Clinical trial NCT02969018
Conditions: Chronic Plaque Psoriasis
Keywords: plaque psoriasis
Sponsor: Pfizer
Start date: 2016-12-01; Completion date: 2018-03-01
Enrollment: 212 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The purpose of this study is to determine whether PF-06700841 is safe and effective in the treatment of chronic plaque psoriasis.

Detailed description:

Arms: arm 1: 4 week induction with 60 mg PF-06700841 once daily, followed by 8 week chronic administration of 30 mg PF-06700841 once daily arm 2: 4 week induction with 60 mg PF-06700841 once daily, followed by 8 week chronic administration of 10 mg PF-06700841 once daily arm 3: 4 week induction with 60 mg PF-06700841 once daily, followed by 8 week chronic administration of 100 mg PF-06700841 once weekly arm 4: 4 week induction with 60 mg PF-06700841 once daily, followed by 8 week chronic administration of placebo once daily arm 5: 4 week induction with 30 mg PF-06700841 once daily followed by 8 week chronic administration of 30 mg PF-06700841 once daily arm 6: 4 week induction with 30 mg PF-06700841 once daily, followed by 8 week chronic administration of 10 mg PF-06700841 once daily arm 7: 4 week induction with 30 mg PF-06700841 once daily, followed by 8 week chronic administration of 100 mg PF-06700841 once weekly arm 8: 12 weeks once daily placebo
Interventions: intervention 1: PF-06700841 intervention 2: Placebo
Intervention descriptions: intervention 1: None intervention 2: None

Protocol documents:
Prot_000.pdf: 
PF-06700841
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Final Protocol Amendment 1, 13 February 2017
Page 1
CLINICAL PROTOCOL
A PHASE 2A, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED 
STUDY TO EVALUATE SAFETY AND EFFICACY OF PF-06700841 IN SUBJECTS
WITH MODERATE TO SEVERE PLAQUE PSORIASIS
Investigational Product Number:
PF-06700841
Investigational Product Name:
Tyk2/Jak1
United States (US) Investigational New 
Drug (IND) Number:
131067
European Clinical Trials Database 
(EudraCT) Number:
2016-004049-96
Protocol Number:
B7931004
Phase:
2a


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Document History
Document
Version Date
Summary of Changes and Rationale
Amendment 1
17 January 2017
Protocol title page – added the European Clinical 
Trials Database (EudraCT) Number.
Schedule of activities footnote: clarified that blood 
pressure and other vital signs are to be collected 
with the subject in the sitting position.
Schedule of activities: added an electrocardiogram 
(ECG) assessment at study Day 1, pre-dose. This 
addition was made to ensure a baseline ECG is 
collected just prior to initial study administration. 
Decreased the resting time required prior to vital 
sign and ECG collection, from 10 minutes to 
5 minutes of rest. 
Section 4.2: Added psoriasis medications 
Secukinumab (Cosentyx), and Ixekizumab (Taltz) 
as exclusionary and prohibited during the study.  
Added Apremilast (Otezla) as exclusionary if 
taken within 3 months of first dose of study drug, 
and prohibited during the study.
Section 7.1.1 - added reticulocytes as part of the 
hematology laboratory panel.
Implemented minor clarifications previously 
described in protocol administrative letters dated 
26 Oct 2016 and 3 Nov 2016.
Appendix 4, Prohibited Concomitant Medications: 
are P-gp (MDRI) substrates (eg, digoxin), P-gp 
inhibitor eg, quinidine or OCT2/ MATE substrate 
(eg, dofetilide). Subjects receiving drugs with 
narrow therapeutic index that are P-gp (MDRI) 
substrates (eg, digoxin) and drugs that are 
substrates of OCT2/ MATE (eg, dofetilide) and 
potent inhibitors of P-gp eg, quinidine are 
excluded from participation in the study to limit 
any potential interactions with the investigational 
product.
 
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Original 
protocol
29 August 2016
Not applicable (N/A)
This amendment incorporates all revisions to date, including amendments made at the 
request of country health authorities and institutional review boards (IRBs)/ethics committees 
(ECs).
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TABLE OF CONTENTS
LIST OF TABLES.....................................................................................................................8
LIST OF FIGURES ...................................................................................................................9
APPENDICES ...........................................................................................................................9
PROTOCOL SUMMARY.......................................................................................................10
SCHEDULE OF ACTIVITIES................................................................................................13
1. INTRODUCTION ...............................................................................................................18
1.1. Mechanism of Action/Indication.............................................................................18
1.2. Background and Rationale ......................................................................................18
1.3. Non-Clinical Pharmacokinetics and Metabolism....................................................19
1.4. Non-Clinical Safety Studies....................................................................................20
1.5. Summary of Clinical Experience with PF-06700841 .............................................21
1.5.1. Summary of Clinical Safety Experience with PF-06700841......................22
1.5.2. Pharmacokinetics of PF-06700841.............................................................24
1.6. Study Rationale .......................................................................................................26
1.7. Dose Rationale ........................................................................................................27
1.8. Summary of Benefits and Risks..............................................................................30
2. STUDY OBJECTIVES AND ENDPOINTS.......................................................................31
3. STUDY DESIGN.................................................................................................................33
4. SUBJECT ELIGIBILITY CRITERIA.................................................................................34
4.1. Inclusion Criteria.....................................................................................................34
4.2. Exclusion Criteria....................................................................................................36
4.3. Lifestyle Requirements ...........................................................................................41
4.3.1. Contraception..............................................................................................42
4.4. Sponsor’s Qualified Medical Personnel..................................................................43
5. STUDY TREATMENTS.....................................................................................................43
5.1. Allocation to Treatment ..........................................................................................43
5.2. Breaking the Blind ..................................................................................................44
5.3. Subject Compliance.................................................................................................44
5.4. Investigational Product Supplies.............................................................................44
5.4.1. Dosage Form(s) and Packaging..................................................................44
5.4.2. Preparation and Dispensing........................................................................44


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5.5. Administration.........................................................................................................44
5.6. Investigational Product Storage ..............................................................................45
5.7. Investigational Product Accountability...................................................................46
5.7.1. Destruction of Investigational Product Supplies ........................................46
5.8. Concomitant Treatment(s).......................................................................................46
5.8.1. Permitted Concomitant Medication............................................................46
5.8.2. Prohibited Concomitant Medications .........................................................46
5.8.3. Dietary Supplements...................................................................................47
5.8.4. Vaccinations ...............................................................................................47
5.9. Rescue/Escape Medication......................................................................................48
6. STUDY PROCEDURES .....................................................................................................48
6.1. Screening.................................................................................................................48
6.2. Treatment Period.....................................................................................................48
6.3. Follow-up/End of study Procedures........................................................................48
6.4. Subject Withdrawal/Early Termination ..................................................................48
6.4.1. Withdrawal of Consent...............................................................................48
6.4.2. Lost to follow-up ........................................................................................49
7. ASSESSMENTS..................................................................................................................49
7.1. Safety Assessments .................................................................................................50
7.1.1. Laboratory...................................................................................................50
7.1.2. Pregnancy Testing ......................................................................................51
7.1.3. Serum Creatinine and Serum Cystatin-C....................................................51
7.1.4. Estimated Glomerular Filtration Rate.........................................................52
7.1.5. Interferon Gamma Release Assay Tuberculin Test....................................52
7.1.6. Herpetiform Skin Rash Surveillance ..........................................................53
7.1.7. Medical History, Physical Examination, Height and Weight.....................53
7.1.8. Vital Sign Measurements (Blood pressure, pulse rate, and 
temperature).....................................................................................................53
7.1.9. Electrocardiogram.......................................................................................54
7.1.10. Chest Radiograph......................................................................................54
7.1.11. Subject Diary ............................................................................................55
7.2. Efficacy Assessments..............................................................................................55


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7.2.1. Psoriasis Area and Severity Index (PASI)..................................................55
7.2.2. Linear Method Psoriasis Area and Severity Index (L PASI) .....................56
7.2.3. Physician Global Assessment (PGA) .........................................................56
7.2.4. Body Surface Area (BSA) ..........................................................................56
7.2.5. Target Lesion and Regional Photography (at select study centers)............57
7.3. Patient Reported Outcomes.....................................................................................57
7.3.4. Patient Health Questionnaire – 8 items (PHQ-8) .......................................58
7.3.5. Suicidal Behaviors Questionnaire- revised (SBQ-R) .................................58
7.7. Psychological Assessments.....................................................................................62
7.7.1. Columbia Suicide Severity Rating Scale (C-SSRS)...................................62
7.8. Rater Qualifications.................................................................................................62
8. ADVERSE EVENT REPORTING......................................................................................63
8.1. Requirements...........................................................................................................63
8.1.1. Additional Details on Recording Adverse Events on the CRF...................64
8.1.2. Eliciting Adverse Event Information..........................................................64
8.1.3. Withdrawal From the Study Due to Adverse Events (see also the 
Subject Withdrawal/Early Termination section) .............................................64
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8.1.4. Time Period for Collecting AE/SAE Information......................................64
8.1.4.1. Reporting SAEs to Pfizer Safety...............................................65
8.1.4.2. Recording Non-serious AEs and SAEs on the CRF .................65
8.1.5. Causality Assessment .................................................................................65
8.1.6. Sponsor’s Reporting Requirements to Regulatory Authorities ..................65
8.2. Definitions...............................................................................................................66
8.2.1. Adverse Events...........................................................................................66
8.2.2. Abnormal Test Findings .............................................................................66
8.2.3. Serious Adverse Events ..............................................................................67
8.2.4. Hospitalization............................................................................................67
8.3. Severity Assessment................................................................................................69
8.4. Special Situations ....................................................................................................69
8.4.1. Protocol-Specified Serious Adverse Events...............................................69
8.4.2. Potential Cases of Drug-Induced Liver Injury............................................69
8.4.3. Potential Cases of Decreased eGFR ...........................................................71
8.4.4. Exposure to the Investigational Product During Pregnancy or 
Breastfeeding, and Occupational Exposure.....................................................72
8.4.4.1. Exposure During Pregnancy......................................................72
8.4.4.2. Exposure During Breastfeeding ................................................73
8.4.4.3. Occupational Exposure .............................................................73
8.4.5. Medication Errors .......................................................................................74
8.4.5.1. Medication Errors......................................................................74
9. DATA ANALYSIS/STATISTICAL METHODS...............................................................74
9.1. Sample Size Determination.....................................................................................75
9.2. Efficacy Analysis ....................................................................................................75
9.2.1. Analysis of the Primary Endpoint...............................................................75
9.2.2. Analysis of Secondary Endpoints...............................................................76
9.6. Safety Analysis........................................................................................................77
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9.8. Data Monitoring Committee ...................................................................................78
10. QUALITY CONTROL AND QUALITY ASSURANCE.................................................78
11. DATA HANDLING AND RECORD KEEPING .............................................................79
11.1. Case Report Forms/Electronic Data Record .........................................................79
11.2. Record Retention...................................................................................................80
12. ETHICS..............................................................................................................................80
12.1. Institutional Review Board/Ethics Committee......................................................80
12.2. Ethical Conduct of the Study ................................................................................80
12.3. Subject Information and Consent..........................................................................81
12.4. Reporting of Safety Issues and Serious Breaches of the Protocol or ICH 
GCP ...........................................................................................................................82
13. DEFINITION OF END OF TRIAL...................................................................................82
13.1. End of Trial in a Member State.............................................................................82
13.2. End of Trial in All Other Participating Countries.................................................82
14. SPONSOR DISCONTINUATION CRITERIA ................................................................82
15. PUBLICATION OF STUDY RESULTS..........................................................................82
15.1. Communication of Results by Pfizer ....................................................................82
15.2. Publications by Investigators ................................................................................83
16. REFERENCES ..................................................................................................................85
LIST OF TABLES
Table 1.
Summary of Plasma PF-06700841 Pharmacokinetic Parameters Following 
Single Oral Doses, Study B7931001 ....................................................................24
Table 2.
Summary of Steady State Plasma and Urine PF-06700841 Pharmacokinetic 
Parameters Following Multiple Dose Administration, Study B7931001.............25
Table 3.
Summary of Plasma PF-06700841 Pharmacokinetic Parameters Following 
Multiple Dose Administration in Psoriasis Subjects, Study B7931001 ...............26
Table 4.
Summary of Predicted Total Geometric Mean Plasma PF-06700841 
Pharmacokinetic and Pharmacodynamic Parameters During the Induction 
Period of Multiple Dose Administration ..............................................................28
Table 5.
Summary of Predicted Geometric Mean Total Plasma PF-06700841 
Pharmacokinetic and Pharmacodynamic Parameters During the Chronic 
Period of Multiple Dose Administration ..............................................................29
Table 6.
Permitted Topical Concomitant Psoriasis Treatments..........................................46
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LIST OF FIGURES
Figure 1.
Study Schematic ...................................................................................................33
APPENDICES
Appendix 1. Abbreviations......................................................................................................88
Appendix 2. Cockcroft-Gault Calculation...............................................................................90
Appendix 3. Guidelines for Safety Monitoring and Discontinuation......................................91
Appendix 3.1. Safety Monitoring ............................................................................................91
Appendix 3.2. Discontinuation ................................................................................................92
Appendix 4. Prohibited Concomitant Medications..................................................................94
Appendix 5. Columbia Suicide Severity Rating Scale (C-SSRS)25.........................................95
Appendix 6. Suicidal Behaviors Questionnaire-Revised (SBQ-R)26.....................................101
Appendix 7. Patient Health Questionnaire – 8 items (PHQ-8)27 ...........................................103
Appendix 8. Physician Global Assessment ...........................................................................104
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PROTOCOL SUMMARY
Background and Rationale 
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, and to provide 
therapeutic benefit in the treatment of plaque psoriasis.  In a first in human clinical trial of 
PF-06700841, psoriasis subjects who received active treatment with PF-06700841 once daily 
for 28 days had clinically meaningful decreases in disease activity.  Preliminary safety and 
pharmacodynamic results from that trial support further development of PF-06700841 in 
plaque psoriasis.
This multicenter study is being conducted to provide additional PF-06700841 safety and 
tolerability data, and to further explore the clinical efficacy of PF-06700841 in the treatment 
of moderate to severe plaque psoriasis. Additionally, the study is intended to enable 
selection of oral dose and dosing regimen for the future clinical development of 
PF-06700841. 
Objectives:
Primary Objective

To evaluate the efficacy of PF-06700841 in moderate to severe plaque psoriasis.
Secondary Objectives

To explore the efficacy of PF-06700841 induction and maintenance dosing regimens 
in moderate to severe plaque psoriasis.

To assess the safety and tolerability of PF-06700841 induction and maintenance 
dosing regimens.
Endpoints:
Primary Endpoint

Change from baseline in Psoriasis Area and Severity Index (PASI) score at Week 12.
Key Secondary Endpoint

Proportion of subjects achieving a PASI 75 response at Week 12.
Other Secondary Endpoints

Proportion of subjects achieving 50%, 75% and 90% reduction from baseline PASI at 
time-points specified in the study schedule of activities.


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•
Change from baseline in PASI scores at time-points specified in the study schedule of 
activities.
•
Percent change from baseline in PASI scores at time-points specified in the study 
schedule of activities.
•
Change from baseline in PASI score at Week 4.
Safety Endpoints
•
Incidence and severity of adverse events, serious adverse events and withdrawals due 
to adverse events. 
•
Change from baseline in clinical laboratory values (chemistry, hematology, lipids).
•
Change from baseline in vital signs.
•
Change from baseline in electrocardiogram (ECG) parameters.
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Study Design:
This is a Phase 2, randomized, double-blind, placebo-controlled, parallel group, multicenter 
study in subjects with moderate to severe plaque psoriasis.  During the first 4 week treatment 
period, 2 oral daily dose levels (30 mg and 60 mg) of PF-06700841, plus matching placebo, 
will be investigated.  During the 8 week maintenance treatment period (Weeks 5 through 12), 
subjects will receive either 10 mg or 30 mg PF-06700841 once daily, or a 100 mg once 
weekly regimen of PF-06700841, or matching placebo.  Maintenance dose level and regimen 
will be assigned at the initial time of randomization into the study.  The duration of study 
subject participation will be approximately 26 weeks, including screening, 12 week treatment 
period, and 8 week follow up period. 
Statistical Methods: 
The analysis of the primary endpoint will be change from baseline in PASI score at Week 12, 
with treatment effect in each of the active treatment groups defined as the placebo adjusted 
change from baseline in PASI score at Week 12 (mean change from baseline at Week 12 in 
the active treatment group minus the mean change from baseline at Week 12 in the placebo 
group).
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SCHEDULE OF ACTIVITIES
The schedule of activities table provides an overview of the protocol visits and procedures.  Refer to the STUDY PROCEDURES and 
ASSESSMENTS sections 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 on the schedule of activities table, in order to 
conduct evaluations or assessments required to protect the well-being of the subject.
Study Procedure
Screening Baseline
Induction Period
Maintenance Period
Follow-up Period
Visit Identifier
Week -1 
to -6
Week
0
Week 
1
Week 
2
Week
4
Week
6
Week
8
Week
10
Week 12/
Early 
Terminationb
Week 14
Week 16 /
Early 
Terminationb
*Week 20
(telephone 
follow-up)
Study Daya
Day -42-0
1
8
15
29
43
57
71
85
99
113
141
Visit Window (Days)
based on Day 1 visit 
N/A
1
1
2
2
2
2
2
2
2
N/A
Informed consent
X
Medical historyc and 
demography
X
Complete physical 
examinationd
X
X
X
X
Targeted physical 
examinationd
X
X
X
X
X
Vital signse
X
X
X
X
X
X
X
X
X
12-Lead ECGe
X
X
X
X
Current /Prior Medications
X
Heightf
X
Weightf
X
X
X
X
Chest radiographg
X
Contraception check
X











Eligibility assessment
X
X
Randomization
X
Telephone follow-up 
*X
Laboratory Assessments
Hematology
X
X
X
X
X
X
X
X
X
X
X


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Study Procedure
Screening Baseline
Induction Period
Maintenance Period
Follow-up Period
Visit Identifier
Week -1 
to -6
Week
0
Week 
1
Week 
2
Week
4
Week
6
Week
8
Week
10
Week 12/
Early 
Terminationb
Week 14
Week 16 /
Early 
Terminationb
*Week 20
(telephone 
follow-up)
Study Daya
Day -42-0
1
8
15
29
43
57
71
85
99
113
141
Visit Window (Days)
based on Day 1 visit 
N/A
±1
±1
±2
±2
±2
±2
±2
±2
±2
N/A
**Blood chemistry (full 
panel 1)
X
X
X
X
X
X
X
**Blood chemistry (limited 
panel 2)
X
X
X
X
***Serum Cystatin-C
X
X
Lipid Panel (fasting): total 
cholesterol, LDL, HDL, 
triglycerides
X
X
X
X
X
X
Urinalysish
X
X
X
X
X
X
X
X
X
HBsAg, HBcAb, HCV Ab, 
HCV RNA PCR if HCV Ab 
positivei
X
HIV serologyj
X
X
X
X
X
X
X
X
X
X
X
X
X
FSH
X
Serum β-HCGm
X
Pregnancy Testm
X
X
X
X
X
X
X
X
X
X
IGRA TB testingn
X
Laboratory 
Pharmacodynamics
X
X
X
X
X
X
X
X
X
X
X
X
X
X
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Study Procedure
Screening Baseline
Induction Period
Maintenance Period
Follow-up Period
Visit Identifier
Week -1 
to -6
Week
0
Week 
1
Week 
2
Week
4
Week
6
Week
8
Week
10
Week 12/
Early 
Terminationb
Week 14
Week 16 /
Early 
Terminationb
*Week 20
(telephone 
follow-up)
Study Daya
Day -42-0
1
8
15
29
43
57
71
85
99
113
141
Visit Window (Days)
based on Day 1 visit 
N/A
±1
±1
±2
±2
±2
±2
±2
±2
±2
N/A
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Study treatment
Investigational product 
dispensingq
X
X
X
X
X
X
X
Investigational product
accountabilityp
X
X
X
X
X
X
X
Subject dosing diaryp
X
X
X
X
X
X
X
Clinical Assessments
Clinical Evaluation: PASIr, 
BSAr
X
X
X
X
X
X
X
X
X
X
X
Clinical Evaluation: PGAr
X
X
X
X
X
X
X
X
X
X
 
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
PHQ-8t
X
SBQ-Rt
X
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Study Procedure
Screening Baseline
Induction Period
Maintenance Period
Follow-up Period
Visit Identifier
Week -1 
to -6
Week
0
Week 
1
Week 
2
Week
4
Week
6
Week
8
Week
10
Week 12/
Early 
Terminationb
Week 14
Week 16 /
Early 
Terminationb
*Week 20
(telephone 
follow-up)
Study Daya
Day -42-0
1
8
15
29
43
57
71
85
99
113
141
Visit Window (Days)
based on Day 1 visit 
N/A
1
1
2
2
2
2
2
2
2
N/A
C-SSRSt
X
X
X
X
X
Clinical Evaluation: Plaque 
Lesion Photographyu
X
X
X
X
Additional regular 
monitoring 
Concomitant Treatment(s)
X










Serious and non-serious 
adverse event monitoring
X











Abbreviations: = ongoing/continuous event; ECG = electrocardiogram; 
* Week 20 visit is conducted via telephone follow up.  AE assessment will be conducted verbally over the phone and if needed subject will be asked to come in 
for AE assessment.  Use of contraception will be confirmed over the phone with the subject.  Concomitant treatments will be reviewed and collected if any 
new medications/treatments have been initiated since last visit. 
** Full Serum Chemistry Panel 1 consists of Blood Urea Nitrogen (BUN), Serum Creatinine, Glucose, Ca++, Na+, K+, Cl-, Total CO2, Aspartate 
Aminotransferase (AST), Alanine Aminotransferase (ALT), Total bilirubin, Alkaline phosphatase, Uric acid, Albumin, Total Protein, Lactic Dehydrogenase 
(LDH).  Subjects must be fasting (water only) for 8 hours prior to visits on Day 1, Weeks 2, 4, 8, 12, and 16.  Serum Chemistry Panel 2 consists of 
serum hepatic function testing (AST, ALT, total bilirubin, albumin), and serum creatinine, blood urea nitrogen (BUN). Fasting is not required for visits 
where the limited chemistry panel 2 is collected.  
***Serum Cystatin-C will be collected at baseline (Day 1, pre-dose) and end of treatment (Week 12/ET) for all subjects.  A serum creatinine result above the 
upper limit of normal will trigger cystatin-C reflect testing in order to calculate estimated GFR.  Refer to Section 7 for more details. 
a.
Day relative to start of study treatment (Day 1).
b.
For subjects who discontinue early from the double-blind period prior to Week 12 visit, the procedures scheduled for Week 12 will be performed on the last 
day the subject takes the investigational product or as soon as possible thereafter.  For subjects who discontinue early prior to the Week 16 visit, the 
procedures scheduled for Week 16 will be performed at the early termination visit. 
c.
Medical history includes detailed histories of conditions outlined in Section 7.1.7.
d.
Complete physical examination consists of general appearance, skin, head, eyes, ears, nose and throat (HEENT), heart, lungs, breast (optional), abdomen, 
external genitalia (optional), extremities, neurologic function, back, and lymph nodes.  Targeted physical examination consists of skin, heart, lungs, 
abdomen, and examination of body systems where there are symptom complaints by the subject.


