Participants with a diagnosis of plaque psoriasis (psoriasis vulgaris) for at least 
6 months prior to Baseline/Day 1 (prior to first dose of study drug).
4. Have a PASI score of 12 or greater AND a Physician Global Assessment score of 
3 (“moderate”) or 4 (“severe”) at Baseline/Day 1 (prior to first dose of study drug).
 
Weight:
6. Body weight must be >40 kg.
Informed Consent:
7. Capable of giving signed informed consent as described in Appendix 1, which
includes compliance with the requirements and restrictions listed in the informed 
consent document (ICD) and in this protocol.
8. Must discontinue systemic, topical and/or phototherapy therapies (eg, ultraviolet B 
(UVB) or photochemotherapy (PUVA)) for the treatment of psoriasis per timing 
criteria described in Section 5.2.
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5.2. Exclusion Criteria
Participants are excluded from the study if any of the following criteria apply:
Medical Conditions:
1. Currently have non-plaque forms of psoriasis, eg, erythrodermic, guttate, or pustular 
psoriasis, except for nail psoriasis which is allowed.
2. Evidence of other skin conditions (eg, eczema) at the time of screening or baseline 
visit that would interfere with the evaluation of psoriasis.
3. Current drug-induced psoriasis, eg, a new onset of psoriasis or an exacerbation of 
psoriasis from beta blockers, calcium channel blockers, antimalarial drugs or lithium.
4. If receiving non-prohibited concomitant medications for any reason, must be on a 
stable regimen, which is defined as not starting a new drug or changing dosage within 
7 days or 5 half-lives (whichever is longer) prior to first dose of study drug.
5. Any psychiatric condition including recent (within the past year) or active suicidal 
ideation or behavior that meets any of the following criteria:
a.
Suicidal ideation associated with actual intent and a method or plan in the past 
year: “Yes” answers on items 4 or 5 of the Columbia suicide severity rating scale 
(C-SSRS) (10.9).
b. Previous history of suicidal behaviors in the past 5 years: “Yes” answer (for 
events that occurred in the past 5 years) to any of the suicidal behavior items of 
the C-SSRS. 
c.
In the opinion of the investigator or Sponsor (or designee) exclusion is required.
6. Have any condition possibly affecting oral drug absorption, eg, gastrectomy, 
clinically significant diabetic gastroenteropathy, or certain types of bariatric surgery 
such as gastric bypass.  Procedures such as gastric banding, that simply divide the 
stomach into separate chambers, are NOT exclusionary.
7. Have current or recent (within the past year) history of severe, progressive, or 
uncontrolled renal, hepatic, hematological, gastrointestinal, metabolic, endocrine, 
pulmonary, cardiovascular, or neurological disease.
8. History of any lymphoproliferative disorder (such as Epstein-Barr virus
[EBV] -related lymphoproliferative disorder, history of lymphoma, leukemia, or signs 
and symptoms suggestive of current lymphatic disease.
9. History (single episode) of disseminated herpes zoster or disseminated herpes 
simplex, or a recurrent (more than one episode of) localized, dermatomal herpes 
zoster.


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10. History of infection requiring hospitalization, parenteral antimicrobial therapy, or as 
otherwise judged clinically significant by the investigator within 3 months prior to 
first dose of study drug or a history of infection requiring oral antimicrobial therapy 
within 2 weeks prior to first dose of study drug.
11. Infected with Mycobacterium tuberculosis (TB) (see Section 8.2.1.1).
12. Have known immunodeficiency disorder or a first-degree relative with a hereditary 
immunodeficiency.
13. History of recurrent (≥2) venous thrombosis or any arterial thromboembolism or 
known blood clotting disorders. 
14. History of acute coronary syndrome (eg, myocardial infarction, unstable angina 
pectoris) and any history of cerebrovascular disease within 24 weeks before 
screening.
15. Have any malignancies or a history of malignancies except for adequately treated or 
excised non-metastatic basal cell or squamous cell cancer of the skin or cervical 
carcinoma in situ.
16. Have undergone significant trauma or major surgery within 1 month prior to 
Screening or plan to undergo surgery during treatment period.
17. Other acute or chronic medical or psychiatric condition including recent (within the 
past year) or active suicidal ideation or behavior or laboratory abnormality that may 
increase the risk associated with study participation or investigational product 
administration or may interfere with the interpretation of study results and, in the 
judgment of the investigator, would make the participant inappropriate for entry into 
this study.  For any reason in the opinion of the investigator or sponsor, the 
participant is inappropriate for entry into this study.
Prior/Concomitant Therapy:
18. Planned initiation of, or changes to, concomitant medication that could affect 
psoriasis (eg, beta blockers, calcium channel blockers, antimalarial drugs or lithium) 
are to occur within 2 weeks prior to randomization and/or during the study.
19. Are taking or require oral or injectable (eg, intraarticular, intramuscular or 
intravenous) corticosteroids for any condition. (Must be discontinued for at least 
4 weeks prior to first dose of study drug).
20. Have been vaccinated with live or attenuated live vaccine within the 6 weeks prior to 
the first dose of study drug or expects to be vaccinated with these vaccines during 
treatment, or within the 8 weeks following the last dose of study drug.  (For further 
information regarding avoidance of household contacts who may be vaccinated see 
Section 5.3.2).


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21. Require treatment with prohibited concomitant medications(s) (see Section 6.5) or
have received a prohibited concomitant medication/dietary supplement within 7 days 
or 5 half-lives (whichever is longer) prior to the first dose of study drug. Details 
include specific discontinuation recommendations and, additional details are found in 
Appendix 8.
22. Previous administration with an investigational drug within 30 days (or as determined 
by the local requirement) or 5 half-lives preceding the first dose of investigational 
product used in this study (whichever is longer).
Diagnostic Assessments:
23. Known history of incompletely treated hepatitis B or C, or human immunodeficiency 
virus (HIV) based on documented history with positive serological test, or positive 
HIV serological test at screening.

Participants who are hepatitis C antibody (HCVAb) positive require further 
testing with Hepatitis C virus (HCV) ribonucleic acid (RNA) Polymerase 
chain reaction (PCR) may be eligible if HCV RNA PCR is negative.

Participants who are hepatitis B surface antigen (HBsAg) negative and 
hepatitis B core antibody (HBcAb) positive will be reflex tested for 
Hepatitis B Surface Antibody (HBsAb). If HBsAb is positive, participant 
may be eligible.  If HBsAb is negative, the participant is not eligible. This 
reflex test applies to all countries except Japan. 

Participants who are negative for all three serology tests may be eligible. 

Participants who are HBsAg positive are not eligible. 

In Japan ONLY, all participants will undergo testing for all three tests HBsAg, 
HBcAb, and HBsAb during Screening. 

Participants who have negative HBsAg, positive HBcAb, and negative 
HBsAb are not eligible. 

Participants who have negative HBsAg, negative HBcAb and positive HBsAb 
and provide a documentation of prior Hepatitis B Virus (HBV) vaccination 
may be eligible and will not require HBV DNA monitoring during the study. 

Participants who have negative HBsAg, negative HBcAb and positive HBsAb 
without documentation of prior HBV vaccination, and who have negative 
HBsAg, positive HBcAb and positive HBsAb are required to undergo HBV 
DNA reflex testing.

Participants with detectable HBV DNA are not eligible.


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
Participants without detectable HBV DNA may be eligible. If enrolled, 
HBV DNA will be assessed at Weeks 12 (Investigational Treatment 
Period), Weeks 24, 36 (Extension Treatment Period) and ET (if 
applicable).
24. Screening or baseline standard 12-lead electrocardiogram (ECG) that demonstrates 
clinically relevant abnormalities that may affect participant safety or interpretation of 
study results (eg, baseline corrected QT [QTc] interval >450 millisecond (msec),
complete left bundle branch block [LBBB], signs of an acute or indeterminate-age 
myocardial infarction, ST-T interval changes suggestive of myocardial ischemia, 
second- or third-degree atrioventricular [AV] block, or serious bradyarrhythmias or 
tachyarrhythmias).  If the baseline uncorrected QT interval is >450 msec, this interval 
should be rate-corrected using the Fridericia method and the resulting corrected QT 
interval by Fridericia (QTcF) should be used for decision making and reporting.  If 
QTc exceeds 450 msec, or QRS exceeds 120 msec, the ECG should be repeated 
2 more times and the average of the 3 QTc or QRS values should be used to 
determine the participant’s eligibility.  Computer-interpreted ECGs should be over 
read by a physician experienced in reading ECGs before excluding participants.
25. Participants with ANY of the following abnormalities in clinical laboratory tests at 
screening, as assessed by the study-specific laboratory and confirmed by a single 
repeat, if deemed necessary:

Hemoglobin <11.0 g/dL or hematocrit <30% (<0.30 v/v);

White blood cell count <3.0 x 109/L (<3000 mm3); 

Absolute lymphocyte count of <1.0 x 109/L (<1000/mm3);

Absolute neutrophil count of <1.5 x 109/L (<1500/mm3);

Platelet count <100 x 109/L (<100,000/mm3);

eGFR (estimated glomerular filtration rate) <60 mL/min/1.73 m2 using serum 
creatinine based on the Chronic Kidney Disease Epidemiology Collaboration 
(CKD EPI) calculation;

Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) values 
>2 times the upper limit of normal (ULN);

Total bilirubin ≥1.5 times the ULN; participants with a history of Gilbert's 
syndrome may have a direct bilirubin measured and would be eligible for this 
study provided the direct bilirubin is <ULN.


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In the opinion of the investigator or sponsor, any uncontrolled clinically significant 
laboratory abnormality that would affect interpretation of study data or the 
participant’s participation in the study.
Other Exclusions:
26. Investigator site staff members directly involved in the conduct of the study and their 
family members, site staff members otherwise supervised by the investigator, or 
Sponsor employees, including their family members, directly involved in the conduct 
of the study.
27. Have a history of alcohol or substance abuse, unless in full remission for greater than 
6 months prior to Day 1.
5.3. Lifestyle Considerations
In order to participate in the study, participants must be made aware of the following life 
style guidelines and restrictions that apply during and after the study period.  Details of these 
life style guidelines are provided in sections as noted.

On appropriate study visit days, comply with fasting requirement (water only) for at 
least 8 hours prior to the visit, as indicated in the Schedule of Activities.

On study visit days, do not smoke or ingest caffeine (eg, tea, coffee, some soft 
drinks/colas/energy drinks and power bars) during the 30 minutes prior to blood 
pressure and pulse rate measurements.

Only on study visit days, do not take the dose of study drug until instructed to do so 
by the investigator or designated study site staff while at the study site.

On study visit days, showering or bathing is permitted prior to attending the study 
visit, but do not moisturize.

On study visit days, take prescribed permitted concomitant medication, as needed, 
prior to the study visit, if it can be administered with water only.  Prescribed 
permitted concomitant medications that must be taken with food or after meals should 
not be taken until after the visit procedures have been completed.

Contact the study site investigator if there are any changes or additions to 
concomitant medications.

As needed, participants may use the treatments listed as permitted in Section 6.5 for
the specified body sites described.  On clinic visit days, do not use any of these 
treatments until after the clinic visit is completed.


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
Abstain from strenuous exercise (eg, heavy lifting, weight training, calisthenics, and 
aerobics) for at least 48 hours prior to each blood collection for clinical laboratory 
tests.  Walking at a normal pace is permitted.

Avoid prolonged exposure to the sun and avoid use of tanning booths or other 
ultraviolet light sources during the study.

Herbal supplements must be discontinued 28 days prior to the first dose of study 
medication.  Refrain from excessive consumption of grapefruit or grapefruit juice or 
citrus fruits eg, Seville oranges, pomelos within 7 days prior to the first dose of study 
medication   It is recommended that participants avoid excessive consumption of 
grapefruit or grapefruit juice or citrus fruits eg, Seville oranges or pomelos not to 
exceed 8 ounces (~240 mL) total in a day while in the study.
5.3.1. Contraception 
The investigator or his or her designee, in consultation with the participant, will confirm that 
the participant has selected an appropriate method of contraception for the individual 
participant and his or her partner(s) from the permitted list of contraception methods (see 
Appendix 4 Section 10.4.4) and will confirm that the participant has been instructed in its 
consistent and correct use.  At time points indicated in the Schedule of Activities (SoA), the 
investigator or designee will inform the participant of the need to use highly effective 
contraception consistently and correctly and document the conversation and the participant’s 
affirmation in the participant’s chart (participants need to affirm their consistent and correct 
use of at least 1 or 2 of the selected methods of contraception).  In addition, the investigator 
or designee will instruct the participant to call immediately if the selected contraception 
method is discontinued or if pregnancy is known or suspected in the participant or partner.
Female participants using hormonal contraceptives are required to use an additional 
acceptable barrier method listed in Contraception (Section 10.4.4) during the study and until 
28 days after the last dose of study drug.
5.3.2. Vaccination
Vaccination with live virus, attenuated live virus, or any live viral components is prohibited 
within the 6 weeks prior to Day 1, during the study, and within the 8 weeks following the last 
dose of study drug.  Similarly, current routine household contact with individuals who have 
been vaccinated with live vaccine components should be avoided in the same period.  This is 
due to the potential for virus to be shed in bodily fluids (including stool) following 
vaccination with live component vaccines, leading to a potential risk that the virus may be 
transmitted.
Such vaccines include: FluMist® (intranasal influenza vaccine), attenuated rotavirus vaccine, 
varicella (chickenpox) vaccine, attenuated typhoid fever vaccine, oral polio vaccine, measles, 
mumps, rubella (MMR) vaccine and vaccinia (smallpox) vaccine. 


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5.3.3. Other Lifestyle Requirements
In order to participate in the study, participants must be made aware of the following life 
style guidelines and restrictions that apply during and after the study period.  Details of these 
life style guidelines are provided in sections as noted.
1. On appropriate study visit days, comply with fasting requirement (water only) for at 
least 8 hours prior to the visit, as indicated in the Schedule of Activities.
2. On study visit days, do not smoke or ingest caffeine (eg, tea, coffee, some soft 
drinks/colas/energy drinks and power bars) during the 30 minutes prior to blood 
pressure and pulse (heart) rate measurements.
3. Only on study visit days, do not take the dose of study drug until instructed to do so 
by the investigator or designated study site staff while at the study site.
4. On study visit days, showering or bathing is permitted prior to attending the study 
visit, but do not moisturize.
5. On study visit days, take prescribed permitted concomitant medication, as needed,
prior to the study visit, if it can be administered with water only.  Prescribed 
permitted concomitant medications that must be taken with food or after meals should 
not be taken until after the visit procedures have been completed.
6. Contact the study site investigator if there are any changes or additions to 
concomitant medications.
7. As needed, participants may use the treatments listed as permitted in Section 6.5 for
the specified body sites described.  On clinic visit days, do not use any of these 
treatments until after the clinic visit is completed.
8. Abstain from strenuous exercise (eg, heavy lifting, weight training, calisthenics, and
aerobics) for at least 48 hours prior to each blood collection for clinical laboratory 
tests.  Walking at a normal pace is permitted.
9. Avoid prolonged exposure to the sun and avoid use of tanning booths or other 
ultraviolet light sources during the study.
10. Herbal supplements must be discontinued 28 days prior to the first dose of study 
medication.  
Refrain from excessive consumption of grapefruit or grapefruit juice or citrus fruits 
eg, Seville oranges, pomelos or within 7 days prior to the first dose of study 
medication. It is recommended that participants avoid excessive consumption of 
grapefruit or grapefruit juice or citrus fruits eg, Seville oranges or pomelos 
exceeding 8 ounces (~240 mL) total in a day while in the study.


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5.4. Screen Failures
Screen failures are defined as participants who consent to participate in the clinical study but 
are not subsequently randomly assigned to investigational product. Screen failure data are 
collected and remain as source and are not reported to the clinical database.  A minimal set of 
screen failure information is required to ensure transparent reporting of screen failure 
participants to meet the Consolidated Standards of Reporting Trials (CONSORT) publishing 
requirements and to respond to queries from regulatory authorities.  Minimal information 
includes demography, screen failure details, eligibility criteria, and any serious adverse event 
(SAE).  Individuals who do not meet the criteria for participation in this study (screen failure) 
may be rescreened once. 
Re-screened participants will be re-consented. All screening assessments must be repeated 
during re-screening, with the exception of chest radiograph, HIV, Hepatitis and TB testing, 
provided re-screening is done within 3 months of screening.
6. STUDY INTERVENTION
Study intervention is defined as any investigational intervention(s), marketed product(s), 
placebo, or medical device(s) intended to be administered to a study participant according to 
the study protocol.
For the purposes of this protocol, the term investigational product may be used 
synonymously with study intervention.
6.1. Study Intervention(s) Administered
Blinded PF-06826647 and matching placebo will be provided as tablets for oral 
administration. PF-06826647 will be provided in dosage strengths of 100 mg and 25 mg
tablets.  PF-06826647 and matching placebo will be supplied in blister cards and labeled 
according to local regulatory requirements.


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Intervention Name
PF-06826647 
PF-06826647 
PF-06826647 
PF-06826647 
Placebo
ARM Name
PF-06826647 
50 mg
PF-06826647 
100 mg
PF-06826647 
200 mg
PF-06826647 
400 mg
Placebo
Type
Drug
Drug
Drug
Drug
Drug
Dose Formulation
Tablet
Tablet
Tablet
Tablet
Tablet
Dosage Level(s)
50 mg QD 
100 mg QD 
200 mg QD 
400 mg QD 
Placebo
Number and Type 
of Tablets During 
Investigational 
Treatment Period, 
Day 0 to Week 16 
(Number of 
Tablets)
2 x 25 mg active, 
and
4 x 100 mg size 
placebo
2 x 25 mg size 
placebo, and
1 x 100 mg 
active, and
3 x 100 mg size 
placebo
2 x 25 mg size 
placebo, and
2 x 100 mg 
active, and
2 x 100 mg size 
placebo
2 x 25 mg size 
placebo, and
4 x 100 mg 
active
2 x 25 mg size 
placebo, and
4 x 100 mg size 
placebo
Number and Type 
of Tablets During 
Extension 
Treatment Period, 
Week 16 to Week 
40 (Number of 
Tablets)
2 x 100 mg 
active, and
2 x 100 mg size 
placebo
or
4 x 100 mg 
active
2 x 100 mg 
active, and
2 x 100 mg size 
placebo
or
4 x 100 mg 
active
2 x 100 mg 
active, and
2 x 100 mg size 
placebo
4 x 100 mg 
active
2 x 100 mg 
active, and
2 x 100 mg size 
placebo
or
4 x 100 mg 
active
Route of 
Administration
Oral
Oral
Oral
Oral
Oral
Investigational 
Medicinal Product 
(IMP) and 
Noninvestigational 
Medicinal Product 
(NIMP)
IMP
IMP
IMP
IMP
N/A
Sourcing
Provided 
centrally by the 
sponsor 
IP should be 
provided as 
outlined in the 
Investigational 
Product Manual.
Provided 
centrally by the 
sponsor 
IP should be 
provided as 
outlined in the 
Investigational 
Product Manual.
Provided 
centrally by the 
sponsor 
IP should be 
provided as 
outlined in the 
Investigational 
Product Manual.
Provided 
centrally by the 
sponsor 
IP should be 
provided as 
outlined in the 
Investigational 
Product Manual.
Provided 
centrally by the 
sponsor 
IP should be 
provided as 
outlined in the 
Investigational 
Product 
Manual.
Packaging and 
Labeling
Study 
intervention will 
be provided as 
tablets in blinded 
blister cards.  
Each blister card 
will be labeled as 
required per 
country 
requirement.
Study 
intervention will 
be provided as 
tablets in blinded 
blister cards.  
Each blister card 
will be labeled as 
required per 
country 
requirement.
Study 
intervention will 
be provided as 
tablets in blinded 
blister cards.  
Each blister card 
will be labeled as 
required per 
country 
requirement.
Study 
intervention will 
be provided as 
tablets in blinded 
blister cards.  
Each blister card 
will be labeled as 
required per 
country 
requirement.
Study 
intervention will 
be provided as 
tablets in 
blinded blister 
cards.  Each 
blister card will 
be labeled as 
required per 
country 
requirement.
Participants will receive blinded labeled supplies throughout the study.  To accomplish this, 
all participants will take a total of six tablets per day during the Investigational Treatment 
Period, and four tablets per day during the Extension Treatment Period.


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The participants continuing into the Extension Treatment Period that were originally 
randomized to the 200 mg and 400 mg treatment groups in the Investigational Treatment 
Period will continue on their respective doses, while those randomized to one of the other 
treatment groups including placebo will be randomly assigned at study baseline to either 
receive 200 mg or 400 mg during the Extension Treatment Period. 
6.1.1. Administration
Participants will swallow the investigational product (IP) whole and will not manipulate or 
chew the IP prior to swallowing.  Participants will administer IP as outpatients, except on 
study visit days.  On study visit days, participants should not take their dose of study drug 
until instructed to do so by the investigator or designated study site staff while at the study 
site.
Blinded PF-06826647 tablets and matching placebo for oral administration will be dispensed 
in blisters.  Participants will be provided dosing instructions.
Sites will be trained on how participants should take tablets at home through an 
Investigational Product manual and/or other vehicle(s).  Sites are responsible for 
communicating this information to participants; and site staff should review the dosing 
instructions with participants at every study visit.
Participants should take the IP orally once daily during the Investigational Treatment Period 
and the Extension Treatment Period of the study. 
A temporary hold on dosing of the investigational product during the study for an individual 
participant for up to a maximum of 7 consecutive days is allowed once from Day 1 to 
Day 113, if the principal investigator (PI) deems it necessary because of infections (eg, upper 
respiratory infection, urinary tract infection), gastrointestinal (GI) disorders (eg, diarrhea, 
nausea, vomiting) or hematological abnormalities.  Any temporary hold on dosing of the 
investigational product during the study should be recorded in the case report form (CRF).
It is recommended that the tablets be swallowed whole with ambient temperature water to a 
total volume of approximately 240 mL, and not to manipulate or chew the medication prior 
to swallowing; and it is recommended to be taken with food.  On study visit days, 
participants are to be instructed to refrain from dosing at home and are to take the dose in the 
clinic from their current blister card and the dose from the newly dispensed blister card will 
be taken on the next day at home.
If a dose is missed and the interval to the next dose is less than 8 hours, the missed dose 
should not be administered.
6.2. Preparation/Handling/Storage/Accountability
1. The investigator or designee must confirm appropriate temperature conditions have 
been maintained during transit for all study interventions received and any 
discrepancies are reported and resolved before use of the study intervention, as 
applicable for temperature-monitored shipments. 


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2. Only participants enrolled in the study may receive study intervention and only 
authorized site staff may supply or administer study intervention.  All study 
interventions must be stored in a secure, environmentally controlled, and monitored 
(manual or automated recording) area in accordance with the labeled storage 
conditions with access limited to the investigator and authorized site staff.  At a 
minimum, daily minimum and maximum temperatures for all site storage locations 
must be documented and available upon request.  Data for nonworking days must 
indicate the minimum and maximum temperature since previously documented for all 
site storage locations upon return to business.
3. The investigator, institution, or the head of the medical institution (where applicable) 
is responsible for study intervention accountability, reconciliation, and record 
maintenance (ie, receipt, reconciliation, and final disposition records).  All study 
interventions will be accounted for using an investigational product accountability 
form/record.  The participant will be asked to bring all dispensed investigational 
product (including empty, partially used and unused blister packs) and the dosing 
diary to the clinic at every visit.  Detailed drug accountability records will be 
maintained by study staff for each participant.
4. Further guidance and information for the final disposition of unused study 
interventions are provided in the investigational product (IP) manual.
5. Any storage conditions stated in the SRSD will be superseded by the storage 
conditions stated on the product label. 
6. Study interventions should be stored in their original containers and in accordance 
with the labels. 
7. Site staff will instruct participants on the proper storage requirements for take-home 
study intervention. 
8. Any excursions from the study intervention label storage conditions should be 
reported to the sponsor upon discovery along with any actions taken.  The site should 
actively pursue options for returning the study intervention to the storage conditions 
described in the labeling, as soon as possible.  Once an excursion is identified, the 
study intervention must be quarantined and not used until the sponsor provides 
permission to use the study intervention.  It will not be considered a protocol 
deviation if the sponsor approves the use of the study intervention after the 
temperature excursion.  Use of the study intervention prior to the sponsor’s approval 
will be considered a protocol deviation.  Specific details regarding the definition of an 
excursion and information the site should report for each excursion will be provided 
to the site in the IP manual.


