Clinical trial NCT03469336
Conditions: Psoriasis
Keywords: Psoriasis Topical
Sponsor: Pfizer
Start date: 2018-04-24; Completion date: 2019-03-20
Enrollment: 18 participants; Allocation: RANDOMIZED; Intervention model: SINGLE_GROUP

Brief summary:
The study is a randomized, double blinded, vehicle and active comparator controlled, multiple dose study in subjects with chronic plaque psoriasis. The study will have approximately 15 completers. Each subjects will receive three different topical doses of PF 06763809, PF 06763809 vehicle, and two active comparators. These will be applied to six different treatment fields for 18 days. The total duration of participation in the study will be approximately 7 weeks (minimum) to approximately 11 weeks (maximum), including the interval from Screening to the Follow up phone call visit.

Detailed description:

Arms: arm 1: All subjects will receive all six interventions/treatments applied to six different treatment fields.
Interventions: intervention 1: PF-06763809 intervention 2: Vehicle intervention 3: Calcipotriene/calcipotriol intervention 4: Betamethasone
Intervention descriptions: intervention 1: Three different concentrations will be administered to three different treatment fields: 2.3%, 0.8% and 0.23% intervention 2: Vehicle matching PF-06763809. intervention 3: Calcipotriene/calcipotriol 50 ug/mL solution intervention 4: Betamethasone 1 mg/g solution

Protocol documents:
Prot_001.pdf: 
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A PHASE 1, RANDOMIZED, DOUBLE-BLIND, VEHICLE AND ACTIVE 
COMPARATOR-CONTROLLED, PSORIASIS PLAQUE TEST STUDY TO ASSESS 
SAFETY, TOLERABILITY, AND PSORIATIC SKIN INFILTRATE THICKNESS
FOLLOWING REPEATED, TOPICAL DOSES OF PF-06763809 SOLUTION IN 
SUBJECTS WITH MILD TO MODERATE CHRONIC PLAQUE PSORIASIS
Investigational Product Number:
PF-06763809
Investigational Product Name:
Not applicable
United States (US) Investigational New 
Drug (IND) Number:
Not applicable
European Clinical Trials Database 
(EudraCT) Number:
2017-002684-18
Protocol Number:
C3561001
Phase:
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Document History
Document
Version Date
Summary of Changes and Rationale
Amendment 1
8 February 2018
1. Added blood pressure 
measurements on Day 1 for sentinel 
subjects (Schedule of Activities).
Rationale: To monitor vitals after 
IP administration in sentinel
subjects.
2. Added hematology blood tests for 
sentinel subjects daily on Days 2-8.
Rationale: To monitor hematologic 
parameters after IP administration
in sentinel subjects.
3. Added sentinel dosing (Section
3.1).
Rationale: In accordance with 
Ethics Committee request, to 
minimize risk given first in human 
study. 
4. Added a limit on the number of 
subjects replaced for non-safety 
reasons and clarified that this is at 
sponsor’s discretion (Sections 
3.1 and 6.4).
Rationale: To clarify the maximum 
number of subjects in the study.
5. Added to inclusion criterion # 
1 that subjects have to be ≥18 years 
at the time of consent (Section 4.1).
Rationale: To comply with country 
(Germany) specific requirements.
6. Decreased allowed alcohol 
consumption within 6 months 
before Screening (Exclusion 


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criterion # 4, Section 4.2).
Rationale: To minimize potential 
confounding of efficacy & safety
assessments.
7. Decreased maximum values for 
systolic and diastolic blood 
pressure and added minimum value 
for systolic blood pressure 
(Exclusion criterion # 6, Section
4.2).
Rationale: To minimize risk factors 
and potential confounding of
cardiovascular safety assessments. 
8. Decreased allowed AST, ALT and 
total bilirubin (Exclusion criterion # 
8, Section 4.2), excluded subjects 
with history of Gilbert syndrome.
Rationale: To minimize risk factors 
and potential confounding of 
hepatic safety assessments.
9. Excluded more than occasional 
consumption of tobacco-or 
nicotine-containing products and/or 
in excess of 5 cigarettes per day
(Exclusion criterion # 13 in Section
4.2, Section 4.4.1).
Rationale: To minimize risk factors 
and potential confounding of safety 
assessments. 
10. Added exclusion criterion for 
known hypersensitivity against 
active comparators, any of its 
excipients or dressing material and 
for subjects who consent to biopsy, 
known hypersensitivity to local 
anesthesia (Exclusion criterion #25, 
Section 4.2).
Rationale: To minimize risk to 


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study participants.
11. Added a restriction on biologics to 
5 half-lives (whichever is longer)
(Exclusion criterion #20, Section
4.2).
Rationale: To accommodate prior 
use of investigational biologics with 
an appropriate period since dosing.
12. Allowed site staff administering IP 
to be unblinded in Sections 5.1, 
5.2 and 5.3.
Rationale: To ensure appropriate 
dosing but without bias in 
assessments.
13. Clarified how subjects will be
assigned to treatment (Section 5.1).
Rationale: To clarify treatment 
assignment.
14. Administrative clarifications in 
Section 4.2 (exclusion criterion # 
10), Sections 3.2, 5.2, 5.4.1, 5.4.2, 
5.6 and Appendix 1.
Rationale: To incorporate protocol 
administrative letters and to 
provide additional administrative 
clarifications.
Original protocol
19 September 2017
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................................................................................................14
1. INTRODUCTION ...............................................................................................................16
1.1. Mechanism of Action/Indication.............................................................................16
1.2. Background and Rationale ......................................................................................16
1.2.1. Nonclinical Primary Pharmacology............................................................17
1.2.1.1. In Vitro Assays..........................................................................17
1.2.1.2. In Vivo Studies..........................................................................18
1.2.2. Nonclinical Pharmacokinetics and Metabolism .........................................18
1.2.3. Summary of Toxicology Studies ................................................................19
1.2.4. Calcipotriene/calcipotriol Solution.............................................................19
1.2.5. Betamethasone Solution .............................................................................19
1.2.6. Benefit Risk Assessment Summary............................................................19
1.3. Study Rationale .......................................................................................................19
1.3.1. Design Rationale.........................................................................................20
1.3.1.1. Rationale for Design..................................................................20
21
1.3.2. Dose Rationale............................................................................................21
2. STUDY OBJECTIVES AND ENDPOINTS.......................................................................22
3. STUDY DESIGN.................................................................................................................23
3.1. Study Overview.......................................................................................................23
3.2. Stopping Rules for Dosing in Individual Subjects..................................................24
4. SUBJECT ELIGIBILITY CRITERIA.................................................................................24
4.1. Inclusion Criteria.....................................................................................................25
4.2. Exclusion Criteria....................................................................................................26
4.3. Randomization Criteria ...........................................................................................28
4.4. Lifestyle Requirements ...........................................................................................28
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4.4.1. Alcohol, Caffeine, and Tobacco .................................................................28
4.4.2. Activity .......................................................................................................29
4.4.3. Contraception..............................................................................................29
4.5. Sponsor’s Qualified Medical Personnel..................................................................30
5. STUDY TREATMENTS.....................................................................................................30
5.1. Allocation to Treatment ..........................................................................................31
5.2. Breaking the Blind ..................................................................................................32
5.3. Subject Compliance.................................................................................................32
5.4. Investigational Product Supplies.............................................................................32
5.4.1. Dosage Form and Packaging ......................................................................32
5.4.2. Preparation and Dispensing........................................................................33
5.5. Administration.........................................................................................................33
5.6. Investigational Product Storage ..............................................................................35
5.7. Investigational Product Accountability...................................................................36
5.7.1. Destruction of Investigational Product Supplies ........................................36
5.8. Concomitant Treatment(s).......................................................................................36
6. STUDY PROCEDURES .....................................................................................................36
6.1. Screening.................................................................................................................36
6.2. Study Period ............................................................................................................36
6.3. Follow-up ................................................................................................................37
6.3.1. Follow-up Visit...........................................................................................37
6.4. Subject Withdrawal/Early Termination ..................................................................37
7. ASSESSMENTS..................................................................................................................38
7.1. Safety.......................................................................................................................39
7.1.1. Laboratory Tests .........................................................................................39
7.1.2. Physical Examinations................................................................................40
7.1.3. Temperature................................................................................................41
7.1.4. Blood Pressure and Pulse Rate ...................................................................41
7.1.5. Electrocardiogram.......................................................................................41
.42
42
42
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43
43
43
44
44
8. ADVERSE EVENT REPORTING......................................................................................45
8.1. Requirements...........................................................................................................45
8.1.1. Additional Details on Recording Adverse Events on the CRF...................46
8.1.2. Eliciting Adverse Event Information..........................................................46
8.1.3. Withdrawal From the Study Due to Adverse Events (see also the 
Subject Withdrawal section)............................................................................46
8.1.4. Time Period for Collecting AE/SAE Information......................................46
8.1.4.1. Reporting SAEs to Pfizer Safety...............................................47
8.1.4.2. Recording Non-serious AEs and SAEs on the CRF .................47
8.1.5. Causality Assessment .................................................................................47
8.1.6. Sponsor’s Reporting Requirements to Regulatory Authorities ..................47
8.2. Definitions...............................................................................................................48
8.2.1. Adverse Events...........................................................................................48
8.2.2. Abnormal Test Findings .............................................................................48
8.2.3. Serious Adverse Events ..............................................................................49
8.2.4. Hospitalization............................................................................................49
8.3. Severity Assessment................................................................................................51
8.4. Special Situations ....................................................................................................51
8.4.1. Potential Cases of Drug-Induced Liver Injury............................................51
8.4.2. Exposure to the Investigational Product During Pregnancy or 
Breastfeeding, and Occupational Exposure.....................................................53
8.4.2.1. Exposure During Pregnancy......................................................53
8.4.2.2. Exposure During Breastfeeding ................................................54
8.4.2.3. Occupational Exposure .............................................................54
8.4.3. Medication Errors .......................................................................................55
8.4.3.1. Medication Errors......................................................................55
9. DATA ANALYSIS/STATISTICAL METHODS...............................................................55
9.1. Sample Size Determination.....................................................................................56
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9.2. Efficacy Analysis ....................................................................................................57
9.2.1. Analysis of the Primary Endpoint...............................................................57
9.3. Pharmacokinetic Analysis.......................................................................................58
58
58
9.6. Safety Analysis........................................................................................................58
9.7. Interim Analysis ......................................................................................................58
9.8. Data Monitoring Committee ...................................................................................58
10. QUALITY CONTROL AND QUALITY ASSURANCE.................................................59
11. DATA HANDLING AND RECORD KEEPING .............................................................59
11.1. Case Report Forms/Data Collection Tools/Electronic Data Record.....................59
11.2. Record Retention...................................................................................................60
12. ETHICS..............................................................................................................................60
12.1. Institutional Review Board/Ethics Committee......................................................60
12.2. Ethical Conduct of the Study ................................................................................60
12.3. Subject Information and Consent..........................................................................61
12.4. Reporting of Safety Issues and Serious Breaches of the Protocol or ICH 
GCP ...........................................................................................................................61
13. DEFINITION OF END OF TRIAL...................................................................................61
13.1. End of Trial in a Member State.............................................................................61
13.2. End of Trial in All Other Participating Countries.................................................62
14. SPONSOR DISCONTINUATION CRITERIA ................................................................62
15. PUBLICATION OF STUDY RESULTS..........................................................................62
15.1. Communication of Results by Pfizer ....................................................................62
15.2. Publications by Investigators ................................................................................63
16. REFERENCES ..................................................................................................................64
LIST OF TABLES
Table 1.
Schedule of Activities...........................................................................................14
Table 2.
Safety Laboratory Tests........................................................................................40
Table 3.
Percent Reduction Relative to Comparator in Psoriatic Skin Infiltrate 
Thickness for a Given Sample Size and a Target Power......................................56
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LIST OF FIGURES
Figure 1.
Overall Study Design............................................................................................24
APPENDICES
Appendix 1. Abbreviations......................................................................................................66


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PROTOCOL SUMMARY 
Background and Rationale:  
PF-06763809 is a retinoid acid-related orphan receptor 2 (RORC2; also referred to as 
RORγt) inhibitor.  Inhibition of RORC2-mediated inflammation has the potential to provide 
a novel approach in the topical treatment of plaque psoriasis.  The aim of this first-in-human 
study is to assess the antipsoriatic activity of PF-06763809 solutions in subjects with chronic 
mild to moderate plaque psoriasis in a psoriasis plaque test (PPT).
Objectives and Endpoints:
Primary Objective(s): 
Primary Endpoint(s): 
•
To assess the changes in psoriatic skin infiltrate 
thickness/echo poor band (EPB) in response to 
PF-06763809 2.3%, 0.8% and 0.23% applied 
topically for 18 consecutive days as compared to 
the vehicle control.
•
Change relative to baseline at Day 19 in 
psoriatic skin infiltrate thickness/EPB.
•
To determine the safety and tolerability of 
multiple dose topical administration of 
PF-06763809 in psoriasis subjects.
•
Assessment of adverse events (AEs), clinical 
laboratory tests, vital signs (including blood 
pressure and pulse rate), and cardiac conduction 
intervals as assessed via 12-lead 
electrocardiogram (ECG).
Secondary Objective(s): 
Secondary Endpoint(s):
•
To evaluate the Area Under the Curve (AUC) of 
psoriatic skin infiltrate thickness/EPB for 
PF-06763809 compared to vehicle.
•
AUC of the psoriatic skin infiltrate 
thickness/EPB from Day 1 to Day 19.
•
To assess the effect of PF-06763809 compared to 
calcipotriene/calcipotriol solution in the change 
of psoriatic skin infiltrate thickness/EPB both 
within and following 18 days of treatment.
•
Change relative to baseline in psoriatic skin 
infiltrate thickness/EPB.
•
To assess the effect of PF-06763809 compared to 
betamethasone solution in the change of psoriatic 
skin infiltrate thickness/EPB both within and 
following 18 days of treatment.
•
Change relative to baseline in psoriatic skin 
infiltrate thickness/EPB.
 