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e.
Vital signs and ECG should be performed after the subject has rested quietly for at least 5 minutes and before laboratory blood collection.  Vital signs consist 
of blood pressure, pulse rate, and temperature. Subjects should not smoke or ingest caffeine 30 minutes prior to blood pressure and pulse rate measurements.  
Sitting BP, pulse rate, and temperature will be measured at times specified in the Schedule of Activities.  
f.
Height and weight will be measured without shoes.
g.
Chest X-ray or other appropriate diagnostic imaging (ie, CT or MRI) may be performed up to 12 weeks prior to Day 1.  Official reading must be located in 
the source documentation. 
h.
Dipstick in all cases; microscopy analysis is indicated if urinalysis is positive for blood, nitrite, leukocyte esterase and/or protein.  Urine culture is performed 
if urinalysis is positive for nitrite and/or leukocyte esterase or if clinically indicated.
i.
Subjects who are HCV Ab positive require further testing with HCV RNA PCR.  Subjects with false positive anti-HBc may be enrolled based upon 
consultation with hepatologist confirming no infection with hepatitis B.
j.
If not performed within 12 weeks prior to screening.  Copy of the report should be available in the source document if previously performed.
k.
 
 
l.
To be done in females who are amenorrheic for at least 12 consecutive months. 
m. Required for female subjects of childbearing potential that do not meet the definition of menopause as per the inclusion/exclusion criteria. Serum pregnancy 
test must be performed at screening.  Pregnancy tests (serum/urine) may also be repeated more frequently as per request of IRBs/ECs or if required by local 
regulations.  If serum pregnancy test is borderline positive, the central lab will run a FSH test to confirm menopause, assuming other menopause criteria are 
met per protocol eligibility requirements.
n.
If not performed within 12 weeks prior to screening (see Assessments Section 7.1.4 for details).  (IGRA) (with the following acceptable assays: 
QuantiFERONR-TB Gold (QFT-G) test, QuantiFERON-TB Gold In-Tube test (QFT-GIT) and T-SPOT TB test).
o.
 
 
p.
Drug Accountability procedures are to be performed at Weeks 1, 2, 4, 6, 8, 10, 12, and at the Early Termination visit.
q.
Subjects should take blinded study medication from study Days 1 to 85 during the trial; however, on study visit days, subjects are to be instructed to refrain 
from dosing at home, and are to take the morning dose in the clinic. 
r.
Psoriasis Area and Severity Index (PASI); Body Surface Area (BSA); Physician’s Global Assessment (PGA); 
 
.  
are to be completed at clinic visits prior to other 
clinical assessments and administration of study medication.
s.
 
t.
Subjects who have recent or active suicidal ideation or behavior will be excluded from the study per Section 4.2.
u.
Target lesion and regional photography will be performed at selected study sites.
v.
If not collected on the designated collection day, collect at the next available time point 
 in conjunction with a subject 
visit.
CCI
CCI
CCI
CCI
CCI
CCI
CCI


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1. INTRODUCTION
1.1. Mechanism of Action/Indication
PF-06700841 is a potent TYK2/JAK1 inhibitor with an excellent selectivity profile over the 
other human kinases.  Thus, PF-06700841 is targeted for clinical development for the 
treatment of patients with psoriasis.
The most common variant of psoriasis, plaque psoriasis, is a chronic inflammatory skin 
disease characterized by red, scaly, raised plaques.  In the past, psoriasis had been viewed as 
primarily a disease of epidermal hyperplasia, but more recently psoriasis has come to be 
regarded as an immune-mediated disease.1  Cutaneous and systemic overexpression of 
T cells, as well as type-1 cytokines such as IL-2, IL-6, IL-8, IL-12, IL-23, IL- 17, have been 
implicated in the pathophysiology of chronic plaque psoriasis.2 T-cell infiltration and 
associated pro-inflammatory cytokines drive epidermal hyperplasia characterized by 
increased cell division and aberrant differentiation that result in the psoriatic phenotype.1,3,4  
Chronic plaque psoriasis is a common skin disorder with a worldwide prevalence of 2% and 
afflicts an estimated 5.8-7.5 million Americans.5  Although psoriasis primarily affects the 
skin and is not a life-threatening disease, it can profoundly impact the quality of life resulting 
in impairment akin to other major diseases such as type 2 diabetes, myocardial infarction, 
and arthritis.6
1.2. Background and Rationale
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.7,8  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 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. 
Over activation of TH17 and the main effector cytokines of TH17 cells has been linked to 
various inflammatory diseases, including psoriasis.9 TH17 cells are elevated in psoriatic 
lesions, along with levels of proinflammatory cytokines, including IL-17A, IL-17F, IL-17C, 
which are expressed by TH17 cells and are likely mediators of inflammation and tissue 
damage.9,10  Human genetic studies implicate the TH17 pathway in psoriasis, and have 
uncovered likely risk alleles which include genes involved in IL-23 signaling and genes that 
function downstream of the IL-17 receptor.9 In addition to genetic evidence, several 
effective psoriasis therapies target TH17 cytokine production, suggesting a central role of 


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TH17 and IL-17 in the disease.  Secukinumab selectively targets IL-17A and has been shown 
to be effective in the treatment of psoriasis, and other therapies such as cyclosporine, 
phototherapy, and infliximab inhibit the TH17 pathway.11,12,13,14 The monoclonal antibody 
Ustekinumab, disrupts IL-23 activation of TH17 cells by blocking the IL-23 receptor, and 
has proven to be effective in treating psoriasis.15 Thus, there is strong rationale for targeting 
the TH17 pathway in the treatment of psoriasis.
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, and to provide 
therapeutic benefit in the treatment of plaque psoriasis.  In the first in human clinical trial of 
PF-06700841 (Study B7931001), psoriasis subjects receiving active treatment with 
PF-06700841 (30 mg or 100 mg once daily for 28 days) had clinically meaningful decreases 
in disease activity as measured by PASI.  Preliminary safety, efficacy and pharmacodynamic 
results from Study B7931001 support further development of PF-06700841 in plaque 
psoriasis.
The current trial B7931004 is a Phase 2 study that will assess the safety and efficacy of 
several dose levels of PF-06700841, and will include daily and weekly dosing regimens in 
subjects with moderate to severe chronic plaque psoriasis.
1.3. Non-Clinical Pharmacokinetics and Metabolism
The pharmacokinetics (PK) of PF-06700841 have been studied in rat where the compound 
has shown a plasma clearance of 31 mL/min/kg, a volume of distribution of 2.0 L/kg, and 
oral bioavailability of approximately 80-100%.  The high oral bioavailability indicated high 
absorption from the gut, consistent with its high in-vitro passive permeability properties.  Rat 
in vivo clearance was predicted within approximately 2-fold by both in vitro rat liver 
microsomes and hepatocyte intrinsic clearance highlighting the importance of CYP450 
metabolism.  Systemic exposures of PF-06700841 as measured by Cmax and area under the 
curve at 24 hours (AUC24) in repeat oral pivotal toxicology studies increased with increasing 
dose in rats (up to 55 mg/kg/day) and monkeys (up to 45 mg/kg/day).  Renal and biliary 
elimination of parent PF-06700841 was limited in rat.
Plasma protein binding of PF-06700841 was consistent across rat, monkey, and human with 
a fraction unbound (fu) of approximately 0.6-0.7.  Values of fu were lower in mouse 
(fu = 0.51) and rabbit (fu = 0.36).
Oxidative metabolites of PF-06700841 accounted for the primary routes of biotransformation 
in rat, monkey, and human consistent with CYP450 as the primary clearance route.  No 
unique human metabolites of PF-06700841 were evident compared to the safety species of 
rat and monkey.
Clearance phenotyping of PF-06700841 indicated that CYP3A4 will be the predominant 
mediator of human metabolism with minor contributions from CYP1A2, 2C19, and 2D6.


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PF-06700841 showed a low risk of CYP450 inhibition and induction, uridine glucuronyl 
transferase (UGT) inhibition, OATP1B1/1B3 inhibition, and MDR1 inhibition.  
PF-06700841 showed some potential to inhibit metformin mediated transport by OCT2 
(IC50=1.1 M), MATE1 (IC50=7.7 M) and MATE2K (IC50=17 M) in vitro.  The respective 
unbound Imax/IC50 ratios are 0.65, 0.09, and 0.04 for a predicted 60 mg clinical dose of 
PF-06700841 (unbound Cmax=0.72 M).  SimCYP modeling indicated a low risk of 
drug-drug interactions (DDI) perpetrated by a 60 mg once daily (QD) dose of PF-06700841 
(Cmax/AUC ratios 1.19/1.20).
1.4. Non-Clinical Safety Studies
PF-06700841 was evaluated in single-dose and repeat-dose toxicity studies up to 6 months 
(rats) and 9 months (monkeys) in duration.  Dose range-finding and pivotal embryo-fetal 
development studies (EFD) were conducted with PF-06700841 in rats and rabbits.  Target 
organs identified with PF-06700841 administration in rats and cynomolgus monkeys include 
the immune and hemolymphatic systems (thymus, spleen, lymph nodes, and bone marrow), 
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 and were not adverse because they were not 
associated with adverse clinical signs or adverse changes in hematology parameters, and 
there was no evidence of test article-related infections in these animals.  Gastrointestinal and 
adrenal effects were not adverse because they were either transient, of small magnitude 
and/or severity, and/or lacked associated tissue injury or inflammation, or changes in clinical 
pathology parameters. In addition, there were inconsistent findings in the bone, liver, lung 
and prostate where the relationship to PF-06700841 is less clear.  Adverse findings in the 
central nervous system (decreased activity, mortality, prostration, convulsions) were 
observed at high exposures in pregnant rabbits, and emesis was observed in monkeys at high 
doses in studies 1 month in duration.  In safety pharmacology assessments 
PF-06700841-related effects were observed in the cardiovascular system (blood pressure, 
heart rate, QTc interval) and central nervous system (decreased locomotor activity). Based 
on the lack of adverse findings at any dose, the no observed adverse effect levels (NOAELs) 
in the 6-month rat and 9-month monkey studies were 45 mg/kg/day in rats and 20 mg/kg in 
cynomolgus monkeys.  Exposures at these doses were 6.2x to 40x the predicted efficacious 
human exposure (Cmax= 218 ng/mL and AUC24= 1730 ng•h/mL) from a 50 mg dose.
In the pivotal EFD study in rats, there were no PF-06700841-related maternal effects.  
However, higher incidences of fetal skeletal malformations (in long bones, scapulae, 
sternebrae or palatine bones) and variations (in the ribs, cervical vertebrae or sternebrae) 
occurred at 2 mg/kg/day, and delays in the ossification of the axial and appendicular 
skeleton occurred at 15 mg/kg/day.  In addition, lower embryo-fetal viability; lower mean 
fetal body weights, external malformations (cleft palate) and variations (whole body 
subcutaneous edema or edematous neck) occurred at 15 mg/kg/day.  The maternal NOAEL 
in rats was 15 mg/kg/day (13x and 11x the predicted efficacious human Cmax and AUC24
exposure from a 50 mg dose) and the developmental NOAEL was not determined but was 
<2 mg/kg/day, the lowest dose tested (2.2x and 1.3x the predicted efficacious human Cmax
and AUC24 exposure from a 50 mg dose).  In the pivotal EFD study in rabbits, there were no 


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PF-06700841-related maternal effects.  However, test article-related higher incidences of late 
resorptions and post-implantation loss occurred at 3 mg/kg/day and lower mean numbers of 
viable fetuses occurred at 7 mg/kg/day. Test article-related skeletal variations were observed 
at 3 mg/kg/day, but were not adverse because most of these findings represent delays in 
ossification that would resolve with further growth and development.  The maternal NOAEL 
in rabbits was 7 mg/kg/day, the highest dose tested, (6.6x and 3.2x the predicted efficacious 
human Cmax and AUC24 exposure from a 50 mg dose) and the developmental NOAEL was 
1 mg/kg/day (0.8x and 0.4x the predicted efficacious human Cmax and AUC24 exposure from 
a 50 mg dose).
PF-06700841 was negative for mutagenicity in the bacterial reverse mutation assays.  
Although PF-06700841 was positive in the in vitro micronucleus assays in both CHO and 
TK6 cells, and was aneugenic in vitro (at 72,100 nM), it did not induce micronuclei, in vivo, 
in reticulocytes in the 1-month study in rats (at exposures 35x to 51x the predicted human 
efficacious exposure (unbound Cmax = 218 ng/mL and AUC24 = 1730 ng•h/mL) from a 50 mg 
dose.
Although PF-06700841 absorbs in the ultraviolet A (UVA) and ultraviolet B (UVB) range,
PF-06700841 (100 mg/kg/day [unbound Cmax and AUC24 were 46x and 82x the predicted 
efficacious human exposure from a 50 mg dose]) had no evidence of phototoxicity in the skin 
or eyes of pigmented Long Evans rats in a 3-day phototoxicity study.  This demonstrates that 
PF-06700841 was not a phototoxicant, in vivo.
In summary, the nonclinical studies adequately support the planned clinical trials with 
PF-06700841.
Please refer to the Investigators Brochure for more details on the nonclinical information 
with PF-06700841.
1.5. Summary of Clinical Experience with PF-06700841
The B7931001 first in human study is the single clinical trial of PF-06700841 completed to 
date.  Of the 96 subjects randomized, 74 subjects have received at least one active dose of 
oral PF-06700841 in Study B7931001. This accounts for 41 healthy subjects who 
participated in the single and multiple ascending dose period of the trial who received active 
solution/suspension, 12 healthy subjects from the bioavailability (BA) study who received 
suspension/tablet, and 21 subjects with chronic plaque psoriasis who were randomized to 
receive active solution/suspension over a 28 day treatment period.
The first in human (FIH) study was a Phase 1, randomized, double blind, third party open, 
placebo controlled, single and multiple dose escalation, parallel group study in healthy adult 
subjects and subjects with plaque psoriasis, with a relative bioavailability and food effect 
assessment of a tablet formulation of PF-06700841 in healthy adult subjects. During the 
single ascending dose (SAD) period, 41 healthy subjects received doses of 1, 3, 10, 30, 100, 
or 200 mg of PF-06700841 in a dose escalation format. Twenty-one healthy subjects 
received doses of 10, 30, 100, or 175 mg QD for 10 days during the multiple ascending dose 
(MAD) period. Subjects participating in the 100 mg multiple dose cohort returned for a third 


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period to receive 50 mg PF-06700841 BID for 10 days.  Thirty subjects with moderate to 
severe chronic plaque psoriasis were also randomized into Study B7931001, to receive once 
daily placebo (n=9), 30 mg (n=14), or 100 mg (n=7) PF-06700841 for 28 days, and 
underwent safety monitoring and clinical efficacy assessments.  An additional healthy 
volunteer cohort was included to support the evaluation of the relative bioavailability (BA) of 
a tablet formulation of PF-06700841, and assessment of a high fat meal on tablet 
bioavailability.  12 healthy subjects participated in this BA assessment, and received single 
doses of open label PF-06700841 in a 3-way cross over design (PF-0670841 tablet fasted, 
PF-06700841 solution/suspension fasted, and PF-06700841 tablet under fed conditions).
1.5.1. Summary of Clinical Safety Experience with PF-06700841
PF-06700841 was generally safe and well tolerated in the Phase 1 clinical study B7931001, 
which included both healthy subjects (n=66 randomized) and subjects with plaque psoriasis 
(n=30 randomized).  There were no deaths in the study, no serious adverse events, and no 
severe adverse events. Subjects reported 11 treatment emergent adverse events TEAEs in the 
SAD phase, 22 TEAEs in the MAD phase, 39 TEAEs in the psoriasis phase, and 3 TEAEs in 
the BA phase.  All adverse events (AEs) were mild or moderate in severity.  Dose escalation 
stopping rules were not triggered at any dose level.
The most commonly reported all causality TEAEs across active subjects in both SAD and 
MAD cohorts were blood creatinine increased (reported in 2 subjects during the SAD period 
and 11 subjects during the MAD period), and neutropenia/neutrophil count decreased 
(reported in 4 subjects during the MAD period), which belong to the System Organ Class 
(SOC) categories of Investigations and Blood and Lymphatic System Disorders, respectively.
During the SAD/MAD, the AEs of blood creatinine increased were reported across dose 
levels from 10 mg up to 200 mg of PF-06700841, and occurred with greatest frequency in the 
175 mg QD and 50 mg BID MAD cohorts.  Common terminology criteria for adverse events 
(CTCAE) Grade 3 neutropenia occurred at the 175 mg QD and 50 mg BID dose levels during 
the MAD period.  All laboratory abnormalities reported as AEs were mild in severity, except 
for one case of neutropenia which was reported as moderate in severity (Grade 3 
neutropenia).  No neutrophil counts reached, or fell below 500 cells/mm3 during the study.
Other commonly reported all causality TEAEs during the SAD/MAD by SOC were Nervous 
System Disorders (2 events of headache and 1 event each of dizziness and presyncope during 
the SAD period, and 1 event each of headache, presyncope, and syncope reported during the 
MAD period), and Infections and Infestations (upper respiratory tract infection reported in 
2 subjects during the MAD period). The AEs of upper respiratory tract infection were 
reported in 1 subject who received 10 mg PF-06700841 QD and 1 subject who received 
100 mg PF-06700841 QD. These infections did not require antibiotic therapy (1 subject 
received symptomatic treatment), and did not require study treatment discontinuation.
The most commonly reported all causality TEAEs across active subjects in the psoriasis 
cohorts treated with either 30 mg or 100 mg PF-06700841 were blood creatinine increased 
(reported in 7 subjects in the 30 mg dose group and 6 subjects in the 100 mg dose group), 


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neutrophil count decreased (reported in 1 subject in the 30 mg dose group and 1 subject in 
the 100 mg dose group), which belong to the SOC category of Investigations.
Other commonly reported AEs by SOC in the psoriasis cohorts included Nervous System 
Disorders (headache reported in 1 subject in the 30 mg dose group and 1 subject in the 
100 mg dose group, and paresthesia reported in 1 subject in the 100 mg dose group), 
Gastrointestinal Disorders (constipation reported in 3 subjects in the 30 mg dose group), and 
Infections and Infestations (1 report of upper respiratory tract infection and 1 report of herpes 
zoster infection, both in the 100 mg dose group).
The AE of herpes zoster occurred in a single subject after completing 28-day treatment with 
PF-06700841 at the 100 mg QD dose level.  The subject had a non-disseminated, herpetiform 
rash on the upper left back and left arm that was reported to have presented on Study Day 30 
(2 days after the last dose of PF-06700841).  The AE was mild in severity and was treated 
with acyclovir and Vicodin by the Investigator.
In the BA cohort, the SOCs with subjects reporting AEs were Gastrointestinal Disorders, 
Injury, Poisoning, and Procedural Complications, and Nervous System Disorders, each 
reported by 1 subject. The reported AEs were nausea, contusion, and headache, each of 
which was experienced by 1 subject.  Subjects in the PF-06700841 100 mg oral 
solution/suspension fasted group reported 1 treatment-related TEAE each of nausea and 
headache.  All TEAEs were mild in severity.
Despite the AEs of blood creatinine increased observed in the healthy subjects (n=13 in the 
SAD/MAD cohorts) and psoriasis patients (n=13), review of clinical laboratory parameters 
from Study B7931001 confirmed there have been no noted clinically meaningful changes in 
the blood urea nitrogen, serum electrolytes, urinalysis, or cystatin-c based estimated 
glomerular filtration rate (eGFR) in the subjects with elevated serum creatinine. Serum 
creatinine is primarily filtered by the kidney however; approximately 10-20% is actively 
secreted into the renal proximal tubules.  The active tubular secretion is mediated by 
transporters such as OCT2, OAT2 and MATEs.  The proposed mechanism for the observed 
serum creatinine increases observed in Study B7931001 is inhibition of creatinine transport 
(ie, transporter-mediated rather than direct nephrotoxicity), and is based on PF-06700841 
potential to inhibit OCT2 creatinine transporter (IC50=1.1 M; unbound Imax/IC50 ratio=0.25).  
To differentiate from direct nephrotoxicity, the B7931001 protocol was amended (Protocol 
Amendment 2) to include collection of serum cystatin C.  Serum cystatin C was used to 
calculate eGFR in order to monitor for nephrotoxicity during the trial.  Elevated serum 
creatinine in the absence of clinically meaningful changes in serum cystatin C based 
estimated GFR during Study B7931001 supports the transporter inhibition hypothesis.
Following the implementation of cystatin C based safety monitoring, no subjects were 
discontinued from treatment/study due to renal concerns.
Proof of mechanism for JAK-1 inhibition was demonstrated in Study B7931001 by inhibition 
of pharmacodynamic (PD) biomarkers hs-CRP and IP-10. Safety data generated in Study 
B7931001 support PF-06700841’s further clinical development in patients with 
moderate-severe plaque psoriasis.


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Please refer to the Investigator Brochure (IB) for more details on the clinical safety 
information with PF-06700841.
1.5.2. Pharmacokinetics of PF-06700841
PK data from single doses of 1, 3, 10, 30, 100 and 200 mg and multiple doses of 10, 30, 100 
and 175 mg QD and 50 mg BID mg administered for 10 days are summarized in Table 1 and 
Table 2, respectively. Following single oral doses of 1 mg to 200 mg under fasted
conditions, PF-06700841 was absorbed rapidly with median Tmax of 1 hour or less.
Following the attainment of Cmax, concentrations appeared to decline in monophasic fashion.
Mean terminal t½ ranged from 3.8 to 7.5 hours. In general, both AUCinf and Cmax appear to 
increase proportionally with dose from 1 mg to 100 mg, and there appears to be a trend 
toward more than proportional increases from 100 mg to 200 mg for AUCinf and Cmax.
Table 1.
Summary of Plasma PF-06700841 Pharmacokinetic Parameters Following 
Single Oral Doses, Study B7931001
PF-06700841 Parameter Summary Statisticsa by Treatment
Parameter, units
1 mg
3 mg
10 mg
30 mg
100 mg
200 mg
N, n
7, 2
6, 5
6, 6
6, 6
8, 7
8, 8
AUCinf, ng.hr/mL
NR
145.8 (61)
353.8 (31)
1439 (65)
4797 (62)
18410 (46)
AUClast, ng.hr/mL
17.71 (114)
79.18 (239)
340.4 (30)
1431 (65)
5041 (59)
18400 (46)
Cmax, ng/mL
5.138 (52)
18.21 (92)
79.30 (35)
271.3 (21)
748.4 (35)
2460 (37)
Tmax, hr
1.00
(0.500-2.00)
1.00
(0.500-1.00)
0.500
(0.500-1.00)
1.00
(0.500-1.02)
1.00
(0.500-2.00)
1.00
(0.500-2.00)
t½, hr
NR
4.55 1.81
3.85 1.16
4.36 2.41
7.52 2.82
6.81 1.99
a. Geometric mean (geometric %CV) for all except: median (range) for Tmax; arithmetic mean SD for t½.
N = Number of subjects in the treatment group and contributing to the mean; n= number of subjects where t½, 
AUCinf were determined; NR = Not reported. 
Summary statistics are not presented if fewer than 3 subjects have reportable parameter values.
On Day 10 of multiple-dose administration, PF-06700841 was absorbed rapidly with median 
Tmax of 1.5 hours or less across the entire range of doses, from a total daily dose of 30 mg up 
to 175 mg.  Following attainment of Cmax, the disposition of PF-06700841 was similar with 
that observed following single-dose administration. Mean terminal t½ ranged from 4.9 to 
10.7 hours. In general, both AUCtau and Cmax appear to increase proportionally with dose 
from 10 mg to 175 mg. The mean apparent clearance (CL/F) was 10.8 L/hr to 23.7 L/hr, and 
the mean apparent volume of distribution (Vz/F) was 106.2 L to 249.4 L.


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Table 2.
Summary of Steady State Plasma and Urine PF-06700841 Pharmacokinetic 
Parameters Following Multiple Dose Administration, Study B7931001
PF-06700841 Parameter Summary Statisticsa by Treatment
Parameter, units
10 mg (QD)
30 mg (QD)
100 mg (QD)
50 mg (BID)
175 mg (QD)
N, n
5, 5
3, 3
6, 6
4, 4
4, 4
AUCτ, ng.hr/mL
422.8 (41)
1880 (52)
6089 (38)
3560 (35)
16180 (15)
Cmax, ng/mL
63.4 (11)
286.6 (17)
734.1 (29)
522.0 (31)
2091 (28)
Tmax, hr
1.0 (1.0-1.0)
1.00 (1.00-1.00)
1.5 (1.0-2.0)
1.0 (1.0-2.0)
0.98 (0.50-2.0)
CL/F, L/hr
23.7 (41)
16.0 (51)
16.4 (38)
14.0 (35)
10.8 (16)
t½, hr
5.93 3.333
4.86 1.93
10.67 1.84
9.13 2.26
7.46 2.16
Vz/F, L
177.6 (30)
106.2 (12)
249.4 (45)
180.9 (30)
112.4 (18)
Aeτ%
11.1 (45)
9.33 (57)
7.15a
15.5 (57)
8.91 (44)
CLr, mL/min
43.7 (18)
24.8 (15)
30.5a
36.3 (31)
16.0 (58)
a.
N=1.
Geometric mean (geometric %CV) for all except:  median (range) for Tmax; arithmetic mean SD for t½.
N = Number of subjects in the treatment group and contributing to the mean; n= number of subjects where t½
was determined.
AUC, = Area under the concentration-time curve from zero to 24 hours (QD) or zero to 12 hours (BID) 
postdose at steady state; BID = Twice daily; Cmax = Peak plasma concentration; CL/F = apparent total body 
clearance; CLr = Renal clearance; Ae% = Percent of dose recovered unchanged in urine over the dosing 
interval ; QD = Once daily; Vz/F = apparent volume of distribution.
Urinary recovery of PF-06700841 was low, with approximately <16% of the dose recovered 
unchanged in urine on Day 10 across all doses (geometric mean Ae% of 8.9% to 15.5%).  
Renal clearance ranged from 16.0 mL/min to 43.7 mL/min.
The relative bioavailability (B7931001) of 100 mg PF-06700841 tablets compared to 100 mg 
oral suspension was 96.2% for AUCinf and 94.3% for Cmax. Both of the 90% CIs for the ratio 
were within the 80% to 125% equivalence interval.  When the 100 mg tablets were 
administered under fed conditions, Tmax was delayed with a median value of 4.0 hours, 
compared to a median Tmax 0.5 hours under fasted conditions. For 100 mg tablets fed vs. 
fasted, the ratio (90% CI) of adjusted geometric means for AUCinf and Cmax was 
82.3% (73.5%, 92.3%) and 64.3% (56.0%, 73.8%), respectively.
Listed in Table 3 are the PK parameters following multiple-dose administration of 
PF-06700841 to psoriasis subjects. PF-06700841 was absorbed rapidly with median Tmax of 
1 hour to 2 hours post dose.  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 includes a reported t½ value of 
87.5 hours for one subject with an anomalous data point at 216 hours postdose: all other 
subjects 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.


