Clinical trial NCT03850483
Conditions: Psoriasis
Keywords: psoriasis topical
Sponsor: Pfizer
Start date: 2019-04-08; Completion date: 2021-04-20
Enrollment: 344 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This is a Phase 2b, randomized, double blind, vehicle controlled, parallel group, multicenter study in participants with mild to moderate plaque psoriasis. The duration of study participation will be approximately 22 weeks, including up to a 6 week screening period, 12 week treatment period, and approximately 4 week follow up period. Approximately 280 participants are planned to be randomized into the study.

Detailed description:

Arms: arm 1: Vehicle cream applied once daily (QD) arm 2: PF-06700841 0.1% cream applied once daily (QD) arm 3: PF-06700841 0.3% cream applied once daily (QD) arm 4: PF-06700841 1% cream applied once daily (QD) arm 5: PF-06700841 3% cream applied once daily (QD) arm 6: PF-06700841 0.3% cream applied twice daily (BID) arm 7: PF-06700841 1% cream applied twice daily (BID) arm 8: Vehicle cream applied twice daily (BID) arm 9: PF-06700841 3% cream applied twice daily (BID)
Interventions: intervention 1: PF-06700841 intervention 2: Vehicle (Placebo)
Intervention descriptions: intervention 1: PF-06700841 topical cream intervention 2: Vehicle topical cream

Protocol documents:
Prot_000.pdf: 
PF-06700841
Protocol B7931023
Final Protocol Amendment 1, 20 April 2020
PFIZER CONFIDENTIAL
Page 1
A PHASE 2B, RANDOMIZED, DOUBLE BLIND, VEHICLE-CONTROLLED, 
PARALLEL-GROUP, DOSE RANGING STUDY TO ASSESS EFFICACY, SAFETY, 
TOLERABILITY AND PHARMACOKINETICS OF PF-06700841 TOPICAL 
CREAM APPLIED ONCE OR TWICE DAILY FOR 12 WEEKS IN PARTICIPANTS 
WITH MILD TO MODERATE CHRONIC PLAQUE PSORIASIS
Investigational Product Number:
PF-06700841
Investigational Product Name:
N/A
United States (US) Investigational New 
Drug (IND) Number:
European Clinical Trials Database 
(EudraCT) Number:
2018-003051-38
Protocol Number:
B7931023
Phase:
2b
Short Title: A PHASE 2B DOSE RANGING STUDY TO ASSESS EFFICACY, SAFETY, 
TOLERABILITY AND PHARMACOKINETICS OF PF-06700841 TOPICAL CREAM IN 
PARTICIPANTS WITH CHRONIC PLAQUE PSORIASIS
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 History
Document
Version Date
Summary of Changes and Rationale
Amendment 1
20 April 2020
This amendment is making the following 
substantial changes:

Addition of an option to add an 
additional cohort of participants in BID 
dosing arm (and corresponding vehicle 
arm) as Stage 2 of the study. 

Changes related to the optional, 
additional cohort are in the Protocol 
Summary (Section 1.1, Section 1.2, 
and Section 1.3), Objectives, 
Estimands, and Endpoints 
(Section 3), Study Design 
(Section 4.1, Section 4.2., and 
Section 4.3), Study Assessments and 
Procedures (Section 8.8 and 
Section 8.11), and Statistical 
Considerations (Section 9.2, 
Section 9.4, Section 9.5. and 
Section 9.6) sections.
Rationale: The addition of an additional 
arm is intended to allow more extensive 
exploration of the dose response of the 
PF-06700841 topical cream. 
This Amendment is making following 
non-substantial changes and some editorial 
changes:

Incorporation of all 
changes/clarifications to-date, made via 
Protocol Administrative Clarification 
letters (PACLs).

Changes are in Protocol Summary
(Section 1), Schedule of Activities 
(Section 1.3), Study population 
(Section 5.2 and Section 5.4), Study 


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Assessments and Procedures 
(Section 8.2.1.2 and Section 8.2.2.3), 
and Interim Analysis (Section 9.5.1).
•
In the Protocol Summary (Section 1), 
Introduction (Section 2), and Study 
Design (Section 4) sections, changed 
text from “The oral formulation of 
PF-06700841 has been studied in 
several trials, this is the first clinical 
study for its topical formulation in 
patients”  
to 
“The oral formulation of PF-06700841 
has been studied in several trials, this is 
the first clinical study for its topical 
formulation in patients with mild to 
moderate plaque psoriasis.”
Rationale: At the time of this
Amendment, 2 other clinical studies
(B7931029 and B7931022) evaluated 
topical formulation of PF-06700841 in 
its topical formulation (Section 2.2.2). 
•
In the Protocol Summary (Section 1.1, 
and Section 1.3), Objectives and 
Endpoints (Section 3), Study Design 
(Section 4), and Study Assessments and 
Procedures (Section 8.8 and 
Section 8.11) sections, 
 
 
 
 
 
 
Rationale: As enrollment in Stage 2 will 
be limited to only 1 dosing arm and will 
have limited number of participants,
ie, approximately 40, optional 
assessments will not be offered in 
Stage 2.
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
Updated Figure 1 and Table 2 to clarify 
the timing of Stage 2 in context of 
Stage 1 and to include additional arms
(3% BID PF-06700841 and 
corresponding, BID vehicle arm).
Rationale: Schematic updated to reflect 
the update in the study design.

Updated Clinical Overview Section 
(Section 2.2.2) to match the most current 
IB (September 2019) language; added
newly started, completed and planned 
Phase 1 and Phase 2 studies using oral 
or topical formulations of PF-06700841. 
Rationale: Since the original protocol 
was issued, additional studies were 
completed, started or planned. Details 
were updated to match the updated 
Investigator’s Brochure 
(September 2019). 

Updated dose justification (Section 4.3) 
of newly added dosing arm in Stage 2.
Rationale: As newly added dosing arm 
is of different strength compared to the 
ones being tested in Stage 1, justification 
of dose section is updated accordingly. 

Updated participant
Discontinuation/Withdrawal From the 
Study (Section 7.2) to highlight possible 
reasons of discontinuation or withdrawal 
from the study.
Rationale: Discontuation or withdrawal 
reasons are updated to align with the 
data standards to be used in the study.

Updated Protocol Summary 
(Section 1.1) and Statistical 
Considerations (Section 9.2, Section 9.4, 
Section 9.5, and Section 9.6) sections to 
reflect changes made to the study design 


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due to the additional cohort (in Stage 2).
Rationale: As an additional dosing arm
is being added, justification of number 
of participants selected for this Cohort is 
described. Interim analysis (Section 9.5) 
and PK/PD unblinding section 
(Section 9.6) are also updated 
accordingly.

Added QuantiFERON®-TB Gold Plus
test as an acceptable IGRA assay in 
Study Assessments and Procedures 
(Section 8). 
Rationale: The assay, 
QuantiFERON®-TB Gold Plus test, was 
recently added to the list of acceptable 
IGRA assays by the central laboratory.
Original protocol
26 October 2018
Not applicable (N/A)
This amendment incorporates all revisions to date, including Protocol Administrative 
Clarification letters (PACLs), and amendments made at the request of country health 
authorities and IRBs/ECs.


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TABLE OF CONTENTS
LIST OF TABLES...................................................................................................................12
LIST OF FIGURES .................................................................................................................12
1. PROTOCOL SUMMARY...................................................................................................13
1.1. Synopsis ..................................................................................................................13
1.2. Schema ....................................................................................................................17
1.3. Schedule of Activities (SoA)...................................................................................18
2. INTRODUCTION ...............................................................................................................22
2.1. Study Rationale .......................................................................................................22
2.2. Background .............................................................................................................22
2.2.1. Non-Clinical Experience of PF-06700841 .................................................23
2.2.1.2. Non-Clinical Safety Studies......................................................24
2.2.2. Clinical Overview.......................................................................................25
2.2.2.1. Study B7931001........................................................................30
2.2.2.2. Study B7931009........................................................................30
2.2.2.3. Study B7931004........................................................................31
2.2.2.4. Ongoing Phase 2 Studies...........................................................31
2.2.3. Overview of Clinical Pharmacology ..........................................................32
2.2.3.1. Study B7931001........................................................................32
2.2.3.2. Study B7931009........................................................................32
2.2.3.3. Study B7931004........................................................................33
2.3. Benefit/Risk Assessment.........................................................................................33
3. OBJECTIVES, ESTIMANDS, AND ENDPOINTS ...........................................................34
4. STUDY DESIGN.................................................................................................................37
4.1. Overall Design.........................................................................................................37
4.2. Scientific Rationale for Study Design.....................................................................40
4.3. Justification for Dose ..............................................................................................41
4.4. End of Study Definition ..........................................................................................43
5. STUDY POPULATION......................................................................................................43
5.1. Inclusion Criteria.....................................................................................................43
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5.2. Exclusion Criteria....................................................................................................44
5.3. Lifestyle Considerations..........................................................................................48
5.3.1. Contraception..............................................................................................48
5.3.2. Dietary Supplements...................................................................................48
5.3.3. Vaccination.................................................................................................48
5.3.4. Other Lifestyle Requirements.....................................................................49
5.4. Screen Failures ........................................................................................................49
6. STUDY INTERVENTION..................................................................................................50
6.1. Study Intervention(s) Administered........................................................................50
6.1.1. Administration............................................................................................50
6.1.1.1. Treated Psoriatic Skin Areas.....................................................50
6.1.1.2. General Instructions ..................................................................51
6.2. Preparation/Handling/Storage/Accountability ........................................................52
6.2.1. Preparation and Dispensing........................................................................53
6.2.2. Investigational Product Accountability ......................................................54
6.2.3. Destruction of Investigational Product Supplies ........................................54
6.3. Measures to Minimize Bias: Randomization and Blinding.....................................54
6.3.1. Allocation to Investigational Product .........................................................54
6.3.2. Breaking the Blind......................................................................................55
6.4. Study Intervention Compliance...............................................................................55
6.5. Concomitant Therapy..............................................................................................56
6.5.1. Rescue Medicine.........................................................................................57
6.6. Dose Modification...................................................................................................57
6.7. Intervention After the End of the Study..................................................................57
7. DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL...........................................................................57
7.1. Discontinuation of Study Intervention ....................................................................57
7.1.1. Temporary Discontinuation........................................................................60
7.2. Participant Discontinuation/Withdrawal From the Study.......................................60
7.3. Lost to Follow-up....................................................................................................62
8. STUDY ASSESSMENTS AND PROCEDURES...............................................................62
8.1. Efficacy Assessments..............................................................................................63


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8.1.1. Psoriasis Area and Severity Index ..............................................................63
8.1.2. Physician Global Assessment.....................................................................65
8.1.3. Body Surface Area......................................................................................66
8.1.4. Rater Qualifications....................................................................................67
8.2. Safety Assessments .................................................................................................67
8.2.1. Assessments at Screening Only..................................................................67
8.2.1.1. Tuberculosis Testing .................................................................67
8.2.1.2. Chest Radiograph ......................................................................68
8.2.1.3. Medical History.........................................................................69
8.2.1.4. Suicidal Ideation and Behavior Risk Monitoring......................69
8.2.2. Assessment during Study............................................................................69
8.2.2.1. Full Physical and Brief Physical Examinations ........................69
8.2.2.2. Weight and Height ....................................................................70
8.2.2.3. Vital Signs.................................................................................70
8.2.2.4. Electrocardiograms....................................................................70
8.2.2.5. Clinical Safety Laboratory Assessments...................................71
8.2.2.6. Herpetiform Rash ......................................................................72
8.2.2.7. Creatinine, Cystatin C, and estimates of Glomerular 
Filtration Rate....................................................................................72
8.2.2.8. Local Tolerability Assessment..................................................72
8.2.2.9. Pregnancy Testing.....................................................................73
8.3. Adverse Events and Serious Adverse Events..........................................................73
8.3.1. Time Period and Frequency for Collecting AE and SAE Information.......74
8.3.1.1. Reporting SAEs to Pfizer Safety...............................................74
8.3.1.2. Recording Nonserious AEs and SAEs on the CRF...................74
8.3.2. Method of Detecting AEs and SAEs ..........................................................75
8.3.3. Follow-up of AEs and SAEs.......................................................................75
8.3.4. Regulatory Reporting Requirements for SAEs...........................................75
8.3.5. Exposure During Pregnancy or Breastfeeding, and Occupational 
Exposure ..........................................................................................................76
8.3.5.1. Exposure During Pregnancy......................................................76
8.3.5.2. Exposure During Breastfeeding ................................................76


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8.3.5.3. Occupational Exposure .............................................................76
8.3.6. Medication Errors .......................................................................................76
8.4. Treatment of Overdose............................................................................................77
8.9. Health Economics ...................................................................................................81
8.10. Patient Reported Outcome Measures ....................................................................82
8.10.1. Psoriasis Symptom Inventory...................................................................82
8.10.2. Peak-Pruritus Numerical Rating Scale .....................................................82
9. STATISTICAL CONSIDERATIONS ................................................................................85
9.1. Estimands and Statistical Hypotheses.....................................................................85
9.1.1. Estimands....................................................................................................85
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9.2. Sample Size Determination.....................................................................................86
9.3. Populations for Analysis .........................................................................................87
9.4. Statistical Analyses .................................................................................................87
9.4.1. Efficacy Analyses .......................................................................................88
9.4.2. Safety Analyses ..........................................................................................89
9.4.2.1. Electrocardiogram Analyses......................................................90
9.5. Interim Analyses .....................................................................................................90
9.5.1. Data Monitoring Committee.......................................................................91
9.6. 
PD Unblinding Plan ..........................................................................................91
10. SUPPORTING DOCUMENTATION AND OPERATIONAL
CONSIDERATIONS..........................................................................................................93
10.1. Appendix 1: Regulatory, Ethical, and Study Oversight Considerations...............93
10.1.1. Regulatory and Ethical Considerations ....................................................93
10.1.1.1. Reporting of Safety Issues and Serious Breaches of the 
Protocol or ICH GCP.........................................................................93
10.1.2. Financial Disclosure .................................................................................94
10.1.3. Informed Consent Process ........................................................................94
10.1.4. Data Protection .........................................................................................95
10.1.5. Dissemination of Clinical Study Data ......................................................95
10.1.6. Data Quality Assurance ............................................................................97
10.1.7. Source Documents....................................................................................98
10.1.8. Study and Site Closure..............................................................................98
10.1.9. Publication Policy.....................................................................................99
10.1.10. Sponsor’s Qualified Medical Personnel ...............................................100
10.2. Appendix 2: Clinical Laboratory Tests ...............................................................101
10.3. Appendix 3: Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow-up, and Reporting ....................................................................103
10.3.1. Definition of AE .....................................................................................103
10.3.2. Definition of SAE...................................................................................104
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10.3.3. Recording/Reporting and Follow-up of AEs and/or SAEs.....................105
10.3.4. Reporting of SAEs..................................................................................108
10.4. Appendix 4: Contraceptive Guidance and Collection of Pregnancy 
Information..............................................................................................................110
10.4.1. Male Participant Reproductive Inclusion Criteria..................................110
10.4.2. Female Participant Reproductive Inclusion Criteria...............................110
10.4.3. Woman of Childbearing Potential (WOCBP) ........................................111
10.4.4. Contraception Methods...........................................................................112
10.6. Appendix 6: Liver Safety: Suggested Actions and Follow-up Assessments 
[and Study Intervention Rechallenge Guidelines]...................................................116
10.7. Appendix 7: ECG Findings of Potential Clinical Concern .................................118
10.8. Appendix 8: Country-Specific Requirements .....................................................120
10.8.1. Appendix 8.1: Japan ...............................................................................120
10.9. Appendix 9: Prohibited Medications & Procedures............................................121
10.18. Appendix 18: eGFR calculations ......................................................................143
10.19. Appendix 19: Abbreviations .............................................................................144
11. REFERENCES ................................................................................................................149
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LIST OF TABLES
Table 1.
PF-06700841 Clinical Development Program – Completed, Ongoing, and 
Planned Studies as of September 2019 IB............................................................26
Table 2.
Treatment Groups .................................................................................................39
Table 3.
Exposure Projection Following Topical Application of a PF-06700841 
Cream Formulation, Predicted Margins Relative to 30 mg Oral Once Daily 
and Multiples of Key Cytokines...........................................................................42
Table 4.
Component Scoring Criteria for the Psoriasis Area and Severity Index 
(PASI)...................................................................................................................64
Table 5.
Psoriasis Area and Severity Index (PASI) Area Score Criteria............................64
Table 6.
Area and Severity Index (PASI) Lesions Body Region Weighting .....................65
Table 7.
Component Scoring Criteria for the Physician's Global Assessment (PGA) .......65
Table 8.
Physician's Global Assessment (PGA) Score.......................................................66
Table 9.
Skin Tolerability Grading System ........................................................................73
Table 10.
Protocol-Required Laboratory Assessments.......................................................101
LIST OF FIGURES
Figure 1.
Study Schematic ...................................................................................................38


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1. PROTOCOL SUMMARY 
1.1. Synopsis 
Short Title: A PHASE 2B, DOSE RANGING STUDY TO ASSESS EFFICACY, SAFETY, 
TOLERABILITY AND PHARMACOKINETICS OF PF-06700841 TOPICAL CREAM IN 
PARTICIPANTS WITH CHRONIC PLAQUE PSORIASIS
Rationale
This multicenter, randomized, double-blind, vehicle controlled, parallel group study is being 
conducted to provide data on efficacy, safety, tolerability and pharmacokinetics (PK) of 
PF-06700841 multiple topical formulation concentrations in mild to moderate plaque 
psoriasis.  Additionally, the study is intended to enable selection of dose and dosing regimen 
(once daily, QD, vs twice daily, BID) for the future clinical development of topical 
PF-06700841.  The oral formulation of PF-06700841 has been studied in several trials, this is 
the first clinical study for its topical formulation in patients with mild to moderate plaque 
psoriasis.  The current nonclinical toxicology package supports the planned treatment 
duration of up to 13 weeks.
Objectives, Estimands, and Endpoints
Objectives
Endpoints
Estimands
Primary: 
Primary: 
Primary:

To compare the efficacy of 
multiple dose levels of 
PF-06700841 versus vehicle on 
change from baseline in 
psoriasis area and severity 
index (PASI) score in 
participants with mild to 
moderate plaque psoriasis.

Change from baseline in PASI 
score at Week 12.

Estimand E1: This estimand is 
intended to provide a population 
level estimate of the treatment effect 
of the investigational product (IP)
alone on a continuous endpoint; 
without the benefit of additional 
prohibited medications, regardless 
of participants compliance with the 
IP dosing.
Secondary: 
Secondary: 
Secondary:

To compare the efficacy of 
multiple dose levels of 
PF-06700841versus vehicle on 
physician global assessment 
(PGA) score in participants 
with mild to moderate plaque 
psoriasis.
Key secondary endpoint

Proportion of participants with 
PGA score clear (0) or almost 
clear (1) and 2 points 
improvement from baseline at 
Week 12.

Estimand E2: 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.

To compare the efficacy of 
multiple dose levels of 
PF-06700841versus vehicle on 
the proportion of participants 
with mild to moderate plaque 
psoriasis achieving PASI 75.

Proportion of participants 
achieving PASI 75 (75% or 
greater improvement from
baseline) at time points specified 
in the SoA.

To compare the efficacy of 
multiple dose levels of 
PF-06700841 versus vehicle on

Change from baseline and 
percent change from baseline in 
PASI scores at time points 

All other continuous secondary 
endpoints will be analyzed 
descriptively and using estimand 


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measures of disease and 
symptom severity in 
participants with mild to 
moderate plaque psoriasis.
specified in the SoA.

Absolute score and change from 
baseline in Peak-Pruritus 
Numerical Rating Scale score at 
time points specified in the SoA.

Absolute score and change from 
baseline Psoriasis Symptom 
Inventory at time points specified 
in the SoA.

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.

The proportion of participants 
who achieved a Psoriasis 
Symptom Inventory score of 
0 (not at all) or 1 (mild) on every 
item at time points specified in 
the SoA.
E1 described above when 
appropriate.

All other categorical secondary 
endpoints will be analyzed 
descriptively and using estimand 
E2 described above when 
appropriate.

To assess safety and tolerability 
of PF-06700841 in participants 
with mild to moderate 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 and lipids).

Change from baseline in ECG 
parameters (heart rate, QT, QTc, 
PR and QRS intervals).

Change from baseline in vital 
signs (blood pressure, pulse rate 
and temperature measurements).

Incidence of severity grades in 
skin tolerability at times indicated 
in SoA.

There is no defined estimand for 
these endpoints and they will be 
analyzed using Pfizer data standards 
as applicable.
Overall Design
This is a Phase 2b, randomized, double-blind, vehicle-controlled, parallel group, multicenter 
study in participants with mild to moderate plaque psoriasis.  The study will be conducted in 
2 stages where an additional cohort (Stage 2) of participants may be added, following 
completion of enrollment into Stage 1 and at the discretion of the Sponsor. Investigators, 
study participants, and Pfizer study team members will remain blinded to results of Stage 1.
In addition, this study will use an internal review committee (IRC) for ongoing monitoring of 
safety and efficacy of participants in the study according to the IRC charter.


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Number of Participants
In Stage 1, approximately 240 participants are planned to be randomized into the study to 
allow for approximately 192 evaluable participants (approximately 24 completers per arm, 
8 arms). See Section 9.2 for details.  Participants will be randomized to 1 of 8 treatment 
groups in QD (4 active and 1 vehicle) or BID (2 active and 1 vehicle) dosing regimen in the 
ratio of 1:1:1:1:1:1:1:1.
In Stage 2, approximately 40 participants are planned to be randomized to allow for 
approximately 32 evaluable participants. Participants will be randomized into 1 of 2 
treatment groups in BID (1 active and 1 vehicle) dosing regimen, in the ratio 3:1.
The eligibility criteria for participants enrolled in Stage 1 and Stage 2 are the same.
A study schematic with treatment arms is shown in Section 1.2.
Screen failures are defined as participants who consent to participate in the clinical study but 
are not subsequently randomly assigned to the investigational product/entered in the study. 
All participants randomly assigned to the investigational product (IP) and who apply at least
1 dose of IP will be analyzed according to the product they actually received.  For 
participants who discontinue treatment and/or receive prohibited medication, efficacy data 
(eg primary and key secondary endpoints) will be censored starting at the ET visit.
Intervention Groups and Duration
Once a participant is enrolled, the study duration will be approximately 22 weeks, including 
up to a 6 week screening period, 12 week treatment period, and approximately 4 week follow 
up period in both Stage 1 and Stage 2.  Treatment groups are shown in the table below.  
Vehicle cream contains all excipients as the PF-06700841 cream except for PF-06700841 
(See Section 6.1).
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Stage
Treatment Group
Investigational Product
1
A
Vehicle cream QD
B
PF-06700841 0.1% cream QD
C
PF-06700841 0.3% cream QD
D
PF-06700841 1.0% cream QD
E
PF-06700841 3.0% cream QD
F
Vehicle cream BID
G
PF-06700841 0.3% cream BID
H
PF-06700841 1.0% cream BID
2
I
PF-06700841 3.0% cream BID
J
Vehicle cream BID
The IP application regimen should not be modified.  Temporary discontinuation and/or 
permanent discontinuation of the IP may be appropriate under some circumstances (See 
Section 7.1.1).
Data Monitoring Committee: Yes
This study will use an internal review committee (IRC) to perform safety and efficacy 
analysis for making internal business decisions. The details of the objectives, decision 
criteria, dissemination plan and method of maintaining the study blind will be documented in 
the IRC charter for any analysis that committee is asked to perform. Members of the IRC 
will be qualified and experienced in reviewing and interpreting clinical study data.  They will 
be independent of the study team, and unblinded to treatment.
In addition, an interim analysis will be conducted at the end of Stage 1. Some Pfizer team 
members and other key stakeholders will become unblinded to the results of Stage 1.
Unblinded Pfizer team members will be replaced by blinded team members. Investigators
and study participants will remain blinded to the results of Stage 1. 
An external blinded adjudication committee will be selected on ad-hoc basis, if suspected 
cardiovascular and/or thromboembolic (TE) events are observed during study conduct. Other 
safety events for adjudication may be identified and included in the remit of the safety 
adjudication committee as appropriate.
Statistical Methods
The primary estimand will be the population average treatment effect on change from 
baseline in PASI (psoriasis area and severity index) scores at Week 12 relative to vehicle 
(with the same dosing schedule, QD or BID) 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. 