 
 
 
 
 
 
 
 
 
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Study Design:
The study is proposed as a randomized, double-blinded, vehicle and active 
comparator-controlled, multiple dose study in subjects with psoriasis.  Subjects will receive 
topical doses (2.3%, 0.8% and 0.23%) of PF-06763809, PF-06763809 vehicle, and two active 
comparators.
Study Treatment:
For this study, the investigational products are:
•
PF-06763809 (2.3%, 0.8% and 0.23%);
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•
Matching vehicle.
The comparator agents are: 
•
calcipotriene/calcipotriol 50 μg/mL solution;
•
betamethasone 1 mg/g solution.
Subjects with chronic plaque type psoriasis and with a treatment area sufficient for 
6 treatment fields on 1 to 3 comparable plaques defined as having treatment fields with 
psoriatic skin infiltrate thickness/EPB of at least 200 μm will be enrolled in this study.  All 
subjects will receive each study treatment once daily.  All study treatments will be applied by 
way of Duhring® chambers seated in holes punched in a hydrocolloid dressing (eg,
Varihesive® E [Convatec], Munich, Germany).  The hydrocolloid dressing will be fixed on 
the skin with adhesive patches (eg, BSN Medical, Hamburg, Germany, or comparable) 
containing the same holes for the chambers as the hydrocolloid dressing. 
 
 
 After each test chamber is filled with the 
appropriate volume, the test chambers will be subsequently applied to the test fields.
The chambers will be fixed in place with Leukosilk® (eg, BSN, Hamburg, Germany or 
comparable) and will be removed before each new application.  The distance between the 
chambers must be at least 1.5 cm.  This distance is sufficient to exclude interactions with 
neighboring fields.  The fields will be treated with occlusion for a treatment period of 
18 days. 
Statistical Method:
The sample size determination is based on the primary endpoint of change relative to 
baseline in psoriatic skin infiltrate thickness/EPB at Day 19.  The log-scale of infiltrate 
thickness is used for a more stable variability over the assessed efficacy range and a better 
approximation to normal distribution. 
A sample size of 15 completers was selected based on the power analysis results and 
enrollment should ensure approximately 15 completers.
All subjects who have at least one application of the investigational products and have at 
least one post-baseline assessment of the primary efficacy variable will be included into the 
Full Analysis Set (FAS) which will be the primary analysis set.
The primary endpoint for this study is the change relative to baseline in psoriatic skin
infiltrate thickness/EPB at Day 19
 for
PF-06763809 in comparison to vehicle.  The efficacy assessment of PF-06763809 will be 
performed for the change from baseline in log of the psoriatic skin infiltrate thickness/EPB 
on Day 19 using a longitudinal analysis of covariance model, with treatment, visit, treatment 
by visit interaction as main effects and the log of the psoriatic skin infiltrate thickness/EPB at 
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baseline as covariate.  The CS@UN covariance structure will be assumed to adequately 
model the two within-subject factors (treatment, visit), where the compound symmetric (CS) 
correlation is for repeated measures from different treatments within each visit and the 
unstructured (UN) correlation is for longitudinal measures from different visits.  The point 
estimate and 95% confidence interval (CI) for the difference in log transformed means at Day 
19 visit between treatment groups will be constructed using least square means and 
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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 in the schedule of activities table, in order to conduct evaluations or assessments required to protect the well-being of 
the subject.
Table 1.
Schedule of Activities
[for a list of abbreviations refer to
Appendix 1]
Screen
Treatment Phase (activities at 0 hr before dosing unless otherwise specified)
FU Visit
Visit Identifier/Study Day
-28 to -3
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
27±2a
49±3
Informed consent & demography
x
Outpatient visit
x
x
x 
x 
x
x 
x 
x
x 
x 
x 
x
x 
x 
x
x
x
x
x
x
x
Review inclusion/exclusion criteria
x
x
Medical history
x
x
Review alcohol/tobacco/contraception use
x
x
x
xb
Review prior or concomitant treatments
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
Physical examinationc
x
x
x
Height + body weight
x
Descaling if necessary
xd
Serious and non-serious adverse event 
monitoring
x
x
→
→→
→
→
→
→
→
→
→
→
→
→
→
→
→
→
x
x
x
Single 12-lead ECG
x
x
x
x
Single, supine vital sign assessment
x
xk
 
 
 
 
 
 
x
x
Blood sampling for –
FSH in females amenorrheic ≥12 consecutive 
months, only
x
Clinical laboratory tests (see Section 7.1.1)
x
x
xl
xl
xl
xl
xl
xl
xl
x
x
Urine sampling for –
 
 
 
 
 
 
 
 
 
 
 
 
 
Urine drug test
x
Urinalysis (and microscopy, if needed)
x
x
x
x
Randomization
x
 
 
 
 
 
 
 
 
 
 
 
 
 
Determination of test fields
x
 
 
 
 
 
 
 
 
 
 
 
 
 
Removal of chambers and IMP residues
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
Investigational product administrationf
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
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Table 1.
Schedule of Activities
[for a list of abbreviations refer to
Appendix 1]
Screen
Treatment Phase (activities at 0 hr before dosing unless otherwise specified)
FU Visit
Visit Identifier/Study Day
-28 to -3
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
27±2a
49±3
NOTE: Where applicable, all activities are to be conducted pre-dose unless otherwise noted.
a.
This follow-up visit is only mandatory for subject who have consent to the optional biopsy or who have an open AE following completion of Day 19.
b.
Confirmation of appropriate contraception use, only.
c.
A complete physical examination may be done at Screening or may be deferred to Day 1 at the discretion of the Investigator; at all other time points, limited PE for 
findings during previous PE or new/open AEs only, at Investigator discretion.
d.
5% salicylic acid in Vaseline provided to applicable subjects to apply at home until Day -2 for a maximum of five days.
f.
Investigational product administration will occur every day without regard to food or a meal.
k.
Blood pressure will be taken once pre-dose. For sentinel subjects only, blood pressure will be taken also every 30 min post-dose until 4 hours post-dose. 
l.
For sentinel subjects only, blood samples (for hematology only) will be taken on Days 2-8 inclusive.
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1. INTRODUCTION
1.1. Mechanism of Action/Indication
PF-06763809 is a retinoid acid-related orphan receptor 2 (RORC2; also referred to as 
RORγt) inhibitor that is being developed for topical treatment of adult subjects with mild or
moderate psoriasis vulgaris (plaque psoriasis).
1.2. Background and Rationale
Plaque psoriasis is a chronic inflammatory skin disease of variable severity that is
characterized by red, scaly, raised plaques.  Chronic plaque psoriasis is a common skin 
disorder with a worldwide prevalence of 2%.1 Psoriasis had been viewed as primarily a 
disease of epidermal hyperplasia, but more recently has come to be regarded as an 
immune-mediated disease.2 Cutaneous and systemic overexpression of T cells, as well as 
type 1 cytokines such as interleukin (IL)-2, IL-6, IL-8, IL-12, IL-23, IL- 17, have been 
implicated in the pathophysiology of chronic plaque psoriasis.3 T-cell infiltration and 
associated pro-inflammatory cytokines drive epidermal hyperplasia, which is characterized 
by increased cell division and aberrant differentiation that result in the psoriatic 
phenotype.2,4,5
Although psoriasis is not a life-threatening disease, it can profoundly impact the individual’s
quality of life causing disability (eg, physical and mental functioning) akin to other major 
diseases such as type 2 diabetes, myocardial infarction, and arthritis.6 It is also associated 
with serious co-morbidities, including psoriatic arthritis, depression, malignancy, metabolic 
syndrome, cardiovascular morbidity and mortality.4,7-11,
Nearly all patients with mild psoriasis are treated topically.  Patients with moderate to severe 
disease, who receive systemic therapies or phototherapy, often also apply topical agents to 
recalcitrant areas.  Topical treatment of psoriasis is dominated by corticosteroids and 
vitamin D analogs.  However, to be effective in this disease, corticosteroids must be high 
potency (eg, fluocinonide) or ultra-high potency (eg, clobetasol).  These agents can cause 
skin atrophy and striae with chronic use and hypophyseal-pituitary axis suppression when 
applied over large body surfaces.  Vitamin D analogs are less effective and often irritating, 
but may be used in combination with corticosteroids.  Consequently, there remains an unmet 
medical need for a topical therapy that will provide symptomatic relief with a high degree of 
safety and minimize required doses of systemic medications, ultimately reducing the burden 
of the disease.
RORC2 is a transcription factor that controls the production of the cytokine IL-17A, which 
plays a central role in the pathogenesis of psoriasis.12,13 Psoriasis lesions contain prominent 
inflammatory cell infiltrates that include T cells that produce IL-17A.14 The evidence that 
RORC2 controls IL-17A production in humans is provided by the observation that human 
subjects who are homozygotes for a loss-of-function mutation in RORC gene lack IL-17A+ 
cells in peripheral blood.15 Naïve T cells differentiate into T helper 17 (Th17) cells upon 
antigen presentation in the presence of appropriate cytokines including IL-1β, IL-23, TGFβ, 
and IL-6.  TH17 cells are elevated in psoriatic lesions, along with levels of proinflammatory 
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likely mediators of inflammation and tissue damage.16,17 RORC2 is barely detectable in 
normal naïve T cells and its expression is dramatically increased during the 
Th17 differentiation process.18
In addition to genetic evidence, several effective psoriasis therapies target TH17 cytokine 
production, suggesting a central role of TH17 and IL-17 in the disease.  Secukinumab 
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.19-22 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.23 Collectively, there is strong rationale for targeting RORC2, which is implicated 
in the TH17 pathway and IL-17A in the treatment of psoriasis.  As such, it is hypothesized 
that administration of a RORC2 inhibitor should block its activity in infiltrating T cells in 
psoriatic lesions, thereby reducing the production of pathogenic IT-17A, and ultimately 
improving the clinical signs and symptoms for patients with psoriasis.
Additional information for this compound may be found in the single reference safety 
document (SRSD), which for this study is the Investigator’s Brochure for PF-06763809.  The 
SRSD for the comparator agents calcipotriene/calcipotriol solution (related to a synthetic 
form of vitamin D) and betamethasone solution are the approved product labels.
1.2.1. Nonclinical Primary Pharmacology
1.2.1.1. In Vitro Assays
PF-06763809 inhibited the binding of purified recombinant human RORC2 ligand binding 
domain to steroid receptor coactivator-1 (SRC-1) with an IC50 value of 3.1 nM which 
demonstrates direct interaction of PF-06763809 with RORC2.
Because RORC2 is a transcription factor that directly controls IL-17A expression in 
lymphocytes, the effect of PF-06763809 on IL-17A production was examined.  In human 
lymphocytes subjected to Th17 differentiation, PF-06763809 inhibited IL-17A protein 
production and gene expression with IC50 values of 2.2 and 1.6 nM, respectively, which are 
consistent with the potency of PF-06763809 on RORC2 activation as described above.  This 
effect of PF-06763809 on Th17 lymphocytes was specific because PF-06763809 had 
minimal effect on IFNand IL-13 production by human Th1 and Th2 cells, respectively, and 
no effect on cell viability.  Topical administration of PF-06763809 to human skin in vitro 
with the formulation that will be used in this clinical study caused a dose-dependent 
inhibition of IL-17A gene expression relative to vehicle alone which demonstrates that 
PF-06763809 has IL-17A inhibitory activity in the target organ of psoriasis.
PF-06763809 inhibited IL-17A production in mouse and rat lymphocytes, and minipig 
peripheral mononuclear cells subjected to Th17 differentiation with IC50 of 4.2, 3.2 and 
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1.2.1.2. In Vivo Studies
The efficacy of topically applied PF-06763809 was evaluated in two mouse models of ear 
skin inflammation, namely the imiquimod-induced model and the IL-23-induced model.  
These models partially respond to neutralizing anti-IL-17 mAb which is a highly efficacious 
mechanism in human psoriasis.  In both models, topical PF-06763809 inhibited the increase 
in ear thickness, which is a readout of inflammation, to a similar maximum extent as 
anti-IL-17A neutralizing mAb.  A dose-dependent effect of PF-06763809 in ear swelling was 
observed in the IL-23-induced model.  In addition, 5% topical PF-06763809 statistically 
significantly inhibited IL-17A gene expression in both models, and also inhibited IL-17A 
protein production in imiquimod-induced model.  IL-17A protein determinations in 
IL-23-induced model were very low and close to the limit of detection of the assay so the 
results were inconclusive.  The effect of PF-06763809 on IL-17A gene expression and 
protein levels is consistent with its inhibitory action on RORC2.  Taken together, these data 
suggest that topical PF-06763809 inhibited the production of IL-17A in these mouse models 
to an extent that was sufficient to cause a reduction in inflammation which was similar to 
neutralization of IL-17A by anti-IL-17A mAb.  Systemic exposure of PF-06763809 was 
below its IC50 for inhibition of IL-17A production by mouse lymphocytes in vitro, which 
suggests that the observed effects of PF-06763809 were due to its local action in the skin.
1.2.2. Nonclinical Pharmacokinetics and Metabolism
Following intravenous administration, PF-06763809 exhibited a plasma clearance (CL) in 
rats of 33 mL/min/kg (hepatic blood flow value 70 mL/min/kg) and in mini-pigs of 
22.6 mL/min/kg (hepatic blood flow value 39 mL/min/kg). The steady state volume of 
distribution (Vss) values in rats and mini-pigs were 1.8 and 3 L/kg, respectively with half-life 
values of 1.4 and 2.6 hours, respectively. 
Following topical administration to mini-pigs as part of the topical toxicology study, the 
Day 28 estimated topical bioavailability was approximately 1%.
PF-06763809 was highly bound in rat, mini-pig, and human plasma with fraction unbound 
values of 0.00887, 0.0225, and 0.0268, respectively. The blood to plasma ratios were 0.62, 
0.83, and 0.8, respectively.
The major route of metabolism of PF-06763809 in human hepatocytes was oxidation in the 
cyclopentane ring. All metabolites observed in human hepatocytes were present in 
hepatocytes from preclinical species. Following topical administration to min-pigs, only 
parent PF-06763809 was observed circulating in plasma.
CYP3A4 is the major cytochrome P450 (CYP) responsible for the metabolism of 
PF-06763809, with minor contributions from CYP2C8, 2C9, 2C19, and 3A5.
Based on the relatively low predicted systemic exposure following topical administration, 
PF-06763809 is not expected to cause a CYP mediated drug interaction by inhibition or 
induction. It is possible that CYP3A4 inhibitors will significantly increase the exposure of 
PF-06763809 on co-administration. However, based on the large potential safety margins, 
this interaction is highly unlikely to have clinical consequences.