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Table 3.
Summary of Plasma PF-06700841 Pharmacokinetic Parameters Following 
Multiple Dose Administration in Psoriasis Subjects, Study B7931001
Parameter Summary Statisticsa by Treatment
Parameter, units
PF-06700841 30 mg QD (P)
PF-06700841 100 mg QD (P)
N, n
7, 7
5, 5
AUCτ, ng.hr/mL
990.0 (103)
7672 (43)
Cmax, ng/mL
204.7 (43)
924.2 (13)
Tmax, hr
1.00 (0.983-2.00)
2.00 (1.00-2.00)
CL/F, L/hr
30.30 (103)
13.04 (43)
MRT, hr
6.072 (92)
8.534 (36)
PTF
3.414 (44)b
2.654 (42)
t½, hr
16.01 31.58
6.032 1.712
Vz/F, L
245.4 (206)
109.6 (18)
a. Geometric mean (geometric %CV) for all except: median (range) for Tmax; arithmetic mean SD for t½.
b. 4 subjects contributing to the mean in this group.
N = Number of subjects in the treatment group and contributing to the mean; n= number of subjects where t½, 
Vz/F and MRT were determined.
In general, dose normalized exposure was higher in the 100 mg group than in the 30 mg 
group although the highest individual dose normalized values for both AUCand Cmax were 
observed in one subject in the 30 mg group. Note that the subject in the 30 mg group with 
the highest Cmax and AUCvalues (Subject 10011092) is not the same subject with the
anomalous 87.5 hour t½ value (Subject 10011117).
1.6. Study Rationale
This multicenter, placebo controlled study is being conducted to provide additional 
PF-06700841 safety and tolerability data, and to further explore the clinical efficacy of 
PF-06700841 in the treatment of moderate to severe plaque psoriasis following clinical 
results from the B7931001 Phase 1 study. Additionally, the study is intended to enable 
selection of oral dose and dosing regimen (daily vs. weekly chronic administration) for the 
future clinical development of PF-06700841. The current nonclinical toxicology package 
supports the planned treatment duration of up to 12 weeks.
The completed B7931001 Phase 1 study included Single Ascending Dosing (SAD) and 
Multiple Ascending Dosing (MAD) in healthy volunteers, Proof of Mechanism (PoM) and 
small efficacy investigations in patients with psoriasis. The study demonstrated acceptable 
safety and PK profile at single PF-06700841 doses from 1 to 200 mg, and once daily doses 
(QD) from 10 to 175 mg, and 50 mg twice daily (BID) for ten days. Dose escalation 
stopping rules were not triggered at any dose level during the SAD/MAD investigations.
Additionally, clinical benefit was seen in subjects with chronic plaque psoriasis as measured 
by the change from baseline in PASI scores over the 28 day treatment period.  In subjects 
completing through study Day 28, the mean placebo adjusted change from baseline in PASI 
score at Week 4 was -9.6 for the 30 mg cohort (n=7), and -14.2 for the 100 mg cohort (n=5).  
Sustained efficacy was observed at approximately 1 month after last dose of 100 mg 
PF-06700841, and approximately 1 week after the last dose of PF-06700841 30 mg, both 
dose levels administered QD over 28 days. This suggests that less frequent dosing may offer 


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patients clinical benefit. The current B7931004 study design will test both daily and weekly 
dosing regimens (Figure 1).
The total treatment duration of 12 weeks in B7931004 will allow further exploration of the 
clinical efficacy observed in the 4 week small efficacy study completed in the Phase 1 study 
B7931001. Continuous change from baseline in PASI score at Week 12 will be used as the 
primary endpoint to gain sensitivity and efficiency regarding statistical power.  The once 
daily PF-06700841 induction doses to be explored in the current study will be below the 
100 mg dose level, (eg, 30 mg and 60 mg) in order to adequately evaluate clinical efficacy 
while minimizing safety risk. To further improve the risk/benefit, the study will explore a 
step down maintenance daily dosing with PF-06700841 10 mg and 30 mg for 8 weeks after 
the initial 4 week dosing with 30 mg or 60 mg QD. PF-06700841 100 mg once weekly 
(QW) will also be investigated in order to evaluate the clinical utility of a weekly 
maintenance dosing in subjects with plaque psoriasis.
Given the assumed PF-06700841 mediated inhibition of creatinine transport in the kidney, 
the inclusion of serum cystatin –C collection at baseline, end of treatment, and as indicated 
during the trial (see Section 7.1.3) will facilitate calculation of eGFR at these time points to 
provide a reliable assessment of renal function.
1.7. Dose Rationale
The dose selection strategy was designed to balance pharmacology and safety. A global PK 
model was developed using the data from the first-in-human study (Protocol B7931001). PK 
was assumed to be similar between healthy subjects and psoriasis subjects. The activity of 
the JAK inhibitors was assessed by measurement of various PD markers and markers of 
safety that were collected in the FIH study and analyzed using indirect response modeling.
The magnitude of change in these markers required for efficacy and/or safety is poorly 
understood.
The predicted PK parameters for PF-06700841 based on simulations using the global PK 
model and predicted PD during the induction period (4 weeks) are provided in Table 4.


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Table 4.
Summary of Predicted Total Geometric Mean Plasma PF-06700841
Pharmacokinetic and Pharmacodynamic Parameters During the 
Induction Period of Multiple Dose Administration
Dose
mg 
QD
Total 
Cmax
ng/mL
Predicted
Margins
Cmaxa
Total 
AUCtau
ng.hr/mL
Predicted
Margins
AUCa
Percent Reduction from Baseline
hsCRP
IP-10
Neutrophils Reticulocytes
Induction (4 weeks)
30
206.7 
(27)
15
1619 (44)
9.1
80 (7.5)
44 (29)
23 (66)
33 (40)
60
433.3 
(27)
7.2
3797 (43)
3.9
84 (6.4)
51 (21)
32 (70)
50 (34)
a. 9 month oral monkey NOAEL-20 mg/kg; mean male and female Cmax(free) = 2263 ng/mL; 
Cmax (total) = 3100 ng/mL; AUCtau (free) = 10731 ng•h/mL; AUCtau (total) = 14700 ng•h/mL, 
monkey (fu) = 0.73; human fu = 0.61
AUCtau = Area under the concentration-time curve from zero to 24 hours postdose at steady state; 
Cmax = Peak plasma concentration; QD = Once daily; ( ) = Coefficient of variation expressed as a 
percentage.
The predicted exposure based on total drug during the induction period at the maximum dose 
of 60 mg QD for 4 weeks is projected to maintain approximately a 7.2- and 3.9-fold safety 
margins for Cmax and AUCtau, respectively.
In Study B7931001, mechanistic biomarkers of efficacy eg hsCRP and IP-10 related to IL-6 
and IFN-gamma, respectively, were measured in healthy subjects. Based on indirect 
response modeling, the predicted percent reductions in the hsCRP levels during the induction 
period ranged between 80% and 84% over the dose range 30-60 mg. Similarly, the reduction 
of IP-10 levels ranged between 44% and 51% over the same dose range. Modeling and 
simulations predicted maximum reductions in neutrophils and reticulocytes of 32% and 50%, 
respectively following 60 mg QD.
The predicted PK parameters for PF-06700841 based on simulations using the global PK 
model and predicted PD during the chronic dosing period (8 weeks) are provided in Table 5.


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Table 5.
Summary of Predicted Geometric Mean Total Plasma PF-06700841 Pharmacokinetic 
and Pharmacodynamic Parameters During the Chronic Period of Multiple Dose 
Administration
Induction
Dose mg 
QD
Chronic 
Dose mg
Total 
Cmax
ng/mL
Predicted
Margins
Cmax
a
Total 
AUCtau
ng.hr/mL
Predicted
Margins
AUCa
Percent Reduction from Baseline
hsCRP
IP-10
Neutrophils
Reticulocytes
Chronic Dosing (8 weeks)
30
30 QD
206.7 
(27)
15
1619 (44)
9.1
81 (9.6)
45 
(29)
28 (50)
34 (40)
30
10 QD
57.1 
(29)
54
418.7 (44)
35
71 (19)
31 
(38)
14 (48)
15 (43)
30
100 QW
746.8 
(28)
4.2
6709 (45)
2.2
59 (28)
28 
(46)
15 (55)
15 (41)
60
Placebo
NA
NA
NA
NA
NA
NA
NA
NA
60
10 QD
60.2 
(30)
51
455.9 (45)
32
73 (20)
33 
(37)
15 (42)
15 (41)
60
30 QD
200.5 
(28)
15
1675.9 
(43)
8.8
82 (7.7)
47 
(26)
30 (45)
36 (35)
60
100 QW
727.0 
(28)
4.3
6242 (45)
2.4
58 (26)
27 
(40)
14 (51)
14 (44)
a. 9 month oral monkey NOAEL-20 mg/kg; mean male and female Cmax(free) = 2263 ng/mL; Cmax (total) = 3100 ng/mL; 
AUCtau (free) = 10731 ng•h/mL; AUCtau (total) = 14700 ng•h/mL, monkey (fu) = 0.73; human fu = 0.61.
AUCtau = Area under the concentration-time curve from zero to 24 hours postdose at steady state; Cmax = Peak plasma concentration; 
NA = not applicable; QD = Once daily; QW = once weekly; ( ) = Coefficient of variation expressed as a percentage.


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The 100 mg once weekly (QW) regimen during the chronic dosing period (8 weeks) was 
used to provide guidance as to the minimum projected safety margins during this period. The 
projected safety margins for Cmax and AUCtau are approximately 4.3- and 2.4-fold, 
respectively.
During the chronic dosing period the 30 mg QD induction and maintenance dose or the 
60 mg QD induction dose followed by 30 mg QD are projected to reduce hsCRP and IP-10 
by approximately 82% and 47%, respectively. These doses are projected to reduce 
neutrophils by approximately 30% and reticulocytes by 36%.  The regimens that included 
100 mg QW in the chronic dosing period are projected to reduce hsCRP and IP-10 by 
approximately 58% and 27%, respectively.  The associated changes for neutrophils and 
reticulocytes are expected to be minimal (~14%). Overall, the doses selected for this study 
are expected to demonstrate clinically relevant efficacy in subjects with moderate to severe 
psoriasis.
1.8. Summary of Benefits and Risks
Overall, the safety profile observed during the Phase 1 program for PF-06700841 appears to 
be acceptable at dosages up to 175 mg administered orally as multiple doses over 10 days.  A 
longer dosing duration was explored in psoriasis patients, who received the maximum 
PF-06700841 dose level of 100 mg daily for 28 days.  No serious or severe AEs were 
reported in the Phase 1 study. However, there was one AE of herpes zoster infection in a 
psoriasis subject treated with 100 mg PF-6700841 for 4 weeks.  As with other 
immunomodulators, the risk of infection is potential concern due to the immunosuppressive 
effects of PF-06700841.  To limit this risk, a maximum daily dose below 100 mg (the dose 
associated with infection in the Phase 1 study B7931001) will be used in this Phase 2 trial.  
In addition, a variety of step down approaches including a weekly dosing will be tested in 
this study in order to identify a dose(s) and dosing regimen(s) with an acceptable risk /benefit 
profile.
Additional information for this compound may be found in the single reference safety 
document (SRSD), which for this study is the Investigator’s Brochure.
CCI


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2. STUDY OBJECTIVES AND ENDPOINTS
Primary Objective(s):
Primary Endpoint(s):
•
To evaluate the efficacy of PF-06700841 in 
moderate to severe plaque psoriasis.
•
Change from baseline in PASI score at 
Week 12.
Secondary Objective(s):
Secondary Endpoint(s):
•
To explore the efficacy of PF-06700841 
induction and maintenance dosing regimens in 
moderate to severe plaque psoriasis.
•
Key secondary: Proportion of subjects 
achieving a PASI 75 response at Week 12.
•
Proportion of subjects achieving 50%, 75% and 
90% reduction from baseline PASI at 
time-points specified in the SoA.
•
Change from baseline in PASI scores at 
time-points specified in the SoA.
•
Percent change from baseline in PASI scores at 
time-points specified in the SoA.
•
Change from baseline in PASI score at Week 4.
•
To assess the safety and tolerability of 
PF-06700841 induction and maintenance dosing 
regimens.
•
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 vital signs (blood 
pressure, pulse rate, oral or tympanic 
temperature measurements).
•
Change from baseline in ECG parameters (heart 
rate, QT, QTc, PR and QRS intervals).
CCI
CCI
CCI
CCI


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CCI
CCI
CCI
CCI


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3. STUDY DESIGN
This is a Phase 2a, randomized, double-blind, placebo-controlled, parallel group, multicenter 
study in subjects with moderate to severe plaque psoriasis. The first part of the study, 
following a screening period (up to 6 weeks), is a 4 week induction period with double blind 
daily treatment.  At the end of Week 4, all subjects switch to their predefined double blind 
maintenance treatment regimen for Week 5 through Week 12.
Approximately 200 subjects are planned to be randomized into the study, to allow for 
approximately 160 evaluable subjects (20 completers per arm).  The randomization ratio will 
be 7:1, active: placebo.  During the first 4 week treatment period, 2 oral daily dose levels 
(30 mg and 60 mg) of PF-06700841, plus matching placebo, will be investigated. During the 
8 week maintenance treatment period (Weeks 5 through 12), subjects will receive either 
10 mg or 30 mg PF-06700841 once daily, or a 100 mg once weekly regimen of 
PF-06700841, or matching placebo.  Maintenance dose level and regimen will be assigned at 
the initial time of randomization into the study. All subjects, regardless of assigned regimen 
(ie, QD or QW) will receive blinded QD dosing throughout the study treatment period to 
maintain the study blind.
The duration of study subject participation will be approximately 26 weeks, including 
screening, 12 week treatment period, and 8 week follow up period. 
Figure 1.
Study Schematic


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4. SUBJECT ELIGIBILITY CRITERIA
This study can fulfill its objectives only if appropriate subjects are enrolled.  The following 
eligibility criteria are designed to select subjects 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 subject is suitable for this protocol.
Subject eligibility should be reviewed and documented by an appropriate member of the 
investigator’s study team before subjects are included in the study.
4.1. Inclusion Criteria
Subjects must meet all of the following inclusion criteria to be eligible for enrollment into the 
study:
1. Evidence of a personally signed and dated informed consent document indicating that 
the subject (or a legally acceptable representative) has been informed of all pertinent 
aspects of the study.
2. Willing and able to comply with scheduled visits, treatment plan, laboratory tests and 
other study procedures.
3. Male or female subjects between 18 and 75 years of age, inclusive, at time of 
informed consent.
4. Have had a diagnosis of plaque psoriasis (psoriasis vulgaris) for at least 6 months 
prior to Baseline/Day 1 (prior to first dose of study drug).
5. Have a PASI score of 12 or greater AND a PGA score of 3 (“moderate”) or 
4 (“severe”) at Baseline/Day 1 (prior to first dose of study drug).
6. Have plaque-type psoriasis covering at least 10% of total body surface area (BSA) at 
Baseline/Day 1 (prior to first dose of study drug).
7. Considered by investigator to be a candidate for systemic therapy or phototherapy of 
psoriasis (either naïve or history of previous treatment).
8. Female subjects of non-childbearing potential must meet at least 1 of the following 
criteria:

Achieved postmenopausal status, defined as follows: cessation of regular menses 
for at least 12 consecutive months with no alternative pathological or 
physiological cause; and have a serum follicle-stimulating hormone (FSH) level 
confirming the postmenopausal state;

Have undergone a documented hysterectomy and/or bilateral oophorectomy;

Have medically confirmed ovarian failure.


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All other female subjects (including female subjects with tubal ligations) are 
considered to be of childbearing potential.
9. Must agree to avoid prolonged exposure to the sun and avoid use of tanning booths or 
other ultraviolet light sources during the study.
10. If receiving non prohibited concomitant medications for any reason, must be on a 
stable regimen, which is defined as not starting a new drug or changing dosage within 
7 days or 5 half-lives (whichever is longer) prior to first dose of study drug. 
11. If received any of the following treatment regimens, for any reason, are eligible 
providing the following minimum washout criteria are observed:
Must be discontinued for at least 12 weeks prior to first dose of study drug:
a.
Any investigational or experimental therapy or procedure for psoriasis, psoriatic 
arthritis or rheumatoid arthritis;
Exception: Investigational biologics should be discussed with the Pfizer Medical 
Monitor (or designee) to confirm period of discontinuation required.

Ustekinumab (Stelara).
Must be discontinued for at least 10 weeks prior to first dose of study drug:
a.
Adalimumab (Humira);
b. Certolizumab pegol (Cimzia);
c.
Infliximab (Remicade);
d. Alefacept (Amevive).
Must be discontinued for at least 4 weeks prior to first dose of study drug:
a.
Etanercept (Enbrel);
b. Systemic treatments other than biologics that could affect psoriasis, eg, oral or 
injectable (eg, intraarticular, intramuscular, or intravenous) corticosteroids, 
retinoids, methotrexate, cyclosporine, fumaric acid derivatives, sulfasalazine, 
hydroxycarbamide (hydroxyurea), azathioprine, intramuscular gold;
c.
Psoralen + UVA phototherapy (PUVA).


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Must be discontinued for at least 2 weeks prior to first dose of study drug:

Topical treatments that could affect psoriasis, eg, corticosteroids, tars, 
keratolytics, anthralin, vitamin D analogs, and retinoids.
Exceptions – the following topical treatments are allowed: non medicated emollients 
for use over the whole body; low or least potent (Class 6 or 7) topical corticosteroids 
for the palms, soles, face, and intertriginous areas only; tar and salicylic acid 
preparations for the scalp only, and shampoos free of corticosteroids for the scalp 
only. Refer to Table 6 for details regarding Permitted Concomitant Topical Psoriasis 
Treatments.

UVB (narrowband or broadband) phototherapy.
4.2. Exclusion Criteria
Subjects with any of the following characteristics/conditions will not be included in the 
study:
1. Currently have non-plaque forms of psoriasis, eg, erythrodermic, guttate, or pustular 
psoriasis, with the exception of nail psoriasis which is allowed.
2. Have evidence of skin conditions (eg, eczema) at the time of screening or baseline 
visit that would interfere with the evaluation of psoriasis.
3. Have current drug-induced psoriasis, eg, a new onset of psoriasis or an exacerbation 
of psoriasis from beta blockers, calcium channel blockers, antimalariala drugs or 
lithium.
4. If planned initiation of, or changes to, concomitant medication that could affect 
psoriasis (eg, beta blockers, calcium channel blockers, antimalarial drugs or lithium) 
are to occur within 2 weeks prior to randomization and/or during the study.
5. Cannot discontinue systemic therapies and/or topical therapies for the treatment of 
psoriasis and cannot discontinue phototherapy (UVB or PUVA).
6. Are taking or require oral or injectable (eg, intraarticular, intramuscular or 
intravenous) corticosteroids for any condition.
7. Any psychiatric condition including recent or active suicidal ideation or behavior that 
meets any of the following criteria:

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) (Appendix 5).


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
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. 

Suicidal behaviors questionnaire –revised (SBQ-R) (Appendix 6) total score 8.

Clinically significant depression: patient health questionnaire – 8 items (PHQ-8) 
(Appendix 7) when the total score 15.

The presence of any current major psychiatric disorder that is not explicitly 
permitted in the inclusion/exclusion criteria. 

In the opinion of the investigator or Pfizer (or designee) exclusion is required.
8. Subjects 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);

Absolute neutrophil count of <2.5 x 109/L (<2500/mm3);

Platelet count <100 x 109/L (<100,000/mm3);

Serum creatinine level above the upper limit of normal (ULN) at Screening or an 
Estimated creatinine clearance Filtration Rate (GFR) value 80 mL/min based on 
the Cockcroft-Gault calculation at Screening (Appendix 2, Cockcroft-Gault 
equation);

Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) values 
greater than 2 times the upper limit of normal (ULN);

Any uncontrolled clinically significant laboratory abnormality that would affect 
interpretation of study data or the subject’s participation in the study.
9. Pregnant female subjects; breastfeeding female subjects; fertile male subjects and 
female subjects of childbearing potential who are unwilling or unable to use 2 highly 
effective methods of contraception as outlined in this protocol for the duration of the 
study and for at least 28 days after the last dose of investigational product. 
10. Have current or recent history of severe, progressive, or uncontrolled renal, hepatic, 
hematological, gastrointestinal, metabolic, endocrine, pulmonary, cardiovascular, or 
neurological disease.


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11. Have 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.
12. Have a history (single episode) of disseminated herpes zoster or disseminated herpes 
simplex, or a recurrent (more than one episode of) localized, dermatomal herpes 
zoster.
13. Have a history of infection requiring hospitalization, parenteral antimicrobial therapy, 
or as otherwise judged clinically significant by the investigator within 6 months prior 
to first dose of study drug.
14. Have a history of infection requiring oral antimicrobial therapy within 2 weeks prior 
to first dose of study drug.
15. Infected with Mycobacterium tuberculosis (TB) as defined by the following:
a.
A positive Interferon Gamma Release Assay (IGRA) test performed at or within 
the 12 weeks prior to Day 1 is exclusionary; a negative test is required for 
eligibility.  The following are acceptable IGRA assays: QuantiFERON- TB 
Gold test (QFT-G), QuantiFERON- TB Gold In-Tube test (QFT-GIT) and 
T-SPOT.

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.

Subjects with repeat indeterminate IGRA results may be enrolled after 
consultation with pulmonary or infectious disease specialist that determines 
low risk of infection (ie, subject would be acceptable for immunosuppressant 
treatment without additional action).

Subjects who test positive for QFT-G/ QFT-GIT test, but in the opinion of the 
Investigator are at low risk of TB infection may be referred to pulmonary or 
infectious disease specialist for consultation and potential IGRA test repeated 
once. Subjects will be eligible if the repeat test is negative before the 
randomization.
b. Chest radiograph taken at screening with changes suggestive of active TB 
infection, unless previously performed normal and documented chest radiograph 
within 12 weeks prior to Day 1.
c.
A history of either untreated or inadequately treated latent or active TB infection.
d. A subject who has been treated or is currently being treated for active or latent TB 
infection is to be excluded.