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9. The sponsor or designee will provide guidance on the destruction of unused study 
intervention (eg, at the site).  If destruction is authorized to take place at the 
investigator site, the investigator must ensure that the materials are destroyed in 
compliance with applicable environmental regulations, institutional policy, and any 
special instructions provided by the sponsor, and all destruction must be adequately 
documented.
Additional details about accountability, storage, destruction, and excursion reporting can be 
found in the IP manual.
6.2.1. Preparation and Dispensing
The investigational product will be dispensed using an interactive response technology (IRT)
drug management system at each visit per SoA.  A qualified staff member will dispense the 
investigational product via unique container numbers in the blister cards provided, in 
quantities appropriate for the study visit schedule.  The participant/caregiver should be 
instructed to maintain the product in the blister cards provided throughout the course of 
dosing and return the blister cards (including empty, partially used and unused blister packs) 
to the site at the next study visit.
6.2.2. Investigational Product Accountability 
The investigator site must maintain adequate records documenting the receipt, use, loss, or 
other disposition of the investigational product supplies.  All investigational products will be 
accounted for using a drug accountability form/record.  All blister cards of investigational 
product must be returned to the investigator by the participant at every visit and at the end of 
the trial.
The participant will be asked to bring all dispensed investigational product (including empty, 
partially used and unused blister packs) and the dosing diary to the clinic at every visit.  
Detailed drug accountability records will be maintained by study staff for each participant.
The original investigational product accountability log, or equivalent document, must be 
accurately completed, signed by the Investigator, and retained at the study site (with a copy 
supplied to the sponsor) when the study is complete.
6.2.3. Destruction of Investigational Product Supplies 
The investigator will keep the entire investigational product returned by the participants until 
destruction is authorized. 
The sponsor or designee will provide guidance on the destruction of unused study 
intervention (eg, at the site).  If destruction is authorized to take place at the investigator site, 
the investigator must ensure that the materials are destroyed in compliance with applicable 
environmental regulations, institutional policy, and any special instructions provided by the 
sponsor, and all destruction must be adequately documented.


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Further guidance and information for the final disposition of unused study interventions are 
provided in the IP manual.
6.3. Measures to Minimize Bias: Randomization and Blinding
Allocation to treatment will occur via an Interactive Response Technology (IRT) system.  
The system will be programmed with blind-breaking instructions.  Refer to subsections 6.3.1
Allocation to Investigational Product and 6.3.2 Breaking the Blind for further details. 
6.3.1. Allocation to Investigational Product
Allocation of participants to treatment groups will proceed through the use of an interactive 
response technology (IRT) system (interactive Web-based response [IWR]).  The site 
personnel (study coordinator or specified designee) will be required to enter or select 
information including but not limited to the user’s identification (ID) and password, the 
protocol number, and the participant number.  The site personnel will then be provided with a 
treatment assignment, randomization number, and dispensable unit (DU) or container number 
when investigational product is being supplied via the IRT system.  The IRT system will 
provide a confirmation report containing the participant number, randomization number, and
DU or container number assigned.  The confirmation report must be stored in the site’s files. 
Investigational product will be dispensed at the study visits summarized in the SoA. 
Returned investigational product must not be redispensed to the participants.
The study-specific IRT reference manual and IP manual will provide the contact information 
and further details on the use of the IRT system.
6.3.2. Breaking the Blind 
At the initiation of the study, the investigator site will be instructed on the method for 
breaking the blind.  The method will be an electronic process.  The IRT will be programmed 
with blind-breaking instructions. In case of an emergency, the investigator has the sole 
responsibility for determining if unblinding of a participant’s treatment assignment is 
warranted. Participant safety must always be the first consideration in making such a 
determination.  If the investigator decides that unblinding is warranted, the investigator 
should make every effort to contact the sponsor prior to unblinding a participant’s treatment 
assignment unless this could delay further management of the participant.  However, 
discussion with the sponsor in advance of unblinding is not required. If a participant’s 
treatment assignment is unblinded, the sponsor must be notified within 24 hours after 
breaking the blind. The date and reason that the blind was broken must be recorded in the 
source documentation and case report form (CRF).  Any cases of unblinding will be 
documented in the clinical study report.  The study-specific IRT reference manual and IP 
manual will provide the contact information and further details on the use of the IRT system.


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6.4. Study Intervention Compliance
The participant will take the investigational product at home; compliance will be captured 
daily by the participant using a Dosing Diary and instructions provided by the site.  The 
participant will be instructed to complete the Dosing Diary (each time investigational product 
is provided in the clinic or at home) starting with the first dose provided in the clinic on 
Day 1, then daily through Week 16 and through Week 40.
Participant compliance with investigational product will be assessed at each visit.  If a visit is 
missed consult the Medical Monitor.  Compliance will be assessed by review of the 
participant-completed Dosing Diary and source documents will be placed in the participant’s 
study file.  Participants will be instructed to bring the Dosing Diary and all dispensed 
investigational product supplies in the original packaging (used as well as unused) to every 
study visit.
Non-compliance is defined as less than 80% or more than 120% of IP dosing as directed by 
the dosing instructions.  The investigator and the sponsor have the discretion to withdraw any 
participant from the study for reasons of non-compliance with the dosing regimen.  
Investigators should indicate on the appropriate CRF page noncompliance with study 
intervention and provide an explanation.  Inventory control of all investigational products 
must be rigorously maintained throughout the duration of the study until all medication has 
been accounted for and/or returned to the sponsor.  Any discrepancies noted between drug 
dispensing records and the drug inventory must be reported to the sponsor.
6.5. Concomitant Therapy
Permitted Concomitant Medication
Body Region
Permitted Topical Treatments
Palms, soles, face, and intertriginous areas
Low or least potent (Class 6 or 7) topical corticosteroids
Hydrocortisone ≤1% and hydrocortisone acetate ≤1% are the 
only topical corticosteroids permitted
Scalp
Tar preparations
Salicylic acid preparations
Shampoos free of corticosteroids
All body regions
Study supplied non-medicated emollient, Cetaphilmoisturizing 
cream
Prohibited Concomitant Medications
1. The following hydrocortisones are NOT permitted:

Hydrocortisone 17 butyrate.

Hydrocortisone valerate.

Hydrocortisone/hydrocortisone acetate with concentration higher than 1%.


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2. If received any of the following treatment regimens, for any reason, are eligible 
providing the following minimum washout criteria are observed:
Must be discontinued for at least 12 weeks prior to first dose of study drug:
a.
Any investigational or experimental therapy or procedure for psoriasis, 
psoriatic arthritis or rheumatoid arthritis;
b. efalizumab (Raptiva®), secukinumab (Cosentyx) or Ixekizumab (Taltz) or 
other anti-IL-17, tofacitinib (Xeljanz) or treatment with apremilast (Otezla).
Must be discontinued for at least 10 weeks prior to first dose of study drug:
a.
Adalimumab (Humira®);
b. Certolizumab pegol (Cimzia®);
c.
Infliximab (Remicade®);
d. Alefacept (Amevive®).
Must be discontinued for at least 4 weeks prior to first dose of study drug:
a.
Etanercept (Enbrel®);
b. Systemic treatments other than biologics that could affect psoriasis, eg, oral or 
injectable (eg, intraarticular, intramuscular, or intravenous) corticosteroids, 
retinoids, methotrexate, cyclosporine, fumaric acid derivatives, sulfasalazine, 
hydroxycarbamide (hydroxyurea), azathioprine, intramuscular gold;
c.
Psoralen + UVA phototherapy (PUVA).
Must be discontinued for at least 2 weeks prior to first dose of study drug:
a.
Topical treatments that could affect psoriasis, eg, corticosteroids, tars, 
keratolytics, anthralin, vitamin D analogs, and retinoids.
b. Exceptions – the following topical treatments are allowed: non medicated 
emollients for use over the whole body; low or least potent (Class 6 or 7) 
topical corticosteroids for the palms, soles, face, and intertriginous areas only; 
tar and salicylic acid preparations for the scalp only, and shampoos free of 
corticosteroids for the scalp only.  See details in Permitted Concomitant 
Topical Psoriasis Treatments.
c.
UVB (narrowband or broadband) phototherapy.


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3. Any cell-depleting agents including but not limited to rituximab within 12 months of 
first dose of study drug or 5 half-lives (if known), whichever is longer, or until 
lymphocyte count returns to normal, whichever is longer.
4. Any prior treatment with ustekinumab (Stelara®), guselkumab (gene recombinant), 
risankizumab (gene recombinant) or non B cell-specific lymphocyte depleting 
agents/therapies (eg, alemtuzumab [CamPath®], alkylating agents 
[eg, cyclophosphamide or chlorambucil], total lymphoid irradiation, etc); participants 
who have received rituximab or other selective B-lymphocyte depleting agents 
(including experimental agents) within 6 months of first dose of study drug or 
5 half-lives (if known), whichever is longer, or until lymphocyte count returns to 
normal, whichever is longer.
5. Participants who are likely to receive during the study any moderate-strong CYP1A2
and CYP3A4 inhibitors/inducers or CYP2D6 inhibitors or MATE substrates as listed 
in Appendix 8. 
Participants will abstain from all concomitant medications as described in Exclusion sections 
of the protocol and Appendix 8 Prohibited Concomitant Medications.
Participants should be instructed at each visit to contact the study site investigator promptly if 
there are any intended changes or additions to concomitant medications.
It is recommended that participants avoid changing other prescription or non-prescription 
drugs, vitamins, and dietary supplements within 7 days or 5 half-lives (whichever is longer) 
prior to the first dose of study medication and throughout the study.
All concomitant medication taken during the study must be recorded with indication, daily 
dose, and start and stop dates of administration.
Medications taken after informed consent is obtained (but before the first dose of study 
medication) will be documented as prior medications.  Medications taken after the first dose 
of study drug has been administered will be documented as concomitant medications.
6.5.1. Rescue Medicine
There is no rescue therapy to reverse the adverse events (AEs) observed with PF-06826647; 
standard medical supportive care must be provided to manage the AEs. 
6.6. Dose Modification
Treatment assignment in the Extension Treatment Period will be predetermined according to 
the Scheme shown in Section 1.2.  Participants who are in the placebo, 50 mg, or 100 mg 
treatment arms will be assigned to either 200 mg or 400 mg PF-06826647 in the Extension 
Treatment Period.  Allocation to either dose in the Extension Treatment Period will be based 
on an initial treatment assignment at randomization.  No dose adjustment is allowed during 
the study. 


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6.7. Intervention after the End of the Study
No intervention will be provided to study participants at the end of the study.
7. DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL
7.1. Discontinuation of Study Intervention
In rare instances, it may be necessary for a participant to permanently discontinue the 
investigational product.  Per the study estimands, if investigational product is permanently 
discontinued, the participant will proceed to Early Termination per Schedule of Activities.  
The site will inform sponsor medical monitor or sponsor clinician if the below criteria for 
permanent discontinuation of the IP are triggered.
Any participant meeting discontinuation criteria must have an Early Termination visit with 
their first visit occurring 1 week after their last dose whenever possible and continue visits 
per Investigator’s discretion until the event has returned to normal or baseline levels or is 
deemed clinically stable. 
The only exception to this is when a participant specifically withdraws consent for any 
further contact with him or her or persons previously authorized by the participant to provide 
this information.  
Note that discontinuation of the investigational product does not represent withdrawal from 
the study.
Participants experiencing a thrombotic event as part of a serious adverse event must be 
discontinued from further IP administration and referred to a specialist for further evaluation 
of possible hypercoagulable state, as per local guidelines.
ECG Changes
A participant who meets either bulleted criterion below based on the average of triplicate 
ECG readings will be withdrawn from the IP administration. 

QTcF >500 msec;

Change from baseline: QTc >60 msec.
If a clinically significant finding is identified (including, but not limited to, changes from 
baseline in QTcF after enrollment), the investigator or qualified designee will determine if 
the participant can continue in the study and if any change in participant management is 
needed.  This review of the ECG printed at the time of collection must be documented.  Any 
new clinically relevant finding should be reported as an AE.


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Laboratory Abnormalities
All the following laboratory abnormalities require discontinuation if they are confirmed.  
Confirmation through re-testing should occur within 48 hours:
Laboratory Variable
Laboratory Value
Hematology
Absolute Neutrophil Count
<1000/mm3; <1.0 x109/L
Hemoglobin
<10.0 g/dL; <6.2 mmol/L; <100 g/L
Platelet count
<75,000/mm3; <75.0x109/L
Lymphocytes
<500/mm3; <0.5x109/L
Chemistry
ASTa
>3x ULN
ALTa
>3x ULN
Total bilirubinb
>1.5x ULN
a.
Additional investigations, such as review of ethanol, recreational drug and dietary supplement consumption 
should be done; testing for acute hepatitis A, B or C infection and biliary tract imaging should be promptly 
discussed with sponsor medical monitor.
b.
Total bilirubin >1.5 x ULN; participants with a history of Gilbert's syndrome may have a direct bilirubin 
measured and would be eligible for this study provided the direct bilirubin is <ULN.
Pregnancy
If pregnancy is confirmed by serum beta human chorionic gonadotropin (-hCG) testing at 
any time, then the sponsor clinician or sponsor medical monitor should be notified 
immediately.
Suicidality
Participants triggering criteria for suicidal ideation and behavior as described in 
Section 8.2.5.1.
See the SoA for data to be collected at the time of intervention discontinuation and follow-up 
and for any further evaluations that need to be completed.
7.2. Participant Discontinuation/Withdrawal from the Study
A participant may withdraw from the study at any time at his/her own request or may be 
withdrawn at any time at the discretion of the investigator for safety, behavioral, compliance, 
or administrative reasons.
At the time of discontinuing from the study, if possible, an early termination visit should be 
conducted.  See the SoA for assessments to be collected at the time of study discontinuation 
and follow-up and for any further evaluations that need to be completed. 


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The Early Termination visit applies only to participants who are randomized and then are 
prematurely withdrawn from the study.  Participants should be questioned regarding their 
reason for withdrawal.  The participant will be permanently discontinued both from the study 
intervention and from the study at that time.
If a participant withdraws from the study, he/she may request destruction of any remaining 
samples, but data already generated from the samples will continue to be available and may 
be used to protect the integrity of existing analyses.  The investigator must document any 
such requests in the site study records.
If the participant withdraws from the study and also withdraws consent (see below) for 
disclosure of future information, no further evaluations should be performed, and no 
additional data should be collected.  The sponsor may retain and continue to use any data 
collected before such withdrawal of consent.
When a participant withdraws from the study because of an SAE, the SAE must be recorded 
on the CRF and reported on the Clinical Trial (CT) SAE Report.
Lack of completion of all or any of the withdrawal/early termination procedures will not be 
viewed as protocol deviations so long as the participant’s safety was preserved.
For participants who discontinue early from the Investigational Treatment Period prior to the 
Week 16 visit, or those who discontinue early from the Extension Treatment Period prior to 
the Week 40 visit, should perform the procedures scheduled at the Early Termination (ET) 
visit.
See Section 10 for Guidelines for Safety Monitoring and Discontinuations.
Withdrawal of Consent: 
Participants who request to discontinue receipt of study treatment will remain in the study
and proceed to ET visit as soon as possible.  Whenever possible, these participants should 
have one visit approximately two weeks after the last dose (Week 20 or 44 Follow up visit 
assessments) and/or at least 28 days after the last dose of IP was administered.
The only exception to this is when a participant specifically withdraws consent for any 
further contact with him or her or persons previously authorized by the participant to provide 
this information.  Participants should notify the investigator in writing of the decision to 
withdraw consent from future follow-up, whenever possible.  The withdrawal of consent 
should be explained in detail in the medical records by the investigator, as to whether the 
withdrawal is only from further receipt of investigational product or also from study 
procedures and/or posttreatment study follow-up, and entered on the appropriate CRF page.  
In the event that vital status (whether the participant is alive or dead) is being measured, 
publicly available information should be used to determine vital status only as appropriately 
directed in accordance with local law.


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7.3. Lost to Follow-up 
All reasonable efforts must be made to locate participants to determine and report their 
ongoing status.  This includes follow-up with persons authorized by the participant as noted 
below. 
A participant will be considered lost to follow-up if he or she repeatedly fails to return for 
scheduled visits and is unable to be contacted by the study site.
The following actions must be taken if a participant fails to return to the clinic for a required 
study visit:

The site must attempt to contact the participant and reschedule the missed visit as 
soon as possible and counsel the participant on the importance of maintaining the 
assigned visit schedule and ascertain whether or not the participant wishes to and/or 
should continue in the study;

Before a participant is deemed lost to follow-up, the investigator or designee must 
make every effort to regain contact with the participant (where possible, 3 telephone 
calls and, if necessary, a certified letter to the participant’s last known mailing 
address or local equivalent methods). These contact attempts should be documented 
in the participant’s medical record;

The investigator should inquire about the reason for withdrawal, request that the 
participant return all unused investigational product(s), request that the participant
return for a final visit, if applicable, and follow up with the participant regarding any 
unresolved adverse events (AEs);

Should the participant continue to be unreachable, he/she will be considered to have 
withdrawn from the study. 
Discontinuation of specific sites or of the study as a whole is handled as part of Appendix 1.
8. STUDY ASSESSMENTS AND PROCEDURES
The investigator (or an appropriate delegate at the investigator site) must obtain a signed and 
dated ICD before performing any study-specific procedures.
Study procedures and their timing are summarized in the SoA. Protocol waivers or 
exemptions are not allowed.
Immediate safety concerns should be discussed with the sponsor immediately upon 
occurrence or awareness to determine if the participant should continue or discontinue study 
intervention.
Adherence to the study design requirements, including those specified in the SoA, is essential 
and required for study conduct.


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All screening evaluations must be completed and reviewed to confirm that potential 
participants meet all eligibility criteria. The investigator will maintain a screening log to 
record details of all participants screened and to confirm eligibility or record reasons for 
screening failure, as applicable.
Every effort should be made to ensure that protocol-required tests and procedures are 
completed as described.  However, it is anticipated that from time to time there may be 
circumstances outside the control of the investigator that may make it unfeasible to perform 
the test.  In these cases, the investigator must take all steps necessary to ensure the safety and 
well-being of the participant.  When a protocol-required test cannot be performed, the 
investigator will document the reason for the missed test and any corrective and preventive 
actions that he or she has taken to ensure that required processes are adhered to as soon as 
possible.  The study team must be informed of these incidents in a timely manner.
For samples being collected and shipped, detailed collection, processing, storage, and 
shipment instructions and contact information will be provided to the investigator site prior 
to initiation of the study.
The total blood sampling volume for individual participants will be outlined in the Lab 
Manual.  Additional blood samples may be taken for safety assessments at times specified by 
Sponsor, provided the total volume taken during the study does not exceed 550 mL during 
any period of 60 consecutive days.
8.1. Efficacy Assessments
Measures of psoriasis efficacy that will be collected throughout the study are outlined in this 
section.  These efficacy measures will be evaluated by an experienced physician, 
dermatologist, or qualified medical professional and should be performed by the same 
clinician throughout the study whenever possible.
Detailed descriptions for the PGA and patient reported outcomes (PROs) are provided in 
Appendices 10-17.
8.1.1. Psoriasis Area and Severity Index (PASI)
The Psoriasis Area and Severity Index quantifies the severity of a participant’s psoriasis 
based on both lesion severity and the percentage of body surface area affected.
Lesion severity: the basic characteristics of psoriatic lesions – erythema, induration and 
scaling – provide a means for assessing the severity of lesions.  Assessment of these three 
main signs is performed separately for four areas of the body: head, upper limbs, trunk, and 
lower limbs.  Average erythema, induration and scaling are rated for each body area 
according to a 5-point scale: 0, no involvement; 1, slight; 2, moderate; 3, marked; 4, very 
marked.


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Body surface area (BSA) involvement: the extent (%) to which each of the four areas of the 
body is affected by psoriasis is assigned a numerical score according to the following area 
scoring criteria: 0, no involvement; 1, >0 to 9%; 2, 10 to 29%; 3, 30 to 49%; 4, 50 to 69%; 
5, 70 to 89%; 6, 90 to 100%.
Component Scoring Criteria for the Psoriasis Area and Severity Index (PASI)
Component Score
Description
Erythema (E)
0
No involvement
None; may have residual hyperpigmentation
1
Slight
Pink or light red
2
Moderate
Darker pink-red
3
Marked
Red
4
Very Marked
Extremely red, “beefy” red
Induration (I)
0
No involvement
None
1
Slight
Minimal elevation relative to normal surrounding skin
2
Moderate
Easily palpable with rounded edges
3
Marked
Elevated with hard, sharp borders
4
Very Marked
Very elevated with very hard, sharp borders
Scaling (S)
0
No involvement
None
1
Slight
Mainly fine scale, some lesion partially covered
2
Moderate
Coarser thin scale, most lesions partially covered
3
Marked
Coarser thick scale, nearly all lesions covered, rough
4
Very Marked
Very thick scale, all lesions covered, very rough
Percent BSA with Psoriasis: the extent (%) to which each of the four body regions is 
involved with psoriasis is categorized using a non-linear scaling method to a numerical area 
score according to the following BSA scoring criteria (Table 4). 
Table 4.
Psoriasis Area and Severity Index (PASI) Area Score Criteria
Percent Body Surface Area 
(BSA) with Psoriasis
Area Score
0% (no involvement)
0
>0-9%
1
10-29%
2
30-49%
3
50-69%
4
70-89%
5
90-100%
6


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Calculating PASI
Body Region Weighting: each body region is weighted according to its approximate 
percentage of the whole body (Table 5).
Table 5.
Psoriasis Area and Severity Index (PASI) Area Score Criteria
Body Region
Body Region Weighting
Head and Neck
0.1
Upper Limbs
0.2
Trunk (including axillae and groin)
0.3
Lower Limbs (including buttocks)
0.4
In each body region, the sum of the Severity Scores for erythema, induration and scaling is 
multiplied by the Area Score and by the Body Region Weighting to provide a body region 
value, which is then summed across all four body regions resulting in a PASI score as 
described in the following equation: 
PASI =
0.1Ah(Eh + Ih + Sh) + 0.2Au(Eu + Iu + Su) +
0.3At(Et + It + St) + 0.4Al(El + Il + Sl)
where A = Area Score; E = erythema; I =induration; S = scaling; h = head; u = upper limbs; t = trunk; 
l = lower limbs.
The PASI score can vary in increments of 0.1 units from 0.0 to 72.0, with higher scores 
representing increasing severity of psoriasis.  The PASI score will be used for the primary 
analysis.
Calculation of PASI will be done centrally by sponsor programmers.
Linear Method Psoriasis Area and Severity Index (L PASI)
A second method of calculating PASI will also be performed.  A linear scaling method will 
be applied to the Psoriasis Area and Severity Index calculation, adapting the classic 
calculation by using the actual percentage body surface area involved in psoriasis rather than 
categorizing the percentage involvement on a 7 point scale. 
The linear scaling method will be calculated from the study database; investigator sites will 
only perform the classic PASI calculation during the study.  The L PASI score will be used 
for a sensitivity analysis.
L-PASI Calculation
L-PASI =
0.1(6xBh)x(Eh + Ih + Sh) + 0.2(6Bu)x(Eu + Iu + Su) +
0.3(6xBt)x(Et + It + St) + 0.4(6xBl)x(El + Il + Sl)
where B = percentage area of involvement; E = erythema; I =induration; S = scaling; h = head; u = upper 
limbs; t = trunk; l = lower limbs


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8.1.2. Physician Global Assessment (PGA)
The Physician Global Assessment of psoriasis is 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 are rated separately over the whole body according to a 
5-point severity scale, scored from 0 to 4, with appropriate morphologic descriptors.  The 
severity rating scores are summed and the average taken – the total average is rounded to the 
nearest whole number score to determine the PGA (See Appendix 17).
The 5-point scale for PGA is: 0, “clear”; 1, “almost clear”; 2, “mild”; 3, “moderate”; 
4 “severe” (Table 7).
Table 6.
Component Scoring Criteria for the Physician's Global Assessment (PGA)
Score
Description
Erythema (E)
0
No evidence of erythema (post-inflammatory hyperpigmentation 
and/or hypopigmentation may be present)
1
Light pink
2
Light red
3
Red
4
Dark, deep red
Induration (I)
0
No evidence of plaque elevation
1
Barely palpable
2
Slight, but definite elevation, indistinct edges
3
Elevated with distinct edges
4
Marked plaque elevation, hard/sharp borders
Scaling (S)
0
No evidence of scaling
1
Occasional fine scale
2
Fine scale predominates
3
Coarse scale predominates
4
Thick, coarse scale predominates


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Table 7.
Physician's Global Assessment (PGA) Score
Physician’s Global Assessment
Description
0
Clear
Cleared, except for any residual discoloration
1
Almost Clear
Majority of lesions have individual scores for (E + I 
+ S)/3 that rounds to 1
2
Mild
Majority of lesions have individual scores for (E + I 
+ S)/3 that rounds to 2
3
Moderate
Majority of lesions have individual scores for (E + I 
+ S)/3 that rounds to 3
4
Severe
Majority of lesions have individual scores for (E + I 
+ S)/3 that rounds to 4
Note: Calculated arithmetic average of individual signs severity scores [(E + I + S)/3] is 
rounded to the nearest whole number score (eg, if total ≤2.49, score = 2; if total ≥2.50, 
score = 3).  Calculation will be done centrally by sponsor programmers.
 