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Further details of the nonclinical pharmacokinetic profile of PF-06763809 are provided in the 
current Investigator Brochure.
1.2.3. Summary of Toxicology Studies
In nonclinical safety studies with PF-06763809 in rats (oral) and mini-pigs (dermal) of up to 
1-month in duration, the cardiovascular and immune systems have been identified as 
potential key systemic targets and vehicle-related mild to moderate skin irritation by the 
topical route of administration.  The no observed adverse effect levels (NOAELs) in the 
pivotal toxicity studies were 200 mg/kg in rats (Cmax, 6280 ng/mL and AUC24, 
71,000 ng•h/mL) and the maximum feasible dose, 2.3% formulation applied at 
0.02 mL/cm2/dose to ~10% body surface area, twice daily (BID), in minipigs (Cmax, 
41.3 ng/mL and AUC24, 309 ng∙h/mL).  PF- 06763809 was not identified with mutagenic or 
clastogenic potential from in vitro and in vivo studies.  PF-06763809 did not demonstrate 
phototoxicity potential and did not demonstrate a sensitization potential in the in vitro 
sensitivity assays.  Details of the nonclinical safety program are provided in the current 
Investigator’s Brochure.
1.2.4. Calcipotriene/calcipotriol Solution 
PF-06763809’s anti-psoriatic activity will be benchmarked against that of calcipotriene
solution.  In a similar designed study, Daivonexsolution reduced the skin inflammatory 
infiltrate by 38% relative to vehicle with a within standard deviation (SD) of 0.435 (data on 
file; bioskin). 
1.2.5. Betamethasone Solution
PF-06763809’s anti-psoriatic activity will be benchmarked against that of betamethasone
solution. In a similar designed study, Betnesolsolution reduced the skin inflammatory 
infiltrate by 79% relative to vehicle (data on file; bioskin). 
While betamethasone solution is approved for scalp psoriasis, the proposed use being highly 
limited on other skin surfaces in this study, does not significantly increase the risks (or 
decrease acceptability of risks) associated with the use of this product.  As noted earlier, the 
SRSD is the approved product label.
1.2.6. Benefit Risk Assessment Summary
There is no known benefit for the subjects with plaque psoriasis participating in this study
since only small test fields will be treated.  Based on the clinical safety profile as well as the 
projected low systemic availability of PF-06763809, the risk to the subjects with plaque 
psoriasis is deemed to be minimal.
1.3. Study Rationale 
Inhibition of RORC2-mediated inflammation has the potential to provide a novel approach in 
the topical treatment of plaque psoriasis.  This first-in-human study will evaluate 
PF-06763809 solution, applied topically to skin surface areas in subjects with chronic mild to 
moderate plaque psoriasis.  The primary study objective using the psoriasis plaque test is to 


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assess the reduction in psoriatic skin infiltrate thickness/ echo poor band (EPB) as a measure 
of disease activity in response to study treatment; appropriate vehicle and active controls 
(calcipotriene/calcipotriol and betamethasone) will also be included.  Safety and tolerability 
of PF-06763809 solution applied topically will also be assessed. Evidence of short-term 
clinical activity with PF-06763809 will systematically inform subsequent development of a 
formulation more suitable for topical use.
1.3.1. Design Rationale
1.3.1.1. Rationale for Design
The psoriasis plaque test (PPT) is a commonly employed methodology in the early 
assessment of topical agents for the treatment of psoriasis.  Indeed, the skin infiltrate 
thickness/EPB thickness is considered an important indicator of disease activity in psoriasis 
and has been shown to correspond with increased inflammatory cell infiltrates, capillary 
congestion, and/or edema in the superficial dermis as identified by histopathology.24,25 Given 
that the extent of the psoriatic infiltrate is an important clinical endpoint in psoriasis, the PPT
relies on an objective biophysical measurement of psoriatic skin infiltrate thickness/EPB
 to support traditional clinical endpoints in psoriasis.
Testing is conducted under optimized conditions using small skin surface areas located on 
stable psoriatic plaques in subjects with plaque psoriasis.  The reduction in psoriatic skin 
infiltrate thickness/EPB in response to PF-06763809 solution (2.3%, 0.8%, and 0.23%),
when applied topically at 180 μL to 1.1 cm2 skin surface areas (a volume of 180 μL applied 
to a 1.1 cm2 surface, equivalent to 164 μL/cm2), will be measured in subjects with stable 
chronic plaque psoriasis.  At the end of study treatment, the change relative to baseline in 
psoriatic skin infiltrate thickness of treated areas with PF-06763809’s will be compared with 
vehicle as well as two active controls, calcipotriene/calcipotriol solution (50 μg/mL) and 
betamethasone (1 mg/g). The treated areas will be clinically assessed throughout the study. 
The study will also assess the safety and tolerability of topically applied 
PF-06763809 solution (2.3%, 0.8%, and 0.23%) in subjects with stable chronic plaque 
psoriasis.
This first-in-human study will enroll subjects with psoriasis and body mass index (BMI) of
≥17.5 and ≤35.5 kg/m2. Use of this increased BMI range is justified to balance the need for 
an otherwise healthy subject population in this first study with PF-06763809 and permit 
recruitment of subjects with psoriasis who have higher prevalence for obesity.26
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1.3.2. Dose Rationale
The nonclinical safety profile of PF-06763809 has been adequately characterized in rat and 
mini-pig to support progression into human clinical studies up to 4 weeks in duration (See 
Section 1.2.3).  Dose strengths selected for this are 2.3%, 0.8%, and 0.23%.  The highest 
strength was selected based on the maximum solubility of the PF-06763809 in the vehicle 
and the results from the animal studies. 
 
 
 
 
 
 The doses applied in the study, are 
unlikely to be associated with clinically relevant systemic pharmacology based on the 
integration of the in vitro pharmacology and predicted exposure levels and as such, the safety 
monitoring implemented is reduced from what would be evaluated following oral 
administration in a first-in-human study.  The proposed doses in this study showed efficacy 
in various animal efficacy models.
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2. STUDY OBJECTIVES AND ENDPOINTS
Primary Objective(s): 
Primary Endpoint(s): 
•
To assess the changes in psoriatic skin infiltrate 
thickness/EPB in response to 
PF-06763809 2.3%, 0.8% and 0.23% applied 
topically for 18 consecutive days as compared to 
the vehicle control.
•
Change relative to baseline at Day 19 in 
psoriatic skin infiltrate thickness/EPB.
•
To determine the safety and tolerability of 
multiple dose topical administration of 
PF-06763809 in psoriasis subjects.
•
Assessment of adverse events (AEs), clinical 
laboratory tests, vital signs (including blood 
pressure and pulse rate), and cardiac conduction 
intervals as assessed via 12-lead 
electrocardiogram (ECG).
Secondary Objective(s): 
Secondary Endpoint(s): 
•
To evaluate the Area Under the Curve (AUC) of 
psoriatic skin infiltrate thickness/EPB for 
PF-06763809 compared to vehicle .
•
AUC of the psoriatic skin infiltrate 
thickness/EPB from Day 1 to Day 19.
•
To assess the effect of PF-06763809 compared to 
calcipotriene/calcipotriol solution in the change 
of psoriatic skin infiltrate thickness/EPB both 
within and following 18 days of treatment.
•
Change relative to baseline in psoriatic skin 
infiltrate thickness/EPB.
•
To assess the effect of PF-06763809 compared to 
betamethasone solution in the change of psoriatic 
skin infiltrate thickness/EPB both within and 
following 18 days of treatment.
•
Change relative to baseline in psoriatic skin 
infiltrate thickness/EPB.
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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3. STUDY DESIGN
3.1. Study Overview
The study is proposed as a randomized, double-blinded, vehicle and active 
comparator-controlled, multiple dose study in subjects with psoriasis.  Subjects will receive 
topical doses (2.3%, 0.8% and 0.23%) of PF-06763809, PF-06763809 vehicle, and two active 
comparators in this study.  In order to mitigate any unanticipated safety risks, sentinel dosing 
approach will be employed for this study.  Two sentinel subjects will be dosed first for 
18 days with all six treatments.  The sponsor medical monitor will communicate with the 
investigator as soon as sentinel subjects complete Day 19, in order to determine whether it is 
safe to proceed with dosing of remaining subjects.
A total of approximately 15 subjects with chronic plaque type psoriasis and with a treatment 
area sufficient for 6 treatment fields on 1 to 3 comparable plaques defined as having 
treatment fields with psoriatic skin infiltrate thickness/EPB of at least 200 μm will be 
randomized to achieve approximately 15 evaluable subjects.  The effect of the
PF-06763809 solutions will be assessed in comparison to the corresponding vehicle, 
calcipotriene/calcipotriol and betamethasone solutions using the PPT, which also allows 
within subject comparison of treatments.  Subjects will be screened within 28 days prior to 
application of investigational product to confirm that they meet the subject selection criteria 
for the study.  The total duration of participation in the study will be approximately 7-weeks 
(minimum) to approximately 11-weeks (maximum), including the interval from Screening to 
the Follow-up phone call visit (Day 49).  The six test fields will be selected on Day 1.  A 
visual examination of the skin will be completed including measurement of psoriatic skin 
infiltrate thickness/EPB 
 and clinical assessment.  
 