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16. Have been vaccinated with live or attenuated live vaccine within the 6 weeks prior to 
the first dose of study drug, or expects to be vaccinated with these vaccines during 
treatment, or within the 8 weeks following the last dose of study drug.  (For further 
information regarding avoidance of household contacts who may be vaccinated see 
Section 5.8.4).
17. Any cell-depleting agents including but not limited to rituximab within 6 months of 
first dose of study drug or 5 half-lives (if known), whichever is longer, or until 
lymphocyte count returns to normal, whichever is longer.
18. Any prior treatment with non B cell-specific lymphocyte depleting agents/therapies 
(eg, alemtuzumab [CamPath], alkylating agents [eg, cyclophosphamide or 
chlorambucil], total lymphoid irradiation, etc); subjects who have received rituximab 
or other selective B-lymphocyte depleting agents (including experimental agents) 
within 6 months of first dose of study drug or 5 half-lives (if known), whichever is 
longer, or until lymphocyte count returns to normal, whichever is longer.
19. Have previously been treated with efalizumab (Raptiva).
20. Have previously been treated with secukinumab (Cosentyx) or Ixekizumab (Taltz).
21. Have undergone treatment with tofacitinib within 3 months of first dose.
22. Have undergone treatment with apremilast (Otezla) within 3 months of first dose.
23. Have any condition possibly affecting oral drug absorption, eg, gastrectomy, 
clinically significant diabetic gastroenteropathy, or certain types of bariatric surgery 
such as gastric bypass.  Procedures such as gastric banding, that simply divide the 
stomach into separate chambers, are NOT exclusionary.
24. Have a history of alcohol or substance abuse, unless in full remission for greater than 
6 months prior to first dose of study drug.
25. Have a Screening or Baseline/Day 1 12-lead ECG that demonstrates clinically 
relevant abnormalities which may affect subject safety or interpretation of study 
results.
26. Have a known immunodeficiency disorder or a first-degree relative with a hereditary 
immunodeficiency.
27. 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.
28. Any medical history of disease [ie, Gilbert’s disease] that has the potential to cause a 
rise in total bilirubin over the upper limit of normal (ULN).  Subjects with borderline 


PF-06700841
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clinical laboratory values outside the reference range may be included in the study if 
the Investigator deems that the values are not clinically significant.
29. Have undergone significant trauma or major surgery within 1 month prior to 
Screening.
30. Require treatment with prohibited concomitant medications(s) (see Appendix 4) 
including prohibited dietary supplements (see Section 5.8.3) or have received a 
prohibited concomitant medication/dietary supplement within 7 days or 5 half-lives 
(whichever is longer) prior to the first dose of study drug.  Note: amiodarone requires 
discontinuation at least 290 days (~5 half-lives) prior to the first dose of study drug.
31. Infected with hepatitis B or hepatitis C viruses; for Hepatitis B, all subjects will 
undergo testing for Hepatitis B Surface Antigen (HBsAg) and Hepatitis B Core 
Antibody (HVcAB).  Subjects who are HBsAg positive are not eligible for the study.  
Subjects who are HBsAg negative and HBcAb positive will 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 subject is not eligible for the study.  Subjects who 
are HCV Ab positive require further testing with HCV RNA PCR.  Subjects with 
false positive anti-HBc may be enrolled based upon consultation with hepatologist 
confirming no infection with hepatitis B.
32. Participation in other studies using an investigational or experimental therapy or 
procedure within 4 weeks or 5 half-lives (whichever is longer) before the study 
begins and/or during study participation.  Exception: any investigational or 
experimental therapy or procedure for psoriasis, psoriatic arthritis or rheumatoid 
arthritis must be discontinued for at least 12 weeks prior to first dose of study drug.  
Exposure to investigational biologics should be discussed with the Pfizer Medical 
Monitor (or designee).  Subjects cannot participate in studies of other investigational 
or experimental therapies or procedures at any time during their participation in this 
study.
33. Other acute or chronic medical or psychiatric condition or laboratory abnormality that 
may increase the risk associated with study participation or investigational product 
administration or may interfere with the interpretation of study results and, in the 
judgment of the investigator, would make the subject inappropriate for entry into this 
study.
34. 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 
subjects who are Pfizer employees, including their family members, directly involved 
in the conduct of the study.
35. Refrain from consumption of grapefruit or grapefruit juice or citrus fruits eg, Seville 
oranges, pomelos within 7 days prior to the first dose of study medication until 
collection of the final pharmacokinetic blood sample.


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36. Subjects who received or are likely to receive during the study any moderate-strong 
inhibitors eg, itraconazole, erythromycin, ketoconazole, protease inhibitors, verapamil 
or diltiazem or inducers eg rifampin of CYP3A4.
4.3. Lifestyle Requirements
In order to participate in the study, subjects must be made aware of the following life style 
guidelines and restrictions that apply during and after the study period.  Details of these life 
style guidelines are provided in sections as noted.

On appropriate study visit days, comply with fasting requirement (water only) for at 
least 8 hours prior to the visit, as indicated in the Schedule of Activities.

On study visit days, do not smoke or ingest caffeine (eg, tea, coffee, some soft 
drinks/colas/energy drinks and power bars) during the 30 minutes prior to blood 
pressure and pulse (heart) rate measurements.

On study visit days, do not take the morning dose of study drug until instructed to do 
so by the investigator or designated study site staff.

On study visit days, showering or bathing is permitted prior to attending the study 
visit, but do not moisturize.

On study visit days, take prescribed permitted concomitant medication, as needed, 
prior to the study visit, if it can be administered with water only.  Prescribed 
permitted concomitant medications that must be taken with food or after meals should 
not be taken until after the visit procedures have been completed.

Discontinue and avoid using certain medications and treatments (see Inclusion 
Criteria and list of prohibited concomitant medications in Section 4.1, Section 5.8.2
and Appendix 4).

Contact the study site investigator if there are any changes or additions to 
concomitant medications.

Refrain from consumption of grapefruit or grapefruit juice or citrus fruits eg, Seville 
oranges, pomelos within 7 days prior to the first dose of study medication until 
collection of the final pharmacokinetic blood sample.

Avoid having elective surgery.

Agree to use proper contraceptive methods (See Section 4.3.1).

As needed, subjects may use the treatments listed as permitted in Section 5.8 for the 
specified body sites described. On clinic visit days, do not use any of these 
treatments until after the clinic visit is completed.


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4.3.1. Contraception
In this study, fertile male subjects and female subjects who are of childbearing potential as 
applicable to the study will receive PF-06700841, which has been associated with
demonstrated teratogenicity/fetotoxicity in animals. Subjects who are, in the opinion of the 
investigator, sexually active and at risk for pregnancy with their partner(s) must agree to use
2 methods of highly effective contraception throughout the study and for at least 28 days
after the last dose of investigational product.  The investigator or his or her designee, in 
consultation with the subject, will confirm that the subject has selected 2 appropriate methods 
of contraception for the individual subject and his/her partner(s) from the list of permitted 
contraception methods (see below) and will confirm that the subject has been instructed in 
their consistent and correct use.  At time points indicated in the Schedule of Activities, the 
investigator or designee will inform the subject of the need to use 2 highly effective methods 
of contraception consistently and correctly and document the conversation, and the subject’s 
affirmation, in the subject’s chart.  In addition, the investigator or designee will instruct the 
subject to call immediately if 1 or both of the selected contraception methods is discontinued 
or if pregnancy is known or suspected in the subject or partner.
Highly effective methods of contraception are those that, alone or in combination, result in a 
failure rate of less than 1% per year when used consistently and correctly (ie, perfect use) and 
include the following:
1. Established use of hormonal methods of contraception associated with inhibition of 
ovulation (eg, oral, inserted, injected, implanted, transdermal), provided the subject or 
male subject’s female partner plans to remain on the same treatment throughout the 
entire study and has been using that hormonal contraceptive for an adequate period of 
time to ensure effectiveness.
2. Correctly placed copper-containing intrauterine device (IUD).
3. Male condom or female condom used WITH a separate spermicide product (ie, foam, 
gel, film, cream, or suppository). For countries where spermicide is not available or 
condom plus spermicide is not accepted as highly effective contraception, this option 
is not appropriate.
4. Male sterilization with absence of sperm in the postvasectomy ejaculate.
5. Bilateral tubal ligation/bilateral salpingectomy or bilateral tubal occlusive procedure 
(provided that occlusion has been confirmed in accordance with the device’s label).
All sexually active male subjects must agree to prevent potential transfer to and exposure of 
partner(s) to drug through ejaculate by using a condom consistently and correctly, beginning 
with the first dose of investigational product and continuing for at least 28 days after the last 
dose of investigational product.


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4.4. 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 Binder.
To facilitate access to appropriately qualified medical personnel on study-related medical 
questions or problems, subjects are provided with a contact card. The contact card contains, 
at a minimum, protocol and investigational product identifiers, subject study 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 
subject’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 subject directly, and if a subject calls that number, he 
or she will be directed back to the investigator site.
5. STUDY TREATMENTS
For the purposes of this study, and per International Conference on Harmonisation (ICH)
guidelines, investigational product is defined as a pharmaceutical form of an active 
ingredient or placebo being tested or used as a reference/comparator in a clinical trial, 
including a product with a marketing authorization when used or assembled (formulated or 
packaged) in a way different from the approved form, or when used for an unapproved 
indication, or when used to gain further information about an approved use (ICH E6 1.33).
For this study, the investigational product is PF-06700841. The designation PF-0670841-15 
indicates a salt of the drug substance.  References to either PF-06700841 or PF-0670841-15 
indicate the same biological entity.
5.1. Allocation to Treatment
Allocation of subjects to treatment groups will proceed through the use of an interactive 
response technology (IRT) system (interactive Web-based response [IWR]).  The site 
personnel (study coordinator or specified designee) will be required to enter or select 
information including but not limited to the user’s identification (ID) and password, the 
protocol number, and the subject number. The site personnel will then be provided with a 
treatment assignment, randomization number, and dispensable unit (DU) or container number 
when investigational product is being supplied via the IRT system.  The IRT system will 
provide a confirmation report containing the subject 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 will provide the contact information and further 
details on the use of the IRT system.


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5.2. Breaking the Blind
At the initiation of the study, the investigator site will be instructed on the method for 
breaking the blind.  The method will be an electronic process.  Blinding codes should be 
broken only in exceptional circumstances when knowledge of the actual treatment code is 
absolutely essential for further management of the subject. Investigators are encouraged to 
discuss with a member of the study team if they believe that unblinding is necessary. When 
the blinding code is broken, the reason must be fully documented and entered on the case 
report form (CRF).
5.3. Subject Compliance
For self-administration of PF-06700841-15 tablets at home, compliance will be captured and 
completed by the subject on a dosing diary.  Subject compliance will be verified by the 
accounting of investigational product at each visit. When investigational product is 
administered at the research facility, it will be administered under the supervision of study 
personnel.
5.4. Investigational Product Supplies
5.4.1. Dosage Form(s) and Packaging
Blinded PF-06700841-15 tablets and matching placebo will be provided as tablets for oral 
administration.  The PF-06700841-15, 5 mg and 25 mg tablets and their matching placebos 
will be supplied in blisters and labeled according to local regulatory requirements.
5.4.2. Preparation and Dispensing
The investigational product will be dispensed using an IRT drug management system at each 
visit from Week 0 to Week 10. A qualified staff member will dispense the investigational 
product via unique container numbers in the blister cards provided, in quantities appropriate 
for the study visit schedule. The subject/caregiver should be instructed to maintain the 
product in the bottle (or blister cards, as appropriate) provided throughout the course of 
dosing and return the bottle (or blister cards, as appropriate) to the site at the next study visit.
5.5. Administration
Subjects will receive investigational product (IP) as outpatients.  PF-06700841-15 tablets and 
matching placebo for oral administration will be dispensed in blisters.  Subjects will be 
provided dosing instructions.
All subjects, regardless of assigned treatment regimen (ie, QD or QW) will receive blinded 
QD dosing throughout the study treatment period to maintain the study blind.
Sites will be trained on how subjects should take tablets at home through an IP manual and/or 
other vehicle(s).  Sites are responsible for communicating this information.
Subjects should take the medication orally for 12 weeks from study Days 1 to 85 during the 
trial; Subjects should swallow the tablets with ambient temperature water to a total volume of 
approximately 240 mL; Subjects will swallow the investigational product whole, and will not 


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manipulate or chew the medication prior to swallowing; IP may be taken with or without 
food; however, for study visit days, subjects are to be instructed to refrain from dosing at 
home, and are to take the dose in the clinic from their previous blister card and dose from the 
newly dispensed blister card on the next day at home.
If a dose is missed and the interval to the next dose is less than 8 hours, the missed dose 
should not be administered.
5.6. Investigational Product Storage
The investigator or an approved representative, eg, pharmacist, will ensure that all 
investigational products are stored in a secured area with controlled access under required 
storage conditions and in accordance with applicable regulatory requirements.
Investigational products should be stored in their original containers and in accordance with 
the labels.
Any storage conditions stated in the SRSD will be superseded by the storage conditions 
stated on the product label.
Site systems must be capable of measuring and documenting (for example, via a log), at a 
minimum, daily minimum and maximum temperatures for all site storage locations (as 
applicable, including frozen, refrigerated, and/or room-temperature products).  This should 
be captured from the time of investigational product receipt throughout the study.  Even for 
continuous-monitoring systems, a log or site procedure that ensures active evaluation for 
excursions should be available.  The intent is to ensure that the minimum and maximum 
temperature is checked each business day to confirm that no excursion occurred since the last 
evaluation and to provide the site with the capability to store or view the minimum/maximum 
temperature for all non-working days upon return to normal operations.  The operation of the 
temperature monitoring device and storage unit (for example, refrigerator), as applicable, 
should be regularly inspected to ensure they are maintained in working order.
Any excursions from the product label storage conditions should be reported to Pfizer upon 
discovery.  The site should actively pursue options for returning the product to the storage 
conditions described in the labeling, as soon as possible.  Deviations from the storage 
requirements, including any actions taken, must be documented and reported to Pfizer.
Once an excursion is identified, the investigational product must be quarantined and not used 
until Pfizer provides permission to use the investigational product.  It will not be considered a 
protocol deviation if Pfizer approves the use of the investigational product after the 
temperature excursion. Use of the investigational product prior to Pfizer approval will be 
considered a protocol deviation. Specific details regarding information the site should report 
for each excursion will be provided to the site.
Receipt of materials, door opening and closing, and other routine handling operations where 
the products are briefly out of the temperature range described in the labeling are not 
considered excursions.


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Site staff will instruct subjects on the proper storage requirements for take home 
investigational products.
5.7. Investigational Product Accountability 
Drug Accountability procedures are to be performed at Weeks 1, 2, 4, 6, 8, 10, 12, and at the 
end of treatment Early Termination visit.
The investigator site must maintain adequate records documenting the receipt, use, loss, or 
other disposition of the investigational product supplies.  All investigational products will be 
accounted for using a drug accountability form/record.
Subjects must be instructed to return all blister cards of study drug (and any unused study 
drug) to the investigator at every visit and at the end of the trial.
5.7.1. Destruction of Investigational Product Supplies
The sponsor or designee will provide guidance on the destruction of unused investigational 
product (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.
5.8. Concomitant Treatment(s)
5.8.1. Permitted Concomitant Medication
Concomitant psoriasis therapies are not permitted during the study, with the exception of:
Table 6.
Permitted Topical Concomitant Psoriasis Treatments
Body Region
Permitted Topical Treatments
Palms, soles, face, and intertriginous 
areas
Low or least potent (Class 6 or 7) topical corticosteroids
Hydrocortisone 1% and hydrocortisone acetate 1% are the 
only topical corticosteroids permitted
Scalp
Tar preparations
Salicylic acid preparations
Shampoos free of corticosteroids
All body regions
Study supplied non-medicated emollient, Cetaphil
moisturizing cream
5.8.2. Prohibited Concomitant Medications
The following hydrocortisones are NOT permitted:

Hydrocortisone 17 butyrate.

Hydrocortisone valerate.

Hydrocortisone/hydrocortisone acetate with concentration higher than 1%.


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Subjects will abstain from all concomitant medications as described in the Inclusion and
Exclusion sections of the protocol and Appendix 4 Prohibited Concomitant Medications.
Subjects should be instructed at each visit to contact the study site investigator promptly if 
there are any intended changes or additions to concomitant medications.
It is recommended that subjects avoid changing other prescription or non-prescription drugs, 
vitamins, and dietary supplements within 7 days or 5 half-lives (whichever is longer) prior to 
the first dose of study medication and throughout the study.
All concomitant medication taken during the study must be recorded with indication, daily 
dose, and start and stop dates of administration.
A subject who is receiving digoxin or metformin as concomitant medication must allow at 
least two hours after taking either medication and before taking study medication.
Medications taken after informed consent is obtained (but before the first dose of study 
medication) will be documented as prior medications.  Medications taken after the first dose 
of study drug has been administered will be documented as concomitant medications.
5.8.3. 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 the first dose of 
investigational product.
5.8.4. Vaccinations
Vaccination with live virus, attenuated live virus, or any live viral components is prohibited 
within the 6 weeks prior to the first dose of study drug, during the study, and for 8 weeks
after the last dose of study medication.  Similarly, current routine household contact with 
individuals who have been vaccinated with live vaccine components should be avoided 
during treatment and for 8 weeks following completion of treatment.
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.  Following vaccination 
with live component vaccines, the virus may be shed in bodily fluids, including stool, and 
there is a potential risk that the virus may be transmitted.


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5.9. Rescue/Escape Medication
Permitted Topical Concomitant Psoriasis Treatments can be found in Section 5.8.1.
6. STUDY PROCEDURES
6.1. Screening
For screening procedures, see Schedule of Activities and ASSESSMENTS section.
6.2. Treatment Period
For treatment period procedures, see Schedule of Activities and ASSESSMENTS section.
6.3. Follow-up/End of study Procedures
For follow-up and end of study procedures, see Schedule of Activities and ASSESSMENTS
section.
6.4. Subject Withdrawal/Early Termination
Subjects may withdraw from the study at any time at their own request, or they may be 
withdrawn at any time at the discretion of the investigator or sponsor for safety (see also the 
Withdrawal From the Study Due to Adverse Events section) or behavioral reasons, or the 
inability of the subject to comply with the protocol-required schedule of study visits or 
procedures at a given study site (see Schedule of Activities for procedures to be followed at 
the Early Withdrawal Visit).
Subjects who withdraw from the study may be replaced at the discretion of the investigator 
upon consultation with the sponsor.
For subjects who discontinue early from the double-blind treatment period prior to the 
Week 12 visit, the procedures scheduled for Week 12 will be performed on the last day the 
subject takes the investigational product or as soon as possible thereafter.  For subjects who 
discontinue early from the follow up period prior to the Week 16 visit, the procedures 
scheduled for Week 16 will be performed at the Early Termination visit. 
See Appendix 3 for Guidelines for Safety Monitoring and Discontinuations.
6.4.1. Withdrawal of Consent
If the subject withdraws from the study, and also withdraws consent 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.
Subjects 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 
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detail in the medical records by the investigator, as to whether the withdrawal is only from 
further receipt of investigational product or also from study procedures and/or post-treatment 
study follow-up, and entered on the appropriate CRF page. In the event that vital status 
(whether the subject 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.
6.4.2. Lost to follow-up
All reasonable efforts must be made to locate subjects to determine and report their ongoing
status. This includes follow-up with persons authorized by the subject as noted below. Lost 
to follow-up is defined by the inability to reach the subject after a minimum of 2 documented 
phone calls, faxes, or e-mails as well as lack of response by the subject to 1 registered mail 
letter.
All attempts should be documented in the subject’s medical records. If it is determined that 
the subject has died, the site will use locally permissible methods to obtain the date and cause 
of death. If the investigator’s use of a third-party representative to assist in the follow-up 
portion of the study has been included in the subject’s informed consent, then the investigator 
may use a sponsor-retained third-party representative to assist site staff with obtaining the 
subject’s contact information or other public vital status data necessary to complete the 
follow-up portion of the study. The site staff and representative will consult publicly 
available sources, such as public health registries and databases, in order to obtain updated 
contact information. If, after all attempts, the subject remains lost to follow-up, then the 
last-known-alive date as determined by the investigator should be reported and documented 
in the subject’s medical records.
If a subject does not return for a scheduled visit, every effort should be made to contact the 
subject.  All attempts to contact the subject and information received during contact attempts 
must be documented in the subject’s medical record).  In any circumstance, every effort 
should be made to document subject outcome, if possible.  The investigator should inquire 
about the reason for withdrawal, request that the subject return all unused investigational 
product(s), request that the subject return for a final visit, if applicable, and follow up with 
the subject regarding any unresolved adverse events (AEs).
7. ASSESSMENTS
Every effort should be made to ensure that the protocol-required tests and procedures are 
completed as described. However, it is anticipated that from time to time there may be 
circumstances outside of the control of the investigator that may make it unfeasible to 
perform the test. In these cases the investigator will take all steps necessary to ensure the 
safety and well-being of the subject. When a protocol-required test cannot be performed, the 
investigator will document the reason for this and any corrective and preventive actions that 
he or she has taken to ensure that normal processes are adhered to as soon as possible. The 
study team will be informed of these incidents in a timely manner.


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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.
7.1. Safety Assessments
Standard safety assessments include physical examination, vital signs, 12-lead 
electrocardiogram (ECG), clinical laboratory evaluations (full and abbreviated chemistry 
panel), lipid panel, and urinalysis.  Subject safety monitoring and discontinuation guidelines 
are provided in Appendix 3.
7.1.1. Laboratory
The following safety laboratory tests will be performed at times defined in the Schedule of 
Activities.
Laboratory Tests
Hematology
Chemistry
Urinalysisj
Other
Hemoglobin
Hematocrit
RBC count
Platelet count
WBC count
Total neutrophils 
(Abs)
Eosinophils (Abs)
Monocytes (Abs)
Basophils (Abs)
Lymphocytes (Abs)
Reticulocytes (Abs)
PT/INR/PTT
BUN/Urea and 
Creatinine
Cystatin Ca
Glucose 
Calcium
Sodium
Potassium
Chloride
AST, ALT
Total Bilirubin
Direct bilirubinb
Alkaline phosphatase
Uric acid
Albumin
Total protein
Creatine kinase (CK)
CK fractionationc
Total Cholesterold
Triglyceridesd
HDLd
LDLd
pH
Glucose (qual)
Protein (qual)
Blood (qual)
Ketones
Nitrites
Leukocyte esterase
Microscopye
FSHf,g
β-hCGh
Hepatitis B, C and HIVg
QFT-G or other IGRAg
hsCRP
IP-10
 
 
 
 
 
 
 
 
  
CCI
CCI
CCI
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a.
At baseline, end of study, and when creatinine is elevated above ULN.
b.
Only if total bilirubin is elevated. 
c.
Only if CK is elevated.
d.
Fasting (water only), 8 hours prior to collection.
e.
Only if urine dipstick is positive for blood, protein, nitrites or leukocyte esterase.  Urine culture is 
performed if urinalysis is positivie for nitrite and/or leukocyte esterase or if clinically indicated.
f.
In females who are amenorrheic for at least 12 consecutive months. 
g.
Complete at screening.
h.
If serum pregnancy test is borderline positive, the central lab will run a FSH test to confirm menopause, 
assuming other menopause criteria are met per protocol eligibility requirements.
j.
Dipstick in all cases.
7.1.2. Pregnancy Testing
All pregnancy tests used in this study, either urine or serum, must have a sensitivity of at 
least 25 mIU/mL and must be performed by a certified laboratory.  For female subjects of 
childbearing potential, 2 negative pregnancy tests are required before receiving 
investigational product/study treatment(s) (1 negative serum pregnancy test at screening and 
1 at the baseline visit immediately before investigational product/study treatment 
administration).  Following a negative pregnancy test result at screening, appropriate 
contraception must be commenced and the second negative pregnancy test result will then be 
required at the baseline visit and within 5 days after the first day of the menstrual period 
(counting the first day of the menstrual period as Day 1) before the subject may receive the 
investigational product/study treatment.  In the absence of regular menstrual bleeding, the 
study candidate should have used 2 forms of contraception for at least 1 month before the 
second pregnancy test.  Pregnancy tests will also be repeated at every visit and at the end of 
the study to confirm that the subject has not become pregnant during the study.  Pregnancy 
tests will also be done whenever 1 menstrual cycle is missed during the active treatment 
period and when potential pregnancy is otherwise suspected, and may be repeated if 
requested by institutional review boards (IRBs)/ethics committees (ECs) or if required by 
local regulations.  In the case of a positive confirmed pregnancy, the subject will be 
withdrawn from administration of investigational product and from the study.
7.1.3. Serum Creatinine and Serum Cystatin-C
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.  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.16
Cystatin C is a low molecular weight protein that is used as an alternative to serum creatinine 
for monitoring of renal function.  It seems to correlate more closely with GFR than does 
serum creatinine concentration and may be a more sensitive detector of early renal 
dysfunction.17,18 While use of cystatin C has been limited, its independence of demographic 
factors (eg, race) has made it an interesting means of determining changes in renal function 
C
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in clinical settings and it is included in the 2012 Kidney Disease: Improving Global 
Outcomes (KDIGO) guidelines.  Estimated GFR may be calculated via the 2012 CKD-EPI 
creatinine, cystatin C, or creatinine-Cystatin C equations.19
Serum creatinine will be measured as part of serum chemistry at times specified in the 
Schedule of Activities section of the protocol. Serum creatinine based eGFR will be 
calculated.  Serum cystatin C and cystatin C based eGFR will be measured at baseline and 
end of treatment (EOT).  An increase in serum creatinine above the upper limit of normal 
(ULN) as defined by the laboratory reference range should trigger a reflex test for serum 
cystatin-C in order to facilitate both cystatin C based and serum creatinine based eGFR 
calculations.
7.1.4. Estimated Glomerular Filtration Rate
Serum creatinine and serum cystatin-C based estimated GFR (eGFR) will be calculated at 
baseline and end of study treatment period for all subjects, in order to facilitate calculation of 
eGFR at these time points.  When cystatin-C reflex testing is performed, corresponding 
serum creatinine and cystatin-C based eGFR will be determined to assess renal function.
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.20
7.1.5. Interferon Gamma Release Assay Tuberculin Test
Subjects may be screened for TB using an IGRA per local guidelines.  Interferon gamma 
release assay will be tested during screening or within 12 weeks prior to Day 1.  The 
following are acceptable IGRA assays: 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.  Ensure 
incubation steps are followed as appropriate.
An IGRA is preferred for subjects with a prior Bacillus Calmette-Guerin (BCG) vaccination, 
but may be used for any subject.  Documentation of IGRA product used and the test result 
must be in the subject’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.
Subjects with repeat indeterminate IGRA results may be enrolled after consultation with 
pulmonary or infectious disease specialist that determines low risk of infection (ie, subject 
would be acceptable for immunosuppressant (eg, anti-TNF) treatment without additional 
action).
Subjects 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. Subjects will be eligible if the repeat test 
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Refer to lab manual for any additional processing information and shipping instructions.
7.1.6. Herpetiform Skin Rash Surveillance 
For any occurrence of a suspected herpetiform rash (eg, herpes zoster and herpes simplex), 
additional specimens for viral DNA analysis will be obtained for confirmation. 
 