 
 
 
 
 
 
 
 
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8.1.4. Rater Qualifications 
For specific rating assessments, only qualified raters will be allowed to evaluate and/or rate 
participants in this study.  The minimum qualifications a rater must meet for each study 
rating assessment will be outlined in the Rater Assessment Manual provided to each 
participating site.  The level of experience with the target population (or equivalent), specific 
scale experience (or equivalent), and certification required (if applicable) will be listed and 
used to determine whether a rater is approved for a given assessment.  Proposed raters who 
do not meet specific criteria but who may be qualified based on unique circumstances may be 
individually reviewed by the study clinical team to determine whether or not a waiver may be 
issued.  The rater must become certified to perform selected study assessments before they
can participate in the conduct of the study.  For specifically defined assessments, rater 
training and standardization exercises may be conducted, and written and signed 
documentation will be provided by the site for each rater’s certification.  In return, each site 
will be provided written and signed documentation outlining each rater’s certification for 
specific study assessments.  Recertification may be required at periodic intervals during the 
study.  The raters who administer specific study assessments will be documented in a 
centralized location and all site staff who administer ratings will be verified in the site study 
documentation during the conduct of the study.
8.2. Safety Assessments
Planned time points for all safety assessments are provided in the SoA.  Unscheduled clinical 
laboratory measurements may be obtained at any time during the study to assess any 
perceived safety concerns.
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8.2.1. Assessments at Screening only
8.2.1.1. Tuberculosis (TB) Testing
Participants should be screened for TB using an Interferon gamma release assay (IGRA) per 
local guidelines.  IGRA will be tested during screening or within 12 weeks prior to 
Screening.  The following are acceptable IGRA assays:  T SPOT® TB test (preferable, where 
available), QuantiFERON® TB Gold In Tube test (QFT GIT) and QuantiFERON® TB Gold 
test (QFT G).  Site personnel should follow the processing and analyses steps based on the 
assay chosen.  Ensure incubation steps are followed as appropriate.   
Documentation of IGRA product used and the test result must be in the participant’s source 
documentation.
If the results of the IGRA are indeterminate, the test may be repeated once, and if a negative 
result is obtained, enrollment may proceed.  A positive test on repeat is exclusionary.
Participants with repeat indeterminate IGRA results may be enrolled after consultation with 
pulmonary or infectious disease specialist that determines low risk of infection (ie, 
participant would be acceptable for immunosuppressant (eg, anti-TNF tumor necrosis factor) 
treatment without additional action).
Participants who test positive for QFT-G/QFT-GIT test, but in the opinion of the PI are at 
low risk of TB infection may be referred to pulmonary or infectious disease specialist for 
consultation and potential IGRA test repeated once. Participants will be eligible if the repeat 
test is negative before the randomization.
8.2.1.2. Chest Radiograph
Participants must have chest radiograph taken at Screening and read by a qualified 
radiologist.  Documentation of the official reading must be located and available in the 
source documentation.
If chest radiograph has been taken within 12 weeks prior to Day 1 and read by a qualified 
radiologist as normal, this does not have to be repeated at screening, provided documentation 
is available.
Chest radiograph may include chest x-ray (posterior-anterior and lateral views are 
recommended, however local guidelines should be followed) or other appropriate diagnostic 
image (ie, computed tomography or magnetic resonance imaging [MRI]). Participants with 
evidence of currently active TB, general infections, heart failure or malignancy will be 
excluded.  Participants with changes suggestive of untreated latent or active TB infection 
may be enrolled after consultation with a pulmonary or infectious disease specialist who 
determines a low risk of infection.


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8.2.1.3. Medical History
Investigators should make all reasonable efforts to obtain an accurate and complete medical 
history and history of prior medication use when evaluating whether a participant is eligible 
for the study.  The following will be collected at Screening: complete medical history, 
psoriasis disease history (including disease duration and prior treatments), and alcohol and 
tobacco use history.
If the status of a participant’s medical history is in doubt or information pertaining to a 
critical variable is conflicting, every reasonable step to secure proper documentation of 
correct medical status should be attempted.  Documentation of the medical and medication 
histories over the protocol defined time periods should be available for sponsor review 
during the source data verification process.  Questions about prior medications or eligibility 
should be directed to the sponsor clinician or sponsor medical monitor.
8.2.1.4. Suicidal Ideation and Behavior Risk Monitoring
The Columbia Suicide Severity Rating Scale (C-SSRS Appendix 9) is a validated tool to 
evaluate suicidal ideation and behavior.11 At the screening and baseline visit, if there are 
“yes” answers on items 4, 5 in the past year, or on any question in the suicidal behavior 
section of the C-SSRS in the past 5 years, the participant will be excluded from the study.
8.2.2. Assessment During Study
8.2.2.1. Full Physical and Brief Physical Examinations
Full physical examinations must be performed by the investigator, sub-investigator, or a 
qualified healthcare professional per local guidelines.  A full physical examination will 
include assessments of the general appearance, skin, head, eyes, ears, nose, throat, 
cardiovascular, respiratory (lung), gastrointestinal, and neurological systems.  Investigators 
should pay special attention to clinical signs related to previous serious illnesses.
A brief examination will include assessments of the skin (both psoriasis and non-psoriasis 
skin) and body systems with any symptoms reported by the study participants. 
Any clinically significant changes from the most recent physical examination should be 
recorded as adverse events (AEs).  Investigators should pay special attention to clinical signs 
related to previous serious illnesses.
Full and brief physical exams will be performed as specified in Schedule of Activities.
8.2.2.2. Weight and Height
It is recommended that weight be measured in kilograms (kg) and that height be measured in 
centimeters (cm).  Height and weight will be measured to one decimal place.
For measuring weight, a scale with appropriate range and resolution should be used and must 
be placed on a stable, flat surface.  Participants should remove shoes, bulky layers of 
clothing, and jackets so that only light clothing remains. 


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8.2.2.3. Vital Signs (Blood pressure, pulse rate, and temperature)
Single sitting blood pressure (BP), pulse rate, and temperature will be measured at times 
specified in the Schedule of Activities.  Additional collection times or changes to collection 
times will be permitted, as necessary to ensure appropriate collection of safety data.
Vital signs should be performed before laboratory blood collection after at least 5 minutes 
rest. 
Sitting blood pressure (preferred but not required) will be measured with the participant’s 
arm supported at the level of the heart and recorded to the nearest mm Hg.  It is preferred that 
the same arm be used throughout the study.
The same size BP cuff, which has been properly sized and calibrated, will be used to measure 
BP each time.  The use of automated devices for measuring BP and pulse rate is acceptable, 
although, when done manually, pulse rate will be measured in the brachial/radial artery for at 
least 30 seconds.  When the timing of these measurements coincides with a blood collection, 
it is preferred that vital signs be obtained prior to the nominal time of blood collection.
Body temperature may be collected using tympanic, oral (preferred), or axillary methods and 
that the same method be used consistently throughout the study.
8.2.3. Electrocardiograms
Six singlicate standard 12-Lead ECGs should be collected at times specified in the SoA
section of this protocol using an ECG machine that automatically calculates the heart rate and 
measures pulse rate (PR), QT, and QTc intervals and QRS complex.  All scheduled ECGs 
should be performed after the participant has rested quietly for at least 10 minutes.  
Consistent methods across visits is recommended.
ECGs should be performed before laboratory blood collection, BP, and pulse rate.
To ensure safety of the participants, a qualified individual (eg, sub-investigator) at the 
investigator site will make comparisons to baseline measurements taken at baseline.  A copy 
of the ECG should be available as source documents for review.  ECGs will be read locally 
during the dosing period.
If a postdose QTc interval remains ≥30 msec from the baseline and is >450 msec; or b) an 
absolute QTc value is ≥500 msec for any scheduled ECG for greater than 4 hours (or sooner,
at the discretion of the investigator), or QTc intervals get progressively longer, the participant
should undergo continuous ECG monitoring.  A cardiologist should be consulted if QTc 
intervals do not return to less than the criterion listed above after 8 hours of monitoring (or 
sooner, at the discretion of the investigator). 


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In some cases, it may be appropriate to repeat abnormal ECGs to rule out improper lead 
placement as contributing to the ECG abnormality.  It is important that leads be placed in the 
same positions each time in order to achieve precise ECG recordings.  If a machine-read QTc 
value is prolonged, as defined above, repeat measurements may not be necessary if a 
qualified medical provider’s interpretation determines that the QTc values are in the 
acceptable range.
ECG values of potential clinical concern are listed in Appendix 7.
8.2.4. Clinical Safety Laboratory Assessments
See Appendix 2 for the list of clinical safety laboratory tests to be performed and the SoA for 
the timing and frequency.
The investigator must review the laboratory report, document this review, and record any 
clinically relevant changes occurring during the study in the AE section of the CRF.  
Clinically significant abnormal laboratory findings are those which are not associated with 
the underlying disease, unless judged by the investigator to be more severe than expected for 
the participant's condition.
All laboratory tests with values considered clinically significantly abnormal during 
participation in the study or within 28 days after the last dose of study intervention should be 
repeated until the values return to normal or baseline or are no longer considered clinically 
significant by the investigator or medical monitor.
If such values do not return to normal/baseline within a period judged reasonable by the 
investigator, the etiology should be identified, and the sponsor notified.
All protocol-required laboratory assessments, as defined in Appendix 2, must be conducted 
in accordance with the laboratory manual and the SoA.
If laboratory values from non-protocol-specified laboratory assessments performed at the 
institution’s local laboratory require a change in participant management or are considered 
clinically significant by the investigator (eg, SAE or AE or dose modification), then the 
results must be recorded in the CRF.
8.2.5. Suicidal Ideation and Behavior Risk Monitoring 
Participants meeting exclusionary criteria (Section 5.2) for suicidal ideation/behavior will be 
excluded from study participation.  It is recommended the participant’s primary care 
physician (PCP) is informed if this exclusion criterion is met, and the participant referred to a 
mental health professional, either by the PCP or the investigator according to their usual 
practice.


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8.2.5.1. Columbia Suicide Severity Rating Scale 
The Columbia Suicide Severity Rating Scale (C-SSRS)11 is a validated tool to evaluate 
suicidal ideation and behavior (Appendix 9).  “Lifetime” version will be used at screening 
and baseline and the “since last visit” version will be used in all subsequent visits.
If at any visit, there are “YES” answers on items 4, 5 or on any behavioral question of the 
C-SSRS, a risk assessment should be done immediately by a qualified medical health 
practitioner for appropriate evaluation and treatment.  If the participant cannot be seen by a 
mental health professional within 24 hours, then the participant should be sent to a local 
emergency room for psychiatric assessment.  If these answers occurred after IP dosing
(ie, post-Day 1), IP will be temporarily discontinued until further evaluation.  This evaluation 
will help determine whether it is safe for the participant to continue to participate in the trial.  
Participants who answer “YES” on items 4, 5 or on any behavioral question of the C-SSRS 
on more than one occasion during a trial will be discontinued from the trial.
8.2.6. Herpetiform Rash Surveillance 
For any occurrence of a suspected herpetiform rash (eg, herpes zoster and herpes simplex), 
specimens for viral deoxyribonucleic acid (DNA) analysis will be obtained: A swab of the 
affected area will be collected for confirmation; a blood sample for viral surveillance will be 
collected for the analysis of viral load.  Details for these collections will be provided in the 
laboratory manual.
8.2.7. Glomerular Filtration Rate
Serum creatinine is the best known standard test for monitoring renal function.  Serum 
creatinine will be measured as part of serum chemistry at times specified in the Schedule of 
Activities section of the protocol.  Serum creatinine elevations above the ULN will be 
followed until resolution or baseline.  Serum creatinine based eGFR will be calculated.  
eGFR will be calculated at corresponding times per Schedule of Activities. 
The eGFR will be calculated using the equation developed by the Chronic Kidney Disease 
Epidemiology Collaboration (CKD-EPI).12
8.2.8. Pregnancy Testing
Pregnancy tests may be urine or serum tests, as indicated in SoA, but must have a sensitivity 
of at least 25 mIU/mL.  Pregnancy tests will be performed in women of child-bearing 
potential (WOCBP) at the times listed in the SoA.  Following a negative pregnancy test result 
at screening, appropriate contraception must be commenced, and a second negative 
pregnancy test result will be required at the baseline visit prior the participant’s receiving the 
investigational product.  Pregnancy tests will also be done whenever 1 menstrual cycle is 
missed during the active treatment period (or when potential pregnancy is otherwise 
suspected) and at the end of the study.  Pregnancy tests may also be repeated if requested by 
institutional review boards (IRBs)/ethics committees (ECs) or if required by local 
regulations.  If a urine test cannot be confirmed as negative (eg, an ambiguous result), a 
serum pregnancy test is required.  In such cases, the participant must be excluded if the 
serum pregnancy result is positive.


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8.3. Adverse Events and Serious Adverse Events
The definitions of an AE and an SAE can be found in Appendix 3.
AEs will be reported by the participant (or, when appropriate, by a caregiver, surrogate, or 
the participant's legally authorized representative).
The investigator and any qualified designees are responsible for detecting, documenting, and 
recording events that meet the definition of an AE or SAE and remain responsible to pursue 
and obtain adequate information both to determine the outcome and to assess whether it 
meets the criteria for classification as an SAE or that caused the participant to discontinue the 
PF-06826647 (see Section 7). 
In addition, the investigator may be requested by Pfizer Safety to obtain specific follow-up 
information in an expedited fashion.
8.3.1. Time Period and Frequency for Collecting AE and SAE Information
The time period for actively eliciting and collecting AEs and SAEs (“active collection 
period”) for each participant begins from the time the participant provides informed consent, 
which is obtained before the participant’s participation in the study (ie, before undergoing 
any study-related procedure and/or receiving investigational product), through and including 
a minimum of 28 calendar days, except as indicated below, after the last administration of the 
investigational product.
For participants who are screen failures, the active collection period ends when screen failure 
status is determined.
Medical occurrences that begin before the start of study intervention but after obtaining 
informed consent will be recorded on the Medical History/Current Medical Conditions 
section of the case report form (CRF), not the AE section.
Follow-up by the investigator continues throughout and after the active collection period and 
until the event or its sequelae resolve or stabilize at a level acceptable to the investigator, and 
Pfizer concurs with that assessment.
Investigators are not obligated to actively seek AEs or SAEs after conclusion of the study 
participation.  However, if the investigator learns of any SAE, including a death, at any time 
after a participant has been discharged from the study, and he/she considers the event to be 
reasonably related to the study intervention or study participation, the investigator must 
promptly notify the sponsor.
8.3.1.1. Reporting SAEs to Pfizer Safety
All SAEs occurring in a participant during the active collection period are reported to Pfizer 
Safety on the CT SAE Report Form immediately and under no circumstance should this 
exceed 24 hours, as indicated in Appendix 3. The investigator will submit any updated SAE 
data to the sponsor within 24 hours of it being available.


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SAEs occurring in a participant after the active collection period has ended are reported to 
Pfizer Safety if the investigator becomes aware of them; at a minimum, all SAEs that the 
investigator believes have at least a reasonable possibility of being related to investigational 
product must be reported to Pfizer Safety.
8.3.1.2. Recording Nonserious AEs and SAEs on the CRF
During the active collection period, both nonserious AEs and SAEs are recorded on the CRF.
8.3.2. Method of Detecting AEs and SAEs
The method of recording, evaluating, and assessing causality of AEs and SAEs and the 
procedures for completing and transmitting SAE reports are provided in Appendix 3.
Care will be taken not to introduce bias when detecting AEs and/or SAEs.  Open-ended and 
nonleading verbal questioning of the participant is the preferred method to inquire about 
AE occurrences.
8.3.3. Follow-up of AEs and SAEs
After the initial AE/SAE report, the investigator is required to proactively follow each 
participant at subsequent visits/contacts. For each event, the investigator must pursue and 
obtain adequate information until resolution, stabilization, the event is otherwise explained, 
or the participant is lost to follow-up (as defined in Section 7.3).
In general, follow-up information will include a description of the event in sufficient detail to 
allow for a complete medical assessment of the case and independent determination of 
possible causality.  Any information relevant to the event, such as concomitant medications 
and illnesses, must be provided.  In the case of a participant death, a summary of available 
autopsy findings must be submitted as soon as possible to Pfizer Safety. 
Further information on follow-up procedures is given in Appendix 3.
8.3.4. Regulatory Reporting Requirements for SAEs
Prompt notification by the investigator to the sponsor of an SAE is essential so that legal 
obligations and ethical responsibilities towards the safety of participants and the safety of a 
study intervention under clinical investigation are met.
The sponsor has a legal responsibility to notify both the local regulatory authority and other 
regulatory agencies about the safety of a study intervention under clinical investigation.  The 
sponsor will comply with country-specific regulatory requirements relating to safety 
reporting to the regulatory authority, institutional review boards (IRBs)/ethics committees 
(ECs), and investigators.
Investigator safety reports must be prepared for suspected unexpected serious adverse 
reactions (SUSARs) according to local regulatory requirements and sponsor policy and 
forwarded to investigators as necessary.


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An investigator who receives an investigator safety report describing an SAE or other 
specific safety information (eg, summary or listing of SAEs) from the sponsor will review 
and then file it along with the investigator’s brochure and will notify the IRB/EC, if 
appropriate according to local requirements.
8.3.5. Exposure During Pregnancy or Breastfeeding, and Occupational Exposure
Exposure to the investigational product under study during pregnancy or breastfeeding and 
occupational exposure are reportable to Pfizer Safety within 24 hours of investigator 
awareness.
8.3.5.1. Exposure During Pregnancy
Details of all pregnancies in female participants and, if indicated, female partners of male 
participants will be collected after the start of study intervention and until at least 5 terminal 
half-lives or approximately 7 to 11 days after the last dose.
If a pregnancy is reported, the investigator should inform the sponsor within [24 hours] of 
learning of the pregnancy and should follow the procedures outlined in Appendix 4.
Abnormal pregnancy outcomes (eg, spontaneous abortion, fetal death, stillbirth, congenital 
anomalies, ectopic pregnancy) are considered SAEs.
8.3.5.2. Exposure During Breastfeeding
Scenarios of exposure during breastfeeding must be reported, irrespective of the presence of 
an associated SAE, to Pfizer Safety within 24 hours of the investigator’s awareness, using the 
CT SAE Report Form.  An exposure during breastfeeding report is not created when a Pfizer 
drug specifically approved for use in breastfeeding women (eg, vitamins) is administered in 
accord with authorized use.  However, if the infant experiences an SAE associated with such 
a drug’s administration, the SAE is reported together with the exposure during breastfeeding.
8.3.5.3. Occupational Exposure
An occupational exposure occurs when, during the performance of job duties, a person 
(whether a healthcare professional or otherwise) gets in unplanned direct contact with the 
product, which may or may not lead to the occurrence of an AE.
An occupational exposure is reported to Pfizer Safety within 24 hours of the investigator’s 
awareness, using the CT SAE Report Form, regardless of whether there is an associated 
SAE.  Since the information does not pertain to a participant enrolled in the study, the 
information is not recorded on a CRF; however, a copy of the completed CT SAE Report 
Form is maintained in the investigator site file.
8.3.6. Medication Errors
Medication errors may result from the administration or consumption of the investigational 
product by the wrong participant, or at the wrong time, or at the wrong dosage strength.


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Exposures to the investigational product under study may occur in clinical trial settings, such 
as medication errors.
Safety Event
Recorded on the CRF
Reported on the CT SAE Report 
Form to Pfizer Safety Within 
24 Hours of Awareness
Medication errors 
All (regardless of whether 
associated with an AE)
Only if associated with an SAE
Medication errors include:
•
Medication errors involving participant exposure to the investigational product;
•
Potential medication errors or uses outside of what is foreseen in the protocol that do 
or do not involve the study participant.
Such medication errors occurring to a study participant are to be captured on the medication 
error page of the CRF, which is a specific version of the AE page.
In the event of a medication dosing error, the sponsor should be notified immediately.
Whether or not the medication error is accompanied by an AE, as determined by the 
investigator, the medication error is recorded on the medication error page of the CRF and, if 
applicable, any associated AE(s), serious and nonserious, are recorded on an AE page of the 
CRF. 
Medication errors should be reported to Pfizer Safety within 24 hours on a CT SAE Report 
Form only when associated with an SAE.
8.4. Treatment of Overdose
For this study, any dose of PF-06826647 greater than 1600 mg of investigational product
within a 24-hour time period will be considered an overdose.
Sponsor does not recommend specific treatment for an overdose.
In the event of an overdose, the investigator should:
1. Contact the medical monitor immediately.
2. Closely monitor the participant for any AEs/SAEs and laboratory abnormalities until 
PF-06826647 can no longer be detected systemically (at least 3 days).
 
 
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4. Document the quantity of the excess dose as well as the duration of the overdose in 
the CRF.
5. Overdose is reportable to Safety only when associated with an SAE.
Decisions regarding dose interruptions or modifications will be made by the investigator in 
consultation with the medical monitor based on the clinical evaluation of the participant.
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
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Unless prohibited by local regulations or IRB/EC decision, participants will be asked to 
indicate on the consent document whether they will allow their banked samples to also be 
used to design and conduct research in order to gain a further understanding of other diseases 
and to advance science, including development of other medicines for patients.  This 
component of the sampling banking is optional for participants; they may still participate in 
the study even if they do not agree to the additional research on their banked samples.  The 
optional additional research does not require the collection of any further samples.
See Appendix 5 for information regarding genetic research. Details on processes for 
collection and shipment of these samples can be found in the laboratory manual. 
8.9. Health Economics
Medical resource utilization is not evaluated in this study.  However, the study does include 
the EQ5D-5L, a questionnaire that assesses patient preference for a given health state and 
which will be utilized for cost-effectiveness/utility modeling.  The EQ5D-5L is summarized 
below in the patient reported outcomes measures section. 
8.10. Patient Reported Outcome Measures
Every effort should be made for the participant to complete all patient reported outcome 
(PRO) questionnaires before any other assessments except at Baseline when eligibility needs 
to be confirmed.  All PROs should be completed in the following order: Psoriasis Symptom 
Inventory (PSI), Peak-Pruritus Numerical Rating Scale (PP-NRS), 
 
 will be completed as a diary from baseline to Day 15.  Post Day 15, these scales 
will be completed at the site.  At site visits participants will complete PROs in the following 
order: Psoriasis Symptom Inventory (PSI), PP-NRS,
 
 
 The amount 
of time required for a participant to complete the PRO questionnaires is approximately 
10-25 minutes (depending on the visit and associated PROs). 
Once participants meet all eligibility criteria, they will be provided a handheld device 
(provided by the sponsor) for the PSI (both 24-hour recall and 7-day recall), PP-NRS, a
 
to be completed at home prior to first dose of the day.  .  All PROs are 
to be completed as per the time points defined in the Schedule of Activities. 
Delegated site staff will oversee the use of electronic Patient Reported Outcomes (ePRO) 
devices.  Completion of PROs will be monitored for adherence.  Delegated site staff will 
review adherence to all applicable PROs with participants at each visit and counsel as 
appropriate.  If a participant has repeated non-adherence, the participant should be retrained 
on use of the device.  If a participant is unable to complete ePROs due to documented 
technical issue or disability or other limitation (eg, difficulty with manual dexterity or 
vision), the participant will be permitted to enter or remain in the study and a valid alternate 
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source of data entry is completed and reviewed by investigational site staff.  This may 
include for example reading the questions verbatim to the participant and entering participant 
selection of responses by the site staff.
8.10.1. Psoriasis Symptom Inventory
The Psoriasis Symptom Inventory (PSI) is a self-administered 8 item questionnaire that 
measures the severity of psoriasis symptoms over the past 24 hours and the past 7 days
(Appendix 10).13  For the first 2 weeks up to Week 2 visit (inclusive), the PSI will be 
administered daily using a recall period of 24 hours.  After Week 2 visit, the PSI will be 
administered according to the Schedule of Activities using a recall period of past 7 days.  The 
measure includes concepts of itch, pain, burning, stinging, cracking, scaling, flaking, and 
redness.  Participants are asked to respond to each item using a 5-point Likert response scale: 
0: not all severe, 1: mild, 2: moderate, 3: severe and 4: very severe.  PSI should be completed
as described in the Schedule of Activities.
8.10.2. Peak-Pruritus Numerical Rating Scale
The intensity of pruritus will be assessed by a Peak-Pruritus Numerical Rating Scale 
(PP-NRS), an 11-category numeric rating scale from 0 to 10, which is patient reported 
(Appendix 11)14,15  Participants will be asked to assess their itch over the past 24 hours, 
anchored by the terms “no itch” (0) and “worst itch imaginable” (10) at the ends. 
 
 
 
  
 
 
 
  
 
 
 
 
 
 
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9. STATISTICAL CONSIDERATIONS
Detailed methodology for summary and statistical analyses of the data collected in this study 
is outlined here and further detailed in a statistical analysis plan (SAP), which will be 
maintained by the sponsor.  The SAP may modify what is outlined in the protocol where 
appropriate; however, any major modifications of the primary endpoint definitions or their 
analyses will also be reflected in a protocol amendment.
9.1. Estimands and Statistical Hypotheses
9.1.1. Estimands
The primary estimand will be the population average treatment effect on PASI 90 rates at 
Week 16 relative to placebo without regard to compliance in the absence of prohibited 
medication.  Measurements after the initiation of prohibited medication will be censored and 
treated as missing data.  Missing data due to censoring, study withdrawal or other reasons 
will have data imputed using a control based multiple imputation strategy assuming these 
participants no longer receive an efficacy benefit from the IP but rather, have a response 
similar to participants assigned to placebo.  The population based treatment effect will be the 
differences in the proportions of successes in each treatment arm compared to the 
corresponding placebo.
All other secondary continuous clinical endpoints will be analyzed using estimand E2, while 
all other key secondary categorical clinical endpoints will be analyzed using the primary 
estimand E1 as described above.  
 