Approximately 180 μL of each liquid preparation and 180 μL of each comparator will be 
applied
under Duhring® chambers (12 mm inside diameter, 14 mm outside 
diameter) seated in holes punched in hydrocolloid dressing (eg, Varihesive®, Bristol-Myers 
Squibb Gruppe, Munich, Germany).  The fields will be treated under occlusion for 18 days.  
Subjects will return daily to the center for re-application of the test substances daily during 
the 18-day treatment period.  Before each new application any remaining residue of the 
previously applied preparation will be removed gently by cleansing each test field with a 
clean soft tissue.  Following this regimen, each preparation will be left in contact with 
lesional skin under a Duhring® chamber until removal for inspection at the next visit.  This 
ensures that there is exposure to each preparation almost continually for the 18 days of the 
treatment phase of the study.
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Safety will be assessed by monitoring of vital signs, safety laboratory tests (see
Section 7.1.4 and 7.1.1 respectively) and by recording of adverse events (AEs) and serious 
adverse events (SAEs) (see Section 8).  Special attention will be given to local safety (ie, 
signs of skin irritation at the application sites).  Skin reactions will be recorded as AEs.
The overall study design is summarized in Figure 1.
Figure 1.
Overall Study Design 
In this study, subjects who prematurely discontinue for non-safety related reasons may be 
replaced, at the discretion of the Sponsor.  Up to 5 subjects may be replaced.
3.2. Stopping Rules for Dosing in Individual Subjects
At investigator discretion, for subjects’ safety, dosing with any or all double-blinded 
investigational product/s, may be stopped in an individual subject – either temporarily or
permanently.  In such cases, any open TEAEs (treatment emergent adverse events) must be 
followed to resolution or until such time that the event is viewed to have stabilized – refer to 
Section 8 for details.
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.
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4.1. Inclusion Criteria
Subjects must meet all of the following inclusion criteria to be eligible for enrollment in the 
study:
1. Healthy female subjects of non-childbearing potential and/or male subjects with 
psoriasis who, at the time of consent and Screening, are ≥18 years.  Healthy is defined 
as no clinically relevant abnormalities identified by a detailed medical history, full 
physical examination, including blood pressure and pulse rate measurement, 12-lead 
electrocardiogram (ECG) or clinical laboratory tests, as assessed by the investigator. 
2. Female subjects must be of non-childbearing potential to enroll into this study and as 
such, must meet at least one of the following criteria:
a.
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 post-menopausal state (with a single repeat permitted if deemed 
necessary by Investigator);
b. Have undergone a documented hysterectomy and/or bilateral oophorectomy;
c.
Have medically confirmed ovarian failure.
All other female subjects (including female subjects with tubal ligations) are 
considered to be of childbearing potential.
3. Body mass index (BMI) of 17.5 and 35.5 kg/m2; and a total body weight >50 kg 
(110 lbs). 
4. Evidence of a personally signed and dated informed consent document indicating that 
the subject has been informed of all pertinent aspects of the study. 
5. Subjects who are willing and able to comply with all scheduled visits, treatment 
plans, laboratory tests, and other study procedures.
6. Subjects with psoriasis vulgaris in a chronic stable phase and with a plaque area of 
mild to moderate severity sufficient for six treatment fields located in up to three 
plaque areas.
7. The target lesion(s) should be on the trunk or extremities (excluding palms/soles).
a.
Psoriatic lesions on the knees or elbows are not to be used as a target lesion.
b. Test areas to be treated should have a comparable psoriatic skin infiltrate 
thickness/EPB of at least 200 m.


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c.
The visual examination of the skin must be without disease findings unless the 
investigator considers an abnormality to be irrelevant to the outcome of the 
clinical trial.
4.2. Exclusion Criteria
Subjects with any of the following characteristics/conditions will not be included in the 
study:
1. Evidence of clinically significant hematological, renal, endocrine, pulmonary, 
gastrointestinal, cardiovascular, hepatic, psychiatric, neurological, or allergic disease 
(including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at 
the time of dosing) in the assessment of the investigator.
2. Subject-reported history of skin sensitivity to topical prescription or non-prescription 
products such as creams, lotions and cosmetics.
3. A positive urine drug test at Screening.
4. History of regular alcohol consumption 6 or more drinks/week for female subjects or 
12 or more drinks/week for male subjects (1 drink = 5 ounces [150 mL] of wine or 
12 ounces [360 mL] of beer or 1.5 ounces [45 mL] of hard liquor) within 6 months 
before screening.

Subjects may undergo an alcohol breath test or blood alcohol test at the discretion 
of the investigator.
5. Treatment with an investigational drug within 30 days (or as determined by the local 
requirement) or 5 half-lives preceding the first dose of investigational product
(whichever is longer).
6. Screening supine blood pressure (BP) >140 mm Hg (systolic) or >90 mm Hg 
(diastolic) or <100 mm Hg (systolic), following at least 5 minutes of supine rest.  If 
BP is >140 mm Hg (systolic) or >90 mm Hg (diastolic) or <100 mm Hg (systolic), 
the BP should be repeated 2 more times and the average of the 3 BP values should be 
used to determine the subject’s eligibility.
7. Screening supine 12-lead ECG demonstrating a corrected QT (QTc) interval 
>450 msec or a QRS interval >120 msec.  If QTc exceeds 450 msec, or QRS exceeds 
120 msec, the ECG should be repeated 2 more times and the average of the 3 QTc or 
QRS values should be used to determine the subject’s eligibility.
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 test, if deemed necessary:

Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) level >1.0x 
upper limit of normal (ULN);


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
Total bilirubin level >1.0x ULN;

NOTE: Subjects with a history of Gilbert syndrome are not eligible. 
9. Subjects with history of hepatitis, or positive result at screening for human 
immunodeficiency virus (HIV), hepatitis B, or hepatitis C; hepatitis B surface antigen 
(HepBsAg), hepatitis B core antibody (HepBcAb), or hepatitis C antibody (HCVAb):

As an exception, a positive HepBsAb result due to vaccination or healed hepatitis 
B, is permissible.
10. Pregnant female subjects; breastfeeding female subjects; male subjects with partners 
currently pregnant; fertile male subjects who are unwilling or unable to use a highly 
effective method of contraception as outlined in this protocol (Section 4.4.3) for the 
duration of the study and for at least 28 days after the last dose of investigational 
product.
11. Blood donation (excluding plasma donations) of approximately 1 pint (500 mL) or 
more within 60 days prior to first dose of investigational product. 
12. Unwilling or unable to comply with the criteria in the Lifestyle Requirements section 
of this protocol described in Section 4.4.
13. Use of tobacco-or nicotine-containing products if consumed more than occasionally 
and/or in excess of 5 cigarettes per day (see Section 4.4).
14. Subjects who are 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.
15. Other acute or chronic medical or psychiatric condition including recent (within the 
past year) or active suicidal ideation or behavior or laboratory abnormality that may 
increase the risk associated with study participation or investigational product 
administration or may interfere with the interpretation of study results and, in the 
judgment of the investigator, would make the subject inappropriate for entry into this 
study.
16. Other skin disease noted on physical examination that is considered by the 
investigator to be relevant to the outcome of the trial.
17. Subjects with psoriasis guttata, psoriasis punctata, psoriasis erythrodermatica, and 
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18. Treatment with any locally acting medications (including anti-psoriasis medications 
like topical corticosteroids, vitamin D analogues, dithranol) which in the opinion of 
the investigator might counter or influence the trial aim within 4 weeks preceding the 
treatment phase of the trial and during the trial.
19. Treatment with any systemic medications which in the opinion of the investigator 
might counter or influence the trial aim (including anti-psoriasis medications, eg, 
corticosteroids, cytostatics or retinoids) or medications which are known to provoke 
or aggravate psoriasis (eg, beta-blocker, anti-malarial drugs, lithium [unless on a 
stable dose for 3 months before dosing is initiated]) or phototherapy/psoralen+UVA 
(PUVA) within 8 weeks preceding the treatment phase of the trial and during the trial.
20. Treatment with any biologics (eg, tumor necrosis factor (TNF) blockers, apremilast, 
ustekinumab, and anti-IL17 agents) within 3 months or five half-lives (whichever is 
longer) prior to Day 1 of the trial and during the trial.
21. Ultraviolet (UV)-therapy within 8 weeks before first treatment and during the study.
22. Current treatment with anticoagulant drugs (applicable for subjects consenting to the 
biopsy procedures).
23. Contraindications according to summary of product characteristics of the active 
comparators (see also Summary of Product Characteristics).
24. Subject is institutionalized because of legal or regulatory order.
25. Known hypersensitivity against active comparators, any of its excipients or dressing 
material.  In addition, subjects who consent to biopsy must not have known 
hypersensitivity to local anesthesia. 
4.3. Randomization Criteria 
Subjects will be randomized into the study provided they have satisfied all subject eligibility 
criteria.
4.4. Lifestyle Requirements
The following guidelines are provided:
4.4.1. Alcohol, Caffeine, and Tobacco

Nicotine-containing products are permitted during participation in the study only if 
consumed occasionally and not in excess of 5 cigarettes per day.

Subjects may undergo an alcohol breath test or blood alcohol test at the discretion of 
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4.4.2. Activity

The dressings are not to be soaked through (swimming, bathing, sauna not allowed).  
Short showering is allowed as long as the treated plaques are shielded from water.

In case of accidental contact with the test fields, it is recommended to wash the hands.

The application of any lotions or creams to the area of assessment other than those 
provided by site staff is prohibited from Day 1 until the on-site Follow-up visit.

As additional precautionary measure, the subjects should avoid natural or artificial 
UV irradiation (solarium) during the treatment with the study treatments.

Subjects will abstain from strenuous exercise (eg, heavy lifting, weight training, 
calisthenics, aerobics) for at least 48 hours prior to each blood collection for clinical 
laboratory tests.  Walking at a normal pace will be permitted.
4.4.3. Contraception
All fertile male subjects who are, in the opinion of the investigator, sexually active and at risk 
for pregnancy with their partner(s) must agree to use a highly effective method of 
contraception consistently and correctly for the duration of the active treatment period 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 an
appropriate method of contraception for the individual subject and his or her partner(s) from 
the permitted list of contraception methods (see below) and will confirm that the subject has 
been instructed in its 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 highly 
effective contraception consistently and correctly and document the conversation and the 
subject’s affirmation in the subject’s chart (subjects need to affirm their consistent and 
correct use of at least 1 of the selected methods of contraception).  In addition, the 
investigator or designee will instruct the subject to call immediately if the selected 
contraception method 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), by the male subject’s 
female partner(s) and the female partner(s) 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). 