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The secondary estimand will be the population average treatment effect on the PGA 
(Physician Global Assessment) response rate: percentage of participants with a score of 
clear (0) or almost clear (1) and ≥2 point improvement from baseline at Week 12 relative to 
vehicle (with the same dosing schedule, QD or BID) without regard to compliance with IP in 
the absence of prohibited medication. 
All other key secondary continuous clinical endpoints will be analyzed using the primary 
estimand, while all other key secondary categorical clinical endpoints will be analyzed using 
the secondary estimand described above. 
The sample size is based on the primary efficacy endpoint, PASI change from baseline at 
Week 12.
1.2. Schema


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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.
Schedule of Activities
Visit Identifiera
Screening Day 1u Week 1u Week 2u Week 4u Week 6u Week 8u Week 10u Week12/
ETb,u
Week 14 
Follow-upu
Week 16 
Follow-up/ETb,u
Visit Day/Windowa
Day -42 
to -1
Day 1
Day 8
±1 day
Day 15
±2 days
Day 29 
±2 days
Day 43 
±2 days
Day 57 
±2 days
Day 71 
±2 days
Day 85
±2 days
Day 100
±3 days
Day 118
±3 days
Enrollment Procedures
Informed consent
X
Eligibility assessment
X
X
Medical history 
X
Medication history
X
Demography
X
Randomization
X
Clinical assessments 
Full physical examination 
X
X
X
Brief physical examination
X
X
X
X
X
X
X
Vital signs
X
X
X
X
Weight
X
X
X
X
Height
X
ECGc
X
X
X
X
Chest radiographd
X
C-SSRS
X
Local tolerability assessment
X
X
X
X
X
X
X
X
X
X
Clinical assessments of psoriasis
PASI
X
X
X
X
X
X
X
X
X
X
X
PGA
X
X
X
X
X
X
X
X
X
X
X
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Visit Identifiera
Screening Day 1u Week 1u Week 2u Week 4u Week 6u Week 8u Week 10u Week12/
ETb,u
Week 14 
Follow-upu
Week 16 
Follow-up/ETb,u
Visit Day/Windowa
Day -42 
to -1
Day 1
Day 8
±1 day
Day 15
±2 days
Day 29 
±2 days
Day 43 
±2 days
Day 57 
±2 days
Day 71 
±2 days
Day 85
±2 days
Day 100
±3 days
Day 118
±3 days
Laboratory samples
Safety labs (Hematology, Blood chemistry, Urinalysis)e
X
X
X
X
X
X
X
X
X
X
X
Lipid panel (Fasting)e
X
X
Serum cystatin Ce
X
X
X
X
X
X
X
X
X
X
Blood pregnancy testf
X
X
Urine pregnancy teste,f
X
X
X
X
X
X
X
X
X
X
FSHg
X
Hepatitis tests
X
Xh
HIV test
X
Tuberculosis testi
X
 
 
IP-related
Identify treatment eligible psoriasis areasl
X
X
Provide treatment area list to study participant 
X
Review and update (as needed) treatment area listm
X
X
X
X
X
X
Dispensing of IP
X
X
X
X
X
X
X
IP application, observationn
X
X
X
X
X
X
X
Xo
Collect and Weigh Previous IP Tubes (prior to 
dispensing new IP)
X
X
X
X
X
X
X
Training on and dispensing dosing e-diary/ePRO device
X
Filling in dosing e-diary
X
→
→
→
→
→
→
X
Dosing e-diary review and re-training as needed
X
X
X
X
X
X
X
X
Collecting e-diary/ePRO device
X
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Visit Identifiera
Screening Day 1u Week 1u Week 2u Week 4u Week 6u Week 8u Week 10u Week12/
ETb,u
Week 14 
Follow-upu
Week 16 
Follow-up/ETb,u
Visit Day/Windowa
Day -42 
to -1
Day 1
Day 8
±1 day
Day 15
±2 days
Day 29 
±2 days
Day 43 
±2 days
Day 57 
±2 days
Day 71 
±2 days
Day 85
±2 days
Day 100
±3 days
Day 118
±3 days
Monitoring
Contraception checkp
X
X
X
X
X
X
X
X
X
X
X
Concomitant Treatment(s)
X
→
→
→
→
→
→
→
→
X
Serious and non-serious adverse event monitoring
X
→
→
→
→
→
→
→
→
→
X
Patient Reported Outcomesq
Psoriasis Symptom Inventoryr
X
→
X
X
X
X
X
X
X
X
Peak-Pruritus Numerical Rating Scaler
X
→
X
X
X
X
X
X
X
X
Training on ePRO device
X
Review of ePRO entries
X
X
X
X
X
X
X
X
 
 
 
 
Abbreviations: →= ongoing/continuous event; 
; C-SSRS= Columbia Suicide Severity Rating Scale; ECG = electrocardiogram; ePRO = Electronic 
patient reported outcomes; ET = Early Termination; FSH= follicle stimulating hormone; HIV= human immunodeficiency virus; 
 
IP = Investigational Product; 
; PASI = Psoriasis Area and Severity Index; PGA= Physician’s Global Assessment;
; PRO = patient reported outcome;
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a.
Day relative to start of study treatment (Day 1).
b.
For participants who discontinue from the study prior to Week 12 visit, the procedures scheduled for Week 12 will be performed as soon as possible.  Whenever possible, 
these participants should have one visit approx. two weeks after the last dose (Week 14 Follow up visit assessments) and the last visit at least 28 days after the last dose of IP 
was administered (Week 16 Follow-up visit assessments). For participants who discontinue from the study after Week 12 visit, the procedures scheduled for Week 16 will be 
performed.
c.
Local read, single ECG at all scheduled time points.  Triplicate ECG will be conducted as appropriate as described in Section 8.2.2.4.
d.
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.
e.
Participants must be fasting (water only) for at least 8 hours prior to visits, when lipid panel is being taken.  Lipid panel includes total cholesterol, LDL, HDL, triglycerides.  
Protocol-specified safety laboratory tests may be performed at a local laboratory, where allowable by law or local guidance, if the study participant is unable to visit the study 
site. Local laboratory reference ranges and a copy of local lab results should be included in participant’s source documents.
f.
Required for female participants of childbearing potential. Pregnancy tests (serum/urine) may also be repeated more frequently as per request of IRBs/ECs or if required by 
local regulations.  Pregnancy tests will also be done whenever 1 menstrual cycle is missed during the active treatment period (or when potential pregnancy is otherwise 
suspected).  Two negative pregnancy tests are required before receiving IP (one negative serum pregnancy test at screening and one negative urine pregnancy test at Day 1 
visit).  If urine pregnancy test is positive after IP application, serum pregnancy test will be conducted, IP paused and sponsor clinician and sponsor medical monitor notified 
immediately (See Section 7.1.1).
g.
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). See Section 10.4.3.
h.
In Japan only: HBV DNA reflex test.  See Sections 10.2 and 10.8.
i.
If performed within 12 weeks prior to Day 1 and documentation is available, this does not have to performed during Screening.
 
l.
Potential treatment area(s) will be identified at Screening, and final selection will be made at Day 1. 
m.
If participants develop new treatment areas after Day 1 between clinic visits, participants should contact the Investigator and determine if these may be eligible for treatment 
as described in Section 6.1.1.1.  This may result in an additional unscheduled visit and dispensing of IP.
n.
Except for Day 1, participants will apply IP after all assessments have been completed.  Participants will also apply IP in between visits. For BID dosing regimen, only one 
dose will be observed in the clinic.
o.
Last dose for both BID and QD dosing will be applied either prior to or during the Week 12 clinic visit.  Participants on both dosing regimen will receive only one dose on 
their last day.  IP application will not be performed during early termination visit.
p.
To confirm that contraception, if assigned, is used consistently and correctly.
q.
Every effort should be made for the participant to complete all patient reported outcome (PRO) questionnaires before any other assessments.
t.
Participants who consent to these optional assessments, may be trained on and have devices issued after participant eligibility has been confirmed.  This will be part of 
Screening but may take place at a different in-clinic visit no later than 1 week prior to Day 1.  See Section 8.11.2 for details on how long devices should be worn.
u.
In the event that any in-clinic study visit cannot be conducted, including scheduled follow-up visit, the participant site visits may be changed to phone calls or video visits (if 
permitted by law or local guidance) to reduce risk of potential participant exposure to COVID-19.
C
C
I
C
C
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2. INTRODUCTION
PF-06700841 is a dual inhibitor of human tyrosine-protein kinase 2 (TYK2) and Janus 
kinase 1 (JAK1) that is currently being investigated in participants with multiple indications.  
The oral formulation of this compound has been studied in several studies, including in 
patients with psoriasis.  This study is the first study for the topical formulation of 
PF-06700841 in patients with mild to moderate plaque psoriasis. 
2.1. Study Rationale 
The purpose of this multicenter, randomized, double-blind, vehicle controlled, parallel group 
study is to determine efficacy, safety, tolerability and pharmacokinetics of PF-06700841 in 
its topical formulation in participants with mild to moderate psoriasis.  In addition, data from 
this study will be used to select a topical dose and dosing regimen (once daily vs. twice daily 
application) for the future clinical development of PF-06700841.  Oral formulation of 
PF-06700841 has been studied in several trials, this is the first clinical study for its topical 
formulation in patients with mild to moderate plaque psoriasis.
2.2. Background 
The most common variant of psoriasis, plaque psoriasis, is a chronic inflammatory 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 5.8-7.5 million 
Americans.1  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 an
impairment akin to other major diseases, such as type 2 diabetes, myocardial infarction, and
arthritis.2
The Janus kinase (JAK) family, including 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.3,4  JAK2 homodimers are critical for the signaling of hematopoietic cytokines 
and hormones including erythropoietin (EPO), IL-3, granulocyte-macrophage 
colony-stimulating factor (GM-CSF) and prolactin.
JAK1-dependent cytokines include IFN-alpha, IFN-gamma, IL-6, IL-21, and IL-22.  IL-6 
and IL-21 play a critical role in the development of Th17 cells and production of IL-17, 
which is a target of several efficacious biologic therapies.  JAK1-selective inhibitors are 
expected to spare dose-limiting effects of pan-JAK inhibition by preserving JAK2 
homodimer signaling and thus provide the potential for more efficacious oral treatments for 
several inflammatory diseases including psoriasis.  The previous positive psoriasis studies 
with two JAK1 selective inhibitors, INCB39110 and GSK2586184, have provided clinical 
support for JAK1 inhibition as a novel approach to treat plaque psoriasis.5,6


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Increased activation of Th17 and the main effector cytokines of Th17 cells has been linked to 
various inflammatory diseases, including psoriasis.7 The number of Th17 cells are elevated 
in psoriatic lesions, along with levels of proinflammatory cytokines, including IL-17A and
IL-17F, which are expressed by Th17 cells and are likely mediators of inflammation and 
tissue damage.7,8  Human genetic studies implicate the Th17 pathway in psoriasis, and have 
uncovered likely risk alleles which include genes involved in IL-23 signaling (including 
TYK2, which mediates IL-23 receptor signaling) and genes that function downstream of the 
IL-17 receptor.7
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. Secukinumab and 
ixekizumab selectively target IL-17A and have been shown to be effective in the treatment of 
psoriasis.9 Other therapies such as cyclosporine, phototherapy, and infliximab also inhibit 
the IL-17 pathway.10-12  The monoclonal antibodies ustekinumab and guselkumab, which are 
also effective in treating psoriasis,13-15 disrupt IL-23 activation of Th17 cells.16  Thus, there is 
strong rationale for targeting the Th17 pathway in the treatment of psoriasis.
In the skin, cytokines mediated by JAK signaling impact several cellular inflammatory 
functions, such as apoptosis of inflammatory T cell infiltrates and T helper cell 
differentiation.  C-X-C motif chemokine ligand 10 (CXCL10), chemokine ligand 
26 (CCL26) and matrix metallopeptidase (MMP12) have been reported to be induced by 
cytokines acting via the JAK class of kinases17-20 and are implicated in inflammatory and 
autoimmune conditions of the skin.21-26 In addition, impairment of the skin barrier protein 
filaggrin has also been implicated in inflammatory and autoimmune diseases of the skin27
and its expression has been reported to increase upon inhibition of JAK enzymes.20  
Following topical application of the clinical formulation to freshly excised human skin, 
PF-06700841 caused a dose-dependent inhibition of gene expression of pro-inflammatory 
molecules CXCL10, CCL26 and MMP12 (measured by changes in messenger ribonucleic 
acid [mRNA] in the presence and absence of PF-06700841) and a dose-dependent 
stimulation of the skin barrier protein, filaggrin.  Thus, PF-06700841 showed 
pharmacological modulation in human skin by the topical application, consistent with the 
known activity of PF-06700841 on JAK1 and TYK2 enzymes.
PF-06700841 is a dual TYK2/JAK1 inhibitor with good selectivity profile over other human 
kinases.  Based on its cytokine inhibition profile, PF-06700841 is expected to target the 
Th17 pathway directly by inhibiting TYK2 and indirectly by inhibiting JAK1, thereby 
providing therapeutic benefit in the treatment of plaque psoriasis.
2.2.1. Non-Clinical Experience of PF-06700841
 
 
  
 
 
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Further details are provided in the current Investigator’s Brochure.
2.2.1.2. Non-Clinical Safety Studies
No adverse findings were observed in a 13-week dermal repeat-dose toxicity study with 
PF-06700841 in minipigs.  PF-06700841-related nonadverse target organs identified from 
topical application included the skin (erythema, edema, eschar) and the immune and
hematolymphopoietic systems (thymus and peripheral blood).  In addition, vehicle-related 
nonadverse erythema and edema were observed.  The findings in the thymus (lower weights 
without correlating microscopic changes) and peripheral blood (decreased lymphocytes) are 
consistent with the pharmacological activity of PF-06700841.  PF-06700841 was negative for 
skin sensitization potential in the mouse local lymph node assay when applied topically as a 
solution (up to 50%) or cream formulation (3%).  The no-observed-adverse-effect-level 
(NOAEL) in the 13-week dermal toxicity study for PF-06700841 by topical administration 
was the highest dose of 1.28 mg/cm2/day (3% cream formulation), resulting in systemic 
mean unbound Cmax and AUC24 exposures of 108 ng/mL and 1760 ng•h/mL, respectively.
No adverse findings were observed in oral repeat-dose toxicity studies with PF-06700841 in 
rats and monkeys up to 6 and 9 months in duration, respectively.  PF-06700841-related, 
nonadverse, target organs identified include the immune and hematolymphopoietic systems 
(thymus, spleen, lymph nodes, and bone marrow), cardiovascular system (blood pressure, 
heart rate, QTc interval), gastrointestinal tract (body weight and weight gain effects), and 
adrenal gland (vacuolation).  The findings in the thymus, spleen, lymph nodes, and bone 
marrow are consistent with the pharmacological activity of PF-06700841. The NOAELs in 
the 6-and 9-month toxicity studies were 45 mg/kg/day in rats (unbound Cmax of 8280 ng/mL 
and AUC24 of 69,700 ng•h/mL) and 20 mg/kg/day in monkeys (unbound Cmax of 2260 ng/mL 
and AUC24 of 10,700 ng•h/mL).  Adverse findings in the central nervous system (decreased 
activity, mortality, prostration, convulsions) were observed at high systemic exposures in 
pregnant, but not in nonpregnant rabbits. 
In oral embryo-fetal development studies in rats and rabbits, adverse PF-06700841-related 
developmental effects occurred (lower embryo-fetal viability and mean fetal body weights, 
fetal skeletal malformations, external malformations). The developmental NOAEL in rabbits 
was 1 mg/kg/day (unbound Cmax of 174 ng/mL and AUC24 of 608 ng•h/mL).  The 
developmental NOAEL in rats was not established and is <2 mg/kg/day (unbound Cmax of 
482 ng/mL and AUC24 of 2240 ng•h/mL), the lowest dose tested.  No effects on female
reproductive organs, as assessed by histopathologic examination, were noted in either the rat 
or monkey repeat-dose toxicity studies.  PF-06700841 is not mutagenic in bacterial reverse 
mutation assays.  Although PF-06700841 was positive for micronuclei formation in vitro 
(through an aneugenic mechanism), it did not induce micronuclei in vivo in rats at 
55 mg/kg/day (unbound Cmax = 7730 ng/mL and AUC24 = 88,300 ng•h/mL), the highest dose 
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tested in the 1-month oral toxicity study. No evidence of PF-06700841-related phototoxicity 
in the skin or eyes of pigmented rats in a 3-day oral phototoxicity study was observed up to 
the highest dose tested of 100 mg/kg/day, demonstrating that PF-06700841 was not a 
phototoxicant, in vivo.
Further details of the nonclinical safety program are provided in the current Investigator’s 
Brochure.
2.2.2. Clinical Overview
To date, the clinical development program for PF-06700841 comprises Phase 1 studies in 
adult healthy Western participants (B7931001; single ascending dose [SAD] and multiple 
ascending dose [MAD] study, B7931010; PK profile and relative bioavailability study, 
B7931014 (ongoing); an absorption, distribution, metabolism and excretion of
[14C PF-06700841] study, B7931019 (ongoing); effect on QTc interval study, and B7931033
(planned); studying the effect of multiple oral doses of itraconazole on a single oral dose of 
PF-06700841 PK study) and in Japanese participants (B7931009; placebo-controlled 
multi-dose study and B7931029; vehicle and white petrolatum-controlled study to assess skin 
irritation potential study), and Phase 1 and 2 studies in participants with chronic plaque
psoriasis (B7931001, B7931004), alopecia areata (B7931005), atopic dermatitis (B7931022),
systemic lupus erythematosus (B7931028), psoriatic arthritis (B7931030), ulcerative colitis 
(B7981005), Crohn’s disease (B7981007), vitiligo (B7981019), and hidradenitis suppurativa
(C2501007; ongoing).  The studies conducted to date described in this section have all used 
oral administration of PF-06700841, except for B7931022 (ongoing) and B7931029 
(completed) which used multiple dose strengths of topical cream formulation of 
PF-06700841 in participants with mild-to-moderate atopic dermatitis and healthy Japanese 
participants, respectively.
As of the latest update to the Investigator’s Brochure (IB, September, 2019), PF-06700841 
was generally safe and well tolerated in healthy participants (B7931001 and B7931009); 
psoriasis (B7931001 and B7931004) and alopecia areata participants (B7931005).  There 
were no clinically meaningful findings in vital signs, ECG, suicidal behavior or ideation, or 
potential Hy’s Law cases reported during these studies.  A summary is provided below, 
further details are provided in the current Investigator’s Brochure (September 2019).


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Table 1.
PF-06700841 Clinical Development Program – Completed, Ongoing, and Planned Studies
as of September 2019 IB
Study ID
Description
PF-06700841 Dose/Regimen
# of Participants
Phase 1 Studies:
B7931001
(completed)
The study consisted of 3 parts:
1. Within Cohort, randomized,
double-blind, placebo-controlled, 
single and multiple dose
escalation, parallel group to 
assess safety, tolerability, PK, and 
PD of PF-06700841 in healthy 
adult Western participants.
SAD: 1, 3, 10, 30, 100, and 
200 mg; 
MAD: 10, 30, 100, or 175 mg 
QD or 50 mg BIDa for 10 days
54 (8/cohort) 
(6 active: 
2 placebo)
2. Randomized, placebo-controlled, 
4-week treatment period in adult 
participants with PsO to assess 
PF-06700841 safety, tolerability 
and effect on disease activity 
measured by PASI.
Placebo, 30, or 100 mg QD for 
28 days
30 (9 placebo; 
14 at 30 mg QD; 
7 at 100 mg QD)
3. Bioavailability assessment of a 
tablet formulation relative to 
suspension formulation and the 
effect of food on a tablet 
formulation of PF-06700841.
Single dose: 100 mg in a 3-way 
cross-over design
12
B7931009 
(completed)
Randomized, double-blind, 
placebo-controlled, multiple dose 
study in healthy Japanese adult 
participants.
100 mg QD for 10 days
8
(6 active: 
2 placebo)
B7931010
(Completed)
An open-label, single dose, 
2-period, 2-sequence crossover 
study in healthy volunteers to 
characterize PF-06700841 PK 
profile and relative bioavailability 
following single oral dose 
formulation of IR tablets and MR 
tablets.
Sequence 1: a single oral dose 
of 30 mg PF-06700841 IR 
tablets to a single oral dose of 
30 mg PF-06700841 MR tablets
Sequence 2: a single oral dose 
of 30 mg PF-06700841 MR 
tablets to a single oral dose of
30 mg PF-06700841 IR tablets
8 enrolled and 
completed
B7931014
(Ongoing)
A Phase 1, open label, 
non-randomized, 2 period, fixed 
sequence study to investigate the 
absorption, distribution, 
metabolism and excretion of
[14C PF-06700841] and to assess 
the absolute bioavailability and 
fraction absorbed of PF-06700841 
in healthy male participants using a 
14C microtracer approach.
Period A: an oral dose of 60 mg 
PF-06700841 containing 
300 nCi 14C-PF-06700841; 
Period B: an oral dose of 60 mg 
unlabeled PF-06700841 
followed by an IV dose of
30 µg 14C labeled PF-06700841 
(300 nCi)
6 enrolled and 
completed


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Table 1.
PF-06700841 Clinical Development Program – Completed, Ongoing, and Planned Studies
as of September 2019 IB
Study ID
Description
PF-06700841 Dose/Regimen
# of Participants
B7931019
(Ongoing)
Phase 1, 6-sequence, 3-period, 
participant and investigator blinded 
and sponsor-open, crossover study 
in healthy volunteers to evaluate 
the PF-06700841 effect on QTc 
interval. Each participant
randomized will receive placebo, 
PF-06700841 200 mg and 
moxifloxacin (open label) in one of 
the 6 sequences. Moxifloxacin is 
positive control to demonstrate the 
study sensitivity and PF-06700841 
effect on QTc will be assessed by 
concentration-QT analysis.
Sequence 1: single dose of 
PF-06700841 200 mg to 
placebo to moxifloxacin 400 mg
Sequence 2: single dose of 
PF-06700841 200 mg to 
moxifloxacin 400 mg to placebo 
Sequence 3: placebo to 
PF-06700841 200 mg to 
moxifloxacin 400 mg
Sequence 4: placebo to 
moxifloxacin 400 mg to 
PF-06700841 200 mg
Sequence 5: moxifloxacin 
400 mg to PF-06700841 
200 mg to placebo
Sequence 6: moxifloxacin 
400 mg to placebo to 
PF-06700841 200 mg
33 enrolled
32 completed
B7931029
(Completed)
A Phase 1, single center, 
randomized, vehicle and white 
petrolatum-controlled, evaluator 
blinded study to assess the skin 
irritation potential with a range of 
concentrations of PF-06700841 
cream including vehicle and empty 
patch with white petrolatum under 
occlusive conditions in adult 
Japanese healthy participants.
PF- 06700841 cream 0% 
[vehicle], 0.1%, 0.3%, 1%, 3%,
and empty patch with white 
petrolatum)
20 participants 
enrolled and 
completed
B7931033
(Planned)
A Phase 1, open-label, 
fixed-sequence, 2-period study to 
investigate the effect of multiple 
oral doses of itraconazole on a 
single oral dose of PF-06700841 
PK in healthy volunteers.
Period 1: a single oral dose of 
30 mg PF-06700841 tablets 
Period 2: Itraconazole 200 mg 
once daily on Days 1-7 with a 
single oral dose of 30 mg 
PF-06700841 tablets 
administered approximately 
1 hour after itraconazole dosing 
on Day 4
12 Planned
Phase 2 Studies:
B7931004 
(completed)
A Phase 2a, randomized, 
double-blind, placebo-controlled
study to evaluate safety and 
efficacy of PF-06700841 in 
participants with moderate to 
severe plaque psoriasis. The study 
consisted of 4 weeks of induction 
and 8 weeks of maintenance 
therapy periods.
Placebo,
PF-06700841: 
60 mg QD to 30 mg QD
60 mg QD to 10 mg QD
60 mg QD to 100 mg
QW
60 mg QD to placebo
30 mg QD
212 (189 active 
and 23 placebo )