Other estimands may be used for some of the primary and 
secondary endpoints as a means to examine the robustness of the results and to compare to 
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available literature as needed.  Details of these analyses will be presented in the statistical 
analysis plan (SAP).
9.2. Sample Size Determination
The primary endpoint in this study is the PASI 90 response rate at Week 16.  Assuming a 
PASI 90 response rate as 5% for the placebo group, and placebo corrected effect 35% or 
greater for one of the treatment groups, a total of N=128 completers are needed to ensure at 
least 90% power for the lower doses due to Bonferroni multiplicity adjustment with 1-sided 
type-I error rate of 5% and 2:1:1:2:2 allocation ratio of placebo, 50 mg, 100 mg, 200 mg, and 
400 mg.  The total sample size includes a sample size of 32 completers per arm for placebo, 
200 mg and 400 mg, and 16 completers per arm for 50 mg and 100 mg.  Accounting for a 
20% chance of drop out, approximately a total of 160 participants will be enrolled in this 
study.
9.3. Populations for Analysis
For purposes of analysis, the following populations are defined:
Population
Description
Safety Analysis Set
All participants randomly assigned to IP and who take at least 
1 dose of IP.  Participants will be analyzed according to the 
product they actually received.
Defined Population for 
Analysis
Description
Modified Intention to 
Treat (mITT)
All participants randomly assigned to IP and who take at least 
1 dose of IP.  
 
9.4. Statistical Analyses
The SAP will be developed and finalized before database lock and will describe the 
participant populations to be included in the analyses, and procedures for accounting for 
missing, unused, and spurious data.  This section is a summary of the planned statistical 
analyses of the primary and secondary endpoints.
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9.4.1. Efficacy Analyses
Endpoint
Statistical Analysis Methods
Primary and 
key 
secondary: 
PASI 90 and 
PASI 75 at 
Week 16
A landmark analysis of the composite endpoint; achieving a PASI 90 
response (a score of 90% improvement from Baseline) without prohibited 
medication, while remaining on study and providing data.  The analysis will 
use the mITT analysis set.  Based on the definition of the composite 
endpoint all participants in the mITT set will have a response for all visits 
(ie, there is no missing data).  The proportions responding and the risk 
difference between treated arms and their corresponding placebo arm will be 
analyzed using an unconditional exact method: risk differences and 
corresponding 2-sided unconditional exact 90% confidence intervals will be 
computed using the Chan and Zhang (1999) method.  Multiplicity 
adjustment will be utilized; details of multiplicity adjustment will be 
provided in the SAP.
Other continuous secondary endpoints at time points specified in the Schedule of Activities
including; absolute PASI, change from baseline PASI, percent change from baseline PASI, 
absolute and change from baseline Itch Severity Score, absolute and change from baseline 
Psoriasis Symptom Inventory will be analyzed as described for the E2 estimand along with 
descriptive statistics and possibly graphical displays.  No adjustments for multiplicity will be 
made for these endpoints.
Other binary secondary endpoints at time points specified in the Schedule of Activities
including, PASI 50, PASI 100, PGA of clear or almost clear and proportions of participants 
achieving a Psoriasis Symptom Inventory Score of 0 or 1 will be analyzed as described for 
the primary estimand along with descriptive statistics and possibly graphical displays. No 
adjustments for multiplicity will be made for these endpoints.
 
All endpoints in Extension Treatment Period will be analyzed with descriptive statistics and 
graphical displays when appropriate.  Details of the analyses of the Investigational Treatment 
Period and Extension Treatment Period will be included in the Statistical Analysis Plan 
(SAP).
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9.4.2. Safety Analyses
All safety analyses will be performed on the safety population.
Endpoint
Statistical Analysis Methods
Primary
The safety data will be summarized in accordance with Pfizer Data 
Standards.  All participants who receive IP (safety population) will be 
included in the safety analyses.  All safety data will be summarized 
descriptively through appropriate data tabulations, descriptive statistics, 
categorical summaries, and graphical presentations.  Safety endpoints for the 
study include:
•
Treatment-emergent AEs and SAEs.
•
Withdrawals from active treatment due to AEs.
•
Serious infections, defined as any infection (viral, bacterial, and 
fungal) requiring hospitalization or parenteral antimicrobials.
•
Safety laboratory tests (eg, hematology [including coagulation 
panel], chemistry and lipid profiles).
•
Vital signs.
Change from baseline on laboratory data and vital signs will be additionally 
summarized.  Participant listings will also be produced for these safety 
endpoints.
 
9.4.2.1. Electrocardiogram Analyses
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 postdose 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
In addition, participants with QTcF values >500 msec will be listed.
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9.5. Interim Analyses
Interim analyses may be performed to assess efficacy and safety after at least 60% of the 
planned participants, ie, approximately 80 participants, complete their study participation 
through Week 12.  Interim analysis results will be used for internal business decisions 
regarding future study planning or stopping for futility.  Before the interim analysis is 
instigated, the details of the objectives, decision criteria, dissemination plan and method of 
maintaining the study blind as per Pfizer’s SOPs will be documented and approved in the
internal review committee (IRC) charter.  In addition, the analysis details will be documented 
and approved in an interim analysis SAP or final SAP.
9.5.1. Data Monitoring Committee 
This study will not use a data monitoring committee (DMC).  This study will use an internal 
review committee (IRC) which will be comprised of internal Pfizer experts, independent of 
the study team.
Members of the study team will not be part of the IRC.  An unblinded sponsor statistician or 
a clinician who is not directly involved with the study will perform the interim analyses and 
provide the results only to the IRC.  No randomization information for individual participants
will be reported to the IRC as part of the interim analysis; however, unblinded aggregate 
results will be reported.
The IRC will be responsible for evaluating safety of participants in the study according to the 
IRC Charter.  The recommendations made by the IRC to alter the conduct of the study will 
be forwarded to Pfizer for final decision.  Pfizer will forward such decisions, which may 
include summaries of aggregate analyses of endpoint events and of safety data that are not 
endpoints, to regulatory authorities, as appropriate.
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9.5.2. Safety Adjudication Committees
The identification of events requiring submission to an adjudication/review committee may 
be made by the study site and communicated to Pfizer or designee.  Events requiring review, 
including cardiovascular and venous thromboembolic events may also be identified by the 
Pfizer study team or designee during the review of subject data listings or by site monitors 
during routine monitoring of participant’s study records.  The Pfizer study team or designee 
will notify the study site of any events if identified. 
The Pfizer Study Team or designee will provide a listing of specific documents needed to 
support event adjudication by the Adjudication/Review Committees. Obtaining and 
submitting the documentation will be the responsibility of the study site. Event 
documentation will vary with the event requiring adjudication and may include (but not be 
limited to): hospital discharge summaries, operative reports, clinic notes, diagnostic tests, 
pathology reports, autopsy reports and death certificate information, as applicable.
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
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10. SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS
10.1. Appendix 1: Regulatory, Ethical, and Study Oversight Considerations
10.1.1. Regulatory and Ethical Considerations
This study will be conducted in accordance with the protocol and with the following:

Consensus ethical principles derived from international guidelines including the 
Declaration of Helsinki and Council for International Organizations of Medical 
Sciences (CIOMS) International Ethical Guidelines;

Applicable International Council for Harmonisation (ICH) Good Clinical Practice 
(GCP) guidelines;

Applicable laws and regulations, including applicable privacy laws.
The protocol, protocol amendments, ICD, investigator’s brochure (IB), and other relevant 
documents (eg, advertisements) must be reviewed and approved by the sponsor and 
submitted to an IRB/EC by the investigator and reviewed and approved by the IRB/EC 
before the study is initiated.
Any amendments to the protocol will require IRB/EC approval before implementation of 
changes made to the study design, except for changes necessary to eliminate an immediate 
hazard to study participants.
The investigator will be responsible for the following:

Providing written summaries of the status of the study to the IRB/EC annually or 
more frequently in accordance with the requirements, policies, and procedures 
established by the IRB/EC;

Notifying the IRB/EC of SAEs or other significant safety findings as required by 
IRB/EC procedures;

Providing oversight of the conduct of the study at the site and adherence to 
requirements of 21 Code of Federal Regulations (CFR), ICH guidelines, the IRB/EC, 
European regulation 536/2014 for clinical studies (if applicable), and all other 
applicable local regulations.
10.1.1.1. Reporting of Safety Issues and Serious Breaches of the Protocol or ICH GCP
In the event of any prohibition or restriction imposed (ie, clinical hold) by an applicable 
regulatory authority in any area of the world, or if the investigator is aware of any new 
information that might influence the evaluation of the benefits and risks of the investigational 
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In addition, the investigator will inform Sponsor immediately of any urgent safety measures 
taken by the investigator to protect the study participants against any immediate hazard, and 
of any serious breaches of this protocol or of ICH GCP that the investigator becomes aware 
of.
10.1.2. Financial Disclosure
Investigators and subinvestigators will provide the sponsor with sufficient, accurate financial 
information as requested to allow the sponsor to submit complete and accurate financial 
certification or disclosure statements to the appropriate regulatory authorities. Investigators 
are responsible for providing information on financial interests during the course of the study 
and for 1 year after completion of the study.
10.1.3. Informed Consent Process
The investigator or his/her representative will explain the nature of the study to the 
participant or his/her legally authorized representative and answer all questions regarding the 
study.
Participants must be informed that their participation is voluntary. Participants or their 
legally authorized representative will be required to sign a statement of informed consent that 
meets the requirements of 21 CFR 50, local regulations, ICH guidelines, Health Insurance 
Portability and Accountability Act (HIPAA) requirements, where applicable, and the IRB/EC 
or study center.
The investigator must ensure that each study participant is fully informed about the nature 
and objectives of the study, the sharing of data related to the study, and possible risks 
associated with participation, including the risks associated with the processing of the 
participant’s personal data. 
The participant must be informed that his/her personal study-related data will be used by the 
sponsor in accordance with local data protection law. The level of disclosure must also be 
explained to the participant.
The participant must be informed that his/her medical records may be examined by Clinical 
Quality Assurance auditors or other authorized personnel appointed by the sponsor, by 
appropriate IRB/EC members, and by inspectors from regulatory authorities.
The investigator further must ensure that each study participant is fully informed about his or 
her right to access and correct his or her personal data and to withdraw consent for the 
processing of his or her personal data.
The medical record must include a statement that written informed consent was obtained 
before the participant was enrolled in the study and the date the written consent was obtained.
The authorized person obtaining the informed consent must also sign the ICD.
Participants must be reconsented to the most current version of the ICD(s) during their 
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A copy of the ICD(s) must be provided to the participant or the participant’s legally 
authorized representative.
A participant who is rescreened is required to sign another ICD.
 
 
 
 
 
10.1.4. Data Protection
All parties will comply with all applicable laws, including laws regarding the implementation 
of organizational and technical measures to ensure protection of participant data.
Participants’ personal data will be stored at the study site in encrypted electronic and/or paper
form and will be password protected or secured in a locked room to ensure that only 
authorized study staff have access.  The study site will implement appropriate technical and 
organizational measures to ensure that the personal data can be recovered in the event of 
disaster.  In the event of a potential personal data breach, the study site shall be responsible 
for determining whether a personal data breach has in fact occurred and, if so, providing 
breach notifications as required by law.
To protect the rights and freedoms of natural persons with regard to the processing of 
personal data, participants will be assigned a single, participant-specific numerical code.
Any participant records or data sets that are transferred to the sponsor will contain the 
numerical code; participant names will not be transferred. All other identifiable data 
transferred to the sponsor will be identified by this single, participant-specific code. The 
study site will maintain a confidential list of participants who participated in the study, 
linking each participant’s numerical code to his or her actual identity. In case of data 
transfer, the sponsor will protect the confidentiality of participants’ personal data consistent 
with the clinical study agreement and applicable privacy laws.
10.1.5. Dissemination of Clinical Study Data
Pfizer fulfills its commitment to publicly disclose clinical study results through posting the 
results of studies on www.clinicaltrials.gov (ClinicalTrials.gov), the European Clinical Trials 
Database (EudraCT), and/or www.pfizer.com, and other public registries in accordance with 
applicable local laws/regulations.  In addition, Pfizer reports study results outside of the 
requirements of local laws/regulations pursuant to its standard operating procedures (SOPs).
In all cases, study results are reported by Pfizer in an objective, accurate, balanced, and 
complete manner and are reported regardless of the outcome of the study or the country in 
which the study was conducted.
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www.clinicaltrials.gov
Pfizer posts clinical trial US Basic Results on www.clinicaltrials.gov for Pfizer-sponsored 
interventional studies (conducted in patients) that evaluate the safety and/or efficacy of a 
product, regardless of the geographical location in which the study is conducted.  US Basic 
Results are generally submitted for posting within 1 year of the primary completion date 
(PCD) for studies in adult populations or within 6 months of the PCD for studies in pediatric 
populations.
PCD is defined as the date that the final participant was examined or received an intervention 
for the purposes of final collection of data for the primary outcome, whether the clinical 
study concluded according to the prespecified protocol or was terminated.
EudraCT
Pfizer posts European Union (EU) Basic Results on EudraCT for all Pfizer-sponsored 
interventional studies that are in scope of EU requirements.  EU Basic Results are submitted 
for posting within 1 year of the PCD for studies in adult populations or within 6 months of 
the PCD for studies in pediatric populations.
www.pfizer.com
Pfizer posts public disclosure synopses (CSR synopses in which any data that could be used 
to identify individual participants have been removed) on www.pfizer.com for 
Pfizer-sponsored interventional studies at the same time the US Basic Results document is 
posted to www.clinicaltrials.gov.
Documents within marketing authorization packages/submissions
Pfizer complies with the European Union Policy 0070, the proactive publication of clinical 
data to the European Medicines Agency (EMA) website.  Clinical data, under Phase 1 of this 
policy, includes clinical overviews, clinical summaries, CSRs, and appendices containing the 
protocol and protocol amendments, sample CRFs, and statistical methods.  Clinical data, 
under Phase 2 of this policy, includes the publishing of individual participant data.  
Policy 0070 applies to new marketing authorization applications submitted via the 
centralized procedure since 01 January 2015 and applications for line extensions and for new 
indications submitted via the centralized procedure since 01 July 2015.
Data Sharing
Pfizer provides researchers secure access to patient-level data or full CSRs for the purposes 
of “bona-fide scientific research” that contribute to the scientific understanding of the 
disease, target, or compound class. Pfizer will make available data from these trials 
24 months after study completion.  Patient-level data will be anonymized in accordance with 
applicable privacy laws and regulations.  CSRs will have personally identifiable information 
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Data requests are considered from qualified researchers with the appropriate competencies to 
perform the proposed analyses. Research teams must include a biostatistician. Data will not 
be provided to applicants with significant conflicts of interest, including individuals 
requesting access for commercial/competitive or legal purposes.
10.1.6. Data Quality Assurance
All participant data relating to the study will be recorded on printed or electronic CRF unless 
transmitted to the sponsor or designee electronically (eg, laboratory data). The investigator is 
responsible for verifying that data entries are accurate and correct by physically or 
electronically signing the CRF.
The investigator must maintain accurate documentation (source data) that supports the 
information entered in the CRF.
The investigator must ensure that the CRFs are securely stored at the study site in encrypted 
electronic and/or paper form and are password protected or secured in a locked room to 
prevent access by unauthorized third parties.
The investigator must permit study-related monitoring, audits, IRB/EC review, and 
regulatory agency inspections and provide direct access to source data documents.  This 
verification may also occur after study completion.  It is important that the investigator(s) 
and their relevant personnel are available during the monitoring visits and possible audits or 
inspections and that sufficient time is devoted to the process.
Monitoring details describing strategy (eg, risk-based initiatives in operations and quality 
such as risk management and mitigation strategies and analytical risk-based monitoring), 
methods, responsibilities, and requirements, including handling of noncompliance issues and 
monitoring techniques (central, remote, or on-site monitoring), are provided in the
monitoring plan.
The sponsor or designee is responsible for the data management of this study, including 
quality checking of the data.
Study monitors will perform ongoing source data verification to confirm that data entered 
into the CRF by authorized site personnel are accurate, complete, and verifiable from source 
documents; that the safety and rights of participants are being protected; and that the study is 
being conducted in accordance with the currently approved protocol and any other study 
agreements, ICH GCP, and all applicable regulatory requirements.
Records and documents, including signed ICDs, pertaining to the conduct of this study must 
be retained by the investigator for 15 years after study completion unless local regulations or 
institutional policies require a longer retention period. No records may be destroyed during 
the retention period without the written approval of the sponsor. No records may be 
transferred to another location or party without written notification to the sponsor. The 
investigator must ensure that the records continue to be stored securely for as long as they are 
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When participant data are to be deleted, the investigator will ensure that all copies of such 
data are promptly and irrevocably deleted from all systems.
The investigator(s) will notify the sponsor or its agents immediately of any regulatory 
inspection notification in relation to the study.  Furthermore, the investigator will cooperate 
with the sponsor or its agents to prepare the investigator site for the inspection and will allow 
the sponsor or its agent, whenever feasible, to be present during the inspection.  The 
investigator site and investigator will promptly resolve any discrepancies that are identified 
between the study data and the participant's medical records.  The investigator will promptly 
provide copies of the inspection findings to the sponsor or its agent.  Before response 
submission to the regulatory authorities, the investigator will provide the sponsor or its 
agents with an opportunity to review and comment on responses to any such findings.
10.1.7. Source Documents
As used in this protocol, the term CRF should be understood to refer to either a paper form or 
an electronic data record or both, depending on the data collection method used in this study.
A CRF is required and should be completed for each included participant.  The completed 
original CRFs are the sole property of Pfizer and should not be made available in any form to 
third parties, except for authorized representatives of Pfizer or appropriate regulatory 
authorities, without written permission from Pfizer.
The investigator has ultimate responsibility for the collection and reporting of all clinical, 
safety, and laboratory data entered on the CRFs and any other data collection forms (source 
documents) and ensuring that they are accurate, authentic/original, attributable, complete, 
consistent, legible, timely (contemporaneous), enduring, and available when required.  The 
CRFs must be signed by the investigator or by an authorized staff member to attest that the 
data contained on the CRFs are true.  Any corrections to entries made in the CRFs or source 
documents must be dated, initialed, and explained (if necessary) and should not obscure the 
original entry. 
In most cases, the source documents are the hospital or the physician participant chart.  In 
these cases, data collected on the CRFs must match the data in those charts. 
In some cases, the CRF may also serve as the source document.  In these cases, a document 
should be available at the investigator site and at Pfizer that clearly identifies those data that 
will be recorded on the CRF, and for which the CRF will stand as the source document.
Source documents provide evidence for the existence of the participant and substantiate the 
integrity of the data collected. Source documents are filed at the investigator site.
Data reported on the CRF or entered in the electronic CRF (eCRF) that are transcribed from 
source documents must be consistent with the source documents or the discrepancies must be 
explained. The investigator may need to request previous medical records or transfer 
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Definition of what constitutes source data can be found in the study monitoring plan.
10.1.8. Study and Site Closure
The sponsor designee reserves the right to close the study site or terminate the study at any 
time for any reason at the sole discretion of the sponsor. Study sites will be closed upon 
study completion. A study site is considered closed when all required documents and study 
supplies have been collected and a study-site closure visit has been performed.
The investigator may initiate study-site closure at any time upon notification to the contract 
research organization (CRO) if requested to do so by the responsible IRB/EC or if such 
termination is required to protect the health of study participants.
Reasons for the early closure of a study site by the sponsor may include but are not limited 
to:

Failure of the investigator to comply with the protocol, the requirements of the 
IRB/EC or local health authorities, the sponsor's procedures, or GCP guidelines;

Inadequate recruitment of participants by the investigator;

Discontinuation of further study intervention development.
Study termination is also provided for in the clinical study agreement.  If there is any conflict 
between the contract and this protocol, the contract will control as to termination rights.
10.1.9. Publication Policy
Pfizer supports the exercise of academic freedom and has no objection to publication by the 
principal investigator (PI) of the results of the study based on information collected or 
generated by the PI, whether or not the results are favorable to the Pfizer product.  However, 
to ensure against inadvertent disclosure of confidential information or unprotected 
inventions, the investigator will provide Pfizer an opportunity to review any proposed 
publication or other type of disclosure of the results of the study (collectively, “publication”) 
before it is submitted or otherwise disclosed.
The investigator will provide any publication to Pfizer at least 30 days before it is submitted 
for publication or otherwise disclosed.  If any patent action is required to protect intellectual 
property rights, the investigator agrees to delay the disclosure for a period not to exceed an 
additional 60 days.
The investigator will, on request, remove any previously undisclosed confidential 
information before disclosure, except for any study or Pfizer product related information 
necessary to the appropriate scientific presentation or understanding of the study results.


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If the study is part of a multicenter study, the investigator agrees that the first publication is 
to be a joint publication covering all investigator sites, and that any subsequent publications 
by the PI will reference that primary publication.  However, if a joint manuscript has not 
been submitted for publication within 12 months of completion or termination of the study at 
all participating sites, the investigator is free to publish separately, participant to the other 
requirements of this section.
For all publications relating to the study, the institution will comply with recognized ethical 
standards concerning publications and authorship, including Section II “Ethical 
Considerations in the Conduct and Reporting of Research” of the Uniform Requirements for 
Manuscripts Submitted to Biomedical Journals, http://www.icmje.org/index.html#authorship, 
established by the International Committee of Medical Journal Editors.
Publication of study results is also provided for in the clinical study agreement (CSA)
between Pfizer and the institution.  In this section entitled Publications by Investigators, the 
defined terms shall have the meanings given to them in the CSA.
If there is any conflict between the CSA and any attachments to it, the terms of the CSA 
control.  If there is any conflict between this protocol and the CSA, this protocol will control 
as to any issue regarding treatment of study participants, and the CSA will control as to all 
other issues.
10.1.10. Sponsor’s Qualified Medical Personnel
The contact information for the sponsor's appropriately qualified medical personnel for the 
study is documented in the study contact list located in the study team on demand (SToD) 
system. 
To facilitate access to appropriately qualified medical personnel on study-related medical 
questions or problems, participants are provided with a contact card.  The contact card 
contains, at a minimum, protocol and investigational product identifiers, participant numbers, 
contact information for the investigator site, and contact details for a contact center in the 
event that the investigator site staff cannot be reached to provide advice on a medical 
question or problem originating from another healthcare professional not involved in the 
participant’s participation in the study.  The contact number can also be used by investigator 
staff if they are seeking advice on medical questions or problems; however, it should be used 
only in the event that the established communication pathways between the investigator site 
and the study team are not available.  It is therefore intended to augment, but not replace, the 
established communication pathways between the investigator site and the study team for 
advice on medical questions or problems that may arise during the study.  The contact
number is not intended for use by the participant directly, and if a participant calls that 
number, he or she will be directed back to the investigator site.


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10.2. Appendix 2: Clinical Laboratory Tests
The following safety laboratory tests will be performed at times defined in the SoA section of 
this protocol.  Additional laboratory results may be reported on these samples as a result of 
the method of analysis or the type of analyzer used by the clinical laboratory; or as derived 
from calculated values.  These additional tests would not require additional collection of 
blood.  Unscheduled clinical laboratory measurements may be obtained at any time during 
the study to assess any perceived safety concerns.
Hematologya
Chemistrya
Urinalysisa
Other
Hemoglobin
Hematocrit
RBC count
MCV
MCH
MCHC
Reticulocyte count
Platelet count
WBC count with differential
Total neutrophils (%, Abs)
Eosinophils (%, Abs)
Monocytes (%, Abs)
Basophils (%, Abs)
Lymphocytes (%, Abs)
Coagulation Panel
Activated Partial 
Thromboplastin Time 
(aPTT)
Prothrombin 
Time/International 
Normalized Ratio 
(PT/INR)
BUN/urea and creatinine
Glucose
Calcium
Sodium
Potassium
Chloride
Total CO2 (bicarbonate)
AST, ALT
GGT
Total, indirect and direct 
bilirubin
Alkaline phosphatase
Uric acid
Albumin
Total protein
Creatine kinase (CK) 
Lipid Profile Panelb
Total Cholesterol
Triglycerides
HDL-C
LDL-C
pH
Glucose (qual)
Protein (qual)
Blood (qual)
Ketones
Nitrites
Leukocyte esterase
Urobilinogen
Urine bilirubin
Microscopyc
At screening only:
•
FSHd
•
HIV
•
TB teste
•
HBsAg, HBcAb, HepB reflex 
(HBsAb), if applicable HCVAb 
and/or HBVf.
At visits per SoA:
•
Pregnancy test (β-hCG)g
•
Skin swabs for herpetiform 
rashh
•
 
Abbreviations: Abs = absolute; ALT = alanine aminotransferase; aPTT = activated partial thromboplastin time; 
AST = aspartate aminotransferase; β-hCG = beta-human chorionic gonadotropin; BUN = blood urea nitrogen; 
CO2 = carbon dioxide; FSH = follicle-stimulating hormone; GGT = Gamma Glutamyl Transferase; HBV= hepatitis B 
virus; HCV= hepatitis C virus; HDL = high density lipoprotein cholesterol; HIV = Human Immunodeficiency Virus; 
 IGRA = Interferon Gamma Release Assay; INR = international normalized 
ratio; LDL =low density lipoprotein cholesterol; MCH = mean corpuscular hemoglobin; MCHC = mean corpuscular 
hemoglobin concentration; MCV = mean corpuscular volume; 
 PCR = polymerase chain reaction; PPD 
= purified protein derivative; qual = qualitative; PT = prothrombin time; QFT-G = quantiferon-TB-Gold; RBC = red blood 
cell; 
 WBC = white blood cell.
a.
Safety labs include hematology, chemistry and urinalysis.  Fasting not required unless lipid panel taken.
b.
Lipid panel requires fasting (water only) at least 8 hours prior to collection.
c.
Only if urine dipstick is positive for blood, protein, nitrites, or leukocyte esterase.
d.
A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a 
postmenopausal state in women.
e.
TB test must be Interferon Gamma Release Assay (IGRA).
f.
HepB reflex testing only if HBsAg negative but HBcAb positive at Screening. If result of HCVAb is positive, or if 
Hepatitis C Virus antibody result is indeterminate, then an HCV RNA AMPLIPREP TAQMAN 2.0 will automatically 
be performed. HBV DNA monitoring may be applicable in Japan.
g.
Serum/urine pregnancy test for WOCBP.
h.
In cases of suspected herpetiform rash (eg, suspected herpes zoster and herpes simplex).
Investigators must document their review of each laboratory safety report.
CCI
CCI
CCI
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10.3. Appendix 3: Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow-up, and Reporting
10.3.1. Definition of AE
AE Definition

An AE is any untoward medical occurrence in a patient or clinical study participant, 
temporally associated with the use of study intervention, whether or not considered 
related to the study intervention.