 
 
Details for these collections will be 
provided in the laboratory manual.
7.1.7. Medical History, Physical Examination, Height and Weight
Medical history will be collected at the Screening visit and will include history of drug, 
alcohol and tobacco use.  Medical history also includes collection of details on (i) Family 
history of diabetes mellitus, hypertension, and premature coronary heart disease (CHD), 
where premature CHD is defined as (a) CHD in a male first degree relative <55 years of age, 
or (b) CHD in a female first degree relative <65 years of age, (ii) Any prior rheumatologist 
confirmed diagnosis of psoriatic arthritis or rheumatoid arthritis, (iii) Any prior diagnosis of 
dry eye disease/syndrome, and (iv) Any previous history of liver biopsy.  Smoking status and 
average weekly alcohol consumption (units/week) will also be collected, where a unit 
contains 12 g of pure alcohol, an amount equivalent to that contained in 5 oz (a glass) of 
wine, 12 oz of beer, or 1.5 oz of 90 proof of spirits.
Complete physical examinations must be performed by the investigator, sub-investigator, or 
a qualified healthcare professional per local guidelines.  A complete physical examination 
will include general appearance, skin, head, eyes, ears, nose and throat (HEENT), heart, 
lungs, breast (optional), abdomen, external genitalia (optional), extremities, neurologic 
function, back, and lymph nodes.
Targeted physical examinations must be performed by the investigator, sub-investigator, or a 
qualified healthcare professional per local guidelines. Targeted physical examination 
consists of skin, heart, lungs, abdomen, and examination of body systems where there are 
symptom complaints by the subject.
Complete and Targeted physical examinations are performed at specified time points (see 
Schedule of Activities).
Height and weight will be measured without the subject wearing shoes.  Height (inches or 
centimeters) will be measured and recorded at the Screening visit only and weight (lbs or kg) 
will be measured and recorded at various time points (see Schedule of Activities).
7.1.8. Vital Sign Measurements (Blood pressure, pulse rate, and temperature)
Single sitting blood pressure (BP), pulse rate, and temperature will be measured at times 
specified in the Schedule of Activities.  Additional collection times or changes to collection 
times will be permitted, as necessary to ensure appropriate collection of safety data.
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Vital signs should be performed before laboratory blood collection. 
Sitting blood pressure will be measured with the subject’s arm supported at the level of the 
heart, and recorded to the nearest mm Hg.  It is preferred that the same arm (preferably the 
dominant arm) be used throughout the study.
The same size BP cuff, which has been properly sized and calibrated, will be used to measure 
BP each time.  The use of automated devices for measuring BP and pulse rate is acceptable, 
although, when done manually, pulse rate will be measured in the brachial/radial artery for at 
least 30 seconds.  When the timing of these measurements coincides with a blood collection, 
it is preferred that vital signs be obtained prior to the nominal time of blood collection.
It is preferred that body temperature be collected using tympanic, oral, or axillary methods 
and that the same method be used consistently throughout the study.
7.1.9. Electrocardiogram
Twelve (12) lead ECGs should be collected at times specified in the Schedule of Activities.
ECGs should be performed before laboratory blood collection.
All scheduled ECGs should be performed after the subject has rested quietly for at least 
5 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.
To ensure safety of the subjects, a qualified individual (eg, sub-investigator) at the 
investigator site will make comparisons to baseline measurements taken at screening.  A 
copy of the ECG should be available as source documents for review.  ECGs will be read 
locally during the dosing period. 
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 are placed in the 
same positions each time in order to achieve precise ECG recordings.  If a machine-read QTc 
value is prolonged, repeat measurements may not be necessary if a qualified physician’s 
interpretation determines that the QTc values are in the acceptable range.
7.1.10. Chest Radiograph
Chest x-ray (posterior-anterior and lateral views are recommended however local guidelines 
should be followed) or other appropriate diagnostic image (ie, computed tomography [CT] or 
magnetic resonance imaging [MRI]) with no current evidence of untreated latent or active 
TB infection or evidence of currently active TB, general infections, heart failure or 
malignancy taken at screening or within the 12 weeks prior to Day 1 and read by a qualified 
radiologist.  Documentation of the official reading must be located and available in the 
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7.1.11. Subject Diary
Subjects will be provided with a diary to record their daily dosing for all 12 weeks of 
treatment.  
 
7.2. Efficacy Assessments
Measures of psoriasis efficacy that will be collected throughout the study are outlined in this 
section.  These efficacy measures will be evaluated by an experienced physician, 
dermatologist, or qualified medical professional.  Detailed descriptions for the Physician 
Global Assessment, 
, and 
are 
provided in the Appendices.
7.2.1. Psoriasis Area and 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%.
Calculating PASI
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.21
PASI =
0.1Ah(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.  The PASI score will be used for the primary 
analysis.
Calculation of PASI will be done centrally by Sponsor programmers.
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7.2.2. Linear Method Psoriasis Area and Severity Index (L PASI)
A second method of calculating PASI will also be performed.  A linear scaling method will 
be applied to the Psoriasis Area and Severity Index calculation, adapting the classic 
calculation by using the actual percentage body surface area involved in psoriasis rather than 
categorizing the percentage involvement on a 7 point scale. 
The linear scaling method will be calculated from the study database; investigator sites will 
only perform the classic PASI calculation during the study.  The L PASI score will be used 
for a sensitivity analysis.
L-PASI Calculation
L-PASI =
0.1(6xBh)x(Eh + Ih + Sh) + 0.2(6Bu)x(Eu + Iu + Su) +
0.3(6xBt)x(Et + It + St) + 0.4(6xBl)x(El + Il + Sl)
where B = percentage area of involvement; E = erythema; I =induration; S = scaling; h = head; u = upper 
limbs; t = trunk; l = lower limbs
7.2.3. Physician Global Assessment (PGA)
The Physician Global Assessment of psoriasis is scored on a 5-point scale, reflecting a global 
consideration of the erythema, induration and scaling across all psoriatic lesions.  Average 
erythema, induration and scaling are rated separately over the whole body according to a
5-point severity scale, scored from 0 to 4, with appropriate morphologic descriptors.  The 
severity rating scores are summed and the average taken – the total average is rounded to the 
nearest whole number score to determine the PGA (See Appendix 8).
The 5-point scale for PGA is: 0, “clear”; 1, “almost clear”; 2, “mild”; 3, “moderate”; 
4 “severe”.
7.2.4. 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 BSA22 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.

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The extent (%) to which each of the four areas of the body is affected is captured on the CRF 
(to 2 decimal places, as necessary).  A weighting factor is applied to each of the four areas in 
calculation of the total body surface area affected: head x0.1; upper limbs x0.2; trunk x0.3; 
lower limbs x0.4, as the four areas correspond to approximately 10%, 20%, 30% and 40% of 
the total BSA, respectively.22  The sum of the weighted percent involvement obtained for 
each of the four body areas is the overall psoriatic BSA.
7.2.5. Target Lesion and Regional Photography (at select study centers)
Standardized digital photographs of target lesions and surrounding region photography will 
be taken at selected study sites using a professional quality digital camera.  These 
photographs are for illustrative purposes only.
Regional Photography: Regional photographs of each target lesion and surrounding area 
will also be taken at select study centers.  Once the camera/lens is set at the appropriate 
magnification, proper focusing technique will help ensure that photographs are all taken from 
the same set distance from the camera.  Photographs will be taken in duplicate with lighting, 
framing, and exposure held constant.
Digital study images will be captured on memory cards.  The contents of those cards will be 
uploaded to Canfield Scientific, Inc. using Canfield’s secure, compliant website.  All study 
images received will be monitored and archived in a fully validated, 21 Code of Federal 
Regulations (CFR) Part 11 Food and Drug Administration (FDA) compliant system.  A copy 
of each subject's Week 0 photographs will be provided to the investigational sites for the 
subject file in order to confirm the location/field of view to be photographed at the end of 
treatment.  Photography will be performed at Week 0, Week 4, Week 12/Early Termination, 
and follow-up visit Week 16/ Early Termination.  Additional instructions related to target 
lesion and Regional Photography can be located in the study manual.
7.3. Patient Reported Outcomes
Patient Reported Outcomes (PRO) data will be collected using the 
 
, an 
 item, and a 
.  The 
subject will complete the questionnaires at the clinic prior to other clinical activities or the 
administration of study medication.  The amount of time required for subjects to complete 
the PRO questionnaires at each visit is approximately 10 minutes.
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7.3.4. Patient Health Questionnaire – 8 items (PHQ-8)
Patient health questionnaire – 8 items (Appendix 7) is a patient-report questionnaire consists 
of 8 items to assess subject depression level. 
At Screening Visit, if PHQ-8 total score ≥15, the subject will not be included in the study.
7.3.5. Suicidal Behaviors Questionnaire- revised (SBQ-R)
Suicidal behaviors questionnaire- revised (Appendix 6) is a patient-report questionnaire 
consists of 4 items to assess suicidal ideation, suicide attempts, threat of suicidal behavior, 
and likelihood of suicidal behavior.
At Screening Visit, if SBQ-R total score ≥8, the subject will not be included in the study.
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7.4.1. High-Sensitivity C-Reactive Protein (hsCRP)
Blood samples for determination of hsCRP will be obtained at the times specified in the 
Schedule of Activities.
Instructions and supplies for collection, processing, and shipment of samples will be supplied 
under separate cover by Pfizer, the designated laboratory vendor, and the vendor laboratory 
manual.
7.4.2. Interferon Gamma-Induced Protein 10 (IP-10)
Blood samples for the analysis of IP-10 will be collected into appropriately labeled tubes 
containing no preservative, anticoagulant or serum separator according to the times outlined
in the Schedule of Activities.
Instructions and supplies for collection, processing, and shipment of samples will be supplied 
under separate cover by Pfizer, the designated laboratory vendor, and the vendor laboratory 
manual.
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7.7. Psychological Assessments
7.7.1. Columbia Suicide Severity Rating Scale (C-SSRS)
Columbia suicide severity rating scale is a validated tool to evaluate suicidal ideation and 
behavior (Appendix 5).
At Screening Visit and Baseline Visit, if there are “yes” answers on items 4, 5 or on any 
suicidal behavioral question of the C-SSRS, the subject will not be included in the study.
At any post-baseline visits, if there are “yes” answers on items 4, 5 or on any behavioral 
question of the C-SSRS, the subject will be discontinued from the study and referred to a 
mental health professional for appropriate evaluation and treatment.
If the subject cannot be seen by a mental health professional within 24 hours, then then 
subject should be sent to a local emergency room for psychiatric assessment.
7.8. Rater Qualifications
Clinical evaluations of psoriasis will be performed by an experienced and qualified 
dermatologist or other health professional with experience with PASI scoring after 
consultation and approval by the Sponsor.
The evaluator must receive and document protocol specific and applicable efficacy 
assessment scales training prior to performing these evaluations.  To assure consistency and 
reduce variability, the same evaluator should assess all PASI evaluations for any 
individual subject throughout the study whenever possible (at a minimum, the same 
evaluator must perform the PASI assessment at baseline and at Week 12); a back-up 
experienced and qualified, protocol-trained evaluator will only be allowed and documented 
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in case of emergency or special situations when the designated evaluator is unable to perform 
the evaluation.
8. ADVERSE EVENT REPORTING
8.1. Requirements
The table below summarizes the requirements for recording safety events on the CRF and for 
reporting safety 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) non-serious adverse events (AEs); and (3) exposure to the investigational product under 
study during pregnancy or breastfeeding, and occupational exposure.
Safety Event
Recorded on the CRF
Reported on the CT SAE Report 
Form to Pfizer Safety Within 
24 Hours of Awareness
SAE
All
All
Non-serious AE
All
None
Exposure to the investigational 
product under study during 
pregnancy or breastfeeding, and 
occupational exposure
All (regardless of whether 
associated with an AE), except 
occupational exposure
Exposure during pregnancy, 
exposure via breastfeeding, 
occupational exposure (regardless 
of whether associated with an AE)
All observed or volunteered events regardless of treatment group or suspected causal 
relationship to the investigational product(s) will be reported as described in the following 
paragraphs.
Events listed in the table above that require reporting to Pfizer Safety on the CT SAE Report 
Form within 24 hours of awareness of the event by the investigator are to be reported 
regardless of whether the event is determined by the investigator to be related to an 
investigational product under study.  In particular, if the SAE is fatal or life-threatening, 
notification to Pfizer Safety must be made immediately, irrespective of the extent of available 
event information.  This time frame also applies to additional new (follow-up) information on 
previously forwarded reports.  In the rare situation that the investigator does not become 
immediately aware of the occurrence of an event, the investigator must report the event 
within 24 hours after learning of it and document the time of his/her first awareness of the 
event.
For each event, the investigator must pursue and obtain adequate information both to 
determine the outcome and to assess whether it meets the criteria for classification as an SAE 
(see the Serious Adverse Events section below).  In addition, the investigator may be 
requested by Pfizer Safety to obtain specific follow-up information in an expedited fashion.  
This information is more detailed than that recorded on the CRF.  In general, this 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 
subject death, a summary of available autopsy findings must be submitted as soon as possible 
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Report Form; additional source documents (eg, medical records, CRF, laboratory data) are to 
be sent to Pfizer Safety ONLY upon request.
As part of ongoing safety reviews conducted by the sponsor, any non-serious AE that is 
determined by the sponsor to be serious will be reported by the sponsor as an SAE.  To assist 
in the determination of case seriousness, further information may be requested from the 
investigator to provide clarity and understanding of the event in the context of the clinical 
study.
8.1.1. Additional Details on Recording Adverse Events on the CRF
All events detailed in the table above will be recorded on the AE page(s) of the CRF.  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.
8.1.2. Eliciting Adverse Event Information
The investigator is to record on the CRF all directly observed AEs and all AEs spontaneously 
reported by the study subject/legally acceptable representative.  In addition, each study 
subject/legally acceptable representative will be questioned about the occurrence of AEs in a 
non-leading manner.
8.1.3. Withdrawal From the Study Due to Adverse Events (see also the Subject 
Withdrawal/Early Termination section)
Withdrawal due to AEs should be distinguished from withdrawal due to other causes, 
according to the definition of AE noted below, and recorded on the CRF.
When a subject withdraws from the study because of an SAE, the SAE must be recorded on 
the CRF and reported, as appropriate, on the CT SAE Report Form, in accordance with the 
Requirements section above.
8.1.4. Time Period for Collecting AE/SAE Information
The time period for actively eliciting and collecting AEs and SAEs (“active collection 
period”) for each subject begins from the time the subject provides informed consent, which 
is obtained before the subject’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 after the last administration of the investigational product.
For subjects who are screen failures, the active collection period ends when screen failure 
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8.1.4.1. Reporting SAEs to Pfizer Safety
All SAEs occurring in a subject during the active collection period are reported to Pfizer 
Safety on the CT SAE Report Form.
SAEs occurring in a subject 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.
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.
8.1.4.2. Recording Non-serious AEs and SAEs on the CRF
During the active collection period, both non-serious AEs and SAEs are recorded on the 
CRF.
Follow-up by the investigator may be required until the event or its sequelae resolve or 
stabilize at a level acceptable to the investigator, and Pfizer concurs with that assessment.
8.1.5. Causality Assessment
The investigator’s assessment of causality must be provided for all AEs (serious and 
non-serious); the investigator must record the causal relationship on the CRF, and report such 
an assessment in accordance with the SAE reporting requirements, if applicable.  An 
investigator’s causality assessment is the determination of whether there exists a reasonable 
possibility that the investigational product caused or contributed to an AE; generally the facts 
(evidence) or arguments to suggest a causal relationship should be provided.  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.  If the investigator's causality assessment is “unknown but not 
related” to investigational product, this should be clearly documented on study records.
In addition, if the investigator determines that an SAE is associated with study procedures, 
the investigator must record this causal relationship in the source documents and CRF, and 
report such an assessment in the dedicated section of the CT SAE Report Form and in 
accordance with the SAE reporting requirements.
8.1.6. Sponsor’s Reporting Requirements to Regulatory Authorities
AE reporting, including suspected unexpected serious adverse reactions, will be carried out 
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8.2. Definitions
8.2.1. Adverse Events
An AE is any untoward medical occurrence in a study subject administered a product or 
medical device; the event need not necessarily have a causal relationship with the treatment 
or usage.  Examples of AEs include, but are not limited to:

Abnormal test findings.

Clinically significant signs and symptoms.

Changes in physical examination findings.

Hypersensitivity.

Progression/worsening of underlying disease.

Drug abuse.

Drug dependency.
Additionally, AEs may include signs and symptoms resulting from:

Drug overdose.

Drug withdrawal.

Drug misuse.

Drug interactions.

Extravasation.

Exposure during pregnancy (EDP).

Exposure via breastfeeding.

Medication error.

Occupational exposure.
8.2.2. Abnormal Test Findings
Abnormal objective test findings should be recorded as AEs when any of the following 
conditions are met:

Test result is associated with accompanying symptoms; and/or


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
Test result requires additional diagnostic testing or medical/surgical intervention; 
and/or

Test result leads to a change in study dosing (outside of any protocol-specified dose 
adjustments) or discontinuation from the study, significant additional concomitant 
drug treatment, or other therapy; and/or

Test result is considered to be an AE by the investigator or sponsor.
Merely repeating an abnormal test, in the absence of any of the above conditions, does not 
constitute an AE.  Any abnormal test result that is determined to be an error does not require 
recording as an AE.
8.2.3. Serious Adverse Events
A serious adverse event is any untoward medical occurrence at any dose that:

Results in death.

Is life-threatening (immediate risk of death).

Requires inpatient hospitalization or prolongation of existing hospitalization.

Results in persistent or significant disability/incapacity (substantial disruption of the 
ability to conduct normal life functions).

Results in congenital anomaly/birth defect.
Or that is considered to be:

An important medical event.
Medical and scientific judgment is exercised in determining whether an event is an important 
medical event.  An important medical event may not be immediately life-threatening and/or 
result in death or hospitalization.  However, if it is determined that the event may jeopardize 
the subject or may require intervention to prevent one of the other AE outcomes, the 
important medical event should be reported as serious.
Examples of such events are 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.
8.2.4. Hospitalization
Hospitalization is defined as any initial admission (even less than 24 hours) in a hospital or 
equivalent healthcare facility, or any prolongation of an existing admission.  Admission also 
includes transfer within the hospital to an acute/intensive care unit (eg, from the psychiatric 
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tuberculosis unit).  An emergency room visit does not necessarily constitute a hospitalization; 
however, the event leading to the emergency room visit is assessed for medical importance.
Hospitalization does not include the following:

Rehabilitation facilities.

Hospice facilities.

Respite care (eg, caregiver relief).

Skilled nursing facilities.

Nursing homes.

Same-day surgeries (as outpatient/same-day/ambulatory procedures).
Hospitalization or prolongation of hospitalization in the absence of a precipitating clinical 
AE is not in itself an SAE.  Examples include:

Admission for treatment of a preexisting condition not associated with the 
development of a new AE or with a worsening of the preexisting condition (eg, for 
workup of a persistent pretreatment laboratory abnormality).

Social admission (eg, subject has no place to sleep).

Administrative admission (eg, for yearly physical examination).

Protocol-specified admission during a study (eg, for a procedure required by the study 
protocol).

Optional admission not associated with a precipitating clinical AE (eg, for elective 
cosmetic surgery).

Hospitalization for observation without a medical AE.

Preplanned treatments or surgical procedures.  These should be noted in the baseline 
documentation for the entire protocol and/or for the individual subject.
Diagnostic and therapeutic noninvasive and invasive procedures, such as surgery, should not 
be reported as SAEs.  However, the medical condition for which the procedure was 
performed should be reported if it meets the definition of an SAE.  For example, an acute 
appendicitis that begins during the reporting period should be reported if the SAE 
requirements are met, and the resulting appendectomy should be recorded as treatment of the 
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8.3. Severity Assessment
If required on the AE page of the CRF, the investigator will use the adjectives MILD, 
MODERATE, or SEVERE to describe the maximum intensity of the AE.  For purposes of 
consistency, these intensity grades are defined as follows:
MILD
Does not interfere with subject's usual function.
MODERATE
Interferes to some extent with subject's usual function.
SEVERE
Interferes significantly with subject's usual function.
Note the distinction between the severity and the seriousness of an AE.  A severe event is not 
necessarily an SAE.  For example, a headache may be severe (interferes significantly with 
the subject's usual function) but would not be classified as serious unless it met one of the 
criteria for SAEs, listed above.
8.4. Special Situations
8.4.1. Protocol-Specified Serious Adverse Events
There are no protocol-specified SAEs in this study.  All SAEs will be reported to Pfizer 
Safety by the investigator as described in previous sections, and will be handled as SAEs in 
the safety database.
8.4.2. 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 subjects, transaminase elevations are a harbinger of a more 
serious potential outcome.  These subjects fail to adapt and therefore are "susceptible" to 
progressive and serious liver injury, commonly referred to as drug-induced liver injury 
(DILI).  Subjects 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 lab 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.


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The threshold of laboratory abnormalities for a potential DILI case depends on the subject’s 
individual baseline values and underlying conditions.  Subjects 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:

Subjects 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 subjects 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).
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 subject 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, 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, alkaline phosphatase and acetaminophen drug and/or protein adduct levels.  
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) may be warranted.


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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 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.
8.4.3. Potential Cases of Decreased eGFR
In FIH study B7931001, blood creatinine elevation was reported across dose levels in healthy 
volunteer and psoriasis patients (Section 1.5.1).
Abnormal values in serum creatinine concurrent with absence of increase in blood urea 
nitrogen (BUN) that meet the below criteria, in the absence of other causes of kidney injury, 
are considered potential cases of acute kidney injury and should be considered important 
medical events.
An increase in serum creatinine above the upper limit of normal (ULN) as defined by the 
laboratory reference range should trigger a reflex testing for serum cystatin-C in order to 
facilitate both cystatin C based and serum creatinine based eGFR calculations.
Based on these measurements, estimated GFR using serum creatinine and serum cystatin C 
will be determined at the time of elevation in serum creatinine above ULN.  All subjects will 
also have serum creatinine based and serum cystatin-C based eGFR calculated at baseline 
upon entry into the study.
If an individual subject demonstrates a CONCOMITANT serum creatinine based AND 
serum cystatin C based eGFR decline of 30% compared to the subject’s baseline eGFR, 
then the subject 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 PI.
If the subject cannot be seen by a nephrologist within 24 hours (as described above), 
then the subject should be sent to a local emergency room for evaluation and treatment 
as clinically indicated.
Subjects should return to the investigational site and be evaluated as soon as possible, 
preferably within 24-48 hours from awareness of the abnormal eGFR result for a safety 
follow-up visit.  This evaluation 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 BUN, serum 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 


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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 Pfizer for review immediately upon receipt by 
the PI.
This requirement applies to all subjects, all cohorts.
8.4.4. Exposure to the Investigational Product 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.
8.4.4.1. Exposure During Pregnancy
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 subject or subject’s partner becomes or is found to be pregnant during the subject’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 subject 
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).