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Table 1.
PF-06700841 Clinical Development Program – Completed, Ongoing, and Planned Studies
as of September 2019 IB
Study ID
Description
PF-06700841 Dose/Regimen
# of Participants
B7931005b
(ongoing)
Phase 2a randomized, double-blind, 
placebo-controlled, multicenter
study with two extension periods to 
evaluate the efficacy and safety 
profile of PF-06651600 and 
PF-06700841 in participants with 
moderate to severe AA. This 
includes a 24-week treatment 
period, a 4-week drug holiday (#1), 
an up to 12 month single-blind 
extension period, a 4-week drug 
holiday (#2), and a 6-month 
cross-over open label extension 
Period.
PF-06700841: 60 mg QD in 
4-week induction and 30 mg QD 
in 20-week maintenance or
placebo
142 enrolled
(47 on active 
PF-06700841 and 
47 on placebo)/
115 completed
(36 on active 
PF-06700841 and 
34 on placebo)
In extension 1, 
96 participants 
entered
single-blind 
extension (SBE) 
period, 
32 received 
PF-06700841 and 
25 completed the
study
In extension 2, 
23 participants 
entered 
cross-over (CO)
extension period 
and 5 participants 
received 
PF-06700841
B7931022
(Ongoing)
A Phase 2B, randomized, double 
blind, vehicle controlled, parallel 
group, dose ranging study to assess 
the efficacy, safety, tolerability and 
pharmacokinetics of PF-06700841 
cream applied once or twice daily 
for 6 weeks in participants with 
mild or moderate atopic dermatitis.
PF-06700841 (topical) 
0.1%
0.3%
1%
3% 
Vehicle
32 randomized 
(out of 280
planned)
(as of 
22-Aug-2019)
B7931028
(Ongoing)
A randomized, controlled, 
double-blinded study to evaluate 
the efficacy and safety of 3 doses of 
PF-06700841 compared to placebo 
in patients with active systemic 
lupus erythematosus receiving 
concomitant standard of care 
therapy.
PF-06700841 15 mg/day oral
PF-06700841 30 mg/day oral
PF-06700841 45 mg/day oral 
Placebo
46 enrolled
(as of 12 Aug 
2019)


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Table 1.
PF-06700841 Clinical Development Program – Completed, Ongoing, and Planned Studies
as of September 2019 IB
Study ID
Description
PF-06700841 Dose/Regimen
# of Participants
B7931030
(Ongoing)
A Phase 2B, randomized, 
double-blind, placebo-controlled, 
dose-range,parallel group study of 
PF-06700841 to evaluate the
efficacy of PF-06700841 at 
16 weeks and to evaluate the safety 
and efficacy up to 1 year in 
participants with active psoriatic 
arthritis.
PF-06700841 60 mg QD, 30 mg 
QD, and 10 mg QD or placebo
3 enrolled (out of 
196 planned)
(as of 
22-Aug-2019)
B7981005b
(ongoing)
Double-blind, randomized, 
placebo-controlled, parallel group,
multi-center dose-ranging study of 
oral PF-06651600 and 
PF-06700841 as induction and 
chronic therapy in participants with 
moderate to severe ulcerative 
colitis. The study has 8-weeks of 
double-blind and 
placebo-controlled induction
treatment period followed by a
24-week of chronic active treatment 
period.
Induction treatment period: 
PF-06700841 60 mg QD, 
30 mg QD, and 10 mg QD or
placebo
Chronic treatment period: 
PF-06700841 30 mg QD
216 enrolled 
(360 planned
71 completed 
(as of 09 Sep 
2019)
B7981007b
(ongoing)
Double-blind, randomized, 
placebo-controlled, parallel group
study to evaluate the efficacy and 
safety of oral PF-06651600 and 
PF-06700841 as induction and open 
label extension treatment in 
participants with moderate to 
severe Crohn’s disease (CD). The 
study has a 12-week induction 
treatment period followed by a 
52-week open label active 
treatment period. 
Induction treatment period: 
PF-06700841 60 mg QD or 
placebo
Extended open label active 
treatment period: PF-06700841 
30 mg QD
73 enrolled/250 
planned
2 completed
(as of 12 Sep 
2019) 
B7981019b
Ongoing
A Phase 2b randomized, 
double-blind, placebo-controlled, 
multicenter, dose-ranging study to 
evaluate the efficacy and safety 
profile of PF-06651600 with a 
partially blinded extension period 
to evaluate the efficacy and safety 
of PF-06651600 and PF-06700841 
in participants with active 
non-segmental vitiligo.  The study 
has a 4-week induction, 20-week 
maintenance with PF-06651600.  
After the 4-week of drug holiday, 
participants may receive 
During extension treatment
period:
PF-06700841 60 mg QD 
(4 weeks) to 30 mg QD 
(16 weeks)
1(enrolled)/60 
(planned) 
as of 11 Sep 2019


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Table 1.
PF-06700841 Clinical Development Program – Completed, Ongoing, and Planned Studies
as of September 2019 IB
Study ID
Description
PF-06700841 Dose/Regimen
# of Participants
PF-06700841 during extended 
treatment period.
C2501007
Planned
A planned Phase 2a, multicenter, 
randomized, double blind 
placebo-controlled, 16-week study 
evaluating the safety and efficacy 
of IRAK4 inhibitor PF-06650833, 
TYK2/JAK1 inhibitor 
PF-06700841, Tyk2 inhibitor
PF-06826647 in adult with 
moderate to severe hidradenitis 
suppurativa (HS).
PF-06700841 45 mg QD
192 (Planned)
AA = Alopecia areata; BID = Twice daily; CD = Crohn’s disease; IRAK4 = interleukin-1 receptor-associated 
kinase 4; MAD = multiple ascending dose; PASI = Psoriasis Area and Severity Index; PD = pharmacodynamic; 
PK = Pharmacokinetic; Mg = milligram; PsO = Psoriasis; QD = Once daily; QW = Once weekly; SAD = Single 
ascending dose; UC = Ulcerative colitis.
a.
Participants who completed the 100 mg SAD and 100 mg MAD periods continued in the 50 mg BID period 
and received either placebo or PF-06700841 twice daily according to original treatment assignment when 
randomized into the 100 mg SAD period.
b.
Platform study that will assess efficacy and safety of PF-06700841 and a second investigational agent 
(PF-06651600) separately.  PF-06651600 is an orally bioavailable small molecule that irreversibly inhibits
JAK3.
2.2.2.1. Study B7931001
In B7931001 study, the most commonly reported all causality TEAEs across active healthy 
participants were blood creatinine increased, reported in 2 participants during the SAD
(single ascending dose) period and 11 participants during the MAD (multiple ascending 
dose) period, without any changes in Cystatin C measured renal function.  Neutropenia was 
reported in four participants during the MAD period, most of them were mild in severity 
except one with moderate, and none of them reached <500/mm3 during the study.  The most 
frequently observed laboratory abnormalities in healthy participants were elevated LDL and 
serum creatinine.  There were no deaths or SAEs reported in the Phase 1 studies.  One 
psoriasis participant receiving 100 mg QD of IP in B7931001 experienced an adverse event 
of herpes zoster during the follow up period, after completing 28-day treatment.
2.2.2.2. Study B7931009
PF-06700841 demonstrated acceptable safety and tolerability by oral administration in study 
B7931009, which included 8 Japanese participants who were treated and completed the 
study.  Six (6) participants received the treatment of PF-06700841 100 mg QD and 
2 participants received matching placebo orally for 10 days.


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2.2.2.3. Study B7931004
A total of 189 psoriasis participants out of 212 enrolled in B7931004 were exposed to at least
one dose of PF-06700841 during the study. The proportion of participants with all-causality 
treatment-emergent adverse events (TEAEs) was comparable across all treatment groups but 
numerically higher in the active treatment groups (64.0% to 76.7%) than the placebo group 
(56.5%).  The majority of participants in all treatment groups experienced mild or moderate 
all-causality TEAEs, and only 5.2% experienced severe all-causality TEAEs.  Overall, there 
were no dose dependent increases in the all-causality TEAEs.  Most TEAEs in the Infection 
and Infestation were mild to moderate except one participant who had two serious infections 
after taking a single dose of 60 mg PF-06700841 on Day 1.  One participant in the 30 mg QD 
to 100 mg QW group had squamous cell carcinoma of skin reported on Day 2 of treatment. 
One participant in the 30 to 10 mg group was confirmed to be pregnant after in the study 
42 days and discontinued from the study with obstetrical ultrasound demonstrating fetal cleft 
lip.
Decreased reticulocytes, hemoglobin, and neutrophils were observed in the participants on 
active treatment during 4-week induction phase and returned toward baseline level during 
8-week maintenance phase.  Increases in serum creatinine from baseline were observed in all 
active treatment groups with no association of change in cystatin C based renal function 
measurement.  Other commonly reported laboratory abnormalities were elevation of low 
density lipoprotein (LDL) with no clinical meaningful changes in LDL/high-density 
lipoprotein (HDL) ratio.  There were no clinically meaningful changes from baseline 
observed in creatine kinase (CK) during the study.  CK levels >10 × upper limit of normal
(ULN) were observed in two participants without adverse event.  One moderate AE of 
CK-MB increased reported by one participant in the 30 to 10 mg QD group during the 
induction period, which was considered to be related to the IP by the investigator.  No 
participant was discontinued from the study due to CK elevation.
2.2.2.4. Ongoing Phase 2 Studies 
Oral PF-06700841 is currently being investigated in several studies: alopecia areata 
(B7931005), ulcerative colitis (B7981005), atopic dermatitis (B7931022), psoriatic arthritis 
(B7931030), vitiligo (B7981019), systemic lupus erythematosus (B7931028), Hidradenitis 
Suppurativa (C2501007), and Crohn’s disease (B7981007).  B7931005 study results from 
interim CSR are included below.
2.2.2.4.1. Study B7931005
47 alopecia areata participants were exposed to at least one dose of PF-06700841 in the 
B7931005 study.  
 
 
 
 
 
 
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2.2.3. Overview of Clinical Pharmacology
2.2.3.1. Study B7931001 
Following single oral doses of PF-06700841, peak plasma concentrations generally occurred 
at or before 1 hour for doses of 1 mg to 200 mg.  In general, both AUCinf and Cmax appear to 
increase proportionally with dose from 1 mg to 100 mg, with a suggestion of more than 
proportional increase from 100 mg to 200 mg.  Mean terminal t½ was 3.8 to 7.5 hours.
Cmax and AUCinf of the 100 mg PF-06700841 tablets compared with 100 mg oral suspension
were within the 80% to 125% equivalence interval indicating similar bioavailability of the 
tablet and oral solution/suspension.  A high fat meal decreased AUCinf and Cmax of the 
100 mg tablet by approximately 18% and 36%, respectively and delayed Tmax with a median 
value of 4.0 hours, compared to a median Tmax 0.5 hours under fasted conditions. 
PF-006700841 can be administered with or without food. 
On Day 10 of multiple-dose administration in healthy participants, median Tmax was at or 
before 1.5 hours postdose across the entire range of doses from a total daily dose of 10 mg up 
to 175 mg.  Plasma Cmax and AUCτ both appeared to increase proportionally with dose from 
10 mg QD to 100 mg QD with a trend towards more than proportional increase from 
100 mg to 175 mg QD.  Mean terminal t½ ranged from 4.9 to 10.7 hours.  Steady state 
generally appeared to have been reached by Day 8 of once daily (QD) or twice daily (BID) 
dosing.  Urinary recovery of PF-06700841 was low, with less than 16% of the dose 
recovered unchanged.
On Day 28 of multiple-dose administration in psoriasis participants, median Tmax was 1 hour 
to 2 hours.  In general, dose-normalized exposure was higher in the 100 mg QD group than in 
the 30 mg QD group.  Mean terminal t½ was 16 hours in the 30 mg group and 6 hours in the 
100 mg group.  The mean t½ value in the 30 mg group included a reported t½ value of 
87.5 hours for one participant with an anomalous data point at 216 hours postdose.  All other 
participants in the dose group had concentrations below the lower limit of quantification 
(LLOQ) after 24 hours and t½ values of 6.48 hours or less which is in the range observed for 
healthy participants.
2.2.3.2. Study B7931009 
Following a single oral 100 mg dose of PF-06700841 under fasted conditions in Japanese 
participants, absorption was rapid with a median Tmax of 1 hour and a range of 0.5 to 2 hours
on Day 1.  Following multiple oral dosing on Day 10, median Tmax was 0.76 hours with a 
range of 0.5 to 4.0 hours.  Steady-state generally appears to have been achieved by Day 6. 
The mean terminal t½ was 8.9 hours following last dose of 100 mg on Day 10. Urinary 
recovery of PF-06700841 was similar to Western participants, with less than 16% of the dose 
recovered unchanged.
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PF-06700841 exposures at steady state in Japanese participants appeared to be higher than 
the exposures in Western participants observed in Study B7931001 (n=6 in each group of 
Japanese or Western participants). 
2.2.3.3. Study B7931004 
Overall the PF-06700841 PK behaved consistently across different dose regimens in that the 
higher concentrations were achieved with higher daily doses in either induction or 
maintenance periods. Plasma concentrations of PF-06700841 observed over the treatment 
period indicated that the expected drug exposure was achieved in participants with moderate 
to severe psoriasis.  There was no substantial difference in PF-06700841 concentration-time 
profiles in psoriasis participants compared to those in healthy participants..
2.3. Benefit/Risk Assessment
There is no clinical experience to date for the topical treatment of patients with psoriasis with 
PF-06700841.  The current study is the first study of PF-06700841 administered topically for 
the treatment of patients with mild to moderate plaque psoriasis. Based on the clinical data
from study B7931004 in patients with moderate to severe psoriasis treated with PF-06700841 
orally for 12 weeks, it is anticipated that topical PF-06700841 will have acceptable 
benefit/risk balance in patients with mild to moderate psoriasis. 
More detailed information about the known and expected benefits and risks and reasonably 
expected adverse events (AEs) of PF-06700841 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
Objectives
Endpoints
Estimands
Primary: 
Primary: 
Primary:

To compare the efficacy of 
multiple dose levels of 
PF-06700841 versus vehicle on 
change from baseline in PASI 
score in participants with mild 
to moderate plaque psoriasis.

Change from baseline in PASI 
score at Week 12.

Estimand E1: 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 mild to 
moderate 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.

Population level summary: The mean 
difference between treated and vehicle 
control arms of the change from 
baseline PASI score.
Secondary: 
Secondary: 
Secondary:

To compare the efficacy of 
multiple dose levels of 
PF-06700841 versus vehicle on 
PGA score in participants with 
mild to moderate plaque 
psoriasis.
Key secondary endpoint

Proportion of participants with 
PGA score clear (0) or almost 
clear (1) and 2 points 
improvement from baseline at 
Week 12.

Estimand E2: 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 mild to 
moderate 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.

To compare the efficacy of 
multiple dose levels of 
PF-06700841versus vehicle on 
the proportion of participants 
with mild to moderate plaque 
psoriasis achieving PASI 75.
Proportion of participants 
achieving PASI 75 (75% or 
greater improvement from 
Baseline) at time points 
specified in the Schedule of 
Activities (SoA).


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Objectives
Endpoints
Estimands
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 vehicle response rates.

To compare the efficacy of 
multiple dose levels of 
PF-06700841 versus vehicle on 
measures of disease and 
symptom severity in 
participants with mild to 
moderate plaque psoriasis.

Change from baseline and 
percent change from baseline in 
PASI scores at time points 
specified in the SoA.

Absolute score and change from 
baseline in Peak-Pruritus 
Numerical Rating Scale score at 
time points specified in the 
SoA.

Absolute score and change from 
baseline Psoriasis Symptom 
Inventory at time points 
specified in the SoA.

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.

The proportion of participants 
who achieved a Psoriasis 
Symptom Inventory score of 
0 (not at all) or 1 (mild) on 
every item at time points 
specified in the SoA.

All other continuous secondary 
endpoints will be analyzed 
descriptively and using estimand 
E1 described above when appropriate.

All other categorical secondary 
endpoints will be analyzed 
descriptively and using estimand 
E2 described above when appropriate.

To assess safety and tolerability 
of PF-06700841 in participants 
with mild to moderate 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).

Change from baseline in ECG 
parameters (heart rate, QT, 
QTc, PR and QRS intervals).

Change from baseline in vital 
signs (blood pressure, pulse rate 
and temperature 
measurements).

Incidence of severity grades in
skin tolerability at times 
indicated in SoA.

There is no defined estimand for these 
endpoints and they will be analyzed 
using Pfizer data standards as 
applicable.


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Objectives
Endpoints
Estimands
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Objectives
Endpoints
Estimands
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
4. STUDY DESIGN
4.1. Overall Design
This is a Phase 2b, randomized, double-blind, vehicle-controlled, parallel group, multicenter 
study in participants with mild to moderate plaque psoriasis.  The duration of study 
participation will be approximately 22 weeks, including up to a 6 week screening period, 
12 week treatment period, and approximately 4 week follow-up period in both Stage 1 and 
Stage participants.
The study will be conducted in 2 stages where an additional cohort (Stage 2) of participants 
may be added, following completion of enrollment into Stage 1 and at the discretion of the 
Sponsor. Investigators, study participants, and Pfizer study team members will remain 
blinded to results of Stage 1.
In Stage 1, approximately 240 participants are planned to be randomized into the study, to 
allow for approximately 192 (20% drop out rate) evaluable participants (approximately 
24 completers per arm, 8 arms).  Participants will be randomized to 1 of 8 treatment groups 
in the ratio of 1:1:1:1:1:1:1:1. Participants will be randomized to 1 of 8 treatment groups in 
QD (4 active and 1 vehicle) or BID (2 active and 1 vehicle) dosing regimen in the ratio of 
1:1:1:1:1:1:1:1.
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Stage 2 will be undertaken at the discretion of the Sponsor, in order to provide more 
extensive exploration of the dose response curve. In Stage 2, approximately 40 participants 
are planned to be randomized to allow for approximately 32 evaluable participants. 
Participants will be randomized into 1 of 2 treatment groups in BID (1 active and 1 vehicle) 
dosing regimen, in ratio 3:1.
The eligibility criteria for participants enrolled in Stage 1 and Stage 2 are the same. 
A study schematic is shown in Figure 1, treatment groups are shown in Table 2.  
Figure 1.
Study Schematic


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Table 2.
Treatment Groups
Stage
Treatment 
Group
Target Number of 
Participants 
Randomized
Approx. 
Number of 
Completers 
Investigational Product
1
A
30
24
Vehicle cream QD
B
30
24
PF-06700841 0.1% cream QD
C
30
24
PF-06700841 0.3% cream QD
D
30
24
PF-06700841 1.0% cream QD
E
30
24
PF-06700841 3.0% cream QD
F
30
24
Vehicle cream BID
G
30
24
PF-06700841 0.3% cream BID
H
30
24
PF-06700841 1.0% cream BID
2
I
30
24
PF-06700841 3.0% cream BID
J
10
8
Vehicle cream BID
 
 
 
 
Throughout the 12-week treatment period, participants will treat all psoriatic areas identified 
on Day 1, regardless of clearing or improvement.  Any new psoriatic areas occurring after
Day 1 will also be treated with IP, provided they are treatment eligible (See Section 6.1.1.1).
Investigators, participants, and the sponsor study team (with the exception of the sponsor 
supply chain lead) will be blinded as to investigational drug (PF-06700841 cream vs placebo 
cream [vehicle]) assignment during the conduct of the trial.
An interim analysis will be conducted at the end of Stage 1. Some Pfizer team members and 
other key stakeholders will become unblinded to the results of Stage 1. Unblinded Pfizer 
team members will be replaced by blinded team members. Investigators and study 
participants will remain blinded to the results of Stage 1.  
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 10.9 should be followed. 
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4.2. Scientific Rationale for Study Design
This study is being conducted to provide data on efficacy, safety, tolerability and 
pharmacokinetics of PF-06700841 topical cream in the treatment of mild to moderate plaque 
psoriasis.  Oral formulation of PF-06700841 has been studied in several studies, this is the 
first clinical study for its topical formulation in patients with mild to moderate plaque 
psoriasis.  The study is intended to enable selection of a dose and dosing regimen (QD vs 
BID) for the future clinical development of topical PF-06700841.  The length of the study is 
based on the nonclinical toxicology package, which supports the planned treatment duration 
of up to 13 weeks.
Since this is one of the first topical application studies of PF-06700841,
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Patient reported outcomes will evaluate changes in psoriasis symptoms and health related 
quality of life.  The Psoriasis Symptom Inventory (PSI) and the Peak Pruritus Numeric 
Rating Scale (PP-NRS) are assessments of the symptoms associated with psoriasis, 
predominantly itching, redness, scaling, burning, stinging, cracking, flaking and pain. 
 
 
 
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Stage 2 of the study is planned to assess the highest PF-06700841 formulation strength of 
3% in BID regimens to allow more extensive exploration of the dose response for 
PF-06700841 topical cream. The corresponding vehicle arm is also planned with participants 
being randomized in 3:1 ratio in active versus vehicle arms as enrollment in Stage 2 of the 
study will commence after completion of Stage 1 enrollment. 
4.3. Justification for Dose
The nonclinical safety profile of PF-06700841 following systemic administration to rats and 
monkeys and following topical application to minipigs supports topical human clinical 
studies (Section 2.2.1).  Dose strengths selected for this study are 0.1%, 0.3%, 1%, and 
3% PF-06700841.  The highest strength cream was selected based on the maximum solubility 
of the PF-06700841 in the vehicle.  The 0.1% was the lowest concentration tested in in vitro 
systems and it showed pharmacological activity in human skin in CXCL10 and MMP12, 
borderline activity in filaggrin and no activity in CCL26, suggesting that it is the 
concentration at which we begin to observe loss of activity.  The clinical translation of these
in vitro systems is unknown.
Human systemic exposure following topical application of the PF-06700841 cream 
formulation was estimated by integrating information from the oral and IV studies in the 
minipig to provide an estimate of bioavailability and clearance from healthy participants 
(Study B7931001) following oral administration of 30 mg of PF-06700841, assuming an oral
bioavailability (F) of 0.8.  The bioavailability following topical application to humans was 
assumed to be the same as that observed in the minipig (F=0.053).  The target dose 
application is defined as 2 mg formulation/cm2.  With the low project topical bioavailability, 
it is anticipated that there will be limited contribution to efficacy from systemic drug 
concentrations.  However, the projected systemic concentrations (Cav) will be benchmarked 
against those achieved following oral QD dosing of 30 mg PF-06700841 which has shown 
clinically relevant efficacy in psoriasis (Section 2.2.2.1).  
 