NOTE: An AE can therefore be any unfavorable and unintended sign (including an 
abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally 
associated with the use of study intervention.
Events Meeting the AE Definition

Any abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) 
or other safety assessments (eg, ECG, radiological scans, vital sign measurements), 
including those that worsen from baseline, considered clinically significant in the 
medical and scientific judgment of the investigator (ie, not related to progression of 
underlying disease).

Exacerbation of a chronic or intermittent preexisting condition including either an 
increase in frequency and/or intensity of the condition.

New conditions detected or diagnosed after study intervention administration even 
though it may have been present before the start of the study.

Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction.

Signs, symptoms, or the clinical sequelae of a suspected overdose of either study 
intervention or a concomitant medication. Overdose per se will not be reported as an 
AE/SAE unless it is an intentional overdose taken with possible 
suicidal/self-harming intent. Such overdoses should be reported regardless of 
sequelae.
Events NOT Meeting the AE Definition

Any clinically significant abnormal laboratory findings or other abnormal safety 
assessments which are associated with the underlying disease, unless judged by the 
investigator to be more severe than expected for the participant’s condition.

The disease/disorder being studied or expected progression, signs, or symptoms of 
the disease/disorder being studied, unless more severe than expected for the 


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participant’s condition.

Medical or surgical procedure (eg, endoscopy, appendectomy): the condition that 
leads to the procedure is the AE.

Situations in which an untoward medical occurrence did not occur (social and/or 
convenience admission to a hospital).

Anticipated day-to-day fluctuations of preexisting disease(s) or condition(s) present 
or detected at the start of the study that do not worsen.
10.3.2. Definition of SAE
If an event is not an AE per definition above, then it cannot be an SAE even if serious 
conditions are met (eg, hospitalization for signs/symptoms of the disease under study, death 
due to progression of disease).
An SAE is defined as any untoward medical occurrence that, at any dose:
Results in death
Is life-threatening
The term “life-threatening” in the definition of “serious” refers to an event in which the 
participant was at risk of death at the time of the event. It does not refer to an event that
hypothetically might have caused death if it were more severe.
Requires inpatient hospitalization or prolongation of existing hospitalization
In general, hospitalization signifies that the participant has been detained (usually involving 
at least an overnight stay) at the hospital or emergency ward for observation and/or 
treatment that would not have been appropriate in the physician’s office or outpatient 
setting.  Complications that occur during hospitalization are AEs.  If a complication 
prolongs hospitalization or fulfills any other serious criteria, the event is serious. When in 
doubt as to whether “hospitalization” occurred or was necessary, the AE should be 
considered serious.
Hospitalization for elective treatment of a preexisting condition that did not worsen from 
baseline is not considered an AE.
Results in persistent disability/incapacity

The term disability means a substantial disruption of a person’s ability to conduct 
normal life functions.

This definition is not intended to include experiences of relatively minor medical 
significance such as uncomplicated headache, nausea, vomiting, diarrhea, influenza, 


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and accidental trauma (eg, sprained ankle) which may interfere with or prevent 
everyday life functions but do not constitute a substantial disruption.
Is a congenital anomaly/birth defect
Other situations:

Medical or scientific judgment should be exercised in deciding whether SAE 
reporting is appropriate in other situations such as important medical events that may 
not be immediately life-threatening or result in death or hospitalization but may 
jeopardize the participant or may require medical or surgical intervention to prevent 
one of the other outcomes listed in the above definition. These events should usually 
be considered serious.

Examples of such events include invasive or malignant cancers, intensive treatment 
in an emergency room or at home for allergic bronchospasm, blood dyscrasias or 
convulsions that do not result in hospitalization, or development of drug dependency 
or drug abuse.
10.3.3. Recording/Reporting and Follow-up of AEs and/or SAEs
AE and SAE Recording/Reporting
The table below summarizes the requirements for recording adverse events on the CRF and 
for reporting serious adverse events on the Clinical Trial (CT) Serious Adverse Event (SAE) 
Report Form to Pfizer Safety.  These requirements are delineated for 3 types of events: (1) 
SAEs; (2) nonserious adverse events (AEs); and (3) exposure to the investigational product 
under study during pregnancy or breastfeeding, and occupational exposure. 
It should be noted that the CT SAE Report Form for reporting of SAE information is not the 
same as the AE page of the CRF.  When the same data are collected, the forms must be 
completed in a consistent manner.  AEs should be recorded using concise medical 
terminology and the same AE term should be used on both the CRF and the CT SAE Report 
Form for reporting of SAE information.
Safety Event
Recorded on the CRF
Reported on the CT SAE 
Report Form to Pfizer 
Safety Within 24 Hours of 
Awareness
SAE
All
All
Nonserious AE
All
None


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Exposure to the 
investigational product 
under study during 
pregnancy or 
breastfeeding, and 
occupational exposure
None
All (and exposure during 
pregnancy [EDP]
supplemental form for 
EDP)  

When an AE/SAE occurs, it is the responsibility of the investigator to review all 
documentation (eg, hospital progress notes, laboratory reports, and diagnostic 
reports) related to the event.

The investigator will then record all relevant AE/SAE information in the CRF.

It is not acceptable for the investigator to send photocopies of the participant’s 
medical records to Pfizer Safety in lieu of completion of the CT SAE Report 
Form/AE/SAE CRF page.

There may be instances when copies of medical records for certain cases are 
requested by Pfizer Safety. In this case, all participant identifiers, with the exception 
of the participant number, will be redacted on the copies of the medical records 
before submission to Pfizer Safety.

The investigator will attempt to establish a diagnosis of the event based on signs, 
symptoms, and/or other clinical information. Whenever possible, the diagnosis (not 
the individual signs/symptoms) will be documented as the AE/SAE.
Assessment of Intensity
The investigator will make an assessment of intensity for each AE and SAE reported during 
the study and assign it to 1 of the following categories: 

Mild: An event that is easily tolerated by the participant, causing minimal discomfort 
and not interfering with everyday activities.

Moderate: An event that causes sufficient discomfort and interferes with normal 
everyday activities.

Severe: An event that prevents normal everyday activities. An AE that is assessed as 
severe should not be confused with an SAE.  Severe is a category utilized for rating 
the intensity of an event; and both AEs and SAEs can be assessed as severe.
An event is defined as “serious” when it meets at least 1 of the predefined outcomes as 
described in the definition of an SAE, NOT when it is rated as severe.


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Assessment of Causality

The investigator is obligated to assess the relationship between study intervention 
and each occurrence of each AE/SAE.

A “reasonable possibility” of a relationship conveys that there are facts, evidence, 
and/or arguments to suggest a causal relationship, rather than a relationship cannot 
be ruled out.

The investigator will use clinical judgment to determine the relationship.

Alternative causes, such as underlying disease(s), concomitant therapy, and other 
risk factors, as well as the temporal relationship of the event to study intervention 
administration will be considered and investigated.

The investigator will also consult the investigator’s brochure (IB) and/or product 
information, for marketed products, in his/her assessment.

For each AE/SAE, the investigator must document in the medical notes that he/she 
has reviewed the AE/SAE and has provided an assessment of causality.

There may be situations in which an SAE has occurred and the investigator has 
minimal information to include in the initial report to the sponsor. However, it is 
very important that the investigator always make an assessment of causality for 
every event before the initial transmission of the SAE data to the sponsor.

The investigator may change his/her opinion of causality in light of follow-up 
information and send an SAE follow-up report with the updated causality 
assessment.

The causality assessment is one of the criteria used when determining regulatory 
reporting requirements.

If the investigator does not know whether or not the investigational product caused 
the event, then the event will be handled as “related to investigational product” for 
reporting purposes, as defined by the sponsor.  In addition, if the investigator 
determines that an SAE is associated with study procedures, the investigator must 
record this causal relationship in the source documents and CRF, and report such an 
assessment in the dedicated section of the CT SAE Report Form and in accordance 
with the SAE reporting requirements.


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Follow-up of AEs and SAEs

The investigator is obligated to perform or arrange for the conduct of supplemental 
measurements and/or evaluations as medically indicated or as requested by the 
sponsor to elucidate the nature and/or causality of the AE or SAE as fully as 
possible. This may include additional laboratory tests or investigations, 
histopathological examinations, or consultation with other healthcare professionals.

If a participant dies during participation in the study or during a recognized 
follow-up period, the investigator will provide Pfizer Safety with a copy of any 
postmortem findings including histopathology.

New or updated information will be recorded in the originally completed CRF.

The investigator will submit any updated SAE data to the sponsor within 24 hours of 
receipt of the information.
10.3.4. Reporting of SAEs
SAE Reporting to Pfizer Safety via an Electronic Data Collection Tool

The primary mechanism for reporting an SAE to Pfizer Safety will be the electronic 
data collection tool.

If the electronic system is unavailable, then the site will use the paper SAE data 
collection tool (see next section) in order to report the event within 24 hours.

The site will enter the SAE data into the electronic system as soon as the data
become available.

After the study is completed at a given site, the electronic data collection tool will be 
taken off-line to prevent the entry of new data or changes to existing data.

If a site receives a report of a new SAE from a study participant or receives updated 
data on a previously reported SAE after the electronic data collection tool has been 
taken off-line, then the site can report this information on a paper SAE form (see 
next section) or to Pfizer Safety by telephone.


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SAE Reporting to Pfizer Safety via CT SAE Report Form

Facsimile transmission of the CT SAE Report Form is the preferred method to transmit 
this information to Pfizer Safety.

In circumstances when the facsimile is not working, notification by telephone is 
acceptable with a copy of the CT SAE Report Form sent by overnight mail or courier 
service.

Initial notification via telephone does not replace the need for the investigator to 
complete and sign the CT SAE Report Form pages within the designated reporting 
time frames.


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10.4. Appendix 4: Contraceptive Guidance and Collection of Pregnancy Information
10.4.1. Male Participant Reproductive Inclusion Criteria
No contraception methods are required for male participants in this study, as the calculated 
safety margin is ≥100-fold between the estimated maternal exposure due to seminal transfer 
and the NOAEL for serious manifestations of developmental toxicity in nonclinical studies.
10.4.2. Female Participant Reproductive Inclusion Criteria
A female participant is eligible to participate if she is not pregnant or breastfeeding and at 
least 1 of the following conditions applies:

Is not a WOCBP (see definitions below in Section 10.4.3).
OR

Is a WOCBP and using a contraceptive method that is acceptable and highly effective 
(with a failure rate of <1% per year), with high user dependency, as described below 
during the intervention period and for at least 28 days after the last dose of study 
intervention, which corresponds to the time needed to eliminate any study 
intervention(s).  In addition, a second effective method of contraception, as described 
below, must be used (except for sexual abstinence).  
The investigator should evaluate the effectiveness of the contraceptive method in 
relationship to the first dose of study intervention.
The investigator is responsible for review of medical history, menstrual history, and 
recent sexual activity to decrease the risk for inclusion of a woman with an early 
undetected pregnancy. 
10.4.3. Woman of Childbearing Potential (WOCBP)
A woman is considered fertile following menarche and until becoming postmenopausal 
unless permanently sterile (see below).
If fertility is unclear (eg, amenorrhea in adolescents or athletes) and a menstrual cycle cannot 
be confirmed before the first dose of study intervention, additional evaluation should be 
considered.
Women in the following categories are not considered WOCBP:
1. Premenopausal female with 1 of the following:

Documented hysterectomy;

Documented bilateral salpingectomy;

Documented bilateral oophorectomy.


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For individuals with permanent infertility due to an alternate medical cause other than 
the above, (eg, mullerian agenesis, androgen insensitivity), investigator discretion 
should be applied to determining study entry.
Note: Documentation for any of the above categories can come from the site 
personnel’s review of the participant’s medical records, medical examination, or 
medical history interview.  The method of documentation should be recorded in the 
participant’s medical record for the study.
2. Postmenopausal female:

A postmenopausal state is defined as age 60 years or older or no menses for 
12 months without an alternative medical cause. 

A high follicle-stimulating hormone (FSH) level in the postmenopausal range 
may be used to confirm a postmenopausal state in women not using hormonal 
contraception or hormone replacement therapy (HRT). 

Females on HRT and whose menopausal status is in doubt will be required to use 
one of the nonestrogen hormonal highly effective contraception methods if they 
wish to continue their HRT during the study.  Otherwise, they must discontinue 
HRT to allow confirmation of postmenopausal status before study enrollment.
10.4.4. Contraception Methods
Highly Effective Methods with Low User Dependency are preferred.  (Failure rate of <1% 
per year when used consistently and correctly). 
1. Implantable progestogen-only hormone contraception associated with inhibition of 
ovulation*.
2. Intrauterine device (IUD).
3. Intrauterine hormone-releasing system (IUS)*.
4. Bilateral tubal occlusion.
5. Vasectomized partner:

Vasectomized partner is a highly effective contraceptive method provided that the 
partner is the sole sexual partner of the woman of childbearing potential and the 
absence of sperm has been confirmed. If not, an additional highly effective 
method of contraception should be used. The spermatogenesis cycle is 
approximately 90 days.
* This requirement may be removed if supported by the outcome of ongoing oral contraceptive PK interaction 
study (Study C2501005); investigators will be notified and notifications as per local regulatory requirements 
will be completed, as applicable.


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Highly Effective Methods that are User Dependent 
One of the acceptable barrier methods (described below) must be used in addition to the 
highly effective methods that are user dependent except for sexual abstinence.
1. Combined (estrogen- and progestogen-containing) hormonal contraception associated 
with inhibition of ovulation:

Oral;

Intravaginal;

Transdermal;

Injectable.
2. Progestogen-only hormone contraception associated with inhibition of ovulation.
3. Sexual abstinence:

Sexual abstinence is considered a highly effective method only if defined as 
refraining from heterosexual intercourse during the entire period of risk associated 
with the study intervention.  The reliability of sexual abstinence needs to be 
evaluated in relation to the duration of the study and the preferred and usual 
lifestyle of the participant.
Acceptable Contraceptive Barrier Methodsa
1. Male or female condom with or without spermicideb
2. Cervical cap, diaphragm, or sponge with spermicide
3. A combination of male condom with either cervical cap, diaphragm, or sponge with 
spermicide (double barrier methods)
a.
Considered effective, but not highly effective methods - failure rate of ≥1% per year. Note that periodic 
abstinence (calendar, symptothermal, post-ovulation methods), withdrawal (coitus interruptus), spermicides 
only, and lactational amenorrhoea method (LAM) are not acceptable methods of contraception.
b.
Male condom and female condom should not be used together (due to risk of failure with friction).


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Collection of Pregnancy Information
For both unapproved/unlicensed products and for marketed products, an exposure during 
pregnancy (EDP) occurs if:

A female becomes, or is found to be, pregnant either while receiving or having been
exposed (eg, because of treatment or environmental exposure) to the investigational 
product; or the female becomes or is found to be pregnant after discontinuing and/or 
being exposed to the investigational product;

An example of environmental exposure would be a case involving direct contact 
with a Pfizer product in a pregnant woman (eg, a nurse reports that she is pregnant 
and has been exposed to chemotherapeutic products).

A male has been exposed (eg, because of treatment or environmental exposure) to the 
investigational product prior to or around the time of conception and/or is exposed 
during his partner’s pregnancy.
If a participant or participant’s partner becomes or is found to be pregnant during the 
participant’s treatment with the investigational product, the investigator must report this 
information to Pfizer Safety on the CT SAE Report Form and an EDP supplemental form, 
regardless of whether an SAE has occurred.  In addition, the investigator must submit 
information regarding environmental exposure to a Pfizer product in a pregnant woman (eg, a 
participant reports that she is pregnant and has been exposed to a cytotoxic product by 
inhalation or spillage) to Pfizer Safety using the EDP supplemental form.  This must be done 
irrespective of whether an AE has occurred and within 24 hours of awareness of the 
exposure.  The information submitted should include the anticipated date of delivery (see 
below for information related to termination of pregnancy).
Follow-up is conducted to obtain general information on the pregnancy and its outcome for 
all EDP reports with an unknown outcome.  The investigator will follow the pregnancy until 
completion (or until pregnancy termination) and notify Pfizer Safety of the outcome as a 
follow-up to the initial EDP supplemental form.  In the case of a live birth, the structural 
integrity of the neonate can be assessed at the time of birth.  In the event of a termination, the 
reason(s) for termination should be specified and, if clinically possible, the structural 
integrity of the terminated fetus should be assessed by gross visual inspection (unless 
preprocedure test findings are conclusive for a congenital anomaly and the findings are 
reported).
If the outcome of the pregnancy meets the criteria for an SAE (ie, ectopic pregnancy, 
spontaneous abortion, intrauterine fetal demise, neonatal death, or congenital anomaly [in a 
live-born baby, a terminated fetus, an intrauterine fetal demise, or a neonatal death]), the 
investigator should follow the procedures for reporting SAEs.


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Additional information about pregnancy outcomes that are reported to Pfizer Safety as SAEs 
follows: 

Spontaneous abortion includes miscarriage and missed abortion;

Neonatal deaths that occur within 1 month of birth should be reported, without regard 
to causality, as SAEs.  In addition, infant deaths after 1 month should be reported as 
SAEs when the investigator assesses the infant death as related or possibly related to 
exposure to the investigational product. 
Additional information regarding the EDP may be requested by the sponsor.  Further 
follow-up of birth outcomes will be handled on a case-by-case basis (eg, follow-up on 
preterm infants to identify developmental delays).  In the case of paternal exposure, the 
investigator will provide the participant with the Pregnant Partner Release of Information 
Form to deliver to his partner.  The investigator must document in the source documents that 
the participant was given the Pregnant Partner Release of Information Form to provide to his 
partner.


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CCI


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10.6. Appendix 6: Liver Safety: Suggested Actions and Follow-up Assessments 
Potential Cases of Drug-Induced Liver Injury
Humans exposed to a drug who show no sign of liver injury (as determined by elevations in 
transaminases) are termed “tolerators,” while those who show transient liver injury, but adapt 
are termed “adaptors.”  In some participants, transaminase elevations are a harbinger of a 
more serious potential outcome.  These participants fail to adapt and therefore are 
"susceptible" to progressive and serious liver injury, commonly referred to as drug-induced 
liver injury (DILI).  Participants who experience a transaminase elevation above 3 times the 
upper limit of normal (× ULN) should be monitored more frequently to determine if they are 
an “adaptor” or are “susceptible.”
In the majority of DILI cases, elevations in aspartate aminotransferase (AST) and/or alanine 
aminotransferase (ALT) precede total bilirubin (TBili) elevations (>2 × ULN) by several 
days or weeks.  The increase in TBili typically occurs while AST/ALT is/are still elevated 
above 3 × ULN (ie, AST/ALT and TBili values will be elevated within the same laboratory 
sample).  In rare instances, by the time TBili elevations are detected, AST/ALT values might 
have decreased.  This occurrence is still regarded as a potential DILI.  Therefore, abnormal 
elevations in either AST OR ALT in addition to TBili that meet the criteria outlined below 
are considered potential DILI (assessed per Hy’s law criteria) cases and should always be 
considered important medical events, even before all other possible causes of liver injury 
have been excluded.
The threshold of laboratory abnormalities for a potential DILI case depends on the 
participant’s individual baseline values and underlying conditions.  Participants who present 
with the following laboratory abnormalities should be evaluated further as potential DILI 
(Hy’s law) cases to definitively determine the etiology of the abnormal laboratory values:

Participants with AST/ALT and TBili baseline values within the normal range who 
subsequently present with AST OR ALT values >3 × ULN AND a TBili value 
>2 × ULN with no evidence of hemolysis and an alkaline phosphatase value 
<2 × ULN or not available.

For participants with baseline AST OR ALT OR TBili values above the ULN, the 
following threshold values are used in the definition mentioned above, as needed, 
depending on which values are above the ULN at baseline:

Preexisting AST or ALT baseline values above the normal range: AST or ALT 
values >2 times the baseline values AND >3 × ULN; or >8 × ULN (whichever is 
smaller).

Preexisting values of TBili above the normal range: TBili level increased from 
baseline value by an amount of at least 1 × ULN or if the value reaches >3 × ULN 
(whichever is smaller).


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Rises in AST/ALT and TBili separated by more than a few weeks should be assessed 
individually based on clinical judgment; any case where uncertainty remains as to whether it 
represents a potential Hy’s law case should be reviewed with the sponsor. 
The participant should return to the investigator site and be evaluated as soon as possible, 
preferably within 48 hours from awareness of the abnormal results.  This evaluation should 
include laboratory tests, detailed history, and physical assessment. 
In addition to repeating measurements of AST and ALT and TBili for suspected cases of 
Hy’s law, additional laboratory tests should include albumin, creatine kinase (CK), direct and 
indirect bilirubin, gamma-glutamyl transferase (GGT), prothrombin time (PT)/international 
normalized ratio (INR), total bile acids, and alkaline phosphatase.  Consideration should also 
be given to drawing a separate tube of clotted blood and an anticoagulated tube of blood for 
further testing, as needed, for further contemporaneous analyses at the time of the recognized 
initial abnormalities to determine etiology.  A detailed history, including relevant 
information, such as review of ethanol, acetaminophen (either by itself or as a coformulated 
product in prescription or over-the-counter medications), recreational drug, supplement 
(herbal) use and consumption, family history, sexual history, travel history, history of contact 
with a jaundiced person, surgery, blood transfusion, history of liver or allergic disease, and 
potential occupational exposure to chemicals, should be collected.  Further testing for acute 
hepatitis A, B, C, D, and E infection and liver imaging (eg, biliary tract) and collection of 
serum sample for acetaminophen drug and/or protein adduct levels may be warranted. 
All cases demonstrated on repeat testing as meeting the laboratory criteria of AST/ALT and 
TBili elevation defined above should be considered potential DILI (Hy’s law) cases if no 
other reason for the liver function test (LFT) abnormalities has yet been found.  Such 
potential DILI (Hy’s law) cases are to be reported as SAEs, irrespective of availability of all 
the results of the investigations performed to determine etiology of the LFT abnormalities. 
A potential DILI (Hy’s law) case becomes a confirmed case only after all results of 
reasonable investigations have been received and have excluded an alternative etiology.


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10.7. Appendix 7: ECG Findings of Potential Clinical Concern
ECG Findings That May Qualify as Adverse Events (AEs)

Marked sinus bradycardia (rate <40 beats per minute (bpm)) lasting minutes.

New PR interval prolongation >280 msec.

New prolongation of QTcF to >480 msec (absolute) or by ≥60 msec from baseline.

New-onset atrial flutter or fibrillation, with controlled ventricular response rate: 
ie, rate <120 bpm.

New-onset type I second-degree (Wenckebach) AV block of >30 seconds’ 
duration.

Frequent premature ventricular contraction/complexes [per Abbreviations] (PVCs),
triplets, or short intervals (<30 seconds) of consecutive ventricular complexes.
ECG Findings That May Qualify as Serious Adverse Events (SAEs)

QTcF prolongation >500 msec.

New ST-T changes suggestive of myocardial ischemia.

New-onset left bundle branch block (QRS >120 msec).

New-onset right bundle branch block (QRS >120 msec).

Symptomatic bradycardia. 

Asystole:

In awake, symptom-free patients in sinus rhythm, with documented periods of 
asystole ≥3.0 seconds or any escape rate <40 bpm, or with an escape rhythm 
that is below the AV node; 

In awake, symptom-free patients with atrial fibrillation and bradycardia with 
1 or more pauses of at least 5 seconds or longer; 

Atrial flutter or fibrillation, with rapid ventricular response rate: rapid = rate 
>120 bpm.

Sustained supraventricular tachycardia (rate >120 bpm) (“sustained” = short 
duration with relevant symptoms or lasting >1 minute).

Ventricular rhythms >30 seconds’ duration, including idioventricular rhythm (rate 
<40 bpm), accelerated idioventricular rhythm (40< x <100), and 


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monomorphic/polymorphic ventricular tachycardia >100 bpm (such as torsades de 
pointes).

Type II second-degree (Mobitz II) AV block.

Complete (third-degree) heart block.
ECG Findings That Qualify as Serious Adverse Events

Change in pattern suggestive of new myocardial infarction. 

Sustained ventricular tachyarrhythmias (>30 seconds’ duration).

Second- or third-degree AV block requiring pacemaker placement.

Asystolic pauses requiring pacemaker placement.

Atrial flutter or fibrillation with rapid ventricular response requiring cardioversion.

Ventricular fibrillation/flutter.

At the discretion of the investigator, any arrhythmia classified as an adverse 
experience.
The enumerated list of major events of potential clinical concern are recommended as “alerts” or 
notifications from the core ECG laboratory to the investigator and Pfizer study team, and not to be 
considered as all inclusive of what to be reported as AEs/SAEs.