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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 post vasectomy 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).
NOTE: Sexual abstinence, defined as completely and persistently refraining from all 
heterosexual intercourse (including during the entire period of risk associated with the study 
treatments) may obviate the need for contraception ONLY if this is the preferred and usual 
lifestyle of the subject.
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.
Females of child-bearing potential are not eligible for this study.
4.5. 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 supporting study documentation. 
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. For sites other than 
a Pfizer CRU, 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 vehicle 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 


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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 products are:

PF-06763809 (2.3%, 0.8%, and 0.23%);

Matching vehicle.
The comparator agents are: 

calcipotriene/calcipotriol 50 g/mL solution;

betamethasone 1 mg/g solution.
5.1. Allocation to Treatment
The investigator’s knowledge of the treatment should not influence the decision to enroll a 
particular subject or affect the order in which subjects are enrolled.
Each eligible subject will receive six treatments at six different test fields in a random order.  
There will be no subdivision into treatment groups.
The test fields will be numbered 1-6.  As far as possible the following procedure for 
numbering will be followed: The numbering should begin with the uppermost or most 
proximal site on the left from the investigator’s view.  Fields along the same line should be 
numbered from left to right.  If more than one plaque is included, numbers for the fields on 
the next plaque will be assigned likewise starting with the next free number.  The exact 
location of each test field in relation to the outline of the plaque(s) will be traced on a 
transparent plastic sheet which will be kept with the subject’s source data.  The location of 
the test fields will be documented in the Case Report Form (CRF) as:
Upper/lower left/right arm,
Upper/lower left/right leg,
Front/back trunk.
At screening, a subject will be assigned a subject number.  Once the subject meets all 
eligibility criteria, the subject will be randomized into the study according to the 
randomization schedule, which is generated through the Pfizer randomization system.  
Randomization will be performed by permutation of the six treatments.  At randomization, 
each eligible subject will be assigned a randomization number, which corresponds to a 
random permutation of six treatments.  The treatment listed first in the respective treatment 
sequence will be assigned to test field number 1, the second treatment to test field number 2, 
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Subjects are blinded to the treatment sequence throughout the study.  Investigators will be 
blinded to the treatment sequence except exceptional circumstances described in Section 5.2.  
Limited site staff who administer the treatments will be unblinded.
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 a manual 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).
The investigator site staff, blinded study monitor, if assigned, and Pfizer study team will be 
blinded to study treatment.  The blinded study monitor, if assigned, will remain blinded to 
treatment until all monitoring for the study has been completed.  To minimize the potential 
for bias, treatment randomization information will be kept confidential and will not be 
released to the blinded investigator or blinded investigator site personnel until the study 
database has been locked or the investigator requests unblinding of individual subjects for 
safety reasons.  However, it is anticipated that a limited number of site staff administering the 
IP (Investigational Product) will be unblinded.  The blinded and unblinded site personnel will 
be documented at the site.
5.3. Subject Compliance
Investigational product will be administered by unblinded investigator site personnel.
5.4. Investigational Product Supplies
5.4.1. Dosage Form and Packaging
 
PF-06763809 and vehicle will be packaged in open-label dosing vials and provided to the site
for topical application by site personnel.
Active comparators calcipotriene/calcipotriol (50 μg/mL) solution and betamethasone 1 mg/g
solution will be sourced by a pharmacy and used as marketed materials without repackaging 
and relabeling.
All study treatments will be labeled according to the requirements of local law and 
legislation.
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5.4.2. Preparation and Dispensing
Within this protocol, preparation refers to the investigator site activities performed to make 
the investigational product ready for administration or dispensing to the subject/caregiver by 
qualified staff.  Dispensing is defined as the provision of investigational product, 
concomitant treatments, and accompanying information by qualified staff member(s) to a 
healthcare provider, subject, or caregiver in accordance with this protocol.  Local health 
authority regulations or investigator site guidelines may use alternative terms for these 
activities.
 
 Prepared doses will be provided in containers 
labeled in accordance with Pfizer regulations and the investigator site’s labeling 
requirements.
Calcipotriene/calcipotriol (50 μg/mL) solution and betamethasone (1 mg/g) solution will be 
dispensed from bulk materials as described in Section 5.5.
At the clinical site, an unblinded administrator will dispense the study drugs according to a 
randomization schedule into Duhring® chambers. A second unblinded site staff member will 
observe the correct dispensing and administration of study drugs.
  The 
site will take all necessary precautions to maintain the Investigator and site personnel blind
(except for the unblinded administrators).  All subjects in the study will be blinded to the 
study treatments.
5.5. Administration
The dosing volume for all study treatments is 180 μL (164 μL/cm2), applied topically once 
daily to 1.1 cm2 skin surface area during an 18 day treatment period.  Hence, subjects will be 
exposed to:
Study Treatment 1:
2.3% PF-06763809 solution
Daily dosage: approximately 4.1 mg PF-06763809
Study Treatment 2:
0.8% PF-06763809 solution.
Daily dosage: approximately 1.4 mg PF-06763809
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Study Treatment 3:
0.23% PF-06763809
Daily dosage: approximately 0.41 mg PF-06763809
Study Treatment 4 (vehicle):
Active ingredient-free vehicle to PF-06763809 treatments
Study Treatment 5 (positive control):
Calcipotriene/ calcipotriol (50 μg/mL)
Daily dosage of calcipotriol: approximately 0.01 mg
Study Treatment 6 (positive control):
Betamethasone (1 mg/g)
Daily dosage of approximately 0.18 mg
All subjects will receive each study treatment once daily.  All study treatments will be 
applied by way of Duhring® chambers seated in holes punched in a hydrocolloid dressing 
(eg, Varihesive® E [Convatec], Munich, Germany).  The hydrocolloid dressing will be fixed 
on the skin with adhesive patches (eg, BSN Medical, Hamburg, Germany, or comparable) 
containing the same holes for the chambers as the hydrocolloid dressing. 
 
 
 The filled chamber will then be placed on 
the skin at the location of the relevant test fields. After each test chamber is filled with the 
appropriate volume, the test chambers will be subsequently applied to the test fields.
The chambers will be fixed in place with Leukosilk® (eg, BSN, Hamburg, Germany or 
comparable) and will be removed before each new application.  In previous studies the 
hydrocolloid dressing has been shown to be well tolerated.  The lack of a therapeutic 
influence of the dressing on the psoriasis has been verified by determination of the psoriatic 
skin infiltrate thickness/EPB before and after application. 
 
  The fields will be treated with occlusion for a treatment period of 
18 days (Day 1 through 18).  Before each new application remaining preparation residues 
will be removed by gently cleansing each test field with a separate soft tissue.  The 
hydrocolloid dressing will be renewed on Days 1 and all subsequent 
 
measurement days or as necessary.
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In case of a missed day of treatment/evaluation, the subject is advised to keep the dressing on 
the plaques until he/she can return to the investigator site. The subject should return to the 
investigator site at the next occasion. Study procedures performed will be such that any 
procedures that were to be performed on the missed day are performed at the next scheduled 
visit if not already planned.  Subjects who miss >1 dose may be discontinued and replaced at 
the discretion of the investigator or sponsor.
5.6. Investigational Product Storage 
The investigator or an approved representative, eg, pharmacist, will ensure that all 
investigational products, including any comparator and/or marketed 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 single reference safety document (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. 
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5.7. Investigational Product Accountability
The investigator site must maintain adequate records documenting the receipt, use, loss, or 
other disposition of the investigational product supplies.  All investigational products will be 
accounted for using a drug accountability form/record. 
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)
All concomitant treatments taken during the study must be recorded with indication, daily 
dose, and start and stop dates of administration.  All subjects will be questioned about 
concomitant treatment as defined in the Schedule of Activities (Table 1).
Treatments taken within 28 days before the dose of investigational product will be 
documented as a prior treatment.  Treatments taken after dosing of investigational product 
will be documented as concomitant treatments.
Subjects are permitted to be on stable doses of background medications for the management 
of their concomitant medical condition(s).  Whenever possible, attempts must be made to not
alter the doses and regimens of the concomitant medications after Day 1 and until the on-site 
Follow-up visit (on Day 27).
6. STUDY PROCEDURES
6.1. Screening
Refer to Schedule of Activities Table 1 for the study procedures to be completed at the 
Screening visit.
Subjects will be screened within 28 days prior to administration of the investigational 
product to confirm that they meet the subject selection criteria for the study.  The investigator 
(or an appropriate delegate at the investigator site) will obtain informed consent from each 
subject in accordance with the procedures described in the Subject Information and Consent
section (Section 12.3).
To prepare for study participation, subjects will be instructed on the Lifestyle Requirements 
(Section 4.4) and Concomitant Treatment(s) (Section 5.8) of the protocol. 
6.2. Study Period
Refer to Schedule of Activities Table 1 for the study procedures to be completed.
 
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If a subject has any clinically significant, study-related abnormalities, the Pfizer medical 
monitor (or designated representative) should be notified and an appropriate course of action 
will be determined.
6.3. Follow-up 
6.3.1. Follow-up Visit
In this study, there are two Follow-up visits, as follows: 
1st is an on-site visit where only subjects who have consented to the optional biopsy or who 
have an open AE following completion of Day 19 will return to the CRU on 
Day 27 (8 2 days following Day 19);
2nd is a telephone contact to occur for all subjects who participated in the study, on Day 
49 (31 3 days following the last dose of investigational product);
Refer to Schedule of Activities—Table 1 for the study procedures to be completed at each of 
the two Follow-up visits.
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 investigator site.  The early termination visit applies only to subjects 
who are randomized and then are prematurely withdrawn from the study.
If a subject does not return for a scheduled visit, every effort should be made to contact the 
subject.  The Investigator or site staff should attempt to contact the subject twice.  After two 
attempts, CRU staff may send a registered letter.  If no response is received from the subject, 
the subject will be considered lost to Follow-up.  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 for a final visit, if applicable, and Follow-up with the subject regarding any 
unresolved adverse events (AEs).
It may be appropriate for the subject to return to the clinic for final safety assessments to be 
scheduled as early as practically feasible following the decision to withdraw from the study.  
Subjects should be questioned regarding their reason for withdrawal.  At the early withdrawal 
visit, every effort must be made to complete the following assessments:

Conduct an inquiry about any spontaneously reported AEs by asking the subject to 
respond to a non-leading question such as “how do you feel?”;

Perform a limited physical examination, if there is a new or open AE or clinically 
significant abnormal physical finding from the last visit at PI discretion;


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
Obtain supine, single, standard, 12-lead ECG (refer to Section 7.1.5);

Obtain supine, single set of blood pressure and pulse rate measurements (refer to
Section 7.1.4);

Collect blood and urine specimens, for clinical laboratory tests (refer to Section 7.1.1)
and pregnancy test if applicable.
Lack of completion of all or any of the withdrawal/early termination procedures will not be 
viewed as protocol deviations so long as the subject’s safety was preserved.
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 who withdraw from the study for non-safety reasons may be replaced at the 
discretion of the sponsor.  Up to 5 subjects may be replaced.
Withdrawal of consent: 
Subjects who request to discontinue receipt of study treatment will remain in the study and 
must continue to be followed for protocol-specified follow-up procedures.  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.  
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 
detail in the medical records by the investigator, as to whether the withdrawal is only from 
further receipt of investigational product or also from study procedures and/or posttreatment 
study follow-up, and entered on the appropriate CRF page.  In the event that vital status 
(whether the 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.
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 above.  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, 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.
7. ASSESSMENTS
Every effort should be made to ensure that protocol-required tests and procedures are 
completed as described.  However, it is anticipated that from time to time there may be 
circumstances outside the control of the investigator that may make it unfeasible to perform 