 
 
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he exposure from application of this formulation 
strength BID is not expected to be associated with a change in the risk:benefit. 
IFNα regulates genes involved in antiviral and antiproliferative activities.  The 3% cream 
formulation applied BID or QD is projected to modulate the cytokine at the level of 3.3 and 
1.65 x IFNα in vitro IC50.  The long-term consequences of this level of inhibition are 
unknown.  The Cav of the lower BID and QD formulation strengths were generally at or 
below the in vitro IC50 value(Table 3). 
IL-12 and IL-23 have been implicated in the pathophysiology of chronic plaque psoriasis.  
The projected systemic Cav concentrations following either BID or QD topical application are 
lower (Table 3) than the in vitro IC50 values for both cytokines except for the 
3% formulation applied BID which is predicted to modulate the IL-12 cytokine level at 
1.5 x the in vitro IC50. 
 
 
Table 3.
Exposure Projection Following Topical Application of a PF-06700841 
Cream Formulation, Predicted Margins Relative to 30 mg Oral Once Daily 
and Multiples of Key Cytokines
Cream 
Formulation
Strength (%)
Absorbed 
Dose
mg/kg
Predicted
Cav, free
(nM)
Predicted Margins 
Relative to Oral
30 mg QD Cav, free
Multiple 
of IFNα
In vitro 
IC50 
Multiple
of IL-12 
In vitro
IC50
Multiple 
of IL-23
In vitro 
IC50 
3 BID
0.28
99.0
1.25
3.3
1.5
0.82
3 QD
0.14
49.5
2.5
1.65
0.76
0.41
1 BID
0.090
33.0
3.7
1.1
0.50
0.28
1 QD
0.045
16.5
7.4
0.55
0.25
0.14
0.3 BID
0.028
9.90
12.5
0.33
0.15
0.082
0.3 QD
0.014
4.95
25
0.165
0.076
0.041
0.1 QD
0.0045
1.65
74
0.055
0.025
0.014
BID = twice daily; 
; IFNα = interferon alpha, IC50 free = 30 nM (human whole blood 
(lymphocytes); IL-12, IC50 free = 65 nM (human whole blood (lymphocytes); IL-23, IC50 free = 120 nM (human whole 
blood (lymphocytes) Cav, free (30 mg QD healthy participants) =122 nM; fu human=0.61; molecular weight =389; 
1 ng/mL = 2.568 nM; QD = daily.
 
 
This is based on data
from the oral toxicology program, using the Cav of 1145 nM which was achieved at the 
NOAEL in the 9 month monkey toxicology study. 
The NOAEL in the pivotal topical PF-06700841 13-week study in minipigs was 1.28 mg
PF-06700841/cm2/day, resulting in an ~10-fold dose margin based on an anticipated 
application rate of 2 mg product/cm2 and the nonclinical dose of 20 mg product/cm2.
CCI
CCI
CCI
C
CC
CC
CC
CC
CC
CC
C
CCI
CCI


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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.
The end of the study is defined as the date of the last visit of the last participant in the study 
for the last participant in the trial globally.
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 particular 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 of 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 the time of informed consent 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 with a diagnosis of plaque psoriasis (psoriasis vulgaris) for at least 
6 months prior to Day 1.
3. Participants with a Physician Global Assessment (PGA) score of mild (2) or 
moderate (3) at Screening and Day 1.
4. At Screening and Day 1, have plaque psoriasis covering 2%-15% (inclusive) of total 
body surface area (BSA) on the trunk and/or limbs. Only areas to be treated with the 
IP will be included in this calculation (See Section 6.1.1.1).
5. Participants who are willing and able to comply with all scheduled visits, treatment 
plan, laboratory tests, lifestyle considerations (Section 5.3), and other study 
procedures.


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Weight:
6. Body Mass Index (BMI) 17.5-35 kg/m2 (inclusive) and body weight 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.
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, with the exception of nail psoriasis which is allowed.
2. Evidence of other skin conditions (eg, eczema) at the time of screening or Day 1 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. Any psychiatric condition, including recent or active suicidal ideation or behavior that 
meets any of the following criteria at Screening or Day 1:

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) (Section 10.10);

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;

Any lifetime history of serious or recurrent suicidal behavior;

In the opinion of the investigator or Pfizer (or designee) exclusion is required.
5. Current or history of severe, progressive, or uncontrolled renal, hepatic, 
hematological, gastrointestinal, metabolic, endocrine, pulmonary, cardiovascular, or
neurological disease.
6. 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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7. History of infection requiring hospitalization, parenteral antimicrobial therapy, or as 
otherwise judged clinically significant by the investigator within 3 months prior to 
Day 1.  History of infection requiring oral antimicrobial therapy within 2 weeks prior 
to Day 1.
8. Infected with Mycobacterium tuberculosis (TB) as defined by the following:
a.
A positive Interferon Gamma Release Assay (IGRA) test or positive 
Mantoux/Purified Protein Derivative (PPD) tuberculin skin test See
Section 8.2.1.1 for details;
b. Participants with chest radiograph with changes suggestive of or evidence of 
untreated latent or active TB infection will be excluded. See Section 8.2.1.1 for 
details;
c.
A participant who has been treated or is currently being treated for active or latent 
TB infection is to be excluded.
9. Have a known immunodeficiency disorder or a first degree relative with a hereditary 
immunodeficiency.
10. Have any malignancies or have a history of malignancies with the exception of 
adequately treated or excised non-metastatic basal cell or squamous cell cancer of the 
skin or cervical carcinoma in situ.  These excluded malignancies include but are not 
limited to having a 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.
11. Have undergone significant trauma or major surgery within 1 month prior to 
Screening.
12. 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 IP application 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.
Prior/Concomitant Therapy:
13. Require treatment with prohibited medications(s) and/or procedures (Section 10.9).
14. Require concomitant medications other than those allowed (See Section 6.5), or 
require new concomitant medications or change in dosage within 7 days or 
5 half-lives (whichever is longer) prior to Day 1 or any time between Day 1 and last 
visit unless allowed in Section 6.5.


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Prior/Concurrent Clinical Study Experience:
15. Previous administration with an investigational drug within 30 days (or as determined 
by the local requirement) or 5 half-lives prior to Day 1 (whichever is longer). 

Exception: Investigational biologics should be discussed with the Sponsor 
Medical Monitor to confirm period of discontinuation required.

Exception: Previous administration with any investigational oral or topical 
TYK2 or JAK inhibitors within 3 months or 5 half- lives prior to Day 1
(whichever is longer).
Diagnostic Assessments:
16. Infected with human immunodeficiency virus (HIV), hepatitis B or hepatitis C 
viruses. 

Participants who are hepatitis C (HCV) antibody (Ab) positive require further 
testing with HCV ribonucleic acid (RNA) Polymerase chain reaction (PCR) and 
are allowed to enroll if HCV RNA PCR negative.

Participants who are HBsAg positive are not eligible for the study.

Participants who are HBsAg negative and HBcAb positive should be reflex tested 
for Hepatitis B Surface Antibody (HBsAb) and if HBsAb is positive, may be 
enrolled in the study; if HBsAb is negative, the participant is not eligible for the 
study.
For Japan only, see Country-Specific Requirements on hepatitis B exclusion 
criteria (Section 10.8).
17. 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 (<1,000/mm3);

Absolute neutrophil count of <1.5 x 109/L (<1500/mm3);

Platelet count <100 x 109/L (<100,000/mm3);


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
estimates of glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 using serum 
creatinine or cystatin C based calculation (Section 10.18);

Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) values 
greater than 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; 

Creatinine kinase (CK) >3 times ULN;

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.
18. Screening 12-lead electrocardiogram (ECG) that demonstrates clinically significant 
abnormalities requiring treatment (eg, acute myocardial infarction, serious tachy- or 
brady-arrhythmias) or that are indicative of serious underlying heart disease 
(eg, cardiomyopathy, major congenital heart disease, low voltage in all leads,
Wolff-Parkinson-White syndrome) and other clinically relevant abnormalities which 
may affect participant safety or interpretation of study results.  If QTcF exceeds 
450 ms, the ECG should be repeated two more times and the average of the three 
QTcF should be used to determine the participant eligibility.  Participants with 
average screening value QTcF >450 milliseconds (ms) should be excluded. 
19. A history of additional risk factors for torsade de pointes (TdP) (eg, heart failure 
[New York Heart Association status of class III or IV], hypokalemia, family history 
of Long QT Syndrome).
Other Exclusions:
20. 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 
Pfizer employees, including their family members, directly involved in the conduct of 
the study.
21. Have a history of alcohol or substance abuse, unless in full remission for greater than 
6 months prior to Day 1.
22. Donation of blood in excess of 500 mL within 8 weeks prior to Day 1.
23. In the opinion of the investigator or Sponsor, the participant is inappropriate for entry 
into this study.


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5.3. Lifestyle Considerations
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 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.
5.3.2. Dietary Supplements
For the purposes of this protocol, dietary supplements are defined as vitamins, minerals, 
purified food substances, and herbals with pharmaceutical properties.  Vitamins, minerals 
and purified food substances are allowed in amounts not known to be associated with adverse 
effects (such as hypervitaminosis).
Herbals supplements are only allowed on a case by case basis; please contact the Pfizer staff.  
Herbals eg, St. John’s Wort that are known to have an effect on drug metabolism must be 
discontinued at least 4 weeks or 5 half-lives (whichever is longer)  before Day 1.
Participants should not consume grapefruit or grapefruit juice or citrus fruits eg, Seville 
oranges, omelos within 7 days prior to Day 1 and until collection of the final 
pharmacokinetic blood sample.
5.3.3. 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 until the last Follow up visit.  
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, MMR 
(measles, mumps, rubella) vaccine and vaccinia (smallpox) vaccine. 


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5.3.4. Other Lifestyle Requirements
•
Participants should not apply occlusive dressing(s) to the areas treated with IP.
•
Participants should not swim, bathe, be bathed or have treatment areas washed for at 
least 4 hours after application of the IP.
•
Use of sunscreen and regular moisturizes is permitted, but only on areas which are
not treated with IP.
•
Participants should avoid prolonged exposure to the sun and not use tanning booths, 
sun lamps or other ultraviolet light sources during the study.  Please see Section 10.9
for details on prohibited light therapy.
•
The participant should avoid wiping the IP off the skin and the IP should not be 
re-applied to areas that were inadvertently wiped until the next scheduled dose.
•
When applying the IP, the participant will not be required to wear gloves.  However, 
participants should be instructed to wash their hands with mild soap and water before 
and after each application. 
•
If study participants need someone else to assist with applying the IP on hard to reach 
areas (eg, back), this person must wear gloves to avoid exposure to the IP. 
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/entered in the study. 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 if they fail screening due to transitory conditions.  Re-screening due to 
failing inclusion/exclusion criteria with respect to PGA
is not permitted. 
Rescreened participants should be assigned a new participant number. 
All screening assessments must be repeated during re-screening, with the exception of chest 
radiograph, HIV, Hepatitis and TB testing.  These assessments do not have to be repeated if 
re-screening is done within 12 weeks of the initial screening visit and these assessments were 
performed during the initial screening visit.
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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
For this study, investigational products are the following:

PF-06700841 cream, in 0.1%, 0.3%, 1%, and 3% (w/w) strengths; may also be 
referred to as 1 mg/g, 3 mg/g, 10 mg/g, and 30 mg/g, respectively.

Vehicle cream; contains all excipients as the PF-06700841 cream except for 
PF-0670084; may also be referred to as vehicle and/or placebo.
Creams are formulated to contain PF-06700841 in designated strength, light mineral oil, 
white petrolatum, oleyl alcohol, emulsifying wax, diethylene glycol monoethyl ether, 
polyethylene glycol 400, 2-phenoxyethanol, and purified water.
Vehicle (no active drug in the formulation) contains light mineral oil, white petrolatum, oleyl 
alcohol, emulsifying wax, diethylene glycol monoethyl ether, polyethylene glycol 400, 
2-phenoxyethanol, and purified water.
All active and vehicle creams will be packaged in laminate tubes containing approximately
54 or 57 grams of either vehicle cream or PF-06700841 cream for topical application.  All 
tubes will be provided in cartons and both will be labeled in a blinded fashion according to 
local regulatory requirements. 
6.1.1. Administration
6.1.1.1. Treated Psoriatic Skin Areas 
Psoriasis treatment areas will be those affected by psoriasis on the trunk and/or limbs 
and will not include scalp, face, neck, palms or soles, nails or intertriginous areas. 
Before the initial IP application is performed on Day 1, the psoriasis treatment areas will be 
identified during the Day 1 Visit and documented in the participant’s source document study 
records.  The participant will be provided with documentation of the designated treatment 
areas.
Treated Psoriatic Areas identified on Day 1 should continue to be treated for the entire 
duration of the treatment period (12 weeks) even if substantial improvement or clearing of 
psoriasis occurs. 


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If new psoriatic areas eligible for treatment (as defined in this section above) emerge during 
the study, IP should be applied to these new areas after consultation with the Investigator.  
This may result in an additional unscheduled visit and dispensing of IP.  These new areas 
should also be captured in the participant’s source document study records including the date 
of occurrence.  Site staff will review the treatment area list with study participant and update 
as per Schedule of Activities.
If a participant misses applying a dose, the participant should apply this dose provided this 
dose should have been applied within the last 6 hours. For longer intervals, the dose should 
be skipped.  The missed dose should be recorded in the dosing diary.  The next dose should 
be applied according to the regular dosing regimen.
6.1.1.2. General Instructions
IP should be applied once a day (around the same time of the day) or twice daily 
(approximately every twelve hours) based on the assigned treatment arm to all eligible 
psoriasis treatment areas (See Section 6.1.1.1) starting at Day 1 through Week 12 visit.  Last 
dose for both BID and QD dosing will be applied either prior to or during the Week 12 clinic 
visit in the morning.
Investigational site staff will demonstrate to the participant the application of IP during Day 1 
visit.  Site staff will also provide instructions for application of IP at home.  During all 
subsequent in-clinic visits through Week 10 (and potentially Week 12), site staff will observe
the application of study IP by study participants and re-train participants if/as needed.  The IP 
will be applied per the instructions in the IP manual.
Site staff will also train the participant on completion of the Dosing Diary starting with the 
first dose applied in the clinic on Day 1 and continuing through the Week 12 visit.  This will 
be filled in by the participant each time the IP is applied. 
Those participants having difficulty reaching treatment-eligible areas (eg, back) may be 
assisted by another person who will need to apply the IP to the participant according to the IP
application instructions.  The person assisting with the application must wear gloves to avoid 
any exposure to the IP.
Participants will be instructed not to wipe the IP off the skin, avoid applying an occlusive 
dressing to the treated areas, and refrain from swimming or bathing/washing the treated areas 
within 4 hours after application.
Throughout the study period, topical products described in Section 10.9 are not allowed on 
areas being treated with the IP.
The investigational drug application regimen should not be modified.  Temporary
discontinuation and/or permanent discontinuation of the investigational product may be 
appropriate under some circumstances (See Section 7.1.1).


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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. 
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.
4. Further guidance and information for the final disposition of unused study 
interventions are provided in the 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 Pfizer 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 Pfizer provides permission 
to use the study intervention.  It will not be considered a protocol deviation if Pfizer 
approves the use of the study intervention after the temperature excursion.  Use of the 
study intervention prior to Pfizer 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 Pfizer, 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
Within this protocol, preparation refers to the investigator site activities performed to make 
the IP ready for application or dispensing to the participant by qualified staff.  Dispensing is 
defined as the provision of IP, concomitant treatments, and accompanying information by 
qualified staff member(s) to a healthcare provider, participant, or caregiver in accordance 
with this protocol.  Local health authority regulations or investigator site guidelines may use 
alternative terms for these activities.
The IP will be dispensed in a blinded fashion using an interactive response technology (IRT)
system at each in-clinic visit from Day 1 Visit to Week 10 Visit.  A qualified staff member 
will dispense the IP via unique container numbers on the cartons provided, in quantities 
appropriate for the study visit schedule 
For doses to be administered at home, the participant should be instructed to maintain the 
product in its original package provided throughout the course of dosing and return the 
product and its original package (including empty, partially used and unused tubes) to the site 
at the next study visit.  All previously dispensed IP tubes will be retained by the site.  For 
each participant, IP tubes with caps will be weighed individually or collectively by the study 
site before dispensing and after return and the weights will be recorded.  The sponsor will use 
the recorded weights to estimate usage (eg, mg/cm2/application) for each participant.  Note 
that the weight recorded on the IP label is a nominal weight of the IP itself without the 
weight of the tube.
IP will be assigned to participants during Day 1 Visit once the participant is successfully 
randomized through the IRT system.  The investigator or appropriate delegate at the site will 
access the IRT system at the Day 1 visit and all subsequent scheduled visits (until Week 10) 
to receive the correct tube numbers to be dispensed to the participant.  All tubes of the IP
dispensed or returned will be recorded and documented.
The tool to standardize the IP need calculation across participants and study sites may be 
provided by the sponsor.
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6.2.2. Investigational Product Accountability 
The investigator site must maintain adequate records documenting the receipt, use, loss, or 
other disposition of the IP supplies.  All investigational products will be accounted for using 
a drug accountability form/record.  All tubes of IP 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 IP (including empty, partially used and
unused tubes) and the dosing diary to the clinic at every visit.  Detailed drug accountability 
records, including tube weights measured in the clinic, will be maintained by study staff for 
each participant.
The original IP 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 all the IP 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 
Pfizer, and all destruction must be adequately documented.
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 Section 6.3.1
Allocation to IP and Section 6.3.2 Breaking the Blind for further details. 
6.3.1. Allocation to Investigational Product
For this study, the IP is PF-06700841 (or its matching vehicle) topical cream.  Participants 
will be randomized into one of the doses in QD dosing arm or BID dosing arm of 
PF-06700841 or its matching vehicle. 
At the Day 1 visit, provided all inclusion/exclusion criteria have been met, the participant 
will be randomized to trial medication.  The investigative site will contact an interactive 
response technology (IRT) system (interactive Web-based response [IWR]).  Allocation of 
participants to treatment groups will proceed through IRT.  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 


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participant number.  The site personnel will then be provided with a treatment assignment, 
randomization number, and dispensable unit (DU) or container number when the IP 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. 
The study-specific IRT reference manual and the IP manual will provide the contact 
information and further details on the use of the IRT system.
Returned IP must not be redispensed to the participants.
6.3.2. Breaking the Blind 
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 Clinician or Sponsor Medical 
Monitor 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).
The study-specific IRT reference manual and IP manual will provide the contact information 
and further details on the use of the IRT system.
Participants whose code is broken will be discontinued from treatment, complete early 
termination visit and follow-up period per Schedule of Activities. Any cases of unblinding 
will be documented in the study report.
6.4. Study Intervention Compliance
The participant will apply the IP at home and during scheduled in clinic visits as per SoA.  
Participants will be instructed to complete the Dosing Diary each time IP is applied, starting 
with the first dose applied in the clinic on Day 1, then through Week 12.  Participants will be 
instructed to bring the Dosing Diary and all dispensed IP supplies in its original package 
(used as well as unused) to the clinic for weighing at all visits.  Participant compliance with 
IP application will be assessed by site staff at each visit by reviewing e-diary (ie, application 
of IP each day between in clinic visits).  In addition, tube weights will be used to assess 
compliance by the study team at the end of the study. 
Participants with missed doses of IP or additional doses of IP beyond dosing regimen will be 
re-trained by the site.  This re-training will occur at a minimum if participant meets the 
definition of noncompliance (less than 80% or more than 120% of IP applications as directed 
by the dosing instructions) but may re-training may be performed by the site even if 
participants missed a few doses or apply a few additional doses.  The sponsor will have the 


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discretion to withdraw any participant from the study due to non-compliance with the topical 
application of IP.  Investigators should indicate on the appropriate CRF page noncompliance 
with study intervention and provide an explanation.  Inventory control of all IPs 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 Pfizer.
6.5. Concomitant Therapy
Medications taken during Screening will be documented as prior medications.  Medications 
taken after the first dose of IP has been administered will be documented as concomitant 
medications.  All concomitant medications taken during the study must be recorded in study 
records with indication, daily dose, and start and stop dates of administration.  Participants 
will be queried about concomitant medication (including topical medications and treatments, 
over-the-counter and prescription medications and treatments, and vaccinations) at each visit.  
Any new concomitant medications or dose changes to current concomitant medications 
should be evaluated for potential new or worsening adverse events.
See Section 10.9 on prohibited medications and procedures.
The following concomitant medications are allowed unless excluded in Prohibited 
Medications (Section 10.9):

Antihistamines.

Selective leukotriene receptor antagonists (eg, montelukast sodium, zafirlukast), mast 
cell stabilizers (eg, cromolyn sodium or nedocromil sodium).

Acetaminophen/paracetamol and ibuprofen.

Medications for regulation of thyroid function.

Corticosteroid inhalers and intranasal sprays (provided participants receiving stable 
dose for at least 1 week before Day 1 and during the treatment period).

Ophthalmic corticosteroids (provided participants receiving stable dose for at least 
1 week before Day 1 and during the treatment period).

Medications for chronic stable medical conditions (eg, hypertension) provided these
are not expected to affect the study assessments.  Change in medication for 
hypertension is allowed.

Hormone replacement therapy (HRT) and hormone contraception as described in 
Appendix 4 (Section 10.4).


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
Topical treatments applied to areas not treated with IP unless prohibited in 
Section 10.9. 

Sunscreen and regular moisturizers applied to areas not treated with IP. 

Any other concomitant medication not specifically prohibited in Section 10.9 may be 
considered on a case by case basis by the investigator in consultation with the 
Sponsor Medical Monitor.
6.5.1. Rescue Medicine
There is no rescue therapy to reverse the adverse events (AEs) observed with PF-06700841; 
standard medical supportive care must be provided to manage the AEs.
6.6. Dose Modification
Not applicable.
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 IP. 
Per the study estimands, if IP is permanently discontinued, the participant will proceed to 
early termination and follow up visits 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 enter into the Follow up Period with 
their first follow up visit occurring 1 week after their last dose whenever possible (instead of 
two weeks in Schedule of Activities) and continue visits per Investigator’s discretion until 
the event has returned to normal or baseline levels or is deemed clinically stable. 
The procedures scheduled for Week 12 (end of treatment) Visit will be performed on the last 
day the participant takes the IP or as soon as possible thereafter.  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.  Additional 
follow up visits may occur as needed until any clinically relevant abnormalities or adverse 
events have resolved, returned to a baseline state, or are deemed clinically stable.
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.
Note that discontinuation of the IP does not represent withdrawal from the study.


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ECG Changes
A participant who meets either bulleted criterion below based on the average of triplicate 
ECG readings (see Section 8.2.2.4) will be withdrawn from the IP application. 

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.
Local Tolerability Assessment
If a participant experiences severity Grade 3 (severe) or 4 (very severe) on the local 
tolerability assessment (Section 8.2.2.8, Table 9), the IP will be discontinued permanently 
and participant will proceed to ET visit and Follow-up period as described in Schedule of 
Activities. 
If a participant experiences application site reaction of Grade 2 (moderate) on the local 
tolerability assessment, investigator may temporarily discontinue application of IP for up to 
one week after consultation with the Sponsor Medical Monitor.  This dosing gap may occur 
only once for the same participant. 
Adverse Events 

Serious infections, defined as any infection (viral, bacterial, and fungal) requiring 
parenteral antimicrobial therapy or hospitalization for treatment, or meeting other 
criteria that require the infection to be classified as a serious adverse event.