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10.8. Appendix 8: Prohibited Concomitant Medications
This is not an all-inclusive list.  Study personnel should stay current and consult with their 
pharmacy to exclude all concomitant medications that fall into the categories in the list 
below: 
CYP1A2, CYP3A4, CYP2D6 
Inhibitors (Moderate to Strong)
CYP1A2, CYP3A4, 
Inducers (Moderate to 
Strong)
MATE substrates 
with Narrow 
Therapeutic Index
CYP 1A2
CYP 1A2
Ciprofloxacin
Phenytoin
Dofetilide
Clinafloxacin
Rifampin
Enoxacin
Ritonavir
Fluvoxamine
Teriflunomide
Oltipraz
Rofecoxib
Zafirlukast
Etintidine
Idrocilamide
Methoxsalen
Mexiletine
Phenylpropanolamine
Pipemidic acid
Propafenone
Propranolol
Troleandomycin
Vemurafenib
CYP 2D6
Quinidine
Fluoxetine
Dacomitinib
Paroxetine
Buproprion
Cinacalcet
Terbinafine
Tipranavir
Moclobemide
Rolapitant
Mirabegron
Duloxetine
Eliglustat
Dronedarone


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CYP1A2, CYP3A4, CYP2D6 
Inhibitors (Moderate to Strong)
CYP1A2, CYP3A4, 
Inducers (Moderate to 
Strong)
MATE substrates 
with Narrow 
Therapeutic Index
CYP3A4
CYP3A4
Viekira pak
Rifampin
Indinavir
Mitotane
Tipranavir
Avasimibe
Ritonavir
Phenytoin
Cobicistat
Carbamazepine
Amiodarone
Ketoconazole
Enzalutamide
Troleandomycin
St. John’s wort
Telaprevir
Rifabutin
Danoprevir
Phenobarbital
Elvitegravir
Saquinavir
Semagacestat
Lopinavir
Efavirenz
Itraconazole
Bosentan
Voriconazole
Genistein
Mibefradil
Thioridazine
Clarithromycin
Nafcillin
Posaconazole
Talviraline
Telithromycin
Lopinavir
Grapefruit Juice***, Marmalade
Modafanil
Conivaptan
Etravirine
Nefazodone
Lersivirine
Nelfinavir
Saquinavir
Idelalisib
Boceprevir
Erythromycin
Fluconazole
Atazanavir
Darunavir
Diltiazem
Dronedarone
Crizotinib
Aprepitant
Casopitant
Amprenavir
Faldaprevir
Imatinib
Verapamil
Netupitant


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CYP1A2, CYP3A4, CYP2D6 
Inhibitors (Moderate to Strong)
CYP1A2, CYP3A4, 
Inducers (Moderate to 
Strong)
MATE substrates 
with Narrow 
Therapeutic Index
Nilotinib
Tofisopam
Cyclosporine
Ciprofloxacin
Isavuconazole
Cimetidine

All prohibited drugs that are CYP1A2, CYP3A and CYP2D6 inhibitors require at least a 7 day or 
5 half-lives (whichever is longer) prior to the first dose of study drug.  Note: Amiodarone requires 
discontinuation at least 290 days (~5 half-lives, half-life averages ~58 days) prior to the first dose of IP.

All prohibited drugs that are CYP1A2 and CYP3A inducers require at least a 28 day or 5 half-lives 
(whichever is longer) prior to the first dose of IP.

***It is recommended that subjects avoid excessive consumption of grapefruit juice exceeding 8 ounces 
(~240 mL) total in a day while in the study.

In a situation where appropriate medical care of a subject requires the use of a prohibited 
inhibitor or inducer:
Moderate to potent inhibitors of CYP1A2, CYP3A and CYP2D6 and inducers of CYP1A2 and CYP3A are 
not permitted in the study EXCEPT in emergency situations requiring no more than one day of 
administration.  Note: Amiodarone and mitotane are not permitted for any duration due to their long 
half-lives.  Topical (including skin or mucous membranes) application of antimicrobial and antifungal 
medications is permitted.


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10.9. Appendix 9: Columbia Suicide Severity Rating Scale (C-SSRS) for Screening and 
Baseline Visit 


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C-SSRS for any post-baseline visits “since last visit version”:


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10.10. Appendix 10: Psoriasis Symptom Inventory (PSI) (Daily Assessment)


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Psoriasis Symptom Inventory (PSI)-7 day


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10.11. Appendix 11: Peak Pruritus Numeric Rating Scale (PP-NRS)
CENTER
SUBJECT ID
Protocol ID:  ________________
DATE OF VISIT
-
-
dd
MMM
yyyy
Visit:  
_______________________________
PEAK PRURITUS-NRS
(1) NOT DONE
Language administered:     
(44) English for USA
On a scale of 0 to 10, with 0 being “no itch” and 10 being “worst itch imaginable”, how 
would you rate your itch at the worst moment during the previous 24 hours?
0
1
2
3
4
5
6
7
8
9
10
No 
itch
Worst 
itch 
imaginable
Simpson E, Beck L, Abhijit G, et al. Defining a responder on the Peak Pruritus Numerical Rating Scale (NRS) 
in patients with moderate-to-severe atopic dermatitis: Detailed analysis from randomized trials of dupilumab. 
J Am Acad of Dermatol 2017; 76:AB93.
Yosipovitch G, Reaney M, Mastey V, et al. Validation of the peak pruritus numerical rating scale: Results from 
clinical studies of dupilumab in adult patients with moderate to severe atopic dermatitis.  J Am Acad of 
Dermatol 2017; 76:AB278.
©Regeneron Pharmaceuticals, Inc. and Sanofi (2017).


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CCI


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10.17. Appendix 17: Physician Global Assessment


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10.18. Appendix 18: eGFR Calculations
The estimated GFR (eGFR) will be calculated using the set of equations developed by the 
Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI).
CKD-EPI2009Scr
If female and serum creatinine (SCr) is ≤0.7 mg/dL:

GFR (mL/min/1.73 m2) = 144 x (Scr/0.7) – 0.329 x 0.993age (x 1.159, if black).
If female and SCr is >0.7 mg/dL:

GFR (mL/min/1.73 m2) = 144 x (Scr/0.7) – 1.209 x 0.993age (x 1.159, if black).
If male and SCr is ≤0.9 mg/dL:

GFR (mL/min/1.73 m2) = 141 x (Scr/0.9) – 0.411 x 0.993age (x 1.159, if black).
If male and SCr is >0.9 mg/dL:

GFR (mL/min/1.73 m2) = 141 x (Scr/0.9) – 1.209 x 0.993age (x 1.159, if black).


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10.19. Appendix 19: Abbreviations
The following is a list of abbreviations that may be used in the protocol.
Abbreviation
Term
Abs
Absolute
ADA
antidrug antibodies
AE
adverse event
ALT
alanine aminotransferase
AST
aspartate aminotransferase
AUC
area under the curve
AUC24
area under the concentration time curve from zero to 24 hours after 
single dose
AV
Atrioventricular
BA
Bioavailability
β-hCG
beta-human chorionic gonadotropin
BID
Two times per day
BMI
Body mass index
BP
blood pressure
bpm
beats per minute
BUN
blood urea nitrogen
CFR
Code of Federal Regulations
CIOMS
Council for International Organizations of Medical Sciences
CK
creatine kinase
CKD-EPI
Chronic Kidney Disease Epidemiology
CL/F
apparent oral clearance
Cmax
Total maximum observed concentration
CO2
carbon dioxide (bicarbonate)
CONSORT
Consolidated Standards of Reporting Trials
CRF
case report form
CRO
contract research organization
CSA
clinical study agreement
CSR
clinical study report
C-SSRS
Columbia Suicide Severity Rating Scale
CT
clinical trial
DILI
drug-induced liver injury
DMC
data monitoring committee
DNA
deoxyribonucleic acid
DU
dispensable unit
EBV
epstein barr virus
EC
ethics committee
ECG
electrocardiogram
CCI
CCI
CCI


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Abbreviation
Term
eCRF
electronic case report form
EDP
exposure during pregnancy
EE
ethinylestradiol
eGFR
estimated glomerular filtration rate
EMA
European Medicines Agency
EPO
epogen
ePRO
electronic patient reported outcomes
ET
early termination
EU
European Union
EudraCT
European Clinical Trials Database
FACS
Fluorescence-activated cell sorting
fm
Fraction metabolized
FSH
follicle-stimulating hormone
GCP
Good Clinical Practice
GGT
gamma-glutamyl transferase
HBcAb
hepatitis B core antibody
HBsAB
hepatitis B surface antibody
HBsAg 
hepatitis B surface antigen
HBV
hepatitis B virus
HCV
hepatitis C virus
HCVAb
hepatitis C antibody
HIPAA
Health Insurance Portability and Accountability Act
HIV
human immunodeficiency virus
HRQoL
Health related quality of life
HRT
hormone replacement therapy
IB
investigator’s brochure
IC50
50% inhibitory concentration
ICD
informed consent document
ICH
International Council for Harmonisation
ID
identification
IFN
interferon
IGRA
interferon gamma release assay
IMP
investigational medicinal product
IND
investigational new drug 
INR
international normalized ratio
IP
investigational product
IP manual
investigational product manual
IRB
institutional review board
IRC
internal review committee
IRT
interactive response technology
IUD
intrauterine device
CCI
CCI


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Abbreviation
Term
IUS
intrauterine hormone-releasing system
IV
intravenous
IWR
interactive Web-based response
JAK
Janus kinase
LBBB
left bundle branch block
LAM
lactational amenorrhea method
LFT
liver function test
MAD
Multiple ascending dose
MATE1
multidrug and toxin extrusion protein
MCH
mean corpuscular hemoglobin
MCHC
mean corpuscular hemoglobin concentration
MCV
mean corpuscular volume
MDR1
multidrug resistant protein 1
MMR
Measles, mumps, rubella
MRI
Magnetic resonance imaging
MRP2
multidrug resistance-associated protein
msec
millisecond 
N/A
not available 
NIMP
noninvestigational medicinal product
NOAEL
no-observed-adverse-effect level
NTCP
sodium/taurocholate co-transporting polypeptide
OATP
organic anion transporting polypeptide
OC
oral contraceptives
OCT
organic cation transporter
PASI
Psoriasis Area and Severity Index
PCD
primary completion date
PCP
Primary care physician
PCR
Polymerase chain reaction
PD
pharmacodynamic(s)
PGA
Physicians global assessment
P-gp
P glycoprotein
PI
principal investigator
PK
pharmacokinetic(s)
PP-NRS
Peak-Pruritus Numerical Rating Scale
PR
Pulse rate
PRO
Patient reported outcome
PSI
Psoriasis symptom inventory
pSTAT
Phosphorylated signal transducer and activator of transcription
PT
prothrombin time
PUVA
Psoralen + UVA phototherapy
PVC
premature ventricular contraction/complex
CCI
CCI


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Abbreviation
Term
QD
Once daily
QFT GIT
QuantiFERON TB Gold In Tube test
QFT G
QuantiFERONR TB Gold
QoL
Quality of Life
QTc
corrected QT
QTcF
corrected QT (Fridericia method)
qual
qualitative
RBC
red blood cell
RNA
ribonucleic acid
SAD
Single ascending dose
SAE
serious adverse event
SAP
statistical analysis plan
SCr
Serum creatinine
SDD
Spray dried dispersion
SoA
schedule of activities
SOP
standard operating procedure
SRSD
single reference safety document
SToD
study team on demand
SUSAR
suspected unexpected serious adverse reaction
TB
Tuberculosis
TBili
total bilirubin
TEAE
Treatment emergent adverse event
TNF
Tumor necrosis factor
TYK2
tyrosine kinase 2
UGT
UDP-glucuronosyltransferase enzymes 
ULN
upper limit of normal
US
United States
UVB
Ultraviolet band
Vss
Apparent volume of distribution at steady state
VTE
venous thromboembolic events
WBC
white blood cell
WOCBP
woman of childbearing potential
CCI


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11. REFERENCES
1.
Feldman SR, Goffe B, Rice G, Mitchell M, Kaur M, Robertson D, Sierka D, Bourret JA, 
Evans TS, and Gottlieb A. The Challenge of Managing Psoriasis: Unmet Medical Needs 
and Stakeholder Perspectives. Am Health Drug Benefits. 2016 Dec; 9(9):504-513. 
2.
Farhad S, Khoshmirsafa M, Aazami H,  Mohsenzadegan M, Sedighi G and Bahar M. 
The role of JAK-STAT signaling pathway and its regulators in the fate of T helper cells 
Cell Commun Signal. 2017;15: 23.
3.
Floss DM, Klöcker T, Schröder J, Lamertz L, Mrotzek S, Strobl B, Herman H, and 
Schellera J. Defining the functional binding sites of interleukin 12 receptor β1 and 
interleukin 23 receptor to Janus kinases. Mol Biol Cell. 2016 Jul 15; 27(14):2301–2316.
4.
Tesmer LA, Lundy SK, Sarkar S, and Fox DA. Th17 cells in human disease Th17 cells 
in human disease. Immunol Rev. 2008 Jun;223:87-113.
5.
Zambrano-Zaragoza JF, Romo-Martínez EJ, Durán-Avelar J, García-Magallanes N, and 
Vibanco-Pérez N. Th17 Cells in Autoimmune and Infectious Diseases Int J 
Inflam.2014; 2014: 651503.
6.
Suomela S, Kainu K, Onkamo P, Tiala I, Himberg J, Koskinen L, Snellman E, 
Karvonen SL, Karvonen J, Uurasmaa T, Reunala T, Kivikäs K, Jansén CT, Holopainen 
P, Elomaa O, Kere J, Saarialho-Kere U. Clinical associations of the risk alleles of HLA-
Cw6 and CCHCR1*WWCC in psoriasis. Acta Derm Venereol. 2007;87(2):127-34.
7.
Beatrice Marinoni, Angela Ceribelli, Marco S. Massarotti, and Carlo Selmi The Th17 
axis in psoriatic disease: pathogenetic and therapeutic implications Auto Immun 
Highlights. 2014 Jun; 5(1): 9–19.
8.
Papp et al. Phase 2 Trial of Selective Tyrosine Kinase 2 Inhibition in Psoriasis; The 
New England Journal of Medicine. 2018; 379:1313-1321.
9.
Kim and Krueger. Highly Effective New Treatments for Psoriasis Target the 
IL-23/Type 17 T Cell Autoimmune Axis. Annu.Rev. Med. 2017; 65: 255-269.
10.
Long CC, Finlay AY, Averill RW. The rule of hand: 4 hand areas = 2FTU = 1g. Arch 
Dermatol 1992;128 (8):1129-30.
11.
Posner K, Brown GK, Stanley B, Brent DA, Yershova KV, Oquendo MA, Currier GW, 
Melvin GA, Greenhill L, Shen S, Mann JJ. The Columbia–Suicide Severity Rating 
Scale: Initial Validity and Internal Consistency Findings From Three Multisite Studies 
With Adolescents and Adults. American Journal of Psychiatry. 168:1266–77.
12.
Zhu Y, Ye X, Zhu B, et al. Comparisons between the 2012 New CKD-EPI (Chronic 
Kidney Disease Epidemiology Collaboration) Equations and Other Four Approved 
Equations. PLoS ONE 9(1): e84688. 


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Page 137
13.
Wilson, H. D. et al. Reliability and Validity of the Psoriasis Symptom Inventory in 
Patients With Psoriatic Arthritis. Arthritis Care & Research 67,1750-1756,(2015).
14.
Stander, S. et al. Validation of the Itch Severity Item as a Measurement Tool for 
Pruritus in Patients with Psoriasis: Results from a Phase 3 Tofacitinib Program. Acta 
dermato-venereologica 98, 340-345,(2018).
15.
Kimball, A. B. et al. Psychometric properties of the Itch Numeric Rating Scale in 
patients with moderate-to-severe plaque psoriasis. The British Journal of Dermatology 
175, 157-162,(2016).
16.
Finlay AY, Khan GK. Dermatology Life Quality Index (DLQI) – a simple practical 
measure for routine clinical use. Clin Exp Dermatol 1994; 19(3):210-6.
17.
Ware, J. et al. Development. User's Manual for the SF-36v2® Health Survey. Lincoln 
(RI): QualityMetric Incorporated (2007).
18.
EuroQol--a new facility for the measurement of health-related quality of life. Health 
policy (Amsterdam, Netherlands) 16, 199-208;(1990).
19.
Herdman, M. et al. Development and preliminary testing of the new five-level version 
of EQ-5D (EQ-5D-5L). Quality of life research : an international journal of quality of 
life aspects of treatment, care and rehabilitation 20, 1727-1736,(2011).
20.
Janssen, M. F. et al. Measurement properties of the EQ-5D-5L compared to the EQ-5D-
3L across eight patient groups: a multi-country study. Quality of life research: an 
international journal of quality of life aspects of treatment, care and rehabilitation 
22,1717-1727,(2013).

SAP_001.pdf: 
Protocol C2501004 (PF-06826647) Statistical Analysis Plan
PFIZER CONFIDENTIAL 
Page 1
Protocol C2501004
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 
Statistical Analysis Plan 
(SAP)
Version:
3.0
Author:
Date:
29-Nov-2020  
PPD
CCI


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PFIZER CONFIDENTIAL 
Page 2
TABLE OF CONTENTS
LIST OF TABLES.....................................................................................................................4
APPENDICES ...........................................................................................................................4
1. VERSION HISTORY............................................................................................................6
2. INTRODUCTION .................................................................................................................6
2.1. Study Objectives, Endpoints, and Estimands............................................................8
2.1.1. Primary Estimand(s)...................................................................................13
2.1.2. Secondary Estimand(s)...............................................................................14
2.1.3. Additional Estimand(s)...............................................................................14
2.2. Study Design ...........................................................................................................15
2.3. Schema ....................................................................................................................15
3. ENDPOINTS AND BASELINE VARIABLES: DEFINITIONS AND 
CONVENTIONS ................................................................................................................16
3.1. Investigational Treatment Period ............................................................................16
3.1.1. Primary Endpoint(s)....................................................................................16
3.1.2. Secondary Endpoint(s)................................................................................16
3.2. Extention Treatment Period ....................................................................................18
3.2.1. Primary Endpoint(s)....................................................................................18
3.3. Baseline Variables...................................................................................................18
3.4. Safety Endpoints .....................................................................................................19
3.4.1. Adverse Events...........................................................................................19
3.4.2. Laboratory Data..........................................................................................19
3.4.3. Vital Signs, including Height and Weight..................................................20
3.4.4. Physical Examinations................................................................................20
4. ANALYSIS SETS (POPULATIONS FOR ANALYSIS)...................................................20
4.1. Full Analysis Set (FAS) ..........................................................................................20
4.2. Safety Analysis Set..................................................................................................20
4.4. Treatment Misallocations and Missing Data...........................................................20
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4.5. Handling of Missing Data due to COVID-19 Pandemic.........................................22
5. GENERAL METHODOLOGY AND CONVENTIONS....................................................22
5.1. Hypotheses and Decision Rules ..............................................................................22
5.2. General Methods .....................................................................................................23
5.2.1. Analyses for Binary Endpoints...................................................................23
5.2.2. Analyses for Continuous Endpoints ...........................................................23
5.2.3. Analyses for Categorical Endpoints ...........................................................24
5.2.4. Analyses for Time-to-Event Endpoints ......................................................24
5.3. Methods to Manage Missing Data ..........................................................................24
6. ANALYSES AND SUMMARIES ......................................................................................24
6.1. Primary Endpoint(s) ................................................................................................24
6.1.1. Proportion of Participants Achieving PASI90 at Week 16 ........................24
6.1.1.1. Main Analysis ...........................................................................24
6.1.1.2. Sensitivity/Supplementary Analyses.........................................25
6.2. Secondary Endpoint(s) ............................................................................................25
6.2.1. Proportion of Participants Achieving PASI75............................................25
6.2.1.1. Main Analysis ...........................................................................25
6.2.1.2. Sensitivity/Supplementary Analysis .........................................25
6.2.2. Proportion of Participants with PGA 0/1, PGA 0/1 and ≥2 Points 
Improvements ..................................................................................................26
6.2.2.1. Main Analysis ...........................................................................26
6.2.2.2. Sensitivity/Supplementary Analysis .........................................26
6.2.3. Change and Percent Change From Baseline in PASI Score at Week 
16......................................................................................................................26
6.2.3.1. Main analysis.............................................................................26
6.2.3.2. Sensitivity/Supplementary Analysis .........................................27
6.2.4. Secondary Endpoints: Continuous Data.....................................................27
6.2.5. Secondary Endpoint: Binary Data ..............................................................27
6.2.5.1. Main Analysis ...........................................................................28
6.2.5.2. Sensitivity/Supplementary Analyses.........................................28
6.3. Clinical Laboratory Values, ECG ...........................................................................28
6.5. Skin Biopsy .............................................................................................................29
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6.6. Subset Analyses.......................................................................................................29
6.7. Baseline and Other Summaries and Analyses.........................................................29
6.7.1. Baseline Summaries....................................................................................29
6.7.2. Study Conduct and Participant Disposition................................................29
6.7.3. Study Treatment Exposure .........................................................................29
6.7.4. Concomitant Medications and Nondrug Treatments..................................29
6.8. Safety Summaries and Analyses .............................................................................30
6.8.1. Adverse Events...........................................................................................30
6.8.2. Laboratory Data..........................................................................................31
6.8.3. Vital Signs ..................................................................................................31
6.8.4. Electrocardiograms.....................................................................................31
6.8.5. Physical Examination .................................................................................31
7. INTERIM ANALYSES.......................................................................................................31
7.1. Introduction .............................................................................................................31
7.2. Interim Analyses and Summaries............................................................................31
8. REFERENCES ....................................................................................................................32
LIST OF TABLES
Table 1.
Summary of Changes..................................................................................6
APPENDICES
Appendix 1. Summary of Efficacy Analyses...........................................................................33
Appendix 2. Data Derivation Details.......................................................................................34
Appendix 2.1. Definition and Use of Visit Windows in Reporting.........................................34
Appendix 2.2. Endpoint Derivations .......................................................................................35
Appendix 3. Statistical Methodology Details..........................................................................39
Appendix 4. SAS Code for Estimand 2 –Change from Baseline in PASI Score.....................40
Appendix 5. SAS Code for the Generalized Linear Mixed Model for Binary 
Longitudinal Data .....................................................................................42
Appendix 6. SAS Code for Estimand 1 – Risk Difference using (Chan and Zhang 
1999)2........................................................................................................43
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Appendix 7. SAS Code for the Confidence Interval of a Binomial Proportion 
(Blyth-Still-Casella)..................................................................................44
Appendix 8. List of Abbreviations...........................................................................................45
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1. VERSION HISTORY
Table 1.
Summary of Changes
Version
Version Date
Specific Changes
1.0
18 Dec 2019
N/A
2.0
19 Jun 2020
•
Section 4.5: has been added specifying COVID-19 
data handling.
•
Section 6.2.4: the endpoint PP-NRS ≥4 has been 
removed.
•
Section 6.4: has been edited.
•
Appendix 2.1: visit windows has been adjusted.
•
Appendix 4: SAS codes have been adjusted.
3.0
29 Nov 2020
Changes were made per the planned analyses reduction 
on some Secondary 
•
Section 2.1.2: removed the not applicable 
endpoints for Estimand E2.
•
Section 3.1.2: deleted the abosolute values for 
PP-NRS and PSI as the secondary endpoints, only 
kept change from baseline.
•
 