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Follow-up is conducted to obtain general information on the pregnancy and its outcome for 
all EDP reports with an unknown outcome.  The investigator will follow the pregnancy until 
completion (or until pregnancy termination) and notify Pfizer Safety of the outcome as a 
follow-up to the initial EDP supplemental form.  In the case of a live birth, the structural 
integrity of the neonate can be assessed at the time of birth.  In the event of a termination, the 
reason(s) for termination should be specified and, if clinically possible, the structural 
integrity of the terminated fetus should be assessed by gross visual inspection (unless 
pre-procedure 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 subject with the Pregnant Partner Release of Information Form 
to deliver to his partner.  The investigator must document in the source documents that the 
subject was given the Pregnant Partner Release of Information Form to provide to his 
partner.
8.4.4.2. 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.
8.4.4.3. 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.


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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 subject 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.
8.4.5. Medication Errors
Other exposures to the investigational product under study may occur in clinical trial settings, 
such as medication errors.
Safety Event
Recorded on the CRF
Reported on the CT SAE 
Report Form to Pfizer Safety 
Within 24 Hours of Awareness
Medication errors
All (regardless of whether 
associated with an AE)
Only if associated with an SAE
8.4.5.1. Medication Errors
Medication errors may result from the administration or consumption of the investigational 
product by the wrong subject, or at the wrong time, or at the wrong dosage strength.
Medication errors include:

Medication errors involving subject 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 participating subject.
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 non-serious, 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.
9. DATA ANALYSIS/STATISTICAL METHODS
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.


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9.1. Sample Size Determination
The sample size is based on the primary efficacy endpoint, PASI change from baseline at 
Week 12. With an assumption of standard deviation of 10, a total of 200 randomized 
subjects in the 8 treatment groups will provide approximately 95% power to detect a 
-11.8 placebo adjusted PASI change from baseline at Week 12 (difference between 
PF-06700841 and placebo) at significance level of 0.05 (one-sided) using Dunnet test for 
multiplicity adjustment. Approximately 160 completers (20 completers per treatment group) 
can be achieved with an assumption of 20% dropout rate.
9.2. Efficacy Analysis
The primary analysis is based on the classic PASI scores described in the sample size
determination section.
Analysis of efficacy 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.
All analyses will be detailed in the Statistical Analysis Plan (SAP).
9.2.1. Analysis of the Primary Endpoint 
The primary endpoint is the change from baseline in PASI score at Week 12. The treatment 
effect in each of the active treatment groups is defined as the placebo adjusted change from 
baseline of the PASI score at Week 12 (mean change from baseline at Week 12 in the active 
treatment group minus the mean change from baseline at Week 12 in the placebo group).  
The estimates for treatment effect will be obtained by fitting the mixed-effect models
repeated measures (MMRM) assuming missing at random to the PASI change from baseline 
score. The model will include treatment (active doses and placebo), visit, treatment by visit 
interaction as fixed effects and baseline value as a covariate. We will allow an unstructured 
variance-covariance matrix. Covariance matrices with other structure will be considered in 
sensitivity analysis. Estimates and the appropriate confidence intervals will be presented.
All 7 active treatment groups will be compared with placebo, and Dunnet test will be used 
for multiplicity adjustment.
Analysis of covariance (ANCOVA) will be implemented as sensitivity analysis. This 
additional estimate of the treatment effect relies on the subset of observations (Week 12 and 
baseline). It is potentially less efficient than the estimate based on the MMRM but eliminates 
the complexity of modeling the covariance between the repeated measures of outcome 
observed at different visits. Estimates and the appropriate confidence intervals will be 
presented for each of these methods.
The linear PASI (L-PASI) score will be analyzed as additional sensitivity analysis using 
MMRM and ANCOVA.
In addition to the primary analysis based on the evaluating contrasts of the treatment effects, 
data permitting, dose-response relationship for the primary endpoint may be explored.


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9.2.2. Analysis of Secondary Endpoints
Binary endpoints (ie, proportions of subjects achieving 50%,75% and 90% reduction from
baseline PASI response rates and proportions of subjects with Physician Global Assessment
of ‘clear’ or “almost clear”) will be analyzed by reporting a proportion of subjects with the
event of interest in each of the treatment groups at each visit. Estimate and 90% confidence 
interval for the difference of proportions (each of the active doses against placebo) will be 
calculated, using normal approximation to the distribution of the observed difference in
proportions.
Logistic regression/odds ratio modeling approach will be employed as a sensitivity analysis
unless the proportion of the events in one of the groups is too small for the applicability of
this method.
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9.6. Safety Analysis
All subjects who receive study medication (safety population) will be included in the safety
analyses. All the safety data will be summarized descriptively through appropriate data
tabulations, descriptive statistics, categorical summaries, and graphical presentations.  Safety
endpoints for the study include:
•
On-treatment adverse events (AEs) and serious adverse events (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.
•
Vital signs.
•
ECG parameters.
Safety data will be reviewed and summarized on an ongoing basis during the study to
evaluate the safety of subjects. A set of safety summary tables by treatment will be produced
to evaluate any potential risk associated with the safety and toleration of administering the
study medication, continuous outcomes (eg, blood pressure, heart rate etc) will be
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summarized using N, Mean, Median, Standard Deviation etc. Categorical outcomes
(eg, occurrence of any adverse event) will be summarized by subject counts and percentage.  
Change from baseline on laboratory data and vital signs will be additionally summarized.
Subject listings will also be produced for these safety endpoints. The safety endpoints will
be listed and summarized in accordance with Pfizer Data Standards. The safety analyses will
be carried out in the safety population, detailed analyses will be described in the SAP.
The analyses of adverse events under the 3-tier approach are considered exploratory. There
will be no adjustment for multiple comparisons or stratification factor in the analyses unless
specified.
Nominal p-values (Tier 1 events only) and 95% confidence intervals (Tier 1 and Tier 2
events) will be provided for between treatment differences in the percentage of subjects with
events. Reporting p-values and confidence intervals will follow Pfizer standard practice in
the 3-tier approach.
 
9.8. Data Monitoring Committee
This study will use an internal review committee (IRC).
The IRC will be responsible for ongoing monitoring of the
 and safety of 
subjects in the study according to the Charter. The recommendations made by the IRC to 
alter the conduct of the study will be forwarded to the study team 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.
10. QUALITY CONTROL AND QUALITY ASSURANCE
Pfizer or its agent will conduct periodic monitoring visits during study conduct to ensure that 
the protocol and Good Clinical Practices (GCPs) are being followed.  The monitors may 
review source documents to confirm that the data recorded on CRFs are accurate.  The 
investigator and institution will allow Pfizer monitors/auditors or its agents and appropriate 
regulatory authorities direct access to source documents to perform this verification.  This 
verification may also occur after study completion.
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During study conduct and/or after study completion, the investigator site may be subject to 
review by the IRB/EC, and/or to quality assurance audits performed by Pfizer, or companies 
working with or on behalf of Pfizer, and/or to inspection by appropriate regulatory 
authorities.
The investigator(s) will notify Pfizer or its agents immediately of any regulatory inspection 
notification in relation to the study. Furthermore, the investigator will cooperate with Pfizer 
or its agents to prepare the investigator site for the inspection and will allow Pfizer 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 subject's medical records.  The investigator will promptly provide copies of the 
inspection findings to Pfizer or its agent.  Before response submission to the regulatory 
authorities, the investigator will provide Pfizer or its agents with an opportunity to review 
and comment on responses to any such findings.
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.
11. DATA HANDLING AND RECORD KEEPING
11.1. Case Report Forms/Electronic Data Record
As used in this protocol, the term CRF should be understood to refer to either a paper form or 
an electronic data record or both, depending on the data collection method used in this study.
A CRF is required and should be completed for each included subject.  The completed 
original CRFs are the sole property of Pfizer and should not be made available in any form to 
third parties, except for authorized representatives of Pfizer or appropriate regulatory 
authorities, without written permission from Pfizer.
The investigator has ultimate responsibility for the collection and reporting of all clinical, 
safety, and laboratory data entered on the CRFs and any other data collection forms (source 
documents) and ensuring that they are accurate, authentic/original, attributable, complete, 
consistent, legible, timely (contemporaneous), enduring, and available when required.  The 
CRFs must be signed by the investigator or by an authorized staff member to attest that the 
data contained on the CRFs are true. Any corrections to entries made in the CRFs or source 
documents must be dated, initialed, and explained (if necessary) and should not obscure the 
original entry. 
In most cases, the source documents are the hospital or the physician subject chart.  In these 
cases, data collected on the CRFs must match the data in those charts. 
In some cases, the CRF may also serve as the source document.  In these cases, a document 
should be available at the investigator site and at Pfizer that clearly identifies those data that 
will be recorded on the CRF, and for which the CRF will stand as the source document.


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11.2. Record Retention
To enable evaluations and/or inspections/audits from regulatory authorities or Pfizer, the 
investigator agrees to keep records, including the identity of all participating subjects 
(sufficient information to link records, eg, CRFs and hospital records), all original signed 
informed consent[/assent] documents, copies of all CRFs, safety reporting forms, source 
documents, and detailed records of treatment disposition, and adequate documentation of 
relevant correspondence (eg, letters, meeting minutes, and telephone call reports).  The 
records should be retained by the investigator according to the ICH guidelines, according to 
local regulations, or as specified in the clinical study agreement (CSA), whichever is longer.
If the investigator becomes unable for any reason to continue to retain study records for the 
required period (eg, retirement, relocation), Pfizer should be prospectively notified.  The 
study records must be transferred to a designee acceptable to Pfizer, such as another 
investigator, another institution, or an independent third party arranged by Pfizer.
Investigator records must be kept for a minimum of 15 years after completion or 
discontinuation of the study or for longer if required by applicable local regulations.
The investigator must obtain Pfizer's written permission before disposing of any records, 
even if retention requirements have been met.
12. ETHICS
12.1. Institutional Review Board/Ethics Committee
It is the responsibility of the investigator to have prospective approval of the study protocol, 
protocol amendments, informed consent documents, and other relevant documents, 
eg, recruitment advertisements, if applicable, from the IRB/EC.  All correspondence with the
IRB/EC should be retained in the investigator file.  Copies of IRB/EC approvals should be 
forwarded to Pfizer.
The only circumstance in which an amendment may be initiated prior to IRB/EC approval is 
where the change is necessary to eliminate apparent immediate hazards to the subjects.  In 
that event, the investigator must notify the IRB/EC and Pfizer in writing immediately after 
the implementation.
12.2. Ethical Conduct of the Study
The study will be conducted in accordance with the protocol, legal and regulatory 
requirements, and the general principles set forth in the International Ethical Guidelines for 
Biomedical Research Involving Human Subjects (Council for International Organizations of 
Medical Sciences 2002), ICH Guideline for Good Clinical Practice, and the Declaration of 
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12.3. Subject Information and Consent
All parties will ensure protection of subject personal data and will not include subject names 
or other identifiable data in any reports, publications, or other disclosures, except where
required by law.
When study data are compiled for transfer to Pfizer and other authorized parties, subject 
names, addresses, and other identifiable data will be replaced by numerical codes based on a 
numbering system provided by Pfizer in order to de-identify study subjects. The investigator
site will maintain a confidential list of subjects who participated in the study, linking each 
subject’s numerical code to his or her actual identity.  In case of data transfer, Pfizer will 
maintain high standards of confidentiality and protection of subjects’ personal data consistent 
with applicable privacy laws.
The informed consent documents and any subject recruitment materials must be in 
compliance with ICH GCP, local regulatory requirements, and legal requirements, including 
applicable privacy laws.
The informed consent documents used during the informed consent process and any subject 
recruitment materials must be reviewed and approved by Pfizer, approved by the IRB/EC
before use, and available for inspection.
The investigator must ensure that each study subject, or his or her legally acceptable 
representative is fully informed about the nature and objectives of the study and possible 
risks associated with participation.
Whenever consent is obtained from a subject’s legally acceptable representative, the 
subject’s assent (affirmative agreement) must subsequently be obtained when the subject has 
the capacity to provide assent, as determined by the IRB/EC.  If the investigator determines 
that a subject’s decisional capacity is so limited he/she cannot reasonably be consulted, then, 
as permitted by the IRB/EC and consistent with local regulatory and legal requirements, the 
subject’s assent may be waived with source documentation of the reason assent was not 
obtained.  If the study subject does not provide his or her own consent, the source documents
must record why the subject did not provide consent (eg, minor, decisionally impaired adult), 
how the investigator determined that the person signing the consent was the subject’s legally 
acceptable representative, the consent signer’s relationship to the study subject (eg, parent, 
spouse), and that the subject’s assent was obtained or waived.  If assent is obtained verbally,
it must be documented in the source documents.
The investigator, or a person designated by the investigator, will obtain written informed 
consent from each subject or the subject's legally acceptable representative before any 
study-specific activity is performed. The investigator will retain the original of each subject's 
signed consent document.


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12.4. 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.
In addition, the investigator will inform Pfizer immediately of any urgent safety measures 
taken by the investigator to protect the study subjects against any immediate hazard, and of 
any serious breaches of this protocol or of ICH GCP that the investigator becomes aware of.
13. DEFINITION OF END OF TRIAL
13.1. End of Trial in a Member State
End of trial in a Member State of the European Union is defined as the time at which it is 
deemed that a sufficient number of subjects have been recruited and completed the study as 
stated in the regulatory application (ie, clinical trial application [CTA]) and ethics application 
in the Member State.  Poor recruitment (recruiting less than the anticipated number in the 
CTA) by a Member State is not a reason for premature termination but is considered a 
normal conclusion to the study in that Member State.
13.2. End of Trial in All Other Participating Countries
End of trial in all other participating countries is defined as last subject last visit (LSLV).
14. SPONSOR DISCONTINUATION CRITERIA
Premature termination of this study may occur because of a regulatory authority decision, 
change in opinion of the IRB/EC, or investigational product safety problems, or at the 
discretion of Pfizer.  In addition, Pfizer retains the right to discontinue development of 
PF-06700841 at any time.
If a study is prematurely terminated, Pfizer will promptly notify the investigator.  After 
notification, the investigator must contact all participating subjects and the hospital pharmacy 
(if applicable) within a time period set by Pfizer.  As directed by Pfizer, all study materials 
must be collected and all CRFs completed to the greatest extent possible.
15. PUBLICATION OF STUDY RESULTS
15.1. Communication of Results by Pfizer
Pfizer fulfills its commitment to publicly disclose clinical trial 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 all cases, study results are reported by Pfizer in an objective, accurate, balanced, and 
complete manner and are reported regardless of the outcome of the study or the country in 
which the study was conducted.


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www.clinicaltrials.gov
Pfizer posts clinical trial US Basic Results on www.clinicaltrials.gov for Pfizer-sponsored 
interventional studies (conducted in patients) that evaluate the safety and/or efficacy of a 
Pfizer product, regardless of the geographical location in which the study is conducted.  US 
Basic Results are 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 subject 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 (clinical study report synopses in which any data 
that could be used to identify individual patients has 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.
15.2. Publications by Investigators
Pfizer supports the exercise of academic freedom and has no objection to publication by the 
principal investigator (PI) of the results of the study based on information collected or 
generated by the PI, whether or not the results are favorable to the Pfizer product.  However, 
to ensure against inadvertent disclosure of confidential information or unprotected 
inventions, the investigator will provide Pfizer an opportunity to review any proposed 
publication or other type of disclosure of the results of the study (collectively, “publication”) 
before it is submitted or otherwise disclosed.
The investigator will provide any publication to Pfizer at least 30 days before it is submitted 
for publication or otherwise disclosed. If any patent action is required to protect intellectual 
property rights, the investigator agrees to delay the disclosure for a period not to exceed an 
additional 60 days.
The investigator will, on request, remove any previously undisclosed confidential 
information before disclosure, except for any study- or Pfizer product-related information 
necessary to the appropriate scientific presentation or understanding of the study results.


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If the study is part of a multicenter study, the investigator agrees that the first publication is 
to be a joint publication covering all investigator sites, and that any subsequent publications 
by the PI will reference that primary publication. However, if a joint manuscript has not 
been submitted for publication within 12 months of completion or termination of the study at 
all participating sites, the investigator is free to publish separately, subject to the other 
requirements of this section.
For all publications relating to the study, the institution will comply with recognized ethical 
standards concerning publications and authorship, including Section II - “Ethical 
Considerations in the Conduct and Reporting of Research” of the Uniform Requirements for 
Manuscripts Submitted to Biomedical Journals, http://www.icmje.org/index.html#authorship, 
established by the International Committee of Medical Journal Editors.
Publication of study results is also provided for in the CSA between Pfizer and the 
institution.  In this section entitled Publications by Investigators, the defined terms shall have 
the meanings given to them in the CSA.
If there is any conflict between the CSA and any attachments to it, the terms of the CSA 
control.  If there is any conflict between this protocol and the CSA, this protocol will control 
as to any issue regarding treatment of study subjects, and the CSA will control as to all other 
issues.


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16. REFERENCES
1.
Lowes MA, Bowcock AM, Krueger JG. Pathogenesis and therapy of psoriasis. Nature 
2007; 445(7130):866-73.
2.
Asadullah K., Döcke WD, Volk HD, et al. The pathophysiological role of cytokines in 
psoriasis. Drugs Today (Barc) 1999; Dec;35(12):913-24.
3.
Villadsen LS, Schuurman J, Beurskens F, et al. Resolution of psoriasis upon blockade 
of IL-15 biological activity in a xenograft mouse model. J Clin Inv 2003; 
112(10):1571–80.
4.
Schon MP, Boehncke WH. Psoriasis. New Engl J Med 2005; 352(18):1899-912.
5.
Parisi R, Symmons DP, Griffiths CE, et al. Identification and Management of Psoriasis 
and Associated ComorbidiTy (IMPACT) project team . Global epidemiology of 
psoriasis: a systematic review of incidence and prevalence. J Invest Dermatol 2013; 
133(2):377–85.
6.
Rapp SR, Feldman SR, Exum ML, et al. Psoriasis causes as much disability as other 
major medical diseases. J Am Acad Dermatol 1999; 41(3 pt 1):401-7.
7.
Murray PJ. The JAK-STAT signaling pathway: input and output integration. J 
Immunol. 2007; 178(5):2623-9. Review
8.
O'Sullivan LA, Liongue C, Lewis RS, et al. Cytokine receptor signaling through the 
Jak-Stat-Socs pathway in disease. Mol Immunol. 2007; 44(10):2497-506.
9.
Martin D, Towne J, Kricorian G, et al. The emerging role of IL-17 in the pathogenesis 
of psoriasis: preclinical and clinical findings. J Invest Dermatol 2013; 133:17-26.
10.
Lowes MA, Kikuchi T, Fuentes-Duculan J, et al. Psoriasis vulgaris lesions contain 
discrete populations of Th1 and Th17 T cells. J Invest Dermatol 2008; 128:1207.
11.
Langley RG, Elewski BE, Lebwohl M, et al. Secukinumab in plaque psoriasis-results of 
two phase 3 trials. N Engl J Med 2014; 371:326.
12.
Haider AS, Lowes MA, Suárez-Fariñas M, et al. 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. J Immunol 2008; 180:1913.
13.
Rácz E, Prens EP, Kurek D, et al. Effective treatment of psoriasis with narrow-band 
UVB phototherapy is linked to suppression of the IFN and Th17 pathways. J Invest 
Dermatol 2011; 131:1547.


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14.
Zaba LC, Suárez-Fariñas M, Fuentes-Duculan J, et al. Effective treatment of psoriasis 
with etanercept is linked to suppression of IL-17 signaling, not immediate response 
TNF genes. J Allergy Clin Immunol 2009; 124:1022.
15.
Krueger JG, Ferris LK, Menter A, et al. 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. J Allergy 
Clin Immunol 2015; 136:116.
16.
Hoek FJ, Kemperman FAW, Krediet RT. A comparison between cystatin C, plasma 
creatinine and the Cockcroft and Gault formula for the estimation of glomerular 
filtration rate. Nephrology Dialysis Transplantation 2003; 18(10): 2024-31.
17.
Newman DJ, Thakkar H, Edwards RG, et al. Serum cystatin C measured by automated 
immunoassay: A more sensitive marker of changes in GFR than serum creatinine. 
Kidney International 1995; 47(1): 312-8.
18.
Dharnidharka VR, Kwon c, Stevens G. Serum cystatin C is superior to serum creatinine 
as a marker of kidney function: A meta-analysis. American Journal of Kidney Diseases
2002; 40(2): 221-6.
19.
Inker LA, Schmid CH, Tighiouart H, et al. Estimating Glomerular Filtration Rate from 
Serum Creatinine and Cystatin C. New England Journal of Medicine 2012; 367(1):20-9.
20.
Zhu Y, Ye X, Zhu B, et al. Comparisons between the 2012 New CKD-EPI (Chronic 
Kidney Disease Epidemiology Collaboration) Equations and Other Four Approved 
Equations. PLoS ONE 9(1): e84688. doi: 10.1371/journal.pone.0084688.
21.
Fredriksson T, Pettersson U. Severe psoriasis – oral therapy with a new retinoid. 
Dermatologica 1978; 157(4):238-44.
22.
Long CC, Finlay AY, Averill RW. The rule of hand: 4 hand areas = 2FTU = 1g. Arch 
Dermatol 1992; 128(8):1129-30.
23.
Finlay AY, Khan GK. Dermatology Life Quality Index (DLQI) – a simple practical 
measure for routine clinical use. Clin Exp Dermatol 1994; 19(3):210-6.
24.
Mazzotti E, Picardi A, Sampogna F, et al. Sensitivity of the Dermatology Life Quality 
Index to clinical change in patients with psoriasis. Br J Dermatol 2003; 149(2):318-22.
25.
Posner KM, Oquendo A, Gould M, et al. Columbia Classification Algorithm of Suicide 
Assessment (C-CASA): Classification of Suicidal Events in the FDA’s Pediatric 
Suicidal Risk Analysis of Antidepressants. The American journal of psychiatry 2007; 
164(7):1035-43.


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26.
Osman A, Bagge CL, Gutierrez PM et al. The Suicidal Behaviors Questionnaire-
Revised (SBQ-R): validation with clinical and nonclinical samples. Assessment 2001; 
8(4):443-54.
27.
Kroenke KSR. The PHQ-9: A new depression diagnostic and severity measure. 
Psychiatric Annals 2002; 32:509-15.