Other serious or severe AEs will be considered, after consultation with the Sponsor 
clinician or Sponsor Medical Monitor.
Potential Cases of Decreased eGFR 
If an individual participant demonstrates CONCOMITANT serum creatinine-based AND 
serum Cystatin C-based eGFR decline of 30% (See Section 10.18) compared to the 
participant’s baseline eGFR, then the participant should not be further dosed and adequate, 
immediate, supportive measures including immediate evaluation by a nephrologist 
(preferably within 24 hours) with appropriate management and treatment as clinically 
indicated. Results should be repeated as indicated by the nephrologist or weekly at a 
minimum until the eGFR returns to baseline 15%, or the renal parameters are deemed to be 
stable by the nephrologist and/or the investigator.


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If the participant cannot be seen by a nephrologist within 24 hours (as described above), then
the participant should be sent to a local emergency room for evaluation and treatment as 
clinically indicated.
Follow-up evaluations should include laboratory tests, detailed history, and physical 
assessment.  In addition to repeating serum creatinine and serum cystatin C, laboratory tests 
should also include: serum blood urea nitrogen (BUN), serum creatine kinase (CK), serum
electrolytes (including at a minimum potassium, sodium, phosphate/phosphorus, calcium), in 
addition to urine dipstick, urine microscopic examination, and urinary indices.  All cases 
confirmed on repeat testing as meeting the laboratory criteria for acute kidney injury, with no 
other cause(s) of laboratory abnormalities identified should be considered as potential cases 
of drug-induced kidney injury irrespective of availability of all the results of the 
investigations performed to determine etiology of the abnormal serum creatinine.
All relevant test results will be forwarded to Sponsor Medical Monitor for review 
immediately upon receipt by the PI.
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
ASTb
>2.5x ULN
ALT
>2.5x ULN
Total bilirubina
>1.5x ULN
a.
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.
b.
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.
Pregnancy
Pregnancy confirmed by serum -hCG testing.  Sponsor Clinician or Sponsor Medical 
Monitor should be notified immediately.


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
Two negative pregnancy tests are required before receiving IP (one negative serum 
pregnancy test at screening and one negative urine pregnancy test at Day 1 visit).  If 
urine pregnancy test is positive after IP application, serum pregnancy test will be 
conducted, IP paused and sponsor clinician and sponsor medical monitor notified 
immediately.
7.1.1. Temporary Discontinuation 
Temporary discontinuations of IP:

Will occur for woman of childbearing potential (WOCBP) in cases of positive urine 
pregnancy test which if confirmed by serum pregnancy test will lead to permanent 
discontinuation (see Pregnancy in Section 7.1).

May apply in case of application site reaction as described in Local Tolerability 
Assessment in Section 7.1. 

Additional instances of temporary discontinuation may be appropriate (eg, surgery, 
infection, etc). 
All temporary discontinuations should be discussed with Sponsor Clinician or Sponsor 
Medical Monitor to determine if participant may continue in the study.  If possible, the site 
will consult with the sponsor prior to temporary discontinuation. 
7.2. Participant Discontinuation/Withdrawal From the Study
A participant may withdraw from the study at any time at his/her own request.  Reasons for 
discontinuation from the study include the following:

Adverse event;

Refused further follow-up;

Lost to follow-up;

Death;

Study terminated by sponsor;

Pregnancy;

Physician decision;

Other.


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At the time of discontinuing from the study, if possible, an early discontinuation 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. 
The early discontinuation visit applies only to participants who are enrolled/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.
Withdrawal of Consent: 
Participants who request to discontinue receipt of study treatment will proceed to ET visit as 
soon as possible.  Whenever possible, these participants should have one visit approx. two 
weeks after the last dose (Week 14 Follow up visit assessments) and the last visit at least 
28 days after the last dose of IP was administered (Week 16 Follow-up visit assessments). 
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 study intervention 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 
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;

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.
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.


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Procedures conducted as part of the participant’s routine clinical management (eg, blood 
count) and obtained before signing of the ICD may be utilized for screening or baseline 
purposes provided the procedures met the protocol-specified criteria and were performed 
within the time frame defined in the SoA.
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 in this study is approximately 
205 mL.  The actual collection times of blood sampling may change.  Additional blood 
samples may be taken for safety assessments at times specified by Pfizer, provided the total 
volume taken during the study does not exceed 550 mL during any period of 60 consecutive 
days.
8.1. Efficacy Assessments
All efficacy assessments of psoriatic skin will be based only on areas treated with IP, 
described in Section 6.1.1.1.
Efficacy assessments for the same participant should be performed by the same clinician 
throughout the study whenever possible.
8.1.1. Psoriasis Area and Severity Index 
The Psoriasis Area and Severity Index (PASI) quantifies the severity of a participant’s
psoriasis based on both lesion severity and the percentage of 
 affected.28
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.  Appropriate morphologic descriptors for each severity score are shown in Table 4.
CCI


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Table 4.
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 5). 
Table 5.
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
Calculating PASI
Body Region Weighting: each body region is weighted according to its approximate 
percentage of the whole body (Table 6).


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Table 6.
Area and Severity Index (PASI) Lesions Body Region Weighting
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.
8.1.2. Physician Global Assessment 
The Physician Global Assessment (PGA) 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
(Table 7).  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” (Table 8).
Table 7.
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


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Score
Description
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
Table 8.
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.
8.1.3. Body Surface Area 
Assessment of body surface area (BSA) involved in psoriasis is performed separately for four 
areas of the body: head, upper limbs, trunk (including axillae and groin), and lower limbs 
(including buttocks).  The percentage surface area affected by psoriasis is estimated by 
means of the “handprint method”, where the full hand of the participant (ie, the participant’s 
fully extended palm, fingers and thumb together) represents approximately 1% of the total 
BSA.29
Body region value is then summed across all four body regions resulting in a total BSA with 
psoriasis as described in the following equation:
BSA (%) =0.1Sh + 0.2Su + 0.3St + 0.4Sl
(where S = body region surface area with psoriasis; h = head & neck; u = upper limbs; 
t = trunk; l = lower limbs).  Calculation will be done centrally by Sponsor programmers.


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BSA calculation will be used to determine the number of tubes with IP to be dispensed.  BSA 
assessment and BSA calculation may be also performed during unscheduled visit if 
participant develops additional treatment eligible psoriatic areas in between in clinic visits. 
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 he or 
she 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.
8.2.1. Assessments at Screening Only
8.2.1.1. Tuberculosis Testing
Participants will be screened for infection with Mycobacterium tuberculosis (TB) either 
using Interferon Gamma Release Assay (IGRA) test or Mantoux/Purified Protein Derivative 
(PPD) tuberculin skin test.  This will be performed at Screening. If either of these TB tests 
were performed within 12 weeks prior to Day 1 and the documentation is available, this does 
not have to be performed during Screening. 
It is recommended that participants with a history of Bacille Calmette Guérin (BCG) 
vaccination be tested with the IGRA test since the Mantoux/PPD tuberculin skin test may be 
positive due to vaccination.


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8.2.1.1.1. Interferon Gamma Release Assay Tuberculin Test
The following are acceptable IGRA assays: QuantiFERON®-TB Gold Plus test, 
QuantiFERON-TB Gold test (QFT-G), QuantiFERON-TB Gold In-Tube test (QFT-GIT) 
and T-SPOTTB test.  Site personnel should follow the processing and analyses steps based 
on the assay chosen. 
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, 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) 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.
8.2.1.1.2. Mantoux/Purified Protein Derivative (PPD) Tuberculin Skin Test
Participants can be TB screened using the Mantoux/PPD Tuberculin Skin Test.  
Mantoux/PPD testing can also be performed if there are indeterminate QFT-G test results.
Participants must have a Mantoux/PPD tuberculin skin test administered and then evaluated 
by a health care professional 48 to 72 hours later.  A positive Mantoux/PPD tuberculin skin 
test is exclusionary.
8.2.1.2. Chest Radiograph
Local guidelines should be followed with respect to whether chest radiograph should or 
should not be taken at Screening. For example, in the United States, local guidelines require 
chest radiograph in high-risk population. In the event a chest radiograph is taken, it should 
be read by a qualified radiologist. In addition, local guidelines should be followed as to 
which imaging method should be used. Examples of imaging methods are X-ray 
(posterior-anterior and lateral views are recommended), computed tomography (CT) or 
magnetic resonance imaging (MRI). Documentation of the official reading should 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. 


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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.
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.
History of alcohol and tobacco use, current smoking status and average alcohol consumption 
will be collected in units.  A unit of alcohol contains 12 g of pure alcohol, an amount 
equivalent to that contained in 5 oz/150 mL (a glass) of wine, 12 oz/360 mL of beer, or 
1.5 oz/45 mL of 90 proof of spirits. 
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 
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. 
8.2.1.4.1. Columbia Suicide Severity Rating Scale 
The Columbia Suicide Severity Rating Scale (C-SSRS) is a validated tool to evaluate suicidal 
ideation and behavior30 (Section 10.10). 
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, gastrointestinal, and neurological systems. Height and weight
will also be measured and recorded.  Investigators should pay special attention to clinical 
signs related to previous serious illnesses. 


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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. 
8.2.2.3. Vital Signs
Temperature (Oral, Tympanic, Axillary or Temporal), pulse rate and blood pressure will be 
assessed.  It is preferred that body temperature be collected using the same method for the 
same participant throughout the study.
Blood pressure and pulse rate measurements will be assessed with a completely automated 
device either in supine or sitting position. The same position should be used consistently for 
the same participant throughout the entire study. Manual techniques will be used only if an 
automated device is not available.  It is preferred that the same arm (preferably the dominant 
arm) be used throughout the study.  Blood pressure and pulse rate measurements should be 
preceded by at least 5 minutes of rest.
8.2.2.4. Electrocardiograms
Single 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 PR, 
QT, and QTc intervals and QRS complex. Additional ECG may be performed upon request 
by the Sponsor Clinician or the Sponsor Medical Monitor.  All scheduled ECGs should be 
performed after the participant has rested quietly for at least 10 minutes in a supine position.  
When the timing of these measurements coincides with a blood collection, the ECG should be 
obtained prior to the nominal time of the blood collection, BP, and pulse rate. 
ECGs will be read and interpreted locally.  To ensure safety of the participants, a qualified
individual (eg, investigator, sub-investigator) at the investigator site will make comparisons 
to baseline measurements taken at Day 1.  ECG parameters (heart rate, QT, QTcF, PR and 
QRS intervals) should be recorded on the Case Report Form (CRF). A copy of the ECG 
should be available as source documents for review. 


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During screening, if participants have initial screening value QTcF >450 milliseconds (ms), 
ECG should be repeated two more times and the average of the three QTcF should be used to 
determine the participant eligibility.
If at any subsequent time QTcF 500 msec or change from baseline QTc 60 msec, ECG 
should be repeated two more times and an average of these values should be used to 
determine withdrawal from IP (see Section 7.1).  If the average is above these thresholds, 
participants should be monitored hourly with triple ECGs. 
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). 
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.
8.2.2.5. 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 of time 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.


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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.
8.2.2.6. Herpetiform Rash 
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.
8.2.2.7. Creatinine, Cystatin C, and estimates of Glomerular Filtration Rate
Serum creatinine is the best known standard test for monitoring renal function.  However, 
serum creatinine based estimates of glomerular filtration rate (eGFR) may be affected by 
factors other than renal function, including chronic and acute illness.  Serum cystatin C is a
test that can be used either as an adjunct to or a replacement for serum creatinine.  The most 
reliable estimates of GFR use both test results. 
Serum creatinine will be measured as part of serum chemistry at times specified in the 
Schedule of Activities section of the protocol.  Creatinine elevations above the ULN will be 
followed until resolution or baseline. Serum creatinine based eGFR will be calculated.  
Serum cystatin C will be measured and cystatin C based eGFR will be calculated at 
corresponding times per Schedule of Activities. 
The eGFR will be calculated using the 2 sets of equations developed by the Chronic Kidney 
Disease Epidemiology Collaboration (CKD-EPI),31 which utilize serum creatinine (SCr) and 
serum Cystatin C (S Cystatin C) respectively (Section 10.18). 
8.2.2.8. Local Tolerability Assessment 
The investigator or designee will assess tolerability at the site of IP application.  This 
assessment will focus on the treated non-lesional skin surrounding the plaques using scale32
in Table 9.  See Section 7.1 for permanent and temporary discontinuation criteria based on 
local tolerability assessment. 


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Table 9.
Skin Tolerability Grading System
Grade
Severity
Description
0
None
No evidence of local intolerance
1
Mild
Minimal erythema and/or oedema, slight glazed appearance
2
Moderate
Definite erythema and/or oedema with peeling and/or cracking 
but needs no adaptation of posology
3
Severe (to be 
reported as
an AE)
Erythema, oedema glazing with fissures, few vesicles or papules: 
consider removing topical agent (if still in place)
4
Very severe 
(to be 
reported as 
an AE)
Strong reaction spreading beyond the treated area, bullous 
reaction, erosions: removal of topical agent (if still in place)
8.2.2.9. Pregnancy Testing 
Pregnancy tests may be urine or serum tests, but must have a sensitivity of at least 
25 mIU/mL.  Pregnancy tests will be performed in 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.
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 
[study intervention] [study] (see Section 7). 


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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.
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
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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.
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.


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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 28 days after the 
last dose of IP. 
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.
Exposures to the investigational product under study may occur in clinical trial settings, such 
as medication errors.


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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 investigational product greater than BID dosing 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 
investigational product can no longer be detected systemically (at least 7 days).
3. Obtain a blood sample for pharmacokinetic (PK) analysis within 1 day from the date 
of the last dose of study intervention if requested by the medical monitor (determined 
on a case-by-case basis).


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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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8.9. Health Economics
Health economics/medical resource utilization and health economics parameters are not 
evaluated in this study.
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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.  All PROs should be completed in the 
following order: Psoriasis Symptom Inventory (PSI), Peak-Pruritus Numerical Rating Scale 
(PP-NRS),
 
  The 
amount of time required for a participant to complete the PRO questionnaires is 
approximately 10-30 minutes (depending on the visit and associated PROs). 
Once participants meet all inclusion/exclusion criteria, they will be provided a handheld 
device (provided by the Sponsor) for dosing diary and ePROs completion 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 
source of daily 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.33
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.  Patients 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 
(Section 10.11).34,35  Participants will be asked to assess their itch over the past 24 hours, 
with the terms “no itching” (0) and “worst possible itching” (10). 
The PP-NRS should be completed as described in the Schedule of Activities, preferably the 
same time of the day. 
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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 change from 
baseline in PASI scores at Week 12 relative to vehicle (with the same dosing schedule, QD 
or BID) 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 vehicle.  Participants with inadequate compliance will have their 
recorded PASI scores used as-is in the analysis.  The population based treatment effect will 
be the differences in the mean change from baseline in each treatment arm compared to the 
corresponding vehicle. 
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The secondary estimand will be the population average treatment effect on the PGA response 
rate (percentage of participants with a score of clear (0) or almost clear (1) and ≥2 point 
improvement from baseline at Week 12 relative to vehicle (with the same dosing schedule, 
QD or BID) without regard to compliance with IP in the absence of prohibited medication.  
This is a composite estimand where success is defined as achievement of a PGA response 
while remaining on study, providing data and not taking prohibited medication; lack of 
compliance or adverse events will not be counted as a failure.  The population based 
treatment effect will be the differences in the proportions of successes in each treatment arm 
compared to the corresponding vehicle. 
All other key secondary continuous clinical endpoints will be analyzed using the primary 
estimand, while all other key secondary categorical clinical endpoints will be analyzed using 
the secondary estimand 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 
available literature as needed.  Details of these analyses will be presented in the statistical 
analysis plan (SAP).
9.2. Sample Size Determination
The sample size of Stage 1 and Stage 2 are based on the primary efficacy endpoint, PASI 
change from baseline at Week 12.  With an assumed standard deviation of 4.2 and treatment 
difference of 4.5, a total of 240 randomized participants with 8 treatment groups from 
Stage 1 will provide approximately 90% power for individual comparisons of active groups 
versus vehicle groups at a one-sided significance of 0.05 using a Bonferroni multiplicity 
adjustment.  This calculation allows for an approximate 20% dropout rate, that is 
24 participants evaluable per arm at Week 12, where evaluable is defined as included in the 
mITT set (defined in Section 9.3). 
Participants enrolled in Stage 2 will be randomized to either the 3% BID treatment group or 
the corresponding vehicle BID group in 3:1 randomization ratio. During the final analysis
process, participants from BID vehicle group from both Stage 1 and Stage 2 will be pooled 
together for the comparisons of the BID treatment groups. With an assumed standard 
deviation of 4.2 and treatment difference of 4.5, a total of 40 participants in Stage 2 will 
provide approximately 90% power with one-sided significance level using Bonferroni 
correction on 7 pairwise comparisons. 
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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 apply at least 
1 dose of IP.  Participants will be analyzed according to the 
product they actually received.  For participants who 
discontinue treatment and/or receive prohibited medication, 
efficacy data (eg, primary and key secondary endpoints) will 
be censored starting at the ET visit.
Defined Population for 
Analysis
Description
mITT analysis set
All participants randomly assigned to IP and who apply at least 
1 dose of IP.  
 
9.4. Statistical Analyses
The SAP will describe the participant populations to be included in the analysis, 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: 
Change from 
Baseline 
PASI at 
Week 12
A landmark analysis using analysis of covariance of change from 
baseline PASI, adjusting for the baseline PASI score, to estimate the 
effect of the initially randomized treatment in the absence of prohibited 
medication regardless of treatment compliance.  The analysis will use 
the mITT analysis set. At the interim, BID treatment groups 
(PF-06700841 1% and 0.3% BID) will be compared against the 
available BID vehicle group data, whereas all BID treatment groups
will be compared against the pooled BID vehicle group from two stages
during the final analysis. Missing data due to any cause including 
censoring due to initiation of prohibited medication will be imputed 
using the corresponding vehicle arm, missing data in a vehicle arm will 
be imputed using data from the vehicle arm assuming data are missing 
at random (MAR).  The analysis will combine the results from the 
multiple imputations using Rubin’s rule’s as implemented in SAS 
PROC MIANALYZE.  The overall family wise Type I error rate will 
be controlled at the one-sided 0.05 level using the Hochberg step up 
procedure.
Secondary –
PGA 
Response at 
Week 12
A landmark analysis of the composite endpoint; achieving a PGA 
response (a score of clear(0) or almost clear(1) and 2 point 
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 vehicle control 
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. No adjustments for multiplicity will be made. 
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 primary estimand along 
with descriptive statistics and possibly graphical displays.  No adjustments for multiplicity 
will be made for these endpoints.


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Other binary secondary endpoints at time points specified in the Schedule of Activities
including, 
, PASI75, 
, 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 secondary estimand along with descriptive statistics and possibly graphical 
displays.  No adjustments for multiplicity will be made for these endpoints.
 
Sensitivity analysis on baseline charactersistics about the primary and key secondary
endpoints by stage and treatment may be conducted and the details of those analysis will be 
presented in the statisticial analysis plan (SAP) and will be finalized before Stage 1 interim
analysis.  
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.
 
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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, the number of participants with uncorrected QT values >500 msec will be 
summarized.
 
 
 
 
 
 
 
 
 
9.5. Interim Analyses
An interim analysis will be performed by an Internal Review Committee (IRC) which will 
include safety and efficacy for making internal business decisions regarding future study 
planning. If the IRC is asked to perform an analysis of the data, then, the 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.  Members of the IRC will be qualified and 
experienced in reviewing and interpreting clinical study data.  They will be independent of 
the study team, and unblinded to treatment. In addition, the analysis details must be 
documented and approved in an interim analysis SAP or final SAP.  
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In addition, an interim analysis will be conducted at the end of Stage 1. Some Pfizer team 
members and other key stakeholders will become unblinded to the results of Stage 1. 
Unblinded Pfizer team members will be replaced by blinded team members. Investigators
and study participants will remain blinded to the results of Stage 1.
9.5.1. Data Monitoring Committee 
This study will use an internal review committee (IRC).  The IRC will be responsible for 
ongoing monitoring of safety and efficacy of participants in the study according to the 
charter.  Members of the IRC will be qualified and experienced in reviewing and interpreting 
clinical study data.  They will be external to and independent of the study team, and 
unblinded to treatment.  The recommendations made by the IRC to alter the conduct of the 
study will be forwarded to Pfizer for final decision.  This will not include the members of the 
study team.  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. 
In addition, an external blinded adjudication committee will be selected on ad-hoc basis if
suspected cardiovascular and/or thromboembolic events (TE) are observed during the study 
conduct. The adjudication committee members will consist of external experts and the 
decisions of the adjudication committee may be databased and used for the analyses of the 
secondary endpoint and other endpoints.  Specific details on this process and additional 
information can be obtained in the central adjudication committee charter. Other safety 
events for adjudication may be identified and included in the remit of the safety adjudication 
committee as appropriate.
9.6.
PD Unblinding Plan
A 
PD unblinding plan approved by the clinical lead, clinical pharmacology lead and 
statistical lead will be in place to describe the procedures to be employed in safeguarding the 
study blind for members of the study team.  These procedures will be in accordance with 
applicable Pfizer SOPs for releasing randomization codes and breaking the study blind.
Under this plan a group of statisticians, 
PD data provider, 
PD analyst and 
PD 
support would be unblinded in order to initiate the building of statistical models of the PK, 
dose/response as well as exposure/response analysis models and conduct associated 
simulations.  The aim of this work would be to facilitate a fuller interpretation of the study
upon completion (at appropriate interim milestone).  This group will not serve on the study
team during the period of early unblinding.  The unblinding may occur after approximately 
50% of the participants have completed treatment in Stage 1 and Stage 2. The details of the 
procedures will be described in the 
PD Unblinding Plan for Modelling and Simulation for 
Study B7931023 which will be finalized prior to the start of the 
PD unblinding.
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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 
product, Pfizer should be informed immediately. 


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In addition, the investigator will inform Pfizer 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.


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Participants must be reconsented to the most current version of the ICD(s) during their 
participation in the study.
A copy of the ICD(s) must be provided to the participant or the participant’s legally 
authorized representative.
Participants who are rescreened are required to sign a new 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).
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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.
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.


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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 
redacted.
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 
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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 
maintained.
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
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 
records, depending on the study. Also, current medical records must be available.
Definition of what constitutes source data can be found in Study completion guidelines.
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.


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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
The results of this study may be published or presented at scientific meetings by the 
investigator after publication of the overall study results or 1 year after end of the study (or 
study termination), whichever comes first. 
The investigator agrees to refer to the primary publication in any subsequent publications 
such as secondary manuscripts, and submits all manuscripts or abstracts to the sponsor 
30 days before submission. This allows the sponsor to protect proprietary information and to 
provide comments and the investigator will, on request, remove any previously undisclosed 
confidential information before disclosure, except for any study- or Pfizer 
intervention-related information necessary for the appropriate scientific presentation or 
understanding of the study results.
For all publications relating to the study, the investigator will comply with recognized ethical 
standards concerning publications and authorship, including those established by the 
International Committee of Medical Journal Editors.
The sponsor will comply with the requirements for publication of the overall study results 
covering all investigator sites.  In accordance with standard editorial and ethical practice, the 
sponsor will support publication of multicenter studies only in their entirety and not as 
individual site data.  In this case, a coordinating investigator will be designated by mutual 
agreement.
Authorship of publications for the overall study results will be determined by mutual 
agreement and in line with International Committee of Medical Journal Editors authorship 
requirements. 
If publication is addressed in the clinical study agreement, the publication policy set out in 
this section will not apply.