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the test.  In these cases, the investigator must 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 the missed test and any corrective and preventive 
actions that he or she has taken to ensure that required processes are adhered to as soon as 
possible.  The study team must be informed of these incidents in a timely manner.
For samples being collected and shipped, detailed collection, processing, storage, and 
shipment instructions and contact information will be provided to the investigator site prior 
to initiation of the study.
7.1. Safety
7.1.1. Laboratory Tests
The following safety laboratory tests will be performed at times defined in the Schedule of 
Activities Table 1 of this protocol.  Additional laboratory results may be reported on these 
samples as a result of the method of analysis or the type of analyzer used by the clinical 
laboratory; or as derived from calculated values.  These additional tests would not require 
additional collection of blood.  Unscheduled clinical laboratory measurements may be 
obtained at any time during the study to assess any perceived safety concerns.
Any remaining serum/plasma/urine from samples collected for clinical safety laboratory 
measurements at baseline and at all times after dose administration may be retained and 
stored for the duration of the study.  Upon completion of the study, these retained safety 
samples may be used for the assessment of exploratory safety biomarkers or unexpected 
safety findings.  These data will not be included in the clinical study report (CSR).  Samples 
to be used for this purpose will be shipped to either a Pfizer-approved Biospecimen Banking 
System (BBS) facility or other designated laboratory and retained for up to 1 year following 
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Table 2.
Safety Laboratory Tests
Hematology
Chemistry
Urinalysis
Other
Hemoglobin
Hematocrit
RBC count
MCV
MCH
MCHC
Platelet count
WBC count
Total neutrophils 
(Abs)
Eosinophils (Abs)
Monocytes (Abs)
Basophils (Abs)
Lymphocytes (Abs)
BUN/urea and creatinine
Glucose
Calcium
Sodium
Potassium
Chloride
Total CO2 (bicarbonate)
AST, ALT
Total bilirubin
Direct bilirubind,e
Indirect bilirubind,e
Alkaline phosphatase
Uric acid
Albumin
Total protein
pH
Glucose (qual)
Protein (qual)
Blood (qual)
Ketones
Nitrites
Leukocyte esterase
Urobilinogen
Urine bilirubin
Microscopya
Other tests as part of clinical 
laboratory tests: 
Serum FSHb
Urine drug testc
Bloodd for HIV, 
HepBsAg, HepBcAb, 
HCVAb 
Additional Tests (Needed for Hy’s Law) – also refer to Section 8.4.1
AST, ALT (repeat)
Total bilirubin (repeat)
Albumin (repeat)
Alkaline phosphatase (repeat)
Direct bilirubin
Indirect bilirubin
Creatine kinase
GGT
PT/INR
Total bile acids
Acetaminophen drug and/or protein adduct levels
a.
Only if urine dipstick is positive for blood, protein, nitrites or leukocyte esterase.
b. At Screening, and only in females who are amenorrheic for 12 consecutive months. 
c.
At Screening only; with minimum requirements including cocaine, tetrahydrocannabinol (THC), opiates/opioids, 
benzodiazepines and amphetamines.
d. At Screening ONLY.
e.
After Screening, direct and indirect bilirubin assessed when total bilirubin is >ULN, only.
Subjects may undergo random urine drug testing at the discretion of the investigator.  Drug 
testing conducted prior to dosing must be negative for subjects to receive investigational 
product. 
7.1.2. Physical Examinations
Physical examinations may be conducted by a physician, trained physician's assistant, or 
nurse practitioner as acceptable according to local regulation.  A full physical examination 
will include head, ears, eyes, nose, mouth, skin, heart and lung examinations, lymph nodes, 
and gastrointestinal, musculoskeletal, and neurological systems.  The limited or abbreviated 
physical examination will be focused on general appearance, the respiratory and 
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For measuring weight, a scale with appropriate range and resolution is used and must be 
placed on a stable, flat surface. Subjects must remove shoes, bulky layers of clothing, and 
jackets so that only light clothing remains.  They must also remove the contents of their 
pockets and remain still during measurement of weight. 
7.1.3. Temperature 
Temperature will be measured orally during Physical Examinations.  No eating, drinking, or 
smoking is allowed for 15 minutes prior to the measurement.
7.1.4. Blood Pressure and Pulse Rate
BP and pulse rate (PR) will be measured at times specified in the Schedule of Activities
section of this protocol.  Additional collection times, or changes to collection times, of BP
and PR will be permitted, as necessary, to ensure appropriate collection of safety data.
Supine blood pressure and pulse rate will be measured with the subject’s arm supported at 
the level of the heart, and recorded to the nearest 5 mm Hg after approximately 5 minutes 
of rest.  The same arm (preferably the dominant arm) will be used throughout the study.  
Subjects should be instructed not to speak during measurements. 
The same properly sized and calibrated blood pressure cuff will be used to measure blood 
pressure each time.  The use of an automated device for measuring BP and pulse rate is 
acceptable, although, when done manually, pulse rate will be measured in the brachial/radial 
artery for 30 seconds. 
7.1.5. Electrocardiogram 
12-Lead ECGs should be collected at times specified in the Schedule of Activities section of 
this protocol.
All scheduled ECGs should be performed after the subject has rested quietly for 10 minutes 
in a supine position. 
The ECG measurements collected at Day 1, 0H will serve as the baseline, during study 
conduct. 
To ensure safety of the subjects, a qualified individual at the investigator site will make 
comparisons to baseline measurements.  If the QTc interval is increased by ≥45 msec from 
the baseline, or an absolute QTc value is 500 msec for any scheduled ECG, then 
2 additional ECGs will be collected, approximately 2-4 minutes apart, to confirm the original 
measurement.  If either of the QTc values from these repeated ECGs remains above the 
threshold value (≥45 msec from the baseline; or is 500 msec), then a single ECG must be 
repeated at least hourly until QTc values from 2 successive ECGs fall below the threshold 
value that triggered the repeat measurement. 


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If the average of QTc values from the triplicate measurements remains above the threshold 
value (≥45 msec from the baseline; or is ≥500 msec), then the subject will be transferred to 
their primary care physician or a cardiologist for additional monitoring.
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, as defined above, repeat measurements may not be necessary if a 
qualified medical provider’s interpretation determines that the QTc values are in the 
acceptable range.
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
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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 


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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 
to Pfizer Safety.  Any pertinent additional information must be reported on the CT SAE 
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.  In addition, each study subject 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 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 
in accordance with applicable local regulations.


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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 
wing to a medical floor, medical floor to a coronary care unit, or neurological floor to a 
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.


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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 
AE.


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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. 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.
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:


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
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. 
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.


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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.
8.4.2. 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.
8.4.2.1. 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).
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 
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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.
8.4.2.2. 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.
8.4.2.3. Occupational Exposure
An occupational exposure occurs when, during the performance of job duties, a person 
(whether a healthcare professional or otherwise) gets in unplanned direct contact with the 
product, which may or may not lead to the occurrence of an AE.
An occupational exposure is reported to Pfizer Safety within 24 hours of the investigator’s 
awareness, using the CT SAE Report Form, regardless of whether there is an associated 
SAE.  Since the information does not pertain to a 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.


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8.4.3. 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 
8.4.3.1. 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 and finalized prior to the unblinding of the study.  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 
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9.1. Sample Size Determination
The sample size determination is based on the primary endpoint of change relative to 
baseline in psoriatic skin infiltrate thickness/EPB at Day 19.  The log-scale of infiltrate 
thickness is used for a more stable variability over the assessed efficacy range and a better 
approximation to normal distribution. 
Data from three psoriasis plaque test (PPT) studies conducted at bioskin® GmbH were used 
to generate the assumption for sample size calculation.  In these three studies, the 
calcipotriene/calcipotriol solution demonstrated 36% - 44% reduction in infiltrate thickness 
relative to vehicle.  The observed within-subject standard deviation (SD) estimates for 
calcipotriene/calcipotriol solution relative to vehicle ranged from 0.331-0.435.  Power 
analyses were performed for samples sizes of N=15 and N=20 under within-subject SDs of 
0.38, 0.435 and 0.5 with 2-sided type-I error rate of 5% and results were summarized in 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
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A sample size of 15 completers was selected based on the above results and enrollment 
should ensure approximately 15 completers.
9.2. Efficacy Analysis
All subjects who have at least one application of the investigational products and have at 
least one post-baseline assessment of the primary efficacy variable will be included in the 
Full Analysis Set (FAS).  The Per Protocol Set (PPS) is a subset of the FAS.  Subjects with 
major protocol deviations and subjects who discontinued the study prematurely will be 
excluded from the PPS.  The PPS definition will be defined in the SAP and the subject 
assignment to the analysis sets will be carried out jointly by the medical advisor, the study 
manager and the statistician before breaking the blind during the blinded data review 
meeting.  The intent-to-treat (ITT) analysis of efficacy based on the FAS will be considered 
as primary.  The per-protocol (PP) analysis based on the PPS will be provided as a sensitivity 
analysis.
Change from baseline in the natural log-transformed psoriatic skin infiltrate thickness/EPB 
will be determined by subtraction of the baseline assessment from each post-baseline 
assessment. 
The area under the curve (AUC) of the psoriatic skin infiltrate thickness/EPB from Day 1 to 
Day 19 will be determined using the linear trapezoidal rule.  The log AUC will be performed 
by the natural logarithm of the AUC of the psoriatic skin infiltrate thickness/EPB. 
9.2.1. Analysis of the Primary Endpoint
The primary endpoint for this study is the change relative to baseline in psoriatic skin
infiltrate thickness/EPB at Day 19
for
PF-06763809 in comparison to vehicle.  The efficacy assessment of PF-06763809 will be 
performed for the change from baseline in log of the psoriatic skin infiltrate thickness/EPB 
on Day 19 using a longitudinal analysis of covariance model, with treatment, visit, treatment 
by visit interaction as main effects and the log of the psoriatic skin infiltrate thickness/EPB at 
baseline as covariate.  The CS@UN covariance structure will be assumed to adequately 
model the two within-subject factors (treatment, visit), where the compound symmetric (CS) 
correlation is for repeated measures from different treatments within each visit and the 
unstructured (UN) correlation is for longitudinal measures from different visits.  If there are 
convergence issues, alternative covariance structure will be examined and adopted.  The 
point estimate and 95% confidence interval (CI) for the difference in log transformed means 
at Day 19 visit between treatment groups will be constructed using least square means and 
appropriate standard errors.  The assessment of the primary endpoint will be performed at a 
two-sided significance level of 0.05.  In this primary analysis, the missing data will be 
assumed as missing at random and no imputation will be made for missing data.
In addition, a landmark analysis of covariance (ANCOVA) model analysis of the primary 
endpoint at Day 19 will be performed to examine the robustness of the conclusion drawn 
from the primary longitudinal analyses.  The landmark ANCOVA model will include 
treatment as the main effect, log-transformed psoriatic skin infiltrate thickness/EPB at 
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baseline as covariate and a random subject effect to account for correlation among repeated 
measures from different treatments for each subject.  Missing assessments of psoriatic skin 
infiltrate thickness/EPB at Day 19 will be imputed using the last observation carried forward 
(LOCF) procedure.  In case of treatment discontinuation the last assessment prior to 
treatment discontinuation will be imputed for the following planned assessment of psoriatic 
skin infiltrate thickness/EPB. 
 
 
 
 
 
9.6. Safety Analysis
Safety analysis will be performed for all subjects who had any investigational product 
dispensed.
AEs, ECGs, BP, PR, and safety laboratory data will be reviewed and summarized on an 
ongoing basis during the study to evaluate the safety of subjects.  Any clinical laboratory, 
ECG, BP, and PR abnormalities of potential clinical concern will be described.  Safety data 
will be presented in tabular and/or graphical format and summarized descriptively, where 
appropriate.
Medical history and physical examination and neurological examination information, as 
applicable, collected during the course of the study will be considered source data and will 
not be required to be reported, unless otherwise noted.  However, any untoward findings 
identified on physical and/or neurological examinations conducted during the active 
collection period will be captured as AEs, if those findings meet the definition of an AE. 
Data collected at screening that are used for inclusion/exclusion criteria, such as laboratory 
data, ECGs, and vital signs, will be considered source data, and will not be required to be 
reported, unless otherwise noted.  Demographic data collected at screening will be reported.
9.7. Interim Analysis 
No formal interim analysis will be conducted for this study.
9.8. Data Monitoring Committee 
This study will not use a data monitoring committee (DMC).
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10. QUALITY CONTROL AND QUALITY ASSURANCE
Pfizer or its agent will conduct periodic monitoring visits during study conduct for studies 
conducted at non-Pfizer investigator sites, 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.
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.
For studies conducted at non-Pfizer investigator sites, 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/Data Collection Tools/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 
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In most cases the source documents are the hospital or the physician's chart.  In these cases, 
data collected on the CRFs must match 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.
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 documents, copies of all CRFs, safety reporting forms, source documents, 
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 to 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 laws. 
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 is fully informed about the nature and 
objectives of the study and possible risks associated with participation. 
The investigator, or a person designated by the investigator, will obtain written informed 
consent from each subject before any study-specific activity is performed.  The investigator 
will retain the original of each subject's signed consent document.
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.


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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) 
reflected by completion of the 2nd Follow-up visit for the last subject randomized in the 
study.
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-06763809 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 7 days.  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 study results through posting the 
results of studies on www.clinicaltrials.gov (ClinicalTrials.gov), the European Clinical Trials 
Database (EudraCT), and/or www.pfizer.com, and other public registries in accordance with 
applicable local laws/regulations.
In all cases, study results are reported by Pfizer in an objective, accurate, balanced, and 
complete manner and are reported regardless of the outcome of the study or the country in 
which the study was conducted.
www.clinicaltrials.gov
Pfizer posts clinical trial US Basic Results on www.clinicaltrials.gov for Pfizer-sponsored 
interventional studies (conducted in patients) that evaluate the safety and/or efficacy of a 
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.