•
Section 6.2.3: added the detailed analysis for 
change and percent change from baseline of PASI 
at Week 16.
•
Section 6.2.4 and Section 6.2.5: updated the 
analyses per the planned reduction.
•
Appendix 1: updated and corrected the summary 
of analyses for efficacy endpoints.
Other changes:
•
Corrected some typos.
•
Appendix 2.1: added footnotes to clarify some 
special cases for Week 16 and Week 18, adjusted 
the Week 40 visit window, clarified the handling 
of multiple obsevations in a same window.
•
Appendix 2.3: deleted.
2. INTRODUCTION
PF-06826647 is a potent tyrosine kinase 2 (TYK2) inhibitor with a good selectivity profile 
over other human kinases and is being investigated in participants with plaque psoriasis.  
Based on its cytokine inhibition profile, PF-06826647 is expected to target the T-helper 
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1 (Th1), T-helper 17 (Th17), and Types I interferon signaling pathways directly by inhibiting 
TYK2.  This should provide therapeutic benefit in the treatment of inflammatory conditions 
driven by Th1/Th17 and interferon immune responses. 
The purpose of this multicenter, placebo controlled double blind study is to provide 
additional efficacy, safety, tolerability 
 data regarding PF-06826647 in 
the oral treatment of moderate to severe plaque psoriasis.  It is intended to enable dose 
selection for the future development of PF-06826647.
The most common variant of psoriasis or plaque psoriasis, is a chronic inflammatory 
autoimmune skin disease characterized by red, scaly, raised plaques.  Chronic plaque 
psoriasis is a common skin disorder with a worldwide prevalence of 2% and afflicts an 
estimated 7.4 million Americans.  Although psoriasis primarily affects the skin and is not a 
life threatening disease, it can profoundly impact the patient’s quality of life (QoL) resulting 
in impairment akin to other major diseases, such as diabetes, cardiovascular disease, and 
psoriatic arthritis.1
The Janus kinase (JAK) family, which includes JAK1, JAK2, JAK3 and TYK2, is a group of 
cytoplasmic tyrosine kinases that mediate signal transduction via interactions with Type 1 
and Type 2 cytokine receptors critical for immune cell function, survival, activation, and 
proliferation.  TYK2 pairs with JAK1 to mediate type I interferon (IFN) signaling and with 
JAK2 to transmit interleukin (IL) IL-12 and IL-23 signaling.  Both of these key cytokines are 
implicated in the pathophysiology of plaque psoriasis.  IL-12 and IL-23 require TYK2 for 
signal transduction, indicating that inhibition of TYK2 mediated signaling could be 
efficacious in the treatment of these inflammatory conditions.
Over activation of Th17 and the main effector cytokines of Th17 cells has been linked to 
various inflammatory diseases, including psoriasis (see the protocol) Th17 cells are elevated 
in psoriatic lesions, along with levels of proinflammatory cytokines, including IL-17A, 
IL-17F, IL-17C, which are expressed by Th17 cells and are likely mediators of inflammation 
and tissue damage (see the protocol).  Human genetic studies implicate the Th17 pathway in 
psoriasis, and have uncovered likely risk alleles which include genes involved in IL-23 
signaling and genes that function downstream of the IL-17 receptor.  In addition to genetic 
evidence, several effective psoriasis therapies target Th17 cytokine production, suggesting a 
central role of Th17 and IL-17 in the disease.  The newest and most effective therapeutics are 
directed to the cytokines and cytokine signaling of interleukin-23/type 17 T cell (IL-23/T17) 
axis.  Additionally, the TYK2-selective inhibitor, BMS-986165, recently showed efficacy in a 
Phase 2 psoriasis study.  Thus, there is strong rationale for targeting the Th17 pathway in 
the treatment of psoriasis.
This statistical analysis plan (SAP) provides the detailed methodology for summary and 
statistical analyses of the data collected in Study C2501004.  This document may modify the 
plans outlined in the protocol; however, any major modifications of the primary endpoint 
definition or its analysis will also be reflected in a protocol amendment.
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2.1. Study Objectives, Endpoints, and Estimands
Objectives
Endpoints
Estimands
Primary: 
Primary:
Primary: 
To compare the efficacy of multiple 
dose levels of PF-06826647 versus 
placebo on the proportion of 
participants with moderate to severe 
plaque psoriasis achieving PASI 90.
•
Proportion of 
participants achieving 
PASI 90 (90% or greater 
improvement from 
Baseline) at Week 16.
Estimand E1:
This estimand is intended to 
provide a population level 
estimate of the treatment effect of 
the IP alone on a binary responder 
endpoint; without the benefit of 
additional prohibited medications, 
regardless of participant’s 
compliance with the IP dosing.
Population: Participants with 
moderate to severe plaque 
psoriasis as defined by the 
inclusion and exclusion criteria 
without the benefit of additional 
prohibited medication regardless 
of compliance.
Intercurrent Events: A) Prohibited 
medication –response will be 
considered negative for 
participants after receiving 
prohibited medication.  B) 
Withdrawal and all other events 
leading to missing data will be 
treated as in A).  C) Inadequate 
compliance – participants data 
will be used as recorded.
Population level summary: The 
difference in proportions between 
treated and placebo response 
rates.
Secondary: 
Secondary:
Secondary: 
To compare the efficacy of multiple 
dose levels of PF-06826647 versus 
placebo on the proportion of 
participants with moderate to severe 
plaque psoriasis achieving PASI 75.
Key secondary endpoint:
•
Proportion of 
participants achieving 
PASI 75 (75% or greater 
improvement from 
Baseline) at time points 
specified in the Schedule 
of Activities (SoA).
The binary secondary endpoints, 
when appropriate, will be analyzed 
descriptively and using estimand 
E1.
To compare the efficacy of multiple 
dose levels of PF-06826647 versus 
placebo on PGA score in participants 
with moderate to severe plaque 
psoriasis.
•
Proportion of 
participants with PGA 
score clear (0) or almost 
clear (1) and ≥2 points 
improvement from 
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Objectives
Endpoints
Estimands
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.
To compare the efficacy of multiple 
dose levels of PF-06826647 versus 
placebo on the proportion of 
participants with moderate to severe 
plaque psoriasis achieving PASI 50 
and PASI 100.
•
Proportion of 
participants achieving 
PASI 50 (50% or greater 
improvement from 
Baseline), PASI 100 
(100% from Baseline) at 
time points specified in 
the SoA.
To compare the efficacy of multiple 
dose levels of PF-06826647 versus 
placebo on PGA and PASI scores in 
participants with moderate to severe 
plaque psoriasis.
•
Change from baseline 
and percent change from 
baseline in PASI scores at 
time points specified in 
the SoA.
Estimand E2: 
This estimand is intended to 
provide a population level 
estimate of the treatment effect of 
the IP alone on a continuous 
endpoint; without the benefit of 
additional prohibited medications, 
regardless of participant’s 
compliance with the IP dosing.
Population: Participants with 
moderate to severe plaque 
psoriasis as defined by the 
inclusion and exclusion without 
the benefit of additional prohibited 
medications regardless of 
compliance.
Intercurrent Events: A) Prohibited 
medication – all scores after 
participants receive prohibited 
medication will be omitted 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 will 
be treated similarly as in A).  
C) Inadequate compliance –
participants data will be used as 
recorded.
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Objectives
Endpoints
Estimands
To compare the effect of multiple dose 
levels of PF-06822647 versus placebo 
in Peak-Pruritus Numerical Rating 
Scale score in participants with 
moderate to severe plaque psoriasis.
•
Absolute score and 
change from baseline in 
Peak-Pruritus Numerical 
Rating Scale score at time 
points specified in the 
SoA.
Population level summary: 
The mean difference between 
treated and placebo arms of the 
change from baseline PASI score.
All continuous endpoint, when 
appropriate will be analyzed 
descriptively and using estimand E2 
described above when appropriate.
To assess the safety and tolerability of 
PF-06826647 in participants with 
moderate to severe plaque psoriasis.
•
Incidence and severity of 
adverse events, serious 
adverse events and 
withdrawals due to 
adverse events. 
•
Change from baseline in 
clinical laboratory values 
(chemistry, hematology & 
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).
There is no defined estimand for 
these endpoints and they will be 
analyzed using Pfizer data 
standards as applicable.
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.
•
Absolute score and 
change from baseline 
Psoriasis Symptom 
Inventory at time points 
specified in the SoA.
This endpoints will be analyzed 
descriptively and using estimand E2 
described above when appropriate.
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Study Objectives, Endpoints and Estimands -- Extension Treatment Period
Objectives
Endpoints
Estimands
Primary: 
Primary:
Primary: 
To assess the safety and tolerability 
of PF-06826647 in participants with 
moderate to severe plaque psoriasis.
•
Incidence and severity of 
adverse events, serious 
adverse events and 
withdrawals due to adverse 
events. 
•
Change from baseline in 
clinical laboratory values 
(chemistry, hematology & 
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).
Not Applicable, will be analyzed 
descriptively and according to the 
Pfizer standard.
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2.1.1. Primary Estimand(s)
The primary estimand will provide a population level estimate of the treatment effect of 
PF-06826647 on the proportion of participants with moderate to severe plaque psoriasis 
achieving PASI 90 (90% or greater improvement from Baseline) under the hypothetical 
scenario that prohibited medications are not used regardless of dosing compliance.
•
Population: Participants with moderate to severe plaque psoriasis as defined by the 
inclusion and exclusion criteria without the benefit of additional prohibited 
medication regardless of compliance.
•
Variable: Proportion of participants achieving PASI 90 (90% or greater improvement 
from Baseline) at Week 16.
•
Intercurrent events: A) Prohibited medication –response will be considered negative 
for participants after receiving prohibited medication.  B) Withdrawal and all other 
events leading to missing data will be treated as in A).  C) Inadequate compliance –
participants data will be used as recorded.
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•
Population-level summary: The difference in proportions between treated and 
placebo response rates.
The primary estimand strategy will be applied to the following secondary endpoints:
•
Proportion of participants with PGA score clear (0) or almost clear (1) and ≥2 points 
improvement (daily and weekly) 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 with PSI overall score ≤8 with 0 or 1 for every individual 
domain time points specified in the SoA.
•
The primary estimand will also be used for PASI 75 response at all time points 
specified in the Schedule of Activities.
2.1.2. Secondary Estimand(s)
The secondary estimand will provide a population level estimate of the treatment effect of 
PF-06826647 on continuous endpoints, especially the change from baseline and the percent 
change from baseline in PASI scores under the hypothetical scenario that prohibited 
medication is not used regardless of dosing compliance.
•
Population: Participants with moderate to severe plaque psoriasis as defined by the 
inclusion and exclusion without the benefit of additional prohibited medications 
regardless of compliance.
•
Variable: Change from baseline or the percentage change from baseline in PASI at 
Week 16.
•
Intercurrent Events: A) Prohibited medication – all scores after participants receive 
prohibited medication will be omitted 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 will be treated similarly as in A).  C) Inadequate compliance –
participants data will be used as recorded.
•
Population-level summary: The mean difference between treated and placebo arms of 
the change from baseline/percentage change from baseline PASI score. 
2.1.3. Additional Estimand(s)
There is no defined estimand for other endpoints, and they will be analyzed using Pfizer data 
standards as applicable.
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2.2. Study Design
This is a Phase 2b, randomized, double blind, placebo controlled, parallel group, multicenter 
study in participants with moderate to severe plaque psoriasis.  After a screening period 
of - up to 6 weeks, eligible participants will be randomized in a 2:1:1:2:2 ratio such that 
participants will receive placebo or either one of four PF-06826647 daily dose levels 
(50 mg, 100 mg, 200 mg or 400 mg) every day during the Investigational Treatment Period 
for 16 weeks in a blinded fashion.  All participants completing the 16 week Investigational 
Period will continue on to a 24 week non-placebo controlled Extension Treatment Period 
with double blind oral daily treatment, if per the Investigator judgment the participant is 
compliant with study procedures and continued participation presents no safety risks.  The 
participants continuing into the Extension Treatment Period that were originally randomized 
to the 200 mg and 400 mg treatment groups will continue on their respective doses, while 
those randomized to one of the other treatment groups (including placebo) will be randomly 
assigned (at study baseline) to receive either 200 mg or 400 mg during the Extension 
Treatment Period.  Participants who discontinue prior to Week 16 visit will enter the 
Follow-Up period and will not be eligible for the Extension Period.
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) 
will be randomly assigned to a treatment group in order to ensure a minimum of 
128 evaluable participants completing Week 16 (assuming a 20% dropout rate).
2.3. Schema
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The total duration of study participation will be approximately 50 weeks, including up to 
6 weeks Screening Period, 16 week Investigational Treatment Period, the 24 week Extension 
Treatment Period and a Follow-Up visit 4 weeks after the Extension Treatment Period.
Investigators, participants, and the sponsor study team (with the exception of the sponsor 
supply chain lead) will be blinded as to investigational drug.  
If a participant is withdrawn from IP treatment, the participant will proceed with the Early 
Termination (ET) and Follow up visits per Schedule of Activities.  If a participant uses 
prohibited medication, guidance in Section 10.8 of the protocol should be followed.
3. ENDPOINTS AND BASELINE VARIABLES: DEFINITIONS AND 
CONVENTIONS
3.1. Investigational Treatment Period
3.1.1. Primary Endpoint(s)
•
Proportion of participants achieving PASI 90 (90% or greater improvement from 
Baseline) at Week 16.
3.1.2. Secondary Endpoint(s)
•
Proportion of participants achieving PASI 75 (75% or greater improvement from 
Baseline) at time points specified in the Schedule of Activities (SoA) of the protocol.
•
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 from 
Baseline), 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 Peak-Pruritus Numerical Rating Scale score at time points 
specified in the SoA. 
•
Proportion of participants with PSI overall score ≤8 with 0 or 1 for every individual 
domain time points specified in the SoA.
•
Incidence and severity of adverse events, serious adverse events and withdrawals due 
to adverse events. 
•
Change from baseline in clinical laboratory values (chemistry, hematology & lipids).
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•
Incidence of clinically significant changes in ECG (heart rate, QT, QTc, PR and QRS 
intervals). 
Note: For heart rate, the clinically significant abnormal criteria are < 40 or > 120 
beats per minute (bpm).  
•
Change from baseline in vital signs (blood pressure, pulse rate and temperature 
measurements).
•
Change from baseline Psoriasis Symptom Inventory at time points specified in the 
SoA.
 
 
 
 
 
 
 
 
 
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3.2. Extention Treatment Period
3.2.1. Primary Endpoint(s)
•
Incidence and severity of adverse events, serious adverse events and withdrawals due 
to adverse events. 
•
Change from baseline in clinical laboratory values (chemistry, hematology & 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).
 
 
 
 
 
 
 
 
3.3. Baseline Variables
Baseline will be defined as the last available measurement prior to randomization on Day 1, 
if a Day 1 measurement is not available, the value from the Screening visit can be used.  For 
the PRO endpoints baseline will be defined as the average of all values/values recorded on 
Day 1 or the last available screening vists when missing Day 1 measurement.  
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3.4. Safety Endpoints
Safety will be assessed by the spontaneous reporting of AEs, physical examinations, and 
clinical laboratory results in all subjects 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 and change from baseline in selected clinical 
laboratory values, ECG measurements, and vital signs.
The safety endpoints will be defined in accordance with Clinical Data Interchange Standards 
Consortium (CDISC) and Pfizer Standards (CaPS).
3.4.1. Adverse Events
An adverse event will be considered a Treatment-Emergent Adverse Event (TEAE) if the 
event started during the effective duration of treatment.  All events that start on or after the 
first dosing day (after the first application of IP) and time/start time, if collected, but before 
the last dose plus the lag time will be flagged as TEAEs.  The algorithm will not consider any 
events that started prior to the first dose date. 
A 3-tier approach will be used to summarize AEs. Under this approach, AEs are classified 
into 1 of 3 tiers. Different analyses will be performed for different tiers (see Section 6.8.1).
Tier 1 events: These are prespecified events of clinical importance and are maintained in a 
list in the product’s Safety Review Plan.
Tier 2 events: These are events that are not tier 1 but are “common.” A Medical Dictionary 
for Regulatory Activities (MedDRA) preferred term (PT) is defined as a Tier 2 event if there 
are at least 4 in any treatment group.
Tier 3 events: These are events that are neither Tier 1 nor Tier 2 events.
3.4.2. Laboratory Data
Below is a list of hematology and serum chemistry test parameters.
•
Hematology: hemoglobin, hematocrit, red blood cell count, reticulocyte count, 
platelet count, white blood cell count with differential, total neutrophils, eosinophils, 
monocytes, basophils, lymphocytes, coagulation panel.
•
Serum chemistry: blood urea nitrogen, creatinine, creatine phosphokinase, glucose, 
sodium, potassium, chloride, calcium, total bicarbonate, aspartate aminotransferase, 
alanine aminotransferase, gamma-glutamyl transferase, bilirubin, alkaline 
phosphatase, uric acid, albumin, total protein, total cholesterol, low-density 
lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides.
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3.4.3. Vital Signs, including Height and Weight
Vital sign measurements are body temperature, pulse rate, and blood pressures.
Weight is collected at pre- and post-treatment.
3.4.4. Physical Examinations
Complete physical examinations consist of assessments of the general appearance, skin, 
head, eyes, ears, nose, throat,cardiovascular, respiratory (lung), gastrointestinal, and 
neurological systems.
4. ANALYSIS SETS (POPULATIONS FOR ANALYSIS)
4.1. Full Analysis Set (FAS)
As specified in the protocol, the analysis of the efficacy, patient reported outcome 
 
 endpoints will be performed for the modified intent-to-treat (mITT) population, 
defined as all randomized subjects who receive at least 1 dose of investigational product 
(PF-06826647 or placebo). This population is also called the Full Analysis Set (FAS). 
4.2. Safety Analysis Set 
The safety analysis set (SAS) will be all subjects who receive at least 1 dose of 
investigational product.  The final safety database will include all reported safety data at the 
time of database release. 
 
 
4.4. Treatment Misallocations and Missing Data
If a subject was: 
•
Randomized but not treated: the subject will appear on the subject evaluation table as 
randomized but not treated; this is the extent of how much the subject will be 
reported; 
•
Treated but not randomized: the subject will be reported under the treatment they 
actually received for all safety analyses, but will not be included in the efficacy 
analyses; 
•
Randomized but took incorrect treatment: If a subject received the incorrect treatment 
for the whole duration of the study, then the subject will not be reported for any 
efficacy analysis, but will be summarized under the treatment they actually received 
for all safety analyses; if a subject received the incorrect treatment at only some 
dosing occasions then the subject will be reported under their randomized treatment 
group for both efficacy and safety analyses. If sufficient doses were incorrect and 
therefore deemed a major protocol deviation, the subjects may be excluded as 
sensitivity analysis. 
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For the continuous PRO variables such as pruritus NRS,
 rules suggested by 
the developers of these instruments will be followed in calculating the missing values.  If 
these rules are not enough for imputing a value, then the missing values will be handled in 
the same way as non-PRO variables.
Data for all participants will be assessed to determine if participants meet the criteria for 
inclusion in each analysis population prior to unblinding and releasing the database and 
classifications will be documented per standard operating procedures.
Population
Description
Full analysis set
All participants randomly assigned to IP and who apply at 
least 1 dose of IP.  
 
 
Safety
All participants who receive at least 1 dose of study 
intervention. Participants will be analyzed according to the 
intervention they actually received. A randomized but not 
treated participant will be excluded from the safety analyses.  
The following patient level data descriptions are also required for defining the pre-specified 
analyses:
Defined Analysis Data 
set (at the data level) –
endpoint specific
Description
Primary Estimand 
Categorical Endpoint Set
This set will include all patients in the mITT population.  All 
data for a subject after the initiation of prohibited medications, 
withdrawl of either study drug or the study itself will be set to 
a failure.  Any additional missing data will be recorded as a 
failure.  Subjects will have either a success or failure in the 
dataset for all scheduled visits.
Secondary Estimand 
Continuous Endpoint Set
This set will include all patients in the mITT population.  All 
data for a subject after the initiation of prohibited medications 
will be set to missing.
Note the secondary estimand requires multiple imputation 
which will be performed on this dataset, the multiple 
imputations themselves will not be saved in the database.
Observed Efficacy Set
This set will include all patients in the mITT population and all 
observed data and includes all data recorded from the CRF 
pages.  No data will be set to missing or modified from the 
original CRF record.
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4.5. Handling of Missing Data due to COVID-19 Pandemic
Due to the COVID-19 pandemic, as part of control measures some of the important endpoint 
data, such as PASI and PGA scores, are being collected via remote visit. If data are available
for those visits, then those will be incorporated in the analysis; any incomplete data or 
missing data collected via remote visit will be removed from the primary analysis. Hence no 
non-responder imputation will be done on missing binary data collected via remote visit.
All participants that are discontinued due to COVID-19 will be removed from the primary 
and secondary efficacy endpoint analyses. 
All missing data due to COVID-19 pandemic will be used ‘as is’ for the sensitivity analysis
and the safety analysis.
5. GENERAL METHODOLOGY AND CONVENTIONS
The primary analysis will be performed when all randomized subjects have either completed 
their 16-week study participation period  or withdrawn early or should the study be stopped 
prematurely due to any reason, and the database is released. An interim analysis may be 
performed for making internal business decisions regarding future study planning.  In that 
case, before any interim analysis is instigated, the details of the objectives, decision criteria, 
dissemination plan and method of maintaining the study blind as per Pfizer’s SOPs will be 
documented and approved in the IRC charter.
5.1. Hypotheses and Decision Rules
Statistical inference will be made on the primary endpoint: Proportion of participants 
achieving PASI 90 (90% or greater improvement from Baseline) at Week 16 based on an 
analysis of the Primary Estimand Endpoint Set.  The global null hypothesis is that there is no 
difference between any arm of PF-06826647 and placebo arm.  The alternative hypothesis is 
that one of the PF-06826647 arms being tested is superior to the placebo arm at Week 16.  
The study will be considered positive, if this null hypothesis is rejected.
Since test statistic corresponding to each of the PF-06826647 arms are indendepent with each 
others satisfying the distributional assumption about the use of Hochberg step-up procedure, 
the familywise error-rate will be controlled in strong sense at the 1-sided 0.05 level for these 
tests with a Hochberg step-up procedure (Hochberg, A sharper Bonferroni procedure for 
multiple significance testing 1988)3 (Hochberg and Tamhane, Multiple Comparison 
Procedures 1987)4 (Marcus, Peritz and Gabriel 1976). The p-values from the 3 comparisons 
will be ordered from smallest to largest, p[1], p[2], and p[3]. Testing will begin with the 
largest p-value, p[3], if significant at the 0.05 level that comparison and all other 
comparisions will be declared significant. If it is not significant, p[2] will be compared to an 
alpha of 0.05/2, if p[2] ≤0.05/2 it and all remaining hypotheses will be declared significant. 
If not significant, the process will continue using 0.05/3.
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5.2. General Methods
5.2.1. Analyses for Binary Endpoints
Landmark (cross-sectional) analyses of key binary endpoints will calculate and test for risk 
differences using the method of (Chan and Zhang 1999).2 Covariates will not be included in 
the primary analyses.  Risk differences and 90% confidence intervals will be presented.
For all key binary endpoints such as PASI75, PASI90 and PGA scores etc that are measured 
repeatedly over time, will be analyzed using generalized linear mixed effect model (GLMM) 
with treatment group (defined as factor variable), visit, treatment group by visit interaction 
and subjects as the random effect.  An unstructured covariance matrix will be used to fit such 
model. In case, if the model fails to converge, a covariance structure such as compound 
symmetry or autoregressive model may be used. Bayesian information criterion (BIC) will 
be used to assess the goodness of fit of the models. The model with the smallest BIC will be 
selected for inference. P-values and inference for relative risks between treatments will be 
provided based on the link function of logit.
For all binary endpoints, a summary based on the mITT Observed Efficacy Set of the number 
of subjects in each category based on observed cases in each treatment arm at each time point 
will be produced and the response rate will also be plotted against time, by treatment group.  
Explortatory categorical analyses that include or assess the effects of covariates may be done 
on an exploratory basis.  Exploratory longitudinal analyses may also be performed including 
appropriate covariates of interest.
5.2.2. Analyses for Continuous Endpoints
Landmark (cross-sectional) analysis of key continuous endpoints will use analysis of 
covariance (ANCOVA). The ANCOVA model will include terms for treatment arm and 
baseline score of the dependent variable. Least-squares means at the mean overall baseline 
score will be presented along with 90% confidence intervals.
Mixed model repeated measures (MMRM) models will be used.  The fixed effects of 
treatment, visit (Weeks 1 2, 4, 6, 8, 12 and 16), and treatment-by-visit interaction will be 
included.  Visit will be modeled as a categorical covariate.  Unstructured covariance matrix 
will be assumed for the model errors. Compound symmetry covariance matrix will be used if 
the model with unstructured covariance doesn’t converge.
When modeling the change from baseline values, the variable for visit will start with the first 
post-baseline visit, and the actual baseline value will be included as a covariate.  At each 
visit, estimates of least square mean (LSM) values and the LSM differences between the 
PF-06826647 treated groups and placebo group will be derived from the model.  The 
corresponding p-values and 90% confidence intervals will also be derived from the model.
Unless stated otherwise, descriptive summary statistics for all continuous variables will be 
presented on mITT Observed Efficacy Set by treatment group and will include the following: 
n, mean, median, standard deviation, minimum and maximum.
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5.2.3. Analyses for Categorical Endpoints
NA.
5.2.4. Analyses for Time-to-Event Endpoints
NA.
5.3. Methods to Manage Missing Data
The primary analysis will use the primary estimand binary endpoint set.  This dataset by 
definition has no missing data since all missing values will have been set to a failure.  
Summaries will use the Observed Efficacy Set and will report results on an observed case 
(OC) basis. For continuous endpoint data, each landmark analysis (eg, Cross sectional 
analysis by week) missing data will be imputed using a control based imputation method.  
PROC MI will first be called at the visit and a control based method (implemented with the 
MNAR (Missing Not At Random)--option) will impute missing placebo observations under 
the assumption data are missing at random (MAR) and impute missing treatment 
observations assuming they are similar to corresponding placebo patients.  Imputation will 
use the full conditional specification (FCS) method, the imputed data for the placebo arm 
will be combined for the analysis.
Summaries of continuous data will use the observed data only and no additional 
considerations are needed.
6. ANALYSES AND SUMMARIES
Analysis will be done pairwise between each of the PF-06826647 treated groups and the 
placebo group.  An analysis with point estimates of the difference, the associated 
90% confidence intervals and p-values will also be reported. 
A summary of analyses for clinical efficacy endpoints is provided in Appendix 1.  Visit 
windows to be used for all efficacy analyses and some relevant safety analyses are detailed in 
Appendix 2.1.
6.1. Primary Endpoint(s)
6.1.1. Proportion of Participants Achieving PASI90 at Week 16
6.1.1.1. Main Analysis
•
Estimand strategy: Primary Estimand (Section 2.1.1) use a composite endpoint 
strategy. 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: mITT (Section 4.1) using data prepared in the description of the Primary
Estimand Categorical Endpoint Set.
•
Analysis methodology: Risk differences will be analyzed using the method of (Chan 
and Zhang 1999)2 in PROC BINOMIAL. 
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•
Intercurrent events and missing data: These have been accounted for in the 
preparation of the Primary Estimand Categorical Endpoint Set (Section 4.4). This 
prepared data set has no missing values.
•
Proprotions, risk differences and 90% confidence intervals will be presented. 
6.1.1.2. Sensitivity/Supplementary Analyses
•
Estimand strategy: Primarily this estimand is intended to provide an estimate of the 
treatment effect in the population level assunming missing data are either MCAS 
(Missing Completely at Random) or MAR (Missing at Random). Applicable 
statistics will be calculated at Week 16.
•
Population: mITT.
•
Analysis methodology: GLMM and descriptive statistics.
•
Missing Data: Observed Data.
6.2. Secondary Endpoint(s)
6.2.1. Proportion of Participants Achieving PASI75
6.2.1.1. Main Analysis
•
Estimand strategy: Primary Estimand (Section 2.1.1) use a composite endpoint 
strategy. 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. Applicable statistics will be calculated at time points 
specified in the SoA.
•
Analysis set: mITT (Section 4.1) using data prepared in the description of the Primary
Estimand Categorical Endpoint Set.
•
Analysis methodology: Risk differences will be analyzed using the method of (Chan 
and Zhang 1999)2 in PROC BINOMIAL. 
•
Intercurrent events and missing data: These have been accounted for in the 
preparation of the Primary Estimand Categorical Endpoint Set (Section 4.4). This 
prepared data set has no missing values.
•
Proprotions, risk differences and 90% confidence intervals will be presented.
6.2.1.2. Sensitivity/Supplementary Analysis
•
Estimand strategy: Primarily this estimand is intended to provide an estimate of the 
treatment effect in the population level assunming missing data are either MCAS 
(Missing Completely at Random) or MAR (Missing at Random). Applicable 
statistics will be calculated at time points specified in the SoA.
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•
Population: mITT.
•
Analysis methodology: GLMM and descriptive statistics. 
•
Missing Data: Observed Data.
6.2.2. Proportion of Participants with PGA 0/1, PGA 0/1 and ≥2 Points Improvements
6.2.2.1. Main Analysis
•
Estimand strategy: Primary Estimand (Section 2.1.1 ) use a composite endpoint 
strategy.  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: mITT (Section 4.1) using data prepared in the description of the Primary
Estimand Categorical Endpoint Set.
•
Analysis methodology: Risk differences will be analyzed using the method of (Chan 
and Zhang 1999)2 in PROC BINOMIAL. 
•
Intercurrent events and missing data: These have been accounted for in the 
preparation of the Primary Estimand Categorical Endpoint Set (Section 4.4). This 
prepared data set has no missing values.
•
Proprotions, risk differences and 90% confidence intervals will be presented.
6.2.2.2. Sensitivity/Supplementary Analysis
•
Estimand strategy: Primarily this estimand is intended to provide an estimate of the 
treatment effect in the population level assunming missing data are either MCAS 
(Missing Completely at Random) or MAR (Missing at Random). Applicable 
statistics will be calculated at time points specified in the SoA.
•
Population: mITT.
•
Analysis methodology: GLMM and descriptive statistics. 
•
Missing Data: Observed Data.
6.2.3. Change and Percent Change From Baseline in PASI Score at Week 16
6.2.3.1. Main analysis
•
Estimand strategy: Seconday Estimand (Section 2.1.2) use a composite endpoint 
strategy. 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.
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•
Analysis set: mITT (Section 4.1) using data prepared in the description of the 
Seconday Estimand Continuous Endpoint Set.
•
Analysis methodology: ANCOVA model with treatments arms and baseline score as 
dependent variable. 
•
Intercurrent events and missing data:These have been accounted for in the estimand 
(Section 2.1.2) and missing data will be imputed using a contro based imputation 
method (Section 5.3).
•
Mean difference of change/percent change from baseline PASI score and 90% 
confidence intervals will be presented.
6.2.3.2. Sensitivity/Supplementary Analysis
•
Estimand strategy: Primarily this estimand is intended to provide an estimate of the 
treatment effect in the population level assuming missing data are either MCAS 
(Missing Completely at Random) or MAR (Missing at Random). Applicable 
statistics will be calculated at time points specified in the SoA.
•
Population: mITT.
•
Analysis methodology: MMRM and descriptive statistics.
•
Missing Data: Observed Data.
6.2.4. Secondary Endpoints: Continuous Data
Analyses of all continuous endpoints such as PASI, 
 PP-NRS, PSI, 
 