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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 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.
Table 10.
Protocol-Required Laboratory Assessments
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)
BUN/urea and creatinine
Cystatin C
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)b
pH
Glucose (qual)
Protein (qual)
Blood (qual)
Ketones
Nitrites
Leukocyte esterase
Urobilinogen
Urine bilirubin
Microscopyd
At screening only:
•
FSHe
•
HIV
•
Hepatitis B Surface Antigen 
(HBsAg)
•
Hepatitis B Core Antibody 
(HBcAb)
•
Hepatitis B Surface Antibody 
(HBsAb)f
•
Hepatitis C antibody (HCV 
Ab)
•
Hepatitis C RNA PCRg
•
TB testh
•
aPTT
•
PT/INR
At visits per SoA:
•
Pregnancy test (β-hCG)i
•
HBV DNAj (Japan only) 
•
Skin swabs for herpetiform 
rashk
•
Lipid Profile Panelc
Total Cholesterol
Triglycerides
HDL
   LDL
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; 
HBcAb = Hepatitis B Core Antibody; HBsAb = Hepatitis B Surface Antibody; HBsAg = Hepatitis B Surface Antigen; 
HBV DNA = viral load; HC Ab = Hepatitis C Virus Antibody; HCV RNA = Hepatitis C Virus Ribonucleic Acid; 
HDL = high density lipoproteins; HIV = Human Immunodeficiency Virus;
 
 IGRA = Interferon Gamma Release Assay; INR = international normalized ratio; LDL =low density 
lipoproteins; 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
C
C
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a.
Safety labs include hematology, chemistry and urinalysis.  Lipid panel will be performed at times indicated in 
Schedule of Activities. Fasting not required unless lipid panel taken.
Safety laboratory tests may be performed at a local laboratory, where allowable by law or local guidance, if the 
study participant is unable to visit the study site. Local laboratory reference ranges and a copy of local lab results 
should be included in participant’s source documents.
b.
CK fractionationation if CK > 3x ULN.
c.
Lipid panel requires fasting (water only) at least 8 hours prior to collection.
d.
Only if urine dipstick is positive for blood, protein, nitrites, or leukocyte esterase.
e.
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).
f.
HBsAb reflex testing only if HBsAg negative but HBcAb positive.
g.
HCV RNA reflex testing only if positive for HCV Ab.
h.
TB test may be Interferon Gamma Release Assay (IGRA) or Mantoux/Purified Protein Derivative (PPD).
i.
For women of childbearing potential.
j.
For participants who are HBsAg negative, HBcAb positive, and HBsAb positive OR for participants who are 
HBsAg negative, HBcAb negative and HBsAb positive without documentation of prior HBV vaccination.
k.
In cases of suspected herpetiform rash (eg, suspected herpes zoster and herpes simplex).
Investigators must document their review of each laboratory safety report.


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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.

“Lack of efficacy” or “failure of expected pharmacological action” per se will not 
be reported as an AE or SAE.  Such instances will be captured in the efficacy 
assessments. However, the signs, symptoms, and/or clinical sequelae resulting 
from lack of efficacy will be reported as an AE or SAE if they fulfill the definition 
of an AE or SAE.


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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 
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:
a. Results in death
b. 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.
c.
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.


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Hospitalization for elective treatment of a preexisting condition that did not worsen from 
baseline is not considered an AE.
d. 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, and accidental trauma (eg, sprained ankle) which may interfere with or 
prevent everyday life functions but do not constitute a substantial disruption.
e.
Is a congenital anomaly/birth defect
f.
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.


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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
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 


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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.
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 


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accordance with the SAE reporting requirements.
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
Male participants are eligible to participate if they agree to the following requirements 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 study intervention(s):

Refrain from donating sperm.
PLUS either:

Be abstinent from heterosexual intercourse with a female of childbearing potential as 
their preferred and usual lifestyle (abstinent on a long-term and persistent basis) and 
agree to remain abstinent.
OR

Must agree to use a male condom when engaging in any activity that allows for
passage of ejaculate to another person.
In addition to male condom use, a highly effective method of contraception may be 
considered in WOCBP partners of male participants (refer to the list of highly effective 
methods below in Section 10.4.4).
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 highly effective (with a failure 
rate of <1% per year), with low 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).  The 
investigator should evaluate the effectiveness of the contraceptive method in 
relationship to the first dose of study intervention.
OR

Is a WOCBP and using a contraceptive method that is 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 


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used.  The investigator should evaluate the effectiveness of the contraceptive method 
in relationship to the first dose of study intervention. 
OR 

Is a WOCBP and is abstinent 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 be the preferred and 
usual lifestyle of the participant.
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.
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. 


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
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 That Have Low User Dependency
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 WOCBP 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.
Highly Effective Methods That Are User Dependent (must be used with another 
effective method, see below)
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:

oral;


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
injectable.
Effective Methods
1. Male or female condom with or without spermicide.
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).
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 


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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.
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 [and 
Study Intervention Rechallenge Guidelines]
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 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 complexes (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: Country-Specific Requirements
10.8.1. Appendix 8.1: Japan
Exclusion criterion for hepatitis B
In Japan, all participants must undergo testing for HBV surface antigen (HBsAg), HBV core 
antibody (HBcAb), and HBV surface antibody (HBsAb).  This will be performed in CLIA 
(Clinical Laboratory Improvement Amendments) certified laboratory.

Participants who are negative for all three serology tests may be eligible.

Participants who are HBsAg positive will be excluded. 

Participants who are HBsAg negative, HBcAb negative and HBsAb positive and 
provide a documentation of prior HBV vaccination, may be eligible for the study and 
will not require HBV DNA monitoring during the study.

Participants who are HBsAg negative, HBcAb negative and HBsAb positive without 
documentation of prior HBV vaccination AND participants who are HBsAg negative, 
HBcAb positive, and HBsAb positive, will have HBV DNA assessed at screening. 

If detectable HBV DNA, participants will be excluded.

If not detectable HBV DNA, participants may be eligible.  If enrolled, HBV DNA 
will be also assessed at Week 12 for these participants.


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10.9. Appendix 9: Prohibited Medications & Procedures
The following medications & procedures are prohibited until the last Follow-up visit, unless 
stated otherwise.  If a participant receives prohibited medication or procedure, the 
investigator should either 1) ask the participant to stop IP immediately and schedule ET visit
as soon as possible with follow-up visits per Schedule of Activities or 2)contact Sponsor 
Clinician or Sponsor Medical monitor to determine if participant may stay in the study.  This 
will be based on the table below.  Medications listed below are prohibited even if used for a
different indication than noted below.
Drug classes and/or drugs and/or procedures 
Timeframe of restriction 
prior to Day 1 visit
If taken, then
stop IP, 
proceed 
to ET and 
F/UP
Contact
Sponsor 
Anti-coagulants or medications known to cause 
thrombocytopenia
Medications prolonging QT interval
5 half lives
X
Light therapy

Narrow-band Ultraviolet B light (UVB);

Broadband phototherapy;

Ultraviolet A light (UVA);

Excimer laser (308 nm).  
1 month
X
Any cell-depleting agents, including but not 
limited to

Rituximab;

Alemtuzumab [CamPath];

Alkylating agents [eg, cyclophosphamide or 
chlorambucil];

Total lymphoid irradiation, etc.
6 months or 5 half-lives, 
whichever is longer OR until 
lymphocyte count returns to 
normal, whichever is longer
X
Anti-psoriasis biologics 

Efalizumab (Raptiva);

Certolizumab pegol (Cimzia);

Alefacept (Amevive®);

Infliximab (Remicade) and biosimilar;

Adalimumab (Humira) and biosimilar.
2 months 
X

Ustekinumab (Stelara);

Secukinumab (Cosentyx);

Ixekizumab (Taltz);

Brodalumab (Siliq);

Guselkumab (Tremfya);

Tildrakizumab;

Risankizumab.
3 months
X

Etanercept (Enbrel) and biosimilar
1 month
X
Systemic treatments other than biologics that 
could affect psoriasis, including but not limited 
to:

oral or injectable (eg, intraarticular, 
intramuscular, or intravenous) corticosteroids;
2 weeks
X


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Drug classes and/or drugs and/or procedures 
Timeframe of restriction 
prior to Day 1 visit
If taken, then
stop IP, 
proceed 
to ET and 
F/UP
Contact
Sponsor 

retinoids;

methotrexate;

cyclosporine;

fumaric acid derivatives;

sulfasalazine;

hydroxycarbamide (hydroxyurea);

azathioprine;

intramuscular gold;

Otezla (Apremilast);

Any herbal medicine;

Other systemic treatments known to possibly 
worsen psoriasis unless on a stable dose for 
>12 weeks (eg lithium, -blockers, 
angiotensin-converting enzyme inhibitors, 
synthetic anti-malarials, anticonvulsants, 
antidepressants, cyclosporine, 
testosterone/estrogens, imiquimod, calcium 
channel blockers, etc).

Psoralens.
1 month
X

Tofacitinib;

Any other oral JAK inhibitors.
1 month or 5 half –live 
whichever is longer
X
Topical treatments applied on psoriasis areas 
treated with IP and which could affect 
psoriasis.  If applied to other areas not treated 
with IP, this is allowed.
Including but not limited to:

Corticosteroids;

Tars;

Keratolytics;

Anthralin;

vitamin D analogues;

retinoids.
2 weeks
X

sunscreens, moisturizers or non-medicated 
emollients.
2 weeks
X

Any topical JAK inhibitors.
1 month or 5 half –live 
whichever is longer
X
CYP3A4, 5, 7 Inhibitors

HIV antivirals:

delavirdine (Rescriptor);

indinavir (Crixivan);

nelfinavir (Viracept);

ritonavir (Kaletra, Norvir);

saquinavir (Fortovase);

cimetidine (Tagamet);

ciprofloxacin (Cipro);
1 month or 5 half-lives, 
whichever is longer
X


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Drug classes and/or drugs and/or procedures 
Timeframe of restriction 
prior to Day 1 visit
If taken, then
stop IP, 
proceed 
to ET and 
F/UP
Contact
Sponsor 

clarithromycin (Biaxin, Prevpac);

diethyl-dithiocarbamate;

diltiazem (Cardizem, Tiazac);

fluconazole (Diflucan);

fluvoxamine (Luvox);

gestodene (Femodene, Melodene, 
Minulette;

Mirelle, Triodene ED);

grapefruit juice and marmalade;

itraconazole (Sporanox);

ketoconazole (Nizoral);

Itraconazole;

Erythromycin;

protease inhibitors;

verapamil;

diltiazem.

Amiodarone.
10 months
X
CYP3A Inducers

Barbiturates;

efavirenz (Sustiva);

nevirapine (Viramune);

barbiturates;

carbamazepine (Carbatrol, Tegretol);

modafinil (Provigil);

phenobarbital;

Phenytoin (Dilantin, Phenytek);

rifampin (Rifadin, Rifamate, Rifater);

St. John’s wort;

troglitazone (Rezulin);

pioglitazone (Actos);

rifabutin (Mycobutin).
1 month or 5 half-lives, 
whichever is longer
X
Strong P-gp inhibitors

Quinidine.
1 month or 5 half-lives, 
whichever is longer
X
Substrates of MDR1

Digoxin.
1 month or 5 half-lives, 
whichever is longer
X
Substrates of OCT2/MATE

Dofetilide.
1 month or 5 half-lives, 
whichever is longer
X
Vaccination with live or attenuated live 
vaccine
(See Section 5.3.3)
6 weeks
X


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10.18. Appendix 18: eGFR calculations
The estimated GFR (eGFR) will be calculated using the 2 sets of equations developed by the 
Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), which utilize serum 
creatinine (SCr) and serum Cystatin C (S Cystatin C) respectively. 
CKD-EPI2009Scr
If female and 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)
CKD-EPI2012cys
If female and Scys is 0.8 mg/L:

GFR (mL/min/1.73 m2) = 133 x (Scys /0.8) –0.499 x 0.996age x 0.932
If female and Scys is >0.8 mg/L:

GFR (mL/min/1.73 m2) = 133 x (Scys /0.8) –1.328 x 0.996age x 0.932
If male and Scys is 0.8 mg/L:

GFR (mL/min/1.73 m2) = 133 x (Scys /0.8) –0.499 x 0.996age
If male and Scys is >0.8 mg/L:

GFR (mL/min/1.73 m2) = 133 x (Scys /0.8) –1.328 x 0.996age


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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
AA
Alopecia aereata
Ab
antibody
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 time 0 to 24 hours 
after dose
AUCinf
area under the concentration-time curve from zero to infinity
AUCtau
area under the concentration-time curve during any dosing interval 
at steady state
AV
atrioventricular
BA
bioavailability
BBS
biospecimen Banking System
BCRP
breast cancer resistance protein
BE
bioequivalence
-hCG
beta-human chorionic gonadotropin
BID
twice daily
BMI
body Mass Index
BP
blood pressure
bpm
beats per minute
BSA
body surface area
BUN
blood urea nitrogen
Cav
Average concentration
CCL26
chemokine ligand 26 
CD
Crohn’s disease
CDK-EPI
Chronic Kidney Disease Epidemiology Collaboration
CFR
Code of Federal Regulations
CI
confidence interval
CIOMS
Council for International Organizations of Medical Sciences
CK
creatine kinase
CL
clearance
CLIA
clinical laboratory improvement amendments
Cmax
maximum observed concentration
CMC
Chemistry, Manufacturing, and Controls
CO
Cross-over
CO2
carbon dioxide (bicarbonate)


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Abbreviation
Term
CONSORT
Consolidated Standards of Reporting Trials
CRF
case report form
CRO
contract research organization
CRU
clinical research unit
CSF
cerebrospinal fluid
CSR
clinical study report
C-SSRS
Columbia suicide severity rating scale
CT
clinical trial; computed tomography
CTCAE
Common Terminology Criteria for Adverse Events
CTMS
clinical trial management system
CV
cardiovascular
CXCL10
C-X-C motif chemokine ligand 10
CYP450
cytochrome P 450
DCT
data collection tool
DDI
drug drug interaction
DILI
drug-induced liver injury
DMC
data monitoring committee
DNA
deoxyribonucleic acid
DRE
disease-related event
DU
dispensable unit
EBV
epstein barr virus
EC
ethics committee
ECG
electrocardiogram
eCRF
electronic case report form
E-DMC
external data monitoring committee 
EDP
exposure during pregnancy
EDR
extemporaneous dispensing record
eGFR
estimates of glomerular filtration rate
EMA
European Medicines Agency
EOT
end of treatment 
EPO
erythropoietin
ePRO
electronic patient reported outcomes 
ET
early termination
EU
European Union
EudraCT
European Clinical Trials Database
F
bioavailability
FACS
fluorescent activated cell sorting
FSH
follicle-stimulating hormone
FU
fraction unbound
GCP
Good Clinical Practice
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Abbreviation
Term
GGT
gamma-glutamyl transferase
GM-CSF
granulocyte-macrophage colony-stimulating factor
HbA1c
hemoglobin A1c
HBcAb
hepatitis b core antibody
HBsAg 
hepatitis b surface antigen
HBV
hepatitis b virus
HCV
hepatitis c 
HCV Ab
hepatitis c antibody
HDL
high-density lipoprotein
HIPAA
Health Insurance Portability and Accountability Act
HIV
human immunodeficiency virus
Hrs
hours
HRT
hormone replacement therapy
HS
hidradenitis suppurativa
IB
investigator’s brochure
ICD
informed consent document
ICH
international council for harmonisation
IFN-alpha
interferon alpha
ID
identification
IGRA
interferon gamma release assay
IL-12
Interleukin 12
IMP
investigational medicinal product
IND
investigational new drug application
INR
international normalized ratio
IP
Investigational product
IR
Immediate release
IRAK
interleukin-1 receptor-associated kinase
IRB
institutional review board
IRC
internal review committee
IRT
interactive response technology
IUD
intrauterine device
IUS
intrauterine hormone-releasing system
IWR
interactive web-based response
JAK
Janus kinase
LBBB
left bundle branch block
LDL
low density lipoprotein
LFT
liver function test
LLOQ
lower limit of quantification
MAD
multiple ascending dose 
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Abbreviation
Term
MATE
multidrug and toxin extrusion
MCH
mean corpuscular hemoglobin
MCHC
mean corpuscular hemoglobin concentration
MCV
mean corpuscular volume
MDR
multi-drug resistance
MMP
matrix metallopeptidase
MMR
measles, mumps, rubella
MR
Modified release
MRI
magnetic resonance imaging
mRNA
messenger ribonucleic acid
msec
Millisecond
N/A
not applicable
NAb
neutralizing antibodies
NADPH
Nicotinamide adenine dinucleotide phosphate
NIMP
noninvestigational medicinal product
NOAEL
no-observed-adverse-effect level
OAT
organic anion transporter
OCT
organic cation transporter
PACL
Protocol administrative change letter
PASI
psoriasis area and severity index
PBMC
peripheral blood mononuclear cell
PCD
primary completion date
PCP
primary care physician
PCR
Polymerase chain reaction
PD
pharmacodynamic(s)
PFS
prefilled syringe
PGA
Physician Global Assessment
PI
principal investigator
PK
pharmacokinetic(s)
PP-NRS
peak-pruritus numerical rating scale
PPD
Purified Protein Derivative
PR
pulse rate
PRO
patient reported outcomes
PSI
psoriasis symptom inventory
PsO
psoriasis
PT
prothrombin time
PVC
premature ventricular contraction/complex
QD
once daily
QFT-G
QuantiFERON-TB Gold
QFT-GIT
QuantiFERON-TB Gold in Tube
QoL
quality of life 
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Abbreviation
Term
QT
Time from start of the Q wave to end of the T wave
QTc
corrected QT
QTcF
corrected QT (Fridericia method)
QW
once weekly
qual
qualitative
RBC
red blood cell
RNA
ribonucleic acid
SAD
single ascending dose
SAE
serious adverse event
SAP
statistical analysis plan
SBE
Single-blind extension
SC
subcutaneous
SCr
serum creatinine
SoA
schedule of activities
SOP
standard operating procedure
SRSD
single reference safety document
SSID
subject study identification number
SToD
study team on demand
SUSAR
suspected unexpected serious adverse reaction
t½
half life
TB
Tuberculosis
TBili
total bilirubin
TdP
torsade de pointes
TE
thromboembolic
TEAE
treatment emergent adverse events
Tmax
time after administration of a drug when the maximum plasma
concentration is reached
TYK
tyrosine-protein kinase
UC
Ulcerative colitis
UGT
uridine diphosphate glucuronosyltransferase
ULN
upper limit of normal
US
United States
Vss
steady state volume of distribution
WBC
white blood cell
WOCBP
woman of childbearing potential
W/W
weight for weight
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Suomela, S., Kariniemi, A. L., Snellman, E. & Saarialho-Kere, U. Metalloelastase 
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Owczarek, W. et al. Analysis of eotaxin 1/CCL11, eotaxin 2/CCL24 and eotaxin 
3/CCL26 expression in lesional and non-lesional skin of patients with atopic dermatitis. 
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Kamsteeg, M. et al. Molecular diagnostics of psoriasis, atopic dermatitis, allergic 
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162, 568-578, doi:10.1111/j.1365-2133.2009.09547.x (2010).
24.
Fujita, H. et al. Lesional dendritic cells in patients with chronic atopic dermatitis and 
psoriasis exhibit parallel ability to activate T-cell subsets. The Journal of allergy and 
clinical immunology 128, 574-582.e571-512, doi:10.1016/j.jaci.2011.05.016 (2011).
25.
Ferrari, S. M. et al. CXCL10 in psoriasis. Advances in medical sciences 60, 349-354, 
doi:10.1016/j.advms.2015.07.011 (2015).
26.
Martel, B. C. et al. Distinct molecular signatures of mild extrinsic and intrinsic atopic 
dermatitis. Experimental dermatology 25, 453-459, doi:10.1111/exd.12967 (2016).
27.
McLean, W. H. Filaggrin failure - from ichthyosis vulgaris to atopic eczema and 
beyond. The British journal of dermatology 175 Suppl 2, 4-7, doi:10.1111/bjd.14997 
(2016).
28.
Feldman, S. & Krueger, G. Psoriasis assessment tools in clinical trials. Annals of the 
Rheumatic Diseases 64, ii65-68, doi:10.1136/ard.2004.031237 (2005).
29.
Long, C. C., Finlay, A. Y. & Averill, R. W. The rule of hand: 4 hand areas = 2 FTU = 1 
g. Archives of dermatology 128, 1129-1130 (1992).
30.
Posner, K. et al. The Columbia-Suicide Severity Rating Scale: initial validity and 
internal consistency findings from three multisite studies with adolescents and adults. 
The American journal of psychiatry 168, 1266-1277, 
doi:10.1176/appi.ajp.2011.10111704 (2011).
31.
Zhu, Y. et al. Comparisons between the 2012 new CKD-EPI (Chronic Kidney Disease 
Epidemiology Collaboration) equations and other four approved equations. PloS one 9, 
e84688, doi:10.1371/journal.pone.0084688 (2014).
32.
Nasir, A. et al. A phase 2a randomized controlled study to evaluate the 
pharmacokinetic, safety, tolerability and clinical effect of topically applied 
Umeclidinium in subjects with primary axillary hyperhidrosis. Journal of the European 
Academy of Dermatology and Venereology: JEADV 32, 145-151, 
doi:10.1111/jdv.14651 (2018).


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Protocol B7931023
Final Protocol Amendment 1, 20 April 2020
PFIZER CONFIDENTIAL
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33.
Wilson, H. D. et al. Reliability and Validity of the Psoriasis Symptom Inventory in 
Patients With Psoriatic Arthritis. Arthritis care & research 67, 1750-1756, 
doi:10.1002/acr.22653 (2015).
34.
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, doi:10.2340/00015555-2856 (2018).
35.
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, doi:10.1111/bjd.14464 (2016).
 