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www.pfizer.com
Pfizer posts public disclosure synopses (CSR synopses in which any data that could be used 
to identify individual patients have been removed) on www.pfizer.com for Pfizer-sponsored 
interventional studies at the same time the US Basic Results document is posted to
www.clinicaltrials.gov.
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.
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.
Parisi R, Symmons DP, Griffiths CE, et al. Global epidemiology of psoriasis: a 
systematic review of incidence and prevalence. J Invest Dermatol 2013; 133(2):377–85.
2.
Lowes MA, Bowcock AM, Krueger JG. Pathogenesis and therapy of psoriasis. Nature 
2007; 445(7130):866-73.
3.
Asadullah K, Döcke WD, Volk HD, et al. The pathophysiological role of cytokines in 
psoriasis. Drugs Today 1999; 35(12):913-24.
4.
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 Invest 2003; 
112(10):1571–80.
5.
Schon MP, Boehncke WH. Psoriasis. New Engl J Med 2005; 352(18):1899-912.
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.
Gelfand JM, Troxel AB, Lewis JD, et al. The risk of mortality in patients with psoriasis: 
results from a population-based study. Arch Dermatol 2007; 143(12):1493–9.
8.
Gelfand JM, Dommasch ED, Shin DB, et al. The risk of stroke in patients with 
psoriasis. J Invest Dermatol 2009; 129(10):2411–8.
9.
Gisondi P, Tessari G, Conti A, et al. Prevalence of metabolic syndrome in patients with 
psoriasis: a hospital-based case–control study. Br J Dermatol 2007;157(1):68–73.
10.
Mehta NN, Azfar RS, Shin DB, et al. Patients with severe psoriasis are at increased risk 
of cardiovascular mortality: cohort study using the General Practice Research Database. 
Eur Heart J 2010; 31(8):1000-6.
11.
Sterry W, Strober BE, Menter A. Obesity in psoriasis: the metabolic, clinical and 
therapeutic implications. Report of an interdisciplinary conference and review. Br J 
Dermatol 2007; 157(4):649–55.
12.
de Carvalho AV, Duquia RP, Horta BL, et al. Efficacy of Immunobiologic and Small 
Molecule Inhibitor Drugs for Psoriasis: A Systematic Review and Meta-Analysis of 
Randomized Clinical Trials. Drugs R D 2017; 17(1):29-51.
13.
Kim J, Krueger JG. The immunopathogenesis of psoriasis. Dermatol Clin 2015; 
33(1):13-23.
14.
Kim J, Bissonnette R, Lee J, et al. The spectrum of mild to severe psoriasis vulgaris is 
defined by a common activation of IL-17 pathway genes, but with key differences in 
immune regulatory genes. J Invest Dermatol 2016; 136(11):2173-2182.


PF-06763809 
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Final Protocol Amendment 1, 8 February 2018
Page 65
15.
Okada S, Markle JG, Deenick EK, et al. IMMUNODEFICIENCIES. Impairment of 
immunity to Candida and Mycobacterium in humans with bi-allelic RORC mutations. 
Science 2015; 349(6248):606-13..
16.
Martin DA, Towne JE, Kricorian G, et al. The emerging role of IL-17 in the 
pathogenesis of psoriasis: preclinical and clinical findings. J Invest Dermatol 2013; 
133(1):17-26.
17.
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(5):1207-11.
18.
Ivanov II, McKenzie BS, Zhou L, et al. The orphan nuclear receptor RORgammat 
directs the differentiation program of proinflammatory IL-17+ T helper cells. Cell 2006;
126(6):1121-33.
19.
Langley RG, Elewski BE, Lebwohl M, et al. Secukinumab in plaque psoriasis--results 
of two phase 3 trials. N Engl J Med 2014; 371(4):326-38.
20.
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(3):1913-20.
21.
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(7):1547-58.
22.
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(5 Nov):1022-30.
23.
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(1):116-124.e7.
24.
el Gammal S, Pieck C, Auer T, et al. [100 MHz ultrasound of psoriasis vulgaris plaque]. 
Ultraschall Med 1998; 19(6):270-4.
25.
Gupta AK, Turnbull DH, Harasiewicz KA, et al. The use of high-frequency ultrasound 
as a method of assessing the severity of a plaque of psoriasis. Arch Dermatol 1996;
132(6):658-62.
26.
Nutrition and Diabetes (2012) 2, e54; doi:10.1038/nutd.2012.26.


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Appendix 1. Abbreviations 
The following is a list of abbreviations that may be used in the protocol.
Abbreviation
Term
Abs
absolute
AE
adverse event
ALT
alanine aminotransferase
ANCOVA
analysis of covariance
AST
aspartate aminotransferase
AUC
area under the curve
BBS
Biospecimen Banking System
BID
twice daily
BMI
body mass index
BP
blood pressure
CI
confidence interval
CL
Plasma clearance
Cmax
maximum observed concentration
CRF
case report form
CS
compound symmetric
CSA
clinical study agreement
CSR
clinical study report
CT
clinical trial
CTA
clinical trial application
CYP
cytochrome P450
DILI
drug-induced liver injury
DMC
data monitoring committee
EC
ethics committee
ECG
electrocardiogram
EDP
exposure during pregnancy
EDTA
edetic acid (ethylenediaminetetraacetic acid)
EPB
echo poor band
EU
European Union
EudraCT
European Clinical Trials Database
FAS
full analysis set
FSH
follicle-stimulating hormone
GCP
Good Clinical Practice
GGT
gamma-glutamyl transferase
HepBcAb
hepatitis B core antibody
HepBsAg 
hepatitis B surface antigen
HCVAb
hepatitis C antibody
HIV
human immunodeficiency virus
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Abbreviation
Term
ICH
International Conference on Harmonisation
ID
identification
IL
interleukin
IND
investigational new drug application
INR
international normalized ratio
IP
Investigational Product
IRB
institutional review board
ITT
intent-to-treat
IUD
intrauterine device
K2EDTA
dipotassium ethylenediaminetetraacetic acid
LFT
liver function test
LOCF
last observation carried forward
LSLV
last subject last visit 
MCH
mean corpuscular hemoglobin
MCHC
mean corpuscular hemoglobin concentration
MCV
mean corpuscular volume
N/A
not applicable
NOAEL
no observed adverse effect level
PCD
primary completion date
PE
physical examination
PI
principal investigator
PK
pharmacokinetics
PPS
per protocol set
PPT
psoriasis plaque test
PR
pulse rate
PT
prothrombin time
PUVA
phototherapy/psoralen+UVA
QTc
corrected QT
qual
qualitative
RBC
red blood cell
RORC2
retinoid acid-related orphan receptor 2
SAE
serious adverse event
SAP
statistical analysis plan
SD
standard deviation
SRC-1
steroid receptor coactivator-1
SRSD
single reference safety document
TEAE
treatment emergent adverse event
TBili
total bilirubin
Th17
T helper 17
THC
tetrahydrocannabinol
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Abbreviation
Term
TNF
tumor necrosis factor
ULN
upper limit of normal
UN
unstructured
US
United States
UV
ultraviolet
Vss
steady state volume of distribution
WBC
white blood cell

SAP_000.pdf: 
Protocol C3561001 (PF-06763809) Statistical Analysis Plan
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Protocol C3561001
A PHASE 1, RANDOMIZED, DOUBLE-BLIND, VEHICLE AND ACTIVE 
COMPARATOR-CONTROLLED, PSORIASIS PLAQUE TEST STUDY TO ASSESS 
SAFETY, TOLERABILITY, AND PSORIATIC SKIN INFILTRATE THICKNESS
FOLLOWING REPEATED, TOPICAL DOSES OF PF-06763809 SOLUTION IN
SUBJECTS WITH MILD TO MODERATE CHRONIC PLAQUE PSORIASIS
Statistical Analysis Plan 
(SAP)
Version:
1.0
Author: 
      (Collegeville)
Date:
3-Apr-2018
PPD


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TABLE OF CONTENTS
LIST OF TABLES...........................................................................................................................3
LIST OF FIGURES .........................................................................................................................3
1. AMENDMENTS FROM PREVIOUS VERSION(S) .................................................................4
2. INTRODUCTION .......................................................................................................................4
2.1. Study Design ...................................................................................................................4
2.2. Study Objectives .............................................................................................................5
2.2.1. Primary Objectives .............................................................................................5
2.2.2. Secondary Objectives .........................................................................................5
6
3. INTERIM ANALYSES, FINAL ANALYSES AND UNBLINDING........................................6
4. HYPOTHESES AND DECISION RULES.................................................................................7
4.1. Statistical Hypotheses .....................................................................................................7
4.2. Statistical Decision Rules................................................................................................8
5. ANALYSIS SETS .......................................................................................................................9
5.1. Full Analysis Set .............................................................................................................9
5.2. Per Protocol Set...............................................................................................................9
5.3. Pharmacokinetic Analysis Set.........................................................................................9
9
5.5. Safety Analysis Set..........................................................................................................9
5.6. Treatment Misallocations................................................................................................9
5.7. Protocol Deviations.........................................................................................................9
5.7.1. Deviations Assessed Prior to Randomization...................................................10
5.7.2. Deviations Assessed Post-Randomization........................................................10
6. ENDPOINTS AND COVARIATES .........................................................................................10
6.1. Efficacy Endpoint(s) .....................................................................................................10
6.1.1. Primary Efficacy Endpoint ...............................................................................10
6.1.2. Secondary Efficacy Endpoint ...........................................................................10
10
6.2. Safety Endpoints ...........................................................................................................10
10
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6.4. Covariates......................................................................................................................11
7. HANDLING OF MISSING VALUES ......................................................................................11
8. STATISTICAL METHODOLOGY AND STATISTICAL ANALYSES ................................11
8.1. Analysis of Primary Efficacy Endpoint ........................................................................12
8.2. Safety Analysis..............................................................................................................12
LIST OF TABLES
Table 1.
Percent Reduction Relative to Comparator in Psoriatic Skin Infiltrate 
Thickness for a Given Sample Size and a Target Power..............................................7
LIST OF FIGURES
Figure 1.
Overall Study Design....................................................................................................5


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1. AMENDMENTS FROM PREVIOUS VERSION(S) 
None.
2. INTRODUCTION
RORC2 is a transcription factor that controls the production of the cytokine IL-17A, which 
plays a central role in the pathogenesis of psoriasis. Psoriasis lesions contain prominent 
inflammatory cell infiltrates that include T cells that produce IL-17A. PF-06763809 inhibited 
the binding of purified recombinant human RORC2 ligand binding domain steroid receptor 
coactivator-1 (SRC-1) with an IC50 value of 3.1nM. In vivo studies data suggest that topical 
PF-06763809 inhibited the production of IL-17A in mouse models to an extent that was 
sufficient to cause a reduction in inflammation which was similar to neutralization of IL-17A 
by anti-IL17A mAb.  
Inhibition of RORC2-mediated inflammation has the potential to provide a novel approach in 
the topical treatment of plaque psoriasis. This first-in-human study will evaluate PF-
06763809 solution, applied topically to skin surface areas in subjects with chronic mild to 
moderate plaque psoriasis. The primary study objective using the psoriasis plaque test (PPT)
is to assess the reduction in psoriatic skin infiltrate thickness/ echo poor band (EPB) as a 
measure of disease activity in response to study treatment; appropriate vehicle and active 
controls (calcipotriene/calcipotriol and betamethasone) will also be included.  Safety and 
tolerability of PF-06763809 solution applied topically will also be assessed.  Evidence of 
short-term clinical activity with PF-06763809 will systematically inform subsequent 
development of a formulation more suitable for topical use.
2.1. Study Design
The study is proposed as a randomized, double-blinded, vehicle and active
comparator-controlled, multiple dose study in subjects with psoriasis. A total of 
approximately 15 subjects with chronic plaque type psoriasis and with a treatment area 
sufficient for 6 treatment fields on 1 to 3 comparable plaques defined as having treatment 
fields with psoriatic skin infiltrate thickness/EPB of at least 200 !m will be randomized.
Subjects will receive topical doses (2.3%, 0.8% and 0.23%) of PF-06763809,
PF-06763809 vehicle, and two active comparators (calcipotriene/calcipotriol and 
betamethasone) in this study. Each eligible subject will receive six treatments at six different 
test fields in a random order. The effect of the PF-06763809 solutions will be assessed in 
comparison to the corresponding vehicle, calcipotriene/calcipotriol and betamethasone 
solutions using the PPT, which also allows within subject comparison of treatments.
The overall study design is summarized in Figure 1.