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Appendix 1. Abbreviations 
The following is a list of abbreviations that may be used in the protocol.
Abbreviation
Term
AE
adverse event
ALT
alanine aminotransferase
AST
aspartate aminotransferase
BBS
Biospecimen Banking System
BP
blood pressure
CK
creatine kinase
CRF
case report form
CSA
clinical study agreement
CSF
cerebrospinal fluid
CSR
clinical study report
CTA
clinical trial application
CTCAE
Common Terminology Criteria for Adverse Events
DILI
drug-induced liver injury
DMC
data monitoring committee
DNA
deoxyribonucleic acid
DU
dispensable unit
EC
ethics committee
ECG
electrocardiogram
E-DMC
external data monitoring committee 
EDP
exposure during pregnancy
EU
European Union
EudraCT
European Clinical Trials Database
FSH
follicle-stimulating hormone
GCP
Good Clinical Practice
GGT
Gamma-glutamyl transferase
HIV
human immunodeficiency virus
HRQL
health-related quality of life
ICH
International Conference on Harmonisation
ID
identification
IND
investigational new drug application
INR
international normalized ratio
IP
investigational product
IRB
institutional review board
IRC
internal review committee
IRT
interactive response technology
IUD
intrauterine device
IWR
interactive web response
K2EDTA
dipotassium ethylenediaminetetraacetic acid
LFT
liver function test


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Abbreviation
Term
LSLV
last subject last visit 
MnB
meningitidis serogroup B
N/A
not applicable
PCD
primary completion date
PD
Pharmacodynamics(s)
PFS
prefilled syringe
PGx
Pharmacogenomics(s)
PI
principal investigator
PK
pharmacokinetic
PT
prothrombin time
RNA
ribonucleic acid
SAE
serious adverse event
SAP
statistical analysis plan
SC
subcutaneous
SOP
standard operating procedure
SRSD
single reference safety document
SUSAR
suspected unexpected serious adverse reaction
TBili
total bilirubin
ULN
upper limit of normal
US
United States


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Appendix 2. Cockcroft-Gault Calculation
The Cockcroft-Gault formula may be used to calculate an estimated creatinine clearance, 
which in turn estimates glomerular filtration rate (GFR).
Est. Creatinine Clearance (mL/min) = ([140-Age(years)] x Weight(kg) x Factora)
(72 x Serum Creatinine [mg/dL])
a Factor is equal to 0.85 in females, and 1.00 in males


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Appendix 3. Guidelines for Safety Monitoring and Discontinuation
The following protocol-specified guidelines for safety monitoring and discontinuation are to 
be implemented to all subjects in Study B7931004.  Additional individual subject monitoring 
is at the discretion of the investigator and dependent on any perceived safety concerns.  
Unscheduled clinical labs may be obtained at any time during the study to assess such 
concerns, and a subject may be withdrawn at any time at the discretion of the investigator.
Appendix 3.1. Safety Monitoring
Subjects with the following laboratory abnormalities require prompt retesting within one 
week (preferably within 48 hours) from awareness of the abnormal results:

Absolute neutrophil count <2000/mm3;

Hemoglobin <11.0 g/dL;

Platelet count below <100,000/mm3.
Subjects with the following laboratory abnormalities require prompt retesting within 
72 hours (but preferably within 48 hours) from awareness of the abnormal results:

Serum creatinine >upper limit of normal (ULN).

If serum creatinine > ULN (see protocol Section 7.1.3 and Section 8.4.3), 
measurement of serum cystatin C (reflex testing) will occur along with eGFR 
calculation.  Decision to discontinue dosing will be based on eGFR, as described 
below in Appendix 3.2.

For women of childbearing potential (any female subject who does not meet at least 
one of the criteria of non-childbearing potential listed in Section 4.1) with any 
positive or indeterminate point-of-service urine -hCG test or with a missed 
menstrual period, the subject will have study drug interrupted and a serum sample 
submitted to the central laboratory for -hCG testing. A subject may not progress 
further in the study unless pregnancy is ruled-out.
Additional individual subject safety monitoring not specified in these guidelines is at the 
discretion of the investigator and dependent on any perceived safety concerns. Unscheduled 
laboratory testing through the central laboratory may be obtained at any time during the study 
to assess such concerns, and a subject may be withdrawn at any time at the discretion of the 
investigator.


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Appendix 3.2. Discontinuation
Treatment with PF-06700841 will be discontinued and the subject withdrawn from this 
study for:
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, after consultation with the Pfizer clinician.
Potential Cases of Decreased eGFR:
If an individual subject demonstrates CONCOMITANT serum creatinine-based AND serum 
Cystatin C-based eGFR decline of 30% compared to the subject’s baseline eGFR, then the 
subject 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 PI.
If the subject cannot be seen by a nephrologist within 24 hours (as described above), 
then the subject should be sent to a local emergency room for evaluation and treatment 
as clinically indicated (see protocol Section 8.4.3).
Psychological Assessment
At any post-baseline visits, if there are “yes” answers on items 4, 5 or on any behavioral 
question of the C-SSRS, the subject will be discontinued from the study and referred to a 
mental health professional for appropriate evaluation and treatment.  If the subjects cannot 
be seen by a mental health professional within 24 hours of initial assessment, then the 
subject should be sent to the local emergency room for psychiatric assessment.
Vital Signs:
The following vital sign abnormality will require discontinuation if it is confirmed.  
Confirmation through re-testing should occur within 1 week:

Diastolic: recurrent or persistent (24 hrs) or symptomatic increase from baseline, in 
same posture, by >20 mm Hg.


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Laboratory Abnormalities:
All the following laboratory abnormalities require discontinuation if they are confirmed.  
Confirmation through re-testing should occur within 48 hours:
Laboratory Variable
Laboratory Value
Hematology
Absolute Neutrophil Count
<1000/mm3; <1.0 x109/L
Hemoglobin
<10.0 g/dL; <6.2 mmol/L; <100 g/L
Platelet count
<75,000/mm3; <75.0x109/L
Lymphocytes
<500/mm3; <0.5x109/L
Chemistry
ASTb
>2.5x ULN
ALT
>2.5x ULN
Total bilirubina
>1.5x ULN
a. Total bilirubin 1.5 x ULN; subjects 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 the Pfizer Medical Monitor or designee.
If an individual subject demonstrates CONCOMITANT serum creatinine-based AND serum 
Cystatin C-based eGFR decline of 30% compared to the subject’s baseline eGFR, then the 
subject should not be further dosed and adequate, immediate, supportive measures including 
referral to nephrologist should be taken for evaluation and treatment as clinically indicated.  
Results should be repeated until eGFR returns to baseline 15% (see protocol Section 8.4.3).
Other:
Pregnancy confirmed by serum -hCG testing.  Pfizer Medical Monitor or designee should 
be notified immediately.
Discontinuation/End of Treatment Monitoring for Adverse Events, Laboratory, and 
Vital Signs:
Any subject 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, 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 subject 
takes the investigational product or as soon as possible thereafter. The only exception to this 
is when a subject specifically withdraws consent for any further contact with him or her or 
persons previously authorized by the subject 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.


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Appendix 4. Prohibited Concomitant Medications
CYP3A4, 5, 7 Inhibitors
CYP3A Inducers
Strong 
P-gp 
inhibitors
Substrates 
of MDR1
Substrates of 
OCT2/MATE
HIV antivirals:
-delavirdine (Rescriptor)
-indinavir (Crixivan)
-nelfinavir (Viracept)
-ritonavir (Kaletra, Norvir)
-saquinavir (Fortovase)
amiodarone (Cordarone, 
Pacerone)
cimetidine (Tagamet)
ciprofloxacin (Cipro)
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)
mifepristone (Mifeprex, 
RU486)
nefazodone (Serzone)
norfloxacin (Shibroxin, 
Noroxin)
Norflouxetine
Mibefradil
verapamil (Calan SR,Covera 
HS, Isoptin SR,
Tarka, Verelan)
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)
Quinidine
Digoxin
Dofetilide


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Appendix 5. Columbia Suicide Severity Rating Scale (C-SSRS)25
C-SSRS for Screening and Baseline Visit 


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CSSRS for any post-baseline visits


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Appendix 6. Suicidal Behaviors Questionnaire-Revised (SBQ-R)26


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Appendix 7. Patient Health Questionnaire – 8 items (PHQ-8)27


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Appendix 8. Physician Global Assessment


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SAP_001.pdf: 
Protocol  B7931004 (PF-06700841)                                            Statistical Analysis Plan 
 
Statistical Analysis Plan v1.0  
Page 1 of 33 
 
   
   
 
Protocol B7931004 
 
A PHASE 2A, RANDOMIZED, DOUBLE-BLIND, 
PLACEBO-CONTROLLED STUDY TO EVALUATE 
SAFETY AND EFFICACY OF PF-06700841 IN 
SUBJECTS WITH MODERATE TO SEVERE 
PLAQUE PSORIASIS 
 
 
Statistical Analysis Plan 
(SAP) 
 
 
Version: 3 
Author: 
, 
 (
, 
, MA) 
Date: 10- April -2018  
PPD
PPD
PPD
PPD


Protocol  B7931004 (PF-06700841)                                            Statistical Analysis Plan 
 
Statistical Analysis Plan v1.0  
Page 2 of 33 
 
   
TABLE OF CONTENTS 
LIST OF TABLES .....................................................................................................................3 
LIST OF FIGURES ...................................................................................................................4 
1. AMENDMENTS FROM PREVIOUS VERSION(S) ...........................................................5 
2. INTRODUCTION .................................................................................................................6 
2.1. Study Design .............................................................................................................7 
2.1.1. Initial Design ................................................................................................7 
2.2. Study Objectives .......................................................................................................8 
2.2.1. Primary Objective .........................................................................................8 
2.2.2. Secondary Objectives ...................................................................................8 
 
 
4. HYPOTHESES AND DECISION RULES ...........................................................................9 
4.1. Statistical Hypotheses ...............................................................................................9 
4.2. Statistical Decision Rules ..........................................................................................9 
4.2.1. Multiplicity Adjustment................................................................................9 
 
5. ANALYSIS SETS ...............................................................................................................10 
5.1. Full Analysis Set .....................................................................................................10 
5.2. Safety Analysis Set ..................................................................................................10 
 
5.4. Treatment Misallocations ........................................................................................10 
5.5. Protocol Deviations .................................................................................................11 
5.5.1. Deviations Assessed Prior to Randomization .............................................11 
5.5.2. Deviations Assessed Post-Randomization ..................................................11 
6. ENDPOINTS AND COVARIATES ...................................................................................11 
6.1. Efficacy Endpoint(s) ...............................................................................................11 
6.1.1. Primary Endpoint ........................................................................................11 
6.1.2. Key Secondary Endpoint ............................................................................11 
6.1.3. Secondary Endpoints ..................................................................................11 
 
6.2. Safety Endpoints .....................................................................................................13 
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6.3. Covariates ................................................................................................................13 
7. HANDLING OF MISSING VALUES ................................................................................13 
7.1. Efficacy Data ...........................................................................................................13 
 
7.3. Safety Endpoints .....................................................................................................14 
8. STATISTICAL METHODOLOGY AND STATISTICAL ANALYSES ..........................15 
8.1. Statistical Methods ..................................................................................................15 
8.1.1. Statistical Methods for Continuous Variables ............................................15 
8.1.2. Statistical Methods for Binary Variables ....................................................16 
8.1.3. Statistical Methods for Safety Data ............................................................17 
8.1.4. Analyses for Time-to-Event Endpoints ......................................................17 
 
 
 
8.2. Statistical Analyses .................................................................................................17 
8.2.1. Standard Analyses ......................................................................................17 
8.2.2. Statistical Analyses for Efficacy, Health Outcomes and 
 ........18 
8.2.2.1. Analysis for the Primary Endpoint ............................................18 
8.2.2.2. Analyses for the Secondary Endpoints ......................................19 
 
8.2.3. Analyses for Time-to-Event Endpoints ......................................................21 
8.2.4. Statistical Analyses for Safety ....................................................................21 
 
8.2.6. Summary of  Major Efficacy Analyses ......................................................23 
9. REFERENCES ....................................................................................................................23 
10. APPENDICES ...................................................................................................................24 
 
LIST OF TABLES 
Table 1 Summary of Major Changes in SAP Amendments ......................................................5 
Table 2. 
Visit Window Definition for Analysis ..................................................................24 
 
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Protocol  B7931004 (PF-06700841)                                            Statistical Analysis Plan 
 
Statistical Analysis Plan v1.0  
Page 4 of 33 
 
   
LIST OF FIGURES 
Figure 1. 
Study Schematic .....................................................................................................8 
 
 
 


Protocol  B7931004 (PF-06700841)                                            Statistical Analysis Plan 
 
Statistical Analysis Plan v1.0  
Page 5 of 33 
 
   
1. AMENDMENTS FROM PREVIOUS VERSION(S)  
This is the first version 1.0 
Table 1 Summary of Major Changes in SAP Amendments 
SAP 
Version 
Change 
Rationale 
1 
No Changes 
 
2 
Added additional 
Safety analyses 
Added to match displays requested by IRC 
 
Changed sensitivity 
analyses 
Changed to produce population average estimates 
 
Added detail to 
multiplicity adjustment 
procedure 
Detail needed for implementation in SAS 
 
Corrected example 
SAS code to have 
consistent alpha levels 
Changed all alpha levels to 0.1 
 
 
 
3 
Added appendix with 
C-SSRS mapping 
algorithm 
Not defined before 
 
Updated appendices 10 
and 11 SAS model 
code from Dose to Trt 
Added consistency with other appendices 
 
Updated section 8.1.1 
to specify additional 
estimates and contrasts 
from existing MMRM 
model  
Added model output needed for EQDD plan 
 
Added SAS code to 
Appendix 8 to  extract 
new estimates and 
contrasts defined in 
section 8.1.1 
Custom code needed byprogramming  
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Protocol  B7931004 (PF-06700841)                                            Statistical Analysis Plan 
 
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Removed requirement 
for Tier 1 display in 
sections 8.1.3 and 8.2.4 
There are no Tier 1 events defined for this program 
 
Section 8.2.4, changed 
Tier 2 events to “…5% 
in any treatment group” 
Aligns displays with reports for other JAK 
compounds 
 
Section 8.2.4 changed 
90%CI to 95% CI 
Aligned SAP with protocol text 
 
 
 
 
 
 
Added additional detail 
on windowing 
algorithm when there 
are multiple 
observations within a 
visit window 
Documents programming algorithm 
 
 
2. INTRODUCTION 
Note: in this document any text taken directly from the protocol is italicized.  
PF-06700841 is a potent TYK2/JAK1 inhibitor with an excellent selectivity profile over the 
other human kinases. Thus, PF-06700841 is targeted for clinical development for the 
treatment of patients with psoriasis. 
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. 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 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 
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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.  
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, and to provide 
therapeutic benefit in the treatment of plaque psoriasis.  In the first in human clinical trial of 
PF-06700841 (Study B7931001), psoriasis subjects receiving active treatment with 
PF-06700841 (30 mg or 100 mg once daily for 28 days) had clinically meaningful decreases 
in disease activity as measured by PASI.  Preliminary safety, efficacy and pharmacodynamic 
results from Study B7931001 support further development of PF-06700841 in plaque 
psoriasis. 
The current trial B7931004 is a Phase 2 study that will assess the safety and efficacy of 
several dose levels of PF-06700841, and will include daily and weekly dosing regimens in 
subjects with moderate to severe chronic plaque psoriasis. 
 (Source: Protocol Section 1) 
2.1. Study Design  
2.1.1. Initial Design 
This is a Phase 2a, randomized, double-blind, placebo-controlled, parallel group, 
multicenter study in subjects with moderate to severe plaque psoriasis.  The first part of the 
study, following a screening period (up to 6 weeks), is a 4 week induction period with double 
blind daily treatment.  At the end of Week 4, all subjects switch to their predefined double 
blind maintenance treatment regimen for Week 5 through Week 12. 
Approximately 200 subjects are planned to be randomized into the study, to allow for 
approximately 160 evaluable subjects (20 completers per arm).  The randomization ratio will 
be 7:1, active: placebo.  During the first 4 week treatment period, 2 oral daily dose levels 
(30 mg and 60 mg) of PF-06700841, plus matching placebo, will be investigated.  During the 
8 week maintenance treatment period (Weeks 5 through 12), subjects will receive either 
10 mg or 30 mg PF-06700841 once daily, or a 100 mg once weekly regimen of 
PF-06700841, or matching placebo.  Maintenance dose level and regimen will be assigned 
at the initial time of randomization into the study.  All subjects, regardless of assigned 
regimen (ie, QD or QW) will receive blinded QD dosing throughout the study treatment 
period to maintain the study blind. 
The duration of study subject participation will be approximately 26 weeks, including 
screening, 12 week treatment period, and 8 week follow up period.  


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Figure 1. Study Schematic 
 
2.2. Study Objectives  
2.2.1. Primary Objective 
x P1: To evaluate the efficacy of PF-06700841 in moderate to severe plaque psoriasis.  
2.2.2. Secondary Objectives 
x S1: To explore the efficacy of PF-06700841 induction and maintenance dosing regimens 
in moderate to severe plaque psoriasis. 
x S2: To assess the safety and tolerability of PF-06700841 induction and maintenance 
dosing regimens. 
 
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 (Source of italicized text: Protocol Section 2) 
  
4. HYPOTHESES AND DECISION RULES 
4.1. Statistical Hypotheses 
Statistical inference will be made on the primary endpoint: change from baseline in PASI 
score at Week 12. The null hypothesis is that there is no difference between any arm of PF-
06700841 (60mg QD-30mg QD, 60mg QD-10mg QD, 60mg QD-100mg QW, 60mg QD-
Placebo, 30mg QD for 12 Weeks, 30mg QD-10mg QD, 30mg QD-100mg QW) and placebo 
on the primary endpoint.  The alternative hypothesis is that one of PF-06700841 arms being 
tested is superior to placebo on the primary endpoint.  
4.2. Statistical Decision Rules 
4.2.1. Multiplicity Adjustment 
Multiplicity adjustments are considered for the primary endpoint. The overall Type I family 
wise error rate (FWER) is controlled at 0.05 (one sided).  Hochberg method (Hochberg, 
1988) is used to maintain appropriate alpha control for rejection of the null hypothesis if a 
significant treatment effect is detected at Week 12. 
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5. ANALYSIS SETS 
The data sets to be used for analyses are defined below. 
5.1. Full Analysis Set 
As specified in the protocol, the analysis of the efficacy, health outcome and 
 
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).  This population is also called the Full Analysis Set (FAS). 
5.2. 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.  
 
5.4. Treatment Misallocations  
If a subject was: 
x 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; 
x 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; 
x Randomized but took incorrect treatment: If a subject received the incorrect treatment 
for the whole duration of the study, then the subject will not be  reported for any  
efficacy analysis, but will be summarized under the treatment they actually received 
for all safety analyses; if a subject received the incorrect treatment at only some 
dosing occasions then the subject will be reported under their randomized treatment 
group for both efficacy and safety analyses.  If sufficient doses were incorrect and 
therefore deemed a major protocol deviation, the subjects may be excluded as 
sensitivity analysis. 
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5.5. Protocol Deviations 
The following sections describe any protocol deviations that relate to the statistical 
analyses.  It is possible that unexpected deviations will arise, becoming known only after 
the study has been active for a long period of time; hence more deviations may be added.  A 
full list of protocol deviations for the study report will be compiled prior to database 
release.  
5.5.1. Deviations Assessed Prior to Randomization 
At screening phase prior to randomization, the investigator will assess and document subjects 
against the inclusion and exclusion criteria as set out in sections 4.1 and 4.2 of the protocol. 
5.5.2. Deviations Assessed Post-Randomization 
Post-randomization deviations include: 
• Subjects who receive excluded concomitant medications or rescue medications during the 
treatment period as described in Section 5.8  of the Protocol; 
• Subjects who were randomized but took incorrect treatment; 
• Subjects not satisfying the eligibility criteria, although, not identified until after 
randomization occurred. 
Any significant deviation or violations from the protocol will be reviewed by the clinical 
team during the course of the study and prior to database release and a decision taken 
regarding evaluation for each analysis set. 
6. ENDPOINTS AND COVARIATES 
For all clinically planned measures, visits should occur within a window of the scheduled 
visit, which can be found in Appendix 1.  
6.1. Efficacy Endpoint(s) 
6.1.1. Primary Endpoint 
• Change from baseline in Psoriasis Area and Severity Index (PASI) score at Week 12. 
6.1.2. Key Secondary Endpoint 
• Proportion of subjects achieving a PASI 75 response at Week 12. 
6.1.3. Secondary Endpoints 
• Proportion of subjects achieving 50%, 75% and 90% reduction from baseline PASI at 
time-points specified in the SoA of the protocol. 
• Change from baseline in PASI scores at time-points specified in the SoA of the protocol. 
• Percent change from baseline in PASI scores at time-points specified in the SoA of the 
protocol. 


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x Change from baseline in PASI score at Week 4. 
 
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6.2. Safety Endpoints 
x Incidence and severity of adverse events, serious adverse events and withdrawals due 
to adverse events. 
x Change from baseline in clinical laboratory values (chemistry and hematology, 
lipids). 
x Change from baseline in vital signs (blood pressure, pulse rate, oral or tympanic 
temperature measurements). 
x Change from baseline in ECG parameters (heart rate, QT, QTc, PR and QRS 
intervals). 
6.3. Covariates  
For variables expressed as change from baseline or percent change from baseline, the 
baseline value will also be included in the analysis model as a covariate. 
7. HANDLING OF MISSING VALUES 
In general missing values will not be imputed for descriptive statistics. 
7.1. Efficacy Data 
For the continues efficacy data such as change from baseline in PASI score at Week 12, the 
observed case (OC) approach will be used.  
For the binary efficacy data such as PASI75 response, non-responder imputation (NRI) will 
be considered, in which case subjects who receive at least one investigational product and 
discontinue from the study will be considered as non-responders, in addition any subjects 
with missing data but included in the FAS will have data imputed using NRI. 
  
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7.3. Safety Endpoints 
Missing data for safety endpoints will not be imputed and will be left as missing. The follow-
up period will be included for the safety endpoint. A sensitivity analysis maybe carried out 
excluding the follow-up period. 
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8. STATISTICAL METHODOLOGY AND STATISTICAL ANALYSES 
All efficacy analyses described in this section will only apply to the data in the treatment 
period to the end of week 20 (Week 0 to 20).   
Percentages will be presented to one decimal place in all summaries.  Minimum and 
maximum values will be presented to the same number of decimal places as collected on the 
CRF or within the laboratory screening panel; mean and median will be presented to one 
further decimal place; standard deviation will be presented to two further places. 
Whilst every effort has been made to pre-specify all analyses in this statistical analysis plan, 
should any additional exploratory analyses be found to be required after unblinding, the 
analyses and the reasons for them will be fully detailed in the clinical study report. 
In all data presentations, results will be sorted in same order as the study schematic in section 
2.1. 
8.1. Statistical Methods 
The following sub-sections contain the descriptions of the methods that will be used in the 
analysis of the various endpoints in this study.  The choice of analysis method will be 
dependent on the endpoint of interest (eg whether the endpoint is a primary, key secondary or 
 endpoint or whether the endpoint is efficacy or safety).  The analysis methods to 
be used for each endpoint will be covered in Section 8.2. 
8.1.1.  Statistical Methods for Continuous Variables 
Unless stated otherwise, descriptive summary statistics for all continuous variables will be 
presented on FAS with OC by treatment group and will include the following:  n, mean, 
median, standard deviation, minimum and maximum 
For longitudinal continuous variables, such as the changes from baseline of PASI score, the 
primary analysis will be conducted using a mixed model repeated measures (MMRM) 
analysis on the FAS  using all available data (no imputation).  Each analysis will be 
performed with a restricted maximum likelihood (REML) MMRM approach. Baseline 
measurement such as baseline score will be used as a covariate. The model will include 
treatment and visit as fixed factors, along with the interactions of treatment by visit and 
baseline score by visit. An unstructured covariance structure will be used to model the 
within-subject variability. In the event there are difficulties with initially fitting an 
unstructured covariance matrix, a variety of methods such as heterogeneous CS, 
heterogeneous AR(1) and antedependence will be used to facilitate the computations. Method 
that gives rise to the smallest AIC will be used in the final model.  The Kenward-Roger 
approximation will be used to estimate the denominator degrees of freedom. The model will 
be fit using SAS PROC MIXED. Least squares (LS) means of the treatment groups at each 
available visit along with 90% CIs will be presented. LS mean difference between treatment 
and placebo for each visit will be presented along with 90% confidence intervals. LS means 
and confidence intervals will be back transformed to an appropriate scale when necessary. In 
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the case of convergence issues, analysis of covariance (ANCOVA) may be performed at each 
time point on the FAS. 
In addition to the above summaries from the MMRM model, the following will also be 
calculated and displayed for PASI, Change from Baseline PASI and Percent Change from 
Baseline PASI: 
• Contrasts of Week 4 versus Week 12 LSmeans (i.e., Week 12 – Week 4) by treatment 
arm. 
• Contrasts at Week 12 of LSmeans with same maintenance dose but different induction 
doses (eg. 60 mg -> 30 mg versus 30 mg -> 30 mg etc.). 
• LSmeans at Weeks 1 2 and 4 by induction dose (i.e., placebo, 30 mg and 60 mg) 
o Contrasts at Weeks 1, 2 and 4  comparing 10 mg induction versus placebo 
induction and 30 mg induction versus placebo induction. 
• LSmeans at Week 12 by combined  maintenance dose (e.g. 30 mg, 10 mg, 100 mg QW 
and placebo. 
o Contrasts at Week 12 of the different combined maintenance arms versus the 
combined placebo arm.  
Secondary analyses for continuous variables will be performed with ANCOVA on the FAS 
at each time point with OC data.. 
8.1.2. Statistical Methods for Binary Variables 
For all binary endpoints, a summary of the number of subjects in each category based on OC 
in each treatment arm at each time point will be produced and the response rate will also be 
plotted against time, by treatment group. In addition, similar summary tables will be 
generated for PASI50/75/90 for each visit with NRI.   
Analysis of binary variables over time such as PASI75 response at Week 12 may be analyzed 
using a marginal logistic regression model fit by pseudo-likelihood in PROC GLIMMIX.  
The model will include fixed effects for treatment, time , and treatment by time interaction, 
the model will not contain any random effects. The model will be fit using restricted pseudo-
likelihood with an expansion about the marginal solution (method=RMPL in PROC 
GLIMMIX).  The residual covariance (R-side matrix) will be modeled as an unstructured 
covariance matrix. If convergence fails with the unstructured covariance structure, the 
following covariance structures will be attempted in order: eg, ANTE(1), CSH, ARH(1), 
AR(1) and CS, the first structure that allows convergence will be used. Upper and lower 2-
sided 90% Wald CIs for the proportions will be calculated using the LSMEANS statement 
with the ILINK option. The denominator degrees of freedom will be approximated using the 
Satterthwaite method. Odds ratios for treatment contrasts along with 90% CIs will also be 


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reported. Two-sided p-value for the test of the 0 difference between PF-06700841 and 
placebo  will be provided. 
If there are convergence issues for marginal logistic regression due to zero responses at a 
visit, then that visit may be dropped from the analysis. If the model still does not converge or 
if there are issues in interpretability then a logistic regression analysis at each time point may 
be performed on the FAS with NRI. 
8.1.3. Statistical Methods for Safety Data 
Test-based methods of constructing exact confidence intervals for the difference in two 
binomial proportions proposed by Chan and Zhang (1999) will be used when needed to 
compare incidence rate of safety strata between active groups and placebo, 95% confidence 
intervals will be formed for tier 2 events. 
The exposure adjusted summaries for Tier 2 events will also be conducted. See Section 8.2.1 
for the calculation of exposure.  
8.1.4. Analyses for Time-to-Event Endpoints 
For time to event endpoint (Time to first PASI50 and first PASI75 response), Kaplan-Meier 
analyses will be used to account for any right censoring, i.e., event not observed. Kaplan-
Meier survival estimates from proc LIFETEST and the number and percentage of subjects 
experiencing the relevant event or being censored will be summarized by treatment group. 
 