 
 
 
 
 
 
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Protocol B7931023(PF-06700841) Statistical Analysis Plan
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Protocol B7931023
A PHASE 2B, RANDOMIZED, DOUBLE BLIND, VEHICLE-CONTROLLED, 
PARALLEL-GROUP, DOSE RANGING STUDY TO ASSESS EFFICACY, SAFETY, 
TOLERABILITY AND PHARMACOKINETICS OF PF-06700841 TOPICAL 
CREAM APPLIED ONCE OR TWICE DAILY FOR 12 WEEKS IN PARTICIPANTS 
WITH MILD TO MODERATE CHRONIC PLAQUE PSORIASIS
Statistical Analysis Plan 
(SAP)
Version:
3.0
Author:
 
 
 
Date:
04-MAY-2021  
PPD


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TABLE OF- CONTENTS
LIST OF TABLES.....................................................................................................................4
LIST OF FIGURES ...................................................................................................................4
APPENDICES ...........................................................................................................................4
1. VERSION HISTORY............................................................................................................5
2. INTRODUCTION .................................................................................................................5
2.1. Study Objectives, Endpoints, and Estimands............................................................7
2.1.1. Primary Estimand(s)...................................................................................10
2.1.2. Secondary Estimand(s)...............................................................................11
2.1.3. Additional Estimand(s)...............................................................................11
2.2. Study Design ...........................................................................................................12
3. ENDPOINTS AND BASELINE VARIABLES: DEFINITIONS AND 
CONVENTIONS ................................................................................................................14
3.1. Primary Endpoint(s) ................................................................................................14
3.2. Secondary Endpoint(s) ............................................................................................14
3.4. Baseline Variables...................................................................................................16
3.5. Safety Endpoints .....................................................................................................17
3.5.1. Adverse Events...........................................................................................17
3.5.2. Laboratory Data..........................................................................................17
3.5.3. Vital Signs, including Height and Weight..................................................18
3.5.4. Physical Examinations................................................................................18
4. ANALYSIS SETS (POPULATIONS FOR ANALYSIS)...................................................18
4.1. Full Analysis Set (FAS) ..........................................................................................18
4.2. Efficacy Analysis Set (EAS)...................................................................................18
4.3. Safety Analysis Set..................................................................................................18
4.5. Treatment Misallocations and Missing Data...........................................................19
5. GENERAL METHODOLOGY AND CONVENTIONS....................................................20
5.1. Hypotheses and Decision Rules ..............................................................................20
5.2. General Methods .....................................................................................................21
5.2.1. Analyses for Binary Endpoints...................................................................21
5.2.2. Analyses for Continuous Endpoints ...........................................................21
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5.2.3. Analyses for Categorical Endpoints ...........................................................22
5.2.4. Analyses for Time-to-Event Endpoints ......................................................22
5.2.5. Analyses of Safety Events ..........................................................................22
5.2.6. Methods to Manage Missing Data..............................................................22
6. ANALYSES AND SUMMARIES ......................................................................................23
6.1. Primary Endpoint(s) ................................................................................................23
6.1.1. Change from Baseline PASI at Week 12....................................................23
6.1.1.1. Main Analysis ...........................................................................23
6.1.1.2. Sensitivity/Supplementary Analyses.........................................24
6.2. Secondary Endpoint(s) ............................................................................................24
6.2.1. Key Secondary Endpoint: PGA Response at Week 12 ..............................24
6.2.1.1. Main Analysis ...........................................................................24
6.2.1.2. Sensitivity/Supplementary Analysis .........................................24
6.2.2. Secondary Endpoints: Continuous Data.....................................................25
6.2.3. Secondary Endpoint: Binary Data ..............................................................25
6.2.3.1. Main Analysis ...........................................................................25
6.2.3.2. Sensitivity/Supplementary Analyses.........................................26
6.4. Clinical Laboratory Values, ECG and Severity of Skin Tolerability......................26
6.7. Subset Analyses.......................................................................................................27
6.8. Baseline and Other Summaries and Analyses.........................................................27
6.8.1. Baseline Summaries....................................................................................27
6.8.2. Study Conduct and Participant Disposition................................................27
6.8.3. Study Treatment Exposure .........................................................................27
6.8.4. Concomitant Medications and Nondrug Treatments..................................27
6.9. Safety Summaries and Analyses .............................................................................28
6.9.1. Adverse Events...........................................................................................28
6.9.2. Laboratory Data..........................................................................................29
6.9.3. Vital Signs ..................................................................................................29
6.9.4. Electrocardiograms.....................................................................................29
6.9.5. Physical Examination .................................................................................29
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7. INTERIM ANALYSES.......................................................................................................29
7.1. Introduction .............................................................................................................29
7.2. Interim Analyses and Summaries............................................................................29
8. REFERENCES ....................................................................................................................30
LIST OF TABLES
Table 1.
Summary of Changes..................................................................................5
Table 2.
Treatment Groups .....................................................................................13
LIST OF FIGURES
Figure 1.
Study Schematic .......................................................................................13
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 .......................................................................................34
Appendix 2.3. Definition of Protocol Deviations That Relate to Statistical 
Analyses/Populations................................................................................37
Appendix 3. Statistical Methodology Details..........................................................................38
Appendix 4. SAS Code for Estimand 1 –Change from Baseline in PASI Score.....................39
Appendix 5. SAS Code for the Generalized Linear Mixed Model for Binary 
Longitudinal Data .....................................................................................41
Appendix 6. SAS Code for Estimand 2 – Risk Difference using (Chan and Zhang 
1999)5........................................................................................................42
Appendix 7. SAS Code for the Confidence Interval of a Binomial Proportion 
(Blyth-Still-Casella)..................................................................................43
Appendix 8. List of Abbreviations...........................................................................................44
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1. VERSION HISTORY
None.
Table 1.
Summary of Changes
Version/
Date
Associated 
Protocol 
Amendment
Rationale
Specific Changes
2.0/
20 APR 2020
Amendment 1 
20 April 2020
Revisions and 
clarification made 
in the statistical 
analysis plan.

Section 2.2 and 5.1. Details about 
interim analsyis.

Section 2.1.1, 2.1.2, 6.1 and 6.2. 
Details regarding to COVID-19
impact are added. 
3.0/
04 MAY 2021
Amendment 1
20 April 2020
Added PGA (0/1 
and ≥2 pts
decrease) and 
PASI 75 subgroup 
analyses based on 
PGA mild and 
PGA moderate at 
the baseline.

Section 3.3. Included the 
endpoints to be analysed.
2. INTRODUCTION
PF-06700841 is a dual inhibitor of human tyrosine-protein kinase 2 (TYK2) and Janus 
kinase 1 (JAK1) that is currently being investigated in participants with multiple indications.  
The oral formulation of this compound has been studied in several studies, including in 
patients with psoriasis.  This study is the first study for the topical formulation of 
PF-06700841. 
The most common variant of psoriasis, plaque psoriasis, is a chronic inflammatory 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 5.8-7.5 million 
Americans (Parisi 2013).25 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 an impairment akin to other major diseases, such as type 2 diabetes, myocardial 
infarction, and arthritis (Rapp 1999).26
The Janus kinase (JAK) family, including 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 (O'Sullivan 2007) (Murray 2007).23,22 JAK2 homodimers are critical for the 
signaling of hematopoietic cytokines and hormones including erythropoietin (EPO), IL-3, 
granulocyte-macrophage colony-stimulating factor (GM-CSF) and prolactin.


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JAK1-dependent cytokines include IFN-alpha, IFN-gamma, IL-6, IL-21, and IL-22.  IL-6 and 
IL-21 play a critical role in the development of Th17 cells and production of IL-17, which is 
a target of several efficacious biologic therapies. JAK1-selective inhibitors are expected to 
spare dose-limiting effects of pan-JAK inhibition by preserving JAK2 homodimer signaling 
and thus provide the potential for more efficacious oral treatments for several inflammatory 
diseases including psoriasis.  The previous positive psoriasis studies with two JAK1 selective 
inhibitors, INCB39110 and GSK2586184, have provided clinical support for JAK1 inhibition 
as a novel approach to treat plaque psoriasis (Ludbrook 2016) (Bissonnette 2016).17,3
Increased activation of Th17 and the main effector cytokines of Th17 cells has been linked to 
various inflammatory diseases, including psoriasis (Martin 2013).20  The number of Th17 
cells are elevated in psoriatic lesions, along with levels of proinflammatory cytokines, 
including IL-17A and IL-17F, which are expressed by Th17 cells and are likely mediators of 
inflammation and tissue damage (Martin 2013) (Lowes 2008).20,16  Human genetic studies 
implicate the Th17 pathway in psoriasis, and have uncovered likely risk alleles which include 
genes involved in IL-23 signaling (including TYK2, which mediates IL-23 receptor signaling) 
and genes that function downstream of the IL-17 receptor (Martin 2013).20
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.  Secukinumab and 
ixekizumab selectively target IL-17A and have been shown to be effective in the treatment of 
psoriasis (Gordon 2013).9  Other therapies such as cyclosporine, phototherapy, and 
infliximab also inhibit the IL-17 pathway (Langley 2014) (Haider 2008) (Zaba 2009).15,10,31  
The monoclonal antibodies ustekinumab and guselkumab, which are also effective in treating 
psoriasis (Krueger 2015) (Reich 2017) (Blauvelt 2017)14,27,4 disrupt IL-23 activation of Th17 
cells (Yeilding 2012).30 Thus, there is strong rationale for targeting the Th17 pathway in the 
treatment of psoriasis.
In the skin, cytokines mediated by JAK signaling impact several cellular inflammatory 
functions, such as apoptosis of inflammatory T cell infiltrates and T helper cell 
differentiation.  C-X-C motif chemokine ligand 10 (CXCL10), chemokine ligand 26 (CCL26)
and matrix metallopeptidase (MMP12) have been reported to be induced by cytokines acting 
via the JAK class of kinases (Bao 2012) (Fenwick 2015) (Xu 2015) (Amano 2015)2,6,29,1 and 
are implicated in inflammatory and autoimmune conditions of the skin (Suomela 2001)
(Owczarek 2010) (Kamsteeg 2010) (Fujita 2011) (Ferrari 2015) (Martel 2016).28,24,13,8,7,19  In 
addition, impairment of the skin barrier protein filaggrin has also been implicated in 
inflammatory and autoimmune diseases of the skin (McLean 2016)21 and its expression has 
been reported to increase upon inhibition of JAK enzymes (Amano 2015).1  Following 
topical application of the clinical formulation to freshly excised human skin, PF-06700841 
caused a dose-dependent inhibition of gene expression of pro-inflammatory molecules 
CXCL10, CCL26 and MMP12 (measured by changes in messenger ribonucleic acid [mRNA] 
in the presence and absence of PF-06700841) and a dose-dependent stimulation of the skin 
barrier protein, filaggrin.  Thus, PF-06700841 showed pharmacological modulation in 
human skin by the topical application, consistent with the known activity of PF-06700841 on 
JAK1 and TYK2 enzymes.


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PF-06700841 is a dual TYK2/JAK1 inhibitor with good selectivity profile over other human 
kinases.  Based on its cytokine inhibition profile, PF-06700841 is expected to target the 
Th17 pathway directly by inhibiting TYK2 and indirectly by inhibiting JAK1, thereby 
providing therapeutic benefit in the treatment of plaque psoriasis.
This statistical analysis plan (SAP) provides the detailed methodology for summary and 
statistical analyses of the data collected in Study B7931023  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.
Throughout this document, the investigational product (IP) is PF-067008741.
2.1. Study Objectives, Endpoints, and Estimands 
Objectives
Endpoints
Estimands
Primary: 
Primary: 
Primary:

To compare the efficacy of 
multiple dose levels of 
PF-06700841 versus vehicle on 
change from baseline in PASI 
score in participants with mild 
to moderate plaque psoriasis. 

Change from baseline in PASI 
score at Week 12.

Estimand E1: 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 mild to 
moderate 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.

Population level summary: The mean 
difference between treated and vehicle
control arms of the change from 
baseline PASI score.
Secondary: 
Secondary: 
Secondary:

To compare the efficacy of 
multiple dose levels of 
PF-06700841versus vehicle on 
PGA score in participants with 
mild to moderate plaque 
psoriasis. 
Key secondary endpoint

Proportion of participants with 
PGA score clear (0) or almost 
clear (1) and 2 points 
improvement from baseline at 
Week 12. 

Estimand E2: 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 


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
To compare the efficacy of 
multiple dose levels of 
PF-06700841versus vehicle on 
the proportion of participants 
with mild to moderate plaque 
psoriasis achieving PASI 75. 
Proportion of participants 
achieving PASI 75 (75% or 
greater improvement from 
Baseline) at time points 
specified in the Schedule of 
Activities (SoA).
participants compliance with the IP 
dosing.

Population: Participants with mild to 
moderate 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 vehicle response rates. 

To compare the efficacy of 
multiple dose levels of 
PF-06700841 versus vehicle on 
measures of disease and 
symptom severity in 
participants with mild to 
moderate plaque psoriasis. 

Change from baseline and 
percent change from baseline 
in PASI scores at time points 
specified in the SoA.

Absolute score and change 
from baseline in Peak-Pruritus 
Numerical Rating Scale score 
at time points specified in the 
SoA.

Absolute score and change 
from baseline Psoriasis 
Symptom Inventory at time 
points specified in the SoA.

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.

The proportion of participants 
who achieved a Psoriasis 
Symptom Inventory score of 
0 (not at all) or 1 (mild) on 
every item at time points 
specified in the SoA.

All other continuous secondary 
endpoints will be analyzed 
descriptively and using estimand 
E1 described above when appropriate.

All other categorical secondary 
endpoints will be analyzed 
descriptively and using estimand 
E2 described above when appropriate.

To assess safety and
tolerability of PF-06700841 in 
participants with mild to 
moderate 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).

Change from baseline in ECG 
parameters (heart rate, QT, 
QTc, PR and QRS intervals).

Change from baseline in vital 

There is no defined estimand for these 
endpoints and they will be analyzed 
using Pfizer data standards as 
applicable.


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signs (blood pressure, pulse 
rate and temperature 
measurements).
•
Incidence of severity grades in 
skin tolerability at times 
indicated in SoA.
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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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-07600841 on change from the baseline Psoriasis Area and Severity Index (PASI) under 
the hypothetical scenario that prohibited medication is not used regardless of dosing 
compliance.
•
Population: Patients with mild to moderate plaque psoriasis as defined by the 
inclusion and exclusion criteria of the study who do not take prohibited medications
and without Week 12 missing visit due to COVID-19 pandemic.
•
Variable: Change from baseline PASI at Week 12.
•
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 vehicle control 
arms of the change from baseline PASI score. 
C
CI


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2.1.2. Secondary Estimand(s)
The key secondary estimand will 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: Patients with mild to moderate plaque psoriasis as defined by the 
inclusion and exclusion criteria of the study who do not take prohibited medications
and without Week 12 missing visit due to COVID-19 pandemic.

Variable: Binary response of a PGA score of of clear (0) or almost clear (1) and 
≥2 point improvement from baseline at Week 12.

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 vehicle 
response rates.
The primary estimand strategy will be applied to the following endpoints:

Change from baseline and percent change from baseline in PASI scores at time points 
specified in the SoA.

Absolute score and change from baseline in Peak-Pruritus Numerical Rating Scale 
score at time points specified in the SoA.

Absolute score and change from baseline Psoriasis Symptom Inventory at time points 
specified in the SoA.
The primary and key secondary estimand strategies will be applied to the following 
endpoints:

The proportion of participants who achieved a Psoriasis Symptom Inventory score of 
0 (not at all) or 1 (mild) on every item at time points specified in the SoA.

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.

The key secondary estimand will also be used for PASI 75 response at all time points 
specified in the Schedule of Activities.
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, vehicle-controlled, parallel group, multicenter 
study in participants with mild to moderate plaque psoriasis. The duration of study 
participation will be approximately 22 weeks, including up to a 6 week screening period, 
12 week treatment period, and approximately 4 week follow-up period in both Stage 1 and 
Stage 2 participants. 
The study will be conducted in 2 stages where an additional cohort (Stage 2) of participants
may be added, following completion of enrollment into Stage 1 and at the discretion of the
Sponsor. Investigators, study participants, and Pfizer study team members will remain
blinded to results of Stage 1.
In Stage 1, approximately 240 participants are planned to be randomized into the study, to 
allow for approximately 192 (20% drop out rate) evaluable participants (approximately 
24 completers per arm, 8 arms). Participants will be randomized to 1 of 8 treatment groups 
in QD (4 active and 1 vehicle) or BID (2 active and 1 vehicle) regimen in the ratio 
of 1:1:1:1:1:1:1:1. 
Stage 2 will be undertaken at the discretion of the Sponsor, in order to provide more
extensive exploration of the dose response curve. In Stage 2, approximately 40 participants
are planned to be randomized to allow for approximately 32 evaluable participants.  
Participants will be randomized into 1 of 2 treatment groups in BID (1 active and 1 vehicle)
dosing regimen, in ratio 3:1.  The eligibility criteria for participants enrolled in Stage 1 and 
Stage 2 are the same.
A study schematic is shown in Figure 1, treatment groups are shown in Table 2.


Protocol B7931023(PF-06700841) Statistical Analysis Plan
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Figure 1.
Study Schematic
Table 2.
Treatment Groups
Stage
Treatment 
Group
Target 
Number of 
Participants
Randomized
Approx. 
Number of 
Completers
Investigational Product
1
A
30
24
Vehicle cream QD
B
30
24
PF-06700841 0.1% cream QD
C
30
24
PF-06700841 0.3% cream QD
D
30
24
PF-06700841 1.0% cream QD
E
30
24
PF-06700841 3.0% cream QD
F
30
24
Vehicle cream BID
G
30
24
PF-06700841 0.3% cream BID
H
30
24
PF-06700841 1.0% cream BID
2
I
30
24
PF-06700841 3.0% cream BID
J
10
8
Vehicle cream BID
 
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Throughout the 12-week treatment period, participants will treat all psoriatic areas 
identified on Day 1, regardless of clearing or improvement.  Any new psoriatic areas 
occurring after Day 1 will also be treated with IP, provided they are treatment eligible.
Investigators, participants, and the sponsor study team (with the exception of the sponsor 
supply chain lead) will be blinded as to investigational drug (PF-06700841 cream vs placebo 
cream [vehicle]) assignment during the conduct of the trial.  
An interim analysis will be conducted at the end of Stage 1. Some Pfizer team members and 
other key stakeholders will become unblinded to the results of Stage 1. Unblinded Pfizer 
team members will be replaced by blinded team members. Investigators and study 
participants will remain blinded to the results of Stage 1.
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 10.9 of the protocol should be followed.
3. ENDPOINTS AND BASELINE VARIABLES: DEFINITIONS AND 
CONVENTIONS
3.1. Primary Endpoint(s)
•
Change from baseline in PASI score at Week 12 (see Protocol Section 6.1.2). The 
baseline will be defined as the PASI total score on Day 1 predose.
3.2. Secondary Endpoint(s)
•
Proportion of participants with PGA score clear (0) or almost clear (1) and ≥2 points 
improvement from baseline at Week 12.
•
Proportion of participants achieving PASI 75 (75% or greater improvement from 
Baseline) at time points specified in the Schedule of Activities (SoA).
•
Change from baseline and percent change from baseline in PASI scores at time 
points specified in the SoA.
•
Absolute score and change from baseline in Peak Pruritus Numerical Rating Scale 
score at time points specified in the SoA.
•
Proportion of participants achieving ≥2pt improvement in Peak Pruritus Numerical 
Rating Scale score at time points specified in SoA.
•
Absolute score and change from baseline Psoriasis Symptom Inventory (PSI) at time 
points specified in the SoA.
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•
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.
•
The proportion of participants who achieved a Psoriasis Symptom Inventory total 
score of ≤8, with 0 (not at all) or 1 (mild) on every item at 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 and hematology, 
lipids).
•
Change from baseline in ECG parameters (heart rate, QT, QTc, PR and QRS 
intervals).
•
Change from baseline in vital signs (blood pressure, pulse rate and temperature 
measurements).
•
Incidence of severity grades in skin tolerability at times indicated in SoA.
The baseline is defined as the total measure on Day 1 predose.
 
 
 
 
 
 
 
 
 
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3.4. 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 (except PtGA) baseline will be defined as the average of all values/values 
recorded on Day 1. The baseline for the endpoint PtGA will be measured as the value on 
Day 1.
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3.5. 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.

Incidence of severity grades in skin tolerability.
The safety endpoints will be defined in accordance with Clinical Data Interchange Standards 
Consortium (CDISC) and Pfizer Standards (CaPS).
3.5.1. Adverse Events
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 6.9.1).
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.
3.5.2. 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.


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•
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, lactate dehydrogenase, uric acid, albumin, total protein, total 
cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), 
triglycerides.
3.5.3. Vital Signs, including Height and Weight
Vital sign measurements are oral or tympanic temperature, pulse rate, and blood pressures.
Weight is collected at pre- and post-treatment.
3.5.4. Physical Examinations
Complete physical examinations consist of assessments of general appearance; skin; head, 
eyes, ears, nose and throat; mouth, heart; lungs; breast (optional); abdomen; external 
genitalia (optional); extremities; neurologic function; and lymph nodes.
4. ANALYSIS SETS (POPULATIONS FOR ANALYSIS)
4.1. Full Analysis Set (FAS)
As specified in the protocol, the analysis of the efficacy, health outcome and biomarker 
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-06700841 or 
placebo). 
4.2. Efficacy Analysis Set (EAS)
Primary and key secondary analysis 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-06700841 or placebo) and Week 12 visits are not missing due to 
COVID-19 pandemic. 
4.3. Safety Analysis Set
The safety analysis set (SAS) will be all subjects who receive at least 1 dose of 
investigational product. The safety analysis set will include the follow up period. The final 
safety database will include all reported safety data at the time of database release. 
 
 
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4.5. 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. 
For the continuous PRO variables such as pruritus NRS, DLQI, EQ-5D-5L, SF-36 etc. 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(FAS)
All participants randomly assigned to IP and who apply at 
least 1 dose of IP.  
Efficacy analysis set 
(EAS)
All participants randomly assigned to IP and who apply at 
least 1 dose of IP and whose Week 12 visit was not missing due 
to COVID-19 pandemic.  
 
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.  
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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 
Continuous Endpoint Set
This set will include all patients in the EAS population. All 
data for a subject after the initiation of prohibited medications 
will be set to missing.
Note the primary estimand requires multiple imputation which 
will be performed on this dataset, the multiple imputations
themselves will not be saved in the database, however, the SAS 
specifications and random number seed will be.
Secondary Estimand 
Categorical Endpoint Set
This set will include all patients in the EAS 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.
Observed Efficacy Set
This set will include all patients in the FAS 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.
5. GENERAL METHODOLOGY AND CONVENTIONS
The primary analysis will be performed when all randomized subjects have either completed 
their 12-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: change from baseline PASI score 
at Week 12 based on an analysis of the Primary Estimand Continuous Endpoint Set. The null 
hypothesis is that there is no difference between any arm of PF-06700841 (3% QD, 1% QD, 
0.3% QD, 0.1% QD, 3% BID, 1% BID and 0.3% BID) and its corresponding vehicle arm 
(ie, the 3% BID, 1% BID and 0.3% BID arms will be compared with the BID vehicle, and 
the remaining QD arms will be compared with the QD vechicle). The alternative hypothesis 
is that one of the PF-06700841 arms being tested is superior to its corresponding vehicle at 
Week 6.  The study will be considered positive, if this null hypothesis is rejected.


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The Type I familywise error-rate will be controlled at the 0.05 level for these tests with a 
Hochberg step-up procedure (Hochberg, A sharper Bonferroni procedure for multiple 
significance testing 1988)11 (Hochberg and Tamhane, Multiple Comparison Procedures 
1987)12 (Marcus, Peritz and Gabriel 1976).18 The p-values from the 6 comparisons will be 
ordered from smallest to largest, p[1], … p[7]. Testing will begin with the largest p-value, 
p[7], if significant at the 0.05 level that comparison and all other comparisions will be 
declared significant. If it is not significant, p[6] will be compared to an alpha of 0.05/2, if 
p[6] ≤0.05/2 it and all remaining hypotheses will be declared significant. If not significant, 
the process will continue using 0.05/3, 0.05/4, 0.05/5, 0.05/6 and lastly 0.05/7.
At the interim analysis, all QD treatment arms will be compared against the QD vehicle arm, 
whereas the 0.3% BID and 0.1% BID treatment arms will be compared against the available
BID vehicle arm data. In Stage 2, participants will only be randomized among 3% BID 
treatment arm and the BID vehicle arm. After Stage 2, pooled BID vehicle arms from two 
the stages will be used to compare against all three BID treatments (3% BID, 1% BID and 
0.3% BID).
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).5  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, PASI100 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.