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Figure 1.
Overall Study Design 
2.2. Study Objectives
2.2.1. Primary Objectives
∀
To assess the changes in psoriatic skin infiltrate thickness/EPB in response to 
PF-06763809 2.3%, 0.8% and 0.23% applied topically for 18 consecutive days as 
compared to the vehicle control.
∀
To determine the safety and tolerability of multiple dose topical administration of 
PF-06763809 in psoriasis subjects.
2.2.2. Secondary Objectives
∀
To evaluate the Area Under the Curve (AUC) of psoriatic skin infiltrate 
thickness/EPB for PF-06763809 compared to vehicle.
∀
To assess the effect of PF-06763809 compared to calcipotriene/calcipotriol solution 
in the change of psoriatic skin infiltrate thickness/EPB both within and following 
18 days of treatment.
∀
To assess the effect of PF-06763809 compared to betamethasone solution in the 
change of psoriatic skin infiltrate thickness/EPB both within and following 18 days of 
treatment.


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DMB02-GSOP-RF16 2.0 STATISTICAL ANALYSIS PLAN TEMPLATE FOR FIRST IN HUMAN (FIH) STUDY
30-Jun-2015
TMF Doc ID: 98.03
 
 
 
3. INTERIM ANALYSES, FINAL ANALYSES AND UNBLINDING
No formal interim analysis will be conducted for this study. 
This is a randomized double-blind study. Subjects are blinded to the treatment sequence 
throughout the study. Investigators will be blinded to the treatment sequence, except 
exceptional circumstances when knowledge of the actual treatment code is absolutely 
essential for management of the subject. Blinded personnel performing the 
 
 ultrasound measurements should not be present during the treatment 
application procedures in order to remain blinded.
It is anticipated that a limited number of site staff administering the treatments will be 
unblinded. Other investigator site staff and Pfizer study team will be blinded to study 
treatment sequence. The blinded study monitor, if assigned, will remain blinded to treatment 
until all monitoring of the study has been completed.
To minimize the potential for bias, treatment randomization information will be kept 
confidential will not be released to the blinded investigator or blinded investigator site staff 
until the study database has been locked or the investigator requests unblinding of individual 
subjects for safety reasons.
Study unblinding will not be performed until the final database has been locked for all 
subjects.  Final analysis will follow the official database release.
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4. HYPOTHESES AND DECISION RULES
4.1. Statistical Hypotheses
This study is designed to show that PF-06763809 has a superior effect against vehicle in the 
primary endpoint of relative change from baseline in infiltrate thickness at Day 19.  The 
following hypotheses will be formally tested first under a significance level of 5% (two-
sided):
∀
The null hypothesis (H01): PF-06763809 has no greater reduction from baseline in 
infiltrate thickness at Day 19 than vehicle.
∀
The alternative hypothesis (H11) is that PF-06763809 has a greater reduction from 
baseline in infiltrate thickness at Day 19 than vehicle.
If the null hypothesis H01 is rejected statistically, then the following hypotheses will be 
formally tested next under a significance level of 5% (two-sided): 
∀
The null hypothesis (H02): PF-06763809 has no greater reduction from baseline in 
infiltrate thickness at Day 19 than calcipotriene/calcipotriol. 
∀
The alternative hypothesis (H12) is that PF-06763809 has a greater reduction from 
baseline in infiltrate thickness at Day 19 than calcipotriene/calcipotriol.
Data from three psoriasis plaque test (PPT) studies conducted at bioskin# GmbH were used 
to generate the assumption for sample size calculation.  In these three studies, the 
calcipotriene/calcipotriol solution demonstrated 36% - 44% reduction in infiltrate thickness 
relative to vehicle.  The observed within-subject standard deviation (SD) estimates for 
calcipotriene/calcipotriol solution relative to vehicle ranged from 0.331-0.435.  Power 
analyses were performed for samples sizes of N=15 and N=20 under within-subject SDs of 
0.38, 0.435 and 0.5 with 2-sided type-I error rate of 5% and results were summarized  
 
1. 
 
 
 
 
 
 
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4.2. Statistical Decision Rules
The primary endpoint for this study is the change relative to baseline in psoriatic skin 
infiltrate thickness/EPB at Day 19
 for 
PF-06763809 in comparison to vehicle.  The efficacy assessment of PF-06763809 will be 
performed for the change from baseline in log of the psoriatic skin infiltrate thickness/EPB 
on Day 19 using a longitudinal analysis of covariance model, with treatment, visit, treatment 
by visit interaction as main effects and the log of the psoriatic skin infiltrate thickness/EPB at 
baseline as covariate. The point estimate and 95% confidence interval (CI) for the difference 
in log transformed means at Day 19 visit between treatment groups will be constructed using 
least square means and appropriate standard errors.  The assessment of the primary 
endpoint will be performed at a two-sided significance level of 0.05.
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5. ANALYSIS SETS
5.1. Full Analysis Set
All subjects, who have at least one application of the investigational products and have at 
least one post-baseline assessment of the primary efficacy variable, will be included in the 
Full Analysis Set (FAS).
5.2. Per Protocol Set
The Per Protocol Set (PPS) is a subset of the FAS.  Subjects with major protocol deviations 
and subjects who discontinued the study prematurely will be excluded from the PPS. The key 
protocol violators will follow the procedure outlined in Section 5.7 below.  
 
 
 
 
 
5.5. Safety Analysis Set
Safety analysis will be performed for all subjects who had any investigational product 
dispensed. Subjects will be analyzed according to the treatment they are actually received. 
5.6. Treatment Misallocations
If a subject takes a treatment that is not consistent with the treatment they are randomized to,
then they will be reported under their randomized treatment group for efficacy analyses, but 
will be reported under treatment they actually received for all other analyses.
5.7. Protocol Deviations
Different protocol deviations may have different impact on the analyses. A full list of 
protocol deviations will be compiled and reviewed prior to database closure. In protocol 
deviation review meetings, the classification of major and minor protocol deviations will be 
carried out by the clinician and statistician prior to unblinding and a decision will be made 
for each subject’s eligibility for PPS analysis set. 
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5.7.1. Deviations Assessed Prior to Randomization
At screening, the investigator will assess subjects against the inclusion and exclusion criteria 
as set out in Sections 4.1 and 4.2 of the protocol.
5.7.2. Deviations Assessed Post-Randomization
Any significant deviation from the protocol will be reviewed prior to database closure and a 
decision taken regarding evaluation for each analysis population.
6. ENDPOINTS AND COVARIATES
6.1. Efficacy Endpoint(s)
6.1.1. Primary Efficacy Endpoint
∀
Change relative to baseline at Day 19 in psoriatic skin infiltrate thickness/EPB.
6.1.2. Secondary Efficacy Endpoint
∀
AUC of the psoriatic skin psoriatic thickness/EPB from Day 1 to Day 19.
∀
Change relative to baseline in psoriatic skin infiltrate thickness/EPB at visit other 
than Day 19.
6.2. Safety Endpoints
Safety endpoints of this study include adverse events (AEs), clinical laboratory tests, vital
signs (including blood pressure and pulse rate), and cardiac conduction intervals as assessed 
via 12-lead electrocardiogram (ECG). These safety data will be analyzed in standard safety 
summaries.
 
 
 
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6.4. Covariates
Baseline values of psoriatic skin infiltrate thickness/EPB will be included as a covariate in 
the longitudinal and landmark analysis of covariance (ANCOVA) analysis of the primary 
endpoint. 
7. HANDLING OF MISSING VALUES
In this primary longitudinal ANCOVA analysis of psoriatic skin infiltrate thickness/EPB, the 
missing data will be assumed as missing at random and no imputation will be made for 
missing data. In the landmark ANCOVA analysis the missing assessment of psoriatic skin 
infiltrate thickness/EPB will be imputed using the last observation carried forward (LOCF) 
procedure. In case of treatment discontinuation the last assessment prior to treatment 
discontinuation will be imputed for the following planned assessment of psoriatic skin 
infiltrate thickness/EPB.    
Any data displays using last observation carried forward will be labeled ‘LOCF’. For other 
data displays LOCF will not be used and subjects with missing values of a particular 
endpoint will not contribute to the analysis. 
8. STATISTICAL METHODOLOGY AND STATISTICAL ANALYSES
The intent-to-treat (ITT) analysis of efficacy based on the FAS will be considered as primary.  
The per-protocol (PP) analysis based on the PPS will be provided as a sensitivity analysis.
Safety analysis will be performed for all subjects who had any investigational product 
dispensed.
Change from baseline in the natural log-transformed psoriatic skin infiltrate thickness/EPB 
will be determined by subtraction of the baseline assessment from each post-baseline 
assessment. 
The area under the curve (AUC) of the psoriatic skin infiltrate thickness/EPB from Day 1 to 
Day 19 will be determined using the linear trapezoidal rule.  The log AUC will be performed 
by the natural logarithm of the AUC of the psoriatic skin infiltrate thickness/EPB.
In additional to the model-based analyses described below, all study endpoints will be 
summarized using descriptive statistics. For binary endpoints, summary statistics including 
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the numbers and percentages will be presented. For continuous endpoints, descriptive 
statistics (n, mean, median, standard deviation, minimum, and maximum) will be presented, 
by each planned measurement time point and treatment group if applicable. Inter-quarter 
ranges and 95% confidence intervals may be provided where meaningful. 
8.1. Analysis of Primary Efficacy Endpoint
The primary endpoint for this study is the change relative to baseline in psoriatic skin 
infiltrate thickness/EPB at Day 19
 for 
PF-06763809 in comparison to vehicle.  The efficacy assessment of PF-06763809 will be 
performed for the change from baseline in log of the psoriatic skin infiltrate thickness/EPB 
on Day 19 using a longitudinal analysis of covariance model, with treatment, visit, treatment 
by visit interaction as main effects and the log of the psoriatic skin infiltrate thickness/EPB at 
baseline as covariate.  The CS@UN covariance structure will be assumed to adequately 
model the two within-subject factors (treatment, visit), where the compound symmetric (CS) 
correlation is for repeated measures from different treatments within each visit and the 
unstructured (UN) correlation is for longitudinal measures from different visits.  If there are 
convergence issues, alternative covariance structure will be examined and adopted.  The 
point estimate and 95% confidence interval (CI) for the difference in log transformed means 
at Day 19 visit between treatment groups will be constructed using least square means and 
appropriate standard errors.  The assessment of the primary endpoint will be performed at a 
two-sided significance level of 0.05.
In addition, a landmark analysis of covariance (ANCOVA) model analysis of the primary 
endpoint at Day 19 will be performed to examine the robustness of the conclusion drawn 
from the primary longitudinal analyses.  The landmark ANCOVA model will include 
treatment as the main effect, log-transformed psoriatic skin infiltrate thickness/EPB at 
baseline as covariate and a random subject effect to account for correlation among repeated 
measures from different treatments for each subject.
8.2. Safety Analysis
The safety endpoints described in Section 6.2 will be listed and summarized in accordance 
with sponsor reporting standards, where the resulting data presentations will consist of 
subjects from the safety analysis set.
AEs, ECGs, BP, PR, and safety laboratory data will be reviewed and summarized on an 
ongoing basis during the study to evaluate the safety of subjects.  Any clinical laboratory, 
ECG, BP, and PR abnormalities of potential clinical concern will be described.  Safety data 
will be presented in tabular and/or graphical format and summarized descriptively, where 
appropriate.
Medical history and physical examination and neurological examination information, as 
applicable, collected during the course of the study will be considered source data and will 
not be required to be reported, unless otherwise noted.  However, any untoward findings 
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identified on physical and/or neurological examinations conducted during the active 
collection period will be captured as AEs, if those findings meet the definition of an AE.  
Data collected at screening that are used for inclusion/exclusion criteria, such as laboratory 
data, ECGs, and vital signs, will be considered source data, and will not be required to be 
reported, unless otherwise noted.  Demographic data collected at screening will be reported.