8.2. Statistical Analyses  
8.2.1. Standard Analyses 
Study conduct and subject disposition 
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The number of subjects randomized, treated, completed and discontinued from the study, as 
well as the number of subjects in each analysis population will be summarized by treatment 
group.  For subjects who did not complete the study, the reasons for withdrawal from the 
study will be presented. 
Demography and baseline characteristics 
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. 
Exposure and compliance 
Exposure to the study therapy is defined as the number of days the subject is known to be on 
study drug.  The exposure is roughly calculated as the date of the last visit (including the 
follow up visits) of the subject in this study minus the date of the first administration of the 
study therapy plus one.  Summary statistics will be provided for exposure by treatment 
group.   
For each subject, percent will then be calculated using the following formula:  
Percent Compliance = # doses actually administrated / # doses planned * 100%. 
The number of doses planned or actually administrated is counted up to the conclusion date 
of the treatment period.  Summary statistics will be provided to percent compliance by 
treatment group. 
Descriptive Statistics 
Descriptive statistics for all primary, secondary and 
 endpoints presented in 
Section 6 will be tabulated.   
8.2.2. Statistical Analyses for Efficacy, Health Outcomes and 
 
Unless stated otherwise, the analyses for efficacy, health outcomes and 
 will be 
based on the FAS, as defined in Section 5.1.  A summary table of the analysis strategy for all 
the efficacy and health outcome is shown in Section 8.2.6.  
8.2.2.1. Analysis for the Primary Endpoint 
The primary efficacy endpoint is the change from baseline in PASI score at Week 12. The 
primary analysis data will be based on the FAS using MMRM as described in Section 8.1.1. 
Baseline is defined as the score for each assessment on Day 1 pre-dose.  
As secondary analyses, ANCOVA will be employed on FAS population with observed cases 
(OC).  
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8.2.2.2. Analyses for the Secondary Endpoints 
8.2.2.2.1. Analyses for the Continuous Secondary endpoints 
The analyses for continuous second endpoints are based on the FAS population. Baseline is 
defined as the score for each assessment on Day 1 pre-dose. These endpoints include: 
x Change from baseline in PASI scores at time-points specified in the SoA of the protocol. 
x Percent change from baseline in PASI scores at time-points specified in the SoA of the 
protocol. 
x Change from baseline in PASI score at Week 4. 
All continuous secondary endpoints including all time points will be analyzed using MMRM 
with OC as described in Section 8.1.1. LS means at each time point will be computed. P 
values and 90% confidence intervals will also be computed for placebo adjusted effect (LS 
mean difference between treatment and placebo) at each time point. Sensitivity analysis will 
be provided using ANCOVA  In case of convergence issues, ANCOVA may be performed at 
each time point with  observed cases. 
8.2.2.2.2. Analyses for the Categorical Secondary Endpoints 
Unless otherwise stated, all primary analyses for the binary secondary endpoints are based on 
the FAS population. Baseline is defined as the score for each assessment on Day 1 pre-dose. 
These endpoints include: 
Key secondary endpoint: 
x Proportion of subjects achieving a PASI 75 response at Week 12. 
Secondary endpoint: 
x Proportion of subjects achieving 50%, 75% and 90% reduction from baseline PASI at 
time-points specified in the SoA of the protocol. 
Marginal logistic regression will be employed on FAS with OC as described in section 8.1.2. 
Additional analysis will be performed by logistic regression at each time point with NRI. In 
the case of convergence issues of the marginal logistic regression logistic regression analysis 
with NRI will be applied.  
 
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8.2.3. Analyses for Time-to-Event Endpoints 
For time to event endpoints (Time to first PASI50 and first PASI75 response), Kaplan-Meier 
analyses will be used to account for any right censoring, i.e., event not observed. Kaplan-
Meier survival estimates and the number and percentage of subjects experiencing the relevant 
event or being censored will be summarized by treatment group. 
 
8.2.4. Statistical Analyses for Safety  
The analysis population for safety is described in Section 5.2.  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 7.3 
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 8.1.3. 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 is a 5% incidence 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 8.1.3.  For tier-1 events p-values may be 
included in the presentations.  AEs will be arranged in the output sorted in descending point 
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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. The exposure adjusted summaries for the Tier 1 and Tier 2 events will also be 
conducted. 
Additionally, 
1) For AST, ALT, WBC, neutrophils, lymphocytes, platelets, reticulocytes, Hemoglobin, 
CK,  hsCRP, TBNK, IP-10, immunoglobulins, creatinine, Cystatin C, creatinine 
eGFR, cystatin C eGFR, HDL, LDL, LDL:HDL ratio, total cholesterol and 
triglycerides: 
a. Descriptive statistics for observed values, change from baseline and percent 
change from baseline summarized as follows: 
i. At all time point by the 8 randomized treatment groups 
ii. At Week 4  by three groups defined by induction dose; everyone who 
had 30 mg Induction (30 mg, 30 mg -> 10 mg, 30 mg -> 100 mg QW) 
, everyone with 60 mg induction (60 mg -> placebo, 60 mg -> 100 mg 
QW, 60 mg -> 10 mg, 60 mg -> 30 mg) and placebo 
iii. At Week 12  by four groups defined by maintenance dose;  100 mg QW 
maintenance (30 mg -> 100 mg QW and 60 mg -> 100 mg QW), 10 
mg QD maintenance (30 mg -> 10 mg, 60 mg -> 10 mg), 30 mg 
maintenance (30 mg, 60 mg -> 30 mg) and placebo (placebo, 60 -> 
placebo 
b. Figures for each lab endpoint over time showing the mean +/- 90% confidence 
interval,  figures and  median figures without confidence intervals. For each 
lab these figures will be repeated three times displaying, observed values, 
change from baseline and percent change from baseline. 
2)Safety AE incidence through week 4 by induction dose; everyone who had 30 mg 
Induction (30 mg, 30 mg -> 10 mg, 30 mg -> 100 mg QW) , everyone with 60 mg 
induction (60 mg -> placebo, 60 mg -> 100 mg QW, 60 mg -> 10 mg, 60 mg -> 30 
mg) and placebo. 
3)Safety AE incidence from week 4  through week 12 by maintenance dose; 100 mg QW 
maintenance (30 mg -> 100 mg QW and 60 mg -> 100 mg QW), 10 mg QD 
maintenance (30 mg -> 10 mg, 60 mg -> 10 mg), 30 mg maintenance (30 mg, 60 mg -
> 30 mg) and placebo (placebo, 60 -> placebo) 
4)Modified Hy’s Law plots with 2.5 times ULN for AST and ALT and 1.5 times ULN for 
bilirubin. 
 
 
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8.2.6. Summary of  Major Efficacy Analyses 
Endpoints 
Primary, 
Secondary, or 
 
Endpoint 
Analysis 
Including 
Follow-UP 
Missing 
Data 
Imputatio
n 
Primary or 
Sensitivity 
Approach 
Change of  PASI 
Primary 
MMRM 
Yes 
OC 
Primary 
 
 
 
 
 
 
Change of  PASI by 
Visit  
Primary 
ANCOVA 
Yes 
OC 
Sensitivity 
PASI50/75/90 
Response 
Secondary 
Marginal 
Logistic 
Regression 
Yes 
OC 
Primary 
PASI50/75/90 
Response 
Secondary 
Logistic 
regression 
Yes 
NRI 
Sensitivity 
Percent change of  
PASI  
Secondary 
MMRM 
Yes 
OC 
Primary 
Percent change of  
PASI by Visit 
Secondary 
ANCOVA 
Yes 
OC 
Sensitivity 
 
9. REFERENCES  
 
1. 
Pfizer Clinical Protocol B7931014: a Phase 2a, Randomized, Double-Blind, Placebo-
controlled Study to Evaluate Safety and Efficacy of PF-06700841 in Subjects with 
Moderate to Severe Plaque Psoriasis. 
2. 
Hochberg, Y, A sharpened Bonferroni procedure for multiple tests of significance, 
Biometrica, 1988, 75, 4: 800-802. 
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3. 
Chan, I. S. F. and Zhang, Z. (1999), "Test-Based Exact Confidence Intervals for the 
Difference of Two Binomial Proportions," Biometrics, 55, 1202–1209. 
10. APPENDICES  
Appendix 1. Definition And Use Of Visit Windows In Reporting  
Note Day 1 in the table below is taken as the first day of dosing with study drug.  It may not 
be the same as the first study date which is the randomization date.  Also note that Day 0 
does not exist, therefore Day -1 is the day before Day 1. In addition, the relative days 
(rel_day) from Day 1 are defined as the visit date minus the first dosing date plus one. Visit 
windows will be used for efficacy variables, and for any safety displays that display by week. 
When multiple observations fall in the same analysis visit window, the observation closest to 
the targeted day will be used. If the observations are with equal distant from the targeted day 
in absolute value, the one before the targeted day will be used. 
 
Table 2. 
Visit Window Definition for Analysis 
Visit 
No. 
Visit Label  
Target Day 
 Visit Window  
1 
Screening  
N/A 
-42 ≤ rel_day ≤ -1 
2 
Baseline* 
1  
Rel_day = 1 
3 
Week 1 
8 
2≤rel_day≤11 
4 
Week 2 
15  
12≤rel_day≤22 
5 
Week 4 
29  
23≤rel_day≤36 
6 
Week 6 
43 
37≤rel_day≤50 
7 
Week 8 
57 
51≤rel_day≤64 
8 
Week 10 
71 
65≤rel_day≤78 
9 
Week 12 
85 
79≤rel_day≤92 
10 
Week 14 
99 
93≤rel_day≤106 
11 
Week 16 
113 
107≤rel_day≤127 
12 
Week 20 
141 
128≤rel_day≤148 
* Baseline analysis visit window may be considered as Rel_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. Psoriasis Area and 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 


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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 Appendix 3. 
 Derivation of PASI score 
In each area, the sum of the severity rating scores for erythema, induration and scaling is 
multiplied by the score representing the percentage of this area involved by psoriasis, 
multiplied by a weighting factor (head 0.1; upper limbs 0.2; trunk 0.3; lower limbs 0.4). The 
sum of the numbers obtained for each of the four body areas is the PASI. 
PASI = 0.1Ah(Eh + Ih + Sh) + 0.2Au(Eu + Iu + Su) + 0.3At(Et + It + St) + 0.4Al(El + Il + 
Sl) 
where A = area of involvement score; E = erythema; I =induration; S = scaling; h = head; u = 
upper limbs; t = trunk; l = lower limbs 
The PASI score can vary in increments of 0.1 units from 0.0 to 72.0, with higher scores 
representing increasing severity of psoriasis. 
PASI 50/75/90 response 
At least 50/75/90% reduction in PASI relative to baseline PASI Score. 
Appendix 3. 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 (i.e., 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. 


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The extent (%) to which each of the four areas of the body is affected is captured on the CRF 
(to 2 decimal places, as necessary). A weighting factor is applied to each of the four areas in 
calculation of the total body surface area affected: head x0.1; upper limbs x0.2; trunk x0.3; 
lower limbs x0.4, as the four areas correspond to approximately 10%, 20%, 30% and 40% of 
the total BSA, respectively. The sum of the weighted percent involvement obtained for each 
of the four body areas is the overall psoriatic BSA. 
Table 2. 
Handprint Determination of Body Region Surface Area (BSA) 
 
Appendix 4. 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". 
CCI


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Appendix 8. Examples of SAS Code for Statistical Analyses – MMRM 
Table 3. 
Input Parameters for MMRM Analyses 
 ID 
Subject’s ID 
 CFB 
Change from baseline  
 VISIT 
Visit of interest (stored as a categorical 
variable). Only the post-baseline visits are 
included. 
 TRT 
Treatment group (stored as a categorical 
variable) 
Baseline 
Baseline observation of the outcome 
 
Create data set ds as described in the 3 and sort it by visit.  The analysis will be implemented 
as follows 
 
CCI
CCI


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proc mixed data=ds; 
class    id trt visit; 
model cfb = trt visit trt*visit baseline /alpha=0.10  ddfm=kr; 
repeated visit /subject= id type= un; 
lsmeans trt*visit /alpha=0.10 cl pdiff; 
ods output diffs= dmmrm; 
run; 
 
Examples of Estimates and Contrasts of Combined Induction doses at Week 4(please extend 
similar code to Weeks 1 and 2 as per analysis section) and Combined maintenance dose.  
Code below assumes that: 
• Visits in data start at Week 1 and continue through week 16 in the following order 
(Week 1, Week 2, Week 4, Week 6, Week 8, Week 10, Week 12, Week 14, and 
Week 16). 
• Treatment is coded by treatment arm in the following order ( 60 -> 30, 60 -> 10, 60 -> 
100 QW, 60 ->plb, 30 ->30, 30 ->10, 30 -> 100 QW, Placebo->Placebo). 
• Furthermore it is assumed that the treatment by visit contrast is order first by treatment 
and then by visit, that is (60->30 week 1, 60->30 week 2, …  60 ->30 week 16, 60-
>10  week 1, …Placebo Week 16). 
• &basemean is a macro variable with the overall mean baseline value for the dataset 
being analyzed. It should match the mean used internally by the LSMeans statement 
which can be verified using the ‘e’ option in the LSmeans. 
NB:  The ‘e’ option can be added to the estimate statements for quality control to verify that 
the correct linear estimate is specified.  They are not necessary for the correct calculation of 
the estimates and contrasts.  The ‘singular’ option with a number close to 1, instead of the 
default value, may be used in the estimate statement if the output indicates that a particular 
estimate is ‘non-estimable’. However, it will then be necessary to check that the estimate 
appears numerically reasonable and the standard error is similar to other estimates, or 
contrasts. 
 
estimate "60 week 4"  intercept 1   avisitn 0 0 1  trtan .25 .25 .25 .25 
         trtan*avisitn 0 0 .25 0 0 0 0 0 0 
                       0 0 .25 0 0 0 0 0 0 
                       0 0 .25 0 0 0 0 0 0 
                       0 0 .25 0 0 0 0 0 0 
        base  &basemean/cl alpha = .1   ; 
 estimate "30 week 4"  intercept 1   avisitn 0 0 1  trtan 0 0 0 0  .3333 .3333 .3333  
         trtan*avisitn 0 0 0 0 0 0 0 0 0 
                       0 0 0 0 0 0 0 0 0 


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                       0 0 0 0 0 0 0 0 0 
                       0 0 0 0 0 0 0 0 0                        
                       0 0 .3333 0 0 0 0 0 0 
                       0 0 .3333 0 0 0 0 0 0 
                       0 0 .3333 0 0 0 0 0 0 
        base  &basemean/ cl  alpha=.1  ; 
 estimate "Placebo week  4"  intercept 1   avisitn 0 0 1  trtan 0 0 0 0  0 0 0 1  
         trtan*avisitn 0 0 0 0 0 0 0 0 0 
                       0 0 0 0 0 0 0 0 0 
                       0 0 0 0 0 0 0 0 0 
                       0 0 0 0 0 0 0 0 0                        
                       0 0 0 0 0 0 0 0 0 
                       0 0 0 0 0 0 0 0 0 
                       0 0 0 0 0 0 0 0 0 
                       0 0 1 0 0 0 0 0 0 
        base  &basemean/ cl alpha =.1   ; 
         
         
         
 estimate "60 vs Plb week 4"  intercept 0   avisitn 0 0 0   
                    trtan .25 .25 .25 .25 0 0 0 -1 
         trtan*avisitn 0 0 .25 0 0 0 0 0 0 
                       0 0 .25 0 0 0 0 0 0 
                       0 0 .25 0 0 0 0 0 0 
                       0 0 .25 0 0 0 0 0 0 
                       0 0 0 0 0 0 0 0 0 
                       0 0 0 0 0 0 0 0 0 
                       0 0 0 0 0 0 0 0 0 
                       0 0 - 1 0 0 0 0 0 0         
                                   
        base  0/cl  alpha=.1  ; 
         
 estimate "30 vs Plb week 4"  intercept 0   avisitn 0 0 0   
         trtan 0 0 0 0  .3333 .3333 .3333 -1  
         trtan*avisitn 0 0 0 0 0 0 0 0 0 
                       0 0 0 0 0 0 0 0 0 
                       0 0 0 0 0 0 0 0 0 
                       0 0 0 0 0 0 0 0 0                        
                       0 0 .3333 0 0 0 0 0 0 
                       0 0 .3333 0 0 0 0 0 0 
                       0 0 .3333 0 0 0 0 0 0 
                       0 0 -1    0 0 0 0 0 0 
        base  0/ cl alpha=.1     
         
 estimate "30 week 12"  intercept 1   avisitn 0 0 0 0 0 0 1  trtan .5 0 0 0 .5  
         trtan*avisitn 0 0 0 0 0 0 .5 0 0 


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                       0 0 0 0 0 0 0 0 0 
                       0 0 0 0 0 0 0 0 0 
                       0 0 0 0 0 0 0 0 0 
                       0 0 0 0 0 0 .5 0 0 
        base  &basemean/cl alpha = .1   ; 
         
         
estimate "10 week 12"  intercept 1   avisitn 0 0 0 0 0 0 1  trtan 0 .5 0 0 0 .5  
         trtan*avisitn 0 0 0 0 0 0 0 0 0 
                       0 0 0 0 0 0 .5 0 0 
                       0 0 0 0 0 0 0 0 0 
                       0 0 0 0 0 0 0 0 0 
                       0 0 0 0 0 0 0 0 0 
                       0 0 0 0 0 0 .5 0 0 
        base  &basemean/cl alpha = .1   ; 
         
estimate "100 week 12"  intercept 1   avisitn 0 0 0 0 0 0 1  trtan 0 0 .5 0 0 0 .5  
         trtan*avisitn 0 0 0 0 0 0 0 0 0 
                       0 0 0 0 0 0 0 0 0 
                       0 0 0 0 0 0 .5 0 0 
                       0 0 0 0 0 0 0 0 0 
                       0 0 0 0 0 0 0 0 0 
                       0 0 0 0 0 0 0 0 0 
                       0 0 0 0 0 0 .5 0 0 
        base  &basemean/cl alpha = .1    singular=1; 
estimate "Placebo week 12"  intercept 1   avisitn 0 0 0 0 0 0 1  trtan 0 0 0 .5 0 0 0 .5  
         trtan*avisitn 0 0 0 0 0 0 0 0 0 
                       0 0 0 0 0 0 0 0 0 
                       0 0 0 0 0 0 0 0 0 
                       0 0 0 0 0 0 .5 0 0 
                       0 0 0 0 0 0 0 0 0 
                       0 0 0 0 0 0 0 0 0 
                       0 0 0 0 0 0 0 0 0 
                       0 0 0 0 0 0 .5 0 0 
        base  &basemean/cl alpha = .1    singular=1; 
         
         
estimate "30 vs Plb week 12"  intercept 0    avisitn  0 0 0 0 0 0 0  trtan .5 0 0 -.5 .5 0 0 -.5  
         trtan*avisitn 0 0 0 0 0 0 .5 0 0 
                       0 0 0 0 0 0 0 0 0 
                       0 0 0 0 0 0 0 0 0 
                       0 0 0 0 0 0 -.5 0 0 
                       0 0 0 0 0 0 .5 0 0 
                       0 0 0 0 0 0 0 0 0 
                       0 0 0 0 0 0 0 0 0 
                       0 0 0 0 0 0 -.5 0 0 


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        base 0/cl alpha = .1  e  ; 
         
estimate "10 vs Plb week 12"  intercept 0   avisitn 0 0 0 0 0 0 0   trtan  0 .5 0 -.5  0 .5 0 -.5  
         trtan*avisitn 0 0 0 0 0 0 0 0 0 
                       0 0 0 0 0 0 .5 0 0 
                       0 0 0 0 0 0 0 0 0 
                       0 0 0 0 0 0 -.5 0 0 
                       0 0 0 0 0 0 0 0 0 
                       0 0 0 0 0 0 .5 0 0 
                       0 0 0 0 0 0 0 0 0 
                       0 0 0 0 0 0 -.5 0 0 
        base  0 /cl alpha = .1   ; 
  estimate "100 vs Plb week 12"  intercept 0   avisitn 0 0 0 0 0 0 0   trtan  0 0 .5 -.5  0 0 .5 -.5  
         trtan*avisitn 0 0 0 0 0 0 0 0 0 
                        0 0 0 0 0 0 0 0 0 
                       0 0 0 0 0 0 .5 0 0 
                       0 0 0 0 0 0 -.5 0 0 
                       0 0 0 0 0 0 0 0 0 
                       0 0 0 0 0 0 0 0 0 
                       0 0 0 0 0 0 .5 0 0 
                       0 0 0 0 0 0 -.5 0 0 
        base  0 /cl alpha = .1   ; 
         
Appendix 9. Examples of SAS Code for Statistical Analyses – ANCOVA 
Using the same input parameters in Table 3, the analysis will be implemented as follows 
proc mixed data=dataset ; 
           by visit; 
           class    id trt visit; 
           model cfb = trt baseline /alpha=0.10 ddfm=kr; 
           lsmeans trt  /alpha=0.10 cl pdiff; 
           ods output diffs=dancova; 
run; 
 
Appendix 10. Example SAS Code for Generalized Mixed Model for Binary Data 
(GMMRM) 
PROC GLIMMIX DATA=xxx NOCLPRINT method=rmpl; 
CLASS ID Visit trt; 
MODEL efrslt(event='1') = trt Visit trt*Visit/ SOLUTION DIST=BINARY LINK=LOGIT  
htype=3  ddfm=sat; 
random Visit / type=un subject=ID  residual; 
lsmeans Dose*Visit / slicediff=Visit or alpha=.1 ilink cl e; ods output lsmeans=lsmout 
slicediffs=diffsout; 


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Run; 
 
Appendix 11. Logistic Regression Code 
PROC GENMOD data=<dataset>  descending; 
  Class trt; 
MODEL efrslt =trt/   dist=bin  link=logit  alpha=0.1  lrci ; 
Run; 
 
 
Appendix 12. 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. 
 
data pvals; 
   Input Test$ Raw_P; 
Datalines; 
Test1 .xxxxx 
Test2 .xxxxx 
….. 
Test6 .xxxxx 
; 
Proc multtest pdata=pvals hoc out=new; 
run; 
 
 
Appendix 13. Details on C-SSRS Mapping 
Columbia-Classification Algorithm of Suicide Assessment (C-CASA) 


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