 etc for their percentage change or absolute change from baseline or 
absolute values:
•
Estimand strategy: Primarily this estimand is intended to provide an estimate of the 
treatment effect in the population level assuming missing data are either MCAS 
(Missing Completely at Random) or MAR (Missing at Random). Applicable 
statistics will be calculated at time points specified in the SoA.
•
Population: mITT.
•
Analysis methodology: MMRM and descriptive statistics.
•
Missing Data: Observed Data.
6.2.5. Secondary Endpoint: Binary Data
Analyses of all binary endpoints such as PASI 50, PASI 75, PASI 90, PASI 100, PGA (0/1), 
PGA (0/1 and ≥2), 
 PSI (≤8 and 0/1), 
for their 
proportions of participants will be as follows:
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6.2.5.1. Main Analysis
•
Estimand strategy: Primary estimand (Section 2.1.1) use a composite endpoint 
strategy.  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: mITT (Section 4.1) using data prepared in the description of the Primary 
Estimand Categorical Endpoint Set.
•
Analysis methodology: Risk differences will be analyzed using the method of (Chan 
and Zhang 1999)2 in PROC BINOMIAL. 
•
Intercurrent events and missing data: These have been accounted for in the 
preparation of the Primary Estimand Categorical Endpoint Set (Section 4.4). This 
prepared data set has no missing values.
•
Proprotions, risk differences and 90% confidence intervals will be presented. 
6.2.5.2. Sensitivity/Supplementary Analyses 
•
Estimand strategy: Primarily this estimand is intended to provide an estimate of the 
treatment effect in the population level assunming missing data are either MCAS 
(Missing Completely at Random) or MAR (Missing at Random). Applicable 
statistics will be calculated at time points specified in the SoA.
•
Population: mITT.
•
Analysis methodology: GLMM and descriptive statistics.
•
Missing Data: Observed Data.
6.3. Clinical Laboratory Values, ECG 
The following endpoints will be summarized using available data and not modeled.
Change from baseline in clinical laboratory values, Change from baseline in ECG parameters 
(hear rate, QT, QTc, PR and QRS intervals). Estimand strategy: No estimand is applicable. 
Summary statistics will be calculated at time points specified in the SoA.
•
Population: Safety Analysis Set.
•
Analysis methodology: Summary statistics.
•
Missing Data: Observed Data.
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6.5. Skin Biopsy
NA.
6.6. Subset Analyses
No subset analyses are planned; however the impact of different baseline subgroups on the 
primary and secondary endpoints may be explored on adhoc basis, and will not be reported in 
Clinical Study Report.
6.7. Baseline and Other Summaries and Analyses
6.7.1. Baseline Summaries
Demographic and baseline characteristics will be summarized by randomized treatment 
group for all randomized and treated subjects.  Continuous variables will be summarized 
using mean and standard deviation. Categorical variables will be summarized using relative 
frequency.  Key demographic and baseline variables to be summarized include: age, gender, 
race, ethnicity, height, weight, body mass index, disease duration, baseline PASI score, 
baseline PGA,
 etc.
6.7.2. Study Conduct and Participant Disposition
Subjects’ evaluation, disposition and discontinuation will be summarized according to CaPS.
6.7.3. Study Treatment Exposure
A summary of dosing compliance by treatment group will be provided.
The exposure to study drug will be summarized by the total number of days of dosing, 
mean/median number of days of exposure and number and percent of subjects in exposure 
duration categories.
6.7.4. Concomitant Medications and Nondrug Treatments
Prior drug and non-drug treatment, concomitant drug and non-drug treatment will be 
summarized according to CaPS.
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6.8. Safety Summaries and Analyses
The analysis population for safety is described in Section 4.4.  Safety and tolerability will be 
assessed by clinical review of all relevant parameters including adverse experiences (AEs) 
and laboratory tests.  A complete list of laboratory parameters can be obtained in 
Section 10.2 of the protocol.
All the tables, listings and graphs for adverse events, lab parameters and vital sign and ECG 
will follow Pfizer standards. 
6.8.1. Adverse Events
The binary safety endpoints including the incidences of on-treatment AEs, withdrawals due 
to AEs and serious AEs will be analyzed using the exact test described in Section 5.2.1.  A 
3-tier approach will be used to summarize AEs. Under this approach, AEs are classified into 
1 of 3 tiers. 
Tier-1 events: These are pre-specified events of clinical importance and are maintained in a 
list in the product’s Safety Review Plan. There are no Tier 1 events for this study.  Tier 1 
displays will not be created.
Tier-2 events: These are events that are not tier-1 but are “common”. A MedDRA Preferred 
Term (PT) is defined as a tier-2 event if there are at least 4 subjects with an event  in in any 
treatment group. 
Tier-3 events: These are events that are neither tier-1 nor tier-2 events.
There will be no adjustment for multiple comparisons or stratification factors in the analyses 
unless specified.  For tier-1 and tier-2 events, the proportion of AEs observed in each 
treatment groups will be presented along with the point estimates and associated 
95% confidence intervals of the risk difference for each active treatment compared with 
placebo using the exact methods described in Section 5.2.1.  For tier-1 events p-values may 
be included in the presentations.  AEs will be arranged in the output sorted in descending 
point estimate of the risk difference within system organ class.  Footnotes in the outputs will 
include the methods used to derive any p-values and confidence intervals as per Pfizer 
standards.
It should be recognized that most studies are not designed to reliably demonstrate a causal 
relationship between the use of a pharmaceutical product and an adverse event or a group of 
adverse events. Except for select events in unique situations, studies do not employ formal 
adjudication procedures for the purpose of event classification. As such, safety analysis is 
generally considered as an exploratory analysis and its purpose is to generate hypotheses for 
further investigation. The 3-tier approach facilitates this exploratory analysis.
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6.8.2. Laboratory Data
Laboratory data will be listed and summarized in accordance with the CaPS reporting 
standards.  Summaries of subjects meeting pre-specified discontinuation criteria will be 
created using methods for categorical data.
6.8.3. Vital Signs
Vital signs will be summarized at all visits per SoA.  
6.8.4. Electrocardiograms
ECG parameters, if applicable, will be summarized at baseline, Week 4, Week 16/End of 
Treatment visits and at Week 40.
6.8.5. Physical Examination
Physical examinations will be summarized at all-available post-baseline visits.
7. INTERIM ANALYSES
7.1. Introduction
There will be an interim analyses for this study. Interim analyses will be performed to assess 
efficacy and safety after at least 60% of the planned participants, ie, approximately 
80 participants, complete their study participation through Week 12.  Interim analysis results 
will be used for internal business decisions regarding future study planning or stopping for 
futility.  Before the interim analysis is instigated, the details of the objectives, decision 
criteria, dissemination plan and method of maintaining the study blind as per Pfizer’s SOPs 
will be documented and approved in the internal review committee (IRC) charter.  
7.2. Interim Analyses and Summaries
A separate interim analysis plan may be developed, if needed.
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8. REFERENCES
1.
Casella G. Refining binomial confidence intervals. Can J Statist 1986; 14: 113–129.
2.
Chan ISF and Zhang Z. Test based exact confidence intervals for the difference of two 
binomial proportions. Biometrics, 1999, 55:1201–1209.
3.
Hochberg, Y. 1988. ". A sharper Bonferroni procedure for multiple significance 
testing." Biometrika 75: 800-802.
4.
Hochberg, Y., and AC. Tamhane. 1987. Multiple Comparison Procedures. New Yrok: 
Wiley.
5.
Marcus R, Peritz E, Gabriel KR. On closed testing procedure with special reference to 
ordered analysis of variance. Biometrika, 1976, 63:655–660.
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Appendix 1. Summary of Efficacy Analyses
Endpoint
Analysis Type
Population
Data Inclusion and 
Rules for Handling 
Intercurrent Events 
and Missing Data 
Analysis 
Model
Proportion of 
achieving PASI90 at 
Week 16
Main Analysis
FAS
Prohibited 
medication/withdrawal 
and all other missing 
data will be treated as 
tratment failure
Chan and 
Zhang
Binary endpoints for 
PASI 75, PASI 90, 
PGA (0/1 and ≥2), 
PGA (0/1) at all time 
points
Sensitivity/Sup
plementary 
Analysis
FAS
Observed data
GLMM
Binary endpoints for  
PASI 75, PASI 90,  
PGA (0/1 and ≥2), 
PGA (0/1), 
 
 PSI (≤8 and 
0/1),
 
Main Analysis
FAS
Prohibited 
medication/withdrawal 
and all other missing 
data will be treated as 
treatment failure
Chan and 
Zhang
Continuous 
endpoints for PASI 
Main Analysis
FAS
Multiple Imputation
ANCOVA
Continuous 
endpoints for PASI, 
 PP-NRS, PSI, 
Sensitivity/
Supplementary 
Analysis
FAS
Observed data
MMRM
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Appendix 2. Data Derivation Details
Appendix 2.1. 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 Windowd
1
Screening 
N/A
-42 ≤ day ≤ -1
2
Baselinea
1 
day = 1
3
Week 1
8
2≤day≤11
4
Week 2
15 
12≤day≤21
5
Week 4
29 
22≤day≤35
6
Week 6
43
36≤day≤49
7
Week 8
57
50≤day≤70
8
Week 12
85
71≤day≤98
9
Week 16b
118
99≤day≤MIN (129, first dosing day 
at Week 18 -1) 
10
Week 18b
127
MIN (129, first dosing day at 
Week 18 -1)+1≤day≤133
11
Week 20
141
134≤day≤154
12
Week 24
169
155≤day≤182
13
Week 28
197
183≤day≤210
14
Week 32
225
211≤day≤238
15
Week 36
253
239≤day≤266
16
Week 40c
281
267≤day≤305
a.
Baseline analysis visit window may be considered as day ≤1 in some analyses (eg, those involving 
change from baseline).  That is, in case that Day 1 observation is missing, the last observation by the 
first dosing date may be considered as the baseline.  The baseline measurements for demography, 
height, pre-study medical history and medications will be collected at the “Screening” visit.
b.
If the nominal week 16 assessments happened at the same day as Week 18 dosing, for all the 
efficacy and safety endpoints analyses by visit, that day will be counted as Week 16 visit, but for the 
dosing and compliance analysis, that day will be counted as Week 18 visit.
c.
For the last on treatment visit of Week 40, we extended the visit window to include more data 
collected in the study. And here day 305 is the day before the scheduled target day of follow-up visit 
(309±3).
d.
For multiple observations fall into a same window, following algorithm will be takento identify the 
observation for analysis:
1.
The observation closest to the targeted day will be used.
2.
If the observations are with equal distant from the targeted day in absolute value, the one 
after the targeted day will be used.
All observations will, however, be included in the listings.
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Appendix 2.2. Endpoint Derivations
Psoriasis Area Severity Index (PASI)
The Psoriasis Area and Severity Index quantifies the severity of a subject's psoriasis based on 
both lesion severity and the percentage of body surface area affected. Lesion severity: the 
basic characteristics of psoriatic lesions - erythema, induration and scaling - provide a means 
for assessing the severity of lesions. Assessment of these three main signs is performed 
separately for four areas of the body: head, upper limbs, trunk, and lower limbs. Average 
erythema, induration and scaling are rated for each body area according to a 5-point scale: 
0, no involvement; 1, slight; 2, moderate; 3, marked; 4, very marked.
Body surface area (BSA) involvement: the extent (%) to which each of the four areas of the 
body is affected by psoriasis is assigned a numerical score according to the following area 
scoring criteria: 0, no involvement; 1, >0 to 9%; 2, 10 to 29%; 3, 30 to 49%; 4, 50 to 69%; 
5, 70 to 89%; 6, 90 to 100%. For details see Table 5 of the protocol.
Derivation of PASI score
In each area, the sum of the severity rating scores for erythema, induration and scaling is 
multiplied by the score representing the percentage of this area involved by psoriasis, 
multiplied by a weighting factor (head 0.1; upper limbs 0.2; trunk 0.3; lower limbs 0.4). The 
sum of the numbers obtained for each of the four body areas is the PASI.
PASI = 0Ah(Eh + Ih + Sh) + 0.2Au(Eu + Iu + Su) + 0.3At(Et + It + St) + 0.4Al(El + Il + Sl)
where A = area of involvement score; E = erythema; I =induration; S = scaling; h = head; 
u = upper limbs; t = trunk; l = lower limbs
The PASI score can vary in increments of 0.1 units from 0.0 to 72.0, with higher scores 
representing increasing severity of psoriasis.
PASI 50/75/90/100 response
At least 50/75/90/100% reduction in PASI relative to baseline PASI Score.
 
 
 
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Physician Global Assessment (PGA)
The Physician Global Assessment of psoriasis is 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 are rated separately over the whole body according to a 
5-point severity scale, scored from 0 to 4, with appropriate morphologic descriptors. The 
severity rating scores are summed and the average taken - the total average is rounded to the 
nearest whole number score to determine the PGA. The 5-point scale for PGA is: 0, "clear"; 
1, "almost clear"; 2, "mild"; 3, "moderate"; 4 "severe".
 
 
 
 
 
 
 
 
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Peak Pruritus Numerical Rating Scale (PP-NRS)
The intensity of pruritus will be assessed by a numerical rating scale (NRS), an 11-category 
numeric rating scale from 0 to 10.  Pruritus will be evaluated by asking participants to assign 
a numerical score representing the worst imaginable itch over the last 24 hours on a scale 
from 0 to 10, with 0 indicating no symptoms and 10 indicating the worst imaginable 
symptoms. This item will be administered to all participants.
 
 
 
 
 
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Appendix 3. Statistical Methodology Details
Hochberg Testing Procedure
Consider testing  null hypotheses H01, …H06 and let pi, i=1,…,6 denote the corresponding 
1-sided p-values from the individual pairwise comparisons against the placebo arm prior to 
multiplicity adjustment.  Furthermore, let [1], ….[6] denote the order of the p-values so that 
p[1] ≤p[2] ≤…. P[6].  The procedure starts with the largest p-value p[6] as follows:
1. If p[6] < α reject all null hypotheses, otherwise go to next step.
2. If p[5] < α/2 reject hypotheses H0[1] through H0[6], otherwise go to next step.
3. If p[k] < α/(6-k +1), reject hypotheses H0[1] through H0[k].
4. If p[1] < α/6, reject H0[1], otherwise stop and do not reject any hypotheses.
Alternatively, the unadjusted raw p-values can be read into Proc Multtest and 
adjusted using the HOC option in SAS’s PROC MULTTEST.
data pvals;
   Input Test$ Raw_P;
Datalines;
Test1 .xxxxx
Test2 .xxxxx
…..
Test6 .xxxxx
;
Proc multtest pdata=pvals hoc out=new;
run;
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Appendix 4. SAS Code for Estimand 2 –Change from Baseline in PASI Score
libname C2501004  "/Volumes/app/…… /data_vai" ;
data adps; 
set C2501004.adps; 
if paramcd="PASI0246" and 2<avisitn<=9 and ANL01FL="Y" ;
keep subjid avisitn aval base trtan paramcd anl01fl;
run;
**example data for a single visit;
**created from systemic study ;
**ignore values, only used for illustration;
*Multiple Imputation; 
**data already has one record per subject per visit even if; 
**data is missing. Proc Mi needs missing values in order to impute; 
data _data1; 
set ADPS;
where avisitn=9; 
run; 
proc sort data=data1 out=data1 miss;
by trtan;
run;
*imputing aval=observed so range of endpoint 0-72 can be included in; 
*mi procedure; 
proc mi data=data1_miss seed=2501004 nimpute=1000 out=outimp; 
class trtan; 
monotone regpmm(aval= base/details k=5);
mnar model( aval/modelobs = (trtan="1")); 
var base aval; 
run; 
proc univariate data=outimp; 
var aval; 
histogram; 
run; 
data outimp1; 
set outimp; 
chg = aval - base; 
**calculate chg from baseline; 
pchg= ((AVAL - BASE)/BASE)*100; 
**calculate pchg from baseline; 
run; 
proc sort data = outimp1 out = data1; 
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by imputation trtan usubjid; 
run; 
proc mixed data=data1 order=data; 
by imputation; 
class trtan; 
model CHG = trtan base; 
lsmeans trtan/ diff alpha=.1; 
ods output lsmeans=mmmrm diffs=dmmrm(where=(trtan=1)); 
run; 
**now use mianalyze on lsmean; 
**First sort by trtan; 
proc sort data=mmmrm out=lsout1; 
by trtan _imputation_; 
run; 
**now mianalyze by trtan; 
**NB mianalyze only uses estimates and standard errors not CI limits etc.; 
proc mianalyze data=lsout1 alpha=.1; 
**specify alpha for 90% CIs here; 
by trtan; 
modeleffects estimate; 
stderr stderr; 
ods output parameterestimates=lsmean; 
run; 
**now use mianalyze on lsmean differences; 
**First sort by trtan; 
proc sort data=dmmrm out=diffsout1; 
by trtan _imputation_; 
run; 
**now mianalyze by trtan; 
**NB mianalyze only uses estimates and standard errors not CI limits etc.; 
proc mianalyze data=diffsout1 alpha=.1; 
**specify alpha for 90% CIs here; 
by trtan; 
modeleffects estimate; 
stderr stderr; 
ods output parameterestimates=diff; 
run;
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Appendix 5. SAS Code for the Generalized Linear Mixed Model for Binary 
Longitudinal Data 
PROC GLIMMIX DATA =<DATA> METHOD=RMPL;
CLASS SUBJID TRTPN VISIT;
MODEL RESPONSE (EVENT = "1") = TRTPN VISIT TRTPN * VISIT / ALPHA = 0.1 
DIST=BINARY LINK=LOGIT;
RANDOM VISIT /SUBJECT = SUBJID TYPE=UN RESIDUAL;
LSMEANS TRTPN * VISIT / ILINK COV DIFF CL;
RUN;
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Appendix 6. SAS Code for Estimand 1 – Risk Difference using (Chan and Zhang 1999)2
PROC BINOMIAL DATA=<DATASET> GAMMA=0 ALPHA=<Value>;
PD/EX ONE STD;
PO <POPULATION VARIABLE>;
OU <OUTCOME VARIABLE>;
RUN;
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Appendix 7. SAS Code for the Confidence Interval of a Binomial Proportion 
(Blyth-Still-Casella)
PROC BINOMIAL DATA=<DATASET> ALPHA=<value>;
BI/BS;
OU <RESPONSE VARIABLE>;
RUN;
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Appendix 8. List of Abbreviations
Abbreviation
Term
Abs
absolute
AE
adverse event
ANCOVA
analysis of covariance
ANOVA
analysis of variance
ATC
Anatomic Therapeutic Chemical
AUC
area under the curve
BA
bioavailability
BE
bioequivalence
BIC
Bayesian information criterion
BLQ
below the limit of quantitation
BOCF
baseline observation carried forward
BP
blood pressure
BSA
Body Surface Area
CDARS
Clinical Data Analysis and Reporting System (of US Food and Drug 
Administration)
CDISC
Clinical Data Interchange Standards Consortium
CI
confidence interval
Cmax
maximum observed concentration
CMH
Cochran-Mantel-Haenszel
CRF
case report form
CSR
clinical study report
DMC
data monitoring committee
EAC
event adjudication committee
ECG
electrocardiogram
E-DMC
external data monitoring committee 
FAS
full analysis set
FCS
full conditional specification
FDA
Food and Drug Administration (United States)
GCP
Good Clinical Practice
GLIMMIX
generalized linear mixed-effects model with repeated measures
GLMM
generalized linear mixed effect model
GMC
geometric mean concentration
GMFR
geometric mean fold rise
GMR
geometric mean ratio
GMT
geometric mean titer
HDL
high density lipoprotein
ICD
informed consent document
ICH
International Council for Harmonisation
IRC
internal review committee
IST
independent statistical team
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Abbreviation
Term
ITT
intent-to-treat
LDL
low-density lipoprotein
LLOQ
lower limit of quantitation
LOCF
last observation carried forward
LOD
limit of detection
LS
least-squares
LSM
least-squares mean
MAR
missing at random
MCAS
Missing Completely at Random
MedDRA
Medical Dictionary for Regulatory Activities
mITT
modified intent-to-treat
MMRM
mixed-effects model with repeated measures
MNAR
missing not at random
N/A
not applicable
NNB
number needed to benefit
NNH
number needed to harm
NNT
number needed to treat
NOAEL
no-observed-adverse-effect level
OC
observed case
PASI
Psoriasis Area Severity Index
PD
pharmacodynamic(s)
PGA
Physician Global Assessment
PK
pharmacokinetic(s)
PP
per-protocol
PPAS
per-protocol analysis set
PP-NRS
Peak Pruritus Numerical Rating Scale
PRO
patient-reported outcome
PT
preferred term
QoL
quality of life
QTc
corrected QT
QTcF
corrected QT (Fridericia method)
qual
qualitative
RCDC
reverse cumulative distribution curve
RR
relative risk
SAE
serious adverse event
SAP
statistical analysis plan
SAS
safety analysis set
SD
standard deviation
SGS
Statistical Guidance Standards
SoA
schedule of activities
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Abbreviation
Term
SOP
standard operating procedure
SUSAR
suspected unexpected serious adverse reaction
TA
therapeutic area
TEAE
Treatment-Emergent Adverse Event
ULN
upper limit of normal
WHO 
World Health Organization
WHODD
World Health Organization Drug Dictionary
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