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Mixed model repeated measures (MMRM) models will be used.  The fixed effects of 
treatment, visit (Weeks 2, 4, 8 and 12), 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-06700841 treated groups (QD and BID) and the corresponding QD and BID vehicle 
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.
5.2.3. Analyses for Categorical Endpoints
NA
5.2.4. Analyses for Time-to-Event Endpoints
NA
5.2.5. Analyses of Safety Events
Number and percentage of subjects with AEs over the duration of treatment will be provided 
for each treatment group.  Tier-2 events will be analyzed using methods proposed by (Chan 
and Zhang 1999).5 Exact methods will be used for Tier-1 events while an asymptotic method 
will be used for Tier-2 events. Risk differences (each PF-dose group compared to 
corresponding vehicle) and 2-sided 90% CIs will be reported.  
5.2.6. Methods to Manage Missing Data
The primary analysis will use the primary estimand continuous endpoint set.  For each 
landmark analysis (eg, Cross sectional analysis by week) missing data, except missing due to 
COVID-19 pandemic, will be imputed using a control based imputation method.  PROC MI 
will first be called separately for the QD and BID arms at the visit and a control based 
method (implemented with the MNAR option) will impute missing vechicle observations 
under the assumption data are missing at random (MAR) and impute missing treatment 
observations assuming they are similar to corresponding vechicle patients.  Imputation will 
use the full conditional specification (FCS) method, the imputed data for the QD and BID 
arms will be combined for the analysis.
Summaries of continuous data will use the observed data only and no additional 
considerations are needed.


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Analysis of binary data will use the Secondary Estimand Categorical Endpoint Set.  This 
dataset by definition has no missing data since all missing values, except missing due to 
COVID-19 pandemic, will have been set to a failure.  Summaries will use the Observed 
Efficacy Set and will report results on an observed case (OC) basis. 
If a subject misses a visit due to COVID-19, he/she will be excluded from the analysis for 
that visit; If a subject discontinues treatment or withdraws from the study due to COVID-19, 
he/she will be excluded from the analyses after the treatment discontinuation visit or study 
withdrawal visit, respectively.  
6. ANALYSES AND SUMMARIES
Analysis will be done pairwise between each of the PF-06700841 QD treated groups 
(0.1% cream QD, 0.3% cream QD, 1% cream QD,  3% cream QD) and the corresponding 
vehicle cream QD, and (0.3% cream BID,  1% cream BID) and the corresponding vehicle 
cream BID respectively.  An analysis with point estimates of the difference and the 
associated 90% confidence intervals will also be done for the QD versus corresponding BID 
doses without testing any hypotheses. 
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.
Data collected at Week 12 will be displayed in listings only, and will not be part of any 
analyses, unless specifically noted otherwise.
6.1. Primary Endpoint(s)
6.1.1. Change from Baseline PASI at Week 12
6.1.1.1. Main Analysis

Estimand strategy: Primary Estimand (Section 2.1.1). This estimand is intended to 
provide an estimate of the treatment effect in the absence of prohibited medication 
use in a population that may or may not be fully compliant with the treatment.

Analysis set: EAS (Section 4) using data prepared in the description of the Primary 
Estimand Continuous Endpoint Set.

Analysis methodology: Change from baseline will be analyzed using an ANCOVA 
with the observed (or imputed) Week 12 change from baseline PASI score as the 
dependent variable with treatment arm and baseline PASI score as the independent 
variables. 

Intercurrent events and missing data: Data after study drug discontinuation and 
prohibited medication will be excluded and set to missing. Missing data which will 
be multiply imputed using a control-based strategy as described in Section 5.2.6.  
Twenty (100) imputed datasets will be used in the analysis and results combined 
using PROC MIANALYZE.


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
The least-squares (LS) means, the 90% confidence interval for the LS means, the 
difference between the LS means for each pair of treatment groups, and the 
corresponding 90% confidence interval will be presented for change from baseline in 
PASI score. 
6.1.1.2. Sensitivity/Supplementary Analyses
Sensitivity Analyses

To assess the impact of baseline distribution, the main analysis will be repeated with
the ANCOVA model replaced by an ANOVA model (excluding baseline as a 
covariate).

To assess the impact of COVID-19, the main analysis will be repeated with Full 
Analysis Set (FAS).
Supplementary Analyses

An analysis assuming all data is missing at random will be perfomed.  In this analysis 
PROC MI will use and FCS regression approach for all study arms.  This analysis is 
does not penalize the treated arms for intercurrent events and is expected to provide 
an upper bound for a treatment effect estimates.
6.2. Secondary Endpoint(s)
6.2.1. Key Secondary Endpoint: PGA Response at Week 12
6.2.1.1. Main Analysis

Estimand strategy: Secondary 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: EAS (Section 4) using data prepared in the description of the Secondary 
Estimand Categorical Endpoint Set.

Analysis methodology: Risk differences will be analyzed using the method of (Chan 
and Zhang 1999)5 in PROC BINOMIAL. 

Intercurrent events and missing data: These have been accounted for in the 
preparation of the Secondary Estimand Categorical Endpoint Set (Section 4.5). 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

To assess the impact of COVID-19, the main analysis will be repeated with Full 
Analysis Set (FAS).


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•
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 12.
•
Population: FAS.
•
Analysis methodology: GLMM and descriptive statistics.
•
Missing Data: Observed Data.
6.2.2. 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 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: EAS.
•
Analysis methodology: MMRM and descriptive statistics.
•
Missing Data: Observed Data.
6.2.3. Secondary Endpoint: Binary Data
Analyses of all binary endpoints such as 
, PASI 75, 
 PGA (0/1or 
≥2), 
 PSI (≤8 and 0/1), PP-NRS (≥2pt improvement), 
 
 for their proportions of participants will be as follows:
6.2.3.1. Main Analysis
•
Estimand strategy: Secondary 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: EAS (Section 4) using data prepared in the description of the Secondary 
Estimand Categorical Endpoint Set.
•
Analysis methodology: Risk differences will be analyzed using the method of (Chan 
and Zhang 1999)5 in PROC BINOMIAL. 
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•
Intercurrent events and missing data: These have been accounted for in the 
preparation of the Secondary Estimand Categorical Endpoint Set (Section 4.5). This 
prepared data set has no missing values.
•
Proprotions, risk differences and 90% confidence intervals will be presented. 
6.2.3.2. 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.
Using appropriate model such 4 parameter logistic or Emax, dose-response profile for
PF-06700841 in QD and BID form will be explored for Primary and Key secondary 
endpoint.
 
 
 
6.4. Clinical Laboratory Values, ECG and Severity of Skin Tolerability
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). Incidence of severity grades in skin tolerability 
at times indiciated in the SoA.
•
Estimand strategy: No estimand is applicable. Summary statistics will be calculated at 
time points specified in the SoA.
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•
Population: EAS.
•
Analysis methodology: Summary statistics.
•
Missing Data: Observed Data.
 
 
 
 
6.7. Subset Analyses
There are no subset analyses are planned. 
6.8. Baseline and Other Summaries and Analyses
6.8.1. 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: geographic 
region, age, gender, race, ethnicity, height, weight, body mass index, disease duration, 
baseline PASI score, baseline PGA, baseline BSA score etc.
6.8.2. Study Conduct and Participant Disposition
Subjects’ evaluation, disposition and discontinuation will be summarized according to CaPS.
6.8.3. 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.
6.8.4. 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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6.9. Safety Summaries and Analyses
The analysis population for safety is described in Section 4.5.  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. 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 6.9.1. A 3-tier approach will be used to summarize AEs. Under this 
approach, AEs are classified into 1 of 3 tiers. 
6.9.1. Adverse Events
All the tables, listings and graphs for adverse events, lab parameters and vital sign and ECG 
will follow Pfizer standards. 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 6.2.3.  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 6.2.3.  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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6.9.2. Laboratory Data
Laboratory data will be listed and summarized in accordance with the CaPS reporting 
standards.  Summaries of subjects meeting pre-specified monitoring and discontinuation 
criteria will be created using methods for categorical data.
6.9.3. Vital Signs
Vital signs will be summarized at baseline, Weeks 6, and Week 12/End of Treatment visits.  
6.9.4. Electrocardiograms
ECG parameters, if applicable, will be summarized at baseline, Weeks 6, and Week 12/End 
of Treatment visits.
6.9.5. Physical Examination
Physical examinations will be summarized at baseline and 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.  
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.
7.2. Interim Analyses and Summaries
A separate interim analysis plan might be developed, if needed.


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8. REFERENCES
1.
Amano, W. et al. 2015. "The Janus kinase inhibitor JTE-052 improves skin barrier 
function through suppressing signal transducer and activator of transcription 3 
signaling." The Journal of allergy and clinical immunology 136: 667-677. 
doi:10.1016/j.jaci.2015.03.051.
2.
Bao, L., Shi, V. Y. & Chan, L. S. 2012. "IL-4 regulates chemokine CCL26 in 
keratinocytes through the Jak1, 2/Stat6 signal transduction pathway: Implication for 
atopic dermatitis." Molecular immunology 50: 91-97. 
doi:10.1016/j.molimm.2011.12.008.
3.
Bissonnette, R. et al. 2016. "A randomized, double-blind, placebo-controlled, dose-
escalation study of the safety and efficacy of INCB039110, an oral janus kinase 1 
inhibitor, in patients with stable, chronic plaque psoriasis." The Journal of 
dermatological treatment 27: 332-338. doi:10.3109/09546634.2015.1115819.
4.
Blauvelt, A. et al. 2017. "Efficacy and safety of guselkumab, an anti-interleukin-23 
monoclonal antibody, compared with adalimumab for the continuous treatment of 
patients with moderate to severe psoriasis." Journal of the American Academy of 
Dermatology 76: 405-417. doi:10.1016/j.jaad.2016.11.041.
5.
Chan, ISF., and Z. Zhang. 1999. "Test based exact confidence intervals for the 
difference of two binomial proportions." Biometrics 55: 1201–1209.
6.
Fenwick, P. S., Macedo, P., Kilty, I. C., Barnes, P. J. & Donnelly, L. E. 2015. "Effect of 
JAK Inhibitors on Release of CXCL9, CXCL10 and CXCL11 from Human Airway 
Epithelial Cells." PloS one 10: e0128757. doi:10.1371/journal.pone.0128757.
7.
Ferrari, S. M. et al. 2015. "CXCL10 in psoriasis." Advances in medical sciences 60: 
349-354. doi:10.1016/j.advms.2015.07.011.
8.
Fujita, H. et al. 2011. "Lesional dendritic cells in patients with chronic atopic dermatitis 
and psoriasis exhibit parallel ability to activate T-cell subsets." The Journal of allergy 
and clinical immunology 128: 574-582.e571-512. doi:10.1016/j.jaci.2011.05.016.
9.
Gordon, K. B. et al. 2013. "Phase 3 Trials of Ixekizumab in Moderate-to-Severe Plaque 
Psoriasis." The New England journal of medicine 375: 345-356. 
doi:10.1056/NEJMoa1512711.
10.
Haider, A. S. et al. 2008. "Identification of cellular pathways of "type 1," Th17 T cells, 
and TNF- and inducible nitric oxide synthase-producing dendritic cells in autoimmune 
inflammation through pharmacogenomic study of cyclosporine A in psoriasis." Journal 
of immunology (Baltimore, Md. : 1950) 180: 1913-1920.
11.
Hochberg, Y. 1988. ". A sharper Bonferroni procedure for multiple significance 
testing." Biometrika 75: 800-802.


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12.
Hochberg, Y., and AC. Tamhane. 1987. Multiple Comparison Procedures. New Yrok: 
Wiley.
13.
Kamsteeg, M. et al. 2010. "Molecular diagnostics of psoriasis, atopic dermatitis, allergic 
contact dermatitis and irritant contact dermatitis." The British journal of dermatology
162: 568-578. doi:10.1111/j.1365-2133.2009.09547.x.
14.
Krueger, J. G. et al. 2015. "Anti-IL-23A mAb BI 655066 for treatment of moderate-to-
severe psoriasis: Safety, efficacy, pharmacokinetics, and biomarker results of a single-
rising-dose, randomized, double-blind, placebo-controlled trial." The Journal of allergy 
and clinical immunology 136: 116-124.e117. doi:10.1016/j.jaci.2015.01.018.
15.
Langley, R. G. et al. 2014. "Secukinumab in plaque psoriasis--results of two phase 3 
trials." The New England journal of medicine 371: 326-338. 
doi:10.1056/NEJMoa1314258.
16.
Lowes, M. A. et al. 2008. "Psoriasis vulgaris lesions contain discrete populations of Th1 
and Th17 T cells." J Invest Dermatol 128: 1207-1211. doi:10.1038/sj.jid.5701213.
17.
Ludbrook, V. J. et al. 2016. "Investigation of selective JAK1 inhibitor GSK2586184 for 
the treatment of psoriasis in a randomized placebo-controlled phase IIa study." The 
British Journal of Dermatology 174: 985-995. doi:10.1111/bjd.14399.
18.
Marcus, R., E. Peritz, and KR. Gabriel. 1976. "On closed testing procedure with special 
reference to ordered analysis of variance." Biometrika 63: 655–660.
19.
Martel, B. C. et al. 2016. "Distinct molecular signatures of mild extrinsic and intrinsic 
atopic dermatitis." Experimental dermatology 25: 453-459. doi:10.1111/exd.12967.
20.
Martin, D. A. et al. 2013. "The emerging role of IL-17 in the pathogenesis of psoriasis: 
preclinical and clinical findings." J Invest Dermatol 133: 17-26. 
doi:10.1038/jid.2012.194.
21.
McLean, W. H. 2016. "Filaggrin failure - from ichthyosis vulgaris to atopic eczema and 
beyond." The British journal of dermatology 175 Suppl 2: 4-7. doi:10.1111/bjd.14997.
22.
Murray, P. J. 2007. "The JAK-STAT signaling pathway: input and output integration." 
Journal of immunology (Baltimore, Md. : 1950) 178: 2623-2629.
23.
O'Sullivan, L. A., Liongue, C., Lewis, R. S., Stephenson, S. E. & Ward, A. C. 2007. 
"Cytokine receptor signaling through the Jak-Stat-Socs pathway in disease." Molecular 
immunology 44: 2497-2506. doi:10.1016/j.molimm.2006.11.025.
24.
Owczarek, W. et al. 2010. "Analysis of eotaxin 1/CCL11, eotaxin 2/CCL24 and eotaxin 
3/CCL26 expression in lesional and non-lesional skin of patients with atopic 
dermatitis." Cytokine 50: 181-185. doi:10.1016/j.cyto.2010.02.016.


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25.
Parisi, R. et al. 2013. "Global epidemiology of psoriasis: a systematic review of 
incidence and prevalence." prevalence. 133: 377-385. doi:10.1038/jid.2012.339.
26.
Rapp, S. R., Feldman, S. R., Exum, M. L., Fleischer, A. B., Jr. & Reboussin, D. M. 
1999. "Psoriasis causes as much disability as other major medical diseases." Journal of 
the American Academy of Dermatology 41: 401-407.
27.
Reich, K. et al. 2017. "Efficacy and safety of guselkumab, an anti-interleukin-23 
monoclonal antibody, compared with adalimumab for the treatment of patients with 
moderate to severe psoriasis with randomized withdrawal and retreatment." Journal of 
the American Academy of Dermatology 76: 418-431. doi:10.1016/j.jaad.2016.11.042.
28.
Suomela, S., Kariniemi, A. L., Snellman, E. & Saarialho-Kere, U. 2001. 
"Metalloelastase (MMP-12) and 92-kDa gelatinase (MMP-9) as well as their inhibitors, 
TIMP-1 and -3, are expressed in psoriatic lesions." Experimental dermatology 10: 175-
183.
29.
Xu, M. et al. 2015. "JAK inhibition alleviates the cellular senescence-associated 
secretory phenotype and frailty in old age." Proceedings of the National Academy of 
Sciences of the United States of America 112: E6301-6310. 
doi:10.1073/pnas.1515386112.
30.
Yeilding, N. et al. 2012. "Development of the IL-12/23 antagonist ustekinumab in 
psoriasis: past, present, and future perspectives--an update." Annals of the New York 
Academy of Sciences 1263: 1-12. doi:10.1111/j.1749-6632.2012.06670.x.
31.
Zaba, L. C. et al. 2009. "Effective treatment of psoriasis with etanercept is linked to 
suppression of IL-17 signaling, not immediate response TNF genes." The Journal of 
allergy and clinical immunology 124: 1022-1010. doi:10.1016/j.jaci.2009.08.046.


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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
Change from 
baseline to 
Week 16 in 
weekly mean of 
the 24-hour 
average pain 
score measured 
by the NRS
Summary
Evaluable
Separately for observed 
data and imputed data.
N/A
Main analysis
Evaluable
All data collected will 
be included regardless 
of intercurrent events. 
Missing data will be 
imputed.
ANCOVA 
with terms 
XXX, 
XXX
Sensitivity/supp
lementary 
analysis
Evaluable
All data collected will 
be included regardless 
of intercurrent events. 
Missing data will be 
imputed.
ANOVA
Sensitivity/supp
lementary 
analysis
Evaluable
Only data collected are 
included. Missing data 
will not be imputed.
MMRM
XXX


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Appendix 2. Data Derivation Details
Appendix 2.1. Definition and Use of Visit Windows in Reporting
Visit 
No.
Visit Label 
Target Day
Visit Window 
1
Screening 
N/A
-42 ≤ day ≤ -1
2
Baseline*
1 
day = 1
3
Week 1
8
2≤day≤11
4
Week 2
15 
12≤day≤22
5
Week 4
29 
23≤day≤36
6
Week 6
43
37≤day≤50
7
Week 8
57
51≤day≤64
8
Week 10
71
65≤day≤78
9
Week 12
85
79≤day≤92
10
Week 14
100
93≤day≤109
11
Week 16 FUP/ET
118
110≤day≤127
* 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.
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%. 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.


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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 
/75/
 response
At least 
/75
% reduction in PASI relative to baseline PASI Score.
Body Surface Area (BSA)
Assessment of body surface area involved in psoriasis is performed separately for four areas 
of the body: head, upper limbs, trunk, and lower limbs. The percentage surface area affected 
by psoriasis is estimated by means of the "handprint method", where the full hand of the 
subject (ie, the subject's flat hand, thumb and fingers) represents approximately 1% of the 
total BSA2 and a set percentage of each of the four areas of the body:
•
1 handprint corresponds to approximately 10% of the head/neck;
•
1 handprint corresponds to approximately 5% of the arm/upper limbs;
•
1 handprint corresponds to approximately 3.3% of the trunk;
•
1 handprint corresponds to approximately 2.5% of the lower limbs.
 
 
 
 
 
C
CI
CCI
C
CI
CCI
CCI
CCI
CCI


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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".
 
 
 
 
 
 
 
 
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.
CCI
CCI


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Appendix 2.3. Definition of Protocol Deviations That Relate to Statistical 
Analyses/Populations
CCI


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Appendix 3. Statistical Methodology Details
Hochberg Testing Procedure
Consider testing  null hypotheses H01, …H07 and let pi, i=1,…,7 denote the corresponding 
1-sided p-values from the individual pairwise comparisons against the placebo arm prior to 
multiplicity adjustment.  Furthermore, let [1], ….[7] denote the order of the p-values so that 
p[1] ≤p[2] ≤…. P[7].  The procedure starts with the largest p-value p[7] as follows:
1. If p[7] < α reject all null hypotheses, otherwise go to next step
2. If p[6] <α/2  reject hypotheses H0[1] through H0[6], otherwise go to next step
3. If p[k] < α/(7-k +1), reject hypotheses H0[1] through H0[k]
4. If p[1] < α/7, 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.
At the interim analysis time, since there will not be any data related to 3% BID treatment 
group, the corresponding p-value will be set to 1 and the above procedure will be performed.
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 1 –Change from Baseline in PASI Score
libname b7931023  "/Volumes/app/…… /data_vai" ;
data ps;
              set b7931023.adps;
run;
data look;
              set ps;
              where param = "PASI02-Total Sum"  and viswin ne .;
              keep subjid param paramn avisit age sex trta viswin visit xviswin aval base chg pchg trtan;
run;
**example data for a single visit;
**created from systemic study ;
**ignore values, only used for illustration;
**data already has one record per subject per visit even if
**data is missing. Proc Mi needs missing values in order to impute;
data ex1;
              set look;
              where viswin = 9;
              regimen = "BID";
              if trtan  < 6 then regimen = "QD";
              if trtan = 5 then dose=0;
              if trtan = 4 then dose=0.1;
              if trtan = 3 then dose=0.3;
              if trtan = 2 then dose=1.0;
              if trtan = 1 then dose=3.0;
              if trtan = 8 then dose=0;
              if trtan = 7 then dose=0.3;
              if trtan = 6 then dose=1.0;
              keep subjid dose regimen chg aval base;
run;
proc means data=ex1;
              class regimen dose;
              var chg aval;
run;
proc sort data=ex1 out=ex2;
    *data must be sorted by regimen before usin proc mi;
              by regimen dose;
run;
*imputing aval=observed so range of endpoint 0-72 can be included in;
*mi procedure;
proc mi data=ex2 seed=1023 nimpute=20 out=outimp  max=72 min=0;
              by regimen;
              class dose;
              monotone reg(aval= base/details);
              mnar model( aval/modelobs = (dose="0"));
              var base   aval;


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run;
proc univariate data=outimp;
var aval;
histogram ;
run;
data outimp1;
              set outimp;
              chg = aval - base;**calculate chg from baseline
run;
proc sort data = outimp1 out = outimp2;
    by _imputation_ regimen dose subjid;
run;
             
proc mixed data=outimp2;
             by _imputation_;
             class dose regimen;
             model chg = base dose*regimen;
             lsmeans dose*regimen/ diff alpha=.1 ;
             ods output diffs=diffs lsmeans=lsmeans;
run;
             
data diffsout;
              set diffs;
              **only keep within regimen contrasts vs placebo;
              where regimen = _regimen and dose = 0;
run;
**now use mianalyze on lsmean differences;
**First sort by group, regimen and _dose (dose = 0 for all groups);
proc sort data=diffsout out=diffsout1;
              by regimen _dose _imputation_;
run;
**now mianalyze by regimen and _dose;
**NB mianalyze only uses estimates and standard errors not CI limits etc.;
proc mianalyze data=diffsout1  alpha=.1;  **specify alpha for 90% CIs here;
      by regimen _dose;
      modeleffects estimate;
      stderr stderr;
      ods output parameterestimates=parameterestimates;
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 2 – Risk Difference using (Chan and Zhang 1999)5
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
BLQ
below the limit of quantitation
BOCF
baseline observation carried forward
BP
blood pressure
CDARS
Clinical Data Analysis and Reporting System (of US Food and Drug 
Administration)
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
EAS
Efficacy analysis set
ECG
electrocardiogram
E-DMC
external data monitoring committee 
FAS
full analysis set
FDA
Food and Drug Administration (United States)
GCP
Good Clinical Practice
GLIMMIX
generalized linear mixed-effects model with repeated measures  
GMC
geometric mean concentration
GMFR
geometric mean fold rise
GMR
geometric mean ratio
GMT
geometric mean titer
ICD
informed consent document
ICH
International Council for Harmonisation
IRC
internal review committee
IST
independent statistical team
ITT
intent-to-treat
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


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Abbreviation
Term
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
PP
per-protocol
PPAS
per-protocol analysis set
PRO
patient-reported outcome
PT
preferred term
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
SD
standard deviation
SGS
Statistical Guidance Standards
SOP
standard operating procedure
SUSAR
suspected unexpected serious adverse reaction
TA
therapeutic area
ULN
upper limit of normal
WHO 
World Health Organization
WHODD
World Health Organization Drug Dictionary
CC
I